Journal of Functional Biomaterials doi: 10.3390/jfb17050244

Authors: Xin Qiao Kai Liu Jie Tang Shijian Deng Deqin Yang

Background: Impaired angiogenesis and persistent inflammation are hallmarks of chronic diabetic wounds. Extracellular vesicles derived from dental pulp stem cells (DPSC-EVs) represent a promising cell-free therapy for tissue repair; however, their clinical translation is hindered by suboptimal yields and attenuated bioactivity associated with conventional two-dimensional (2D) culture. This study investigated whether a biomimetic three-dimensional (3D) fibrin/gelatin hydrogel system could optimize the therapeutic potency of DPSC-EVs for diabetic wound healing. Methods: DPSCs were encapsulated within 3D fibrin/gelatin scaffolds, followed by comprehensive characterization of cell viability and morphology. 3D-EVs and 2D-EVs were isolated via ultracentrifugation and validated by transmission electron microscopy and nanoparticle tracking analysis. The pro-angiogenic capacity of 3D-EVs was evaluated using human umbilical vein endothelial cells (HUVECs) under high-glucose (HG) stress. Additionally, the immunomodulatory effects were assessed by monitoring macrophage polarization in lipopolysaccharide-stimulated RAW 264.7 cells. The therapeutic efficacy was further validated in vivo using a streptozotocin (STZ)-induced diabetic mouse model with full-thickness cutaneous wounds. Results: The 3D fibrin/gelatin hydrogel provided a supportive microenvironment that significantly augmented the secretory productivity of DPSCs. Compared to 2D-EVs, 3D-EVs exhibited superior functional resilience in restoring HUVEC migration and tube formation under HG-induced oxidative stress. Furthermore, 3D-EVs effectively orchestrated the macrophage transition from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype, thereby modulating the immune microenvironment. In vivo, topical administration of 3D-EVs markedly accelerated wound closure, promoted re-epithelialization, and enhanced microvascular density and collagen maturation in diabetic mice. Conclusions: Our findings demonstrate that the 3D fibrin/gelatin culture system effectively primes the therapeutic profile of DPSC-EVs. These engineered vesicles accelerate diabetic wound healing by synergistically promoting angiogenesis and resolving chronic inflammation, offering a robust and potent cell-free strategy for the management of chronic diabetic ulcers.

Journal of Functional Biomaterials doi: 10.3390/jfb17050243

Authors: Razvan Flueras Ramona Amina Popovici Aniela-Roxana Nodiți-Cuc Andreea-Mihaela Kiș Diana Marian Dana Emanuela Pitic (Cot) Laria-Maria Trusculescu Adina Feher Andreea Salcudean Aura Mara Bodnar Ana Gabriela Seni Norina Consuela Forna Iustin Olariu

Background: The rapid evolution of dental adhesive systems presents both opportunities and challenges for clinical practice, particularly regarding the translation of emerging evidence into routine use. Aim: This study aimed to assess the knowledge, attitudes, and self-reported practices related to modern adhesive systems among Romanian dentists and to explore factors associated with their clinical decision-making. Materials and Methods: An observational cross-sectional study was conducted between November 2025 and February 2026 using a 115-item online questionnaire. A convenience sample of 372 Romanian dentists participated. Statistical analysis included descriptive statistics, chi-square and Kruskal–Wallis tests, and multivariate models (multiple linear regression, binary logistic regression, and multinomial logistic regression). Internal consistency of the knowledge scale was assessed using Cronbach’s alpha. Results: The knowledge scale demonstrated good reliability (Cronbach’s α = 0.873). Although 68.0% of respondents reported familiarity with universal adhesives, a discrepancy between awareness and reported clinical application was observed for several key concepts, including MMP inhibitors and hydrolytic stability. Notably, 14.8% of participants were unaware whether their preferred adhesive system contained 10-MDP. Continuing education frequency was the only independent predictor of higher knowledge scores (β = 1.63, p = 0.024), while greater clinical experience was inversely associated with rubber dam use (OR = 0.550, p = 0.024). Conclusions: The findings suggest a discrepancy between theoretical knowledge and the clinical implementation of modern adhesive concepts. Structured continuing education plays a critical role in improving knowledge and may help bridge this gap in clinical practice.

Journal of Functional Biomaterials doi: 10.3390/jfb17050242

Authors: Tanja Lunić Marija Rakić Maria Sbeih Marina Samardzic Céline des Courtils Biljana Božić Nedeljković

Achieving hemostasis is crucial in neurosurgery, yet conventional methods are not always feasible, making topical hemostatic agents necessary. Current resorbable hemostatic agents allow effective hemostasis but must remain in situ to prevent rebleeding. This can provoke foreign body reactions leading to prolonged microglia-mediated neuroinflammation, which may exacerbate damage and delay recovery. It highlights the need for new hemostatic materials that can be removed after controlling bleeding while being safe for neurons and microglia. One candidate is Hemo-Ionic, a non-resorbable hemostatic compress composed of calcium alginate and zinc (Zn2+). Hemo-Ionic previously demonstrated effective in vitro and in vivo hemostasis, comparable to Surgicel and TachoSil, and pro-repair properties. In this study, Hemo-Ionic’s effect on neuronal and microglial cells was investigated in vitro. Results showed that Hemo-Ionic preserved cell viability and had an antioxidant capacity through protection from lipid peroxidation. Hemo-Ionic also reduced nitric oxide and pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) expression and release by lipopolysaccharide (LPS)-stimulated microglial cells. Finally, neuronal viability was restored when exposed to supernatants of Hemo-Ionic-treated microglia. These findings indicate that Hemo-Ionic’s safety and capacity to reduce neuroinflammation, combined with its hemostatic efficacy and non-resorbable nature, make it a promising alternative to resorbable hemostatic agents used in neurosurgery.

Journal of Functional Biomaterials doi: 10.3390/jfb17050241

Authors: Margarita Aleksiuk Ana Kostenkova Saulius Drukteinis

Background: Biodentine is widely used in vital pulp therapy due to its bioactivity and biocompatibility. However, treatment success depends not only on the material but also on the restorative approach. Clinically, Biodentine may be used as a temporary bulk restoration before delayed placement of a composite or immediately covered with a definitive composite. Aim: To evaluate clinical outcomes reported for delayed composite placement after temporary Biodentine restoration and immediate composite restoration following Biodentine pulp capping in permanent teeth. Methods: A systematic review was conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD420261325248). Searches were performed in multiple databases. Clinical studies on Biodentine pulp capping reporting outcomes for either delayed or immediate composite restoration were included. Study selection, data extraction, and quality assessment were performed by two reviewers using Joanna Briggs Institute tools. Fourteen studies (8 randomized controlled trials and 6 cohort studies) were included. Results: Considerable heterogeneity was observed in study design and clinical protocols. Most included studies evaluated one of the two strategies separately, so the review results could not be interpreted as a direct comparison. In direct pulp capping, success rates ranged from 74–100% (delayed) and 79–100% (immediate). In indirect pulp capping, success rates ranged from 77.8–88% (delayed) and 80–95.2% (immediate). Meta-analysis was not feasible. Conclusion: Based on low certainty of evidence, both strategies show favorable outcomes, but current evidence does not support the superiority of either approach. Further well-designed comparative studies are needed.

Journal of Functional Biomaterials doi: 10.3390/jfb17050240

Authors: Esmanur Oruc Ulas Bulent Aktas Abuzer Acikgoz Serife Yalcin Hatice Gumushan Aktas Ebru Uyar Zeynep Celik

Developing bioactive glasses that simultaneously provide mechanical reliability, cytocompatibility, controlled ion release, and antibacterial functionality remains a major challenge in bone tissue engineering. In this study, borotellurite-based bioactive glasses with the composition (45 − x)TeO2–20Na2O–10CaO–15P2O5–10B2O3–xY2O3 (x = 0–7 mol.%) were designed to elucidate the role of Y2O3 in governing composition–structure–property relationships. Structural, thermal, mechanical, ion-release, bioactivity, cytocompatibility, cell-adhesion, and antibacterial properties were systematically evaluated, and the most promising composition was further modified by silver surface coating. Y2O3 incorporation markedly enhanced thermal stability, hardness, and fracture resistance, with hardness reaching 4.317 GPa at 7 mol.%, while the highest compressive strength was achieved at 1 mol.% Y2O3 (67.97 MPa). Importantly, Y2O3 regulated dissolution behavior and mitigated the severe long-term cytotoxicity of the undoped glass, maintaining all doped compositions above the ISO 10993-5 threshold after 30 days. Higher Y2O3 contents also promoted osteoblast adhesion and facilitated bioactive surface layer formation following SBF immersion. No detectable E. coli adhesion was observed, whereas the TBY3 composition exhibited the lowest S. aureus adhesion, further improved by silver coating. These results demonstrate Y2O3 as an effective multifunctional modifier for engineering mechanically robust, biologically favorable, and antibacterial borotellurite bioactive glasses for bone repair.

Journal of Functional Biomaterials doi: 10.3390/jfb17050239

Authors: Albert D. Luong Moorthy Maruthapandi John H. T. Luong

Chronic wounds remain a major clinical and economic burden due to persistent inflammation, impaired perfusion, microbial biofilms, and dysregulated immune responses that collectively stall epithelialization. Polymicrobial bacterial–fungal biofilms, including Candida species, further delay healing by sustaining inflammation and promoting treatment-resistant infection. Recent advances have accelerated the development of bioengineered skin substitutes, collagen matrices, and placental-derived grafts that modulate macrophage polarization, reactive oxygen species signaling, and extracellular matrix remodeling to restore tissue architecture and promote neovascularization. Their effectiveness, however, depends on integration within structured care pathways that emphasize debridement, moisture balance, and infection control. Artificial intelligence, three-dimensional bioprinting, flexible microelectronic sensors for real-time wound monitoring, and bioactive compounds derived from traditional Chinese medicine, are expanding the therapeutic landscape. Together, these innovations support a shift toward predictive, personalized, and regenerative wound-care strategies. This review aims to provide a mechanistic and clinically contextualized overview of advanced grafting biomaterials, highlighting current applications, limitations, and future directions in chronic wound care.

Journal of Functional Biomaterials doi: 10.3390/jfb17050236

Authors: Yueh-Chang Lee Pei-Lun Lai Chien-Ying Lai Fang-Ling Chang Shang-Yen Wu Po-Yu Lin Chi-Hsuan Chuang Yu-Xin Chou Zhao-Feng Chen Yu-Cheng Wu Chih-Lun Cheng Hsuan Lin Chi-Hou Ng Shang-Chih Yang Jean Lu Rong-Kung Tsai

Direct chemical reprogramming provides a potentially scalable approach for generating retinal lineage-associated cells without genetic manipulation. In this study, human Tenon’s capsule fibroblasts were converted into retinal progenitor-like cells using a defined small-molecule cocktail. Retinal lineage-associated features were evaluated by immunofluorescence staining, quantitative reverse-transcription PCR, Western blot analysis, and bulk RNA sequencing, showing upregulation of neural and retinal markers, including VSX2, and transcriptomic remodeling consistent with transcriptional features associated with neuronal differentiation programs. Functional responsiveness was assessed by glutamate-evoked intracellular calcium imaging, revealing glutamate-responsive intracellular calcium dynamics in induced cells but not in parental fibroblasts. For in vivo assessment, induced cells were delivered via intravitreal transplantation in Wistar rats and subretinal transplantation in Long–Evans rats. One month after transplantation, structural and functional evaluations using optical coherence tomography, electroretinography, and histological analyses showed localized alterations in retinal structure at the subretinal injection site, while no significant differences were observed in scotopic ERG responses under the present experimental conditions. In contrast, fibroblast transplantation showed more prominent structural alterations under similar conditions. Human nuclei-positive signals were detectable in a subset of eyes, exhibiting focal and heterogeneous distribution within retinal regions at the one-month endpoint. Collectively, these suggest the induction of retinal lineage-associated molecular and functional features, with short-term functional tolerability observed in vivo under the present experimental conditions.

Journal of Functional Biomaterials doi: 10.3390/jfb17050238

Authors: Dijana Popovic Grubac Djordje Bozovic Jelena Lecic Ines Kovacic Ognjenka Janjic Pavlovic Aleksandra Zuza Dea Krsticevic Nedeljka Ivkovic

The “all-on-four” concept is a prominent solution for rehabilitating edentulous patients with fixed full-arch restorations. This study aimed to examine the stress distribution pattern, material fatigue, and restoration displacement using different framework materials under static (SL) and dynamic (DL) loading conditions. Six three-dimensional finite element analysis models of an atrophic maxilla rehabilitated via the all-on-four concept were analyzed. Models utilized three different framework materials: Cobalt–Chromium Alloy (CoCr), Zirconia (Zr), and Polyetheretherketone (PEEK). The models were subjected to three types of SL (90, 150, and 200 N) and two cases of DL (150 N) simulating mastication. DL generated higher stress intensities compared to SL. PEEK models showed the highest stress concentrations in the cortical bone (up to 70.44 MPa) and implants across SL models. The PEEK frameworks showed a risk of fatigue-related fracture of the cortical bone around terminal implants. Models utilizing PEEK frameworks exhibited significantly greater structural displacement (up to −0.681 mm horizontally) under DL compared to their rigid counterparts. CoCr and Zr provide better resistance to cyclic loading and reduced displacement, ensuring a higher safety factor. PEEK frameworks demonstrated inferior mechanical resistance under fatigue.

Journal of Functional Biomaterials doi: 10.3390/jfb17050237

Authors: Carlos Alberto Luna-Lara Carlos Roberto Luna-Dominguez Rogelio Oliver-Parra Omaika Victoria Criollo-Barrios María de los Dolores Vaca-Jasso Marco Felipe Salas-Orozco

Background: Metallic and metal oxide nanoparticles are increasingly explored as antimicrobial biomaterials in endodontics due to their multi-target mechanisms of action, largely mediated by metal ion release (e.g., Ag+, Cu+). However, bacterial metal resistance systems, particularly efflux-related proteins, may influence their antimicrobial performance. This study aimed to analyze the prevalence and distribution of metal resistance-associated proteins in bacteria involved in endodontic infections using a bioinformatic approach. Methods: An in silico, cross-sectional bioinformatic analysis was conducted using publicly available genomes from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC). Bacterial species associated with acute apical abscess (AAA), symptomatic apical periodontitis (SAP), asymptomatic apical periodontitis (AAP), and post-treatment apical periodontitis (PTAP) were included. The presence of selected metal resistance-related proteins (CutC, CopA, CzcA, CusA, SilA, P-type ATPase, and PA3920) was assessed using a binary presence/absence framework. Prevalence, group comparisons (Fisher’s exact test), and co-occurrence patterns (Phi coefficient) were analyzed. Results: Metal resistance-associated proteins were widely distributed across all infection types, with prevalence ranging from 70.0% to 82.9% and no significant differences between groups (p > 0.05). CutC was the most prevalent protein, followed by CopA and CzcA, whereas SilA and PA3920 were not detected. Correlation analysis revealed consistent co-occurrence patterns among key taxa, including Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella spp. Conclusions: Metal resistance-related proteins are broadly distributed in endodontic microbiota, indicating a conserved genetic capacity for metal tolerance. These findings suggest that microbial resistance determinants may influence, but do not directly determine, the antimicrobial performance of nanoparticle-based biomaterials. This study provides a hypothesis-generating, bioinformatic framework to support the design and optimization of antimicrobial biomaterials, highlighting the need for experimental validation and integration of phenotypic and biofilm-based analyses.

Journal of Functional Biomaterials doi: 10.3390/jfb17050235

Authors: Xu Cao Caiyun Wang Ran Lu Yanting Mu Jiangqi Hu Bin Luo Su Chen

This study aims to investigate the effects of graphene oxide-modified titanium dioxide nanotube (TNT-GO) coatings on the biological behavior of Schwann cells and to evaluate their potential applications in dental implant surface modification and peripheral nerve regeneration. Titanium dioxide nanotubes (TNTs) were prepared by anodic oxidation, and graphene oxide (GO) was deposited on their surfaces by electrochemical deposition. The surface morphology and physicochemical properties were characterized by scanning electron microscopy (SEM), Raman spectroscopy, atomic force microscopy, X-ray diffraction, and contact angle measurements. The viability, proliferation, and adhesion of Schwann cells were assessed by cell counting kit-8 assay, live/dead staining, and SEM observation. The expression levels of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) were evaluated by immunofluorescence staining and real-time reverse-transcriptase polymerase chain reaction. The results indicated that TNT-GO surface significantly improved surface hydrophilicity and biocompatibility. Compared with the Ti and TNT groups, Schwann cells on TNT-GO surfaces exhibited enhanced proliferation, better spreading morphology, and significantly increased expression levels of NGF and GDNF. Overall, TNT-GO effectively promotes Schwann cell proliferation, adhesion, and neurotrophic factor secretion, suggesting its potential as a novel surface modification strategy to promote peri-implant nerve regeneration and improve osseoperception.

Journal of Functional Biomaterials doi: 10.3390/jfb17050234

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

Objectives: This study aimed to compare vertical bone gain (VBG) and horizontal bone gain (HBG) after guided bone regeneration using titanium-reinforced dense PTFE (TiR-dPTFE) versus reinforced PTFE mesh (RPM) at 9 and 12 months on three-dimensional tomographic imaging, and to perform histological assessment in selected cases. Materials and Methods: This prospective comparative case series included 14 patients (46 vertical ridge defect sites) treated with guided bone regeneration using either Ti-reinforced dPTFE membranes (TiR-dPTFE; n = 23) or resorbable porcine collagen membranes (RPM; n = 23). All sites received a 60:40 mixture of autogenous bone chips and anorganic bovine bone mineral (ABBM). After 9 months, during implant placement, a protective secondary augmentation using a 70:30 ABBM/autogenous mixture was performed and covered with a collagen membrane. Vertical and horizontal bone gain (VBG, HBG) were assessed on standardized matched CBCT cross-sections obtained at 9 and 12 months. Core biopsies were harvested at implant placement (9 months) for histological evaluation. Surgical and healing complications were recorded. Results: Both membranes produced significant VBG. TiR-dPTFE achieved greater VBG than RPM at 9 months (p = 0.045) and 12 months (p = 0.012) and remained stable from 9 to 12 months, whereas RPM showed a significant decline over time (MDa −0.48 mm; 95% CI −0.64 to −0.31; p < 0.001). HBG was similar between groups at both time points (p = 0.918 and p = 0.922). No major clinical complications occurred. Histology at 9 months confirmed vital bone formation and graft integration in both groups. Conclusions: Both TiR-dPTFE and RPM are reliable options for vertical ridge augmentation; TiR-dPTFE yielded superior and more stable vertical gains over 12 months, with comparable horizontal outcomes. Clinical Relevance: TiR-dPTFE may offer enhanced vertical augmentation, while both membranes remain suitable for implant site development.

Journal of Functional Biomaterials doi: 10.3390/jfb17050233

Authors: Selina Wrublewsky Jan Weigl Caroline Bickelmann Matthias W. Laschke

Surgical sutures are widely used biomaterials in clinical practice. Like all other biomaterials, they induce a foreign body response after implantation that involves inflammation and angiogenesis. Although it is well known that these processes differ in males and females, sex-specific differences in the tissue response to sutures have not been investigated so far. To do this in the present study, polypropylene sutures were implanted into the dorsal skinfold chamber and subcutaneous flank tissue of male and female mice to assess their acute and chronic effects on the local tissue microenvironment using intravital fluorescence microscopy and immunohistochemistry over 14 and 28 days, respectively. Microhemodynamic parameters and the numbers of rolling and adherent leukocytes in venules next to the implants were comparable in male and female mice. Immunohistochemical analyses on day 14 revealed a stronger neutrophilic (myeloperoxidase (MPO)+ cells: 526 ± 29 mm−2) and macrophage (CD86+ cells: 188 ± 21 mm−2; CD163+ cells: 269 ± 25 mm−2) response, as well as reduced T-cell activation (CD3+ cells: 31 ± 4 mm−2) in females when compared to males (MPO+ cells: 221 ± 25 mm−2; CD86+ cells: 120 ± 15 mm−2; CD163+ cells: 101 ± 19 mm−2; CD3+ cells: 62 ± 13 mm−2), while microvessel density and collagen deposition in the forming granulation tissue around the implants did not differ between sexes. In the flank model, there were no detectable sex-specific differences in the chronic foreign body response. These findings demonstrate that polypropylene sutures provoke a stronger early activation of the innate immune system in females, whereas the chronic foreign body response to the implants is comparable in both sexes.

Journal of Functional Biomaterials doi: 10.3390/jfb17050232

Authors: Iwona Lasocka Karolina Gregorczyk-Zboroch Aleksandra Krajewska Ewa Skibniewska Michał Skibniewski Lidia Szulc-Dąbrowska

Maintaining an appropriate balance of macrophage subpopulations throughout the wound healing process, using a graphene monolayer as a substrate, may represent a promising therapeutic strategy. In this study, the effect of a graphene monolayer on the polarization of RAW 264.7 macrophages was investigated using flow cytometry, fluorescence microscopy, and ELISA. Analysis of surface M1 (MHC II, CD80, CD86) and M2 (CD163, CD200R, CD206) markers demonstrated generally higher expression of M1 markers in M1-polarized groups (control, CM1; and graphene monolayer, GM1) compared to M2-polarized groups (CM2 and GM2), likely as a result of LPS and IFN-γ stimulation. Culturing macrophages on a graphene monolayer as a substrate for LPS- and IFN-γ-stimulated cells was associated with a trend toward reduced expression of all analyzed M1-associated markers compared with the control M1 group; however, this effect did not reach statistical significance. TNF-α secretion was higher in GM1 compared to CM0, GM0, and CM2. In contrast, surface markers alone were less conclusive for identifying M2 polarization, whereas intracellular markers such as ARG1 provided a more robust indication of the M2 phenotype. ARG1 expression was significantly elevated in CM2 and GM2 groups, with GM2 showing a significant increase relative to the control groups (CM0, CM1) and GM0 and GM1. These findings further support ARG1 and NOS2 as reliable markers of M2 and M1 polarization, respectively. The graphene monolayer did not induce spontaneous macrophage polarization. Only under M1 (LPS and IFN-γ) and M2 (IL-4 and IL-13) stimulation did it show a consistent trend toward modest modulation of macrophage polarization, possibly creating conditions conducive to tissue healing.

Journal of Functional Biomaterials doi: 10.3390/jfb17050231

Authors: Mina Aleemardani Farnaz Ghorbani

Recent years have seen significant progress in functional biomaterials for biomedical applications, driven by advances in materials engineering, nanotechnology, and biological characterization techniques [...]

Journal of Functional Biomaterials doi: 10.3390/jfb17050230

Authors: Giuseppe De Giorgio Barbara Medagli Biagio Matera Katia Rupel Giuseppe Tarabella Gianluca Turco Maddalena Manfredi Benedetta Ghezzi Pasquale D’Angelo

Bone tissue has a remarkable regenerative capacity; however, advanced strategies are needed to support the repair process for critical-sized defects. While autografts and allografts remain the gold standard, their limitations have stimulated alternative approaches in bone tissue engineering, in search of scaffolds capable of mimicking native bone properties to promote effective regeneration. In this study, silk fibroin (SF)-based composite scaffolds incorporating β-tricalcium phosphate (β-TCP) and poly-ε-caprolactone (PCL) were synthesized using a simple and innovative cryogenic foaming method. The proposed fabrication technique overcomes many limitations of current synthesis methods, such as long processing times, the use of solvents, and reliance on complex, energy-intensive equipment. The composites were characterized using infrared spectroscopy to confirm the incorporation of all three components and their chemical bond arrangements. µ-CT, SEM, and ESEM analyses revealed that SF/β-TCP/PCL scaffolds exhibited great porosity and dynamic interaction with water while preserving pore morphology in wet environments. Swelling behavior, indirect cytotoxicity, and cell proliferation tests recognized the greater performance of SF/β-TCP/PCL scaffolds in promoting long-term cell proliferation, maintaining superior mechanical properties. These findings indicate that the proposed original, simple, and relatively low-cost manufacturing approach enabled the fabrication of scaffolds with excellent mechanical performances, controlled and stable porosity under both dry and physiological-like conditions, and high biocompatibility. The resulting constructs demonstrated promising results for cell proliferation and osteoconductive behavior, supporting their potential suitability as artificial bone substitutes.

Journal of Functional Biomaterials doi: 10.3390/jfb17050229

Authors: Nuno Silva Carlota Rodrigues Angel Lobito António Mano Azul Pedro Ferreira Trancoso Vanessa Machado João Botelho

This prospective, single-arm post-market study aimed to evaluate the clinical safety and performance of a synthetic calcium phosphate ceramic used in alveolar bone regeneration procedures. Eighty adult patients requiring bone augmentation were treated with β-tricalcium phosphate (β-TCP) under routine clinical indications. Surgical approaches were adapted to defect morphology. Safety outcomes included adverse events (AEs) and device deficiencies (DDs), while performance outcomes focused on two-dimensional radiographic bone assessment. Radiographic bone consolidation was defined as continuous trabecular radiopacity without radiolucent defects or clinical signs of infection. Patients were followed for six months post-surgery, with clinical and radiographic evaluations, as well as assessment of oral health-related quality of life (OHIP-14). All 80 patients (mean age: 47.2 ± 18.9 years; 51% male) completed the immediate postoperative assessment. Eleven DDs (granule loss) were observed postoperatively (13.8%) and no AEs. At six months, 71 patients (88.8%) completed follow-up. Radiographic bone repair was confirmed in all cases clinically observed and with follow-up X-ray (100%). No AEs or DDs reported (AE-free rate: 100%) at this follow-up. The median OHIP-14 score improved significantly at six months (p = 0.037), indicating better self-reported oral health. Given the observational design, absence of a control group, and partial reliance on non-radiographic follow-up, these findings should be interpreted with caution. Within these limitations, the synthetic calcium phosphate ceramic demonstrated a favorable short-term safety profile and apparent bidimensional radiographic signs of clinical performance under real-world conditions, rather than definitive evidence of effectiveness. Further controlled studies incorporating histological and volumetric analyses are warranted to confirm its regenerative potential.

Journal of Functional Biomaterials doi: 10.3390/jfb17050228

Authors: Renjie Miao Haoyu Wang Yitian Jin Changsheng Liu Hongyan He

Rheumatoid arthritis (RA) treatment is severely hindered by the systemic toxicity and limited joint accumulation of conventional therapeutics. To overcome these critical clinical challenges, we engineered a biomimetic dual-targeted nanoplatform (MTX@HSA@M@HA NPs) to precisely deliver methotrexate (MTX) to inflamed synovia. The rationally designed system encapsulates MTX within human serum albumin (HSA) nanoparticles, which are subsequently cloaked in red blood cell membranes (RBCMs) for robust immune evasion and prolonged systemic circulation. To achieve active targeting, the nanoparticle surface was functionalized with hyaluronic acid (HA) to selectively bind CD44 receptors, which are heavily overexpressed on RA-driving macrophages and fibroblast-like synoviocytes (FLSs). In vitro evaluations demonstrated significantly enhanced cellular internalization by activating RAW264.7 macrophages and FLS, resulting in the potent suppression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) with minimal baseline cytotoxicity. Furthermore, comprehensive in vivo studies using a collagen-induced arthritis (CIA) murine model confirmed that MTX@HSA@M@HA NPs significantly ameliorated joint inflammation, attenuated paw swelling, and rapidly improved functional outcomes compared to free MTX. By synergizing RBCM camouflage with HA-directed active targeting, this nanoplatform maximizes localized therapeutic efficacy while minimizing systemic toxicity, thereby presenting a highly promising and translatable strategy for targeted RA treatment.

Journal of Functional Biomaterials doi: 10.3390/jfb17050227

Authors: Zhen Yang Yueming Tian Jianguo Tan Ti Zhou Xuedong Wang Xinshu Dong Mingyue Liu Yanheng Zhou

High-translucency zirconia (HTZ) has superior esthetic properties, but its unreliable resin bonding limits minimally invasive anterior restorations. An in situ surface modification was developed to synthesize CaZrO3 particulates on pre-sintered HTZ for enhanced bonding durability. HTZ specimens were randomized into control (Zr-c) and calcium-modified (Zr-Ca) groups; Zr-Ca was treated with NaF/HCl mixture, calcium chloride glycerol solution, NaOH incubation (80 °C, 2 h), and sintering. Surface characteristics were characterized by SEM/EDS, AFM, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and FTIR. Flexural strength was tested via three-point bending; shear bond strength (SBS) was evaluated immediately and after 5000 thermocycles with resin cements (with/without 10-MDP). Zr-Ca showed uniform surface particulates, increased roughness, enhanced wettability, and surface Ca; XRD/FTIR/XPS confirmed CaZrO3 and Ca-O-P species (after MDP). Zr-Ca with 10-MDP-containing resin adhesive had significantly higher SBS before/after aging (predominantly mixed failures), with flexural strength within clinical limits. In situ CaZrO3 formation on HTZ strengthens MDP-mediated resin bonding and thermocycling resistance while preserving mechanical integrity, providing a feasible strategy for durable adhesion.

Journal of Functional Biomaterials doi: 10.3390/jfb17050226

Authors: Enes Bardakci Guldeste Aydin Peris Celikel

Aim: The aim of this study is to evaluate the effect of restorative crown materials with different elastic moduli on stress distribution in dentin and supporting tissues of pulpotomized primary anterior teeth under multi-directional loading conditions using the three-dimensional finite element analysis method. Materials and Methods: A three-dimensional model of a maxillary primary central incisor was created based on anatomical data. A clinical pulpotomy scenario was simulated using mineral trioxide aggregate (MTA) and resin-modified glass ionomer cement. Three models were analyzed: healthy tooth (control), Bioflx crown, and prefabricated zirconia crown. Frontal, oblique, and vertical loads were applied to represent functional and traumatic conditions. von Mises and principal stress distributions in the crown, dentin, and supporting tissues were evaluated. Results: In the prefabricated zirconia crown group, higher von Mises stress values were observed under all loading conditions, with significant stress concentrations particularly in the cervical region. In contrast, the Bioflx crown group exhibited lower stress values and a more homogeneous stress distribution. While the stress patterns in the Bioflx group were found to be closer to those of the control group, more localized stress accumulation was observed in the zirconia crowns. No significant differences were observed between the groups in the bone tissue. Conclusions: The elastic modulus of restorative materials plays a decisive role in the stress transfer mechanism. It is believed that materials with dentin-like mechanical properties may provide a more balanced and physiological stress distribution. Multi-directional loading analysis highlights the importance of evaluating the biomechanical behavior of restorative materials under more realistic conditions. Further advanced experimental and clinical studies are needed to clinically validate these findings.

Journal of Functional Biomaterials doi: 10.3390/jfb17050225

Authors: Yaimi Martín-Santana Yadira González-Carranza Leonel Díaz-Tato Arturo Juárez-Hernández Edgar Omar García-Sánchez Myriam Angélica De La Garza-Ramos Edén Amaral Rodríguez-Castellanos Marco Antonio Loudovic Hernández-Rodríguez

The design of implant surfaces that support bone integration while limiting bacterial colonization remains a central challenge in biomaterials science and engineering. In this work, zinc-doped biomimetic calcium phosphate (CaP-Zn) coatings were fabricated on Ti6Al4V through surface activation followed by deposition in supersaturated simulated body fluid (SBF). Acid and alkali–calcium treatments produced a porous, calcium-rich interface that enabled the uniform formation of apatite-like CaP layers. Zinc incorporation was achieved without suppressing the formation of CaP phases and led to systematic changes in coating microstructure and surface chemistry. Spectroscopic and structural analyses indicated Zn incorporation within the CaP matrix, consistent with partial Ca2+ substitution and its association with poorly crystalline domains. These features promoted controlled ionic release and localized dissolution–reprecipitation behavior. Antibacterial testing against Streptococcus mutans revealed a clear Zn-dependent reduction in bacterial viability, while cytocompatibility remained within acceptable limits at moderate Zn levels. Finally, the coatings combine intrinsic bioactivity with ion-mediated antibacterial functionality, offering a multifunctional surface strategy for advanced titanium-based implants.

Journal of Functional Biomaterials doi: 10.3390/jfb17050224

Authors: Cláudia Barbosa Tiago Reis José B. Reis Margarida Franco Catarina Batista Rui B. Ruben Benjamín Martín-Biedma José Martín-Cruces

This study aimed to evaluate the aging effect (6 and 12 months), relative to baseline (0 months), on the dimensional accuracy, morphological stability, and shaping behavior of PolyJet™ 3D-printed teeth (3DPT) produced in two printing orientations (X and Y axes). Specimens (XA0, XA6, XA12, YA0, YA6, YA12) were analyzed using microcomputed tomography before and after root canal preparation with the ProTaper Gold® system. Preoperative analysis included canal volume, centroid, total tooth volume, and total tooth area. Aging-related changes were observed, with significant differences between XA0 and XA12 (p < 0.05), whereas no differences were detected among Y-axis groups (p > 0.05). These findings indicate that X-axis specimens are not comparable over time, while Y-axis specimens maintain baseline consistency. Postoperative evaluation revealed significant differences across aging conditions for most endodontic preparation parameters. Within the limitations of this study, aging had a limited effect on dimensional accuracy but influenced the shaping behavior of 3DPT. Based on these findings, future studies using PolyJet™ 3DPT should report the printing batch and the storage time between fabrication and experimental use, as these factors may influence the comparability and reliability of the results.

Journal of Functional Biomaterials doi: 10.3390/jfb17050220

Authors: Asuka Aka Takashi Matsuura Atsutoshi Yoshimura

This study investigated the physicochemical properties of three endodontic bioceramics: MTA Flow White (F), MTA Repair HP (HP), and Nishika Canal Sealer BG multi (BG). Disc-shaped samples were immersed in deionized water for 28 days to analyze pH, calcium ion concentration, mass change, and water sorption. Additionally, the effect of varying powder-to-liquid (or paste) ratios was investigated for F and BG. All samples exhibited mass loss due to surface degradation. Results showed that F exhibited the highest alkalinity (pH 10.8–11.3) and significantly greater calcium ion release (173.3–523.3 ppm) than other materials (p < 0.05). HP showed moderate alkalinity (pH 10.4–10.7) with lower calcium release (43.3–66.3 ppm), while BG exhibited the lowest alkalinity (pH 9.3–9.4). Regarding the effect of consistency, variations in the powder-to-liquid (or paste) ratio significantly influenced the physical stability of F and BG—notably shifting F from mass loss to mass gain—but did not significantly affect their pH or calcium ion release kinetics (p > 0.05). Consequently, both null hypotheses were rejected, as significant differences were observed among the materials, and consistency significantly affected mass change and water sorption but not alkalinity or ion release.

Journal of Functional Biomaterials doi: 10.3390/jfb17050223

Authors: Elif Koç Dalndushe Abdulai Oyun-Erdene Batgerel Oktay Yazıcıoğlu Raghib Suradi Mehran Moghbel

Background: This in vitro study evaluated the effect of hydroxyapatite nanoparticle (nano-HAp) incorporation on surface roughness and Vickers hardness of a 3D-printed crown resin after thermocycling. Methods: Disk-shaped specimens (N = 84) were modified and fabricated with 0%, 1%, 2%, and 3% nano-HAp. Surface roughness (Ra) and Vickers hardness (VHN) were measured before and after thermocycling (5000 cycles). Surface morphology was qualitatively assessed using FE-SEM. Data were analyzed using two-way mixed-design ANOVA (α = 0.05). Results: Thermocycling increased surface roughness and reduced hardness in all groups. Ra values were highest in the 3% nano-HAp group after thermocycling (1.16 ± 0.47 µm). Baseline Vickers hardness differed significantly among nano-HAp concentrations, and hardness decreased after thermocycling in all groups; however, the 3% nano-HAp group exhibited the highest post-thermocycling hardness values (24.66 ± 1.51 VHN), which should be interpreted in the context of its higher baseline hardness. FE-SEM observations suggested increased surface irregularities with higher nano-HAp concentrations after thermocycling. Conclusions: Nano-HAp incorporation influenced both surface and mechanical properties, with 3% concentration showing higher hardness after aging but increased roughness.

Journal of Functional Biomaterials doi: 10.3390/jfb17050221

Authors: Esteban Padullés-Roig Pablo Sevilla Eugenio Velasco-Ortega Miguel Cerrolaza Darcio Fonseca Jeanne Parache Conrado Aparicio Javier Gil

The increasing prevalence of peri-implantitis has led to a growing clinical use of implantoplasty, a procedure involving intraoral machining of the dental implant surface to remove biofilm. The absence of standardized clinical protocols may contribute to premature fatigue failure of dental implants. The present study aimed to evaluate the influence of machining depth on the cyclic mechanical behavior of dental implants. A total of 250 commercially pure grade 4 titanium dental implants were distributed into four groups according to machining depth: untreated (original), 0.2 mm, 0.4 mm, and 0.6 mm wall reduction. The implant system featured an internal connection with a thread height of 0.4 mm. Finite element analysis was performed for each machining depth to evaluate von Mises stress distribution and simulate fatigue behavior. The numerical models were validated through experimental fatigue testing using a servo-hydraulic MTS Bionix testing machine under ISO 14801:2016 conditions, showing a high correlation between simulated and experimental results (correlation coefficients > 0.9). The results indicated that maximum von Mises stresses were concentrated at the junction between the implant thread and the implant body. The fatigue limit of the untreated implants was approximately 351 N. Implants subjected to 0.4 mm machining exhibited a fatigue limit of 301 N, whereas lower fatigue limits were observed for 0.2 mm (255 N) and 0.6 mm (185 N) reductions. These findings suggest a significant mechanical effect of thread removal: 0.4 mm implantoplasty may provide improved fatigue performance compared to 0.2 mm, potentially due to reduced stress concentration at the thread–body junction. At high applied loads, fracture occurred in the coronal region of the implant, whereas at lower loads failure shifted to the implant–abutment connection. Although a good agreement between numerical and experimental results was observed, these findings should be interpreted with caution due to the in vitro testing conditions and the assumptions inherent to the finite element simulations. Therefore, while the results suggest that implantoplasty depth should not exceed the original thread height, further validation under clinically relevant conditions is required to confirm its impact on long-term mechanical reliability.

Journal of Functional Biomaterials doi: 10.3390/jfb17050222

Authors: Alejandro Bolaños Alejandro Yánez Alberto Cuadrado María Paula Fiorucci

The scientific literature increasingly supports the use of computational models to predict fracture across a wide range of applications, which, when calibrated with experimental data, can yield highly consistent results. Although the extended finite element method (XFEM) is widely used in commercial packages, phase field (PF) methods have emerged as a robust alternative. In this study, a cohesive zone model (CZM) was implemented using both approaches (a PF model with an implicit damage initiation criterion and a standard commercial XFEM solver with an explicit damage initiation criterion) to analyze their robustness and computational efficiency. First, a standardized fracture test of a compact tension (CT) specimen was simulated and compared with experimental data to validate both methods, achieving accurate predictions under plane strain conditions with a dominant mode I fracture behavior. Subsequently, the application of both fracture models was extended to flexible thoracic prostheses across two distinct chest wall reconstruction scenarios: a single-rib unilateral model and a multi-rib bilateral configuration. An extreme-case compressive displacement was assessed to identify critical regions susceptible to fracture initiation and to evaluate the structural limits of the proposed designs. The results showed that the PF approach required a higher computational time, but exhibited more stable convergence. In contrast, the XFEM-based solver required careful mesh calibration to ensure convergence under complex conditions. These results highlight the potential of the PF approach as a practical tool for identifying and improving critical regions of implants, overcoming the limitations of commercial XFEM implementations.

Journal of Functional Biomaterials doi: 10.3390/jfb17050219

Authors: Beyza Güney Elif Yılmaz Biçer Dilan Gizem Doğan Merve Bankoğlu Güngör

Background: Zirconia ceramics are generally used in monolithic restorations, and their microstructural, mechanical, and optical properties continue to improve. Several factors affect the mechanical properties of these restorations; however, the combined effects of yttria content and margin design on the fracture resistance remain unclear. Methods: Sixty monolithic zirconia crowns were fabricated and assigned to six groups (n = 10) based on three different yttria contents (strength-gradient multilayer zirconia containing 3 mol% yttria tetragonal zirconia polycrystals in the dentin region and 5 mol% yttria-partially stabilized zirconia in the occlusal region: 3Y-TZP/5Y-PSZ [ZP], 3 mol% yttria tetragonal zirconia polycrystals: 3Y-TZP [HTML], and 4 mol% yttria-partially stabilized zirconia: 4Y-PSZ [STML]), and two different margin designs (chamfer and rounded shoulder). Crowns were adhesively bonded to standardized 3-dimensional-printed resin dies and subjected to thermal and mechanical aging (10,000 thermocycles at 5–55 °C, and 1.2 million mechanical cycles at 50 N, 1.6 Hz). Fracture resistance values were recorded in Newtons, and fracture types were evaluated. Data were analyzed using a two-way analysis of variance (ANOVA), and Bonferroni adjustment was used for multiple comparisons (α = 0.05). Results: A significant interaction between yttria content and margin design was found (p = 0.005). In the chamfer margin design groups, ZP (2208.5 ± 501.9 N) and HTML (2069.6 ± 463.3 N) showed significantly higher fracture resistance than STML (1444 ± 303.2 N) (p < 0.05). In the rounded shoulder margin design groups, no significant differences were observed among ZP (1662.8 ± 293.8 N), HTML (1940.9 ± 341.6 N), and STML (1795.6 ± 529.6 N) (p > 0.05). ZP and HTML showed higher fracture resistance values with the chamfer margin design, while STML showed higher fracture resistance with the rounded shoulder margin design. Conclusions: The fracture resistance of zirconia restorations is influenced by both the margin design and the yttria content. Designing the margin geometry based on the type of zirconia to be used can enhance the mechanical properties of the restorations and support clinical decision-making.

Journal of Functional Biomaterials doi: 10.3390/jfb17050218

Authors: Kirill Makrinsky Alexey Klyuev Oleg Batishchev

Biodegradable magnesium implants offer significant clinical promise, but their safe use requires reliable real-time in vivo monitoring of coating integrity. Existing methods lack sufficient sensitivity and temporal resolution to detect degradation at early stages, and there are no computational tools able to predict the success of a given sensor design before animal experiments. In the present paper, we present BioElectroSynth—a digital simulator of an implantable zero-resistance ammetry (ZRA) corrosion sensor in a mouse model. The simulator combines electrochemical noise, cardiac and muscular bioelectric interference, and instrumental limitations into a unified model, enabling virtual experiments, which mimic the complexity of the in vivo system. Using Monte Carlo analysis, we establish that a 2% breach in a chitosan coating on an AZ91 magnesium alloy electrode is statistically detectable from approximately 30 recordings of 30 s each, and quantify how electrode area, its location, sampling rate, and coating quality jointly determine detection sensitivity. The framework provides the first quantitative tool for predicting in vivo experiment feasibility from standard in vitro electrochemical data alone. By identifying instrument and design configurations that are statistically underpowered before any animal use, the approach directly supports the 3R principles of humane research.

Journal of Functional Biomaterials doi: 10.3390/jfb17050216

Authors: Zofia Stefanik Paweł Ścierski Maciej Dobrzyński Natalia Stefanik Magdalena Antonowicz-Hüpsch Rafał Wiench

Background: Denture stomatitis is strongly associated with Candida biofilms on prosthetic surfaces and remains difficult to manage due to biofilm persistence and antifungal resistance. Selenium-based nanomaterials, particularly biogenic selenium nanoparticles (SeNPs) functionalized with natural polymers or phytochemicals, have emerged as potential material-centered strategies for biofilm control. Objective: To systematically evaluate the antifungal and antibiofilm effects of selenium-based nanomaterials on Candida biofilms in the context of denture materials. Methods: A systematic review was conducted in accordance with the PRISMA guidelines and registered in PROSPERO. Multiple databases were searched from inception without language restrictions. Eligible studies included experimental investigations of biogenic or functionalized SeNPs or organoselenium compounds targeting Candida biofilms on denture materials or in relevant in vitro models. A qualitative synthesis was performed due to anticipated heterogeneity. Results: Eleven studies met the inclusion criteria. Of these, four studies directly evaluated selenium-based interventions on denture materials, while seven provided supporting mechanistic evidence using in vitro models on non-denture substrates. Across denture-related studies, selenium-based modifications reduced fungal adhesion, biofilm biomass, and colony-forming units, without detrimental effects on material properties. Functionalization with polymers or phytochemicals was associated with enhanced antifungal activity and nanoparticle stability. Mechanistic studies suggested multimodal antifungal effects, including membrane disruption, inhibition of virulence factors, and modulation of biofilm-related pathways. Methodological quality was moderate, with common limitations in reporting and experimental standardization. Conclusions: Functionalized biogenic SeNPs show promising antifungal and antibiofilm activity against Candida in preclinical denture-related models. However, all available evidence is in vitro, with no in vivo or clinical studies identified. Substantial heterogeneity and limited long-term safety data preclude clinical recommendations. Further research should focus on standardized methodologies, clinically relevant in vivo models, and controlled clinical trials to assess translational potential.

Journal of Functional Biomaterials doi: 10.3390/jfb17050217

Authors: Sergio Alexandre Gehrke Jaime Aramburú Junior Tiago Luis Eilers Treichel Antonio Scarano Bruno Freitas Mello Márcio de Carvalho Formiga Sergio Rexhep Tari Gustavo Coura Gustavo Vicentis Oliveira Fernandes

Background: Primary stability and long-term osseointegration depend on bone healing surrounding dental implants. Implant macrogeometry is crucial for controlling insertion torque and the biological reaction of peri-implant bone. This study assessed the impact of an implant design meant to lessen cortical bone compression on early bone healing. Methods: Forty titanium prototype implants (3 × 6 mm) were equally divided into Control (standard macrogeometry) and Test (macrogeometry with healing chambers) groups. Initial insertion torque was measured in vitro using synthetic bone blocks. Subsequently, an in vivo rabbit tibia model was used (n = 10 implants per group) to assess early healing. At 21 days, histological sections were analyzed for bone-to-implant contact (BIC%) at three cervical positions (C1, C2, and C3). Additionally, digital radiographs of the cervical region were evaluated using RGB color mapping, where distinct color channels quantified varying degrees of bone density. Results: The in vitro insertion torque for the Control group was significantly greater than the Test group (8.01 vs. 5.70 Ncm). The in vivo histomorphometric analysis indicated improved integration for the Test design, showing substantially higher BIC% at the C2 (59.30% vs. 40.30%) and C3 (42.10% vs. 17.90%) positions. Furthermore, radiographic RGB analysis revealed that the Test group possessed a higher blue channel contribution, indicating greater mineralized tissue density. Conclusions: These results imply that modifying implant macrogeometry to lower insertion torque and minimize cortical bone compression favorably enhances early cervical bone healing and osseointegration.

Journal of Functional Biomaterials doi: 10.3390/jfb17050214

Authors: Sabina Cristiana Badulescu Emma Adriana Ozon Adina Magdalena Musuc Manuela Diana Ene Rica Boscencu

Over the past 200 years (1820–2020), global life expectancy has nearly tripled, increasing from 26 to 72.91 years, due to factors such as poverty reduction and public health initiatives. Today, society faces different challenges than it did centuries ago. In patient care and healthcare system priorities, the goal is to develop smart, feasible, long-lasting, cost-effective, readily available, adverse-reaction-free, adaptable, and personalized solutions that minimize patient discomfort, reduce caregiver effort, and decrease hospitalization duration and costs. In this context, biomaterials serve as versatile tools capable of performing a wide range of diagnostic, therapeutic, and theragnostic functions. Thanks to their biocompatibility, biodegradability, surface chemistry, and responsiveness, biomaterials are currently addressing issues such as patient compliance (through controlled drug-delivery systems and smart wound dressings), long transplant waiting lists, transplant rejection, non-adaptable prosthetics (artificial organs), oncology treatment efficacy (nano-formulations for theragnostics and multiple tumor targeting), and inconsistent in vitro drug-testing models (organs-on-a-chip). In this review, we focus on biomaterials’ smartness, then explore databases for efficient product design, and finally highlight their applications in the biomedical field, especially in drug delivery, tissue engineering, and regenerative medicine.

Journal of Functional Biomaterials doi: 10.3390/jfb17050215

Authors: Jiyoung Kwon Seung Woo Chae Hyun-Jung Kim

The aim of this study was to evaluate the biological effects of bioactive glass-containing self-adhesive resin cements (SARCs) on human dental pulp stem cells (DPSCs), focusing on cytocompatibility, odontogenic differentiation, and mineralization. Experimental SARCs containing 0–5 wt% BAG (BG0–BG5) were compared with two commercially available SARCs, RelyX U200 and TheraCem. Eluates were prepared and applied to DPSCs for the methylthiazol tetrazolium (MTT) assay, quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence (IF) staining, and Alizarin Red S (ARS) staining. The result showed there were no significant differences in cell viability across all groups (p > 0.05), indicating that the addition of BAG did not affect cell viability, while the early odontogenic differentiation markers, such as RUNX2, ALP, and COL1A1, showed no clear trend among the groups. However, late-stage markers (DMP-1 and DSPP) were significantly higher in the BG2–BG5 groups relative to the OM group (p < 0.05). IF staining revealed intense signals in the BG2–BG5 groups (p < 0.05) and also ARS staining showed a time-dependent increase in mineral deposition. Within the limitations of this study, BAG-containing SARCs do not negatively impact cytocompatibility and promote late-stage odontogenic differentiation and mineral deposition.

Journal of Functional Biomaterials doi: 10.3390/jfb17050213

Authors: Kristian Kniha Lothar Rink Mark Ooms Katharina Schaffrath Stephan Christian Möhlhenrich Frank Hölzle Ali Modabber Marius Heitzer

Aim: This study aimed to compare two-piece zirconia and two-piece titanium implants inserted into the anterior mandible for removable overdentures in a 3-year randomized split-mouth clinical trial. Methods: Twenty fully edentulous mandibular patients received two zirconia and two titanium implants allocated by computer-generated randomization. The primary endpoint was bleeding-on-probing (BOP) at 12 months. Secondary outcomes included implant survival and success (Albrektsson criteria), marginal bone level changes, peri-implant cytokines (IL-1β, IL-6, and TNFα), prosthetic complications, and patient-reported outcomes (PROMs). Results: After 3 years, overall survival was 98.61% and overall success was 84.72%. Titanium implants showed higher success compared with zirconia implants (91.70% vs. 77.78%), while survival was 100% and 97.22%, respectively. Marginal bone loss was significantly greater around zirconia implants at 36 months (p < 0.01). No significant differences were observed in IL-1β, IL-6, or TNFα levels up to 12 months. PROMs revealed a trade-off, with zirconia favored for esthetics and cleaning perception, while titanium was rated superior for stability. Conclusions: Within the limitations of this split-mouth RCT, zirconia implants demonstrated reduced success and inferior marginal bone stability compared with titanium implants in overdenture therapy. Careful case selection and close follow-up appear essential when zirconia implants are used in this indication.

Journal of Functional Biomaterials doi: 10.3390/jfb17050212

Authors: Leonardo D’Elia Lígia Pereira da Silva Patrícia Manarte-Monteiro

Universal adhesives (UAs) exhibit considerable versatility; however, no single commercial product has attained recognition as a clinical gold standard. This study evaluated the functional performance, retention, and marginal integrity of various UA brands in non-carious cervical lesion (NCCL) restorations and examined the effects of different adhesion strategies. A search of electronic databases was conducted for randomized clinical trials (RCTs) published between 2015 and 2025. Only RCTs that assessed the retention and marginal integrity of UAs with follow-ups of 18–48 months, using the USPHS/FDI criteria, were included. This review was registered with PROSPERO (CRD420251026490) and adhered to PRISMA 2020 and PICOS guidelines. Risk of bias was evaluated using the RoB 2 tool; statistical significance was defined as p < 0.05. Of 251 records screened, 23 met the eligibility criteria, resulting in the inclusion of 21 RCTs. Sixteen UA brands exhibited no clear differences in performance outcomes. Etch-and-rinse (ER) and selective enamel-etching (SEE) strategies achieved higher retention rates (median up to 100%; USPHS, p < 0.001), while the self-etch (SE) approach demonstrated lower and more variable retention (median 87.0%). Marginal integrity remained consistently high across all strategies (median 100%; p > 0.05). Although ER and SEE strategies significantly enhance long-term retention, no UA brand showed consistent superiority to be considered a gold standard.

Journal of Functional Biomaterials doi: 10.3390/jfb17050211

Authors: Todor Bogdanov Nadja Radchenkova Raya Grozdanova Dimitar Kosturkov Todor Uzunov

Dental implants are widely used to replace missing teeth, but peri-implantitis remains a major biological complication associated with bacterial biofilm formation on implant surfaces. The increasing incidence of peri-implant infections underscores the need for alternative antimicrobial strategies that effectively decontaminate complex titanium implant surfaces. This study evaluated the inhibitory effect of low-temperature microwave argon plasma on bacteria in an experimental model simulating peri-implant conditions and compared the responses of microorganisms with different biological characteristics. A 3D-printed mandibular bone segment model with an inserted Straumann BLX Roxolid® dental implant was used to reproduce the peri-implant environment. Bacterial suspensions of Streptococcus mutans NBIMCC 1786 and the extremophilic bacterium Chromohalobacter canadensis NBIMCC 9077 have been exposed to a microwave non-equilibrium argon plasma jet (2.45 GHz, atmospheric pressure) for 1–7 min. Optical density measurements and colony growth analysis were used to assess antimicrobial effects. Plasma treatment induced a pronounced reduction in bacterial growth during the early post-treatment period. In C. canadensis, growth inhibition reached a plateau (~47–55% at 24 h) regardless of exposure time. In contrast, S. mutans showed a nonlinear response, with stable inhibition after short exposures (1–3 min) and partial recovery after longer treatments (5–7 min). These findings indicate that microwave argon plasma exhibits significant antimicrobial activity under controlled in vitro conditions, although its effectiveness depends on microorganism-specific biological characteristics. Because the present model was based on simplified single-species systems, direct clinical extrapolation remains limited and should be addressed in future studies using polymicrobial peri-implant biofilm models.

Journal of Functional Biomaterials doi: 10.3390/jfb17050210

Authors: Wencheng Teng Zhuoyi Wang Ziyue Xu Jie Xin Chao Sun Yi Shao Cheng Wang Chenglin Chu Feng Xue Jing Bai

Magnesium (Mg) reinforced polylactic acid (PLA) composites have attracted increasing interest for orthopedic implants to solve the insufficient strength of PLA and to utilize the bioactive advantages of Mg ions in promoting bone formation. However, the weak interfacial adhesion between the Mg and PLA limits the applications of the composite. In this study, a dual interfacial enhancement approach was designed to combine surface fluorination with perforation. During hot pressing, molten PLA infiltrates the pores to form a ‘rivet-like’ mechanical interlocking. This structure significantly alters the load transfer and degradation behaviors of the composite. Compared to pure PLA, the dual treatment significantly elevated the bending strength by 49%, alongside an increase in the bending strain from 15% to 25%. Moreover, in vitro degradation tests revealed that this strategy suppresses H2-induced delamination, and stabilizes both pH and Mg2+ release. Consequently, the bending strength remained at 86% after six weeks of in vitro degradation. In addition, the composite exhibits excellent biocompatibility, with MC3T3-E1 cell viability exceeding 90% in 100% extract. These results demonstrate that the reinforced Mg/PLA composite exhibits excellent mechanical properties, degradation stability, and biocompatibility, showing high potential for load-bearing orthopedic fixation applications.

Journal of Functional Biomaterials doi: 10.3390/jfb17050209

Authors: Cemile Kedici Alp Sena Sumra Kaçmaz Ayşenur Yazım Zeynep Aydin Recep Özkan

This in vitro study evaluated the effect of exposure duration (5, 20, and 40 days) to constant increased ambient pressure (2.4 atmospheres absolute; ATA) on microleakage at the dentin–composite interface of teeth restored with two bulk-fill composites. Specimens stored in distilled water at atmospheric pressure (1 atm) served as controls. A total of 192 extracted human molars with standardized Class V cavities were randomly assigned to two groups: sonic-activated bulk-fill composite (SonicFill) or conventional bulk-fill composite (Filtek One Bulk Fill). Each group was subdivided into controls maintained under atmospheric pressure (1 atm) and specimens under hyperbaric pressure (2.4 ATA), and exposed for 5, 20, or 40 days (total of 12 groups, n = 16 per group). Microleakage was assessed using the dye penetration method and scored under a stereomicroscope according to ISO criteria. Statistical analyses were performed using Fisher’s Exact chi-squared and Fisher–Freeman–Halton Exact tests (α = 0.05). No significant differences were found between materials or pressure conditions at 5 and 20 days (p > 0.05). After 40 days, both composites showed significantly higher microleakage at increased pressure than atmospheric controls (p < 0.05). Microleakage increased over time in the hyperbaric groups, while no time-dependent changes occurred at atmospheric pressure. After 40 days, prolonged exposure to elevated pressure increased microleakage, whereas shorter exposure produced no significant changes. Both materials demonstrated similar susceptibility to pressure-related deterioration.

Journal of Functional Biomaterials doi: 10.3390/jfb17050208

Authors: Mario Ceddia Tea Romasco Natalia Di Pietro Luciano Lamberti Bartolomeo Trentadue

Inter-implant distance (IID) is crucial for peri-implant bone preservation and long-term implant success. Traditionally, a minimum IID of 3 mm is recommended to limit marginal bone loss, although the biomechanical effect of smaller distances remains debated and may depend on multiple biological, prosthetic, and surgical factors. This study uses finite element analysis (FEA) to evaluate the effect of IID on stress distribution in peri-implant bones of D3 and D4 quality, considering crestal versus subcrestal implant placement, and interpreting results within Frost’s mechanostat theory. Implants with an internal conometric connection were modeled within simulated D3 and D4 mandibular bone blocks. IID values of 3 mm, 1.5 mm, and 1 mm were analyzed under masticatory load. Von Mises stresses in cortical and trabecular bone were compared against biomechanical thresholds (2 MPa disuse and 20 MPa remodeling limit). Results: Cortical stress increased with decreasing IID, more pronounced in crestal placement. In D3 bone, maximum cortical stress rose from 7.2 MPa (3 mm IID) to 16.5 MPa (1 mm IID) under crestal placement, while remaining within the mechanostat-based thresholds adopted in the present stress-interpretation framework. In D4 bone, cortical stress approached 20 MPa at 1 mm IID under crestal placement, indicating a less favorable mechanical condition within the interpretive framework adopted. Subcrestal placement reduced cortical stresses in both bone qualities. Trabecular stress remained stable in D3 (~1.7–8 MPa) and increased moderately in D4 (~up to 13 MPa). Conclusions: Within the limitations of this preclinical finite element study, decreasing inter-implant distance was associated with increased cortical stress, while subcrestal placement was associated with lower cortical stress than crestal placement. These findings should be interpreted only as comparative computational results, and no direct clinical conclusion can be drawn regarding the acceptability of a 1 mm inter-implant distance.

Journal of Functional Biomaterials doi: 10.3390/jfb17050207

Authors: Fang Wu Yuan Gao Yongjie Chi Danyang Wang Siqi Zhang Ocean Cheung Kai Zhao Hongsheng Lu Qi Chen Yu Chen Lianyan Wang Yanhua Zhu

Poly(lactic acid-lactic acid) (PLGA) has demonstrated significant application potential in tumor-targeted drug delivery systems due to its excellent biocompatibility, degradability, and multifunctionality for loading various therapeutic agents. PLGA nanoparticles (NPs) can achieve targeted delivery to tumor cells through specific surface modifications and stimulus-responsive release mechanisms, significantly enhancing drug accumulation efficiency at tumor sites while reducing toxic side effects on normal tissues. This review systematically summarizes the fundamental physicochemical properties of PLGA materials and recent advances in tumor-targeting strategies for PLGA NPs. It comprehensively elucidates research breakthroughs in PLGA-based delivery systems regarding stimulus-response mechanisms, passive targeting, active targeting, and tumor combination immunotherapy, while revealing the intrinsic logic of synergistic strategies for enhancing targeting efficiency. Finally, from the perspective of clinical translation and individualized oncology, this review conducts an in-depth assessment of the current challenges and looks forward to future research directions, aiming to provide forward-looking guidance for the development of precision nanomedicine.

Journal of Functional Biomaterials doi: 10.3390/jfb17040206

Authors: Annett Dorner-Reisel Jialin Li Marta Trzaskowska Vladyslav Vivcharenko Jiacheng Chu Emma Freiberger Uwe Ritter Agata Przekora Aneta Zima Tao Wang Jens Moje

Zirconia is known as a strong and bioinert load-bearing material for dental implants. It typically exhibits no antibacterial activity. Inflammation is a crucial problem for dental implant surgery: about 3–5% of all dental implants experience inflammation. This study demonstrates that either fullerene C60 films or a tribomechanical loading of zirconia without the fullerene C60 coating can cause an improvement in antibacterial activity against Gram-positive Staphylococcus aureus. This moderate antibacterial activity is especially important, because a strong antibacterial effect could disturb the sensitive and beneficial oral bacterial biota. In the present study, different fullerene C60 films were examined. In addition to fullerene C60 film in an “as deposited” condition, treatment with nitrogen plasma as well as tribomechanical produced surface patterns with and without plasma post-treatment were tested. An 85.8% (log reduction 0.85) reduction in Gram-positive Staphylococcus aureus bacterial formation was observed on the zirconia with fullerene C60 film. Plasma treatment of the C60 film increases the antibacterial impact to 72.2% (log reduction 0.56) in comparison to zirconia without fullerene C60 film. Also, tribomechanical loaded fullerene C60 films suppress the growth of Gram-positive Staphylococcus aureus. The tribomechanical loading seems to compensate for the effect of the plasma treatment. ZrO2 samples with fullerene C60 film and tribomechanical loading achieve an increase in antibacterial impact of 83.36% (log reduction 0.78). Furthermore, surprisingly yttria-stabilized zirconia bioceramic without fullerene C60 film also shows an improved antibacterial efficacy after a tribomechanical patterning procedure. The addition of surface patterning on the ZrO2 by scratching microgroove arrangements with a diamond tip, increased the antibacterial effect against Gram-positive Staphylococcus aureus by 70.46% (log reduction 0.53).

Journal of Functional Biomaterials doi: 10.3390/jfb17040203

Authors: Muhammad Shafiq Liaqat Zeb

Four-dimensional (4D) printing integrates additive manufacturing with stimuli-responsive materials to fabricate biomedical implants and functional healthcare devices that undergo programmed, time-dependent changes in shape or function. Unlike static 3D-printed constructs, 4D-printed systems can respond to clinically relevant stimuli such as temperature, hydration, pH, light (including near-infrared), magnetic fields, or electrical inputs. These triggers drive defined actuation mechanisms, most commonly thermomechanical shape-memory recovery, swelling-induced morphing, and magnetothermal activation. This review synthesizes the principal material platforms used for biomedical 4D printing, including shape-memory polymers and alloys, hydrogels, liquid-crystal elastomers, and responsive composites, and links material choice to device behavior and translational feasibility. Applications are discussed across self-expanding stents, cardiac occluders, tissue-engineered constructs, implantable drug delivery systems, and adaptive wearables. Key translational challenges include sterilization compatibility, manufacturing reproducibility and quality control, safe stimulus delivery, predictable biodegradation and long-term biocompatibility, and regulatory pathway definition.

Journal of Functional Biomaterials doi: 10.3390/jfb17040205

Authors: Wannapat Chouyratchakarn Burin Boonsri Surasak Tangkamonsri Watchara Thepsupa Chayarop Supanchart Sarawut Kumphune

Titanium and its alloys are used in dental and orthopedic implants. However, long-term stability remains a clinical challenge. To overcome this limitation, surface modification has been investigated to improve surface properties. Our previous study demonstrated that the immobilization of secretory leukocyte protease inhibitor (SLPI) on the titanium surface promotes osteoblast adhesion, proliferation, and differentiation in vitro. The current study demonstrated the first in vivo evaluation of SLPI as a bioactive coating for medical implants. Grade 5 titanium screws were coated with 10 µg/mL of recombinant human SLPI (rhSLPI) for 24 h via simple physical adsorption, and the results were preliminarily validated via FE-SEM and ELISA. These SLPI-coated titanium screws (TiSs) were then placed in the tibia of Sprague–Dawley rats for 4 and 8 weeks. The hematological and biochemical parameters (BUN, Creatinine, AST, and Troponin I) demonstrated no acute systemic alterations within the 8-week period across all groups. Moreover, micro-computed tomography (micro-CT) and histological analysis revealed significantly higher bone volume fraction (%BV/TV) at 4 weeks compared to uncoated controls (20.64% ± 2.452% vs. 11.73% ± 0.524%). Finally, the biomechanical stability of implants, assessed using the removal torque test, showed that TiSs showed higher strength compared to Ti at both 4 and 8 weeks. In conclusion, this study represents a novel approach to transitioning rhSLPI-coated titanium evaluation from in vitro models to an in vivo rat model. rhSLPI surface functionalization enhances early-stage osseointegration and improves implant mechanical stability without acute hematological and biochemical alterations. These proof-of-concept findings suggest the potential of SLPI as a bioactive coating strategy.

Journal of Functional Biomaterials doi: 10.3390/jfb17040204

Authors: Estíbaliz Sánchez-González Fernando Rodríguez-Rojas Oscar Borrero-López

Background: The wear resistance of modern commercial glass-ceramic materials used in dental prostheses was investigated under cyclic contact conditions that included a rotational component. This loading mode has been largely overlooked in conventional in vitro wear testing, yet may be clinically relevant in patients with parafunctional conditions such as bruxism. Methods: Rotational loading was applied using an all-electric testing machine equipped with a biaxial actuator. Loading cycles combined a normal load (50 N) and a rotation (30°), at a frequency of 1 Hz. Microstructure and damage were characterized using advanced microscopy. Results: Rotational loading induced substantial damage across this class of materials, including the formation of glassy tribolayers with limited protective capability under the low-humidity conditions examined. Significant microstructure-dependent variations in wear volume were observed, with specific wear rates indicating severe wear (SWR above 10−6 mm3/N·m threshold) in three of the five materials tested. Lithium disilicate glass-ceramics, characterized by a high fraction of elongated reinforcement crystals, exhibited the greatest resistance to damage, whereas leucite-based glass-ceramics showed the lowest. The dominant wear mechanisms were plastic-deformation-induced grooving and fracture-driven chipping. The findings are interpreted within established wear models for brittle materials (Archard and fracture-based) and supported by numerical simulations of stress fields across multiple length scales. Implications: The results provide mechanistic insight into rotational wear damage in glass-ceramic systems, a material class particularly susceptible to such loading, and inform strategies for material selection and microstructural design aimed at improving prosthetic durability.

Journal of Functional Biomaterials doi: 10.3390/jfb17040202

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

Mineral powder–based bone grafts exhibit excellent osteoconductivity; however, their clinical efficacy is often compromised by insufficient early-stage tissue ingrowth, leading to particle aggregation and pocket formation within the defect site during the initial healing phase. Here, we report a cotton-type nanofiber-guided mineral graft designed to overcome this early integration failure by creating fibrous pathways for tissue ingress. Cotton-type polycaprolactone (PCL) nanofibers were fabricated via electrospinning using a pin-based collector engineered to induce strong inter-fiber repulsion, resulting in a highly expanded, three-dimensional cottony architecture. Tetracalcium phosphate (TTCP) and α-tricalcium phosphate (α-TCP) mineral particles were subsequently deposited onto the surface of the cottony nanofibers, forming a fibrous–mineral hybrid graft (c-NF@T/α-TCP) in which the nanofibers act as a transient, functionally defined tissue-guiding framework during the early healing phase. The cottony nanofiber network effectively prevented mineral particle aggregation and generated continuous pathways within the graft, facilitating early tissue infiltration and vascular ingress during the first week after implantation. In vivo evaluation in a bone defect model demonstrated that c-NF@T/α-TCP significantly reduced tissue pocket formation at early time points and promoted subsequent bone regeneration compared to mineral powder-only grafts. This study highlights the critical importance of early-stage structural guidance in mineral-based bone grafts and introduces cotton-type nanofiber–guided pathway engineering as a simple yet effective strategy to unlock the regenerative potential of conventional inorganic bone substitutes.

Journal of Functional Biomaterials doi: 10.3390/jfb17040201

Authors: Deeksha Rajkumar Adrian Stiller Jurian Wijnheijmer Ireen M. Schimmel Leendert W. Hamoen Leena Hupa Nicole N. van der Wel Payal P. S. Balraadjsing Sebastian A. J. Zaat

Bioactive glass (BAG) S53P4 is a clinically approved bone substitute with antibacterial, osteoconductive and osteostimulatory properties. Its antibacterial effect is associated with ion release, local pH elevation and osmolality, but the precise biochemical and biophysical mode-of-action is unclear. This study investigates the antibacterial mechanism of BAG S53P4 eluates. BAG eluates, collected at 2, 4, 8, and 24 h, eradicated Staphylococcus aureus. Elemental analysis revealed an early increase in concentrations of Si and Na, a later rise in Ca, depletion of P over time and rapid loss of Mg. Membrane disturbances occurred within 5 min, evident by permeability for SYTOX, aligning with time-kill kinetics for S. aureus and Bacillus subtilis. In B. subtilis, 2h-BAG-eluate induced rapid delocalization of marker proteins for cell division and DNA repair, signaling membrane potential collapse and nucleoid condensation. Transcriptomics revealed early transcription remodeling reflecting ionic and energetic imbalance, including disruption of central metabolism, redox homeostasis, and translational stability. Scanning electron microscopy revealed severe cell surface damage and particulate deposits on S. aureus. Transmission electron microscopy showed cell envelop disruptions and cytoplasmic leakage. Energy dispersive X-ray analysis identified Si on bacterial cell surface at 4 h and intracellular accumulation in punctured, empty cells at 24 h. Overall, BAG ionic dissolution products kill bacteria through a stepwise mechanism involving membrane damage, protein delocalization and metabolic impairment, accompanied by Si deposition on bacterial surfaces and loss of Mg. This finally leads to cell wall degradation, cytoplasmic content leakage and further Si deposition on the cells and inside cell ghosts.

Journal of Functional Biomaterials doi: 10.3390/jfb17040200

Authors: Chenao Xiong Hui Feng Liyang Lu Zehao Jing Youhao Wang Yiyuan Yang Dexuan Meng Yichen Zhang Weishi Li Hong Cai

Titanium and its alloys are widely used for orthopedic implants, but their intrinsic bioinertness may hinder osseointegration. In this study, titanium dioxide nanotube (TNT) arrays were fabricated on Ti-6Al-4V scaffolds via anodization, and their effects on the adhesion behavior of human bone marrow mesenchymal stem cells (hBMSCs) were investigated. Surface characterization showed that anodization successfully generated ordered TNT layers, increased surface roughness, enhanced protein adsorption, and induced an apparent superhydrophilic wetting response. Compared to the untreated scaffold and TNT50, the small-diameter TNT10 surface significantly promoted hBMSC adhesion and proliferation. Microscope imaging further revealed enhanced cell spreading, F-actin organization, and vinculin expression on TNT surfaces, with the most prominent focal adhesion-related staining observed in TNT10. Quantitative proteomic analysis showed that TNT10 was associated with coordinated remodeling of adhesion- and cytoskeleton-related molecular programs, including focal adhesion, cell–substrate junction, and regulation of the actin cytoskeleton. In contrast, TNT50, despite supporting obvious cytoskeletal remodeling, was more compatible with a dynamic, higher-turnover adhesion state. Overall, these findings suggest that small-diameter TNTs provide a more favorable interfacial microenvironment for stable early hBMSC adhesion on porous titanium scaffolds.

Journal of Functional Biomaterials doi: 10.3390/jfb17040199

Authors: You Li Wenxin Zhang Zitao Xu Shixin Ma Yufei Xiong Li Yu Huiling Gao Yang Shu Teng Fei

Metal ion-based chemo-immunotherapy is often limited by rigid intracellular metal homeostasis, insufficient reactive oxygen species (ROS) accumulation, and an immunosuppressive tumor microenvironment (TME). To overcome these limitations, we engineered an ATP-responsive, core–shell bimetallic nanoreactor (Cu/ZIF@PDA, termed CZP) featuring a precisely controlled ~25 nm biomimetic polydopamine (PDA) coating. Triggered by elevated tumoral ATP levels, CZP undergoes coordination-induced disassembly and promotes oxidative stress amplification. Specifically, the PDA shell acts as a superoxide dismutase (SOD) mimetic to continuously supply H2O2, fueling Cu2+-mediated Fenton-like reactions to unleash highly toxic hydroxyl radicals (•OH) while aggressively depleting the intracellular glutathione (GSH) pool. This irreversible oxidative damage, coupled with Zn2+-induced mitochondrial dysfunction, triggers profound mitochondrial DNA (mtDNA) leakage. Crucially, this cytosolic DNA robustly activates the cGAS-STING signaling axis, driving a massive surge in immunogenic cell death (ICD) and significantly promoting dendritic cell (DC) maturation. Furthermore, CZP markedly inhibited primary tumor growth in vivo and showed protection in a tumor re-challenge model, accompanied by enhanced dendritic cell maturation. These findings support the potential of this ATP-responsive bimetallic nanoplatform to promote antitumor immune activation.

Journal of Functional Biomaterials doi: 10.3390/jfb17040198

Authors: Yasumitsu Ohtsuka Taichi Tenkumo Masatoshi Takahashi Yasuhiro Nakanishi Hiroaki Takebe Takashi Nezu

Titanium–silver (Ti–Ag) and titanium–copper (Ti–Cu) alloys have been developed to improve the mechanical properties and machinability of titanium (Ti) for dental applications while maintaining corrosion resistance comparable to that of pure Ti. Herein, cylindrical dental implants composed of experimental Ti–20Ag, Ti–30Ag, Ti–5Cu, and Ti–10Cu (mass%) alloys were fabricated and implanted into the jawbones of beagle dogs to evaluate bone compatibility. Pure Ti and Ti–6Al–4V alloy implants were used as controls. Because the implant surfaces were mechanically polished, the experimental alloys, which exhibited higher hardness than Ti, showed lower surface roughness than Ti. Radiographic observations revealed no remarkable bone resorption around any implants during the experimental period. Histological evaluation demonstrated new bone formation and partial bone contact around implants at 1 and 3 months post-implantation. Although the bone–implant contact ratio was relatively low owing to the cylindrical implant design and limited initial stability, no significant differences were observed between the experimental alloys and Ti. These results indicate that Ti–Ag and Ti–Cu alloys improve mechanical properties while maintaining bone compatibility comparable to that of Ti, suggesting their potential as candidate materials for dental implant applications, particularly for narrow dental implants.

Journal of Functional Biomaterials doi: 10.3390/jfb17040197

Authors: Goran Marić Darko Solter Blanka Doko Mandić Jelena Škunca Herman Zoran Vatavuk Damir Godec Davor Vagić Alan Pegan

The reconstruction of complex orbitomaxillary defects requires biomaterials that can simultaneously provide structural stability, biocompatibility, and accurate restoration of facial volume and contour. While rigid polymers such as polyetheretherketone (PEEK) offer reliable mechanical support, they do not adequately replicate the viscoelastic behavior of soft tissues. This report presents a translational revision case employing a personalized hybrid biomaterial approach that combines a 3D-printed PEEK implant for structural orbital floor support with a patient-specific polydimethylsiloxane (PDMS) implant for malar volumetric augmentation. Reconstruction was planned using CT segmentation and contralateral mirroring. Patient-specific implants were subsequently designed using CAD/CAM techniques, combining a rigid PEEK implant for structural orbital support with a flexible PDMS implant for malar volumetric augmentation with complementary mechanical properties. Revision surgery included the removal of inadequately positioned titanium hardware, the release of incarcerated extraocular muscles, and the restoration of orbital anatomy and facial symmetry. Postoperative imaging demonstrated stable implant positioning and sustained orbitomaxillary stability. Despite successful anatomical reconstruction, residual functional sequelae, including strabismus related to the severity of the initial orbital trauma, persisted and were addressed separately in a staged manner, resulting in satisfactory ocular alignment and resolution of diplopia in primary gaze. This case underscores the complementary functional roles of rigid and elastic polymers and highlights the translational potential of PDMS as a permanent, patient-specific implant material for volumetric and contour restoration in craniofacial reconstruction.

Journal of Functional Biomaterials doi: 10.3390/jfb17040196

Authors: Wooseob Kim Eun A. Jang Kyu Nam Kim

Background/Objectives: The subciliary approach offers excellent exposure for orbital and zygomaticomaxillary complex fracture repair but is associated with a relatively high risk of postoperative lower eyelid ectropion. This study evaluated the preventive efficacy of an acellular dermal matrix (ADM; WITHderm®) spacer graft placed during subciliary incision repair. Methods: This prospective observational cohort study included 20 patients who underwent open reduction and internal fixation for orbital wall or zygomaticomaxillary complex fractures using a subciliary approach between June and December 2024. A human-derived ADM (WITHderm®) spacer graft was interposed between the orbital septum and the orbicularis oculi muscle during incision closure. Postoperative outcomes were assessed at three time points: ectropion grading at 1 month and scar outcomes at 3 and 6 months using the Patient and Observer Scar Assessment Scale (POSAS). Results: No patients developed postoperative lower eyelid ectropion at 1-month follow-up (0% incidence). Both patient-reported and observer-reported scar outcomes improved significantly over time. The mean total PSAS score decreased from 21.0 ± 2.85 at 3 months to 11.3 ± 2.13 at 6 months (p < 0.001), while the mean total OSAS score decreased from 21.35 ± 2.25 to 11.4 ± 1.67 (p < 0.001). Overall patient satisfaction and objective scar ratings also showed significant improvement. Conclusions: ADM (WITHderm®) spacer grafting during subciliary incision repair appears to be a safe and effective strategy for preventing early postoperative lower eyelid ectropion and achieving favorable scar outcomes. Further studies are warranted to confirm these findings.

Journal of Functional Biomaterials doi: 10.3390/jfb17040195

Authors: Antonia P. Palankalieva Iva D. Stoykova Milen I. Georgiev Ani B. Belcheva

Silver diamine fluoride (SDF) is widely used in pediatric dentistry for caries arrest; however, concerns exist regarding its cytotoxicity. Green-synthesized nano-silver fluoride (NSF) is a potential alternative to SDF, offering antimicrobial efficacy with improved biocompatibility. This study aimed to evaluate the in vitro safety profile of green-synthesized NSF with 5% (w/v) fluoride using Camellia sinensis extract and to compare it with 38% SDF + potassium iodide (KI) formulation in human gingival fibroblasts (HGFs). Eluates of NSF and SDF+KI were tested at serial concentrations of 5%, 1%, 0.1%, 0.01% and 0.005%. Cell viability was assessed after 24, 48, and 72 h using the MTT assay. Additionally, the formation of reactive oxygen species (ROS) in HGFs was detected through fluorescence microscopy. Exposure to 5% SDF+KI resulted in almost complete loss of cell viability at all time points, whereas NSF demonstrated significantly higher viability under the same conditions. Lower concentrations of both materials maintained acceptable biocompatibility. ROS analysis revealed increased oxidative stress in response to 5% SDF+KI, while NSF induced significantly lower ROS levels. NSF exhibited superior biocompatibility compared to SDF+KI, supporting its potential as a safer silver-based material for caries management. Further in vitro and in vivo studies are needed to confirm its clinical safety profile.

Journal of Functional Biomaterials doi: 10.3390/jfb17040194

Authors: Igor Smojver Roko Bjelica Marko Vuletić Luka Stojić Vlatka Njari Galić Dragana Gabrić

The accuracy of static computer-aided implant surgery (s-CAIS) is fundamental for predictable clinical outcomes. The objective of this study was to evaluate the influence of different guide-support modalities on the linear and angular accuracy of implant placement. In this retrospective clinical investigation conducted at a single specialty hospital, a total of 180 implants were analyzed, divided into three equal groups (n = 60) based on the guide support type: tooth-supported, bone-supported, and mucosa-supported. Accuracy was assessed by superimposing preoperative virtual plans with postoperative cone-beam computed tomography (CBCT) scans, measuring linear deviations at the neck and apex of the implant, as well as angular discrepancies. The type of guide support was found to be a significant factor associated with surgical accuracy (p < 0.001). Tooth-supported guides demonstrated the highest level of accuracy, with a mean angular deviation of 1.81° ± 0.45° and linear deviations at the neck and apex of 0.59 ± 0.18 mm and 0.73 ± 0.19 mm, respectively. These were followed by bone-supported guides (2.14° ± 0.48°; 1.04 ± 0.26 mm; 1.61 ± 0.31 mm), while mucosa-supported guides exhibited the greatest deviations (2.95° ± 0.60°; 1.47 ± 0.29 mm; 1.87 ± 0.37 mm). Significant intergroup differences and large effect sizes were observed, particularly regarding angular and horizontal discrepancies. These findings demonstrate a distinct gradient of accuracy based on guide support, establishing tooth-supported guides as the most accurate, followed by bone-supported and, lastly, mucosa-supported guides. While all modalities are clinically applicable, the use of mucosa-supported guides necessitates increased safety margins to account for the increased risk of linear and angular discrepancies inherent to mucosal tissue displacement.

Journal of Functional Biomaterials doi: 10.3390/jfb17040193

Authors: Dhouha Bouzir Adel Elamri Khmais Zdiri Mohamed Hamdaoui Christelle Delaite Abdelaziz Lallam Omar Anis Harzallah

Modified chitosan (Cs) derivatives were synthesized and evaluated as potential antibacterial and antiviral coatings of medical protective equipment (facial masks, gloves, …). Quaternized chitosan (HTCC) and chitosan–silver nanocomposites (Ag/Cs) were successfully prepared, with structural characterization confirming efficient quaternization and uniform incorporation of silver nanoparticles. Antibacterial testing revealed that HTCC exhibited concentration-dependent activity, while Ag/Cs showed strong broad-spectrum antibacterial effects and enhanced thermal stability. Antiviral assays against SARS-CoV-2 demonstrated significant viral inhibition for HTCC6 and Ag/Cs at non-cytotoxic concentrations (6 mg/mL), highlighting the role of cationic charge and nanoparticle inclusion in antiviral efficacy. These findings indicate that the developed chitosan derivatives are promising candidates for sustainable functional coatings on medical devices, offering potential applications in infection prevention.

Journal of Functional Biomaterials doi: 10.3390/jfb17040192

Authors: Areti Dimitra Vrochari Anastasia Agrafioti Maria Dimitriadi George Eliades

The aim of this study was to evaluate setting time, hardness, solubility, bioactivity and interaction with dentin of four calcium silicate-based sealers (CSBS). Three single-phase CSBS (AH Plus Bioceramic/AHB, CeraSeal/CSL, TotalFill BC/TFL), one powder/liquid CSBS (BioRoot RCS/BRT) and an epoxy control (AH Plus Jet/AHP) were investigated. Setting time was evaluated on glass (G1) and dentin (G2) surfaces, by adding 1%wt purified water to single-phase products. For hardness measurements, the Shore-D hardness test was used. Solubility was assessed according to the ISO 6876:2012 standard. For bioactivity screening, 1-week set specimens were immersed in SBF or water (30 days/37 °C) and examined by ATR–FTIR spectroscopy. Interaction with dentin was tested by ATR–FTIR before and after contact with the sealers. For setting time in G1, all CSBS failed to comply with the ISO standard, while in G2, most materials were set in the range of 6–8 h, except for CSL. The ranking of significant differences in hardness was AHP, BRT > CSL, AHB, TFL. Regarding solubility, AHB, BRT and AHP were found to comply with the ISO standard, whereas CSL and TFL failed. For bioactivity, characteristic peaks of calcium phosphates were found in all CSBS, with TFL being the most bioactive. A chemical interaction between CSBS and dentin was registered, with a strong reduction in collagen peaks and an increase in carbonates. The CSBS tested exhibited great variance in their behaviour regarding the properties assessed, although a strong deproteinating effect was registered on dentin for all.

Journal of Functional Biomaterials doi: 10.3390/jfb17040191

Authors: Aikaterini Petropoulou Maria Dimitriadi Spiros Zinelis Ioannis Papathanasiou George Eliades

In the original publication [...]

Journal of Functional Biomaterials doi: 10.3390/jfb17040190

Authors: Amisha Parekh Arunendu Ettuthaiyil Sambasivan Mikyle Paul Arash Soltani Aya Ali John Tucker Jonathan W. Pegues Nima Shamsaei Amol V. Janorkar Michael D. Roach

With increasing life expectancy and an aging global population, the demand for orthopedic and dental implants is increasing. Recently developed, citric-acid-based anodization processes facilitate the production of more bioactive oxide layers by incorporating important bone minerals such as Ca, P, and Mg and forming bone-like crystalline compounds such as carbonated apatite on titanium implant materials. The primary goal of the present study was to evaluate the applicability of these anodization processes to solid and 3D-printed titanium alloy substrates. The anodized oxides produced on each solid or 3D-printed lattice substrate revealed multi-scaled surface roughness profiles as evidenced by scanning electron microscopy, optical microscopy, and surface roughness analyses. Additionally, each oxide group was shown to incorporate substantial amounts of Ca, P, and Mg bone-mineral dopants and form AB-type carbonated apatite, as shown using a combination of energy-dispersive spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and attenuated total reflectance–Fourier transform infrared spectroscopy analyses. Finally, each oxide group showed sustained Ca, P, and Mg ion release during an inductively coupled plasma spectroscopy dissolution assessment, and demonstrated early apatite-forming ability during simulated body fluid bioactivity testing. The findings of this study show much promise for the applicability of these novel oxide coatings to a wide variety of future titanium implant applications.

Journal of Functional Biomaterials doi: 10.3390/jfb17040189

Authors: Huaxiang Lei Ye Liang Xuechen Li Xiaojing Huang Chengfei Zhang Ting Zou

Although teixobactin, a promising cyclic undecadepsipeptide, exhibits efficacy against Gram-positive bacteria due to its novel mode of action and low potential for resistance, its clinical application is limited by two key shortcomings: ineffectiveness against Gram-negative bacteria and poor penetration of the protective extracellular polymeric substance (EPS) in biofilms. This renders it unsuitable for targeting the polymicrobial biofilms, which are the cause of periodontitis and peri-implantitis. We designed a modified teixobactin analog by integrating rhamnolipid, Ag@Fe3O4 nanoparticles, and L-Chg10-teixobactin to obtain a novel magnetic nanoparticle (MNP). The MNP demonstrates the ability to simultaneously degrade EPS, penetrate biofilm structures, and eliminate both G+ and G− pathogens under a rotating magnetic field (RMF). Rhamnolipid grafting degraded 52.5% of biofilm EPS. MNPs showed broad-spectrum antimicrobial activity, with minimal inhibitory concentrations from 100 to 200 µg/mL. Combined with RMF, biofilm eradication rates reached 97.0% (E. faecalis), 97.7% (S. gordonii), 88.4% (P. gingivalis), and 74.2% (F. nucleatum). The biofilm thickness was reduced from 19.4 ± 2.9 µm to 7.4 ± 1.0 µm, and the biofilm biomass was reduced by 68.5%. This combined strategy integrates enzymatic EPS degradation, magneto-mechanical disruption, and dual antimicrobial action, offering a promising topical therapy for periodontitis and peri-implantitis.

Journal of Functional Biomaterials doi: 10.3390/jfb17040188

Authors: Miruna Dinescu Vlad Gabriel Vasilescu Lucian Toma Ciocan Bianca Voicu-Balasea Ana Maria Cristina Țâncu Alexandra Ripszky Florin Miculescu Sabina-Ana Răuță Alexia-Ecaterina Cârstea Mihaela Pantea Marina Imre

In the continuous development of additive technologies and light-sensitive resins, the biological performance of 3D-printed resins is strongly dependent on photopolymerization efficiency and post-processing conditions. This study evaluated the effect of post-curing duration on the cellular response to two denture base resins using direct contact and indirect eluate-based pathways. Human gingival fibroblasts were assessed through viability, membrane integrity, nitric oxide production, fluorescence live/dead staining, and caspase-3/7 activity. As a result of contact between the cells and the surface interface of the specimen disks, reduced metabolic activity was noticed compared with the control under direct exposure, indicating cellular stress. Extended polymerization has been demonstrated to improve metabolic activity and reduce apoptotic signals for the V-Print dentbase resin, whereas FotoDent Denture presented a less uniform response under the same parameters. Therefore, for evaluating the cytotoxicity of light-sensitive resins, it is not sufficient to assess only the saliva-soluble substances released from the resin, such as residual monomers, but also the 3D printing parameters.

Journal of Functional Biomaterials doi: 10.3390/jfb17040187

Authors: Jonas Neijhoft Hela Weslati Volker Eras Jan Brune Maximilian Leiblein Santiago Bianconi Nicolas Söhling Lewin Busse René Verboket Johannes Frank Ingo Marzi Dirk Henrich

Fused filament fabrication (FFF) enables patient-specific scaffolds for critical-size bone defects, but most filaments are bioinert and difficult to functionalize at high particulate loadings due to segregation, agglomeration, clogging, and diameter instability. We developed a mechanism-guided extrusion toolkit to stabilize polylactic acid (PLA) filaments containing human demineralized bone matrix (DBM) or cortical granulate (CG) up to 70 wt%. PLA was ground, dried, silicone pre-coated, and compounded with DBM or CG (25/40/70 wt%) using starve-fed extrusion, sequential extrusion, and post-die mixing to maintain stable diameters. FFF produced disks and tubes. MSC adhesion was assessed by SEM. qPCR (control vs. osteogenic medium) quantified RUNX2, ALP, BGLAP, COL1A, VEGF, IL-6, MAPK8. Tubes underwent three-point bending. The toolkit yielded printable, dimensionally stable filaments at 25–70 wt% with uniform dispersion and surface-exposed filler. Both composites increased early mesenchymal stromal cells (MSC) adhesion versus PLA. RUNX2 was increased on DBM40 versus PLA. VEGF was elevated on CG25 (DBM40 trend). Under osteogenic medium, IL-6 and MAPK8 were generally reduced. Mechanics were loading-dependent: CG25 exceeded CG70 and DBM25, while DBM40/70 recovered stiffness versus DBM25. A mechanism-guided extrusion toolkit enables high-loading PLA–DBM/CG filaments with excellent printability and material-specific biological and mechanical advantages over PLA.

Journal of Functional Biomaterials doi: 10.3390/jfb17040186

Authors: Sebastian Dominiak Aleksandra Piotrowska Marzena Dominiak Tomasz Gedrange Piotr Dzięgiel Alicja Baranowska Michał Ciszyński Jakub Hadzik Paweł Kubasiewicz-Ross

Background: Atrophy of the alveolar ridge in the posterior maxilla often requires sinus floor elevation prior to implant placement. Photobiomodulation using low-level laser therapy (LLLT) has been suggested as a supportive approach for bone healing, although data based on histological evaluation are still limited. Methods: This study presents histological and radiological secondary outcomes of a randomized clinical trial on bone regeneration after lateral window sinus augmentation. Twenty patients were allocated according to grafting material (allogeneic or xenogeneic) and the use of adjunctive LLLT. After 6 months, bone core biopsies were obtained at the time of implant placement and processed for histological analysis. Radiological bone gain was assessed using CBCT. Results: Bone gain was achieved in all groups, allowing implant placement in every case. Mean bone gain reached 7.53 ± 3.32 mm in LLLT-treated sites and 7.02 ± 2.00 mm in controls, with no statistically significant differences. Histological analysis confirmed trabecular bone formation across all groups. Mild inflammatory cell infiltrates were observed more frequently in LLLT-treated sites (p = 0.029), although this finding was not associated with impaired tissue organization or compromised healing. Conclusions: Both allogeneic and xenogeneic grafts showed good biocompatibility and supported effective bone regeneration after sinus augmentation. The addition of photobiomodulation did not demonstrate statistically significant clinical or radiological benefits within this exploratory cohort, but it may be associated with subtle differences in tissue remodeling.

Journal of Functional Biomaterials doi: 10.3390/jfb17040185

Authors: Yongbin Liu Busra Akay Hacan Junjun Zheng Xueying Ge Dongfang Yu Zhe Chen Yitian Xu Ning Shao Haifa Shen Xuewu Liu Roderic I. Pettigrew Ping-Ying Pan Shu-Hsia Chen Junhua Mai

Although immunotherapy has shown great promise in treating various types of cancer, advanced tumors are often refractory due to a highly immunosuppressive tumor microenvironment (TME). We previously engineered a cancer therapeutic vaccine platform, µGCVax, by co-loading tumor antigen peptides, STING and TLR9 agonists into porous silicon microparticles. While effective in models with lower disease burden, its efficacy against advanced colorectal cancer (CRC) was less promising due to the accumulation of myeloid-derived suppressor cells (MDSCs) in TMEs. In this study, we investigated whether µGCVax-based immunotherapy in advanced CRCs could be potentiated via regulating MDSCs to reprogram the TME. In an advanced CT26 murine CRC model, we assessed µGCVax in combination with oxaliplatin, a standard CRC chemotherapeutic with established immunomodulatory effects. We demonstrated that oxaliplatin was preferentially taken up by monocytic MDSCs (M-MDSCs) and effectively reduced their abundance in the bone marrow, blood, spleen, and tumor. Relief of this immunosuppressive TME increased intratumoral infiltration of antigen-specific CD8+ T cells. Ultimately, the combination of oxaliplatin with µGCVax induced robust regression of established CRC tumors. These findings highlight that oxaliplatin synergizes with µGCVax by overcoming MDSC-mediated immunosuppression and enhancing antitumor immunity, representing a promising chemo-immunotherapy strategy for advanced CRC.

Journal of Functional Biomaterials doi: 10.3390/jfb17040184

Authors: Rosana Farjaminejad Samira Farjaminejad Franklin Garcia-Godoy Anand Marya Ludovica Nucci Abdolreza Jamilian

Tissue engineering integrates concepts from medicine, biology, and engineering to create living constructs capable of repairing, replacing, or supporting damaged tissues. This multidisciplinary field relies on the interplay between biomaterials, cellular sources, and bioactive signaling to achieve functional tissue regeneration. This review provides a comprehensive overview of recent advances in scaffold design, highlighting natural, synthetic, and hybrid materials, as well as innovative fabrication techniques such as electrospinning, 3D bioprinting, and smart biomaterials. It discusses the role of stem cells and growth factors in directing regeneration and examines a wide range of clinical applications, including skin regeneration, cartilage repair, bone tissue engineering, dental and periodontal regeneration, nerve repair, cardiac tissue engineering, liver tissue models, and ophthalmic applications. Current challenges, such as immune responses, limited vascularization, scalability, and regulatory barriers, are addressed alongside emerging strategies aimed at improving clinical translation. By integrating diverse tissue types and engineering approaches within a unified framework, this review offers a broad yet detailed perspective on the current state and future directions of regenerative medicine.

Journal of Functional Biomaterials doi: 10.3390/jfb17040183

Authors: Polina Shabes Julian-Dario Rembe Arzu Mammadova Katharina Henrika Beckamp Markus Udo Wagenhäuser Wiebke Ibing Hubert Schelzig Waseem Garabet

Hemostatic biomaterial agents are widely used during surgery and trauma care to control bleeding, yet their effects on wound healing remain incompletely understood. This study evaluated the impact of oxidized non-regenerated cellulose (ONRC), oxidized regenerated cellulose (ORC), and a gelatin-based hemostat (GELA) on wound healing at 14 and 30 days in a mouse model. Full-thickness wounds were created in C57BL/6J mice (n = 192) and compared to sham controls. Tissue samples were analyzed histologically, supported by immunohistochemistry for Ki-67 and α-SMA and qPCR for VEGF, TGF-β, and FGF-2. Histology demonstrated preserved tissue architecture across groups with progressive resorption of cellulose-based materials, whereas GELA showed localized fibrous structures and enhanced extracellular matrix formation. At day 14, no significant differences were observed in proliferation, contraction, VEGF, or FGF-2 expression; however, TGF-β was significantly reduced in the ORC group. By day 30, GELA significantly increased epidermal proliferation, while contraction markers were elevated in both GELA and ORC. VEGF expression was reduced in GELA and ORC, whereas ONRC showed increased TGF-β expression. FGF-2 remained unchanged across groups. All investigated hemostatic materials were well tolerated during the early postoperative phase (up to day 14), indicating short-term biocompatibility within the scope of this model. In contrast, material-specific differences in cellular activity and growth factor expression became apparent during the later remodeling phase (day 30). These findings suggest differential effects on cellular and molecular aspects of tissue remodeling; however, no conclusions can be drawn regarding overall healing quality or clinical safety, as no quantitative macroscopic or functional outcome measures were assessed.

Journal of Functional Biomaterials doi: 10.3390/jfb17040182

Authors: Hudson Balthazar Cavalcante de Oliveira Jessica Zablocki da Luz Fabio Eduardo de Lima Cauani de Castro Busatto Fernandes Leticia Barbosa Wetter Carolina Silva Schiebel André Vieira Souza Fhernanda Ribeiro Smiderle Daniele Maria-Ferreira Cleber Machado-Souza

Advances in dental material science over recent decades have significantly improved the mechanical, physical, esthetic, and adhesive properties of restorative systems. As clinical performance and durability have reached high standards, research has progressively shifted from purely mechanical replacement toward the development of bioactive materials capable of interacting beneficially with biological tissues. Rather than functioning solely as passive restoratives, contemporary materials are increasingly designed to contribute to disease prevention and tissue repair. Bioactive functionality encompasses both bioprotective and biopromotive effects, including antimicrobial activity, reinforcement of the dental substrate, promotion of remineralization, modulation of inflammatory responses, and stimulation of regenerative pathways. In this context, the surface pre-reacted glass ionomer (S-PRG) particle has emerged as a multifunctional bioactive technology. Its unique three-layer structure enables sustained release of multiple ions, fluoride, strontium, boron, sodium, silicate, and aluminum, associated with mineralization, biofilm inhibition, inflammatory regulation, and activation of cellular signaling pathways. An integrative review was conducted through a literature search in PubMed, SciELO and Scopus using the descriptors “Surface-reaction-type prereacted glass ionomer” and “S-PRG.” Experimental studies evaluating antimicrobial, anti-inflammatory, remineralizing, cellular, or regenerative effects of S-PRG-containing materials were considered eligible. A total of 49 studies met the inclusion criteria and were analyzed through descriptive synthesis. The available evidence indicates that the biological activity of S-PRG-containing materials extends beyond caries prevention, including modulation of inflammatory responses, enhancement of mineralization processes, and stimulation of cellular pathways related to tissue repair. These findings highlight the potential of S-PRG technology as a promising strategy for the development of restorative materials with regenerative and preventive properties.

Journal of Functional Biomaterials doi: 10.3390/jfb17040181

Authors: Yiming Yang Rongpu Liu Yuqi Zhou Lingjun Yuan Zhenxia Li Qian Liao Bing Fang

Titanium implants are widely used in orthopedic and dental fields but often face challenges such as insufficient osseointegration and peri-implant inflammation. While Strontium (Sr) possesses potent bioactive properties, achieving its controlled delivery at the implant-tissue interface remains technically challenging. To address this, we engineered a multidimensional composite coating by constructing a micro/nano-porous TiO2 substrate via micro-arc oxidation (MAO), followed by polydopamine (PDA)-assisted Sr immobilization. This integrated architecture significantly enhanced surface hydrophilicity and facilitated high-content Sr loading with sustained release kinetics. Biological evaluations demonstrated that the PDA-mediated interface promoted superior initial adhesion and spreading of bone marrow mesenchymal stem cells (BMSCs), synergizing with released Sr2+ to markedly upregulate core osteogenic markers (Runx2, ALP). Crucially, the functionalized surface actively optimized the immune microenvironment by inducing M1-to-M2 macrophage polarization and comprehensively suppressing RANKL-induced osteoclastogenesis via the downregulation of TRAP and DC-STAMP. By integrating these pro-osteogenic, anti-inflammatory, and anti-resorptive capabilities, this tri-functional system effectively rebalances the bone remodeling microenvironment. Consequently, it provides a robust, universally applicable strategy for enhancing the therapeutic efficacy of next-generation orthopedic and dental implants.

Journal of Functional Biomaterials doi: 10.3390/jfb17040180

Authors: Shih-Min Hsia Ming-Gene Tu Wen-Hao Yang Tong-Hong Wang Yin-Hwa Shih Tzong-Ming Shieh

Inspired by their biocompatibility and thermoreversible gelation—transitioning from room temperature liquids to body temperature gels—Pluronic hydrogels were employed in this study to optimize intracanal penetration and ensure medicament stability. We developed a silver nanoparticle (AgNP)-loaded Pluronic gel (AgNPs-P-gel) as a biocompatible, easily removable intracanal medicament. Following PRILE 2021 guidelines, AgNPs-P-gels (F127/F68) were evaluated for gelation, AgNP release, and antibacterial activity against Enterococcus faecalis and Streptococcus mutans via minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and growth curves. Biofilms in bovine teeth were quantified using CFUs and scanning electron microscope (SEM) imaging. Biocompatibility was tested in L-929 fibroblasts using MTT assays and RT-qPCR for pro-inflammatory cytokines (IL-6, TNF-α, IL-1β). Removal efficacy from bovine canals was microscopically scored. The optimized formulation (20% F127, 7.5% F68) gelled at 34 °C with sustained release over 168 h. AgNPs-P-gel showed strong antibacterial activity (MIC: 25–50 µg/mL). In ex vivo models, 100 µg/mL AgNPs-P-gel (AgNPs-100-P-gel) reduced bacterial counts comparably to calcium hydroxide and chlorhexidine, but with lower cytotoxicity. Although inducing cytokine expression similar to conventional medicaments, AgNPs-P-gel demonstrated significantly superior removability. Thermoreversible AgNPs-P-gel offers sustained antimicrobial action, favorable biocompatibility, and superior removability, potentially improving endodontic disinfection predictability as a calcium hydroxide alternative.

Journal of Functional Biomaterials doi: 10.3390/jfb17040179

Authors: Konstantin V. Sergienko Sergei V. Konushkin Yaroslava A. Morozova Maria A. Sudarchikova Mikhail A. Kaplan Vadim K. Zhidkov Tatyana M. Sevostyanova Aleksander V. Simakin Ilya V. Baimler Mikhail A. Sevostyanov Alexey G. Kolmakov

The research described in this article is a continuation of a series of studies on biocompatible materials, focused on finding the optimal alloy composition and heat treatment regimes. The use of materials with a low Young’s modulus ensures the long-term safety of the implant by reducing the stress shielding effect, which causes bone resorption. This work investigates the effect of alloying with niobium in the range of (8–10) at. % on the Ti-38Zr alloy, specifically its structure, mechanical properties, Young’s modulus, and superelasticity. In this study, plates of the Ti-38Zr-(8-10)Nb (at. %) alloy were investigated after quenching and subsequent annealing. In Ti-38Zr-(8-10)Nb alloys, quenching from 600 °C fixes the β-phase of Ti. In alloys with (8-9)Nb, this is a metastable β-phase, as evidenced by its superelastic behavior under cyclic tension. Annealing at 400 °C leads to a clear decomposition of the quenched high-temperature β-phase in Ti-38Zr-(8-9)Nb alloys into β- and α′-phases. Based on the mechanical test results, it can be inferred that the precipitation of the brittle ω-phase and the α′-phase occur concurrently, since annealing at 400 °C causes a pronounced embrittlement of the Ti-38Zr-(8–9)Nb alloys (with elongation dropping from ~15% to 0.7–2.5%, respectively) alongside a substantial increase in strength (from 500 MPa to 1010 MPa). For the Ti-38Zr-10Nb alloy, the ductility also declines but remains within acceptable limits (from ~14% to ~10%), while the strength rises from 520 MPa to 630 MPa. The Young’s modulus of the Ti-38Zr-(8-10)Nb alloy after quenching is ~80 GPa. After annealing, it increases to 95 GPa for alloys with (8-9)Nb, while for 10Nb it remains at approximately 80 GPa.

Journal of Functional Biomaterials doi: 10.3390/jfb17040178

Authors: Fiza Ashraf Ataf Ali Altaf

Multiscale interface engineering has influenced the engineering of orthopedic and dental implants through the integration of macroscale architecture, micro-textured surfaces and nanoscale bio-cues. These characteristics help to increase mechanical stability and support early biological responses, as well as increase resistance to microbial colonization. Multiscale interface engineering also helps to explore fabrication schemes that facilitate load-sharing lattices and micro-roughened attachment zones, as well as immune-interactive nano-chemistry. In this study, the biological responses of protein adsorption, osteogenic differentiation, connective-tissue sealing, and macrophage polarization are investigated, together with functional barriers in stress transfer, fatigue resistance and biofilm control. New clinical data with regard to arthroplasty and dental implantology are reviewed to put these factors into perspective. Even though engineered surfaces are reliable in promoting early fixation and initial osseointegration, in the long term, their performance depends on the host’s biological variability, the mechanical forces of loading, coating integrity and peri-implant microbial pressure. Altogether, multiscale interface engineering is an evolving approach to enhancing the lifespan of implants and facilitating biologically sound skeletal and oral reconstruction. A structured literature search was conducted using PubMed, Web of Science, Scopus, and Google Scholar to identify studies published between 2000 and 2025. Approximately 320 articles were initially identified, of which about 140 relevant publications were selected for detailed review.

Journal of Functional Biomaterials doi: 10.3390/jfb17040177

Authors: Jingwen Yang Zihao Zhao Zengtao Song Lei Cao Xifan Mei Xing Zhang

Segmental bone defects are large, non-healing injuries characterized by insufficient structural support and limited bioactivity, posing a significant clinical challenge. In this study, we developed biomimetic chitosan/polyvinyl alcohol–glycerol (CS/PG) scaffolds inspired by porcupine quills, which were fabricated via fused deposition modeling and unidirectional freeze casting. The as-prepared scaffold featured a dense outer layer of polyvinyl alcohol–glycerol (PG) with high compressive strength (24.21 ± 0.11 MPa at 25% strain) and an oriented inner foam of chitosan (CS). The CS foam was further incorporated with poly (3,4-ethylenedioxythiophene) polystyrene sulfonic acid (PEDOT:PSS, denoted as PP) and amorphous zinc phosphate (AZP) to form PP-AZP-CS/PG, aimed at enhancing neural conductivity and stimulating blood vessel formation, respectively. The in vitro results indicated that the biomimetic scaffolds exhibited excellent biocompatibility while significantly enhancing angiogenesis and osteogenesis capabilities. In a rabbit radial segmental defect model, PP-AZP-CS/PG achieved robust bone regeneration, attaining a bone volume/total volume of approximately 26.22% after implantation for 8 weeks. Overall, this biomimetic scaffold demonstrated that integrating hierarchical design with additional bioactive components enhanced mechanical support while promoting new bone regeneration, addressing critical challenges in segmental bone defect repair.

Journal of Functional Biomaterials doi: 10.3390/jfb17040176

Authors: Marija Bubalo Sanja Dugonjic Dejan Dubovina Zdenka Stojanovic Milka Gardasevic Jelena Mijatovic Boban Milovanovic Milovan Stevic Milos Stepovic Dejan Jeremic Zlata Rajkovic Pavlovic

Adequate alveolar bone volume is a prerequisite for predictable and long-term success in dental implant therapy. Physiological post-extraction remodeling frequently results in horizontal and vertical ridge deficiencies, which may compromise optimal implant placement. Guided bone regeneration (GBR) has become a cornerstone procedure in implant dentistry, with clinical outcomes largely influenced by the biological and mechanical characteristics of grafting materials. Different bone grafts and their combinations are currently clinically applicable, each exhibiting distinct osteogenic, osteoinductive, and osteoconductive properties, as well as varying resorption profiles and volumetric stability. This narrative review aims to analyze the biological principles of alveolar ridge augmentation, compare the properties of commonly used graft materials, evaluate clinical outcomes, and discuss emerging regenerative strategies. Literature published between 2000 and 2025 was assessed to synthesize current evidence regarding graft integration, bone formation, desorption dynamics, and clinical indications. Autogenous bone remains the gold standard due to its combined osteogenic, osteoinductive, and osteoconductive potential; however, its limitations have driven the development of alternative materials, including allografts, xenografts, alloplastic substitutes, demineralized tooth matrices, platelet concentrates, and customized scaffolds. While no single material is universally ideal, appropriate selection based on defect characteristics and clinical objectives is essential for predictable outcomes. Future research should prioritize long-term comparative trials, biomaterial standardization, and biologically enhanced regenerative approaches.

Journal of Functional Biomaterials doi: 10.3390/jfb17040175

Authors: Petya Peneva Vesela Kokova Elisaveta Apostolova Plamen Simeonov Nikolay Zahariev Yana Gvozdeva Dimitar Penkov Rayna Hadjikinova Ilia Bivolarski Maria Koleva Plamen Katsarov

The development of effective topical drug delivery systems remains a key challenge in wound management, particularly for bioactive compounds with limited skin permeability. In this study, a nanostructured bigel system incorporating sodium humate-loaded ultra-deformable vesicles (UDVs) was developed and evaluated for wound healing applications. Sodium humate-loaded UDVs were prepared using a thin-layer hydration method, and the influence of key technological parameters (phospholipid/glycerol concentrations, sonication time) on vesicle size and encapsulation efficiency was investigated. An optimized UDV formulation characterized by small particle size, high stability, and high drug encapsulation efficiency was selected and incorporated into a bigel composed of hydroxypropyl methylcellulose hydrogel and andiroba oil oleogel. The developed bigels were characterized in terms of microstructure, physical stability, pH, spreadability, and rheological behavior, demonstrating suitable properties for dermal application. In vivo wound healing evaluation in rat wound models revealed that bigels containing sodium humate-loaded UDVs significantly enhanced wound closure and tissue regeneration compared to control and reference treatments. Histopathological analysis confirmed improved granulation tissue formation and complete epithelialization. Overall, the results demonstrate that the proposed UDV-loaded hybrid bigel represents a promising nanostructured platform for enhanced dermal delivery and wound healing therapy.

Journal of Functional Biomaterials doi: 10.3390/jfb17040174

Authors: Chen Zhang Runyi Lin Jinchao You Yaomei Wang Haopeng Wang Yixian Ru Shunxue Xing Junxiang Wang Shan Chen

Bone defects remain a significant challenge in bone tissue engineering, driving an urgent need for advanced materials with enhanced therapeutic properties. Additive manufacturing highlights a unique capacity for customization, which enables the precise realization of complex and personalized composite scaffolds. This study innovatively integrates the superior mechanical properties of polycaprolactone (PCL) with the antibacterial characteristics of S53P4 bioactive glass. Utilizing thermal melt extrusion processing and fused deposition modeling (FDM) technology, we fabricated gradient-structured S53P4@PCL composite three-dimensional porous scaffolds with varying doping ratios (5 wt%, 10 wt%, 20 wt%). To further improve the antibacterial efficacy of the scaffold, exosomes (EXO) derived from grouper eggs were functionalized with bacteria-targeting aptamers (APTs), a type of functional DNA capable of binding to bacterial peptidoglycan, and EXO-APT-20%S53P4@PCL was fabricated. The resulting EXO-APT-20%S53P4@PCL scaffold was able to facilitate the targeted capture and subsequent eradication of bacteria. This study pioneers the synergistic integration of aptamer-modified exosomes into 3D composite scaffolds. Our analysis confirmed that the incorporation of APTs enabled targeted bacterial capture, and antibacterial EXO further enhanced the overall bacterial killing capability of the S53P4@PCL scaffolds. The fabrication of porous S53P4@PCL scaffolds through an innovative composite-molding strategy, combined with EXO-APT functionalization, establishes a new paradigm for customized bone repair.

Journal of Functional Biomaterials doi: 10.3390/jfb17040171

Authors: Szidonia Krisztina Veress Mihai Vlad Golu Lajos Csönge Bernadette Kerekes-Máthé Melinda Székely Bálint Botond Bögözi

Background/Objectives: Healthcare activities contribute significantly to climate change and environmental pollution. The demand for bone grafting is increasing, and the biological properties of bone substitute materials are critically important. A methodology aimed at preserving BMPs may offer an opportunity to improve the biological properties of donor cadaver-derived bone grafts. The aim of this study was to conduct a life cycle assessment of the BMP-preserving approach used in allograft production in order to enhance the environmental sustainability of bone grafting. Methods: Following primary data collection at the West Hungarian Regional Tissue Bank, environmental impacts were assessed using the OpenLCA software and the ReCiPe v1.03 (2016) midpoint and endpoint impact categories. A sensitivity analysis was also conducted under six alternative scenarios to evaluate which changes would have the greatest beneficial effect on environmental impacts. Results: The greatest environmental impacts of allograft production were observed in the categories of material resources: metals and minerals, terrestrial ecotoxicity, and climate change. The climate change impact was 66.759 kg CO2-eq. The environmental impacts of the production process also had a significant influence on human health, with a total DALY value of 6.58 h. The impacts were primarily driven by electricity consumption and the chemicals used; however, in several impact categories, waste management also contributed substantially. Conclusions: Transitioning to more sustainable energy sources (e.g., wind power) would substantially improve the environmental performance of allograft production. Further research is needed to identify more sustainable alternatives for the chemical agents used during processing.

Journal of Functional Biomaterials doi: 10.3390/jfb17040173

Authors: Hao Wang Yunfeng Li

Piezoelectric biomaterials have attracted considerable interest in osteochondral tissue engineering owing to their inherent ability to produce electrical signals in response to mechanical stimuli without external power, thereby closely mimicking the physiological electrical microenvironment required for tissue regeneration. This review comprehensively summarizes recent insights into biological piezoelectricity from the molecular to the macroscopic level, highlighting its interplay with streaming potentials and its regulatory roles in bone and cartilage regeneration. We critically analyze recent advances in major piezoelectric material systems, including ceramics, polymers, and composite scaffolds, with emphasis on their structural characteristics, bioactive performance, and suitability for tissue-specific repair. Among them, polymer-based composite and hybrid piezoelectric scaffolds appear particularly promising for the development of flexible, high-performance osteochondral repair platforms, as they offer a more favorable balance between mechanical compliance, electromechanical output, and biological adaptability. Despite encouraging preclinical findings, significant challenges remain, including biocompatibility, controlled degradation kinetics, and the precise modulation of electrical cues for specific biological contexts. To address these barriers, future research should focus on optimizing scaffold design, integrating responsive and multimodal stimulation strategies, and establishing standardized protocols for preclinical evaluation and clinical translation. Overall, piezoelectric biomaterials hold substantial potential for the development of innovative regenerative therapies for complex osteochondral defects.

Journal of Functional Biomaterials doi: 10.3390/jfb17040172

Authors: Jie Zhang Xiangyun Zou Mengshuang Li Yaosai Liu

The key challenge in restoring neural function after spinal cord injury stems from a vicious cycle triggered by the collapse of the bioelectrical microenvironment at the injury site: an ‘electrical silence–neuronal degeneration–glial proliferation’ cascade that conventional therapies fail to reverse. This review systematically summarizes the pathological mechanisms of electrical microenvironment imbalance and its critical role in neural regeneration. Furthermore, current intervention strategies based on biomaterials are outlined: evolving from passive reconstruction of electrical pathways using conductive materials to proactive regulation of local electric fields through exogenous electrical stimulation, which activates key signaling pathways, such as voltage-gated calcium channels, and thereby promotes axonal regeneration, stem cell differentiation, and immune modulation. Although existing strategies face challenges in precision and biocompatibility, this review integrates multidisciplinary perspectives from neuroscience and biomaterials to establish a theoretical framework for designing precise, biocompatible electrically modulating biomaterials. Ultimately, we aim to advance spinal cord injury treatment from local electrical environment restoration toward a paradigm shift toward functional neural circuit reconstruction.

Journal of Functional Biomaterials doi: 10.3390/jfb17040170

Authors: Xiang-Ting Huang Ying-Chih Lin Ling-Yun Cheng Yi-Dan Chang Wen-Yu Su

Braided nerve guidance conduits (NGCs) composed of decellularized porcine small intestinal submucosa (SIS) were developed to achieve an appropriate balance between mechanical performance and biological compatibility for peripheral nerve repair. This study aimed to compare four SIS-braided conduits with silicone tubes in terms of bending compliance, tensile strength, swelling behavior, and cytocompatibility. SIS-braided conduit exhibited a favorable combination of flexibility, tensile strength, and dimensional stability. In vitro evaluations using PC12 and SW10 cells demonstrated that SIS-braided conduit supported neurite outgrowth and Schwann cell adhesion, confirming its favorable cytocompatibility. Based on these findings, SIS-braided conduits and silicone tubes were subsequently evaluated in a rat sciatic nerve defect model. Functional recovery assessed using the Sciatic Functional Index suggested preliminary functional recovery in the SIS-braided conduit, and histological analyses revealed evidence of axonal regeneration and myelin formation within the conduit. Overall, the results indicate that the integration of mechanical robustness with biological activity is essential for the design of nerve graft substitutes. The conduit braided from decellularized small intestinal submucosa represents a promising biodegradable alternative, a considerable biodegradable alternative to conventional non-degradable silicone conduits for peripheral nerve repair.

Journal of Functional Biomaterials doi: 10.3390/jfb17040169

Authors: Gayathri Vijayakumar Amrutha Raja Swathi Ganesan Teja Sri Senthil Jainitha Kandasamy Prathiksha Senthil Kumaran Senthil Kumaran Rangarajulu

An eco-friendly green synthesis approach was employed to produce copper nanoparticles (CuNPs) using a polyherbal extract derived from two medicinally important plant species, Hygrophila auriculata (Schumach.) Heine and Leucas aspera (Willd.) Link. The plant extracts were initially subjected to phytochemical screening to identify bioactive constituents potentially involved in nanoparticle synthesis. The synthesized CuNPs were characterized using UV-visible spectroscopy, Fourier-transform infrared spectroscopy (FTIR), gas chromatography–mass spectrometry (GC-MS), field-emission scanning electron microscopy coupled with energy-dispersive X-ray analysis (FESEM-EDAX), X-ray diffraction (XRD), and thin-layer chromatography (TLC). UV-visible spectroscopy revealed a characteristic absorption peak at 233.6 nm. FTIR analysis indicated the presence of functional groups associated with nanoparticle reduction and stabilization, whereas FESEM imaging showed predominantly spherical particles with sizes ranging 63–68 nm. Elemental composition was confirmed using EDAX analysis. XRD analysis demonstrated polycrystalline nature of the CuNPs, with an average crystallite size of 11.5 nm. GC-MS analysis and phytochemical screening further confirmed the presence of bioactive compounds, whereas TLC analysis revealed differences in mobility between the plant extract and synthesized CuNPs. Antibacterial activity of the synthesized CuNPs was evaluated using the agar well diffusion method against clinically relevant bacterial strains, including those of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Streptococcus pyogenes. The polyherbal-derived CuNPs produced larger inhibition zones than the individual plant extracts, particularly against multidrug-resistant pathogens such as P. aeruginosa and S. aureus. Additionally, the nanoparticles exhibited concentration-dependent antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl assay at concentrations ranging 10–50 mg/mL, with radical scavenging activity increasing from 29.9% to 76.5% and a corresponding decrease in absorbance from 0.698 to 0.234 (p < 0.05). Cytotoxic evaluation in HepG2 cells after 48 h of exposure demonstrated dose-dependent morphological changes and reduced cell viability. These findings suggest that polyherbal-derived CuNPs possess antibacterial, antioxidant, and cytotoxic properties with potential relevance for biomedical applications.

Journal of Functional Biomaterials doi: 10.3390/jfb17040168

Authors: Loai Alsofi

Objectives: To evaluate the physicochemical properties of a novel strontium silicate-based root canal sealer (C-Root SP) in comparison with a calcium silicate-based sealer (TotalFill BC) and an epoxy resin-based sealer (AH Plus). Methods: Setting time, net mass change (apparent solubility behavior), pH changes, and surface characteristics were assessed based on ISO 6876 and ANSI/ADA Specification No. 57, with minor methodological modifications. Net mass change and pH were evaluated over 28 days. Surface morphology and elemental composition were analyzed after dry and aqueous aging in deionized water using scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. Data were analyzed using one-way and repeated-measures ANOVA with Tukey’s post hoc test (α = 0.05). Results: AH Plus exhibited the longest initial and final setting times (10.93 ± 0.65 h and 37.33 ± 0.13 h), whereas TotalFill BC showed the shortest (7.98 ± 0.32 h and 30.18 ± 0.20 h); C-Root SP demonstrated intermediate values (9.35 ± 0.38 h and 32.75 ± 0.57 h) (p < 0.001). C-Root SP exhibited positive net mass change values (indicative of net mass loss), ranging from 5.32 ± 4.72% at 24 h to 6.83 ± 5.55% at 28 days, significantly higher than AH Plus and TotalFill BC (p < 0.001), which showed negative values indicative of apparent mass gain. All sealers demonstrated alkaline conditions, with C-Root SP maintaining the highest apparent pH values throughout the evaluation period (p < 0.001). Surface and compositional changes were observed in the bioceramic sealers following aqueous aging, with increased detectable strontium content in C-Root SP. Conclusions: C-Root SP exhibited physicochemical behavior consistent with a strontium-modified calcium silicate-based sealer, characterized by hydration-driven hydroxyl ion release resulting in apparent alkalinity and ion exchange-associated behavior, and dynamic surface changes consistent with those reported for bioceramic materials. Clinical Significance: Strontium incorporation may influence hydration-mediated physicochemical behavior; however, further in vitro and in vivo studies are required to determine its clinical relevance.

Journal of Functional Biomaterials doi: 10.3390/jfb17040162

Authors: Ülkü Tuğba Kalyoncuoğlu Nurten Baysal Gulcin Akca Simel Ayyıldız Burak Yilmaz

The surface characteristics of zirconia may influence both soft tissue response and bacterial colonization. This study evaluated the surface roughness and water contact angle of zirconia fabricated by additive manufacturing (material jetting, NPJ) and subtractive manufacturing (milling), and investigated human gingival fibroblast (HGF-1) viability and Streptococcus mutans (S. mutans) (ATCC 25175) adherence on these surfaces, as well as the possible correlation between roughness and bacterial adhesion. Sixty-four zirconia specimens (1 × 1 × 0.1 cm) were fabricated (n = 32 per group), sintered, and standardized by abrasive polishing. Surface roughness and contact angle were measured. Cell viability was assessed using an MTT assay at 24, 48, and 72 h. Bacterial adhesion was quantified after 24 and 48 h of incubation. Data were analyzed using two-way ANOVA, independent t-tests, and Pearson correlation (α = 0.05). No significant differences in HGF-1 viability were observed at 24 and 48 h; however, at 72 h, subtractively manufactured zirconia demonstrated higher cell viability than additively manufactured specimens (p < 0.001). S. mutans adhesion was significantly greater on additively manufactured zirconia at 24 h (p = 0.002), with no significant difference at 48 h. Manufacturing technique influenced surface properties and early bacterial adhesion. Both materials exhibited acceptable biocompatibility within the tested conditions.

Journal of Functional Biomaterials doi: 10.3390/jfb17040167

Authors: Britney S. Force Xueqin Gao Johnny Huard

Musculoskeletal disorders and injuries are highly prevalent and encompass a broad range of conditions, including bone fractures and segmental defects, tendinopathies and tendon injury, and cartilage disorders such as osteoarthritis, cartilage defects, and intervertebral disc disease. These conditions can arise from diverse causes including trauma and injury, tumor resection, congenital abnormalities, and age-related degeneration. In the past decades, administration of chemically modified mRNA (cmRNA) encoding growth factors and transcriptional regulators has demonstrated effectiveness in repairing musculoskeletal tissues in preclinical studies. This review summarizes recent advancements in bone, tendon, cartilage, intervertebral disc, and muscle regeneration achieved through the localized delivery of protein-encoding mRNAs to express therapeutic target proteins. Delivery of cmRNA encoding growth factors such as BMP-2, BMP-9, VEGF, FGF-18, and IGF-1, or transcriptional regulators including Runx1, to various animal models has shown beneficial effects on bone, tendon, cartilage, and muscle injury repair in preclinical models. Alongside these progresses, the advantages and disadvantages of applying chemically modified mRNA for musculoskeletal tissue regeneration are also discussed. While studies show the promise of cmRNA for therapeutic applications in orthopedic tissue regeneration, more research is required to optimize growth factors and delivery methods, as well as validate long-term safety and efficacy prior to successful translation into new therapies to benefit patients.

Journal of Functional Biomaterials doi: 10.3390/jfb17040165

Authors: Soichiro Fukushima Lupeng Teng Makoto Koizumi Minami Hasegawa-Ogawa Hiroki Ohta Ryosuke Iwai Hirotaka James Okano Takao Ohki

Postoperative aneurysm sac enlargement is a significant clinical issue in endovascular aortic aneurysm repair that is potentially associated with impaired microcirculation in the aneurysmal wall. We developed centimeter-long, fiber-shaped aggregates of human bone-marrow-derived mesenchymal stromal cells (HMSC fiber) to function as a scaffold-free cellular construct applicable to endovascular treatment. HMSC fibers were prepared using a cell self-aggregation technique and optimized by controlling the cell number per unit length to preserve cellular viability and mechanical stability. The resulting fibers retained mesenchymal stromal cell characteristics and endogenous extracellular matrix, facilitating smooth handling and intraluminal delivery without structural collapse. After transcatheter administration into a swine aortic aneurysm model, HMSC fiber-induced fibroconnective tissue formation occurred with capillary-like structures within the aneurysm sac. These findings demonstrate the feasibility of HMSC fiber as a controllable and stable platform for localized endovascular cell delivery. Furthermore, this study established their potential utility as a regenerative adjunct to current endovascular treatment for aortic disease.

Journal of Functional Biomaterials doi: 10.3390/jfb17040166

Authors: Furkan Özay Selim Ersanlı

Numerous chemical and physical surface decontamination methods are used in clinical practice for implant surface decontamination, which constitutes the most critical step in the management of peri-implantitis. The aim of this study was to compare, in vitro, the efficacy of the electrolytic cleaning device GalvoSurge (GalvoSurge, GalvoSurge Dental AG, Widnau, Switzerland) with that of an air-abrasive AIRFLOW unit (AIRFLOW, Master PiezonVR, EMS Electro Medical Systems, Herrliberg, Switzerland). Thirty-two SLA-surfaced dental implants were allocated to two groups (n = 16) and contaminated with permanent ink, after which they were placed into jaw models representing two different defect configurations. After treatment, implants were photographed and, using ImageJ, the residual stain area/percentage within a 4 mm region apical to the implant neck was calculated. Surface topography was further evaluated by SEM and EDS. In the two-way analysis of variance, the effect of the decontamination method was statistically significant. The GalvoSurge group exhibited a lower residual stain percentage than AIRFLOW (overall 28.47 ± 10.13 vs. 37.14 ± 9.60; p = 0.019). This difference was independent of defect type (p > 0.05). These findings indicate that electrochemical cleaning via galvanic current may be more effective, under in vitro conditions, for stain removal and surface decontamination; however, they also demonstrate that residual contamination could not be completely eliminated irrespective of the method.

Journal of Functional Biomaterials doi: 10.3390/jfb17040164

Authors: Carola Millán Isabel Benjumeda-Wijnhoven José I. Contreras Raggio Astrid Muñoz Ignacia Muñoz-Brautigam María F. Álamos Marco A. Lardies Juan F. Santibañez Nelson A. Lagos Juan F. Vivanco

This study presents a comprehensive characterization of Argopecten purpuratus (AP) shells—a marine-derived natural bioceramic composed predominantly of calcium carbonate (CaCO3)—to evaluate their potential as biomaterials for regenerative medicine. Structural and compositional analyses were performed using micro-computed tomography (MicroCT), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). These techniques confirmed a high CaCO3 content (>96 wt%) and revealed distinct microstructural features: the outer surface showed irregular grooves and rough textures, while the inner surface exhibited smoother, foliated morphologies with mixed calcite and aragonite phases. To assess biocompatibility, human gingival mesenchymal stem cells (hGMSCs) were cultured on both shell surfaces. Viability and adhesion were evaluated via MTS assays and fluorescence microscopy at time points ranging from 30 min to four weeks. Both surfaces supported robust early metabolic activity and long-term proliferation, with cells covering the entire surface area after four weeks. Morphometric analysis indicated time-dependent changes in cell shape, transitioning from rounded to elongated morphologies, with minor differences linked to surface topography. The integration of structural, compositional, and biological data demonstrates that AP shells provide a cytocompatible and sustainable natural material platform capable of supporting cell adhesion and proliferation. Their inherent micro- and nanoscale surface features may facilitate protein adsorption and cell–material interactions. These findings highlight the importance of correlating microstructural material properties with cellular responses and support the future exploration of marine-derived bioceramics for regenerative medicine applications.

Journal of Functional Biomaterials doi: 10.3390/jfb17040163

Authors: Thomas Harry Jovic Josh Roberts Feihu Zhao Shareen Heather Doak Iain Stuart Whitaker

Shear stress is a significant consideration in 3D bioprinting systems, with implications for cell viability and behaviour. This study hypothesised that relevant levels of shear stress would be generated during the process of 3D bioprinting human nasoseptal chondrocytes in a nanocellulose alginate bioink, with implications for cell viability and chondrogenic gene expression. Through a combined approach of in silico modelling and in vitro testing, we assessed chondrocyte viability and gene expression immediately within the first 72 h post-printing. Cell viability was determined using live–dead, alamarBlue and lactate dehydrogenase assays immediately and 24 h post-printing compared to cell-only and unprinted cell–biomaterial controls. Gene expression analysis of Type 2 collagen, SOX9, aggrecan and alkaline phosphatase gene expression was performed 4 h and 72 h post-printing. Computational fluid dynamics predicted a shear stress of 292 Pa and maximum fluid velocity of 19 mm/s during the bioprinting process. No statistically significant cell death or cell lysis was detected between groups immediately post-printing; however, statistically significant chondrocyte cell death was observed at 24 h in the printed group (p = 0.047). Moreover, the bioprinting process evoked a transient initial rise in both chondrogenic (SOX9, aggrecan) and osteogenic gene expression (ALP) with a marked suppression in type 2 collagen expression at 72 h (0.05, p = 0.0005), indicating biological effects evoked by shear stress during printing. This study highlights the importance of optimising the bioprinting process to facilitate low shear stress conditions for durable cartilage tissue engineering.

Journal of Functional Biomaterials doi: 10.3390/jfb17040161

Authors: Kamali L. Charles Yunhui Xing Ellen L. Otto Xi Ren Phil G. Campbell David A. Vorp Justin S. Weinbaum

Silk fibroin (SF) is an ideal biomaterial for next-generation clinical wound dressings due to its biocompatibility and tunable mechanical properties. Cell therapies for wound healing have explored using SF as the base for delivering beneficial cargo; however, retention is poor due to exudate “wash out.” To address concerns with the premature release of cargo from SF-fabricated wound dressings, we utilized amine-reactive chemistry to conjugate SF mats with azido-reactive dibenzocyclooctyne (DBCO) that can then attach complementary azido-tagged cargo through chemoselective immobilization. SF mats were made using electrospinning of a 1:1 SF/PCL solution and were then conjugated with N-Hydroxysuccinimide-dibenzocyclooctyne ester (DBCO). PBS soaking was used for control SF mats. SF mats were then imaged and characterized using the following metrics: pore size, fiber alignment, fiber distribution, fiber diameter, ultimate tensile strength, tangent modulus, proteolytic degradation, absorption, and retention. Successful DBCO conjugation of SF mats was confirmed through the presence of the Az-Cy5 dye while exhibiting no significant changes to the DBCO SF mats in any of the tested metrics compared to controls. Our results provide evidence that the amine chemistry responsible for the DBCO conjugation does not alter important SF mat properties. This confirms that DBCO augmentation paired with Az-Cy5 tags may be a viable approach for immobilizing different therapeutic cargoes to aid wound healing efforts.

Journal of Functional Biomaterials doi: 10.3390/jfb17040160

Authors: Alain Manuel Chaple Gil Laura Pereda Vázquez Meylin Santiesteban Velázquez Jorge J. Menéndez

Non-carious cervical lesions (NCCLs) present restorative challenges due to substrate sclerosis and marginal stress concentration, making the adhesive strategy a key determinant of long-term performance. This systematic review and frequentist random-effects network meta-analysis, conducted in accordance with PRISMA 2020 and the PRISMA-NMA extension and prospectively registered in PROSPERO, compared restorative strategies defined by etching approach, adhesive category, and restorative material, with marginal adaptation and retention loss as the primary outcomes. PubMed, Web of Science, Cochrane Library, Embase, and Scopus were searched without restrictions (25 January 2026), supplemented by alternative retrieval methods. Randomized clinical trials in permanent teeth evaluating at least two etching-based strategies (etch-and-rinse, self-etch, selective-etch, and/or resin-modified glass ionomer cement (RMGI)) were included. Risk of bias was assessed using RoB 2 and certainty of evidence with CINeMA. Seventy-four trials were eligible. Connected networks were established for marginal adaptation (57 studies; 28 interventions; 6798 patients; 1772 events) and retention loss (61 studies; 33 interventions; 7338 patients; 584 events). Selective-etch with a universal adhesive and nanocomposite reduced marginal adaptation failure compared with RMGI, whereas certain self-etch and non-universal combinations increased risk. For retention loss, selective-etch and etch-and-rinse protocols combined with universal adhesives and nanocomposites showed lower failure rates, while some self-etch or non-universal adhesive strategies performed less favorably. Overall confidence was predominantly high, with downgrading mainly due to imprecision and heterogeneity. Strategies incorporating selective enamel etching or etch-and-rinse approaches combined with universal adhesives and nanocomposites demonstrated the most consistent clinical advantages.

Journal of Functional Biomaterials doi: 10.3390/jfb17040159

Authors: Abel Remache Wilson Pavon Oscar Jara Vinueza Josseline Chicaiza Jorge Mauricio Fuentes Homero Cadena

Fused deposition modeling (FDM) of carbon fiber-reinforced polycarbonate (PC-CF) is increasingly used in medical applications due to its excellent strength-to-weight ratio and adaptability for custom geometries. However, sterilization is a critical step that may compromise the structural integrity of polymer composites. This study investigates the effects of two low-temperature sterilization methods—ethylene oxide (EO) and hydrogen peroxide vapor (HP)—on the mechanical, thermal, and viscoelastic properties of FDM-printed PC-CF parts. Characterization included tensile, impact, and hardness tests; thermomechanical analysis (TMA); and dynamic mechanical analysis (DMA). EO sterilization resulted in approximately 20% reduced elongation at break and lower glass transition temperature, indicating a loss of ductility and thermal stability. HP-treated samples showed reduced stiffness (16% in Young modulus) but increased Tg and reduced thermal expansion, suggesting improved dimensional stability. DMA results confirmed distinct viscoelastic behavior between treatment types. These findings provide evidence for selecting appropriate sterilization protocols for FDM-manufactured PC-CF components used in functional medical devices.

Journal of Functional Biomaterials doi: 10.3390/jfb17030158

Authors: Swathi N. V. Raghu Yomna Badran Shanmugapriya Periyannan Manuela S. Killian

Modern bioimplants increasingly depend on surface-engineered functionality to elicit adaptive biological responses. One promising strategy involves the electrodeposition of bioresponsive elements such as magnesium (Mg), which plays a critical role in osseointegration. In this study, we present a novel approach for modifying anodized zirconia nanotubes (ZrNTs) via Mg decoration using electrochemical deposition. A controlled pulsed cathodic linear sweep protocol was employed to control Mg deposition behaviour, enabling reduced clustering and improved spatial distribution. Notably, ultraviolet (UV) irradiation was found to influence Mg adsorption dynamics, revealing a distinct pattern of interaction. Comprehensive surface characterization was conducted to assess nanotube morphology, Mg adherence, and distribution. These modified surfaces were subsequently evaluated for their potential in further functionalization, targeting surface chemistries conducive to biomaterial viability. The biomineralization capacity of Mg-decorated ZrNTs was systematically investigated using electrochemical impedance spectroscopy (EIS) and Tafel analysis, demonstrating enhanced apatite formation and improved corrosion resistance. This work establishes Mg decoration of ZrNTs as a viable route for developing bioactive, corrosion-resistant implant surfaces.

Journal of Functional Biomaterials doi: 10.3390/jfb17030157

Authors: Mehmet Ali Fildisi Burcu Oglakci Ozkoc Zumrut Ceren Ozduman Evrim Eliguzeloglu Dalkilic

In computer-aided design/computer-aided manufacturing (CAD/CAM) restorations for severely damaged teeth, the cavity floor or proximal margins may be elevated with composite resin to improve adhesion. This in vitro study investigated how different surface pretreatment methods affect the shear bond strength (SBS) of hybrid CAD/CAM materials to dentin or composite surfaces, simulating clinical situations of composite elevation. Hybrid CAD/CAM samples were bonded to dentin or composite substrates following different surface pretreatment protocols and cemented using a dual-cure adhesive resin cement. The samples were thermocycled and subjected to shear bond strength testing, and failure modes were analyzed. The SBS in the sandblasting (SB)+Dentin group and hydrofluoric acid (HF)+Dentin was significantly higher than that in the SB+Composite and HF+Composite groups (p < 0.05). Untreated+composite and untreated+dentin groups showed significantly lower SBS (p < 0.05). Failure mode analysis revealed a predominance of cohesive failures in the SB+Dentin group, while adhesive failures were more frequently observed in most of the other groups. SB-treated and HF-etched hybrid CAD/CAM materials showed more favorable bonding behavior to dentin than to composite, highlighting that bonding to the elevated composite layer may be less effective than bonding directly to prepared dentin.

Journal of Functional Biomaterials doi: 10.3390/jfb17030156

Authors: Keisuke Nakayama Xueqin Gao Britney S. Force Marc J. Philippon Johnny Huard

Large bone defects resulting from trauma, tumor resection, infection, or degenerative diseases pose a major clinical challenge in orthopedic surgery and regenerative medicine. Despite advances in biomaterials and surgical techniques, successful outcomes are often compromised by poor vascularization, limited osteoinduction, and donor-site morbidity associated with autografts or allografts. However, conventional delivery systems suffer from burst release, rapid clearance, off-target effects, and supraphysiologic dosing, which can lead to undesirable complications such as ectopic ossification and inflammation, with some reports raising concerns about the long-term tumorigenic risk. Heparin, a naturally highly sulfated glycosaminoglycan structurally related to heparan sulfate, has emerged as a particularly attractive candidate for affinity-based biomaterial systems. It naturally binds over 300 growth factors, including bone morphogenetic proteins. By protecting these proteins from enzymatic degradation, enhancing their bioavailability, and mediating receptor clustering, heparin provides both biochemical stability and biofunctional modulation. This review provides a comprehensive overview of heparin-based delivery strategies in bone tissue engineering. We begin by describing the biological functions of heparin in modulating growth factor activity. We then discuss in detail the different heparin-based biomaterials designed to sustain the release of growth factors for bone tissue engineering, including the heparin–polycation coacervate system; heparin-based supramolecules; and heparin-based hydrogels, nanoparticles, and microspheres for sustained release of bone morphogenic proteins and other growth factors for bone tissue engineering. Finally, we assess the clinical and translational relevance of heparin-based systems, identify key challenges, and outline future perspectives, highlighting the potential of these biomaterials for providing safer and more effective therapies for bone regeneration.

Journal of Functional Biomaterials doi: 10.3390/jfb17030155

Authors: Jacob A. Kendra Alexandra G. Naman Rebekah L. Blatt Carla D. Zingariello Richard K. Brow Steven S. Segal Aaron B. Morton

Skeletal muscle myopathy remains a significant cause of disability with limited treatment strategies. Advancements in tissue engineering have led to the development of borophosphate bioactive glasses (BPBGs) capable of enhancing skeletal muscle structure and function. Using a mouse model of severe myopathy (D2.mdx), we investigated muscle force, regeneration, angiogenesis and inflammation at 14, 70 and 140 days post-treatment (dpt). Tibialis anterior (TA) muscles of D2.mdx mice that received a single injection of cobalt oxide-doped BPBG (CoO-TRIM) particles exhibit greater active force, myofiber size, and regeneration through 70 dpt compared to control D2.mdx mice injected with Saline. Vascular endothelial growth factor (VEGF) was elevated up to 70 dpt in D2.mdx CoO-TRIM mice followed by increased muscle vascularity. As a marker of inflammation, interleukin (IL)-6 increased in D2.mdx CoO-TRIM mice compared to D2.mdx Saline controls at 14 dpt, with no differences at 70 or 140 dpt. No differences were observed in outcome measures between wild-type (WT) CoO-TRIM mice and WT Saline controls. We report that CoO-TRIM can stimulate VEGF production and promote restoration of muscle structure and function when inflammation is present. Local injection of an inorganic biomaterial alone can benefit myopathic skeletal muscle.

Journal of Functional Biomaterials doi: 10.3390/jfb17030154

Authors: Meizi Eliezer Ruxandra Christodorescu Alla Belova Darian Rusu Stefan Milicescu Moshe Cohen Stefan-Ioan Stratul

Hyaluronic acid (HA) is a biologically active glycosaminoglycan with recognized roles in wound healing and inflammation modulation, and its adjunctive use in dental and periodontal therapy has gained interest, particularly in medically compromised patients. This narrative review critically evaluated preclinical and clinical evidence on locally applied HA in periodontal, oral surgical, peri-implant, and oral medicine treatments in patients with systemic conditions. A literature search of PubMed/MEDLINE, Scopus, and Web of Science (January 2015–December 2025) identified in vivo translational studies, randomized and controlled clinical trials, and selected systematic reviews involving medically compromised populations. Qualitative synthesis focused on biological plausibility, clinical outcomes, and safety. Nine core studies were included, comprising two preclinical in vivo investigations and seven clinical trials. In diabetic models, cross-linked high-molecular-weight HA reduced macrophage infiltration and delayed collagen membrane degradation without impairing angiogenesis. Clinically, adjunctive HA use in patients with type 2 diabetes mellitus was associated with modest but statistically significant short-term improvements in clinical attachment level (CAL) and enhanced early soft tissue healing following tooth extraction. In peri-implantitis therapy and oncology-related oral complications, HA application was linked to reduced inflammatory markers, decreased lesion severity, and improved patient-reported symptoms. No systemic adverse effects were reported. Overall, HA appears to be a locally safe adjunct that may support early healing and inflammation control in medically compromised patients, although its effects are primarily short-term and do not indicate disease-modifying potential.

Journal of Functional Biomaterials doi: 10.3390/jfb17030153

Authors: Ying Yang Kunlu Lin Zheng Zhou Libangxi Liu Long Liu Haoming Liu Hanyue Mao Xiaoyan Wang

Mesoporous bioactive glass (MBG) has been extensively studied in bone regeneration due to its excellent bioactivity and osteoconductive properties. Here, we prepared amino-modified MBG (MBG-NH2) adsorbed osteopontin (OPN) to form MBG-NH2/OPN composites, enabling the sustained release of OPN and enhancing osteoblast differentiation and mineralization capacity. Interestingly, we observed that MBG-NH2 promotes the formation of osteoid deposits and calcium deposition in vitro. Furthermore, we also found that MBG-NH2/OPN significantly enhances cell adhesion, differentiation, and mineralization. Consistent with these observations, we found the expression of the osteoblast-specific marker gene increased, including bone morphogenetic protein 2 (Bmp2) and Collagen I. Intriguingly, we also found that MBG-NH2/OPN promotes osteoblast differentiation and mineralization through activating the extracellular regulated protein kinases1/2 (Erk1/2) signaling pathway. We concluded that MBG-NH2/OPN enhances osteoblast differentiation and mineralization through the Erk1/2 pathway. These findings indicate that MBG-NH2/OPN is a new potential biomaterial for bone regeneration.

Journal of Functional Biomaterials doi: 10.3390/jfb17030152

Authors: Ekaterina O. Mikhailova

Green synthesis of nanoparticles has become one of the most popular research areas in recent decades due to its environmentally friendly nature and the minimization of harmful chemical by-products. This review focuses on the mechanism of palladium nanoparticle (PdNP) biosynthesis using bacteria, fungi, algae, and plants, and their potential biological activities, such as antibacterial, anticancer, antioxidant, and other properties, with the aim of their further biomedical applications. The role of various biomolecules in these processes is also discussed.

Journal of Functional Biomaterials doi: 10.3390/jfb17030151

Authors: Jaejeong Jo Geonwoo Kang Chankyoung Lee Tran Thi Bao Vo Dooho Choi

Transparent heaters intended for skin-contacting applications must simultaneously satisfy optical transparency, mechanical compliance, thermal uniformity, and operational safety under biologically relevant temperature ranges. Here, we evaluate the applicability of a TiO2/Ag/SiO2 (TAS) dielectric–metal–dielectric transparent heater as a functional biomaterial platform for wearable and skin-integrated thermal systems. By systematically optimizing each layer thickness of the TAS structure, the heater achieves high visible-light transmittance (average of 86.6%) together with low sheet resistance on the order of 7.7 Ω/sq for low-voltage operation. The TAS heater demonstrates rapid and reproducible Joule-heating behavior, showing fast thermal response with short thermal time constants and spatially homogeneous temperature distributions without localized hot spots. Stable electrothermal performance is maintained under repeated on/off cycling and during cyclic mechanical bending down to small radii, confirming excellent mechanical stability under repeated bending relevant to wearable applications. Importantly, direct on-skin evaluations conducted by attaching the device to a human elbow reveal conformal contact, uniform heating at therapeutically relevant temperatures (50–70 °C), and stable operation under dynamic bending and extension. The absence of thermal inhomogeneity during motion highlights the intrinsic stability of the TAS architecture for skin-interfaced use. Given the high optical visibility, mechanical compliance, thermal uniformity, and electrothermal stability, the proposed TAS architecture represents a promising functional biomaterial platform for wearable thermotherapy, skin-mounted healthcare devices, and human-interactive thermal systems operating under continuous mechanical deformation and direct skin contact.

Journal of Functional Biomaterials doi: 10.3390/jfb17030150

Authors: Agnieszka Balicz Agnieszka Szurko Magdalena Jędzierowska Agnieszka Kiełboń Sylwia Wójcik Jakub Adamczyk Martin Starosta Jakub Fiegler-Rudol Tadeusz Morawiec

Background: Oroantral communication (OAC) is a frequent complication after the extraction of maxillary posterior teeth and requires immediate closure to prevent sinus pathology and long-term functional impairment. Objectives: This study aimed to compare the clinical and radiographic outcomes of acute OAC closure using resorbable heterogeneous collagen membranes with those of the conventional buccal advancement flap (Rehrmann method). Methods: Twenty-four patients with OACs diagnosed within 24 h post-extraction were enrolled, and 20 completed follow-up. Patients were allocated to a membrane group treated with a resorbable collagen membrane (Creos Xenoprotect) or a control group treated with a buccal advancement flap. Clinical parameters, including vestibular depth, width of keratinized gingiva, alveolar socket dimensions, postoperative complications, and pain intensity assessed using the Visual Analogue Scale, were evaluated at 1, 7, 14, and 90 days. Radiographic outcomes were assessed using cone-beam computed tomography with linear measurements and normalized bone density analysis in Hounsfield Units at baseline and 90 days. Results: The membrane technique provided significantly better preservation of vestibular depth, keratinized gingiva width, and alveolar socket dimensions, with significantly lower postoperative pain and fewer complications compared with the buccal advancement flap. Higher normalized bone density values were observed in the membrane group, although differences were not statistically significant. Conclusions: Resorbable collagen membranes represent a safe, minimally invasive, and clinically effective alternative to buccal advancement flaps for acute OAC closure.

Journal of Functional Biomaterials doi: 10.3390/jfb17030149

Authors: Mesut Tuzlali Nagehan Baki Nazik İrem Önügören Kübra Aral Erkan Bahçe Cüneyt Asım Aral

Low-density cancellous bone results in reduced trabecular support and may increase crestal cortical strain around implants. Osseodensification (OD) compacts trabecular bone and may create a peri-osteotomy densified zone, but its strain-level effects in osteoporotic-like bone are unclear. This study evaluated whether an OD-inspired peri-implant densified trabecular zone reduces crestal cortical strain compared with conventional drilling (CD) in an osteoporotic-like model. A three-dimensional finite element model of a mandibular posterior segment with a 2.0-mm cortical shell and D4 cancellous core was constructed with a 4.3 × 11.4-mm titanium implant and a cemented monolithic zirconia crown. CD used a 4.0-mm osteotomy in D4 bone. The OD model used the same osteotomy plus a concentric peri-implant densified shell with radial density gradation from D1 to D3. The implant–bone interface was defined as bonded. Static 100 N axial and 45° oblique loads were applied. Outcomes were εeq, εmax, and εmin, summarized as mean top-10 nodal values. OD reduced crestal cortical strains under both loads. Under axial loading, εeq, εmax, and |εmin| decreased by 17.7%, 19.0%, and 24.1%, respectively. Under oblique loading, the corresponding reductions were 9.8%, 8.0%, and 8.9%. Oblique loading produced higher cortical strains than axial loading in both models. OD-inspired peri-implant densification reduced crestal cortical strain in this osteoporotic-like model, whereas oblique loading remained the main driver of elevated strain. These findings support occlusal/prosthetic strategies that minimize oblique forces and warrant experimental and clinical validation.

Journal of Functional Biomaterials doi: 10.3390/jfb17030148

Authors: Rawan Almujaydil Conor J. McCann Linh Nguyen Francesco D’Aiuto

Despite advances in periodontal regenerative therapies, consistent tissue regeneration remains challenging, with cells playing an essential role in successful repair. Therefore, this study tested different dental bone substitutes embedded in the chorioallantoic membrane (CAM) combined with periosteum-derived micrografts obtained using a chair-side device (Rigenera HBW system). Cell populations within the micrografts were identified and characterised via immunofluorescence and flow cytometry (CD31, CD105, CD34, CD90, CD73, and CD45). A CAM model was employed to examine the angiogenic potential of micrografts combined with bone substitutes, which were analysed through quantitative blood vessel/vascularisation assessments using the Ikosa software (2025), along with histological and immunohistochemical evaluations such as smooth muscle actin (SMA), H&E, and Masson’s trichrome staining. Statistical analysis was performed using GraphPad Prism 10. The addition of periosteum-derived micrografts resulted in angiogenic enhancement compared to the controls. Notable enhancement of total vessel area, total length, and branching points were obtained when Fisiograft® (p = 0.0007, p = 0.0002, and p < 0.0001, respectively), New Shore® (p = 0.0006, p = 0.0149, and p = 0.0083, respectively), and Bio-Oss® (p = 0.0038 and p = 0.0010, respectively) were combined with micrografts, compared to the positive controls. The histological and immunohistochemical analyses confirmed increased vascularisation (positive staining for SMA) in the micrograft groups. Periosteum-derived micrografts represent a promising adjunct to conventional bone-grafting materials, promoting vascularisation and potentially enhancing tissue regeneration and healing outcomes.

Journal of Functional Biomaterials doi: 10.3390/jfb17030147

Authors: Alberto Cabrera-Fernández Laura Dominguez-Dominguez Antonio Pérez-Pérez João Miguel Marques dos Santos Aránzazu Díaz-Cuenca Victor Sanchez-Margalet Diana B. Sequeira Juan Jose Segura-Egea Jenifer Martín-González

Vital pulp therapy comprises a group of procedures whose use in the primary dentition is increasingly supported in pediatric dentistry. The clinical management of pediatric patients requires biomaterials that provide precision, ease of handling, and reduced chairside time; in this context, resin-modified calcium silicate-based materials (RM-CSCs) have been introduced as an alternative to conventional calcium silicate formulations. This systematic review and meta-analysis aimed to evaluate the clinical effectiveness of RM-CSCs compared with non-resin calcium silicate-based materials in vital pulp therapy performed in primary teeth. A systematic search was conducted in MEDLINE, Scopus, Embase, and Web of Science in accordance with PRISMA guidelines. Randomized clinical trials were included, the risk of bias was assessed using the RoB 2 tool, and the certainty of evidence was evaluated using the GRADE approach. Of the 605 records initially identified, nine randomized clinical trials were ultimately included, all of which evaluated TheraCal LC as the RM-CSC. Meta-analyses were performed for vital pulp therapy overall and for procedure-specific subanalyses, including indirect pulp capping and pulpotomy. None of the meta-analyses demonstrated statistically significant differences between RM-CSCs and non-resin calcium silicate-based materials in terms of clinical or radiographic success. Therefore, the available evidence supports the use of TheraCal LC as an effective option for indirect pulp capping in primary teeth; however, its use in pulpotomy should be interpreted with caution until further randomized clinical trials become available.

Journal of Functional Biomaterials doi: 10.3390/jfb17030146

Authors: Barbara Illing Jacob Schultheiss Lukas Schumacher Evi Kimmerle-Mueller Ariadne Roehler Alexander Heiss Ulrich E. Klotz Victor O. Okafor Stefanie Krajewski Frank Rupp

Biodegradable zinc (Zn) has attracted increasing interest as a material for temporary implants, primarily due to its moderate degradation kinetics. In recent years, additive manufacturing of Zn alloys using the laser powder bed fusion method (L-PBF) has shown promising results. Compared to as-cast Zn alloys, it offers preferable customized solutions for patient-specific temporary biomedical implants. Due to the novelty of these printed degradable biomaterials and due to reported cytotoxic effects of Zn alloys, this study investigates additively manufactured ZnAgCu, ZnAgCuMn, and ZnAgCuTi alloys, both in as-printed and post-processed conditions, with a focus on L929 and SAOS-2 biocompatibility. In this work, we demonstrate that the increased porosity and therefore larger surface areas compared to polished Zn-alloy samples affect their biocompatibility. Minimal to no cell proliferation was observed on and near the Zn-alloy test plates after 24 h. Undiluted extracts from as-cast Zn and L-PBF-manufactured plates were initially cytotoxic to SAOS-2 cells. However, as passivation proceeded, cytocompatibility was significantly increased from day 3 onward. Zn2+ ion release peaked at 24 h and declined significantly from day 2 to day 10. Compared to the other Zn alloys, ZnAgCuMn exhibited the lowest cytocompatibility. Most intriguingly, 3-month surfaces exhibited reduced cytocompatibility to osteoblasts compared to freshly polished samples. The observed in vitro cytotoxicity motivates further investigation of as-printed and post-processed L-PBF-manufactured Zn alloys, aiming to develop novel surface modification strategies to mitigate the initial ion burst responsible for reduced cytocompatibility and to adjust and tailor the overall degradation kinetics to physiologically tolerable levels tailored to the intended clinical application.

Journal of Functional Biomaterials doi: 10.3390/jfb17030145

Authors: Siri Paulo Ana Margarida Abrantes Mafalda Laranjo Carlos Miguel Marto Anabela Paula Pedro Trancoso Filomena Botelho Arménio Serra Manuel Marques Ferreira

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is characterized by exposed necrotic bone that often progresses with increasing pain and impaired quality of life. Zoledronate, the most potent and widely used bisphosphonate, has been strongly associated with BRONJ development following invasive dental procedures. Given the rising incidence of BRONJ, understanding and implementing effective preventive strategies have become imperative. Biomaterials based on synthetic hydroxyapatite and beta-tricalcium phosphate have been investigated as potential preventive agents. Their therapeutic rationale is supported by two key principles: the well-documented chemical interaction of calcium phosphates with bisphosphonates when used as drug carriers, and the established clinical use of synthetic calcium phosphate biomaterials in dentistry for bone regeneration. This review examines the underlying mechanisms of this preventive therapeutic strategy and evaluates studies investigating synthetic calcium phosphate biomaterials for BRONJ prevention through zoledronate adsorption at jaw wound sites, thereby reducing soft tissue toxicity and promoting healing. The evidence supports the protective effect of these biomaterials as a scientifically grounded preventive approach for BRONJ.