Journal of Functional Biomaterials

14 pages, 5673 KB

Open AccessArticle

Optimal Selection of Biodegradable Polymer Composites for Load-Bearing Bone Tissue Engineering: A Hybrid Fuzzy AHP-TOPSIS Framework with Sensitivity-Based Robustness Analysis

by Lafi Hamidat, Dilber Uzun Ozsahin and Berna Uzun

J. Funct. Biomater. 2026, 17(5), 258; https://doi.org/10.3390/jfb17050258 - 21 May 2026

Viewed by 521

Abstract

The development of biodegradable scaffolds for load-bearing bone tissue engineering (BTE) presents a fundamental multi-criteria optimization challenge, requiring a simultaneous balance among mechanical performance, biological integration, and degradation kinetics. These criteria are inherently conflicting: composite formulations with the highest compressive strength frequently exhibit [...] Read more.

The development of biodegradable scaffolds for load-bearing bone tissue engineering (BTE) presents a fundamental multi-criteria optimization challenge, requiring a simultaneous balance among mechanical performance, biological integration, and degradation kinetics. These criteria are inherently conflicting: composite formulations with the highest compressive strength frequently exhibit suboptimal porosity, while those with superior osteoconductivity often lack sufficient load-bearing capacity. To address this challenge rigorously, this study establishes a hybrid Fuzzy Analytic Hierarchy Process–Technique for Order of Preference by Similarity to Ideal Solution (Fuzzy AHP-TOPSIS) framework to evaluate and rank five clinically relevant biodegradable polymer–ceramic composite candidates: PLA/Hydroxyapatite (PLA/HA), PCL/Hydroxyapatite (PCL/HA), PLGA/Bioactive Glass (PLGA/BG), PLA/Carbon Nanotubes (PLA/CNT), and PLA/Magnesium (PLA/Mg). Quantitative property data were systematically extracted from ten peer-reviewed experimental studies published between 2021 and 2025, and converted into Triangular Fuzzy Numbers (TFNs) to explicitly model inter-study variability arising from differences in fabrication methods, filler loading, and testing conditions. Fuzzy AHP analysis identified Compressive Strength (w = 25.2%) and Cell Viability (w = 21.5%) as the dominant decision criteria for load-bearing cortical bone repair. The Fuzzy TOPSIS ranking identified PLA/HA as the optimal composite candidate (Closeness Coefficient, CCᵢ = 0.677), demonstrating the superior multi-criteria balance required for cortical bone repair applications. Although PLA/CNT achieved the highest mechanical strength, it was outranked due to lower osteoconductivity and elevated cytotoxicity uncertainty at high nanotube concentrations (CCᵢ = 0.544). Sensitivity analysis across five distinct weighting scenarios confirmed the robustness of PLA/HA as the primary candidate. These findings provide a validated, replicable computational blueprint for evidence-based scaffold material selection, with direct implications for reducing the burden of costly trial-and-error experimentation in BTE research. Full article

(This article belongs to the Section Bone Biomaterials)

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19 pages, 5344 KB

Open AccessArticle

Numerical Simulation of Bone Defect Repair Using a Triply Periodic Minimal Surface Scaffold

by Zhouyang Chen, Haifei Chen and Chuanyong Qu

J. Funct. Biomater. 2026, 17(5), 257; https://doi.org/10.3390/jfb17050257 - 21 May 2026

Viewed by 586

Abstract

Polylactic acid (PLA) scaffolds with triply periodic minimal surface (TPMS) structures have become ideal scaffolds in the field of bone defect repair due to their good designability, connectivity, biocompatibility, and degradability. However, it is currently difficult to obtain the scaffold degradation rate and [...] Read more.

Polylactic acid (PLA) scaffolds with triply periodic minimal surface (TPMS) structures have become ideal scaffolds in the field of bone defect repair due to their good designability, connectivity, biocompatibility, and degradability. However, it is currently difficult to obtain the scaffold degradation rate and osteogenic efficacy from in vivo experiments, making it challenging to provide recommendations for scaffold design. In this study, an algorithm to construct a TPMS scaffold–interfacial layer–tissue three-phase composite model was developed using polylactic acid hydrolysis and bone remodeling as the governing equations to simulate scaffold degradation and tissue osteogenesis behavior under an external mechanical stimulus. This method is based on a numerical calculation framework that can more closely simulate the in vivo environment, characterizing the changes in the overall macroscopic mechanical properties of tissue under the influence of scaffold degradation and tissue osteogenesis. The results confirmed the accelerating effect of mechanical stimulation on scaffold degradation and its promoting effect on new bone formation. Under 10% compressive loading, the Schwarz P representative volume element (RVE) lost 33% of its apparent modulus within initial days, while the lidinoid RVE, despite showing a much higher initial modulus, dropped to only 20% of its initial value over the same period. In addition, the mechanical performance of the fused TPMS RVE was not simply linear, even though the surface equations are combined linearly. These results provide a new method for pre-designing scaffold structures based on numerical simulation results using the finite element simulation. Full article

(This article belongs to the Section Bone Biomaterials)

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15 pages, 3263 KB

Open AccessArticle

Structural Behavior Analysis of a Bone-Scaffold System According to the Elastic Modulus of Bone Cement and Pore Size in the Proximal Femur

by Han Kyu Lee, Jun Won Choi and Jung Jin Kim

J. Funct. Biomater. 2026, 17(5), 256; https://doi.org/10.3390/jfb17050256 - 20 May 2026

Viewed by 484

Abstract

Bone scaffolds are porous artificial structures that replace damaged bone tissue and promote bone regeneration. In clinical settings, bone cement is used to provide initial fixation stability between the bone scaffold and surrounding bone tissue. To analyze the performance of bone scaffolds more [...] Read more.

Bone scaffolds are porous artificial structures that replace damaged bone tissue and promote bone regeneration. In clinical settings, bone cement is used to provide initial fixation stability between the bone scaffold and surrounding bone tissue. To analyze the performance of bone scaffolds more accurately, the cement mantle should be considered. This study considers the cement mantle between the bone scaffold and surrounding bone tissue and the structural behavior according to variations in the elastic modulus of the cement mantle and the pore size of the bone scaffold. The results showed that the cement mantle energy ratio increased with increasing pore size, particularly in the femoral head and intertrochanteric region. In the femoral head with a pore size of 1.50 mm, increasing the cement mantle elastic modulus from 7 to 24 GPa reduced the mean strain energy within the bone scaffold from 3.79 μJ to 2.51 μJ, corresponding to a decrease of approximately 33.8%. These findings suggest that as cement mantle stiffness increases, external loads may not be sufficiently transferred to the bone scaffold interior, and the proportion of the load borne by the cement mantle may increase. In the femoral neck, the cement mantle energy ratio also increased with increasing pore size; however, the magnitude of this change was more limited than that in the other regions of interest. These findings highlight the mechanical importance of the cement mantle and suggest that both cement stiffness and scaffold pore size should be jointly considered to ensure appropriate load sharing for bone regeneration. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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13 pages, 13167 KB

Open AccessArticle

Dimensional Stability of Polymer and Titanium Implant Scan Bodies After Repeated Steam Sterilization: A High-Resolution 3D Metrological In Vitro Study

by Igor Smojver, Roko Bjelica, Yuval Reiser, Marko Vuletić, Vladimir Prpić and Dragana Gabrić

J. Funct. Biomater. 2026, 17(5), 255; https://doi.org/10.3390/jfb17050255 - 20 May 2026

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Abstract

The increasing adoption of digital workflows in implant dentistry relies heavily on the accuracy of implant scan bodies (ISBs), which may be affected by repeated sterilization. This in vitro study evaluated the effect of 50 steam sterilization cycles on the dimensional stability of [...] Read more.

The increasing adoption of digital workflows in implant dentistry relies heavily on the accuracy of implant scan bodies (ISBs), which may be affected by repeated sterilization. This in vitro study evaluated the effect of 50 steam sterilization cycles on the dimensional stability of polymer and titanium ISBs. A total of 100 test specimens (n = 50 per material) were scanned before (T0) and after sterilization (T50) using a high-resolution intraoral scanner, generating 900 STL datasets for metrological analysis. Surface deviation, linear displacement, and angular deviation were assessed using validated industrial and dental software, with statistical evaluation performed through paired tests and linear mixed-effects models. Both materials exhibited statistically significant dimensional changes after sterilization (p < 0.001). Titanium scan bodies demonstrated greater linear deformation (69.76 μm) compared to polymer ones (49.50 μm), while maintaining superior angular stability (0.21° vs. −1.69° mean angular change in the polymer group). A significant interaction between material type and sterilization was observed. Despite high baseline precision, repeated autoclaving induced clinically relevant deviations in both materials. These findings indicate that cumulative sterilization cycles adversely affect ISB accuracy and highlight the importance of adhering to manufacturer recommendations to ensure optimal prosthetic outcomes. Full article

(This article belongs to the Special Issue Digital Design and Biomechanical Analysis of Dental Materials)

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35 pages, 9753 KB

Open AccessArticle

An Injectable Biopolymer Hydrogel Complex (PN/HA/B3) for Facial Skin Redensification and General Rejuvenation: Clinical Report on Device Safety and Efficacy

by Alexandre Porcello, Kelly Lourenço, Cíntia Marques, Wassim Raffoul, Marco Cerrano, Lee Ann Applegate and Alexis E. Laurent

J. Funct. Biomater. 2026, 17(5), 254; https://doi.org/10.3390/jfb17050254 - 20 May 2026

Viewed by 777

Abstract

This study evaluated the safety and effectiveness of HYDRAGEL A2, an injectable medical device containing hyaluronic acid (HA), polynucleotides (PN), and niacinamide, for improving facial skin quality. These ingredients are increasingly recognized for their synergistic effects in aesthetic medicine, with HA and PN [...] Read more.

This study evaluated the safety and effectiveness of HYDRAGEL A2, an injectable medical device containing hyaluronic acid (HA), polynucleotides (PN), and niacinamide, for improving facial skin quality. These ingredients are increasingly recognized for their synergistic effects in aesthetic medicine, with HA and PN providing hydration and skin support, and niacinamide offering anti-inflammatory and antioxidant properties. A prospective, open-label clinical investigation was conducted on 42 female subjects (mean age 45 ± 1 years, Fitzpatrick skin phototypes II-V) to assess skin elasticity, hydration, and mild skin depression correction following cheek area injections. Efficacy was measured using the Global Aesthetic Improvement Scale (GAIS), Antera 3D^® (texture), Cutometer^® (elasticity/firmness), Corneometer^® (hydration), and Dermascan^® (density/thickness) devices at baseline (D0), week 2 (W2/D14), and week 6 (W6/D42). GAIS values showed significant overall facial improvement (p < 0.001) by both investigators and subjects, where 100% of subjects rated their appearance as improved immediately post-injection (D0), with sustained improvements at D42. Objective measurements revealed significant improvements in skin texture (reduced roughness), elasticity, firmness, hydration (p < 0.001), density, and thickness, demonstrating the combined benefits of the HA, PN, and niacinamide blend. Injection site reactions, primarily mild and transient, were reported immediately post-injection. Investigators and subjects reported high satisfaction with the product’s ease of use and aesthetic outcomes. Globally, HYDRAGEL A2, leveraging the established benefits of HA, PN, and niacinamide, was well-tolerated and effectively enhanced facial skin quality, demonstrating significant and sustained improvements in monitored skin parameters. The study concludes that this combination of ingredients, formulated in HYDRAGEL A2, provides a well-tolerated approach associated with improvements in skin quality. Full article

(This article belongs to the Special Issue Advances in Multifunctional Hydrogels for Biomedical Application (2nd Edition))

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19 pages, 2526 KB

Open AccessArticle

Histomorphometric Evaluation of Subchronic and Chronic Effects of Novel Experimental Calcium Aluminate- and Calcium Silicate-Based Dental Cement Materials on Rat Liver, Kidney, Brain, and Spleen Tissues

by Veljko Ilić, Sanja Milutinović-Smiljanić, Vladimir Biočanin, Jovana Kuzmanović Pfićer, Tatjana Tasić, Vesna Danilović, Nina Japundžić-Žigon, Smiljana Paraš, Vukoman Jokanović, Dejan Ćetković and Đorđe Antonijević

J. Funct. Biomater. 2026, 17(5), 253; https://doi.org/10.3390/jfb17050253 - 20 May 2026

Viewed by 617

Abstract

Although biocompatible calcium silicate cements (CSCs) and calcium aluminate cements (CACs) may induce local and systemic adverse effects. This study aimed to evaluate the subchronic and chronic effects of experimental CAC and CSC mixtures on rat liver, kidney, brain, and spleen tissue. Two [...] Read more.

Although biocompatible calcium silicate cements (CSCs) and calcium aluminate cements (CACs) may induce local and systemic adverse effects. This study aimed to evaluate the subchronic and chronic effects of experimental CAC and CSC mixtures on rat liver, kidney, brain, and spleen tissue. Two experimental mixtures, CAC with added ZrO₂ (ECCA + ZrO₂) and CSC with added ZrO₂ (ECCS + ZrO₂), and mineral trioxide aggregate (MTA), were implanted intraalveolary in 36 male Wistar rats. Histomorphometry was conducted after 30 and 180 days on liver, kidney, brain, and spleen. Consistent results were observed in all material groups. Liver tissue inflammation ranged from none to minimal for all three materials. In kidney, ECCA + ZrO₂ displayed a slightly better result than other two materials. In brain, after 180 days, both ECCA + ZrO₂ and MTA showed a statistically significant reduction in perineural vacuolation (p < 0.05), and MTA showed a reduction in the percentage of intravascular congestion (p < 0.05). In spleen, a larger lymphoid follicle diameter was observed for ECCS + ZrO₂ chronic group compared to other two materials (p < 0.05). ECCA + ZrO₂, ECCS + ZrO₂, and MTA caused none to minimal changes in liver, kidney, brain, and spleen following subchronic and chronic exposure. Full article

(This article belongs to the Special Issue State of the Art: Biomaterials in Bone Implant and Regeneration (2nd Edition))

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20 pages, 3316 KB

Open AccessArticle

Recombinant Spider Silk Enhances Engineered Cartilage Formation

by Hongji Zhang, Xinyu Huang, Jinwen Zhang, Fengjie Zhang, Fei Sun and Chao Wan

J. Funct. Biomater. 2026, 17(5), 252; https://doi.org/10.3390/jfb17050252 - 19 May 2026

Viewed by 570

Abstract

Articular cartilage is characterized by its avascular, aneural, and alymphatic nature, which confers a limited intrinsic capacity for self-repair. Current regenerative strategies primarily focus on alleviating pain, mitigating symptoms, and restoring joint function. However, their long-term efficacy remains uncertain. Cartilage tissue engineering has [...] Read more.

Articular cartilage is characterized by its avascular, aneural, and alymphatic nature, which confers a limited intrinsic capacity for self-repair. Current regenerative strategies primarily focus on alleviating pain, mitigating symptoms, and restoring joint function. However, their long-term efficacy remains uncertain. Cartilage tissue engineering has emerged as a promising alternative to conventional therapies, offering innovative solutions for articular cartilage regeneration. Central to this approach is the development of functional biomaterials capable of supporting chondrogenic cell adhesion, proliferation, and differentiation, thereby facilitating effective cartilage repair. In this study, we introduce a novel protein-based recombinant spider silk (RSS) as a potential biomaterial for modulating chondrocyte behavior and enabling engineered cartilage formation both in vitro and in vivo. RSS was generated through molecular cloning and processed into silk fibers using biomimetic spinning and acidic coagulation techniques. In micromass cultures of murine chondrocytes, RSS significantly promoted cell aggregation, resulting in increased cell density. Alcian blue and Oil Red O staining demonstrated that RSS-treated cultures produced abundant glycosaminoglycans, a hallmark of chondrogenic activity, while exhibiting minimal lipid accumulation. These findings suggest that RSS supports chondrogenic differentiation and suppresses adipogenic lineage commitment. Real-time PCR analysis revealed upregulation of the chondrogenesis-related gene Sox9 and downregulation of the adipogenic marker PPARγ and the hypertrophic marker Runx2 in RSS-treated micromass cultures. RNA sequencing further corroborated these observations, underscoring the role of RSS in modulating extracellular matrix (ECM) remodeling in chondrocytes. In a subcutaneous transplantation model using severe combined immunodeficiency (SCID) mice, chondrocytes encapsulated in three-dimensional hydrogel scaffolds containing RSS exhibited significantly enhanced ECM accumulation compared to RSS-free controls, indicating that RSS supports the maintenance of the chondrocyte phenotype and promotes cartilage formation in vivo, and underscoring its promising potential as a component of hydrogel composite systems. These findings highlight the potential of RSS as a functional biomaterial to preserve chondrocyte functionality and advance engineered cartilage formation, presenting a promising avenue for cartilage tissue engineering and regeneration. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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12 pages, 1615 KB

Open AccessArticle

Geometric Accuracy of 3D-Printed Composite Dental Restorations Compared with the Original STL Design

by Tommaso Rossi, Giulia Pascoletti, Michele Calì, Giuliana Baiamonte, Fulvia Concetta Rita Monaco, Elisabetta Maria Zanetti, Alberto Audenino, Gianpaolo Serino, Bartolomeo Coppola, Andrea Messina and Nicola Scotti

J. Funct. Biomater. 2026, 17(5), 251; https://doi.org/10.3390/jfb17050251 - 19 May 2026

Viewed by 1515

Abstract

Additive manufacturing (AM) enables customized, efficient restorative workflows, though the accuracy of 3D-printed restorations may be compromised by polymerization, sintering shrinkage, and post-processing. This study evaluated the geometric accuracy of 3D-printed partial restorations compared with the computer-aided design (CAD) reference. The null hypothesis [...] Read more.

Additive manufacturing (AM) enables customized, efficient restorative workflows, though the accuracy of 3D-printed restorations may be compromised by polymerization, sintering shrinkage, and post-processing. This study evaluated the geometric accuracy of 3D-printed partial restorations compared with the computer-aided design (CAD) reference. The null hypothesis stated that no significant differences would be found between Varseo Smile Crown^plus (by BEGO, Italy) and IRIXMax (by DWS System, Italy) materials, which are printed and cured with different technologies. A model was prepared for an overlay and designed with a 1.5 mm uniform thickness. Restorations were produced in two groups with two different printing processes: DLP (digital light processing)-printed Varseo Smile Crown^plus and SLA (stereolithography)-printed IRIXMax. Six samples per group were printed at 90° orientation and scanned. Meshes were aligned to the master geometry via pre-alignment and ICP (Iterative Closest Point) registration. Deviations were quantified in CloudCompare using mean, standard deviation (SD), and 90th percentile values. IRIXMax showed the lowest deviations from the ideal geometry, while Varseo Smile Crown^plus exhibited greater variability. Pairwise comparisons found IRIXMax significantly more accurate than Varseo Smile Crown^plus. Color maps confirmed material-specific deviation patterns. IRIXMax provided the highest geometric accuracy. Material-specific calibration is essential for reliable 3D-printed definitive restorations. Full article

(This article belongs to the Special Issue Biomaterials in Conservative Dentistry and Prosthodontics (2nd Edition))

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13 pages, 1325 KB

Open AccessArticle

Molecular Insights into the Synergistic Effect of Nano-Hydroxyapatite and L-PRF on Osteoporotic Osseointegration: An In Vivo Gene Expression Study

by Ana Carolina Loyola Barbosa, José Augusto Gabarra Júnior, Lilian Eslaine Costa Mendes da Silva, Fernando Nóbrega, Edmara Tatiely Pedroso Bergamo, Bruna Ghiraldini, Roberto Sales e Pessoa, Michel Reis Messora and Sergio Scombatti de Souza

J. Funct. Biomater. 2026, 17(5), 250; https://doi.org/10.3390/jfb17050250 - 17 May 2026

Viewed by 832

Abstract

Poor bone quality in osteoporotic patients remains a major challenge for achieving predictable osseointegration. This study serves as a mechanistic complement to previously reported structural data, aiming to investigate the molecular pathways underlying the synergy between nanostructured surfaces and autologous blood concentrates in [...] Read more.

Poor bone quality in osteoporotic patients remains a major challenge for achieving predictable osseointegration. This study serves as a mechanistic complement to previously reported structural data, aiming to investigate the molecular pathways underlying the synergy between nanostructured surfaces and autologous blood concentrates in compromised bone. Ninety-six Wistar rats were divided into healthy (SHAM) and osteoporotic (OVX) groups. Implants with nanostructured hydroxyapatite (NanoHA) or dual acid-etched (DAE) surfaces were installed in the tibiae, associated or not with leukocyte- and platelet-rich fibrin (L-PRF). Gene expression (RT-qPCR) for Runx2, Alpl, Bglap, Spp1, Tnfrsf11, and Tnfrsf11b was assessed at 7 and 30 days. In compromised systemic conditions (OVX), the NanoHA + L-PRF association promoted a robust “molecular rescue” of bone metabolism. At 30 days, this synergistic group exhibited a significant upregulation of Alpl (mean: 11.69 ± 1.65) and Runx2 (mean: 4.49 ± 0.82) compared to DAE controls (p < 0.05). Crucially, the therapy orchestrated a protective remodeling environment by significantly inducing Tnfrsf11b expression (5.50 ± 0.88), effectively balancing the Tnfrsf11/Tnfrsf11b ratio. Late-stage maturation markers (Bglap and Spp1) were also significantly elevated, effectively mimicking healthy physiological levels observed in the SHAM group. NanoHA biofunctionalization, synergistically with L-PRF, triggers a transcriptional reprogramming of the peri-implant microenvironment, mitigating the catabolic effects of estrogen deficiency. These findings provide a biological foundation for enhanced clinical predictability in high-risk patients, suggesting that local interfacial modifications can overcome systemic bone compromise. Full article

(This article belongs to the Special Issue New Trends in Biomaterials and Implants for Dentistry (2nd Edition))

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Graphical abstract

17 pages, 1587 KB

Open AccessArticle

Do the Pre-Existing Class III and Class V Composite Restorations Affect the Sealing Ability and Integrity of 3D-Printed Laminate Veneer Margins? An In Vitro Study

by Abdulkhaleq Mohammed Qaraghuli, Edoardo Ferrari Cagidiaco and Marco Ferrari

J. Funct. Biomater. 2026, 17(5), 249; https://doi.org/10.3390/jfb17050249 - 17 May 2026

Viewed by 686

Abstract

Background: The application of veneer restorations over previously composite-restored anterior teeth presents significant clinical challenges, particularly in achieving optimal marginal sealing. Aim: This in vitro study aimed to evaluate the marginal integrity and sealing ability of different 3D-printed resin veneer restorations on sound [...] Read more.

Background: The application of veneer restorations over previously composite-restored anterior teeth presents significant clinical challenges, particularly in achieving optimal marginal sealing. Aim: This in vitro study aimed to evaluate the marginal integrity and sealing ability of different 3D-printed resin veneer restorations on sound versus composite-restored anterior teeth. Materials and Methods: Eighty freshly extracted human anterior teeth (40 central incisors and 40 canines) were randomly assigned into two main groups: sound teeth and composite-restored teeth. All the teeth received 3D-printed resin veneer restoration utilizing two different types of 3D-printed resin (GC Temp Print, GC, Tokyo, Japan; and Varseosmile Triniq, BEGO GmbH & Co., Bremen, Germany). The specimens were then subjected to microleakage, marginal fitness, cement void, and cement loss testing. Results: There were no statistically significant differences among all examined groups. Microleakage scores were predominantly 0 across all groups, with median values of 0 at both cervical and proximal surfaces. Marginal fitness showed fit percentages ranging from 20% to 100%, while cement voids and cement loss were rare events (<10%). Statistical analysis confirmed no significant differences between groups (p > 0.05), with p-values ranging from 0.151 to 1.000. Conclusions: No, the presence of pre-existing composite restorations did not adversely affect 3D-printed veneer performance. The marginal integrity and sealing ability of two different 3D-printed resin veneers are not affected by the presence of previous composite restoration on cervical and proximal surfaces for both incisor and canine teeth. 3D-printed veneers applied to sound and restored teeth showed good marginal integrity and proper sealing ability. Full article

(This article belongs to the Special Issue Advances in Restorative Dentistry Materials)

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24 pages, 23717 KB

Open AccessArticle

Fracture Strength of CAD/CAM Endocrown and Post-Core Restorations with Fiber Strip Reinforcement in Mandibular Premolars

by Kerem Yılmaz, Hakan Aydın, Zeynep Soylu, Özge Çiloğlu, Esma Fatıma Delican, Mehmet Mustafa Özarslan and Fehmi Gönüldaş

J. Funct. Biomater. 2026, 17(5), 248; https://doi.org/10.3390/jfb17050248 - 17 May 2026

Viewed by 731

Abstract

This study evaluated the effects of restorative material, restoration type, and fiber strip reinforcement on the fracture strength (FS) of endocrown (EC) and post-core (PC) restorations in endodontically treated premolars. Specimens were allocated according to restorative material [resin-nanoceramic (RNC) or feldspathic ceramic (FC)], [...] Read more.

This study evaluated the effects of restorative material, restoration type, and fiber strip reinforcement on the fracture strength (FS) of endocrown (EC) and post-core (PC) restorations in endodontically treated premolars. Specimens were allocated according to restorative material [resin-nanoceramic (RNC) or feldspathic ceramic (FC)], restoration type (EC or PC), and reinforcement [fiber strip-reinforced (FR) or -non-reinforced (NF)]. FS was determined using a universal testing machine under axial loading. Statistical analysis was performed using three-way ANOVA and Bonferroni tests (α = 0.05). Material, restoration type, and reinforcement significantly affected FS (p < 0.05). RNC restorations exhibited higher FS than FC restorations (861 ± 181 N vs. 715 ± 212 N; p < 0.001). EC restorations exhibited higher FS than PC restorations (828 ± 173 N vs. 748 ± 236 N; p = 0.046). FR groups exhibited higher FS than NF groups (848 ± 180 N vs. 728 ± 222 N; p = 0.003). The highest FS was observed in the RNC–PC–FR group (965 ± 144 N), whereas the lowest occurred in the FC–PC–NF group (480 ± 177 N). Although EC restorations showed higher FS than PC restorations, the effect of restoration type depended on material and reinforcement. Full article

(This article belongs to the Section Dental Biomaterials)

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16 pages, 2872 KB

Open AccessSystematic Review

Effectiveness of β-TriCalcium Phosphate for Alveolar Ridge Preservation: A Systematic Review

by Vitolante Pezzella, Andrea Blasi, Leopoldo Mauriello, Giuseppe Trapanese, Elio Ramaglia, Michele Basilicata, Vincenzo Iorio-Siciliano and Luca Ramaglia

J. Funct. Biomater. 2026, 17(5), 247; https://doi.org/10.3390/jfb17050247 - 15 May 2026

Viewed by 646

Abstract

Alveolar ridge preservation (ARP) aims to reduce post-extraction bone resorption and facilitate implant placement. Among alloplastic grafts, β-tricalcium phosphate (β-TCP) is widely used due to its osteoconductive properties and complete resorbability. This systematic review evaluated the clinical effectiveness of β-TCP for ARP, focusing [...] Read more.

Alveolar ridge preservation (ARP) aims to reduce post-extraction bone resorption and facilitate implant placement. Among alloplastic grafts, β-tricalcium phosphate (β-TCP) is widely used due to its osteoconductive properties and complete resorbability. This systematic review evaluated the clinical effectiveness of β-TCP for ARP, focusing on ridge dimensional changes assessed by cone–beam computed tomography (CBCT). Electronic searches were performed in major scientific databases up to April 2026. Randomized controlled trials (RCTs) reporting CBCT-based dimensional outcomes after at least 4 months were included. Five RCTs met the inclusion criteria. Considerable heterogeneity was observed in biomaterial formulations, socket management, and outcome assessment. When used alone, β-TCP showed variable results, ranging from greater ridge resorption compared with xenograft to outcomes comparable with those of freeze-dried bone allograft. More consistent findings were reported when β-TCP was used in combination with other biomaterials, with outcomes generally comparable to those of deproteinized bovine bone mineral (DBBM). Overall, β-TCP may have a potential role in alveolar ridge preservation; however, evidence remains limited and heterogeneous. Differences between β-TCP alone and composite formulations should be carefully considered, and no definitive conclusions can be drawn regarding its comparative predictability versus xenografts. Further RCTs are needed to clarify its clinical effectiveness and identify optimal applications. Full article

(This article belongs to the Special Issue Biomaterials Applied in Dental Sciences (2nd Edition))

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27 pages, 5265 KB

Open AccessReview

Hyaluronic Acid-Based Biomaterials in Tissue Engineering: From Molecular Properties to Re-Generative Applications

by Chao-Ming Su, Ming-You Shie, Wan-Ni Huang, Fang-Jou Chiu, Hong-Kai Chen, Yi-Wen Chen and Yu-Fang Shen

J. Funct. Biomater. 2026, 17(5), 246; https://doi.org/10.3390/jfb17050246 - 14 May 2026

Viewed by 919

Abstract

Hyaluronic acid (HA), a native non-sulfated glycosaminoglycan of the extracellular matrix, has emerged as a central biomaterial in tissue engineering due to its biocompatibility, hydration capacity, and receptor-mediated bioactivity. Beyond its structural role, HA actively regulates cellular behaviors through interactions with receptors such [...] Read more.

Hyaluronic acid (HA), a native non-sulfated glycosaminoglycan of the extracellular matrix, has emerged as a central biomaterial in tissue engineering due to its biocompatibility, hydration capacity, and receptor-mediated bioactivity. Beyond its structural role, HA actively regulates cellular behaviors through interactions with receptors such as CD44 and RHAMM, with outcomes highly dependent on molecular weight, degradation state, and matrix context. Recent advances in chemical modification and crosslinking strategies have enabled the development of HA-based hydrogels, nanofibers, and composite systems with tunable mechanics and degradation profiles, supporting applications in bone, cartilage, vascular, and skin regeneration, as well as in emerging platforms such as 3D bioprinting and nanomedicine. However, inconsistent biological responses and limited clinical translation remain key challenges. This review integrates current understanding of HA synthesis, physicochemical properties, degradation, and receptor-mediated signaling, and establishes a mechanistic framework linking molecular characteristics, matrix mechanics, and cell responses. Building on this framework, we outline design strategies for multifunctional HA composites, advanced biofabrication approaches, and receptor-targeted systems, providing a basis for the rational engineering of next-generation HA-based biomaterials with improved translational potential. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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14 pages, 6778 KB

Open AccessArticle

Intraoperative Bioactivation of Bone Substitutes Using a Surgical Suction Handle: A Prospective Clinical Pilot Study

by Eleftherios Papaeleftheriou, Andrea Sowislok, Emely Rehage, Alexander Wegner, Marcel Haversath, Melissa Jansen and Marcus Jäger

J. Funct. Biomater. 2026, 17(5), 245; https://doi.org/10.3390/jfb17050245 - 13 May 2026

Viewed by 761

Abstract

Critical size bone defects (CSBD) remain a major challenge in orthopedic surgery. Autologous bone grafting is considered the gold standard but is limited by restricted availability and significant donor-site morbidity. Synthetic bone substitutes offer an alternative; however, these materials are avital and lack [...] Read more.

Critical size bone defects (CSBD) remain a major challenge in orthopedic surgery. Autologous bone grafting is considered the gold standard but is limited by restricted availability and significant donor-site morbidity. Synthetic bone substitutes offer an alternative; however, these materials are avital and lack osteoinductive properties. This study evaluated whether intraoperative bioactivation of bone substitutes using a surgical suction handle can safely enhance their regenerative potential. Fifty patients with CSBD, non-unions, or high-risk defects were enrolled, and calcium phosphate-based ceramics were intraoperatively coated with autologous tissue via a surgical suction handle and implanted into the defects. Clinical outcomes—including pain, range of motion, and wound healing—were scored using a standardized system, with all patients achieving results in the “excellent” range (10–13 points). Radiographic follow-up showed progressive cortical and extracortical bone formation in all patients. Surgeons reported high ease-of-use for the device, and no device-related complications occurred. Although biomaterial resorption was incomplete in some cases (36% with <75% resorption at six months), no patient required revision surgery. Our data indicate that intraoperative bioactivation of bone substitutes using a surgical suction handle is safe, feasible, and promotes local bone regeneration, providing a minimally invasive and practical approach to enhance the performance of synthetic grafts in challenging defects. Full article

(This article belongs to the Special Issue Materials and Techniques for Bone Tissue Engineering: From Scaffolds to Complex Matrices)

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24 pages, 7053 KB

Open AccessArticle

3D Fibrin/Gelatin Hydrogel System Enhances the Therapeutic Potency of DPSC-Derived Extracellular Vesicles Compared to 2D Culture in Accelerating Diabetic Wound Healing via Angiogenesis and Immune Modulation

by Xin Qiao, Kai Liu, Jie Tang, Shijian Deng and Deqin Yang

J. Funct. Biomater. 2026, 17(5), 244; https://doi.org/10.3390/jfb17050244 - 12 May 2026

Viewed by 811

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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14 pages, 605 KB

Open AccessArticle

Knowledge, Attitudes, and Self-Reported Practices Regarding Modern Adhesive Systems Among Romanian Dentists: A Cross-Sectional Survey

by 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 and Iustin Olariu

J. Funct. Biomater. 2026, 17(5), 243; https://doi.org/10.3390/jfb17050243 - 12 May 2026

Viewed by 583

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Advances in Biomaterials and Regenerative Treatments for Oral and Maxillofacial Reconstruction)

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16 pages, 2534 KB

Open AccessArticle

In Vitro Evaluation of Anti-Inflammatory and Antioxidant Properties of a Novel Calcium Alginate–Zinc Hemostatic Biomaterial

by Tanja Lunić, Marija Rakić, Maria Sbeih, Marina Samardzic, Céline des Courtils and Biljana Božić Nedeljković

J. Funct. Biomater. 2026, 17(5), 242; https://doi.org/10.3390/jfb17050242 - 11 May 2026

Viewed by 836

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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16 pages, 680 KB

Open AccessSystematic Review

Clinical Outcomes of Immediate and Delayed Composite Restorations After Pulp Capping with Biodentine: A Systematic Literature Review

by Margarita Aleksiuk, Ana Kostenkova and Saulius Drukteinis

J. Funct. Biomater. 2026, 17(5), 241; https://doi.org/10.3390/jfb17050241 - 10 May 2026

Viewed by 1081

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Advanced Materials for Clinical Endodontic Applications (3rd Edition))

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33 pages, 19233 KB

Open AccessArticle

Multifunctional Y₂O₃-Modified Borotellurite Bioactive Glasses for Bone Tissue Engineering Applications

by Esmanur Oruc Ulas, Bulent Aktas, Abuzer Acikgoz, Serife Yalcin, Hatice Gumushan Aktas, Ebru Uyar and Zeynep Celik

J. Funct. Biomater. 2026, 17(5), 240; https://doi.org/10.3390/jfb17050240 - 9 May 2026

Viewed by 980

Abstract

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–15P₂O₅–10B [...] Read more.

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. Full article

(This article belongs to the Section Bone Biomaterials)

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23 pages, 1081 KB

Open AccessReview

Advanced Grafting Biomaterials and Technologies in Chronic Wound Care: Mechanisms, Clinical Outcomes, and Therapeutic Integration

by Albert D. Luong, Moorthy Maruthapandi and John H. T. Luong

J. Funct. Biomater. 2026, 17(5), 239; https://doi.org/10.3390/jfb17050239 - 9 May 2026

Viewed by 1277

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Biomaterials, Bioconjugated Materials, and Biomaterial Composites with Antimicrobial Properties)

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19 pages, 2994 KB

Open AccessArticle

Influence of Framework Material on Stress, Fatigue, and Stability of “All-on-Four” System Components—Biomechanical Evaluation with Finite Element Analysis

by Dijana Popovic Grubac, Djordje Bozovic, Jelena Lecic, Ines Kovacic, Ognjenka Janjic Pavlovic, Aleksandra Zuza, Dea Krsticevic and Nedeljka Ivkovic

J. Funct. Biomater. 2026, 17(5), 238; https://doi.org/10.3390/jfb17050238 - 8 May 2026

Viewed by 995

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Dental Biomaterials)

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14 pages, 2268 KB

Open AccessArticle

Bioinformatic Resistome Profiling of Metal Tolerance Mechanisms in Endodontic Infections: Implications for Antimicrobial Nanoparticle-Based Biomaterials

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

J. Funct. Biomater. 2026, 17(5), 237; https://doi.org/10.3390/jfb17050237 - 8 May 2026

Viewed by 1063

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Dental Biomaterials)

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31 pages, 12690 KB

Open AccessArticle

Direct Chemical Reprogramming of Human Fibroblasts into Retinal Progenitor-like Cells for Ocular Delivery

by 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 and Rong-Kung Tsai

J. Funct. Biomater. 2026, 17(5), 236; https://doi.org/10.3390/jfb17050236 - 8 May 2026

Viewed by 1317

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Biomaterials for Drug Delivery)

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16 pages, 4123 KB

Open AccessArticle

Graphene Oxide-Modified Titanium Dioxide Nanotubes Promote Schwann Cell Function and Neurotrophic Factor Expression

by Xu Cao, Caiyun Wang, Ran Lu, Yanting Mu, Jiangqi Hu, Bin Luo and Su Chen

J. Funct. Biomater. 2026, 17(5), 235; https://doi.org/10.3390/jfb17050235 - 8 May 2026

Viewed by 1106

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Graphene Materials in Medical Applications)

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18 pages, 1744 KB

Open AccessArticle

Vertical and Horizontal Ridge Augmentation with Titanium-Reinforced Dense PTFE and Reinforced PTFE Mesh: A Prospective Comparative Case Series

by Liliana Andrea Silva, Pedro Sousa Gomes, Maria Helena Fernandes, Marta García-García and Octavi Camps-Font

J. Funct. Biomater. 2026, 17(5), 234; https://doi.org/10.3390/jfb17050234 - 7 May 2026

Viewed by 1116

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Application of Biomaterials and Techniques in Dental Surgical Treatment (2nd Edition))

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14 pages, 4882 KB

Open AccessArticle

Preclinical Analysis of Sex-Specific Differences in the Angiogenic and Inflammatory Tissue Response to Surgical Sutures

by Selina Wrublewsky, Jan Weigl, Caroline Bickelmann and Matthias W. Laschke

J. Funct. Biomater. 2026, 17(5), 233; https://doi.org/10.3390/jfb17050233 - 7 May 2026

Viewed by 1457

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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16 pages, 3087 KB

Open AccessArticle

The Potential of a Graphene Monolayer in Macrophage Polarization Using RAW 264.7 Cells

by Iwona Lasocka, Karolina Gregorczyk-Zboroch, Aleksandra Krajewska, Ewa Skibniewska, Michał Skibniewski and Lidia Szulc-Dąbrowska

J. Funct. Biomater. 2026, 17(5), 232; https://doi.org/10.3390/jfb17050232 - 7 May 2026

Viewed by 1191

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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3 pages, 145 KB

Open AccessEditorial

Novel Biomaterials for Tissue Engineering

by Mina Aleemardani and Farnaz Ghorbani

J. Funct. Biomater. 2026, 17(5), 231; https://doi.org/10.3390/jfb17050231 - 7 May 2026

Viewed by 1077

Abstract

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

(This article belongs to the Special Issue Novel Biomaterials for Tissue Engineering)

22 pages, 15964 KB

Open AccessArticle

Cryogenic Foaming of Silk Fibroin Composite for Scaffolds in Bone and Periodontal Regeneration

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

J. Funct. Biomater. 2026, 17(5), 230; https://doi.org/10.3390/jfb17050230 - 6 May 2026

Viewed by 1323

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Silk Protein-Based Functional and Innovative Materials for Biomedical Applications)

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14 pages, 991 KB

Open AccessArticle

Post-Market Non-Controlled Study on the Clinical Safety of a Synthetic Calcium Phosphate Ceramic in Alveolar Bone Regeneration: A 6-Month Prospective Study

by Nuno Silva, Carlota Rodrigues, Angel Lobito, António Mano Azul, Pedro Ferreira Trancoso, Vanessa Machado and João Botelho

J. Funct. Biomater. 2026, 17(5), 229; https://doi.org/10.3390/jfb17050229 - 6 May 2026

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Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Biomaterials and Strategies for Bone Regeneration and Repair)

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J. Funct. Biomater., Volume 17, Issue 5 (May 2026) – 52 articles

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