Journal of Functional Biomaterials doi: 10.3390/jfb17100508

Authors: Shaghayegh Javadi Enrique Martinez-Campos Raúl Arrabal Endzhe Matykina

Additively manufactured implants may be vulnerable to localized corrosion within narrow gaps, yet the critical crevice geometry and the effectiveness of multilayer coatings under such conditions remain insufficiently understood. This study compares the crevice-corrosion behavior of direct metal laser sintering (DMLS) and conventionally wrought mill-annealed Ti-6Al-4V alloys and evaluates a hierarchical coating comprising a plasma electrolytic oxidation (PEO) layer, a polycaprolactone (PCL) seal, and a porous polylactic acid (PLA) breath-figure topcoat. Electrochemical testing was conducted in simulated body fluid (SBF, pH 7.4, 37 °C) using a tapered crevice cell, followed by microscopic, compositional, and topographical analyses. Both uncoated alloys exhibited passive film breakdown; however, the wrought alloy subsequently repassivated, whereas the DMLS alloy underwent sustained localized attack within the critical crevice gap of ~11.4 µm. The transpassive potentials for DMLS and wrought Ti-6Al-4V with PEO/PCL/PLA coating system were 1.32 V and 1.45 V, respectively. Despite the intrinsic porosity and interfacial gaps of the coating, no crevice-type damage was detected in DMLS Ti-6Al-4V. PCL/PLA hierarchy increased the PEO pore resistance to ~3.5 kΩ cm2, reduced the passive current density by ~2 times, and increased the PEO barrier layer resistance to 107 Ω cm2.

Journal of Functional Biomaterials doi: 10.3390/jfb17100507

Authors: María Concepción Álvarez-García Gabriela Piñón-Zárate César Beato-López Laisa Ximena Contreras-Aguilar Andrés Eliú Castell-Rodríguez Sara Judith Álvarez-Pérez Erick Francisco Sánchez Ortega Alin García-Miranda Jorge Esteban Miranda-Calderón Katia Jarquín-Yáñez

(1) Background: Modern pharmacology and regenerative medicine seek effective, safe drug delivery systems that allow for the controlled and sustained release of active ingredients; in situ forming implants (ISFIs) represent one such option. Systems based on poly(lactic-co-glycolic acid) (PLGA) and the solvent N-methyl-2-pyrrolidone (NMP) offer a safe, biodegradable, and non-invasive alternative. (2) Methods: ISFIs were prepared using NMP and PLGA at 50:50 and 85:15 ratios, combined with the supernatant obtained from umbilical cord Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs). Cellular utility, cytotoxicity, cell proliferation, and in vivo biocompatibility were evaluated using Annexin, 7AAD, Calcein, and PrestoBlue assays, as well as a murine model. Statiscal significance was determined using one way ANOVA followed by Tukey’s post hoc test for multiple comparisons, with the significance level at p < 0.05. (3) Results: Differences in cumulative release profile were observed between the PLGA/NMP 50:50 and 85:15 formulations. PLGA 50:50 exhibited higher early and cumulative release of WJ-MSC-supernatant-derived material, whereas PLGA 85:15 showed a slower and more sustained release profile. (4) Conclusions: Cell-free therapy delivered via PLGA 50:50/NMP ISFIs, incorporating associated immunomodulatory factors as supernatant’s WJ-MSCs, is suitable for an effective controlled-release system.

Journal of Functional Biomaterials doi: 10.3390/jfb17100506

Authors: Egemen Umur Gizem Kaleli-Can Bugra Ayan

Chronic wounds represent a growing clinical and economic burden, and their impaired healing is closely linked to a disrupted redox environment. Reactive oxygen species (ROS) are essential signaling molecules that regulate each phase of wound healing, from hemostasis and inflammation through proliferation and remodeling. ROS at physiological levels regulate antimicrobial defense, angiogenesis and cellular migration. However, the persistent oxidative overload that characterizes chronic wounds sustains inflammation and delays tissue repair. Therefore, restoring redox balance instead of eliminating ROS has emerged as a rational therapeutic strategy. Microneedle (MN) platforms, particularly hydrogel-forming MNs , offer a uniquedelivery approach for this purpose by combining minimally invasive breach of the wound barrier with tunable swelling, high loading capacity, and controlled, localized release of redox-active agents into the wound bed and interstitial fluid. This review examines redox-active MN platforms for ROS modulation in chronic wound management, surveying ROS biology and wound healing physiology, the principal MN geometries and fabrication routes, and three major therapeutic categories: ROS-scavenging systems, ROS-generating systems and material and mechanistic design strategies beyond functional classification. We further discuss current challenges and future directions for translating these platforms toward clinical application. By integrating redox chemistry with MN engineering, hydrogel MN systems provide a versatile route to reestablish redox homeostasis and accelerate healing in chronic wounds. However, redox-active microneedle systems have not yet undergone clinical evaluation. Most efficacy data are derived from experimental animal wound models that do not accurately replicate the complexity of chronic wounds in humans, indicating that clinical translation remains at an early stage.

Journal of Functional Biomaterials doi: 10.3390/jfb17100505

Authors: Jan Łoś Małgorzata Zawrzykraj-Motylińska Milena Deptuła-Knioła Katarzyna Gurzawska-Comis Barbara Kochańska Michał Pikuła

Peri-implantitis is a plaque-associated inflammatory condition characterized by progressive loss of supporting peri-implant bone and remains one of the most challenging biological complications in implant dentistry. Although reconstructive procedures are increasingly used, the relative effectiveness of different regenerative biomaterials and biologically enhanced strategies remains uncertain. This structured narrative review critically evaluates current clinical evidence for regenerative biomaterials used in peri-implantitis treatment and places emerging biological and cell-based approaches within their appropriate translational context. A structured literature search was conducted in PubMed/MEDLINE. Particular emphasis was placed on direct human evidence concerning enamel matrix derivative, porous titanium granules, deproteinized bovine bone mineral (DBBM), hydroxyapatite, biphasic calcium phosphate, and platelet-rich fibrin, while periodontal, endodontic, and preclinical studies were considered indirect or translational evidence where relevant. Available clinical studies indicate that reconstructive procedures can improve radiographic defect fill and selected peri-implant clinical parameters; however, radiographic improvement does not necessarily correspond to complete disease resolution or true re-osseointegration. Among currently evaluated grafting materials, DBBM, porous titanium granules, and hydroxyapatite are supported by direct human clinical evidence, although heterogeneity in HA formulations and accompanying treatment protocols limits material-specific conclusions. BCP-containing reconstructive protocols have also been evaluated clinically, but the independent contribution of BCP remains difficult to isolate. Enamel matrix derivative and platelet-rich fibrin may provide biologically active adjunctive effects, although their independent contribution within multimodal regenerative protocols remains difficult to determine. Emerging cell-based and cell-derived strategies offer additional regenerative potential but remain predominantly supported by preclinical or translational evidence. No single biomaterial has demonstrated universal superiority. Future studies require standardized disease definitions, defect classifications, outcome measures, adequately powered multicentre trials, long-term follow-up, and improved patient and defect stratification to determine which regenerative strategies provide clinically meaningful and durable benefits.

Journal of Functional Biomaterials doi: 10.3390/jfb17100504

Authors: Ceren Turan Gökduman Esra Arılı Öztürk Mediha Büyükgöze-Dindar

Preventing coronal microleakage is crucial for long-term endodontic success; this ex vivo study compared the sealing performance of five intra-orifice barrier (IOB) material application protocols with that of a no-IOB control. Sixty maxillary anterior teeth were randomly assigned to six groups (n = 10): control, flowable composite, universal composite, resin-modified glass ionomer cement (RMGIC), high-viscosity bulk-fill composite, and flowable bulk-fill composite. Following endodontic treatment, 2 mm-thick barriers were placed in five groups. All specimens underwent 1000 thermocycles and 24 h immersion in 2% methylene blue. Linear dye penetration was measured at ×50 using stereomicroscopy and ImageJ. Data were analyzed using one-way ANOVA with Tukey’s HSD test (α = 0.05). Microleakage differed significantly among groups (F (5, 54) = 12.473; p < 0.001). The lowest mean microleakage was observed with the Estelite Sigma Quick (EQ) (1.85 ± 0.59 mm), followed by the Estelite Bulk Fill Flow (EF) (2.28 ± 0.91 mm) and Filtek One Bulk Fill Restorative (FR) (2.48 ± 1.18 mm). No statistically significant differences were detected among these materials; however, each demonstrated significantly less microleakage than the Tetric N-Flow (TNF), Ionoseal (IS), and no-IOB control (p < 0.05), among which no differences were detected (p > 0.05). Under the experimental conditions of this ex vivo study, the protocols involving the EQ and both bulk-fill resin composites (FR, EF) resulted in significantly lower coronal dye penetration than the protocols involving the TNF, IS and the no-IOB control.

Journal of Functional Biomaterials doi: 10.3390/jfb17100503

Authors: Hyung-Gyun Kim Young-Suk Moon Hyunsuk Choi Dong-Seok Sohn

Bone graft materials may undergo biological aging during storage, potentially reducing surface hydrophilicity and early cellular responses. Non-thermal plasma treatment has been investigated as a surface modification strategy to improve the biological performance of graft materials. This study evaluated osteogenic and angiogenic responses associated with non-thermal plasma-treated xenogenic bone grafts using tissues obtained from an 8-mm rabbit calvarial defect model. Twenty-four adult male New Zealand white rabbits were assigned to 2-, 4-, and 8-week healing periods, and defects were filled with untreated or plasma-treated xenografts. Immunohistochemical expressions of PCNA, VEGF, PECAM-1, collagen I, collagen III, ALP, BMP2, BMP4, BMP7, osteocalcin, and osteopontin were assessed semiquantitatively. Most markers showed greater expression in the experimental group during the early and intermediate healing stages. VEGF and PECAM-1 showed significant intergroup differences at 2 and 4 weeks but not at 8 weeks, whereas several osteogenic markers showed lower expression in the experimental group at 8 weeks. These temporal expression patterns suggest that non-thermal plasma treatment is associated with earlier activation of biological responses related to cell proliferation, angiogenesis, and osteogenesis, followed by changes consistent with later tissue maturation and remodeling.

Journal of Functional Biomaterials doi: 10.3390/jfb17100502

Authors: Yoon Seon Lee HyeRyoung Wang Yu-Jin Ahn So Young Park Jihoon Lee Jin Man Kim Juhyuk Moon Won Jun Shon

To establish a lower-alkalinity alternative to calcium silicate-based endodontic materials, this study developed a self-setting magnesium silicate-based cement (MSC) that hardens through magnesium silicate hydrate (M-S-H) formation. MSC was formulated from magnesium oxide, reactive silica, and zirconium oxide. Hydration and phase evolution were characterized by X-ray diffraction, thermogravimetric analysis, thermodynamic modeling, and scanning electron microscopy. pH, early penetration resistance, and compressive strength were compared with ProRoot mineral trioxide aggregate (MTA), and cement extracts were evaluated for human dental pulp cell viability, alkaline phosphatase activity, intracellular calcium mobilization, and YAP localization. MSC hydration involved progressive Mg(OH)2 consumption and formation of an M-S-H-rich matrix. Its pH decreased from approximately 9.7 to 8.9, whereas MTA remained near pH 12. The lower-water formulation containing additives exceeded 40 MPa in compressive strength at 28 days and showed greater early penetration resistance. MSC-0.3 extracts showed higher 7-day cell viability than ProRoot MTA at 1:4 and 1:8 dilutions, increased alkaline phosphatase activity, were accompanied by increased intracellular calcium fluorescence that was not observed following NPS 2143 pretreatment, and increased nuclear YAP localization. These findings identify MSC as a functional cement platform combining moderated alkalinity, progressive strength development, and favorable early pulp-cell responses.

Journal of Functional Biomaterials doi: 10.3390/jfb17100501

Authors: Pyi Phyo Win I-Ying Huang Daniel De-Shing Chen Szu-Yu Lai Yuichi Mine Tong-Hsien Chow I-Ta Lee Chien-Fu Tseng Tzu-Yu Peng

Fixed lingual retainers fabricated from 3D-printed resin (3DR) offer the benefits of geometric freedom; however, conventional approaches frequently rely on encapsulation or oversized retention pads to compensate for limited adhesion, increasing bulk and undermining these advantages. This study evaluated an interface-only bonding protocol using combinations of mechanical and chemical surface treatments for 3DR. Specimens were assigned to five groups: control; airborne-particle abrasion (APA) followed by universal adhesive (UA); APA followed by resin-matrix-penetrating primer (RMPP); non-thermal handheld plasma (NTHP) followed by UA; and NTHP followed by RMPP. Surface roughness, wettability, and chemical composition were characterized using contact profilometry, water-contact angle measurements, and attenuated total reflectance Fourier-transform infrared spectroscopy, respectively. Shear bond strength (SBS) and failure modes were evaluated before and after 10,000 thermal cycles. APA-containing protocols significantly increased surface roughness, whereas NTHP-containing protocols improved wettability without detectable topographical changes. Distinct chemical signals associated with urethane dimethacrylate and 10-methacryloyloxydecyl dihydrogen phosphate were identified in the RMPP- and UA-treated groups, respectively. Pre-aging SBS was comparable among groups, whereas APA followed by RMPP produced the highest post-aging SBS, and UA-containing groups showed the lowest values. These findings suggest that the combination of APA and RMPP improves resistance to in vitro hydrothermal degradation, although intraoral durability of interface-only 3DR retainers requires further clinical validation.

Journal of Functional Biomaterials doi: 10.3390/jfb17100500

Authors: Jacob A. Kendra Jiwei Hao Dillon R. Harris Rebekah L. Blatt Richard K. Brow Aaron B. Morton

Bioactive glasses represent an emerging strategy for localized skeletal muscle repair. Here, we investigated whether an injectable borophosphate bioactive glass [cobalt oxide–time release ion matrix (CoO-TRIM)] can accelerate skeletal muscle regeneration and functional recovery following acute injury. Using a barium chloride (BaCl2) injury model, muscle function, myogenesis, angiogenesis, and inflammation were evaluated in mouse tibialis anterior (TA) and extensor digitorum longus (EDL) muscles at 8 and 14 days post-injury (dpi). Mice were randomly assigned to Untreated, Saline-treated, and CoO-TRIM-treated groups. CoO-TRIM accelerated the regenerative process, with increased myofiber size and restoration of TA contractile function to values not significantly different from Healthy muscle by 14 dpi compared to Injured Untreated and Saline-treated muscles. Vascular endothelial growth factor (VEGF) concentrations were elevated through 14 dpi following CoO-TRIM treatment and accompanied by enhanced muscle vascularity in both TA and EDL muscles. CoO-TRIM modulated the inflammatory response, with increased inflammatory signaling during active regeneration at 8 dpi, followed by an accelerated transition toward a pro-regenerative environment characterized by increased CD163+ M2 macrophages and sustained IL-10 signaling. In contrast, CoO-TRIM produced no detectable effects in healthy contralateral muscles. These findings support ion-releasing bioactive glass as a cell- and growth factor-free strategy for skeletal muscle repair.

Journal of Functional Biomaterials doi: 10.3390/jfb17100499

Authors: Michał Urbaniak Joanna Rywaniak Dominika Szczerbiec Mateusz M. Urbaniak Wojciech Dąbrowski Ireneusz Urbaniak Marek Synder

Idiopathic hip osteoarthritis is a major cause of disability worldwide, and total hip arthroplasty (THA) is the standard treatment for advanced disease; however, the independent effect of femoral stem design on functional outcomes remains unclear. This retrospective cohort study compared clinical, biochemical, and radiographic outcomes between short-stem and standard-stem hip prostheses and identified predictors of superior postoperative function. A total of 70 patients undergoing primary THA for idiopathic coxarthrosis were divided into two equal groups based on implant type. Functional outcomes were assessed using the Harris Hip Score (HHS) and WOMAC preoperatively and 6 weeks postoperatively, along with perioperative laboratory parameters and radiographic evaluation. Both groups showed significant postoperative improvements in HHS and WOMAC scores, with no significant difference in HHS between groups. The short-stem group achieved significantly better WOMAC total and function scores, whereas the standard-stem group showed slightly better stiffness outcomes. No differences were found in postoperative inflammatory response or radiographic alignment. Multivariable analysis identified stem type as the only variable significantly and independently associated with superior functional outcome, with short-stem implants associated with higher odds of favorable results. This association was robust to adjustment for baseline functional status in sensitivity analysis. These findings suggest that both designs are effective, while short-stem prostheses are associated with better early patient-reported functional outcomes at 6 weeks after THA.

Journal of Functional Biomaterials doi: 10.3390/jfb17100498

Authors: Houmam Anees Paul Maria Merkel Lukas Boennen Fahed Al-Arbid Anas Miqdad Aria Balouchkhosravi Ibrahim El Mourabit Gero Knapp Markus Rupp Christian Heiss

Bone defects caused by trauma, infection, tumour resection and impaired healing remain difficult to reconstruct because successful repair requires coordinated mechanical stability, vascularisation, immune regulation and osteogenesis. Natural-based hydrogels provide hydrated, extracellular-matrix-mimicking platforms that can conform to irregular defects and integrate local delivery of bioactive factors, cells, extracellular vesicles and mineral phases. This critical narrative review examines natural-based hydrogels for bone regeneration from a biomaterials-to-clinic perspective, focusing on material design, cell–material interactions, vascularisation, osteoimmunomodulation, controlled therapeutic delivery, injectable and stimuli-responsive systems, composite reinforcement and 3D bioprinting. Human evidence exists for selected gelatin- and hyaluronan-based systems and for clinically adjacent applications such as growth-factor-assisted fracture healing and antibacterial implant coatings; however, most multifunctional regenerative systems remain preclinical. We therefore emphasise translational maturity rather than technological novelty alone. Key barriers include insufficient load-bearing mechanics, variable in vivo degradation, vascularisation at clinically relevant scale, manufacturing and sterilisation constraints, regulatory complexity and limited comparative clinical evidence. The most credible path to clinical adoption is likely to involve indication-specific systems that provide a reproducible biological advantage while remaining surgically compatible, scalable and practically manufacturable.

Journal of Functional Biomaterials doi: 10.3390/jfb17100497

Authors: Vlad Ștefan Proca Andreea-Florentina Gavrilă Alina-Mihaela Apostu Adrian Doloca Nicoleta Ioanid Alice-Arina Pendefunda Ovidiu Dumitru Aungurencei Eugenia-Larisa Țarevici Alice-Teodora Chiriac Petronela Bodnar Violina Budu Raluca-Maria Vieriu Vasilica Toma Ioana Rudnic Oana Țănculescu

Indirect posterior restorations combining complete occlusal coverage with extension onto an axial surface are described inconsistently, and their biomechanical advantage remains uncertain. This review compared failure load and a review-defined severe-failure category of morphology-defined axial-extension restorations with occlusal-only restorations and full-coverage crowns. PubMed, Scopus, Embase, and Web of Science Core Collection were searched from inception and last checked on 22 July 2026; citation searching supplemented the database searches. Eligible studies tested restorations meeting the morphological definition in extracted human posterior teeth. Two reviewers independently selected studies, extracted data, and appraised risk of bias using RoBDEMAT with QUIN as a supplementary appraisal. Multiple eligible intervention arms were combined, and shared comparators were counted once. Exploratory random-effects models estimated average effects across heterogeneous laboratory systems using ratios of means (RoMs) and mean differences (MDs) for failure load and risk ratios (RRs) for review-defined severe failure. Eight studies were included. Five independent studies contributed to the main comparison, restricted to single-surface axial-extension versus occlusal-only restorations. Failure-load estimates were inconclusive (RoM 0.98, 95% CI 0.88 to 1.09; MD −23 N, 95% CI −195 to 149). Severe-failure events were sparse and inconsistently defined across the source studies; exact counts were therefore primary, and the pooled RR was exploratory (RR 1.10, 95% CI 0.65 to 1.86). Three studies compared axial-extension restorations with crowns, but these heterogeneous comparisons were not pooled and remained inconclusive. Current in vitro evidence is insufficient to determine whether the evaluated axial-extension designs affect failure load or the occurrence of review-defined severe failure. Imprecision, methodological heterogeneity, and indirectness for clinical performance preclude claims of clinical superiority. A routine strength benefit of the evaluated axial-extension designs cannot be inferred. Standardized preparation definitions, testing protocols, and failure reporting are required. Registration: OSF, DOI 10.17605/OSF.IO/9PXE5 (retrospective).

Journal of Functional Biomaterials doi: 10.3390/jfb17100496

Authors: Igor A. Eisenach Elena L. Lushnikova Galina A. Lapii Alexey V. Kuznetsov Larisa Y. Kostina

The replacement of polypropylene with biodegradable polymers for surgical reinforcement of musculo-fascial structures is of considerable clinical interest. A study in 98 laboratory rats with implanted polypropylene or biodegradable biopolymer demonstrated the formation of dense irregular connective tissue at the surgical site instead of biopolymer and dense regular connective tissue around the polypropylene. The fibroblastic response to the biopolymer lagged behind that to polypropylene by approximately nine months, reflecting gradual polymer degradation, but did not differ between groups at 12 months, when the biopolymer had completely biotransformed. In both groups, newly formed connective tissue contained numerous elastic fibers and relatively fewer type I (COLI) and type III (COLIII) collagen fibers compared with intact preoperative tissue. In peri-implant tissue from both groups, COLIII fibers significantly predominated over COLI, with a higher volume fraction of COLIII around the polypropylene than around the biopolymer, whereas COLI was significantly more abundant in intact tissues. These findings are consistent with the good extensibility and low tear resistance of newly formed connective tissue. In the polypropylene group, polymer filaments reinforced this tissue mechanically. Further analysis of explanted tissues is required to determine the functional properties of connective tissue remodeled at the site of a degraded biopolymer implant.

Journal of Functional Biomaterials doi: 10.3390/jfb17100495

Authors: Yuehua Li Lei Zheng Bernadette Quah Wei Seong Toh Bozhi Hou Xin Yang Raymond Chung Wen Wong

Polycaprolactone (PCL) is a biodegradable polymer widely used in bone tissue engineering; however, its regenerative performance in cranial defect models remains incompletely characterized. This systematic review and meta-analysis evaluated the effect of PCL scaffolds on bone regeneration in preclinical cranial defect models. PubMed, Embase, Web of Science, and Scopus were systematically searched, and eligible animal studies were selected according to predefined criteria. A total of 37 studies were included in the systematic review. Data on scaffold characteristics, animal models, and osteogenic outcomes were extracted, followed by random-effects meta-analysis and meta-regression to investigate potential sources of heterogeneity. PCL-based scaffolds significantly enhanced bone regeneration at one and two months post-surgery, with pooled mean differences of 1.68 (95% CI: 0.34–3.03; p = 0.01) and 5.60 (95% CI: 3.48–7.72; p < 0.00001), respectively. The treatment effect was greatest at two months but decreased at three months and was no longer statistically significant (MD = 2.22, 95% CI: −1.36–5.80; p = 0.22). Extreme between-study heterogeneity was observed across the time-point analyses, limiting the consistency and generalizability of the pooled estimates. Meta-regression identified animal species as a significant moderator at one month, accounting for 28.8% of the estimated heterogeneity, whereas follow-up duration and defect size were not significant moderators. Overall, PCL-based scaffolds demonstrate a beneficial but potentially time-dependent effect on bone regeneration, while their long-term regenerative performance remains uncertain.

Journal of Functional Biomaterials doi: 10.3390/jfb17100494

Authors: Hayriye Zehra Türk Ebru Akleyin

Objective: The aim of this study was to comparatively evaluate the effects of fluoride- and casein phosphopeptide–amorphous calcium phosphate (CPP-ACP)-containing products and commercial pediatric dentifrices containing herbal ingredients (propolis, ginger, aloe vera, and rosemary) on artificially induced initial caries lesions in primary tooth enamel using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Materials and Methods: Eighty caries-free primary molars were randomly allocated into eight groups (n = 10): two control groups (sound and demineralized enamel), a fluoride group, a CPP-ACP group, and four commercial herbal dentifrice groups containing propolis, ginger, aloe vera, or rosemary. Artificial initial enamel lesions were created in all specimens except those in the positive control group. During a 7-day pH-cycling protocol, the treatment groups received standardized dentifrice slurry applications twice daily for 4 min. At the end of the experimental period, enamel surfaces were evaluated using SEM-EDX. Statistical analyses were performed using one-way analysis of variance (ANOVA) and the Kruskal–Wallis test, as appropriate (p < 0.05). Results: SEM analysis revealed a comparatively compact and homogeneous surface appearance in the fluoride group, while the ginger group showed a relatively homogeneous surface morphology among the commercial herbal dentifrice groups. EDX analysis showed no statistically significant differences among the groups in Ca wt% (p = 0.085), Ca at% (p = 0.077), atomic Ca/P ratio (p = 0.138), or weight Ca/P ratio (p = 0.126). Significant between-group differences were observed for both P wt% (p = 0.008) and P at% (p = 0.005), as well as O wt% (p = 0.022) and O at% (p = 0.020). Conclusions: The tested products produced qualitative differences in enamel surface micromorphology and significant differences in some EDX-derived relative elemental percentages; however, Ca percentages and Ca/P ratios did not differ significantly among the groups. Therefore, the observed numerical and morphological variations should not be interpreted as evidence of superior mineral gain or remineralization efficacy. Further in situ and in vivo studies are required to determine the clinical relevance of these findings.

Journal of Functional Biomaterials doi: 10.3390/jfb17100493

Authors: Ze-Dong Cai Yao-Wen Zhang Xin-Ru Zou Jia Ju Chao Fang Ming-Kai Li Bang-Le Zhang

Diabetic wound healing remains a challenge due to persistent oxidative stress, defective angiogenesis and bacterial infection. Herein, a multifunctional hydrogel Y/PDA@HAPLL was engineered via Schiff-base crosslinking between oxidized hyaluronic acid (OHA) and ε-poly-L-lysine (ε-PLL) and incorporating Y-27632 (Y, R-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride) and polydopamine (PDA). The formulation was optimized using response surface methodology, thus achieving rapid gelation (3.8 s), strong tissue adhesion (10 kPa) and excellent stretchability. Under 808 nm laser irradiation, Y/PDA@HAPLL exhibited stable photothermal conversion and good antibacterial activity to effectively eradicate the bacterial biofilms and achieve >99% killing of S. aureus and E. coli. In vitro, skin re-epithelialization (keratinocyte proliferation and migration) and endothelial repair (tube formation) under high glucose were promoted by Y/PDA@HAPLL. In the diabetic mice with infected wounds, Y/PDA@HAPLL significantly accelerated wound closure and tissue regeneration by combining PTT antibacterial activity, ROS scavenging, endothelial repair, angiogenesis, and re-epithelialization, while concurrently downregulating ROCK1 and p-DRP1, upregulating p-eNOS and CD31, reducing mtROS, and promoting collagen deposition and remodeling. In addition, no organ damage and hepatorenal toxicity were observed during treatment period. Taken together, Y/PDA@HAPLL provided a multifunctional paradigm for the combined therapy of infected diabetic wounds by integrating rapid gelation, PTT antibacterial activity, and regeneration promotion.

Journal of Functional Biomaterials doi: 10.3390/jfb17100492

Authors: Carolyn Clark Megumi Ishii Kyle Chen Mengxue Xia Ahmed Suliman Sameer B. Shah

Objective. This meta-analysis aimed to assess the effectiveness of stem cell–seeded conduits compared with autografts and empty conduits in preclinical models of peripheral nerve repair. Methods. A systematic review and meta-analysis was conducted of in vivo preclinical studies published between 2013 and 2024. Endpoints included muscle mass ratio, sciatic function index (SFI), nerve conduction velocity (NCV), compound muscle action potential (CMAP) amplitude, and nerve conduction latency. Studies were further classified by stem cell type, graft material, species, and defect length. Results. Across 30 studies, both stem cell–seeded conduits and autografts outperformed controls across functional and electrophysiological measures. Early improvements (0–3 months) in muscle mass ratio were observed with both stem cell grafts (p = 0.014) and autografts (p = 0.027). SFI improved significantly in both groups at early time points, with stem cell grafts maintaining significance beyond 3 months (p = 0.04). CMAP amplitude showed early gains for both stem cell grafts (p < 0.001) and autografts (p < 0.001), with autografts performing slightly better initially (p = 0.033). NCV improved in both groups early, with stem cell grafts maintaining significance beyond 3 months (p = 0.007). Autografts showed early improvements in latency (p = 0.048), whereas stem cell grafts trended toward benefit without reaching significance. Conclusions. These findings suggest that stem cell–seeded grafts may provide functional benefits similar to autografts in peripheral nerve repair compared with empty conduits. Clinically, this method could be valuable when autografts are unavailable or when harvesting is contraindicated.

Journal of Functional Biomaterials doi: 10.3390/jfb17100491

Authors: Xincheng Lin Yichun Zheng Ziqiao Zhong Lu Gan Chuanbin Wu Xin Pan Wenhao Wang Ying Huang

Oral mucosal diseases often lead to structural damage and functional impairment due to high recurrence and malignant progression. Current therapeutic outcomes remain unsatisfactory owing to the complex oral microenvironment. Recent reviews have covered individual aspects of oral mucosal drug delivery, such as bioactive materials, mucoadhesive systems, and nanocarriers, but few have considered all four interrelated dimensions, including saliva-mediated adhesive barriers, epithelial permeability, biomechanical adaptability, and translational bottlenecks, in an integrated manner. The present review offers an attempt to consolidate these dimensions into one framework, aiming to provide readers with a more comprehensive perspective on the challenges inherent in this field. To underpin this framework, we conducted a structured literature search covering Web of Science (2015–2026), with predefined inclusion/exclusion criteria, followed by thematic synthesis. We first summarize the clinicopathological features and current treatment landscape of major oral mucosal diseases. We then dissect three critical barriers to transmucosal delivery: adhesive interference by salivary flow, epithelial tight junction resistance, and dynamic biomechanical forces (e.g., chewing, tongue movement). Drawing on saliva and mucosa interfacial physics, we rationalize the need for wet-adhesive material design and survey diverse mucoadhesive polymers and formulations, detailing their binding mechanisms. For epithelial penetration, we highlight design principles of microneedles and nanocarriers while critically discussing their dual-edged safety–efficacy profiles. To cope with the highly deformable oral biomechanical environment, we propose mechanical property matching and asymmetric structural designs. Finally, we outline key translational bottlenecks and future breakthroughs. This review offers an integrated, barrier-informed guide for next-generation oromucosal formulations.

Journal of Functional Biomaterials doi: 10.3390/jfb17100490

Authors: Dhiraj Kumar Taruna Singh Tristen Nies Grace S. Liu Maycoll Johnson David Mei Wandi Gu Conrado Aparicio Isha Mutreja Robert S. Jones

Mesoporous silicate nanoparticles are known for their pore size, pore volume, high surface area, and tunable surface properties and, as a result, have found application in medicine, healthcare, advanced materials, and devices. Furthermore, tailoring the silicate domain with certain metals has advanced the tissue engineering properties by moderating the cellular function at the molecular level for therapeutic response. However, limited efforts have been made to explore systemic synthesis protocols that could change structure or shape of mesoporous metal silicate nanostructures as the change in shape has inherent potential to tailor biological response. Here, we have focused on using Design of Experiments (DoE) to optimize reaction conditions for the synthesis of mesoporous strontium silicate nanostructures (MPSrSiO2 NSs) (nanoparticles—NPs and nanorods—NRs) with different physicochemical properties. The conditions allowed a change in shape from NPs to NRs by tailoring the concentration of liquid ammonia (liq. NH3, NH4OH, 82.7 mM to 248.2 mM) during the pre-synthesis incubation state. The MPSrSiO2 NPs had a significantly higher zeta potential compared to NPs (p = 0.0061). Also, NPs possessed significantly higher surface area (p = 0.0306), pore diameter (p = 0.0003), and pore volume (p = 0.0004) than NRs. In addition, the optimized reaction conditions allowed modulation of the physicochemical properties such as surface area, surface charge, amount of metal, pore diameter, pore volume, tailored degradation profile and release profile of loaded drug (gentamicin). Finally, the protocol has the advantage of allowing incorporation of other metals such as cerium, rhodium, and ruthenium independently and/or in combination.

Journal of Functional Biomaterials doi: 10.3390/jfb17100489

Authors: Elmira Sadat Tabatabaei Ozge Sagir Morgan Bretches David Long Shang-You Yang Eylem Asmatulu

Adjuvant therapy following breast cancer surgery remains challenged by systemic toxicity, poor tumor accuracy, and tumor recurrence. Electrospun nanofibers have emerged to address these concerns. Their high surface area, tunable porosity, and controlled drug release properties enable sustained, site-specific drug release directly to the tumor site while sparing healthy tissues and reducing systemic exposure. The scientific question of the current review is centered on whether the utilization of electrospun nanofibers prevents tumor recurrence after breast cancer surgery. Electrospun nanofiber design determinants, including composition, architecture, creation techniques, and drug-loading strategies, are outlined in the following analysis. Subsequently, it also examines different therapeutic approaches, such as protein- and peptide-loaded fibers, stimuli-responsive nanofibers, natural anticancer compounds, immunomodulators, and combination therapies. Notably, the application of electrospun nanofibers in breast cancer treatment, overcoming tumor microenvironment barriers, and preventing post-surgical recurrence is reported. Finally, limitations associated with clinical translation, such as large-scale production, regulatory approval, sterilization, and long-term efficacy, are also addressed. Collectively, the evidence indicates that electrospun nanofibers show great potential for localized cancer therapy by enabling controlled drug release and reducing systemic exposure, though clinical validation remains the critical unmet step.

Journal of Functional Biomaterials doi: 10.3390/jfb17100488

Authors: Yu Xia Yong Cao Subhan Mahmood Sonia Mukwana Shun Yao

Background: Effective removal of tenacious calculus and extrinsic stains without oral irritation remains a major challenge in dental cleaning. Deep eutectic solvents (DESs) are tunable green solvents, but their potential for dental care is largely unstudied. This study screened DESs assembled from food-grade starting components and evaluated their cleaning efficacy, antibacterial activity and preliminary biosafety. Methods: Twelve DESs were synthesized and characterized. Their solubilization toward dental stain-related components was tested under stirring, ultrasonication and electro-stirring. The best-performing DESs were further assessed on natural dental calculus and stained bovine teeth, with comparison against commercial dental cleaners. Antibacterial effects and biosafety were also determined. Results: Hydrophilic low-pH DES-3 (maleic acid-xylitol) and DES-5 (lactic acid-citric acid-xylitol) efficiently dissolved calcium phosphate and pigments, while hydrophobic DES-12-P emulsion performed best for oily stains. Cleaning performance depended on DES concentration and agitation approaches. The optimized DES outperformed commercial products for complex mixed stains on bovine teeth with no enamel damage. It also displayed potent antibacterial effects against Staphylococcus aureus and Escherichia coli, with good biosafety in zebrafish tests. Conclusions: DESs exhibit favorable cleaning and antibacterial performance under the tested in vitro conditions, suggesting their potential as a candidate strategy for dental hygiene and oral care applications.

Journal of Functional Biomaterials doi: 10.3390/jfb17100487

Authors: Berta Furió-Alonso María del Carmen De Lama-Odría Lucía Pallarés Danica Nikolic-Jovanovic Javier Gil Andreu Puigdollers

Fixed orthodontic appliances create retention sites for bacterial biofilm, increasing the risk of white spot lesions and periodontal complications. Silver ion (Ag) implantation offers a potential solution by conferring antimicrobial properties while preserving mechanical integrity. This study evaluated the physicochemical properties, Ag release, biocompatibility, and antibacterial efficacy of AISI 301 stainless-steel orthodontic brackets (Ormco Bios) modified by silver ion implantation using a Pulsed Filtered Cathodic Arc Vacuum System. Physical and micro-structural surface characterizations—including SEM/EDS, interferometric roughness analysis, contact angle measurements, nanoindentation hardness testing, and friction coefficient determination (under dry and saliva-lubricated conditions)—were conducted directly on the modified brackets. In compliance with international testing standards requiring defined geometric areas, AISI 301 flat samples of same chemical composition and microstructure were used to quantify Ag release in artificial saliva (cumulative silver ion release in artificial saliva was quantified via ICP-MS over time, with measured concentrations corrected for the volume extracted at each sampling interval), as well as to perform in vitro biological (human fibroblast cytocompatibility) and microbiological assays against seven bacterial strains (Streptococcus mutans, Streptococcus gordonii, Lactobacillus salivarius, Lactobacillus acidophilus, Porphyromonas gingivalis, Enterococcus faecalis, and Staphylococcus aureus). SEM/EDS confirmed successful Ag incorporation (0.93 wt.%) on the brackets. Surface roughness remained unchanged (0.16–0.17 mm), whereas hydrophilicity, surface energy, and nano-hardness increased significantly. Friction coefficients decreased under both dry and saliva-lubricated conditions. ICP-MS analysis revealed Ag release stabilizing at 119 ± 5.0 ppb after one week. Biocompatibility testing demonstrated no cytotoxic effects on fibroblasts. Furthermore, modified surfaces exhibited marked antibacterial activity against Lactobacillus spp., P. gingivalis, E. faecalis, and S. aureus, though no significant inhibition was observed against S. mutans or S. gordonii. Ag ion implantation directly improves the mechanical and tribological properties of stainless-steel orthodontic brackets. The use of standardized specimens confirmed steady Ag release, cytocompatibility, and selective antibacterial efficacy, supporting Ag implantation as a viable surface modification strategy for clinical orthodontic applications.

Journal of Functional Biomaterials doi: 10.3390/jfb17100486

Authors: Ecehan Hazar Ahmet Hazar Roda Seseogullari-Dirihan Arzu Tezvergil-Mutluay

Background/Objectives: This study evaluated the effects of endodontic irrigation protocols on the apparent elastic modulus and post-treatment total endogenous matrix metalloproteinase (MMP) activity of mineralized radicular dentin. Methods: Radicular dentin beams obtained from 60 extracted single-rooted teeth were allocated to six groups: distilled water, 2.5% sodium hypochlorite, 17% ethylenediaminetetraacetic acid (EDTA), 7% maleic acid (MA), 1% phytic acid (IP6), and 5% IP6. Apparent elastic modulus was determined before and after immersion using three-point bending, while total MMP activity was quantified using a generic colorimetric assay. Data were analyzed using two-way mixed ANOVA, Welch’s ANOVA with Tamhane’s T2 post hoc test, and Spearman’s correlation (α = 0.05). Results: A significant irrigation protocol × time interaction was observed for apparent elastic modulus (p < 0.001), with the greatest reductions following 7% MA and 5% IP6 treatment. Relative total MMP activity differed significantly among the irrigation protocols [Welch’s F(5, 23.05) = 36.285, p < 0.001] and was highest following 7% MA and 5% IP6 treatment. No statistically significant difference in relative total MMP activity was detected between the 1% IP6 and 17% EDTA protocols (p = 0.086). ΔEM% and relative total MMP activity were negatively correlated in the pooled analysis (rs = −0.679, p < 0.001); however, this association was no longer statistically significant after adjustment for irrigation protocol (partial rs = −0.146, p = 0.288). Conclusions: Protocol-dependent responses were observed. Low-concentration IP6 warrants further investigation as a potential EDTA alternative, although equivalence and clinical substitutability remain unestablished.

Journal of Functional Biomaterials doi: 10.3390/jfb17100485

Authors: Francisco Miguel Sanchez-Sosa Cristina Jimenez-Marcos Julia Claudia Mirza-Rosca Ionelia Voiculescu

Magnesium has been of interest to researchers as a potential biodegradable alternative to metal orthopedic implants due to its biocompatibility and mechanical properties that are similar to those of bone. However, magnesium implants corrode more quickly than would be beneficial. This study focused on the influence of calcium modification on the microstructure and mechanical and electrochemical degradation (in simulated body fluids at 25 °C and 40 °C) of selected Mg-Zn alloys. Four alloys, Mg1Zn, Mg2Zn, Mg1Ca1Zn, and Mg1Ca2Zn, were fabricated by levitation induction melting under an argon atmosphere. Microstructural characterization was performed using optical microscopy and SEM/EDS analysis, mechanical behavior was evaluated by microhardness testing and Gaussian mixture modeling, and corrosion performance was assessed in Ringer’s lactate solution. The results indicated that calcium addition modified the microstructural morphology. Moderate Ca addition modified the distribution of secondary phases and altered the local mechanical response of the Mg matrix. Among the investigated compositions, Mg1Ca1Zn exhibited the best balance between the microstructural characteristics, mechanical properties, and corrosion resistance. These results provide useful criteria for the further development of Mg-based alloys for temporary bone fixation applications, particularly where compressive loading is predominant.

Journal of Functional Biomaterials doi: 10.3390/jfb17100484

Authors: Zhanna Alsar Aisarat Gajimuradova Nurtai Gubaidullin Nurzhan Serik Fariza Zhagipar Zinetula Insepov

Diatomite combines a highly porous structure with strong sorption capacity, making it an attractive material for use in medical face masks. In this study, natural diatomite from the Zhalpak deposit (Mugojar Mountains, Kazakhstan) was subjected to sequential physicochemical modification to develop a sorbent for this application. This treatment sequence substantially altered the chemical composition, pore structure, and crystalline phases of the material, resulting in the modified sorbent DE-H2SO4-600f. Its interaction with Enterococcus faecium differed markedly from that of untreated diatomite: after 7 h of contact, recoverable viable bacterial counts were reduced approximately 1200-fold relative to the initial level. In a separate experiment at a high sorbent-to-liquid ratio, no bacterial growth was detected after 24 h under the tested conditions. These findings demonstrate a pronounced reduction in recoverable viable bacteria following contact with the modified diatomite and support its potential future incorporation as a functional component in medical face masks and related respiratory-protection systems.

Journal of Functional Biomaterials doi: 10.3390/jfb17100483

Authors: Liliana Andrea Silva Pedro Sousa Gomes Maria Helena Fernandes Marta García-García Octavi Camps-Font

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Journal of Functional Biomaterials doi: 10.3390/jfb17100482

Authors: Jan Łoginoff Zuzanna Popińska Agata Majos Marcin Elgalal

Background: Custom subperiosteal implants represent an alternative for severe jaw atrophy, yet long-term quantitative bone predictors remain limited. This retrospective study aimed to evaluate 5-year implant survival and determine preoperative volumetric bone thresholds using 3D CT segmentation. Methods: The unit of analysis was individual implant sites in 40 patients (25 maxillae and 15 mandibles). Primary outcomes were 5-year cumulative implant survival (Kaplan–Meier method) and preoperative total jaw bone volume (cm3) measured via standardized 3D segmentation using BrainLab software (version 1.7.0.116). Group comparisons between surviving and failed sites were performed with 95% confidence intervals (CIs). Results: Overall 5-year Kaplan–Meier implant survival was 77.5% (31/40; 95% CI: 64.6–90.4%). Maxillary sites achieved a survival rate of 80.0% (20/25; 95% CI: 64.3–95.7%), whereas mandibular sites achieved 73.3% (11/15; 95% CI: 51.0–95.6%). Preoperative jaw bone volume was significantly lower in failure cases across both maxillary and mandibular cohorts (p < 0.05). Nine implants failed due to biological (n = 4), mechanical (n = 2), or combined (n = 3) complications. Conclusions: Residual bone volume exhibits a statistically significant association with framework survival, whereas the categorical Cawood and Howell classification showed no statistically significant association in this cohort. These findings suggest that continuous volumetric assessment may serve as a useful exploratory parameter for surgical risk stratification, though predictive superiority requires validation in larger, adjusted multivariable models.

Journal of Functional Biomaterials doi: 10.3390/jfb17100481

Authors: Marcin Wekwejt Kaja Stanisławska Dawid Kozień Anna Ronowska Justyna Kozłowska

Magnesium phosphate cements (MPCs) are promising bone substitutes, but rapid setting, high exothermicity, and poor handling limit their clinical application. This study developed a dual-setting MPC by integrating chitosan-derived hydrogels into the cement matrix. Zinc ion-crosslinked carboxymethyl chitosan (CMCS) and thermosensitive chitosan/β-glycerophosphate (CS/GP) hydrogels were initially evaluated as modifiers of borax-containing (0.5% B) MPC formulations, after which the CS/GP formulation was further optimized by varying the CS (1.0/1.5%) and GP (5.6%/8.0%) concentrations. The effects of these modifications on setting behavior, physicochemical characteristics, mechanical performance, biodegradation, and cytocompatibility were systematically investigated. The B/CS/GP systems prolonged setting time, reduced the reaction temperature, moderated pH evolution, and markedly improved qualitative injectability and cohesion. XRD, FTIR, and SEM confirmed preservation of the characteristic phase composition, chemical structure, and microstructure. All formulations maintained favorable mechanical properties and supported osteoblast viability above the threshold. Among the investigated groups, the cement containing 0.5% B, 1.5% CS, and 5.6% GP exhibited the most balanced performance, combining improved handling characteristics with enhanced compressive strength. These findings demonstrate that the integration of CS-derived hydrogels, particularly the thermosensitive CS/GP system, provides a promising strategy for developing injectable dual-setting MPCs with improved handling characteristics without compromising their fundamental physicochemical and biological properties.

Journal of Functional Biomaterials doi: 10.3390/jfb17100480

Authors: Sarah M. Alnafaiy Nawaf Labban Alhanoof Aldegheishem Refal Albaijan Saad S. AlResayes Mohammed Aldhafyan

Despite the increasing use of additively manufactured restorative materials, comparative information regarding their surface gloss and roughness after different surface treatments and simulated oral challenges remains limited. This study evaluated the gloss and surface roughness of stained and polished 3D-printed resins subjected to acidic storage followed by simulated tooth brushing. Two 3D-printed resins (ONX and Tough 2 [T2]) were compared with a milled material (Lava Ultimate [LU]), which was used as a control. A total of 120 specimens (40 per material) were fabricated, surface-treated (stained or polished), and randomly categorized into acid or water storage/tooth brushing. A gloss meter and non-contact profilometer were used to measure the gloss and surface roughness of the materials. Data analysis was performed using one-way ANOVA, Welch’s pairwise t-tests with Holm adjustment, and HC3-robust Type III factorial models, with significance set at α = 0.05. Gloss significantly decreased, whereas surface roughness (Ra) significantly increased after storage/brushing across the experimental groups (p < 0.05), except for T2 subjected to acid storage/brushing, which showed no significant change in Ra (p = 0.11). Both gloss and Ra were significantly affected by the material type (p < 0.001). For gloss, significant effects of material and surface treatment were observed (p < 0.001). For Ra, significant effects of material, surface treatment, and storage/brushing were detected (p < 0.001). Material type and surface treatment significantly influenced gloss, whereas storage/brushing effect had no significant effect. In contrast, material type, surface treatment, and storage/brushing significantly influenced surface roughness. The milled LU generally exhibited higher gloss and lower roughness than the 3D-printed ONX and T2 materials, particularly among stained specimens, while ONX generally showed more favorable surface properties than T2.

Journal of Functional Biomaterials doi: 10.3390/jfb17090478

Authors: Hale Arikan Kalayci Mustafa Baris Guncu

This study evaluated the effects of misfit type, magnitude, and location on the stress distribution in full-arch screw-retained implant frameworks. A maxillary finite element model with four implants was analyzed under 16 scenarios, characterized by horizontal misfits of 10, 50, 100, and 200 µm; vertical misfits of 10 and 100 µm; and combined 10–10 and 100–100 µm misfits, each positioned anteriorly or posteriorly. Forced seating was simulated using prescribed displacement; no occlusal load or screw preload was applied. Von Mises stresses were evaluated in the framework, occlusal screws, and implants, and principal stresses were assessed in peri-implant bone. Framework stress increased with horizontal misfit magnitude. When the same numerical misfit value (10 or 100 µm) was applied at the same location under otherwise identical model conditions, vertical misfit produced higher framework stress than horizontal misfit, indicating a direction-dependent response associated with different seating deformation modes. The posterior 100–100 µm combined misfit produced the maximum framework (356 MPa), occlusal screw (193 MPa), and implant (250 MPa) stresses. In contrast, the maximum principal stress peaked at the posterior bone site with the anterior 200 µm horizontal misfit (V0 H200 A; 77 MPa), while the most negative minimum principal stress occurred at the posterior bone site with the posterior 200 µm horizontal misfit (V0 H200 P; −52 MPa). Among the tested scenarios, combined misfits yielded the highest framework and screw stresses, whereas implant and bone responses depended on the magnitude and location of the misfit. These findings indicate that the types, magnitudes, and locations of misfits should be considered during framework-fit assessments, with particular attention to combined misfits, before definitive seating.

Journal of Functional Biomaterials doi: 10.3390/jfb17090479

Authors: Saya Hadi Raouf Varvara Platania Argyro Lamprou Youri Arntz Iryna Lysova Diyar Khalid Bakr Niaz Hamaghareeb Hamasaeed Mutlu Özcan Isaac Maximiliano Bugueno

Biodegradable polymeric scaffolds incorporating bioactive mineral phases are a promising approach for dentin-pulp tissue engineering. Although poly(lactic-co-glycolic acid) (PLGA) microparticles have been widely used as scaffolds due to their biocompatibility and tunable degradation profile, their inherent bioactivity is limited. Furthermore, fluorapatite (FAP), a fluoride-substituted apatite ceramic, exhibits enhanced chemical stability and mineral-related properties that may be useful for regenerative biomaterial design. In this study, we investigated the effect of nano-FAP functionalization on the physicochemical properties of porous PLGA microscaffolds and their interaction with human dental pulp stem cells (hDPSCs). Porous PLGA microscaffolds were fabricated using a double-emulsion solvent evaporation method and subsequently functionalized with FAP suspensions ranging from 0.1 to 5 mg/mL (0.01–0.5% w/v). The scaffolds were evaluated using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), electrical conductivity measurements, cell viability assays, and immunofluorescence. Lower and intermediate FAP concentrations-maintained surface pore accessibility and supported hDPSC viability, whereas the highest concentration (5 mg/mL; 0.5% w/v) reduced visible surface pore size and showed less favorable cellular responses. The 2.5 mg/mL (0.25% w/v) FAP condition provided the most favorable overall balance among the evaluated physicochemical and biological parameters. These preliminary in vitro findings support further investigation of FAP-functionalized PLGA microscaffolds in advanced three-dimensional and in vivo models.

Journal of Functional Biomaterials doi: 10.3390/jfb17090477

Authors: Anushri Warang Linfeng Wu Qingsong Yu Liang Hong Hongmin Sun

This study investigates the feasibility of fluoride delivery via fluoride-generating nonthermal atmospheric plasma (FNTAP) and its antimicrobial effects on in vitro triple-species oral biofilms. FNTAPs were generated by adding 5 or 10 sccm (standard cubic centimeters per min) 1,1,1,2-tetrafluoroethane (TFE) to atmospheric argon (3000 sccm) nonthermal plasma (ArNTAP). Reactive plasma species were measured in plasma-treated phosphate-buffered saline (PBS). Twenty-four-hour biofilms were constructed from Streptococcus mutans, Streptococcus sanguinis, and Candida albicans for assessing the antimicrobial effects of FNTAPs via viability assays and colony-forming unit (CFU) assays. FNTAP treatments significantly increased the concentrations of F− and NO2− in PBS compared to ArNTAP treatments (p < 0.01), and decreased the concentrations of H2O2 and NO3− in PBS (p < 0.001, p < 0.05). 5 sccm 2 min FNTAP treatment reduced biofilm viability by 94.12 ± 1.03% (p < 0.001), compared to a 69.32 ± 2.05% (p < 0.001) reduction with ArNTAP. CFU assays showed that FNTAPs were especially efficacious against C. albicans. 5 sccm 3 min FNTAP treatment reduced fungal log10 CFUs by 4.28 ± 0.36 (p < 0.001). Fungal CFUs were below detectable levels for the 10 sccm 2 and 3 min groups, except for two data points in each group. In conclusion, FNTAP effectively produced measurable fluoride in PBS and significantly enhanced antimicrobial efficacy against triple-species biofilms, highlighting its potential as a multifunctional tool for caries control.

Journal of Functional Biomaterials doi: 10.3390/jfb17090476

Authors: Gi-Woong Hong Yerin Park Doo Yeoul Chang Jeesoo Kook Young Bin Lim Ho Lee Kyu-Ho Yi

Background: Hydroxylapatite is a biocompatible calcium-phosphate ceramic used in regenerative biomaterials. Calcium hydroxylapatite (CaHA) fillers combine immediate mechanical support with subsequent extracellular matrix remodeling, and their material behavior depends on microsphere morphology, mineral composition, carrier interactions, and rheology. Objectives: To determine whether a CaHA formulation prepared using Lattice Pore Formation technology (Facetem) exhibits a distinct and internally consistent material profile across microsphere geometry, lattice-pore surface architecture, mineral composition, formulation-level sedimentation, and rheological behavior across dilution ratios, with selected morphology and sedimentation characteristics compared with Radiesse. Methods: Facetem (marketed in the Republic of Korea as DCLASSY) was evaluated as the test product, with Radiesse used as the comparator product. Microspheres were examined using field-emission scanning electron microscopy and laser-diffraction particle-size analysis. Surface morphology was assessed before and after 12 weeks of phosphate-buffered saline (PBS) incubation. Mineral composition was evaluated using X-ray diffraction and inductively coupled plasma optical emission spectroscopy. Extrusion continuity and sedimentation after saline dilution were evaluated, and rheological properties were measured across eight dilution ratios using saline, non-cross-linked hyaluronic acid, and semi-cross-linked hyaluronic acid. Results: Facetem had a mean particle diameter of 34.60 μm, with higher circularity (0.95 versus 0.88) and roundness (0.96 versus 0.85), a lower aspect ratio, and fewer particles below 20 μm (2.10% versus 14.50%) than Radiesse. Micrograin domains formed a lattice-pore surface that showed morphological changes after 12 weeks of PBS incubation while the spherical contour remained recognizable. Hydroxylapatite represented 99.09% of the mineral phase, with a Ca/P ratio of 1.67. Facetem extruded as a continuous strand and showed greater supernatant clarification after dilution. Storage modulus declined with dilution, and semi-cross-linked hyaluronic acid retained more elastic resistance than saline at equivalent ratios. Conclusions: Facetem demonstrated a consistent microsphere population, an organized lattice-pore surface, hydroxylapatite stoichiometry, and diluent-dependent rheology. The integrated analysis defines its physicochemical profile; the PBS findings should be interpreted as morphological stability under non-biological buffer conditions rather than in vivo degradation.

Journal of Functional Biomaterials doi: 10.3390/jfb17090475

Authors: Merve Dede Ozgun Yusuf Ozyilmaz Ozge Doganay Ozyilmaz Gamze Hanci Abay

Evidence regarding tantalum nitride (TaN)-coated gold abutment screws is lacking, and studies on diamond-like carbon (DLC)-coated and anaerobic adhesive-coated abutment screws remain limited. This study evaluated the reverse torque values (RTVs) of abutment screws with different surface modifications. Sixty abutment screws from the same implant system were divided into five groups (n = 12): gold, TaN-coated gold, titanium, DLC-coated titanium, and anaerobic adhesive-coated titanium. Abutments were tightened according to the manufacturer’s recommended torque. Specimens were then subjected to cyclic loading (50 N, 1 Hz, 480,000 cycles) in a dual-axis chewing simulator, after which RTVs were evaluated. ANOVA showed a significant difference only for the uncoated gold screw group (p < 0.05). The lowest RTVs were observed in the gold screws. Although the differences among the modified screw groups were not statistically significant, surface-treated screws demonstrated higher and more stable RTVs than their uncoated counterparts. TaN-, DLC-, and anaerobic adhesive-treated screws exhibited higher RTVs following cyclic loading, suggesting that these surface modifications may enhance screw stability and reduce the risk of abutment screw loosening.

Journal of Functional Biomaterials doi: 10.3390/jfb17090474

Authors: Seyeon Oh Gwahn Woo Cheon Jae Ik Lee Hyoung Moon Kim Min Seung Kim Soo Jeong Heo Kuk Hui Son Kyunghee Byun

Injectable collagen biomaterials are used to modify the dermal extracellular matrix in aged skin; however, whether concentration-dependent rheological differences are associated with distinct fibroblast responses remain unclear. We compared 3% and 6% atelocollagen (AtCOL) and examined three mechanobiological programs: (i) integrin (ITG) α5β1–ERK–cyclin D1 signaling related to proliferation; (ii) ITGβ1–FAK–YAP signaling related to matrix synthesis; and (iii) ITGα11β1/Tensin-1–positive fibrillar adhesion related to collagen assembly. Under the tested oscillatory shear conditions, 6% AtCOL displayed higher storage modulus (G′), loss modulus (G″), and complex viscosity, together with a lower tan δ, than 3% AtCOL. In aged mouse skin, the 6% formulation was associated with greater increases in ITGα5, pERK1/2, cyclin D1, PCNA, pFAK, nuclear YAP, COL1A1, COL3A1, ITGα11β1/Tensin-1 co-expression signal, collagen type I/III ratio, collagen type I fiber bundle width, mature collagen content, dermal collagen density, and an instrument-derived skin elasticity index, while MMP1, MMP2, and MMP9 were reduced. In an H2O2-induced fibroblast senescence model, ITGβ1 knockdown attenuated AtCOL-associated proliferative, matrix-synthetic, and fibrillar-adhesion responses. Complementary ITGβ1 overexpression produced directionally concordant increases in ITGA11 expression, relative fibroblast proliferation, COL1A1, and COL3A1 and decreases in MMP1, MMP2, and MMP9. Collectively, these findings are consistent with a concentration-dependent, ITGβ1-centered mechanotransduction model linking fibroblast proliferation, matrix synthesis, and collagen assembly within a single AtCOL system.

Journal of Functional Biomaterials doi: 10.3390/jfb17090473

Authors: Jiacheng Yu Chengming Wang Xiue Ren Huixia Wang Yiqiang Huang Changren Zhou

Elevated levels of reactive oxygen species (ROS) and persistent inflammatory responses represent principal impediments to efficacious wound healing, particularly in mechanically dynamic or infected wound environments. Consequently, multifunctional hydrogel-based dressings capable of integrating coordinated antioxidant, anti-inflammatory, and antimicrobial activities with robust wet-tissue adhesion are highly sought after, yet their development remains limited. Herein, we introduce a curcumin-functionalized polyurethane composite dressing (designated CPFSD), engineered through the incorporation of dopamine-grafted sodium alginate (SD) and ferrocene (Fc), which collectively confer synergistic ROS modulation alongside durable tissue adhesion. Mechanistically, curcumin provides intrinsic antioxidant and anti-inflammatory properties, while Fc facilitates reversible Fe2+/Fe3+ redox cycling, thereby augmenting ROS scavenging capacity; concurrently, catechol and hydroquinone moieties present on SD establish stable interfacial interactions with moist biological tissues. Comprehensive physicochemical characterization revealed that CPFSD effectively scavenged over 80% of both DPPH and hydroxyl (·OH) radicals, exhibited greater than 80% antibacterial efficacy against Escherichia coli and Staphylococcus aureus, and demonstrated markedly enhanced adhesive performance while preserving mechanical flexibility and cytocompatibility. In vitro assays further indicated that CPFSD significantly attenuated oxidative stress in L929 fibroblasts and RAW264.7 macrophages, accompanied by downregulation of pro-inflammatory cytokine expression. In a murine full-thickness excisional wound model, CPFSD facilitated accelerated epithelialization, angiogenesis, and wound contraction, achieving wound closure at day 11 without observable systemic toxicity. Collectively, these findings underscore that rational multicomponent design strategies can yield adhesion-capable wound dressings endowed with synergistic therapeutic functionalities suitable for addressing complex pathological wound conditions.

Journal of Functional Biomaterials doi: 10.3390/jfb17090472

Authors: Souichiro Honda Daniele Botticelli Erick Ricardo Silva Samuel Porfirio Xavier Giovanna Iezzi Hitoshi Seo Shunsuke Baba

Background: This exploratory study provided a primarily descriptive comparison of two xenogeneic and two synthetic blocks for mandibular onlay augmentation in rabbits. Methods: Twelve rabbits received bilateral block grafts, providing 24 sites allocated to Bio-Oss® Block, SP-Block, ReproBone® Block, or Alos Block (n = 6/material). After 10 weeks, undecalcified sections were evaluated within standardized inferior and superior regions. Newly formed bone was the primary outcome; secondary outcomes included residual graft, IBN-like tissue, soft-tissue components, and cross-sectional augmented area. Mixed-effects models accounted for clustering within animals. Results: No statistically significant difference in newly formed bone percentage was detected among biomaterials (p = 0.475). Residual graft differed significantly (p < 0.001) and was lower for all test materials than for Bio-Oss® Block. ReproBone® Block consistently exhibited IBN-like tissue (17.3 ± 2.9%). SP-Block showed more intra-compartment soft tissue than Bio-Oss® Block. Alos Block had the smallest augmented area (12.9 ± 6.1 mm2; adjusted p = 0.001 versus Bio-Oss® Block), and extra-compartment soft tissue was present in five of six sites. Conclusions: Although newly formed bone percentages did not differ significantly, the biomaterials displayed distinct profiles of scaffold persistence, incorporation, tissue organization, and cross-sectional augmented area at 10 weeks. These features should be considered together when evaluating block biomaterials for onlay augmentation.

Journal of Functional Biomaterials doi: 10.3390/jfb17090471

Authors: Alexander Jon Cresswell-Boyes Aylin Baysan Graham Roy Davis

Background: Pre-clinical training in endodontics relies heavily on typodont teeth to develop operative skills before patient care, but conventional polymer-based typodonts differ from human teeth in their cutting response, requiring greater force and producing an unrealistic cutting experience that often dissatisfies students. Methods: This study evaluated four alternative 3D-printed typodont materials—15 wt.% carbonated hydroxyapatite, 15 wt.% Puraflake® (glass flake filler), 15 wt.% zinc oxide, and a urethane/triethylene glycol dimethacrylate resin composite—based on their cutting force, post-cut surface roughness, and perceived cutting feel relative to extracted enamel, assessed via a five-point Likert scale questionnaire completed by 46 (n = 46) fourth- and fifth-year dental students. Results: No statistically significant differences in cutting force were detected between the four printed materials and extracted enamel, a finding confirmed using formal two one-sided equivalence testing (TOST); larger confirmatory studies would allow this equivalence to be established with greater statistical precision. Perception scores differed significantly between materials, and fifth-year students rated the dental resin composite significantly more favourably than fourth-year students, with only the composite effect surviving stringent Bonferroni correction across all four material comparisons, underscoring the reliability of this specific finding. Post-cut surface roughness showed a strong, statistically robust monotonic association with perception scores at the individual-respondent level (Page’s L trend test, n = 46, p < 0.001), suggesting that surface behaviour during material removal may contribute to perceived haptic similarity. Conclusions: Matching cutting force alone does not guarantee perceptual equivalence. Among the materials tested, the dental resin composite most closely approximated extracted-enamel surface roughness, received the most favourable and consistent perception scores, and is recommended as the preferred material for pre-clinical typodont fabrication where accessible. These 3D-printed typodonts offer a standardised, openly documented alternative to commercial typodonts for pre-clinical training, with digital models and manufacturing workflows openly available via an institutional platform (TactiTooth).

Journal of Functional Biomaterials doi: 10.3390/jfb17090470

Authors: Helin Su Akyol-Kurtca Deger Ongul Bilge Gokcen-Rohlig

Background: This study investigated the fit accuracy of maxillary complete denture bases (CDBs) fabricated using conventional, fully digital, and two hybrid workflows. Methods: Thirteen edentulous patients each received four maxillary CDBs produced via conventional (C), fully digital (FD), hybrid early (HE), and hybrid late (HL) workflows. Group C employed functional impressions and heat-polymerized polymethyl methacrylate (PMMA). Group FD utilized intraoral scanning (IOS), computer-aided design (CAD), and three-dimensional printing. The HE workflow combined digitally designed custom trays with conventional impressions, while the HL workflow digitized conventional master casts prior to digital fabrication. The master cast from the C workflow served as the reference. Deviations were calculated at 22 landmarks across six anatomical regions, with overall and regional analyses performed. Results: Group C exhibited the lowest deviation, followed by HE. HL and FD groups demonstrated significantly higher deviations (p < 0.001), with no significant difference between them. Regional variations were observed across most anatomical areas, except for the posterior palatal seal (p = 0.287). Conclusions: Clinical workflow significantly influences denture base fit accuracy. Conventional and hybrid early workflows provided more predictable adaptation, whereas hybrid late and fully digital workflows showed greater deviation, particularly in functional regions, potentially affecting clinical performance.

Journal of Functional Biomaterials doi: 10.3390/jfb17090469

Authors: Marius Carnaru Vacaru Corneliu Munteanu Fabian Cezar Lupu Grigorii Deleu Ioana Ilinca Volocaru Kamel Earar

Background: The clinical success of modern dental implants requires a balance between mechanical endurance and aesthetic integration. While titanium alloy (Ti-6Al-4V) provides a reliable load-bearing core, yttria-stabilized tetragonal zirconia (Y-TZP) is frequently preferred for the cervical collar to secure optimal peri-implant soft tissue responses. Yet, fusing these materials directly creates a structural challenge, an abrupt stiffness gradient. This discontinuity promotes localized tensile stresses within the brittle ceramic component, elevating the risk of subcritical crack initiation under oblique masticatory loads. Methods: To address this challenge, we conducted a narrative review to establish the rationale for a novel Ti-PEEK-Zr tri-layered concept. This approach integrates materials science and dental biomechanics to provide a theoretical framework prior to experimental testing. Results: The synthesized data supports the integration of polyetheretherketone (PEEK) as an intermediate compliant layer. Rather than serving as an intermediate stiffness layer, PEEK operates as a viscoelastic buffer. This functional transition zone dampens oblique forces, redistributing localized stress away from the fragile rigid–rigid junction and shielding the Y-TZP collar. The modular tri-layered configuration offers a theoretically sound mechanical hypothesis, though its clinical feasibility depends on rigorous validation that must encompass not only biomechanical performance but also biological compatibility, resistance to bacterial colonization, and long-term stability under the challenging conditions of the oral environment. The practical advantages, including manufacturability, surgical handling, and cost-effectiveness, remain to be demonstrated through future experimental and numerical studies. Conclusions: The Ti-PEEK-Zr multi-material concept is a biomechanical hypothesis. By functionally isolating the roles of each material, this paradigm addresses several limitations of traditional hybrid implants, providing the basis for future finite element analyses.

Journal of Functional Biomaterials doi: 10.3390/jfb17090468

Authors: Tuty Fareyhynn Mohammed Fitri Azlin Fazlina Osman Eid Alosime Sinar Arzuria Adnan Nur Hidayah Ahmad Zaidi

The physicochemical properties of buccal films are vital for evaluating their suitability for mucosal applications. By focusing on these properties, researchers can enhance the mechanical functionality and mucoadhesion of the films. This study aimed to overcome the mechanical limitations of neat gellan gum and to produce biocomposite films with enhanced physicochemical properties and mucoadhesive properties for potential use in buccal drug delivery. Biocomposite films composed of gellan gum (GG) and pineapple stem fiber (PSF), with glycerine as a plasticizer, were prepared using the solvent casting method to develop a formulation suitable for this application. Fourier transform infrared (FTIR) spectroscopy, pH and thickness measurements, tensile test, folding endurance, swelling index, scanning electron microscope (SEM), mucoadhesion test and X-ray diffraction (XRD) analysis were conducted to determine the optimal PSF content in the GG-based biocomposite film formulation. The results indicated that the optimal formulation, GG/3PSF, was achieved with the incorporation of 3 wt% PSF relative to the GG mass. Specifically, the GG/3PSF biocomposite film exhibited a tensile strength of 17.10 ± 0.4 MPa (a 50% increase compared to neat GG), an elongation at break of 46.0 ± 2.5%, a tensile toughness of 41 ± 2.0 MPa, and an ex vivo mucoadhesive residence time of at 7.76 ± 0.51 h for GG/3PSF (compared to 3.90 ± 0.24 h for neat GG). Additionally, it maintained a moderate and optimal swelling index of 115.31 ± 2.3% after 60 min of hydration, which prevents structural instability associated with excessive swelling (such as 161.81 ± 4.7% observed in GG/7PSF), while possessing acceptable thickness (0.09 ± 0.005 mm) and neutral pH (7.0 ± 0.05). The developed buccal film is environmentally friendly due to the utilization of pineapple stem fiber, an agricultural by-product that can reduce material costs compared with synthetic fillers and shows considerable potential as a biocomposite film for buccal drug delivery applications.

Journal of Functional Biomaterials doi: 10.3390/jfb17090467

Authors: Fulya Aydin Burcu Öztürk Gülbike Demirel Özgür Irmak Arda Buyuksungur İsmail Hakki Baltacioğlu Özgür Karstarli Kaan Orhan

Self-adhesive flowable resin composites have been developed to simplify restorative procedures by eliminating separate adhesive application; however, their gingival sealing to dentin remains a concern. This study assessed the gingival marginal sealing of resin composites by measuring silver nitrate solution (AgNO3) penetration using micro-computed tomography (µCT). Materials and Methods: Seventy-five human third molars with 150 standardized cavities were allocated into 15 experimental groups based on three surface pretreatments (no pretreatment, sodium hypochlorite solution [NaOCl], and a hypochlorous acid-containing aqueous solution [HCS]) and five restorative materials: three self-adhesive flowable composites (Fusio Self-Adhesive, Vertise Flow, and Nova Compo SF) and two conventional composites (Clearfil Majesty Posterior and Clearfil Majesty Flow). Following thermal cycling, microleakage was quantified by measuring silver nitrate penetration along the gingival floor of the restorations using µCT and statistically analyzed. Results: HCS significantly reduced silver nitrate penetration in all self-adhesive composites (p < 0.05), while NaOCl significantly reduced silver nitrate penetration only in the 10-MDP-containing Nova Compo SF (p < 0.05). Conventional composites bonded with a self-etch adhesive exhibited significantly lower microleakage than self-adhesive materials (p < 0.05). Conclusions: HCS improved the gingival marginal sealing of self-adhesive flowable composites to dentin, whereas the effect of NaOCl was material-dependent. Conventional resin composites used with a self-etch adhesive demonstrated superior gingival marginal sealing compared with self-adhesive flowable composites.

Journal of Functional Biomaterials doi: 10.3390/jfb17090466

Authors: Kaiqi Peng Jingheng Liang Yiyi Huang Yixue Li Feng-Shou Liu Yan Zhou

Conventional hydrogen peroxide (HP) tooth whitening treatments frequently induce structural deterioration of enamel, necessitating the development of biocompatible and highly efficient alternatives. This in vitro study investigated the application of a novel functional biomaterial, the Type I aggregation-induced emission (AIE) photosensitizer CPTQ, for peroxide-free photodynamic tooth whitening. Under white-light irradiation (25 mW/cm2), CPTQ (12.5 μM) demonstrated rapid degradation of representative chromogenic molecules (crystal violet, malachite green, and rhodamine B). Extracted human teeth stained with both model pigments and complex beverage mixtures (coffee, tea, and fruit juices) were allocated into four treatment groups: negative control (NC), CPTQ, 7.5% HP, and 30% HP (n = 6 per group). Colorimetric parameters (ΔE00, Δa*, Δb*, and ΔL*) and enamel-related endpoints—including surface morphology, roughness, mineral composition (Ca/P), and microhardness—were evaluated over 6 h and analyzed using one-way ANOVA. For pigment-stained teeth, the photodynamic whitening efficiency of CPTQ was comparable to that of 30% HP (ΔE00, p > 0.05) during the 6 h treatment period. At 1.5 h, the ΔE00 value in the CPTQ group (23.35 ± 2.32) was significantly greater than those in the NC group (15.70 ± 1.78, p < 0.05) and the 7.5% HP group (15.02 ± 1.63, p < 0.05). For beverage-stained teeth, the whitening efficiency (ΔE00) of CPTQ was significantly greater than that of the control group at 1.5 h (6.22 ± 2.09 vs. 1.82 ± 0.56, p < 0.01) and was significantly greater than that of 7.5% HP at 4.5 h (10.94 ± 2.82 vs. 7.56 ± 1.78, p < 0.05). Crucially, unlike the change observed after 30% HP treatments, CPTQ treatment resulted in no statistically significant differences from NC in preserved enamel surface integrity, including morphology assessed by SEM, surface roughness (Ra and Sa, both p > 0.05), mineral composition (Ca and P, both p > 0.05), and microhardness (ΔHV, p > 0.05). Mechanistic investigations using reactive oxygen species (ROS) scavengers (TBA and DABCO) suggested that hydroxyl radicals generated via the Type I photodynamic pathway are the primary drivers of pigment degradation, reducing ΔE00 from 12.56 to 1.09 upon •OH inhibition. CPTQ achieved measurable in vitro whitening through a predominantly Type I ROS-mediated mechanism while causing limited changes in the evaluated enamel surface endpoints.

Journal of Functional Biomaterials doi: 10.3390/jfb17090465

Authors: Soram Oh

This study aimed to evaluate the micro-shear bond strength (μSBS) of TheraCal PT (TP), Endocem MTA Premixed Heavy (EC), One-Fil Putty (OF), and BC Universal RRM (RM) bonded to a flowable composite resin using two universal adhesives (G-Premio Bond or Prime & Bond Universal) in two etching modes (etch-and-rinse or self-etch). Disc-shaped specimens (n = 60 per pulp capping material) were allowed to set for 72 h and then divided into four groups according to the adhesive and etching mode used. The μSBS was measured using a universal testing machine. Data were analyzed with three-way ANOVA and post hoc tests for the pulp capping material. Failure modes were determined. Spectra were recorded before and after adhesive application using attenuated total reflectance–Fourier transform infrared (ATR-FTIR) spectroscopy. Three-way ANOVA revealed that the effects of the adhesive (p = 0.002), etching mode (p < 0.001), and pulp capping material (p < 0.001) on the μSBS were significant. The interaction between the adhesive and etching mode, as well as the interaction between the adhesive and pulp capping material, was significant (p < 0.001). TP exhibited higher μSBS values than EC, OF, and RM. TP failed in mixed, cohesive, and adhesive modes, whereas EC, OF, and RM failed mostly cohesively within the material. ATR-FTIR spectroscopy confirmed the functional monomer peaks on the material surfaces after adhesive application.

Journal of Functional Biomaterials doi: 10.3390/jfb17090464

Authors: Miloš Lazarević Evelina Herendija Milica Jakšić Karišik Marijana R. Pantović Pavlović Miroslav M. Pavlović Katarina R. Pantović Spajić Nenad L. Ignjatović

The study seeks to develop a multifunctional germanium-enriched nanocomposite coating on titanium and to evaluate its ability to modulate early inflammatory responses while promoting osteogenic differentiation in a dental pulp stem cell (DPSC)-based regenerative model. A multifunctional Ti/Coating composed of nanohydroxyapatite (nHAp) particles, chitosan-oligolactate (ChOL), and germanium (Ge) was developed using a combined anodizing/anaphoretic electrodeposition approach. The Ti/Coating system exhibited good biocompatibility, as confirmed by microscopy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, with cell viability consistently exceeding 90% and moderate LDH release across all time points. Annexin V/PI assay demonstrated a predominance of viable cells (>94%), while intracellular ROS analysis indicated moderate oxidative activity. Gene expression analysis revealed significant downregulation of pro-inflammatory markers (TNF-α, IL-1β, IL-6, COX-2, and MAPK), suggesting attenuation of inflammatory signalling. Flow cytometry further demonstrated reduced CD120b (TNFR2) expression, while intracellular TNF-α levels remained unchanged, indicating selective modulation at the receptor level. In addition, the Ti/Coating promoted osteogenic differentiation, as evidenced by enhanced mineralization, and upregulation of osteogenic genes (ALP, RUNX2, BMP2).

Journal of Functional Biomaterials doi: 10.3390/jfb17090463

Authors: Cristian Niky Cumpătă Călin Rareș Roman Mihaela Jana Ţuculină Ioana Smaranda Cumpătă Alexandru Burcea Cristina Maria Munteanu Mădălina Anca Moldovan Adrian Camen Sebastian Petrescu Paolo Di Francesco

Background/Objectives: Evidence comparing cement- and screw-retained implant-supported restorations remains heterogeneous, particularly in augmented posterior maxillae. This study evaluated the association between definitive retention mode and peri-implant marginal bone level at a minimum 5-year follow-up after maxillary sinus floor elevation. Methods: This retrospective clustered cohort included 248 patients and 528 bone-level implants; radiographic measurements were available for 522 implants from 247 patients. Marginal bone level was assessed by CBCT immediately after implant placement and at least 60 months later. The primary adjusted analysis used generalized estimating equations with patient-level clustering and robust standard errors. Results: Mean marginal bone level at final follow-up was 0.133 mm for cement-retained and 0.105 mm for screw-retained restorations; the unadjusted difference was not statistically significant (Mann–Whitney U = 31,366; p = 0.064). In the primary GEE model, which excluded provisional retention because of its strong collinearity with definitive retention, definitive screw retention was not associated with marginal bone level at follow-up (B = −0.0028 mm; 95% CI: −0.0165–0.0108; p = 0.684). The time × definitive retention interaction was also not significant (B = −0.0069 mm; 95% CI: −0.0187–0.0049; p = 0.249). Conclusions: Definitive retention mode was not significantly associated with marginal bone level in the primary adjusted analysis, and longitudinal marginal bone change did not differ significantly between retention strategies. Sensitivity analyses indicated that estimates were influenced by the strong collinearity between provisional and definitive retention. These observational findings do not demonstrate superiority or equivalence of either retention strategy.

Journal of Functional Biomaterials doi: 10.3390/jfb17090462

Authors: Oğuzhan Çağlayan Nihal Şehkar Oktay Hüseyin Yüce Pınar Yılmaz Atalı Başak Durmuş

Background/Aim: Restorative materials in pediatric dentistry are frequently exposed to acidic oral liquid medications, which may alter their surface properties and color. This in vitro study compared the surface roughness, three-dimensional topography, and color stability (ΔE00) of a glass hybrid restorative system (GH), a polyacid-modified composite resin (PMC), and a nanohybrid bulk-fill resin composite (NHC) following a standardized repeated-exposure protocol to two pediatric antihistamine syrups: ketotifen (Zaditen®) and cetirizine (Zyrtec®). Materials and Methods: Disc-shaped specimens were randomly allocated to three immersion subgroups per material (Zaditen®, Zyrtec®, distilled water). After baseline measurements (t0), specimens underwent 5000 thermal cycles (t1), then immersion in the assigned solution for 5 min, twice daily, for 6 days (t2). Ra and ΔE00 were evaluated quantitatively; surface degradation was further characterized descriptively using 3D optical profilometry and SEM. Data were analyzed using a three-way mixed-design ANOVA (Time × Material × Solution). Results: Antihistamine syrup exposure was associated with significant changes in surface topography and color stability (p < 0.001), with large-to-moderate effect sizes for time and its interactions. GH showed the highest Ra and largest color change, but much of this occurred after thermocycling, before syrup exposure. NHC and PMC generally showed smaller changes than GH. 3D profilometry and SEM revealed material-specific morphologies, interpreted descriptively rather than as confirmed degradation mechanisms. Conclusion: Standardized repeated exposure to ketotifen and cetirizine syrups was associated with material-dependent changes in surface topography and color stability, with GH showing the greatest change and NHC/PMC comparatively greater stability; clinical extrapolation requires further study.

Journal of Functional Biomaterials doi: 10.3390/jfb17090461

Authors: Michela Piccinini Maria Laura Belladonna Chiara Suvieri Sara Meoni Daniela Lanari Silvia Caponi Francesco Bonacci Maurizio Ricci Alessandro Di Michele Valeria Ambrogi

Chronic oral and maxillofacial diseases are frequently associated with progressive alveolar bone loss, leading to impaired structural integrity of the jaw and increased risk of implant failure, microbial colonization, and microfracture formation. Ceramic scaffolds such as those made of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) have attracted considerable attention because of their controlled resorption properties and the promotion of rapid new vital bone formation. The aim of this research is to enhance the performance of scaffolds composed of HA and β-TCP used for guided bone tissue regeneration in oral surgery. HA/β-TCP scaffolds were loaded with simvastatin (SIMV) and coated with multiple layers of alginate (ALG). The proposed strategy was designed to achieve a local and prolonged drug release while simultaneously improving mechanical properties. The scaffolds were characterized in terms of porosity, water absorption, in vitro degradation, in vitro bioactivity, and SIMV release. In addition, microscale mechanical properties were evaluated using Brillouin microscopy before and after the coating process. Cytocompatibility was further evaluated by using murine macrophages as an in vitro cellular model. The results demonstrated that ALG coatings significantly modulated SIMV release, promoting a delayed drug release. Moreover, ALG deposition improved the micromechanical properties of the scaffolds, conferring a dual structure analogous to those of bone tissue. These findings indicate that ALG-coated SIMV-loaded HA/β-TCP scaffolds represent a promising multifunctional platform for the medical field.

Journal of Functional Biomaterials doi: 10.3390/jfb17090460

Authors: Shujiang Zhang Tong He Shuhan Wang Lixin Yuan Hongjiang Liu Ruizhi Li Kun Zhang Shiwei Wang Chen Lai

Objective: This study aimed to evaluate the long-term degradation behavior, biostimulatory effects, and biocompatibility of a novel poly-L-lactic acid-block-polyethylene glycol/hyaluronic acid (PLLA–b–PEG/HA) composite filler for soft tissue augmentation. Methods: PLLA–b–PEG/HA microsphere properties were characterized via scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance hydrogen spectroscopy (1H NMR), thermogravimetry (TG) and differential scanning calorimetry (DSC). A 104-week in vivo rabbit model was established to systematically observe filler degradation and tissue responses. Ultrasound monitoring, histological staining, ELISA and RT-PCR were performed to assess volumetric changes, inflammatory reactions and collagen synthesis-related signaling. Results: Physicochemical property tests demonstrated that PLLA–b–PEG retains the fundamental physicochemical properties of pristine PLLA while exhibiting enhanced hydrophilicity. B-ultrasound demonstrated a presented uniform in vivo distribution without displacement or diffusion over time, confirming steady and predictable degradation. SEM verified progressive morphological degradation and porous evolution of the microspheres. The filler induced a mild, balanced inflammatory microenvironment with early expression of both pro-inflammatory (IL-12, TNF-α) and anti-inflammatory (IL-4) cytokines, which resolved gradually over time. Sustained TGF-β upregulation persisted throughout the 104-week observation period, driving continuous neocollagenesis and prominent neoelastogenesis, thereby achieving favorable and long-term tissue remodeling with excellent biocompatibility. Conclusions: The PLLA–b–PEG/HA composite filler exhibits controllable degradation properties and homeostatic regulatory effects, along with outstanding long-term biosafety and tissue integration capacity. As an ideal biostimulatory filler for soft tissue augmentation, it can effectively facilitate the regeneration of high-quality functional extracellular matrix rich in collagen fibers and elastic fibers, and holds promising clinical prospects for natural and long-lasting soft tissue filling applications.

Journal of Functional Biomaterials doi: 10.3390/jfb17090458

Authors: Gökçen Akgün

Angled abutments and cantilever extensions in bar-supported full-arch implant prostheses may generate bending moments and localized stress concentrations within prosthetic components and peri-implant bone. Implant-supported rehabilitation becomes biomechanically more demanding in completely edentulous patients with posterior bone resorption. Therefore, understanding how connection geometry, cantilever length, and framework material influence prosthetic design is important. In this study, a three-dimensional mandibular model generated from CT data was used to compare conventional and spherical abutment–bar connection designs in All-on-Four prostheses with 30° angled posterior abutments. Cantilever lengths of 8, 10, and 12 mm were evaluated, and Ti6Al4V Grade 5 and PEEK were assigned as alternative bar prosthesis materials. Finite element analyses were performed in ANSYS Workbench, and von Mises stress distributions were evaluated in the bar prosthesis, prosthetic screws, abutments, implants, and surrounding cortical and trabecular bone. The results showed that increasing cantilever length increased stress levels in prosthetic components and bone tissues. The spherical connection design generally reduced stresses in the most critical distal components compared with the conventional design; however, this reduction was not uniform for all components, particularly in the PEEK models. The highest stress value was observed in the posterior angled abutment of the PC-12 model with a PEEK bar prosthesis (1592.2 MPa). Among the implant components, the lowest stress was observed in the anterior implant of the TS-8 model (27.99 MPa). In contrast, the lowest bone stress was recorded in the anterior trabecular bone capsule of the PC-8 model. These findings indicate that cantilever length and connection geometry are critical parameters in designing full-arch implant prostheses. At the same time, the use of PEEK as a bar material should be interpreted with caution under extended-cantilever conditions.

Journal of Functional Biomaterials doi: 10.3390/jfb17090459

Authors: Duaa Abuarqoub Mais Emad Alqassem H. Abuarqoub Majd F. Ellauzi Tala Maragha

Background: Three-dimensional (3D) printing and bioprinting have emerged as transformative technologies in tissue engineering and regenerative medicine. Conventional 3D printing enables the fabrication of complex, customizable scaffolds that mimic the native extracellular matrix (ECM), providing mechanical support essential for cell adhesion, proliferation, and differentiation. In contrast, 3D bioprinting integrates biomaterials, growth factors, and living cells into bioinks, allowing the precise layer-by-layer construction of tissue-like structures. Objective: This review aims to highlight recent advances and applications of both conventional 3D printing and 3D bioprinting in regenerative medicine, with a specific focus on craniofacial tissue regeneration. Particular emphasis is placed on the distinct roles of scaffold-based and cell-laden approaches. Methods: A comprehensive analysis of the current literature was conducted to examine both conventional 3D printing and bioprinting approaches used in craniofacial tissue engineering. Emphasis was placed on printing techniques, bioink composition and selection, scaffold design, and cell sources, as well as their applications across multiple tissue types. Results: Recent developments demonstrate that conventional 3D printing enables the fabrication of customizable scaffolds, whereas 3D bioprinting enables the generation of highly organized, cell-laden constructs that closely resemble native tissue architecture. These technologies have shown promising outcomes in developing patient-specific disease models and regenerative implants for craniofacial tissues, including bone, dental, tracheal, ocular, muscle, and neural tissues. Conclusions: 3D printing and bioprinting offer powerful platforms for craniofacial regenerative medicine. Ongoing advancements in bioink formulation, printing precision, and biological integration are expected to further enhance their translational and clinical potential.

Journal of Functional Biomaterials doi: 10.3390/jfb17090457

Authors: Maria Cristina Moraru Alexandra Iulia Dreanca Romelia Pop Iulian Antoniac Aurora Antoniac Veronica Manescu (Paltanea) Gabriel Cristescu Gheorghe Adrian Martau George Mihail Vlasceanu Diana Cenariu Marius Manole Flaviu Alexandru Tabaran Mariana Ionita Dan Cristian Vodnar Bogdan Sevastre

Background and Objectives: Magnesium-based biomaterials are increasingly investigated due to their biodegradability, bone-like elastic modulus, and potential osteogenic properties. However, alloy composition may influence degradation behavior and local tissue response. This study aimed to assess and compare the local biocompatibility, degradation characteristics, and bone regenerative response induced by Mg-Zn-Mn-Ca and Mg-Nd-Y-Zr-Zn magnesium alloy powders. Materials and Methods: Two magnesium alloys were evaluated through physicochemical characterization, in vitro osteoblast cytocompatibility and antimicrobial assays, and in vivo testing in Sprague–Dawley rats. Standardized cylindrical defects were created in the medial femoral condyle and filled with either Mg-Nd-Y-Zr-Zn or Mg-Zn-Mn-Ca alloy powders, while untreated defects served as controls. Bone remodeling and defect healing were assessed by micro-computed tomography, allowing three-dimensional qualitative and quantitative evaluation of newly formed bone. Scanning electron microscopy was used to analyze surface morphology and degradation features, while histopathological examination assessed inflammation, osteogenesis, and tissue integration at the implant site. Results: Both magnesium alloy powders showed antimicrobial potency and elicited no cytotoxic effects in vitro, while animal studies revealed progressive biodegradation over time, associated with new bone formation within and around the defect area. Micro-CT analysis demonstrated active bone remodeling in experimental groups, with differences in bone distribution and defect-filling patterns between Mg-Nd-Y-Zr-Zn and Mg-Zn-Mn-Ca implants. SEM revealed alloy-specific degradation morphologies. Histological evaluation showed a moderate early inflammatory response that decreased at later time points, together with ongoing osteogenesis and favorable tissue integration. No severe local adverse reactions or persistent inflammation were observed. Conclusions: Both Mg-Nd-Y-Zr-Zn and Mg-Zn-Mn-Ca alloy powders were locally biocompatible and supported bone regeneration in a rat femoral condyle defect model. Differences in degradation behavior and tissue response emphasize the relevance of alloy composition in developing magnesium-based biomaterials for bone defect treatment.

Journal of Functional Biomaterials doi: 10.3390/jfb17090456

Authors: Melania Maglio Maria Sartori Annapaola Parrilli Lucia Martini Enrico Lucarelli Michela Pierini Chiara Bellotti Marzio Piccinini Susanna Prosperi Milena Fini Gianluca Giavaresi

Background: Injectable bone graft substitutes offer a practical alternative to preformed ceramic scaffolds by adapting to irregular bone defects while preserving osteoconductive properties. This study investigated the in vivo performance of hydroxyapatite/tetracalcium phosphate (HA/TTCP) granules, uncoated or alginate-coated, with or without autologous ovine bone marrow concentrate (oBMC), in a standardized sheep bone defect model. Methods: oBMC was characterized for cellular composition, viability, and recovery. Implanted HA/TTCP formulations were evaluated after 6 and 12 weeks by micro-computed tomography and histomorphometry. Results: Uncoated HA/TTCP granules promoted bone formation, integrating with host bone. Alginate coating improved injectability and handling but influenced granule organization and degradation. Uncoated HA/TTCP + oBMC showed a more favorable response than the coated formulation, with higher bone-to-implant contact (p = 0.004) and bone volume (p = 0.031) at 12 weeks. A modest increase in peri-implant bone volume was observed from 6 to 12 weeks in the HA/TTCP + oBMC group, though this did not retain statistical significance once clustering was accounted for. No significant direct effect of oBMC was observed compared with the cell-free formulation. Conclusions: Injectable HA/TTCP granules + oBMC represent a promising single-step strategy for irregular bone defects, although further coating optimization is needed to preserve biological performance while maximizing handling advantages.

Journal of Functional Biomaterials doi: 10.3390/jfb17090455

Authors: Wannapat Chouyratchakarn Nattikan Thongjui Chayanisa Phutiyothin Onnicha Srisopar Surasak Tangkamonsri Chakrit Wiboonsuntharangkoon Pakorn Sang-Ngam Norrapon Vichiansan Nithi Atthi Chayarop Supanchart Sarawut Kumphune

The clinical success rate of titanium (Ti) implants is significantly reduced in elderly patients and by implant-associated bacterial infections. Thus, Ti surfaces were modified using sandblasted large-grit alkaline etching (SLA), argon-nonthermal plasma treatment, and recombinant human secretory leukocyte protease inhibitor (rhSLPI) coating. This study evaluated surface characteristics, human fetal osteoblast (hFOB 1.19) activities, and antibacterial efficacy. The modified surfaces exhibited increased roughness and hydrophilicity compared to Ti. The SBPTi-rhSLPI enhanced 7-day protein retention on the surface. While Ti promoted higher cell proliferation, the modified groups demonstrated superior cell adhesion and mineralization. Specifically, SBPTi-rhSLPI showed the highest cytoplasmic spreading, adhesion-related gene expression (Itgα1, Itgα2, Itgα5, and Itgβ1), and mineralization. Additionally, rhSLPI-coated groups effectively reduced the adhesion of both S. aureus and E. coli. In conclusion, combining SLA modification, argon plasma treatment, and rhSLPI coating provides enhanced effects. This combined approach significantly enhances osteoblast adhesion and mineralization while possessing antibacterial potential, which could be a promising strategy to improve implant success rates.

Journal of Functional Biomaterials doi: 10.3390/jfb17090454

Authors: Neculai Onică Elena-Raluca Baciu Cezara Andreea Onică Florin-Emilian Țurcanu Geta-Mirela Ispas Vlad Nicolae Arsenoaia Loredana Golovcencu Alice Murariu

Patient-specific Ti–6Al–4V fixation systems are increasingly used to stabilise the maxilla following segmental Le Fort I osteotomy; however, the biomechanical responses of complete locking and non-locking patient-specific fixation configurations remain insufficiently characterised. In this study, two patient-specific plate designs (a standard design and a reduced, minimally invasive design) were analysed by linear-elastic finite element analysis, each with locking and non-locking screws. Because they were developed for different indications and evaluated in distinct patient-specific anatomical models, between-model comparisons were considered descriptive. Vertical forces of 97.6, 206.9, and 257.0 N were applied bilaterally to the incisor and premolar regions, and the equivalent von Mises stress and total displacement were evaluated in the bone, plates, and screws. All results scaled linearly with load. Within the standard model, the locking configuration exhibited slightly greater bone, plate, and screw displacement than the corresponding non-locking configuration. Within the reduced model, it exhibited lower maximum bone, plate, and screw displacement by 16.4%, 19.2%, and 16.3%, respectively. Solver-reported local stress maxima were concentrated at the screw-head/plate-hole transition; because these isolated peaks were contact- and mesh-sensitive, they were not used to quantify relative screw loading or predict yielding. The modelled locking and non-locking fixation configurations therefore exhibited different, model-dependent displacement patterns. Further controlled simulations and experimental validation are required to determine the clinical relevance of these findings.

Journal of Functional Biomaterials doi: 10.3390/jfb17090453

Authors: Emma Muiños-López Iñigo Arroyo Olatz Guaresti Uzuri Urtaza Arantza Barco-Martín Asier Ullate-Agote Tania López-Martínez Ane M. Zaldua Manuel M. Mazo Froilán Granero-Moltó Bernardo Hontanilla

Introduction: The clinical translation of biomaterial-based strategies for ear reconstruction remains limited by several challenges, including scaffold design, selection of an optimal cell source, and stability of the new cartilage tissue. Most recent studies still rely on animal-derived cells and fail to demonstrate the long-term maintenance of the chondrogenic phenotype. Methods: In this study, we developed an off-the-shelf poly(lactide-b-ethylene glycol) (PLA-PEG) scaffold combined with clinical-grade alginate (Alg) and cellularized with human nasal chondrocytes for auricular cartilage engineering. Cellularized constructs were evaluated using histological and immunofluorescence analyses to assess extracellular matrix production and quality. In parallel, constructs retrieved after 12 weeks of in vivo implantation were mechanically characterized using a UniVert CellScale testing system to determine variations in compressive strength. Finally, the chondrogenic maturation of the new tissue was evaluated through bulk RNA transcriptomic profiling. Results: Histological, immunofluorescence, and transcriptomic analyses demonstrated robust cartilage matrix deposition with improved compressive properties and high expression of chondrogenic markers, such as ACAN, PRG4, and COL2A1. Furthermore, positive staining for the human-specific Ku80 antibody confirmed the presence of cells of human origin in the newly formed tissue after implantation. Conclusions: Overall, this study provides evidence that the combination of a PLA-PEG + Alg scaffold with human nasal septal chondrocytes represents a promising strategy for future reconstructive applications in auricular tissue engineering.

Journal of Functional Biomaterials doi: 10.3390/jfb17090452

Authors: Tejas Pande Sourav Panda Anurag Satpathy Abhaya Chandra Das Subharchana Das Aditya Kute

Tooth extraction followed by alveolar ridge resorption may compromise the aesthetics and future implant placement, especially in the anterior maxilla. This comparative clinical study assessed the effectiveness of Plasma Rich in Growth Factors (PRGF) for alveolar socket preservation compared with Spontaneous Healing (SH). Twenty extraction sockets were allocated to either of the groups (n = 10 each) and followed for 3 months. Both groups demonstrated dimensional changes following extraction;however, PRGF-treated sockets showed significantly better preservation of the horizontal ridge width at the crest, at 1 mm below the crest, and at 3 mm below the crest compared with SH (all p < 0.001). The PRGF group also demonstrated a significantly smaller decrease in the socket depth and a greater increase in the radiographic bone density (both p < 0.001). Early healing, soft tissue healing, and postoperative pain outcomes were significantly more favorable in the PRGF group during the follow-up period. Histomorphometricanalysis showed no significant difference between the PRGF and SH groups in terms of percentage of new bone formation and connective/ fibrovascular tissue.Though dimensional changes could not be completely prevented, PRGF significantly decreased the post-extraction resorption and improved the tissue quality, signifying its potential as a biologically driven approach for alveolar ridge preservation in the anterior maxilla.

Journal of Functional Biomaterials doi: 10.3390/jfb17090451

Authors: Ulli da Costa Cunha Martins Débora de Souza Ferreira Sávio Roberta Okamoto Carlos Fernando Mourão Richard J. Miron Sérgio Luis Scombatti de Souza Flávia Aparecida Chaves Furlaneto Michel Reis Messora

This study aimed to evaluate bone regeneration in critical-size rat calvarial defects treated with a xenogeneic bone graft alone or combined with autologous platelet concentrates prepared using two distinct centrifugation protocols, one based on horizontal centrifugation to produce horizontal platelet-rich fibrin (H-PRF) and the other based on vertical fixed-angle centrifugation to produce leukocyte–platelet-rich fibrin (L-PRF). Calvarial defects were created in 24 rats and allocated to four groups: blood clot (C), xenograft (XEN), xenograft plus L-PRF (XEN+L-PRF), and xenograft plus H-PRF (XEN+H-PRF) (n = 6/group). Calcein and alizarin were administered at 14 and 30 days, respectively. After 35 days, specimens were analyzed by micro-computed tomography, confocal laser scanning microscopy, histomorphometry, and histopathology. Data were analyzed using ANOVA and Tukey’s post hoc test (p < 0.05). All treated groups showed higher bone volume and lower trabecular separation than group C. The XEN+L-PRF group showed significantly higher bone volume than the XEN group. The XEN+H-PRF group showed higher bone volume, connectivity density, alizarin labeling, mineral apposition rate, and newly formed bone area, as well as lower trabecular separation, than the other groups (p < 0.05). Under the experimental conditions evaluated, both PRF protocols improved bone regeneration when combined with a xenogeneic bone graft, whereas the H-PRF protocol was associated with superior structural and histomorphometric bone regeneration outcomes and with more favorable spatiotemporal mineralization kinetics.

Journal of Functional Biomaterials doi: 10.3390/jfb17090450

Authors: Jiayang Gao Yang Liu Chenxin Zhan Meixi Wu Xinman Wang Yongheng Zhu Yuqin Qiao

Ultrasound-responsive antibacterial therapies represent a cutting-edge approach to combating implant-associated infections, particularly advantageous because of ultrasound’s non-invasive nature, deep penetration, and ability to target infected areas. However, most previous studies have been devoted to ultrasound-responsive nanomaterials, hydrogels, and polymer systems. Research on ultrasound-responsive surfaces on titanium remains in its early stages and is extremely limited. This review primarily focuses on the design principles and construction strategies for ultrasound-responsive antibacterial surfaces on titanium-based implants, key factors affecting acoustic energy conversion efficiency, and the approaches to enhance antibacterial efficiencies. Based on acoustic energy conversion mechanisms and the primary factors responsible for bacterial killing, this review classifies antibacterial surfaces into sonothermal surfaces, sonodynamic surfaces, and multimodal combined surfaces. Moreover, this review discusses perspectives and challenges regarding biocompatibility, long-term antibacterial activity after implantation, and future clinical translation.

Journal of Functional Biomaterials doi: 10.3390/jfb17090449

Authors: Mei Zhang Linjie Zheng Benyong Lou Yanjie Zhang Rongjian Sa Ling Liang Li Feng Longtao Zhang

Bioactive polysaccharides (e.g., fucoidan, β-glucans, and medicinal plant polysaccharides) contain functional groups that interact with drug molecules, and some also retain their own biological activities. Through reversible noncovalent interactions, they can associate with small-molecule drugs and form supramolecular nanocomplexes, defined here as nanoscale assemblies in which the polysaccharide is a main structural component and its association with the drug contributes to assembly or drug retention. Multicomponent composites and bulk local matrices are discussed separately as related or extended systems. The review covers hydrogen bonding, hydrophobic association, electrostatic complexation, π–π stacking, and the cooperation among these interactions, together with the effects of pH, ionic strength, concentration, and solvent composition. Nanoprecipitation/solvent exchange, polyelectrolyte complexation, direct aqueous self-assembly, and microfluidic-assisted assembly are compared with respect to nanostructure formation, process control, and reproducibility. Molecular, colloidal, solid-state, and computational evidence is examined together when interpreting structure–assembly–performance relationships. Reported advantages include improved drug dispersibility, colloidal stability, release control, bioavailability, cellular uptake, biodistribution, and safety. In some systems, the polysaccharide itself may also contribute to therapeutic effects in tumors, inflammatory diseases, and wound healing. Related local-matrix systems are considered separately. Further development of these nanocomplexes will require better quantitative analysis of assembly mechanisms, more consistent polysaccharide characterization, careful biocompatibility assessment, scalable preparation, and longer-term safety evaluation.

Journal of Functional Biomaterials doi: 10.3390/jfb17090448

Authors: George G. Sotiropoulos Michael Solomonov Konstantinos Koutoulas Nikos Pantazis Eleftherios Terry Farmakis

Background: This study aimed to investigate flow, contact angles and capillary penetration of commercially available endodontic sealers by substrate (human root dentin discs [HRD] and gutta-percha [GP]) and by temperature [room (20 °C), or body (37 °C)]. Methodology: Nine commercially available endodontic sealers were tested using the two-plate method, contact angle calculation (measured on HRD and GP surface—for both temperatures), free-flow, and penetration co-efficiency using a capillary permeability test (in 37 °C). Discs, set-ups and sealers were prepared according to the protocol; specimens were photographed; results were collected; and all recordings were statistically analyzed. Results: The chemical composition of each sealer significantly affected rheological properties even in the same chemical group (p < 0.001). Also, recordings from every test made were also significantly influenced by temperature (p < 0.001). More specifically, the behaviour of sealers under higher temperature proved to be sealer-specific. Conclusions: Within the limitation of this study, it was verified that Endodontic sealers’ rheological properties were affected by the substrate’s composition and temperature. Additionally, body temperature significantly influenced thier performance.

Journal of Functional Biomaterials doi: 10.3390/jfb17090447

Authors: Vasanop Vachiramon Tussapon Boonyarattanasoonthorn Kasem Rattanapinyopituk Jeeraprapha Duangbupha Vudhiporn Limprasutr Anusak Kijtawornrat Jovian Wan

(1) Background: Hybrid injectable biomaterials incorporating poly-D,L-lactic acid (PDLLA) and hyaluronic acid (HA) have emerged as an important class of biostimulators in aesthetic medicine, combining immediate soft-tissue augmentation with sustained collagen biostimulation. Although inadvertent intravascular injection is uncommon, it may lead to severe vascular complications. However, experimental data on the intravascular behaviour of PDLLA-HA hybrid biostimulators remain limited. This study evaluated vascular flow changes, countercurrent flow, and tissue response following intra-arterial injection of Juvelook® and Juvelook Volume® (VAIM Co., Ltd., Seoul, Republic of Korea) in a rabbit ear model. (2) Methods: A total of 112 rabbits (56 animals per product) were studied using an identical protocol. Each rabbit received bilateral intra-arterial injections of either 0.1 or 0.2 mL of PDLLA-HA hybrid biostimulator prepared at the manufacturer’s recommended 6 mL reconstitution or at serial dilutions ranging from 12 to 42 mL. Immediate vascular flow, countercurrent flow, macroscopic skin changes, and histopathological findings were evaluated over a 7-day observation period. (3) Results: At an injection volume of 0.1 mL, both products dispersed throughout the arterial system without persistent vascular occlusion or tissue necrosis. At 0.2 mL, transient vascular occlusion occurred in the standard (6 mL) and 12 mL dilution groups, with spontaneous restoration of blood flow within 5 min. Countercurrent flow was observed only in the Juvelook Volume® (VAIM Co., Ltd.) cohort under these conditions. No skin necrosis, intravascular thrombosis, or embolisation was observed. Histopathological examination demonstrated preserved vascular integrity, with only focal perivascular foreign-body reactions consistent with injectable biomaterials. (4) Conclusions: Neither biostimulator caused persistent vascular occlusion or clinically significant tissue injury under the experimental conditions investigated. Injection volume and dilution influenced transient vascular flow disturbance and countercurrent behaviour. These findings provide experimental evidence that improves current understanding of the short-term intravascular behaviour of PDLLA-HA hybrid biostimulators and may contribute to future assessments of vascular safety.

Journal of Functional Biomaterials doi: 10.3390/jfb17090446

Authors: Shanglin Wu Yuriko Komagamine Bohan Tang Tamaki Hada Aung Soe Myint Pong Pongprueksa Manabu Kanazawa

Three-dimensionally (3D)-printed denture teeth are increasingly used in clinical practice; however, their wear resistance and surface hardness may be insufficient for long-term clinical application. Moreover, the effect of post-treatment under elevated temperature and pressure on these properties remains unclear. This study aimed to evaluate the effect of such post-treatment on the wear resistance and Vickers hardness of 3D-printed denture teeth resin. One hundred disk-shaped specimens (10 × 2 mm) were 3D-printed using Dima denture teeth resin and randomly assigned to four post-treatment groups (121 °C at 2 bar for 4, 30, 60, and 90 min) and one untreated control group. Within each group, specimens were allocated for wear resistance (n = 10) and Vickers hardness (n = 10) testing. Wear resistance was measured using an impact-sliding wear testing machine in a polymethyl methacrylate slurry, while Vickers hardness was measured using a hardness tester under a 50 g load with a 15 s dwell time. Statistical analyses included one-way analysis of variance (ANOVA), Kruskal–Wallis, and Welch’s ANOVA (α = 0.05). All post-treatment groups exhibited significantly lower depth loss and higher hardness than the control group (p < 0.05). Specimens post-treated for ≥30 min exhibited significantly lower volume loss than the control group (p < 0.05). The 121 °C/90 min group demonstrated the highest wear resistance and Vickers hardness. Within the limitations of this study, post-treatment under elevated temperature and pressure significantly improved the wear resistance and Vickers hardness of the tested 3D-printed denture teeth resin, with the 90 min protocol yielding the greatest enhancement. Thus, thermal-pressure post-treatment may be a promising approach for enhancing the mechanical performance of additively manufactured denture teeth.

Journal of Functional Biomaterials doi: 10.3390/jfb17090445

Authors: Carolina Caleza-Jiménez María Biedma-Perea Marcela Arenas-González Adrián Curto-Aguilera Asunción Mendoza-Mendoza David Ribas-Pérez

Objective: To compare radiographic changes following regenerative endodontic procedures in immature permanent teeth with pulp necrosis of traumatic or carious origin. Methods: A retrospective study was conducted in 20 immature permanent teeth from 20 patients (10 traumatic and 10 carious cases) treated with a standardized regenerative endodontic protocol. Root length, dentinal wall thickness, periapical status, and type of repair were assessed using standardized periapical radiographs at baseline and 12 months. Radiographs were independently evaluated by two investigators blinded to etiology, and inter-examiner agreement for type of repair was assessed using Cohen’s kappa. Results: No statistically significant differences were found in root-length change between the groups. A statistically significant greater increase in dentinal wall thickness was observed in the carious group compared with the traumatic group; however, the groups differed substantially in tooth type. No statistically significant differences were observed in Periapical Index scores after 12 months of follow-up, and periapical healing (PAI 1–2) was observed in all cases. Periodontal-associated repair was observed in all traumatic cases, whereas pulpal-associated repair was observed in all carious cases. Conclusions: Regenerative endodontic procedures were associated with favorable radiographic outcomes in immature permanent teeth with pulp necrosis of traumatic or carious origin. However, the small sample size, short follow-up, absence of a control group, and substantial differences in tooth type between etiological groups limit causal interpretation of the observed differences.

Journal of Functional Biomaterials doi: 10.3390/jfb17090444

Authors: Elham Eskandarnia Ayah Binrajab Adnan Alsaei Fatema Rahimi Nasser Alahmed Ahmad Zarwi G. Roshan Deen

Hydrogels are hydrated three-dimensional polymeric networks with biomedical potential because they can encapsulate therapeutic agents and provide localised, sustained, or stimulus-responsive drug delivery. Their performance is determined by interacting variables, including polymer composition, synthesis route, crosslinking chemistry, drug loading, swelling, degradation, and the biological microenvironment. This multidimensional design space often makes hydrogel development slow and dependent on trial-and-error experimentation. This review examines the data-driven development of biomedical hydrogels for controlled drug delivery, focusing on clinical applications and emerging machine-learning approaches that support material selection, formulation design, synthesis optimisation, and release prediction. The review first discusses natural and synthetic hydrogels, including alginate, chitosan, gelatin-based systems, hyaluronic acid, and polyethylene glycol, with emphasis on how their physicochemical properties influence biocompatibility, synthesis flexibility, and drug-release behaviour. Key applications are then considered, including wound healing, cancer therapy, glucose-responsive insulin delivery, and inflammatory disease management. Particular attention is given to injectable and stimuli-responsive hydrogels, where formulation conditions and synthesis parameters can be tuned to improve localisation, therapeutic exposure, and release control. The review evaluates machine-learning methods, including random forest, gradient boosting, artificial neural networks, Gaussian process regression, and active learning, for predicting hydrogel properties, modelling release profiles, optimizing synthesis and formulation variables, and prioritizing experimental candidates. Finally, translational challenges are addressed, including small non-standardised datasets, limited external validation, weak in vitro-clinical correlations, material safety, explainability, reproducibility, scalability, and regulatory requirements. By integrating clinical, materials, synthesis, and machine-learning perspectives, this review highlights opportunities for developing safer and clinically relevant hydrogel-based drug-delivery systems.

Journal of Functional Biomaterials doi: 10.3390/jfb17090443

Authors: Ceren Yuksel Simon Kwoon-Ho Chow Ryota Hirose Mayu Morita Qi Gao Takahiro Igei Monica Thukkaram Chao Ma Tony Tam Sophie Clarke Mark Skylar Scott Stuart Goodman Duygu Ege

Complex patient-specific bone defects remain difficult to reconstruct because the regenerative capacity of bone is limited and prefabricated implants cannot readily match defect geometry. In this work, methylcellulose-gelatin-hydroxyapatite (MC/GEL/HA) inks were formulated with varying methylcellulose content and hydroxyapatite incorporation, crosslinked with EDC/NHS, and 3D-printed into porous scaffolds with defined square-pore architectures. Inks were evaluated by oscillatory and steady-shear rheology, and printed scaffolds were characterized for morphology, chemical composition, mechanical performance, physicochemical stability, wettability, apatite-forming bioactivity, and osteogenic responses of human bone marrow mesenchymal stem cells. Methylcellulose content primarily governed ink rheology and printability, and increased compressive strength (up to ~0.38 MPa for 15MC/10GEL/30HA), whereas hydroxyapatite enhanced surface hydrophilicity, promoted apatite nucleation within 7 days in simulated body fluid, and markedly increased alkaline phosphatase activity (>10-fold over HA-free scaffolds), mineralization (~2-fold by Alizarin Red), and the highest osteocalcin expression among the HA-containing formulations (~2.45-fold at day 14). The 15MC/10GEL/30HA formulation showed the most favorable balance of printability, mechanical performance, and osteogenic performance. These complementary functions reconciled structural stability with osteogenic performance, supporting the MC/GEL/HA system as a tunable bioink platform for non-weight-bearing bone regeneration, while warranting further in vivo validation.

Journal of Functional Biomaterials doi: 10.3390/jfb17090442

Authors: Ana Laura de Senne Zonta Biagio Matera Paulo Tambasco de Oliveira Isabela Rodrigues Gonsales Carlos Eduardo Santos Melo Francesca Rossi Daniela Bazan Palioto Benedetta Ghezzi

The host immune response plays a central role in determining biomaterial performance, particularly through early macrophage activation dynamics at the tissue–biomaterial interface. This study evaluated the response of THP-1-derived human macrophages cultured on a fibrous extracellular matrix-like polydioxanone (PDO) mesh under basal (M0), M1-induced, and M2-induced in vitro conditions. Macrophage responses were assessed by gene expression analysis, immunofluorescence staining of macrophage- and polarization-associated markers, scanning electron microscopy (SEM), and metabolic and viability assays. Distinct stimulus- and time-dependent responses were observed across transcriptional, marker distribution, morphological, and metabolic readouts. Pro-inflammatory gene expression increased under M1-polarizing conditions at 72 h and declined at 96 h, whereas anti-inflammatory and M2-associated markers progressively increased under M2 stimulation, reaching higher levels at 96 h. Immunofluorescence confirmed macrophage differentiation under basal conditions and showed condition-dependent distributions of CD86- and CD206-associated signals, consistent with the transcriptional profiles. SEM revealed stable cell–material interactions and polarization-associated morphological heterogeneity. Metabolic and viability assays confirmed viable cells under all conditions, with activity patterns consistent with induced activation states. Under basal (M0) conditions, macrophages cultured on the PDO mesh maintained a basal phenotype without evidence of marked pro-inflammatory activation. Overall, these findings indicate that fibrous PDO meshes support macrophage viability, differentiation, and stimulus-responsive activation, highlighting their potential as immunologically compatible polymeric platforms for regenerative biomaterial applications.

Journal of Functional Biomaterials doi: 10.3390/jfb17090441

Authors: Athanasios Armakolas Amalia Kotsifaki Martha Stathaki Vassilis Paspaliaris Eleni Tsakiri Panagiotis Ntakos Christos Kalligeros Vasilios Spitas Athanasios Foukas

Background: Optimal porosity and surface area of additively manufactured Ti-6Al-4V scaffolds for early human mesenchymal stem cell (hMSC) retention remain unclear, despite their importance in reconstruction of critical-sized bone defects. This study evaluated scaffold architectures fulfilling biomechanical criteria for hMSC and osteocyte survival, proliferation, differentiation, cell cycle, and retention. Methods: Primary hMSCs from four healthy donors were characterized by flow cytometry, immunofluorescence, and Western blotting. Cells were seeded onto Ti-6Al-4V scaffolds with graded porosity (P50–P90, 50–90% porosity) and cultured for 120 h. Viability and retention were measured by trypan blue exclusion, apoptosis and cell cycle by flow cytometry, and osteogenic differentiation by collagen I, osteocalcin, and Akt phosphorylation analyses. Collagen-embedded hMSCs and osteoblasts were used to assess migration and phenotype maintenance. Results: The densest scaffold, P50, consistently retained significantly more viable hMSCs and differentiated osteoblasts than P60 and P70 (p < 0.005 in both cases, One-way ANOVA analysis, significance level a = 0.05 followed by Bonferroni correction). Among the scaffold architectures investigated, P50 demonstrated the most favorable early cellular retention under the present experimental conditions. No scaffold-induced apoptosis or proliferation changes were detected. Osteogenic differentiation and Akt phosphorylation increased during culture. In collagen-containing scaffolds, cells migrated from the matrix and preferentially coated titanium struts, with P50 supporting superior attachment. Conclusions: Among the scaffold architectures investigated, the low-porosity/high-surface-area P50 design provided the most favorable early microenvironment for hMSC and osteoblast retention without cytotoxic effects.

Journal of Functional Biomaterials doi: 10.3390/jfb17090440

Authors: Zeynep Batu Eken Nicoleta Ilie

This study aimed to evaluate the ability of different categories of direct restorative materials to withstand artificial dentin alterations. A total of 360 human dentin specimens were allocated into 18 groups (n = 20). An ion-releasing bulk-fill resin-based composite (Cention Forte/CF), a resin-modified glass ionomer cement (Fuji II LC/FJLC), and an experimental conventional glass ionomer cement (EXP) were applied on sound, artificially hypermineralized, and demineralized dentin. Shear bond strength (SBS) was performed after 1 week and 6 months of storage, followed by fractographic analysis. Statistical analysis was performed using one- and three-way ANOVA, Games–Howell post hoc test, independent t-tests (α = 0.05), and Weibull analysis. SBS and bond reliability of CF on sound and hypermineralized dentin were higher than on other materials after both aging periods. On these two substrates, the SBS values of FJLC were higher than those of EXP, except for sound dentin after 6 months. Demineralized dentin significantly reduced the SBS of all materials under both aging conditions, with a high number of pre-test failures. The impact of aging was significant only in demineralized dentin for all materials. Ion-releasing resin-based composite performed best in terms of bond strength and reliability on sound and hypermineralized dentin. Artificially demineralized dentin severely compromised the bonding performance and maturation of all materials.

Journal of Functional Biomaterials doi: 10.3390/jfb17090439

Authors: Jakub Hadzik Paweł Kubasiewicz-Ross Umberto Romeo Krzysztof Kujawa Nicola Alberto Valente Marzena Dominiak

Objectives: Clinical outcomes of peri-implant soft tissue augmentation remain variable, and baseline-associated factors of treatment response are poorly understood. This exploratory study aimed to evaluate baseline-associated patterns of peri-implant soft tissue gain following augmentation with connective tissue grafts (CTG) and volume-stable collagen matrices (VCMX). Materials and Methods: This study represents a secondary analysis of a randomized clinical trial including 32 implant sites (CTG, n = 16; VCMX, n = 16). Peri-implant soft tissue thickness (STT) was measured using high-frequency ultrasonography at baseline (T0), 3 months (T1), and 12 months (T2). Absolute and relative STT gains were analyzed, and their relationship with baseline thickness was assessed. Results: Both augmentation approaches resulted in significant increases in soft tissue thickness, with most of the gain occurring during the early healing phase. At 12 months, CTG demonstrated greater absolute tissue gain than VCMX. At the mid-buccal measurement site, mean relative gain was approximately 225% with CTG and 147% with VCMX. The strongest inverse correlation between baseline STT and relative gain was also observed at this site in the CTG group (r = −0.815, p < 0.001). Sites with thinner tissues showed greater proportional increases, whereas thicker tissues demonstrated a reduced relative response. Conclusions: Relative soft tissue gain was inversely associated with baseline soft tissue thickness. Thinner tissues exhibit greater proportional increases, whereas thicker tissues demonstrate a lower relative gain. These findings support a phenotype-informed and individualized approach to peri-implant soft tissue management.

Journal of Functional Biomaterials doi: 10.3390/jfb17090437

Authors: Hirotomo Yanagiuchi Daniele Botticelli Erick Ricardo Silva Samuel Porfirio Xavier Giovanna Iezzi Takahito Uwazumi Shunsuke Baba

Background: This study compared four biomaterials after maxillary sinus floor elevation in rabbits, focusing on graft persistence, tissue organization, space maintenance, and Schneiderian membrane response. Methods: Thirteen adult New Zealand White rabbits were enrolled, including 12 males and one female replacement animal; 12 animals provided evaluable specimens, with six assigned to each healing interval. Four elevated sinus compartments per evaluable animal were randomly allocated to Bio-Oss®, mp3®, ReproBone® novo Paste, or Alos Granular. Specimens were collected after 2 or 10 weeks (n = 6 each). Histomorphometry quantified new bone, residual graft, soft tissue, elevated area, mucosal alterations, and IBN-like tissue, defined as areas in which biomaterial and bone could not be reliably separated. A combined graft and IBN percentage was calculated. Results: At 10 weeks, materials differed in residual graft (p = 0.0040) and combined graft and IBN percentage (p = 0.0218); Bio-Oss® showed higher values than Alos Granular for both outcomes (adjusted p = 0.0024 and 0.0219, respectively). IBN-like tissue was higher in ReproBone® novo Paste and Alos Granular than in Bio-Oss® (adjusted p = 0.0219 and 0.0417), whereas only a small proportion occurred in mp3®. New bone did not differ among materials at either interval. Bio-Oss® and mp3® showed predominantly conventional osteoconduction. Alos Granular showed extensive degradation, whereas ReproBone® novo Paste exhibited irregular graft and IBN regions. In the descriptive mucosal assessment, thinning was observed in all groups, whereas perforations were observed only at Bio-Oss®-treated sites; no inferential comparisons were performed for these outcomes. Conclusions: The materials differed in graft persistence, tissue architecture, dimensional stability, and mucosal response. Sinus graft evaluation should extend beyond new bone formation to include residual graft, IBN-like tissue, space maintenance, and mucosal compatibility.

Journal of Functional Biomaterials doi: 10.3390/jfb17090438

Authors: Alena Findrik Balogová Marianna Trebuňová Darina Bačenková Radovan Hudák Jozef Živčák

Biodegradation of fused filament fabrication (FFF)-printed poly(lactic acid)/polyhydroxybutyrate (PLA/PHB) structures is governed by complex interactions between material composition, structural design, and degradation environment. Although these factors have been extensively investigated, they are typically evaluated independently, limiting a comprehensive understanding of their combined influence on degradation behaviour. This study synthesizes experimental evidence from a series of complementary studies on FFF-printed PLA/PHB systems to develop a transport-driven conceptual framework for interpreting biodegradation mechanisms. The integrated findings show that structural porosity increases fluid uptake (approximately 10% in dense structures versus 20% in porous structures) and promotes greater mass loss (25–40% after 45 days), while material modifications, including plasticizers and ceramic additives, influence local pH evolution and mechanical stability during degradation. The degradation response was also strongly dependent on the surrounding medium, with PBS maintaining relatively stable pH, saline and Hank’s solutions promoting acidification, and urea-based media leading to alkalization. Collectively, these observations indicate that fluid absorption and diffusion consistently mediate the interactions between material composition, scaffold architecture, and degradation environment, thereby governing the progression of biodegradation. Based on these experimentally supported relationships, a transport-driven conceptual framework is proposed to provide a unified qualitative interpretation of biodegradation in FFF-printed PLA/PHB structures. Rather than presenting new experimental data, this work offers an integrative perspective that may facilitate the interpretation of degradation behaviour, support the rational design of biodegradable scaffolds, and provide a foundation for future quantitative and predictive models.

Journal of Functional Biomaterials doi: 10.3390/jfb17090436

Authors: Miriam Di Martino Lucia Sessa Giulia Pagliari Daniela Silvestrino Simona Concilio

Injectable thermoresponsive hydrogels are useful for localized drug delivery because they can be administered as low-viscosity formulations and then form, or reinforce, therapeutic depots directly at diseased tissue sites. Their common design principle is a temperature-dependent transition from a flowable formulation before administration to an in situ matrix at physiological temperature, or a thermally regulated change in swelling, mesh size, drug-matrix affinity or degradation. This review focuses on thermoresponsive injectable systems for localized delivery, including PNIPAM-based systems, poloxamers/Pluronics, PEG/polyester block copolymers, polyurethane-based hydrogels, chitosan-based thermogels, hyaluronan- and glycosaminoglycan-based systems, and selected multicomponent or nanocomposite networks. The in vivo application areas considered are local cancer therapy, wound healing and antibacterial treatment, osteoarthritis and intra-articular delivery, and myocardial infarction/cardiac repair. Across these indications, preclinical studies suggest that thermoresponsive hydrogels may prolong local residence time, reduce systemic exposure, enhance delivery of poorly soluble or unstable payloads, and modulate disease-specific microenvironments. Remaining challenges include gelation control, mechanical stability, degradation products, immune response, sterilization, manufacturing reproducibility, disease heterogeneity and robust translational validation.

Journal of Functional Biomaterials doi: 10.3390/jfb17090435

Authors: Siphesihle Cassandra Nonjola Subin Park Jeong In Kim Soonchul Lee

Large bone defects remain difficult to treat because current bone substitutes largely restore mechanical integrity without reconstructing the periosteal microenvironment that orchestrates endogenous bone regeneration. Here, we developed a periosteum-inspired composite scaffold by integrating a regenerated cellulose nanofibrous membrane onto a compressed hydroxyapatite scaffold to simultaneously mimic the biological interface and mineralized framework of native bone. A cellulose acetate electrospun membrane was converted into regenerated cellulose through deacetylation while preserving its extracellular matrix-like fibrous architecture, providing a hydrophilic surface favorable for cell–material interactions. The periosteum-mimetic membrane supported cell attachment and increased cellular metabolic activity, demonstrating its ability to establish a regenerative microenvironment at the scaffold surface. In a critical-sized femoral defect model in SD rats, the composite scaffold markedly enhanced bone regeneration compared with the hydroxyapatite scaffold alone, leading to substantially increased newly formed bone area. Histological analysis further revealed elevated expression of the osteogenic transcription factor Osterix, indicating enhanced osteogenic commitment during bone repair. Rather than functioning solely as a structural covering, incorporation of the engineered periosteal membrane provided a cell-supportive interface associated with enhanced bone regeneration. This biomimetic strategy demonstrates that reconstructing periosteal function represents an effective approach for designing next-generation bone grafts with enhanced biological performance and regenerative capacity.

Journal of Functional Biomaterials doi: 10.3390/jfb17090434

Authors: Cristina Jimenez-Marcos Julia Claudia Mirza-Rosca Madalina Simona Baltatu Petricǎ Vizureanu

New titanium alloys for biomedical applications are being developed to avoid the use of aluminum and vanadium, which may raise concerns regarding their long-term biological effects. In this study, the effect of tantalum content on the microstructure, hardness and electrochemical behavior of Ti–Mo–Zr–xTa alloys (x = 5, 10 and 15 wt.%) obtained by vacuum arc melting (VAR) was investigated. Characterization included assessment of samples via optical microscopy, scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS) analysis and X-ray diffraction (XRD). Mechanical response and corrosion resistance were assessed using Vickers microhardness and electrochemical tests in Ringer’s solution, respectively. The X-ray diffraction results indicated that the β phase was predominant in all three compositions. Furthermore, the increased tantalum content promotes the stability of this phase and reduces the α″ martensite contribution observed in alloys with lower tantalum content. The mean microhardness decreased as the tantalum content increased, although measurements showed less dispersion with increasing indentation load. All alloys exhibited passive behavior in Ringer’s solution, with the Ti–15Mo–7Zr–15Ta alloy showing the lowest corrosion current density and corrosion rate.

Journal of Functional Biomaterials doi: 10.3390/jfb17090433

Authors: Michele Basilicata Giovanni Bruno Gennaro Salvatore Ponticelli Patrizio Bollero Raffaella Docimo Alessandra Fava Stefano Guarino Roberto Montanari Alessandra Palombi Alfio Scuderi Alessandra Varone

This study evaluates the thermal and mechanical behavior of innovative copper–nickel–titanium (CuNiTi) rectangular orthodontic wires featuring rounded edges across two different sizes for clinical applications. Differential scanning calorimetry (DSC) was performed from −20 °C to +80 °C to determine phase transformation temperatures according to ASTM F2004. Three-point bending tests were conducted in accordance with ISO 15841 to evaluate unloading forces (at 3, 2, 1, and 0.5 mm deflections) and permanent residual deflection at 23 °C (room temperature) and 37 °C (oral environment). DSC analysis revealed a single-stage phase transformation within the range 10 °C to 27 °C, indicating near-superelastic behavior at room temperature. Mechanical testing demonstrated reproducible force-deflection profiles and low permanent deformation. At body temperature (37 °C), unloading forces in the 2.0–0.5 mm activation range averaged between 1.9 N and 3.2 N depending on wire cross-section. In conclusion, the evaluated CuNiTi wires provide consistent force delivery during unloading at physiological temperature, offering suitable mechanical properties for orthodontic alignment applications.

Journal of Functional Biomaterials doi: 10.3390/jfb17090432

Authors: Yulin Gao Kai Li Qiang Chen Pingtuo Wang Aoshuang Xun Yi Ding Heng Ji Xuebin Zheng

Surface wettability is a critical factor influencing the biological performance of orthopedic Ti implants. The native TiO2 film on Ti undergoes changes in wettability under ultraviolet (UV) irradiation. However, the limited tissue penetration of UV light compared with near-infrared (NIR) light restricts its potential clinical application. In this study, a black TiO2 (b-TiO2) coating with NIR-responsive wettability was fabricated directly on a Ti substrate using a one-step atmospheric plasma spraying process. Under 808 nm NIR irradiation, the water contact angle of the b-TiO2 coating increased from 0° to 154.4 ± 4.0°, indicating a transition from a superhydrophilic to a stable superhydrophobic state. FTIR and XPS analyses showed that NIR-induced photothermal heating promoted the removal of surface hydroxyl groups and the passivation of oxygen-deficient sites, thereby driving the wettability transition. Among TiO2 coatings with hydrophilic, intermediate-wettability, and hydrophobic surfaces, the hydrophobic coating effectively directed macrophage polarization toward the anti-inflammatory M2 phenotype and delivered slightly superior osteoblast activity. It also markedly inhibited Staphylococcus aureus adhesion, achieving an anti-adhesion efficiency of 98.61%. These findings demonstrate that NIR irradiation can regulate the wettability of plasma-sprayed b-TiO2 coatings and provide concurrent immunomodulatory and antibacterial effects. This approach may support the development of light-responsive surfaces for orthopedic implants.

Journal of Functional Biomaterials doi: 10.3390/jfb17090431

Authors: Kinga Mária Jánosi Diana Cerghizan Izabella Éva Mureșan Aurița Ioana Albu Liana Claudia Dobreci Liana Georgiana Hănțoiu Alpár Kovács Sharukh S. Khajotia Cristina Nicoleta Ciurea

Background: Dentin disinfection plays an important role in prosthodontics, reducing the microbial load, preventing postoperative complications and enhancing the bond strength. This in vitro study aims to evaluate the antimicrobial efficacy of different dentin disinfection protocols, depending on microorganism type, application time, and dentin depth. Methods: A total of 144 extracted human molars were included in the final analysis. The exposed dentin surfaces were contaminated with methicillin-resistant Staphylococcus aureus (MRSA) or Candida albicans (C. albicans). The specimens were disinfected using 2% chlorhexidine digluconate, 3% hydrogen peroxide, or photodynamic therapy with 1% toluidine blue. Microbial growth at superficial and deep dentin was assessed using semi-quantitative visual colony-density scores, resulting in 288 microbiological measurements. Ordinal generalized estimating equation (GEE) models, accounting for within-tooth correlation, were used to evaluate the factors associated with microbial scores. Results: The results showed statistically significant differences among protocols for MRSA (Wald χ2 = 62.98; df = 5; p < 0.001) and for C. albicans (Wald χ2 = 18.77; df = 5; p = 0.002). Specifically, 2% CHX applied for 30 s was associated with the greatest reduction in MRSA microbial scores (OR = 0.121; p = 0.009), whereas 3% H2O2 applied for 60 s was more effective against C. albicans (OR = 0.054; p < 0.001). PDT showed lower and less consistent antimicrobial effects under the tested parameters. Conclusions: The effectiveness of dentin disinfection depends on the microorganism, application time, and dentin depth. Complete elimination of the microbial load cannot be achieved using the disinfectants investigated.

Journal of Functional Biomaterials doi: 10.3390/jfb17090430

Authors: Osama Abuabboud Adrian-George Marinescu Mihai Paven Izabella-Maria Kovacs Luminița-Maria Nica Andrei-Bogdan Faur Liviu Marșavina Dan Ioan Stoia Anca Jivănescu

Background and Objectives: Three-dimensional printing is increasingly used to fabricate dental restorations; however, limited evidence is available on the mechanical performance and fracture behavior of printable resin materials used for endocrown restorations. Fracture load alone may not fully describe material performance, particularly when brittle or defect-sensitive failure occurs. This in vitro study aimed to compare the fracture resistance, Weibull parameters, experimental Mode I fracture toughness parameter, and failure patterns of three 3D-printed resin materials used for endocrown restorations. Materials and Methods: Thirty anatomically identical molar replicas were produced from a single prepared tooth model and restored with endocrowns fabricated from NextDent C&B MFH (NextDent B.V., Soesterberg, The Netherlands), SprintRay Crown (SprintRay Inc., Los Angeles, CA, USA), and BEGO VarseoSmile Crown Plus (BEGO GmbH & Co. KG, Bremen, Germany) (n = 10/group). The restorations were cemented and subjected to compressive loading until fracture. Maximum fracture force values were analyzed using Welch’s ANOVA and Weibull statistics. In parallel, single-edge-notched bend (SENB) specimens were fabricated from the same materials and tested using an ASTM D5045-based configuration to calculate an experimental Mode I fracture toughness parameter. Representative fractured crowns and standardized specimens were examined using stereomicroscopy to assess visible failure morphology. Results: No statistically significant difference in maximum fracture force was found among the three materials (Welch’s ANOVA, p = 0.217). The mean fracture force values were 862.37 N for NextDent C&B MFH, 804.37 N for SprintRay Crown, and 699.43 N for BEGO VarseoSmile Crown Plus. In the complementary analyses, BEGO VarseoSmile Crown Plus showed the highest Weibull modulus (m = 9.36), indicating a narrower distribution of fracture values, and the highest mean experimental Mode I fracture toughness parameter (5.250 MPa·m0.5) under the present experimental conditions. Qualitative stereomicroscopic analysis revealed material-dependent visible failure patterns: SprintRay Crown exhibited more extensive fragmentation, whereas BEGO VarseoSmile Crown Plus showed a more defined visible fracture pattern with less secondary fragmentation. Conclusions: Fracture load alone was insufficient to characterize the mechanical behavior of the tested materials fully. Weibull parameters, the experimental fracture toughness parameter, and failure morphology provided complementary information and should be considered when evaluating 3D-printed resin materials for endocrown restorations.

Journal of Functional Biomaterials doi: 10.3390/jfb17090429

Authors: Nadina Ilincar Vanessa Bolchis Mariana-Ioana Miron Alexandru-Ionut Olari Ramona Dumitrescu Razvan Lacatusu Daniela Jumanca Atena Galuscan

Introduction: White spot lesions (WSLs) are early enamel demineralization lesions associated with increased surface roughness and plaque retention. Profilometry is commonly used to evaluate these surface changes, although methodological variability remains significant. Objective: To critically evaluate the available evidence regarding the validity and reproducibility of profilometry for assessing surface roughness in experimentally induced WSL models and treatment-modified surfaces and to identify methodological factors influencing its application across in vitro studies. Methods: A systematic review of 27 in vitro studies published between 2021 and 2026 was conducted. Methodological characteristics of contact and non-contact profilometry were synthesized, and evidence relevant to validity and reproducibility was qualitatively assessed based on complementary analytical methods and the reporting of standardized measurement procedures. Results: Considerable heterogeneity was identified in specimen sample and preparation, demineralization protocols, profilometric systems, acquisition settings, roughness parameters, and experimental conditions. Both contact and non-contact profilometry detected treatment- and demineralization-related surface changes, with Ra being the most frequent reported parameter. Complementary analytical techniques provided supporting evidence for the interpretation of profilometric findings but did not constitute formal validation. Methodological details relevant to reproducibility were inconsistently reported, and formal repeatability or reproducibility testing was generally lacking, Conclusion: Profilometry appears useful for quantitatively characterizing surface topography in experimentally demineralized enamel as a model of WSLs and treatment-modified enamel; however, substantial methodological variability and limited formal validation and reproducibility testing prevent definitive conclusions regarding its validity and reproducibility. Greater standardization of methodologies of measurement and reporting protocols is required to improve comparability and strengthen the evidence base.

Journal of Functional Biomaterials doi: 10.3390/jfb17090428

Authors: Chen Zong

Mechanical loading of connective tissues is traditionally prescribed by force magnitude. In viscoelastic tissues, a constant external force does not produce a constant internal mechanical environment: stress and strain evolve continuously after load onset, creating a time-varying tissue-level mechanical history relevant to resident cells. This distinction is rarely accounted for in clinical loading protocols or scaffold design. The rate of evolution is governed by the stress relaxation time constant (τ). How τ controls the persistence of mechanical signals under force-controlled sustained loading remains poorly quantified. Thus, we developed a three-dimensional finite element model of the Wistar rat maxillary first molar tooth–periodontal ligament (PDL)–bone complex with a PDL geometry reconstructed from micro-CT imaging by original frame-by-frame manual segmentation and compared outcomes across three τ values spanning two orders of magnitude under identical 0.5 N sustained loading. Under the same applied force, stress retention at 100 s ranged from 68% to 97%, while concurrent deformation creep showed an inverse relationship. These results demonstrate that τ strongly governs the persistence of mechanical signals under sustained force-controlled loading in this model. Supplementary simulations under oblique loading and perturbed PDL modulus confirmed that τ remains the dominant constitutive determinant of stress retention across altered loading directions and stiffness conditions.

Journal of Functional Biomaterials doi: 10.3390/jfb17090427

Authors: Izabela Fornazari Delamura Melissa Koto Murai Arthur Henrique Alécio Viotto Ana Maira Pereira Baggio Natália Saori Izumi Douglas Sadrac de Biagi Ferreira Vinicius Ferreira Bizelli Emanuele di Edoardo Ignazio Scuto Pietro Montemezzi Leonardo Perez Faverani Carlos Fernando Mourão Ana Paula Farnezi Bassi

In the original publication [...]

Journal of Functional Biomaterials doi: 10.3390/jfb17090426

Authors: Dennys Fernández-Conde Eneftali Flores-García Tushar Janardan Pawar Angélica M. Castillo-Paz José Rafael Alanis-Gómez Mario E. Rodríguez-García Enrique Delgado-Alvarado Fabiola Hernández-Rosas Rafael Ramírez-Bon

Implant-associated infections remain a major challenge in bone-related biomedical applications, where bacterial colonization and biofilm formation can compromise tissue integration and clinical performance. This study reports the mechanochemical synthesis, physicochemical characterization, antimicrobial activity, antibiofilm performance, and short-term fibroblast cytocompatibility of a TiO2-containing bovine-derived biogenic hydroxyapatite ceramic composite (BHAp-TiO2). The composite was prepared by high-energy mechanical milling using 10 wt% TiO2 and characterized by X-ray diffraction, Rietveld refinement, Raman spectroscopy, Fourier-transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. XRD/Rietveld analysis identified a multiphase ceramic composite composed of hydroxyapatite, whitlockite, and rutile TiO2, with no evidence of Ti4+ substitution into the hydroxyapatite lattice or detectable anatase within the XRD/Rietveld detection limit. SEM-EDS confirmed the granular agglomerated morphology of the powders and the elemental presence of Ti in BHAp-TiO2. Compared with pristine BHAp, BHAp-TiO2 produced a concentration-dependent reduction in AlamarBlue®-derived bacterial metabolic activity against five clinically relevant planktonic strains. At 200 µg/mL, residual metabolic activity decreased to 10.90–32.90%, depending on the bacterial species, with the strongest response observed for Escherichia coli. In crystal violet assays, BHAp-TiO2 markedly inhibited Pseudomonas aeruginosa biofilm biomass, reaching 91.9 ± 3.4% inhibition at 200 µg/mL. In NIH/3T3 fibroblasts, BHAp-TiO2 preserved short-term cytocompatibility after 24 h of direct exposure within the 0.1–100 µg/mL range, with MTT- and AlamarBlue®-derived responses remaining close to or above the 80% cytotoxicity limit. Overall, BHAp-TiO2 is best interpreted as a rutile TiO2-containing biogenic calcium phosphate ceramic composite with enhanced antimicrobial and antibiofilm performance while maintaining short-term fibroblast cytocompatibility under the evaluated conditions.

Journal of Functional Biomaterials doi: 10.3390/jfb17090425

Authors: Lisa Götz Leyla Dogan Philipp Wörsdörfer Nathaly A. Chicaiza-Cabezas Süleyman Ergün Jürgen Groll Florian Kleefeldt

Insufficient vascularization remains a major limitation in tissue engineering, restricting the survival and maturation of larger bioengineered constructs. While candidate hydrogels are commonly characterized with regard to physicochemical properties, gelation behavior, mechanical performance, and cytocompatibility, simple functional assays that assess their capacity to support vascular sprouting are less frequently integrated into early-stage biomaterial evaluation. Here, we investigated the established ex vivo aortic ring assay (ARA) as an exploratory functional approach for the initial comparison of selected hydrogel formulations. Murine aortic rings were embedded in collagen I (Col I), alginate (Alg), or gelatin methacryloyl (GelMA) and cultured under control conditions or with vascular endothelial growth factor A (VEGF-A) stimulation. These hydrogels were intentionally selected as a proof-of-concept panel of representative, non-equivalent material classes with distinct expected cell-interactive properties. After five days, Col I supported robust capillary-like outgrowth that was further enhanced by VEGF-A, whereas the tested GelMA formulation supported only limited cellular migration and the tested unmodified Alg formulation showed no detectable sprouting under the conditions examined. Cluster of differentiation 31 (CD31) immunostaining supported the presence of an endothelial component within the Col I-supported sprouting structures. These findings demonstrate that the ARA can detect pronounced formulation-dependent differences among the specific hydrogels tested using straightforward morphological and immunostaining readouts. Within the scope of the formulations tested, these findings support the ARA as a complementary functional readout alongside conventional biomaterial characterization before more complex tissue engineering or biofabrication studies are performed.

Journal of Functional Biomaterials doi: 10.3390/jfb17090424

Authors: Adnan Alsaei Ayah Binrajab Shahd Alsaei Fatema Rahimi Ahmad Zarwi Helen N. Zarwi Renad Alansari G. Roshan Deen

Diabetes mellitus continues to impose a substantial global health burden, underscoring the need for therapeutic systems capable of achieving precise, adaptive, and patient-friendly glycemic control. Conventional diabetes treatments, including repeated insulin injections and oral hypoglycemic agents, are often constrained by non-physiological drug release, poor adherence, systemic side effects, and the persistent risk of hypoglycemia. In this context, glucose-responsive nanomedicine has emerged as a promising platform for next-generation diabetes therapy by enabling self-regulated and glucose-triggered delivery of insulin and other antidiabetic agents. This review highlights recent advances in glucose-responsive nanomedicine, focusing on the principal sensing mechanisms, including glucose oxidase-based, phenylboronic acid-based, and lectin-mediated systems, as well as the nanoscale carriers engineered to support them, such as polymeric nanoparticles, nanogels, micelles, liposomes, and hybrid nanostructures. These smart platforms offer significant potential to improve drug stability, enhance targeting efficiency, reduce dosing frequency, and more closely mimic endogenous insulin secretion. The review further examines their emerging role in precision diabetes care, particularly in combination with continuous glucose monitoring technologies, wearable devices, and closed-loop therapeutic systems. Despite notable progress at the preclinical level, important barriers to clinical translation remain, including challenges related to biocompatibility, long-term safety, reproducibility, scalable manufacturing, and regulatory approval. Collectively, glucose-responsive nanomedicine represents a rapidly advancing and clinically relevant field with the potential to redefine diabetes management through intelligent and personalized therapeutic strategies. This review provides a focused overview of current developments, key translational challenges, and future directions toward clinical implementation.

Journal of Functional Biomaterials doi: 10.3390/jfb17080423

Authors: Paweł Maksymiuk Maja Ptasiewicz Joanna Zubrzycka Ilona Wójcik-Chęcińska Katarzyna Sarna-Boś Piotr Stachurski Renata Chałas

Objectives: Initial caries lesions (ICLs) are the earliest manifestation of dental caries, characterized by subsurface porosity that affects enamel’s optical properties while maintaining its surface integrity. Resin infiltration is a minimally invasive approach to managing these lesions by penetrating and sealing pores with low-viscosity resin, potentially modifying their visual appearance. In order to provide a quantifiable, objective assessment of this optical behavior, this study aimed to evaluate the modulation of color coordinates and VITA Classical shade transitions within the initial lesions immediately following infiltration with Icon Smooth Surface (DMG, Hamburg, Germany). Materials and Methods: Forty-nine extracted human premolars with naturally occurring proximal ICLs (subsurface demineralization) were selected. Lesions were assessed for fluorescence level using 655 nm laser fluorescence (DIAGNOdent pen). Reflectance spectrophotometry (SpectroShade Micro) was employed to record color coordinates in the CIELab and CIELCh spaces, alongside VITA Classical shades, before and after resin infiltration. Results: The infiltration procedure resulted in a statistically significant increase in b* (yellowness) and subsequent C* (chroma) parameters (p < 0.05). VITA Classical shade guide analysis showed an insignificant shift in color distribution according to value (p > 0.05). Conclusions: The present exploratory study provides quantitative insights into the immediate color-modifying effects of a resin infiltration procedure on natural initial proximal caries lesions, complementing the existing literature with objective CIELab/CIELCh and VITA Classical measurements. The p-values should be interpreted as descriptive indicators of potential trends rather than definitive statistical proof. Further research with larger cohorts and long-term follow-up is needed to validate the durability and clinical relevance of these esthetic outcomes.

Journal of Functional Biomaterials doi: 10.3390/jfb17080422

Authors: Zhangling Nie Bingqiang Lu Valentina K. Krut’ko Anatoly I. Kulak Feng Chen

Polyphosphate (PolyP) is an inorganic polymer composed of orthophosphate units linked by high-energy phosphate anhydride bonds, widely found in various organisms from bacteria to mammals. In recent years, PolyP has attracted widespread attention in the field of bone tissue engineering due to its unique biological characteristics, possessing both osteoinductive activity and metabolic energy supply functions. This article systematically reviews the molecular structure, physicochemical properties, and multiple mechanisms by which PolyP promotes osteogenic differentiation, as well as biomaterial design strategies based on PolyP. PolyP can synergistically promote osteogenic differentiation through multiple mechanisms, including by acting as a phosphate donor, providing metabolic energy, regulating signaling pathways such as Wnt/β-catenin, and modulating the osteoprotegerin/receptor activator of nuclear factor κB ligand (OPG/RANKL) balance. In terms of material design, PolyP can form nano/microparticles with metal ions such as Ca2+, Sr2+, and Mg2+ and can also be compounded with polymers to construct various forms such as hydrogels, bone cement, and three-dimensional (3D)-printed scaffolds. Preclinical studies have shown that PolyP-incorporated materials exhibit excellent osteogenic performance and biocompatibility in bone defect repair, and preliminary clinical studies have also confirmed its feasibility. This article aims to provide a comprehensive overview of the current applications of PolyP-incorporated materials and delineate future directions, challenges, and necessary pathways for their clinical translation.

Journal of Functional Biomaterials doi: 10.3390/jfb17080421

Authors: Teodora-Alina Tincea Alexia-Ecaterina Cârstea Vlad-Gabriel Vasilescu Andreia Cucuruz Adela Banciu Adrian-Ionuț Nicoară Claudia-Gabriela Mateiaș Ana-Maria Cristina Țâncu Silviu-Mirel Pițuru Marina Imre Lucian-Toma Ciocan

The rapid adoption of vat photopolymerization (3D printing) in restorative and prosthetic dentistry has outpaced the independent biological characterization of the dimethacrylate resins on which it relies, even though incompletely converted networks can release residual monomers that are cytotoxic to the adjacent oral tissues. This study reports a qualitative in vitro cytotoxicity screening of three commercial photopolymer resins optimized for additive manufacturing: a general-purpose resin (ANYCUBIC) and two resins with a declared dental indication (TEMP PRINT and V-PRINT) performed according to the morphological evaluation described in ISO 10993-5. Aqueous extracts were prepared following ISO 10993-12 and applied to normal human fibroblasts (BJ line, ATCC CRL-2522) at 100% and 50% concentration for 24 h; morphological reactivity was graded on the standardized 0–4 scale by inverted light microscopy against an unexposed control, and supported by a semi-quantitative visual estimate of the proportion of affected cells. All three materials produced a concentration-dependent response. TEMP PRINT retained the best cellular compatibility (grade 1 at 50%, grade 2 at 100%), V-PRINT was intermediate, and ANYCUBIC showed the most pronounced reactivity (approaching grade 3 at 100%), giving an estimated cytotoxicity order of ANYCUBIC > V-PRINT > TEMP PRINT. As a qualitative morphological screening, the findings indicate that the dental-grade resins elicited a milder fibroblast response than the general-purpose photopolymer and support the recommendation that general-purpose resins should not be substituted for certified materials in intraoral use. Confirmation by quantitative viability assays with independent replicates is required before firm conclusions are drawn. In line with the qualitative nature of ISO 10993-5 morphological screening, the reported proportions of morphologically affected cells represent visual scoring rather than direct measurements of cell viability, and the study is therefore presented as an initial biological screening.

Journal of Functional Biomaterials doi: 10.3390/jfb17080420

Authors: Robert Mau Georg Schnell Paul Oldorf Hermann Seitz

Background: Micro-reservoirs in implant surfaces represent a promising drug carrier concept for drug delivery systems. For drug loading, inkjet printing enables highly precise droplet positioning. However, droplet drying influences drug crystallization from printed drug solution. This study investigates how evaporation-driven phenomena affect the precision and homogeneity of inkjet-based deposition of a crystallizing drug into exemplary micro-reservoirs. The aim is to guide the selection of suitable solvents and inkjet process parameters. Methods: Laser-drilled micro-reservoirs were fabricated as blind holes with entrance diameters of 100 µm and 400 µm in the surface of specimens of EN 1.4404 (equivalent to AISI 316L) stainless steel, a commonly used biomaterial. The reservoirs were loaded with two different drug solutions using piezoelectric drop-on-demand inkjet printing. Acetylsalicylic acid (ASA) was applied as a model drug representing crystallizing small-molecule drugs. Solvents with markedly different evaporation rates, ethanol (EtOH) as a representative high-volatility solvent and dimethyl sulfoxide (DMSO) as a representative low-volatility solvent, were selected. The number of jetted droplets per dispensing step was varied. Precision and homogeneity of the drug deposition were investigated using light and laser scanning microscopy. Results: Over the course of droplet drying, two phenomena, the coffee-ring effect and creeping, can impair drug deposition quality. The coffee-ring effect leads to inhomogeneous, ring-shaped drug deposits. Creeping is the evaporation-driven spreading of crystalline structures and reduces the precision of drug deposition. The EtOH-based ASA solution (c = 10 g/L) was intensely affected by both phenomena. Inhomogeneities could be partially compensated via tailoring the droplet count per dispensing step. The DMSO-based solution (c = 100 g/L) exhibited a more compact crystallization of ASA (requiring ~20% less volume in an exemplary experiment), no coffee-ring effect, and only minor creeping. Conclusions: The DMSO-based ASA solution enabled a more precise and homogeneous drug deposition than the EtOH-based solution under the investigated printing and crystallization conditions. EtOH-related limitations could be counteracted by controlling the number of jetted droplets per dispensing step.

Journal of Functional Biomaterials doi: 10.3390/jfb17080419

Authors: Ada Ayechu-Abendaño Letizia Cella Carmen Sánchez-González Carmen Sánchez-Matás José Luis López-Villalobos Cristina Díaz-Jiménez Rocío Fernández-Parra Mauro Malvè

Current airway stents, including silicone and metallic devices, remain associated with important complications such as migration, restenosis, mucus retention and the need for repeated interventions. Biodegradable stents offer a promising alternative by providing temporary mechanical support while avoiding the long-term presence of a permanent implant. However, the influence of stent geometry and material properties on their mechanical performance and interaction with airway tissue is still not fully understood. This study presents a computational framework integrating computer-aided design and finite element analysis to investigate the mechanical behaviour of biodegradable tracheobronchial stents. Two stent architectures (X-pattern and W-pattern) were analysed over a range of wire thicknesses using two biodegradable materials: a PLA/PCL; 70/30 wt.% blend and AZ31 magnesium alloy. Radial compression, diameter recovery after radial compression and stent–tissue interaction simulations were performed to evaluate the influence of geometry, material selection and design parameters on device performance. The results suggested that both stent geometry and material properties strongly influence the mechanical behaviour of biodegradable airway stents, although they affect different aspects of the stent–tissue interaction. The X-pattern consistently exhibited greater resistance to radial compression, lower elastic diameter recovery after radial compression and improved maintenance of the expanded lumen compared with the W-pattern. Material properties primarily affected the magnitude of the mechanical response, as further confirmed by the quantitative contact-pressure analysis, with AZ31 providing greater radial support, while the spatial distributions of stress and strain within the tracheal wall were mainly governed by the stent architecture. Based on the computational analyses, X-pattern stents manufactured from the PLA/PCL; 70/30 wt.% blend were selected for in vivo evaluation in a rabbit model. Endoscopic observations revealed tissue features that were qualitatively consistent with the mechanical patterns predicted by the numerical simulations, although no direct causal relationship can be established from the available observations. These findings support the ability of the proposed framework to represent the principal aspects of stent–tissue interaction. The proposed computational framework provides a practical tool for the rational design and mechanical assessment of biodegradable airway stents and may facilitate the future development of customised airway prostheses.

Journal of Functional Biomaterials doi: 10.3390/jfb17080418

Authors: Gabriela Leață Dorin Ioan Cocoș Ramona Feier Corneliu Munteanu Fabian Cezar Lupu Ion Ciucă Kamel Earar

Biodegradable Mg–Ca–Sr alloys are promising candidates for temporary implant applications, but their degradation behavior is strongly influenced by alloy composition and electrolyte chemistry. This comparative short-term study investigated how increasing the Sr content from 0.5 to 1.5 wt.% influences the electrochemical response and surface characteristics of cast Mg–0.5Ca–xSr alloys in 0.9% NaCl and calcium- and magnesium-free Dulbecco’s phosphate-buffered saline (DPBS). Potentiodynamic polarization, electrochemical impedance spectroscopy, scanning electron microscopy, quantitative image analysis, and energy-dispersive X-ray spectroscopy were used. Increasing the Sr content reduced the corrosion-current density from 0.0110 to 0.0039 mA/cm2 in NaCl and from 0.297 to 0.169 mA/cm2 in DPBS, while the corresponding calculated corrosion rates decreased from 2.51 to 0.886 mm/year and from 6.66 to 3.79 mm/year, respectively. Replicated EIS measurements of both alloys showed that Mg–0.5Ca–1.5Sr exhibited higher charge-transfer resistance than Mg–0.5Ca–0.5Sr in both NaCl (253 ± 15 versus 184 ± 14 Ω·cm2) and DPBS (853 ± 48 versus 615 ± 42 Ω·cm2). NaCl-exposed surfaces showed more porous and discontinuous deposits and a greater number of visible pit-like defects, whereas DPBS produced comparatively continuous P-containing deposits. Overall, increasing the Sr content to 1.5 wt.% was associated with lower polarization-derived global corrosion kinetics and a more resistive interfacial response, whereas electrolyte composition strongly influenced both interfacial impedance and surface-deposit morphology. These findings represent comparative short-term electrochemical and surface-characterization data obtained at 23 ± 1 °C and should not be interpreted as measures of long-term physiological degradation or in vivo performance.

Journal of Functional Biomaterials doi: 10.3390/jfb17080417

Authors: Shazah Waqar Tamer A. E. Ahmed Maxwell T. Hincke

Bone loss represents a significant clinical burden that has driven the development of improved orthopedic graft substitutes. Although current grafting options, including autografts, allografts, and xenografts, have demonstrated considerable therapeutic potential, their widespread application is constrained by limitations such as donor scarcity, limited availability, and associated clinical risks. Consequently, biologically derived materials, including avian eggshells and marine bivalve shells, have emerged as promising alternative sources to produce bone precursor materials and next-generation bone graft substitutes. This review summarizes recent advances in avian eggshell- and marine shell-derived calcium carbonate (CaCO3) materials for bone regeneration and examines their preclinical evaluation in diverse animal models, including critical-size defects in calvarial, femoral, radial and mandibular bone. Relevant studies published over the past ten years were systematically analyzed, focusing on natural calcium carbonate systems derived from avian eggshell and marine shells, including oyster, mussel, clam, scallop, cockle, and sea urchins. A structured literature search was conducted using PubMed, Scopus, and Google Scholar to identify studies published between 2015 and 2025 investigating eggshell- and aquatic-derived biomaterials for bone repair and regeneration. Eligible studies were screened, and data were comparatively analyzed with respect to biomaterial source, scaffold fabrication, physicochemical characteristics, mechanical performance, biocompatibility, osteogenic potential, and the use of preclinical animal studies. Eggshell-derived biomaterials currently show the strongest translational evidence, while aquatic shell-derived biomaterials remain promising but underexplored for bone regeneration. Furthermore, this review critically examines the scientific, manufacturing, and regulatory challenges that must be addressed before clinical implementation.

Journal of Functional Biomaterials doi: 10.3390/jfb17080416

Authors: Adrian Lendvai Tobias Weichhart Hans Peter Weitzenböck Christoph Wiesner Rita Seeboeck Narges Zamani Michael Matzner Monika Pichler Bettina Steiner Andrea De Luna Stefan Nehrer Harald Hundsberger

Demineralized bone matrix (DBM)-derived allografts retain extracellular matrix (ECM)-associated factors involved in bone repair, but biochemical protein recovery alone may not predict functional pathway activation. We evaluated the HEK-Blue™ TGF-β Reporter Assay as a targeted method for assessing Smad-dependent reporter activity in DBM-derived materials. ECM proteins were extracted from cortical demineralized bone granules (DBG) using guanidine hydrochloride (GuHCl) or urea and quantified after extraction, dialysis, and sterile filtration. Reporter cells were stimulated with extracted ECM proteins or directly with processed cortical and cancellous products, including DBG, wet heat-treated DBG formulated as Putty (PHT), and gamma-irradiated PHT (PGI). Non-pooled DBM sponge samples were also tested. Secreted embryonic alkaline phosphatase (SEAP) activity served as the functional reporter readout. Material-only no-cell controls assessed material-derived background. PrestoBlue™ readouts served as exploratory quality controls. The urea-derived extract yielded a higher apparent BCA-detectable protein concentration than the GuHCl-derived extract. Only the GuHCl-derived extract induced increasing SEAP activity at matched protein input. Direct stimulation showed reporter activation above the TNF-α pathway-negative cytokine control for cortical DBG, PHT, PGI, and cancellous DBG. DBM sponges also induced detectable SEAP activity. These findings support targeted functional screening of Smad-dependent TGF-β reporter activation in DBM-derived materials, but not total osteoinductivity assessment.

Journal of Functional Biomaterials doi: 10.3390/jfb17080415

Authors: Jiaqi Chen Huiyu Jia Xinyue Zhang Da Liu Xushuang Jia Xintong Gu Hongjuan Wen Ye Jin

DNA hydrogels are an emerging class of biomaterials with programmability, biodegradability, biocompatibility, and dynamic responsiveness, enabling precise regulation of osteoblast and mesenchymal stem cell (MSC) proliferation and differentiation, activation of key signaling pathways, and promotion of angiogenesis and bone matrix mineralization. In contrast, conventional bone repair materials exhibit limitations including poor mechanical strength, uncontrollable degradation, and inadequate matching with native bone properties, restricting their application in osteoporotic defect repair. Current osteoporotic defect therapies, mainly anti-resorptive and anabolic agents, remain insufficient for many patients. Here, we propose pure and hybrid DNA hydrogels as novel therapeutic platforms to restore the dynamic balance between bone resorption and formation, thereby enhancing osteogenesis and facilitating bone regeneration and remodeling under osteoporotic conditions. Although challenges such as high production cost and long-term safety persist, integration with advanced technologies (e.g., 3D printing and gene editing) may provide theoretical support for further investigation of personalized and intelligent therapeutic strategies at the pre-clinical research stage, offering new insights into osteoporotic bone defects and bone tissue regeneration.

Journal of Functional Biomaterials doi: 10.3390/jfb17080414

Authors: Zeliha Başak Çakır Erdil Hüseyin Akıllı Şahin Altuğ Metin Çalışır

Background/Objectives: The aim of this study was to evaluate the effect of intraoperative gaseous ozone applied to the implant osteotomy immediately before implant placement on early implant stability using a split-mouth design and resonance frequency analysis (RFA). Methods: This prospective, randomized controlled split-mouth study included 40 patients receiving 106 implants in bilaterally symmetrical edentulous sites. Patients and outcome assessors were blinded. In the ozone group, ozone gas was applied to the implant site for 60 s immediately before implant placement; the control group underwent the same surgical protocol without ozone application. The primary outcome was the change in implant stability quotient from baseline to three months (ΔISQ). Secondary outcomes included baseline and three-month ISQ values, insertion torque, and postoperative pain assessed using a visual analog scale. Results: All 106 implants were analyzed. No significant between-group differences were observed in baseline ISQ (β = −0.49; 95% CI: −2.73 to 1.75; p = 0.668) or insertion torque (β = −0.62 Ncm; 95% CI: −1.96 to 0.72; p = 0.362). At three months, ISQ was higher in the ozone group (β = 1.91; 95% CI: 0.75 to 3.06; p = 0.001). ΔISQ was also significantly greater in the ozone group (β = 2.40; 95% CI: 0.34 to 4.45; p = 0.022; Cohen’s d = 0.42). Implant stability increased significantly in both groups (both p < 0.001). Postoperative pain did not differ between groups (β = −0.23; 95% CI: −0.83 to 0.36; p = 0.446). Although the effect direction was consistent across sensitivity analyses, ΔISQ was not statistically significant in the patient-level paired analysis (p = 0.089). No adverse events were reported. Conclusions: Intraoperative ozone application was associated with a modest increase in early implant stability without a significant difference in postoperative pain. However, given the small effect size and sensitivity of the findings to the analytical method, further large-scale, multicenter randomized controlled trials are required. Clinically, intraoperative ozone may be considered a potential adjunct to standard implant placement protocols, but the current evidence is insufficient to support its routine use.

Journal of Functional Biomaterials doi: 10.3390/jfb17080413

Authors: Lucian Floare Otilia Cornelia Bolos Ramona Dumitrescu Marioara Nicoleta Caraba Iasmina-Mădălina Petculescu Carmen Opris Octavia Balean Vanessa Bolchis Bianca Ioana Todor Cristina Elena Savencu Atena Galuscan Daniela Jumanca

The interaction between restorative materials and microbial biofilms plays an important role in restoration longevity and the development of secondary caries. This study aimed to perform a multidimensional characterization of four commercially available flowable resin-based dental composites by evaluating their surface roughness, Vickers microhardness, surface morphology, and microbial biofilm formation under standardized in vitro conditions. Filtek™ Bulk Fill Flowable Restorative (3M), Tetric EvoFlow (Ivoclar Vivadent), BRILLIANT Flow (Coltene), and G-ænial™ Universal Injectable (GC) were investigated. Surface roughness was determined by contact profilometry, microhardness was assessed using the Vickers method, and microstructural characteristics were analyzed by scanning electron microscopy (SEM). Microbial biofilm biomass formed by Gram-positive bacteria, Gram-negative bacteria, and Candida albicans, including both reference strains and clinical isolates, was quantified using a crystal violet assay to compare material-dependent microbial colonization. G-ænial™ Universal Injectable exhibited the lowest roughness values, whereas BRILLIANT Flow showed the highest microhardness. SEM analysis revealed a more homogeneous surface morphology for Filtek™ Bulk Fill Flowable Restorative and G-ænial™ Universal Injectable, while Tetric EvoFlow and BRILLIANT Flow displayed increased topographical heterogeneity. Although modest differences in biofilm biomass accumulation were observed among the investigated composites (4.37–12.21% relative biomass reduction compared with the control), no material demonstrated a distinct advantage under the experimental conditions. The integrated evaluation of surface roughness, microhardness, surface morphology, and microbial biofilm formation provides a comparative characterization of commercially available flowable resin-based composites and contributes to a better understanding of material–biofilm interactions. These findings may support the future development of multifunctional restorative biomaterials with improved biofilm-modulating properties.

Journal of Functional Biomaterials doi: 10.3390/jfb17080412

Authors: Jirun Sun

Since the pioneering work of Dr [...]

Journal of Functional Biomaterials doi: 10.3390/jfb17080411

Authors: Iana Schmitt Jorge Perdigão Guilherme Carpena Lopes

The peer-reviewed literature on the use of universal adhesives (UAs) with core build-up composite resins (CBCRs) is limited. UAs may enhance the polymerization of dual-cured composite resins, leading to increased microhardness due to the “touch-cure” effect. This study compared the dentin bond strengths and microhardness of CBCRs bonded with UAs. A total of 480 bovine incisors were randomly allocated into 20 groups (n = 24). Two dual-cured CBCRs, ParaCore (PrCore) and Gradia Core (GrCore), one light-cured CBCR, Clearfil Photo Core (PhotoCore), and Filtek Z250 (Z250) were evaluated. For the dual-cured CBCRs, the UAs from the respective manufacturers were mixed with a dual-cure activator (Act): One Coat 7 Universal (OC7+Act) and G-Premio Bond (GrPB+Act). Three additional UAs were evaluated: Tokuyama Universal Bond II (TUB), Scotchbond Universal Plus Adhesive (SBUP), and Scotchbond Universal Adhesive with Dual Cure Activator (SBU+Act). Shear bond strength was evaluated after 24 h. Additional specimens were prepared for Vickers microhardness (VHN) evaluation, with or without UA application to the bottom surface. Bond strengths ranged from 7.4 ± 4.0 to 37.0 ± 7.5 MPa. GrCore and PrCore showed higher bond strengths with SBU+Act than with their manufacturer-recommended adhesives. Dual-cured CBCRs exhibited lower dentin bond strengths and lower VHN than the light-cured composite resins, and the touch-cure effect was more effective for GrCore and PhotoCore.

Journal of Functional Biomaterials doi: 10.3390/jfb17080410

Authors: Jurica Matijević Anja Baraba Adna Vlahovljak Ferušić Matea Vidov Zoran Karlović Ana Ivanišević

The aim of this study was to evaluate the influence of n-butyl cyanoacrylate (NBCA) coating of freshly mixed mineral trioxide aggregate (MTA) on its microhardness after setting under conditions of moisture and human blood exposure. MicroMega MM-MTA samples were prepared using Teflon molds (6 mm × 4 mm). Four experimental groups (n = 4) were established: control (MTA + phosphate-buffered saline (PBS)), MTA coated with NBCA (PeriAcryl) + PBS, MTA + blood + PBS, and MTA coated with NBCA + blood + PBS. Samples assigned to the blood-exposure groups were exposed to human blood for 15 min, rinsed, and subsequently stored in PBS. Prior to microhardness testing, all samples were incubated in PBS for seven days. Microhardness was measured using a Vickers microhardness tester, with five indentations performed on each specimen (20 measurements per group). Data were analyzed using the Shapiro–Wilk test for normality, Levene’s test, and two-way ANOVA, followed by Tukey’s post hoc test. The analysis revealed significant differences among the experimental groups (p < 0.001). Post hoc analysis demonstrated statistically significant differences between tissue glue-coated and uncoated samples (p < 0.05). Within the limitations of this in vitro study, coating MTA with NBCA tissue glue during the setting period significantly increased its microhardness following exposure to human blood and PBS.

Journal of Functional Biomaterials doi: 10.3390/jfb17080409

Authors: Andrew Blass Watson Matthew J. Atwill Tomoko Fujiwara Ranganathan Gopalakrishnan Jessica Amber Jennings Joel D. Bumgardner

Chitosan and calcium phosphate (CaP) are attractive bioactive coating materials for titanium (Ti) orthopedic implants, but coating approaches must provide uniform deposition, adequate adhesion, and cytocompatibility. This proof-of-concept study evaluated whether CaP microshells could be incorporated into electrosprayed chitosan coatings bonded to silanized Ti substrates without compromising coating properties. CaP microshells were synthesized using carbon microsphere templates and added to chitosan electrospray solutions at 0.25, 0.5, and 1.0 wt% relative to chitosan. Electrospray parameters were adjusted, and coatings were characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, tensile adhesion testing, water contact angle measurements, and W-20-17 bone marrow stromal cell culture. Increasing capillary diameter and reducing pressure enabled stable deposition of uniform composite coatings containing up to 1.0 wt% CaP. CaP microshells were distributed across the coating surfaces and throughout the coating thickness. Silanization significantly increased coating adhesion compared with non-silanized Ti, while CaP incorporation up to 1.0 wt% did not significantly reduce bond strength. All coatings were hydrophilic and supported viable cell attachment and growth over five days. These findings support the feasibility of electrosprayed chitosan–CaP microshell coatings as adhesive, cytocompatible bioactive coating platforms for Ti implant materials.