Journal of Functional Biomaterials

19 pages, 9448 KB

Open AccessArticle

Effects of Hydrodynamic Ozonated Water Processing on the Thermal Stability and Structural Integrity of the Human Amniotic Membrane

by Marcia Guelma Santos Belfort, Francisco Dimitre Rodrigo Pereira Santos, Maycon Crispim de Oliveira Carvalho, Aline Casarin dos Santos, Pedro Augusto Laurindo Igreja Marrafa, João Gomes de Oliveira Neto, Carlos José de Lima and Adriana Barrinha Fernandes

J. Funct. Biomater. 2026, 17(7), 352; https://doi.org/10.3390/jfb17070352 - 20 Jul 2026

Viewed by 381

Abstract

This study aimed to verify the morphology, biochemical composition, and thermal characterization of hydrated human amniotic membrane (HAM) processed in an ozonated water hydrodynamic system. This is an in vitro experimental study in which HAM samples were divided into two groups: in natura [...] Read more.

This study aimed to verify the morphology, biochemical composition, and thermal characterization of hydrated human amniotic membrane (HAM) processed in an ozonated water hydrodynamic system. This is an in vitro experimental study in which HAM samples were divided into two groups: in natura (IN) and ozonated (O₃). Analyses were performed using histology, Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA/DTG), and differential scanning calorimetry (DSC/dDSC). Ozonation for 40 min preserved the biochemical integrity of HAM, maintaining the characteristic vibrational bands of Amides I, II, and III. Histological analysis showed morphological changes in epithelial cells, with partial removal in some regions, while the basement membrane and the scaffold remained preserved. Thermal analysis revealed that the in natura sample presented a bimodal dehydration profile, with a first event occurring between 60 and 65 °C associated with the evaporation of free or weakly bound water, and a second event peaking around 80 °C related to the removal of structural water. In contrast, the ozonated HAM exhibited a unimodal profile, with the mass loss peak shifted to approximately 70 °C. These findings were corroborated by DSC analysis, which showed a reduction in denaturation temperature from approximately 85 °C in the in natura sample to around 75 °C in the ozonated sample. The dDSC analysis confirmed the transition from a bimodal to a unimodal behavior after treatment, indicating a reduced energy barrier for protein denaturation and lower thermal stability of the collagen matrix. These results suggest that ozonation promotes alterations in the epithelial layer, which may favor the loss of both free and bound water. It is concluded that processing with ozonated water induces structural modifications, especially in the epithelial layer, and reduces the thermal stability of hydrated HAM without significantly altering the biochemical signature of collagen. This approach shows potential as an alternative method for membrane processing; however, functional evaluations are required to confirm its clinical applicability. Full article

(This article belongs to the Special Issue Biomaterials in Regenerative Medicine: Design, Functionality, and Biomedical Potential)

► Show Figures

Figure 1

22 pages, 1806 KB

Open AccessReview

Plant-Derived Polynucleotides/Polydeoxyribonucleotides in Skin Biomaterials: Delivery Platforms and Bioactivity Attribution

by Hyun Joo Kim, Jin Woo Lee, Sanghyo Kim and Kuk Hui Son

J. Funct. Biomater. 2026, 17(7), 351; https://doi.org/10.3390/jfb17070351 - 18 Jul 2026

Viewed by 779

Abstract

In the fields of dermatology and skin biomaterials, polynucleotides (PN) and polydeoxyribonucleotides (PDRN) typically refer to deoxyribonucleic acid (DNA)-based polymers or heterogeneous DNA-fragment mixtures rather than ribonucleic acid (RNA) polynucleotides. Recently, plant-derived PN/PDRN preparations, sourced from callus, adventitious roots, and plant cell culture [...] Read more.

In the fields of dermatology and skin biomaterials, polynucleotides (PN) and polydeoxyribonucleotides (PDRN) typically refer to deoxyribonucleic acid (DNA)-based polymers or heterogeneous DNA-fragment mixtures rather than ribonucleic acid (RNA) polynucleotides. Recently, plant-derived PN/PDRN preparations, sourced from callus, adventitious roots, and plant cell culture systems, have emerged as a promising animal-free material class. However, current evidence remains predominantly preclinical and should not be construed as demonstrating clinical equivalence to conventional animal-derived PDRN. This review synthesizes recent reports on plant-derived and other non-animal PN/PDRN and integrates them with delivery platform evidence relevant to skin biomaterials. We distinguish directly demonstrated findings from plant-derived preparations from inferences drawn from animal-derived PDRN, synthetic sequence-defined nucleic acids, or broader biomaterial delivery literature. The review further emphasizes operational molecular definitions, polymer length and fragment distribution reporting, DNA purity and integrity, RNA carryover, residual nucleoproteins and plant-derived macromolecules, free nucleotide/nucleoside or degradation product fractions, enzymatic degradation, delivery matrices, and hypothesis-matched controls. Available data suggest overlapping biological signatures with classical PDRN, including keratinocyte repair, fibroblast extracellular matrix (ECM) remodeling, and A2A receptor-associated readouts; however, A2A receptor dependency has not been directly established for most plant-derived PN/PDRN preparations and should be interpreted as a working mechanistic hypothesis unless perturbation experiments demonstrate pathway dependence. Direct head-to-head studies using matched DNA dose, molecular weight distribution, purity, delivery platform, and exposure conditions remain limited. Accordingly, plant-derived PN/PDRN should be evaluated as a source–process–structure–platform–function system rather than as a DNA fraction alone. Full article

(This article belongs to the Special Issue Functional Biomaterials for Skin Reconstruction and Wound Healing)

► Show Figures

Graphical abstract

17 pages, 3415 KB

Open AccessArticle

Wound Debridement with Copper Oxide Dressings: Bridging the Gap Between Clinical Observations and the Basic Science Underlying Endogenous Autolysis

by Eyal Melamed and Ithamar Cheyne

J. Funct. Biomater. 2026, 17(7), 350; https://doi.org/10.3390/jfb17070350 - 18 Jul 2026

Viewed by 481

Abstract

Objective: The usefulness of available wound debridement strategies, including endogenous autolysis and enzymatic, larval, and surgical approaches, is often limited by poor wound bed biology, availability, and invasiveness. Although copper oxide-containing dressings (CODs) have demonstrated broad wound-healing activity in basic science and clinical [...] Read more.

Objective: The usefulness of available wound debridement strategies, including endogenous autolysis and enzymatic, larval, and surgical approaches, is often limited by poor wound bed biology, availability, and invasiveness. Although copper oxide-containing dressings (CODs) have demonstrated broad wound-healing activity in basic science and clinical studies, their potential to modulate debridement has not been specifically characterized. Methods: We conducted a retrospective analysis of five severe clinical cases (six limbs) characterized with extensive necrosis, impaired perfusion, and frequently compromised systemic conditions. Sequential clinical imaging and detailed follow-up were used to assess wound bed dynamics. All cases demonstrated a period of clinical stagnation prior to COD initiation under standard wound care, ranging from 1–4 weeks in the acute cases to approximately 8 years in the chronic venous ulcer, allowing within-case temporal comparison of wound behavior before and after COD introduction, during which no other major changes in local wound management were made. Observations were interpreted in the context of relevant published basic science. Results: In five of the six limbs, major amputation or revision to a higher level had been indicated prior to COD initiation. In all cases, application of COD was associated with rapid and extensive clearance of devitalized tissue, with major wound-bed changes observed within 2–6 weeks, consistent with activation of endogenous autolytic mechanisms. Relevant published literature identifies copper-dependent pathways (CDPs), including the MMP–TIMP axis, inflammatory signaling via NF-κB, and macrophage polarization, that may provide a biologically plausible explanation for these clinical observations. Analysis of serial photographs demonstrated concurrent emergence of granulation tissue and vascularization, supporting synergism among angiogenesis, granulation tissue formation, and debridement, all induced by COD. Conclusions: The observations support the hypothesis that copper ions and CODs may amplify autolytic tissue clearance through CDPs, with concurrent synergistic interaction between angiogenesis and debridement. Full article

(This article belongs to the Special Issue Biomaterials for Wound Healing and Tissue Repair)

► Show Figures

Graphical abstract

15 pages, 1941 KB

Open AccessArticle

Preclinical Evaluation of a Chitosan-Based Field Hemostatic Sponge in Arterial Bleeding Models with and Without Aspirin Administration

by Quang Thai Vu, Hoang Ngan Nguyen, Thi Xoan Le, Thi Thuy Trang Do and Trong Hung Mai

J. Funct. Biomater. 2026, 17(7), 349; https://doi.org/10.3390/jfb17070349 - 18 Jul 2026

Viewed by 427

Abstract

Background/Objectives: This study evaluated the hemostatic efficacy of a chitosan-based field hemostatic sponge (FHS), the first hemostatic product of this type manufactured in Vietnam, across bleeding models of varying injury severity under both normal physiological conditions and after aspirin administration. Methods: An in [...] Read more.

Background/Objectives: This study evaluated the hemostatic efficacy of a chitosan-based field hemostatic sponge (FHS), the first hemostatic product of this type manufactured in Vietnam, across bleeding models of varying injury severity under both normal physiological conditions and after aspirin administration. Methods: An in vivo experimental study was conducted using two models: (1) a rabbit ear incision model in New Zealand White rabbits and (2) a femoral artery puncture model in Wistar rats and New Zealand White rabbits. Animals were randomly allocated to six groups: medical gauze (control), FHS, Axiostat^® (reference material), and three corresponding aspirin-treated groups (n = 10 per group for non-aspirin conditions; n = 6 per group for aspirin-treated rabbits; n = 10 per group for aspirin-treated rats). Primary outcomes were time to hemostasis (seconds) and blood loss (mg). Results: In the rabbit ear incision model, FHS reduced time to hemostasis by 57.6% and blood loss by 69.9% compared with medical gauze (p < 0.001). In the femoral artery puncture model, reductions were 62–65% and 75–76% (p < 0.001). Under aspirin treatment, FHS maintained significant hemostatic advantages over gauze (55–66% reduction in time to hemostasis and 69–76% reduction in blood loss; p < 0.01). No significant difference was observed between FHS and Axiostat^® in any condition (p > 0.05). Conclusions: FHS demonstrated potent and consistent hemostatic efficacy across multiple injury severities and animal species; the hemostatic efficacy of FHS was maintained after aspirin administration, indicating that the material’s efficacy is not entirely dependent on platelet function. These findings support its potential clinical application in hemorrhage control, including in patients with coagulation disorders or receiving antiplatelet therapy. Full article

(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)

► Show Figures

Graphical abstract

13 pages, 19727 KB

Open AccessArticle

Hydrolytically Stable Organo-Chemical Surface Functionalization of Bioinert High-Performance Ceramics Enables Osseoconduction and Osseointegration In Vivo

by Rald V. M. Groven, Changlin Qi, Philipp Schräder, Deniz D. Özman, Lisa Ernst, Zhen Che, Naeem Assasa, Markus Tingart, Frank Hildebrand, Sabine Neuss-Stein, Horst Fischer and Hanno Schenker

J. Funct. Biomater. 2026, 17(7), 348; https://doi.org/10.3390/jfb17070348 - 17 Jul 2026

Viewed by 426

Abstract

Metal alloys in arthroplasty face limitations including aseptic loosening, material failure, and allergic reactions. High-performance oxide ceramics (HPOCs) represent an alternative but are bioinert, restricting osseointegration and osteoconduction. The aim of this study was to convert bioinert HPOC surfaces into bioactive osteogenic microenvironments [...] Read more.

Metal alloys in arthroplasty face limitations including aseptic loosening, material failure, and allergic reactions. High-performance oxide ceramics (HPOCs) represent an alternative but are bioinert, restricting osseointegration and osteoconduction. The aim of this study was to convert bioinert HPOC surfaces into bioactive osteogenic microenvironments through stable peptide-biofunctionalization with cyclic-arginylglycylaspartic acid (cRGD) or modified-hepatocyte growth factor (mod-HGF). In a rabbit femoral defect model, cylindrical ATZ implants were press-fitted into 4.5 × 8 mm defects and examined after 18 weeks. Three groups were compared: uncoated ATZ, cRGD-coated, and mod-HGF-coated implants (n = 8 each). Histomorphometry (Movat Pentachrome, H&E, Alcian Blue), scanning electron microscopy, and energy-dispersive X-ray spectroscopy were performed. Both cRGD- and mod-HGF-coated implants significantly increased bone formation and bone–implant contact relative to controls. Reduced fibrotic encapsulation and enhanced vascularization were observed in both groups, with the strongest effects in the mod-HGF group. Microscopy and spectroscopy confirmed greater mineralization and continuous bone–implant interfaces in coated implants. These results demonstrate that biologically functionalizing ATZ with cRGD or mod-HGF effectively enhances bone formation and implant integration in vivo while reducing fibrotic responses. We proved through the in vivo experiments that bioinert HPOCs obtain osseointegrative behavior due to the hydrolytically stable organo-chemical surface functionalization. Full article

(This article belongs to the Special Issue 3D Printed and Biofabricated Bone Biomaterials: Enhancing Bone Repair and Regeneration)

► Show Figures

Figure 1

26 pages, 8800 KB

Open AccessArticle

Drug Nanocrystal-Loaded Thermo-Reversible Hydrogels of Dexamethasone Palmitate for Intratympanic Drug Delivery

by Su Yeon Noh, Jee Hyun Kang, In Gyu Yang, Min Young Jeong, Seung Hwan Shin, Jiwon Lee, Hye Ryeong Yoon, Woo Jae Lee, Subin Kim, Seong Su Won, Keum-Jin Yang, Yong Seok Choi, Dong-Kee Kim and Myung Joo Kang

J. Funct. Biomater. 2026, 17(7), 347; https://doi.org/10.3390/jfb17070347 - 17 Jul 2026

Viewed by 473

Abstract

Intratympanic (IT) injection of corticosteroids is a standard clinical treatment for sensorineural hearing loss; however, achieving both biocompatibility and efficient cochlea drug delivery remains a significant challenge. Herein, we engineered a novel drug nanocrystal (NS)-loaded thermo-reversible hydrogel (NS-TG) system of dexamethasone-21-palmitate (DEX-P), a [...] Read more.

Intratympanic (IT) injection of corticosteroids is a standard clinical treatment for sensorineural hearing loss; however, achieving both biocompatibility and efficient cochlea drug delivery remains a significant challenge. Herein, we engineered a novel drug nanocrystal (NS)-loaded thermo-reversible hydrogel (NS-TG) system of dexamethasone-21-palmitate (DEX-P), a lipophilic prodrug of dexamethasone (DEX), for improved IT delivery. NSs with a mean diameter of 835.0 nm were fabricated using a dual centrifugation process with polyvinyl alcohol as the stabilizer. The NS-TG system, comprising NSs in a 19% (w/v) Poloxamer 407 hydrogel, exhibited rapid gelation (2–3 min) and a 31-fold increase in drug solubility (1.57 ± 0.02 mg/mL) compared to NS alone, through micellar solubilization. In vitro cytotoxicity assays in HEI-OC1 cells revealed that NS-TG is highly biocompatible, maintaining cell viability, whereas the commercial lipid emulsion (Lipothason^®) induced significant cytotoxicity. In vivo pharmacokinetic evaluation in mice revealed that IT NS-TG provided superior cochlear drug absorption compared to DEX-SP solutions and DEX-P NS, despite showing lower absorption than the lipid emulsion. These findings suggest that the DEX-P NS-TG system, pending further investigation, could serve as a promising platform for cochlear steroidal delivery, offering an optimal balance between delivery efficiency and local safety for treating inner ear diseases. Full article

(This article belongs to the Special Issue Application of Nanomaterials in Drug Delivery and Drug Release)

► Show Figures

Graphical abstract

14 pages, 2312 KB

Open AccessArticle

Distinct Structural Determinants of Failure in Morse Taper and Internal Hex Implant Systems

by Sergio Alexandre Gehrke, Gustavo Coura, Bruno Freitas Mello, Márcio de Carvalho Formiga, Antonio Scarano, Juliana Campos Hasse Fernandes, Gustavo Vicentis Oliveira Fernandes and Fátima de Campos Buzzi

J. Funct. Biomater. 2026, 17(7), 346; https://doi.org/10.3390/jfb17070346 - 17 Jul 2026

Viewed by 456

Abstract

Objectives: To evaluate the influence of implant–abutment connection design, implant diameter, and simulated marginal bone loss on fracture resistance and failure patterns of dental implant systems. Materials and Methods: A total of 180 implant–abutment assemblies were tested, including Morse taper (MT) [...] Read more.

Objectives: To evaluate the influence of implant–abutment connection design, implant diameter, and simulated marginal bone loss on fracture resistance and failure patterns of dental implant systems. Materials and Methods: A total of 180 implant–abutment assemblies were tested, including Morse taper (MT) and internal hex (IH) connections with diameters of 3.5, 4.0, and 5.0 mm. Implants were embedded at two simulated bone levels (0 and 3 mm) and loaded at 30° until failure, in accordance with ISO 14801:2015. Fracture resistance (N) was analyzed using three-way ANOVA. Results: Connection type, implant diameter, bone level, and their interactions significantly affected fracture resistance (p < 0.001). Internal hex implants showed a marked diameter-dependent increase in resistance and greater reduction under simulated bone loss, particularly in reduced diameters. In contrast, Morse taper implants demonstrated similar resistance values regardless of implant diameter or bone level. Failure patterns also differed between systems: internal hex implants exhibited cervical implant fractures in reduced diameters, whereas Morse taper implants showed progressive abutment deformation and/or abutment fracture without implant body fracture. Conclusions: Implant fracture resistance is strongly influenced by implant–abutment connection geometry. Within the limitations of this static in vitro study, MT systems demonstrated diameter-independent mechanical stability and prosthetic-controlled failure patterns, whereas IH systems were highly sensitive to diameter reduction and simulated bone loss. Full article

(This article belongs to the Section Dental Biomaterials)

► Show Figures

Figure 1

24 pages, 13718 KB

Open AccessArticle

Functionalization of a Shape-Memory 3D-Printed Clear Aligner Resin with Silanized Chitosan Nanoparticles: Antibacterial, Optical, Polymerization, and Mechanical Evaluation

by Saya Mustafa Azeez and Anees Mahmood Mudhir

J. Funct. Biomater. 2026, 17(7), 345; https://doi.org/10.3390/jfb17070345 - 16 Jul 2026

Viewed by 560

Abstract

Directly 3D-printed clear aligners are increasingly adopted for orthodontic treatment, but lack intrinsic antibacterial properties. This study investigates the integration of silanized chitosan nanoparticles (CSNPs) into 3D-printed clear aligner resin to improve antibacterial activity while preserving optical, polymerization, and mechanical performance. Commercial CSNPs [...] Read more.

Directly 3D-printed clear aligners are increasingly adopted for orthodontic treatment, but lack intrinsic antibacterial properties. This study investigates the integration of silanized chitosan nanoparticles (CSNPs) into 3D-printed clear aligner resin to improve antibacterial activity while preserving optical, polymerization, and mechanical performance. Commercial CSNPs were surface modified with 3-(trimethoxysilyl)propyl methacrylate and characterized using FTIR, UV-Vis, TEM, EDS, XRD, DLS and zeta-potential analysis. The silanized CSNPs were incorporated into TA-28 clear aligner resin at 0.01, 0.05, and 0.1 wt%. Antibacterial activity against Streptococcus mutans (S. mutans) and Porphyromonas gingivalis (P. gingivalis) was assessed using bacterial adherence and biofilm assay. Transparency, degree of conversion, tensile and flexural properties were evaluated. Successful silanization was confirmed by characterization analyses. The incorporation of silanized CSNPs reduced bacterial adherence and biofilm formation significantly in comparison with the control group (p < 0.001). The transparency was maintained at 0.01 and 0.05 wt% but reduced significantly at 0.1 wt% (p < 0.001). While all nano-modified groups had a lower DC% than the control group, values remained above 75%. Mechanical performance showed improvements, particularly in stiffness and flexural properties, following nanoparticle incorporation. Among the tested concentrations, the 0.05 wt% CSNPs provided the most favorable overall performance, highlighting their potential for the development of next-generation bioactive clear aligners. Full article

(This article belongs to the Special Issue Dental Biomaterials in Implantology and Orthodontics)

► Show Figures

Figure 1

18 pages, 8819 KB

Open AccessArticle

Bone-like Collagen Matrices Through Rapid Intrafibrillar Mineralisation

by Michael Eugene Doyle, Qiancheng Zhang, Brian J. Rodriguez, Kenneth Dalgarno and Ana Marina Ferreira

J. Funct. Biomater. 2026, 17(7), 344; https://doi.org/10.3390/jfb17070344 - 16 Jul 2026

Viewed by 492

Abstract

An innovative strategy for collagen self-assembly with accelerated intra and extrafibrillar mineralisation is introduced to generate bone scaffolds with biomimetic properties. This method, termed Rapid Fibrillogenic Mineralisation (RFM), leverages coprecipitation with 10× Simulated Body Fluid (10× SBF) during fibril formation to maximise nucleation, [...] Read more.

An innovative strategy for collagen self-assembly with accelerated intra and extrafibrillar mineralisation is introduced to generate bone scaffolds with biomimetic properties. This method, termed Rapid Fibrillogenic Mineralisation (RFM), leverages coprecipitation with 10× Simulated Body Fluid (10× SBF) during fibril formation to maximise nucleation, particularly within intrafibrillar zones at molecular termini. Densification is achieved within minutes via plastic compression driven by capillary action, producing bone-like scaffold density without compromising the collagen matrix. Transmission electron microscopy confirms intrafibrillar hydroxyapatite crystals within 15 min, while X-ray diffraction demonstrates distinct HA peaks across groups. Scanning electron microscopy verified extrafibrillar mineralisation after 4 h, with saturation by 6 h, yielding ‘nanoflower’ crystal clusters. Infrared spectra showed increased carbonate content over time, indicating lattice substitutions characteristic of natural bone. Enhanced mineralisation translated into significant mechanical gains as Dynamic Mechanical Analysis revealed compressive moduli approaching cancellous bone (up to 283 ± 31 MPa). In addition, a decrease in the piezoelectric coefficient occurs with increased mineralisation process, highlighting the effects of mineral inclusions on collagen fibre composition and anisotropy. Biologically, mineralised scaffolds supported cellular growth compared to collagen controls. RFM thus enables rapid, reproducible fabrication of biomimetic bone scaffolds that closely emulate native mineralisation patterns and mechanical behaviour. Beyond offering a practical route for scaffold production in tissue engineering, the process also provides new insights into bone physiology and in vitro modelling. By reshaping collagen into a synthetic echo of nature’s bone, RFM establishes a rapid approach for designing functional biomaterials with translational potential. Full article

(This article belongs to the Special Issue Advancements in Biomaterials for Bone Tissue Engineering)

► Show Figures

Graphical abstract

20 pages, 3713 KB

Open AccessArticle

Influence of ZnO Nanoparticles on the Color and Surface Roughness of Composite and Glass-Ionomer Materials

by Sanja Ilić, Neda Ninkovic, Branislav Sredanovic, Goran Vučić, Ljiljana Božić, Ljubica Škrbić, Jovana Kuzmanovic Pficer and Dragica Manojlovic

J. Funct. Biomater. 2026, 17(7), 343; https://doi.org/10.3390/jfb17070343 - 15 Jul 2026

Viewed by 737

Abstract

Objective: The effect of incorporating various concentrations of 210 nm ZnO nanoparticles (ZnO-NPs) into resin-based composites (RBCs) and glass-ionomer cement (GIC) on their color and surface roughness after immersion in red wine is evaluated. Materials and Methods: 12 experimental groups (n = [...] Read more.

Objective: The effect of incorporating various concentrations of 210 nm ZnO nanoparticles (ZnO-NPs) into resin-based composites (RBCs) and glass-ionomer cement (GIC) on their color and surface roughness after immersion in red wine is evaluated. Materials and Methods: 12 experimental groups (n = 12) were tested, including three commercial restorative materials: a microhybrid RBC (Gradia Direct^®), a nanohybrid RBC (Evetric^®) and a GIC (Fuji IX^®). These were modified with ZnO-NPs at weight concentrations of 1%, 2%, and 3%. Color coordinates (L*,a*,b*) were measured using a spectrophotometer (CIEDE2000 formula) before and after 24 h immersion in red wine (37 °C). Surface roughness (Ra) was analyzed using contact profilometry. Results: The addition of ZnO-NPs increased the lightness (L*) and decreased the a* values in all materials. In resin-based composites, even a 1% concentration of ZnO-NPs caused a color change above the clinical acceptability threshold (ΔE₀₀ > 1.8; observed values ranged from 3.2 to 8.0). After immersion in wine, all materials exhibited further discoloration (ΔE₀₀ up to 12.5 for composites). Surface roughness values increased from 0.42 μm (control composite) to 1.95 μm (3% ZnO-NP-modified GIC). Conclusions: Addition of ZnO-NPs influences the aesthetics and topography of restorative materials. Their concentration must be balanced to maintain visual and surface integrity. Full article

(This article belongs to the Section Dental Biomaterials)

► Show Figures

Figure 1

27 pages, 2999 KB

Open AccessSystematic Review

Biomaterial-Driven Modulation of Macrophage Polarization in an Experimental Environment of Implant-Associated Infection Mediated by Staphylococcus aureus: A Systematic Review of Preclinical Studies

by Giorgia Codispoti, Maria Sartori, Michael Salvatore, Andrea Liberatore, Liliana Gabrielli, Tiziana Lazzarotto and Gianluca Giavaresi

J. Funct. Biomater. 2026, 17(7), 342; https://doi.org/10.3390/jfb17070342 - 14 Jul 2026

Viewed by 650

Abstract

Implant-associated infections (IAIs) caused by Staphylococcus aureus are a major cause of orthopedic implant failure, driven by biofilm formation and chronic inflammation. Macrophages regulate bacterial clearance and tissue repair through polarization into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. This systematic review evaluated preclinical [...] Read more.

Implant-associated infections (IAIs) caused by Staphylococcus aureus are a major cause of orthopedic implant failure, driven by biofilm formation and chronic inflammation. Macrophages regulate bacterial clearance and tissue repair through polarization into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. This systematic review evaluated preclinical in vivo studies according to PICO criteria (Population: IAI animal models; Intervention: functionalized biomaterials; Comparator: non-functionalized controls; Outcome: bacterial burden reduction associated with macrophage reprogramming). A PRISMA-guided search of PubMed, Scopus, Web of Science, and Embase (January 2015–December 2025) identified 23 eligible studies, assessed using SYRCLE’s risk-of-bias tool. Due to heterogeneity, a narrative synthesis was performed without meta-analysis. Effect measures included bacterial CFU reduction, macrophage polarization markers, cytokine expression, and histological outcomes. In 87.5% of studies, macrophage modulation was associated with reduced bacterial load, biofilm disruption, and improved peri-implant tissue repair and bone integration. These findings support immunomodulatory biomaterials as promising strategies to manage IAIs through combined antibacterial and immune-regulatory mechanisms. However, further validation in larger animal models is required, particularly for nanomaterials. The protocol of this systematic review was registered on the Open Science Framework. Full article

(This article belongs to the Special Issue Engineered Surfaces: Functionalization Approaches for Cutting-Edge Biomedical Applications)

► Show Figures

Graphical abstract

14 pages, 18226 KB

Open AccessArticle

Multiphotonic Tuning of Nonlinearities Exhibited by Plasma Polypyrrole

by Carlos Alberto Espinoza-Garcés, Victor Manuel Garcia-de-los-Rios, Axayacatl Morales-Guadarrama, Christopher René Torres-SanMiguel and Carlos Torres-Torres

J. Funct. Biomater. 2026, 17(7), 341; https://doi.org/10.3390/jfb17070341 - 14 Jul 2026

Viewed by 722

Abstract

Polypyrrole (PPy) synthesized via plasma polymerization (PPPy) offers a unique combination of electrical conductivity, biocompatibility and stability. This advanced material has emerged as a promising platform for next-generation optoelectronics and multiphotonic biosensors. However, fully unlocking its potential has been hindered by processing challenges [...] Read more.

Polypyrrole (PPy) synthesized via plasma polymerization (PPPy) offers a unique combination of electrical conductivity, biocompatibility and stability. This advanced material has emerged as a promising platform for next-generation optoelectronics and multiphotonic biosensors. However, fully unlocking its potential has been hindered by processing challenges that restrict the fabrication of tailored specimens for precise optical and mechanical characterization. This work overcomes these limitations by isolating and analyzing the nonlinear optical (NLO) response of PPPy across three distinct architectural paradigms: Electrospinning, Coating on SiO₂ Slides, and Dust of Polymer. Using open- and closed-aperture Z-scan techniques, we demonstrate that PPPy exhibits highly pronounced, architecture-dependent NLO behaviors. Notably, the Electrospinning PPPy morphology triggered a full order-of-magnitude enhancement in the nonlinear refractive index (n₂) alongside low-threshold nonlinear absorption (β × 10⁻⁸ cm/W). Irradiance-dependent properties further revealed an optical anisotropy, directly governed by the structural and morphological orientation inherent to each processing method. Since optical nonlinearities are closely related to mechanical and electronic properties, these findings provide a critical blueprint for developing macromolecular architectures, opening new pathways for biocompatible cutting-edge multiphotonic platforms, innovative coatings and surface modifications for tailored implants. Full article

(This article belongs to the Special Issue Spotlight on Biomedical Coating Materials)

► Show Figures

Figure 1

14 pages, 1253 KB

Open AccessArticle

Static and Dynamic Mechanical Properties of 3D-Printable Aligner Resins: An In Vitro Study with FTIR Chemical Characterization

by Marco Serafin, Elisa Boccalari, Marina Borgese, Alberto Caprioglio, Mario Raspanti, Gilberto Binda and Piero Antonio Zecca

J. Funct. Biomater. 2026, 17(7), 340; https://doi.org/10.3390/jfb17070340 - 14 Jul 2026

Viewed by 844

Abstract

Background: Directly printed aligners are advancing rapidly, but the mechanical behavior of the resins behind them is still only partly understood. This in vitro study compared the static flexural behavior, short-term stress relaxation, and FTIR profiles of five Class IIa-certified 3D-printable resins for [...] Read more.

Background: Directly printed aligners are advancing rapidly, but the mechanical behavior of the resins behind them is still only partly understood. This in vitro study compared the static flexural behavior, short-term stress relaxation, and FTIR profiles of five Class IIa-certified 3D-printable resins for direct orthodontic aligners. Methods: The five resins, TC-85, TA-28, DCA, Clear-A V2, and Ortho Flex, were printed as standardized rectangular bars and tested at 37 °C. Three-point bending to 1 mm deflection yielded the maximum flexural stress and the flexural modulus, while a 30 min hold at fixed deflection captured stress relaxation. FTIR added a qualitative chemical characterization. Results: Differences between resins were substantial. DCA led on every static measure, pairing the highest flexural stress and modulus with the highest final relaxation modulus and the best stiffness retention. Clear-A V2 was also statically stiff but retained force only intermediately, whereas TC-85 combined high stiffness with pronounced relaxation. Ortho Flex performed modestly under static loading yet held on to a moderate fraction of its stiffness, and TA-28 relaxed the most. Conclusions: Directly printed aligner resins are mechanically heterogeneous, and static bending alone did not predict short-term force stability. Relaxation metrics should therefore accompany static testing whenever a resin is selected for a specific clinical purpose. Full article

(This article belongs to the Special Issue Three-Dimensional Printing and Biomaterials for Medical Applications)

► Show Figures

Figure 1

14 pages, 719 KB

Open AccessArticle

Chemical Recycling of Polyethylene Terephthalate (PET) Medical Waste for the Sustainable Production of Biomedical Materials

by Haoming Yang and Yuan Yu

J. Funct. Biomater. 2026, 17(7), 339; https://doi.org/10.3390/jfb17070339 - 13 Jul 2026

Viewed by 554

Abstract

This study systematically evaluates the application prospects of three chemical recycling technologies for resource recovery from PET medical waste and the sustainable production of biomedical materials: catalytic pyrolysis, thermochemical recovery, and enzymatic hydrolysis. Orthogonal experimental designs and Box–Behnken response surface methodologies were used [...] Read more.

This study systematically evaluates the application prospects of three chemical recycling technologies for resource recovery from PET medical waste and the sustainable production of biomedical materials: catalytic pyrolysis, thermochemical recovery, and enzymatic hydrolysis. Orthogonal experimental designs and Box–Behnken response surface methodologies were used to optimise process parameters, and an extended assessment platform covering chemical purity, molecular weight distribution, biocompatibility, and mechanical properties was established. Under optimised conditions (200

°

C, 3% w/w catalyst, 4 h, 6:1 ethylene-glycol-to-PET mass ratio), catalytic pyrolysis with zinc acetate achieved a terephthalic acid (TPA) recovery of 92.3 ± 1.8% at a product purity of 98.2 ± 0.5%, and retained 97.6% of the tensile strength and 97.4% of the elastic modulus of virgin PET. Although the enzymatic process was relatively long at 24 h, it had the best biocompatibility (L929 fibroblast viability 94.1 ± 2.2% and haemolysis 1.82 ± 0.28%) and reduced the carbon footprint by 46.5% compared to catalytic processing. Thermochemical recovery was completed in 1 h at 500

°

C, achieving a TPA recovery of 71.2 ± 3.8%, and is suitable for large-scale processing of low-value medical waste streams. Biocompatibility tests showed that PET regenerated via the three paths met the ISO 10993 series of standards, with a cytotoxicity grade of 0–1 and an endotoxin content below 0.5 EU/mL. Gel permeation chromatography showed that the number-average molecular weight (M_n) of chemically recycled PET was between 21,200 and 24,100 g·mol⁻¹ (compared to 24,500 g·mol⁻¹ for virgin PET), approximately 86.5% to 98.4% of the virgin value, and significantly higher than mechanically recycled PET. The technical route and quality-control system established here provide a scientific basis for the closed-loop recycling of medical-grade PET and support the green transformation of the medical industry. Full article

(This article belongs to the Special Issue Active Biomedical Materials and Their Applications, 2nd Edition)

► Show Figures

Figure 1

15 pages, 3755 KB

Open AccessArticle

Mesoporous Bioactive Glass Nanoparticle-Reinforced Calcium Silicate Sealer for Reduced Microleakage and Enhanced Antibacterial Performance

by Zun Zhang, Qianqian Zhang, Ying Sun, Baiyan Sui and Xin Liu

J. Funct. Biomater. 2026, 17(7), 338; https://doi.org/10.3390/jfb17070338 - 13 Jul 2026

Viewed by 584

Abstract

Long-term success of root canal therapy depends not only on effective disinfection but also on durable sealing of the obturated canal system. However, currently available sealers still face persistent challenges in balancing handling, interfacial stability, bioactivity, and antibacterial performance. Here, we developed an [...] Read more.

Long-term success of root canal therapy depends not only on effective disinfection but also on durable sealing of the obturated canal system. However, currently available sealers still face persistent challenges in balancing handling, interfacial stability, bioactivity, and antibacterial performance. Here, we developed an injectable calcium silicate-based root canal sealer reinforced with mesoporous bioactive glass nanoparticles (MBGN) to improve sealing-related performance. The formulation integrated a hydration-active calcium silicate matrix with a mesoporous bioactive component while maintaining practical handling characteristics. MBGN incorporation enhanced dentin-associated mineralization, promoted intratubular crystal deposition, reduced apical microleakage, and decreased internal porosity after obturation. The 5% MBG formulation showed the most favorable sealing profile, reducing the dye penetration depth from 2.68 ± 0.41 mm in the 0% MBG group to 1.87 ± 0.32 mm, together with decreased open and closed pore parameters in the apical region. In parallel, the MBGN-reinforced sealer preserved acceptable cytocompatibility and exhibited stronger antibacterial activity against Streptococcus mutans than the reference formulations. The improved performance may be associated with effective initial adaptation and bioactive interfacial densification. Together, these findings suggest that MBGN incorporation may be a promising route for engineering more bioactive calcium silicate sealers with improved sealing stability and antibacterial function for endodontic applications. Full article

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

► Show Figures

Graphical abstract

19 pages, 6736 KB

Open AccessArticle

Sustainable Carboxymethyl Cellulose-Based Foams via Deep Eutectic Solvent Processing for pH-Responsive Drug Delivery

by Bruno B. Ravanello, Filipe Silva de Matos, Bruna Ramos Navalhas, Luís Pereira and Nalin Seixas

J. Funct. Biomater. 2026, 17(7), 337; https://doi.org/10.3390/jfb17070337 - 12 Jul 2026

Viewed by 548

Abstract

Carboxymethyl cellulose (CMC)-based materials are widely studied for functional materials and porous platform applications, yet their stability usually requires energy-intensive thermal curing or toxic chemical crosslinkers, which limit process sustainability. In this work, we present a more sustainable approach for the preparation of [...] Read more.

Carboxymethyl cellulose (CMC)-based materials are widely studied for functional materials and porous platform applications, yet their stability usually requires energy-intensive thermal curing or toxic chemical crosslinkers, which limit process sustainability. In this work, we present a more sustainable approach for the preparation of CMC-based foams using deep eutectic solvents (DES) as multifunctional structuring agents. CMC hydrogels were prepared with different DES at room temperature, followed by freeze-drying to obtain foams. Among the tested DES, choline chloride:oxalic acid (1:1) combined with glycerol produced foams with the most favorable properties, including high water uptake (288.24 ± 3.02% after 1 h) and water stability for 28 days. Morphological analysis revealed a homogeneous and interconnected porous network (32.2 ± 13.3 µm), while compression tests demonstrated good mechanical recovery (93.29 ± 3.12% over 10 cycles). Fourier transform infrared spectroscopy suggests interactions between CMC and DES, especially hydrogen bonds. The foams exhibited pH-dependent behavior, with limited resveratrol release under acidic conditions (22.2 ± 4.0% after 24 h), with significant release at pH 7.4 (85.30 ± 5.75%) and total release at pH 13.0. Drug release kinetics suggest a diffusion-controlled mechanism under acidic pH, transitioning to anomalous transport at higher pH values. This study demonstrates that DES can be used to prepare CMC-based foams, providing a more sustainable route to porous materials. Although biological validation is needed to confirm therapeutic safety, this study provides an initial physicochemical basis for using these matrices as tunable and stimuli-responsive porous materials. Full article

(This article belongs to the Special Issue Emerging Natural-Polymer-Based Materials for Biomedical Applications)

► Show Figures

Figure 1

34 pages, 27318 KB

Open AccessArticle

Polyethylene Terephthalate Glycol-Modified (PETG) as a Reusable and Biocompatible Substrate for Cell Culture Applications

by Alessia Vita, Federica Tiberio, Diego Sibilia, Martina Salvati, Domiziano Dario Tosi, Lorena Di Pietro, Antonio Alliva, Carlo Mariella, Ornella Parolini and Wanda Lattanzi

J. Funct. Biomater. 2026, 17(7), 336; https://doi.org/10.3390/jfb17070336 - 11 Jul 2026

Viewed by 676

Abstract

The development of reusable and biocompatible biomaterial-based culture substrates is increasingly relevant for improving sustainability in biomedical research workflows. In this study, polyethylene terephthalate glycol-modified (PETG) was evaluated as a potential alternative to conventional polystyrene (PS) for in vitro cell culture applications. PETG [...] Read more.

The development of reusable and biocompatible biomaterial-based culture substrates is increasingly relevant for improving sustainability in biomedical research workflows. In this study, polyethylene terephthalate glycol-modified (PETG) was evaluated as a potential alternative to conventional polystyrene (PS) for in vitro cell culture applications. PETG substrates were fabricated through laser cutting and tested for their ability to support cell adhesion, viability, proliferation, and lineage-specific differentiation across multiple human cell models, including calvarial mesenchymal stromal cells (CMSCs), bone marrow-derived mesenchymal stromal cells (hBM-MSCs), dermal fibroblasts, LHCN-M2 myoblasts, and SH-SY5Y neuroblastoma cells. Morphological and immunofluorescence analyses demonstrated that PETG supported cell attachment and focal adhesion formation, comparable to standard PS surfaces. Cell viability and proliferation assays confirmed metabolic activity and growth over time. Furthermore, PETG substrates supported osteogenic, adipogenic, myogenic, and neuronal differentiation, as demonstrated by histological staining, myotube formation, neurite outgrowth, and lineage-specific gene expression analyses. Finally, PETG maintained CMSC morphology and metabolic activity after repeated recovery, ethanol/UV treatment, and gelatin re-coating, with comparable results between new substrates and those reused for up to three cycles. These findings support PETG as a biocompatible culture substrate with preliminary short-term reuse potential and possible sustainability benefits for laboratory workflows. Full article

(This article belongs to the Special Issue Biocompatible Research of Materials in Biomedical Applications)

► Show Figures

Figure 1

24 pages, 6971 KB

Open AccessArticle

Copper-Doped Silicate Porous Architectures for Hard Tissue Engineering

by Cristina Cristea, Maria-Eliza Puscasu, Gabriela-Olimpia Isopencu, Ovidiu-Cristian Oprea, Vasile-Adrian Surdu, Mihaela Bacalum, Roberta Moisa, Sorin-Ion Jinga and Cristina Busuioc

J. Funct. Biomater. 2026, 17(7), 335; https://doi.org/10.3390/jfb17070335 - 9 Jul 2026

Viewed by 585

Abstract

Porous silicate scaffolds represent a promising class of grafting materials for hard tissue engineering due to their superior bioactivity, adjustable degradation rates, and ability to stimulate both osteogenesis and angiogenesis. In this work, scaffolds based on an akermanite-targeted (Ca₂MgSi₂O [...] Read more.

Porous silicate scaffolds represent a promising class of grafting materials for hard tissue engineering due to their superior bioactivity, adjustable degradation rates, and ability to stimulate both osteogenesis and angiogenesis. In this work, scaffolds based on an akermanite-targeted (Ca₂MgSi₂O₇) starting composition, including copper-doped variants, were synthesized using sol–gel and combustion routes, followed by 3D printing to achieve porous architectures with controlled pore size and interconnectivity. The powders were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and thermal analysis to evaluate their morphology, composition, and crystalline phases. The scaffolds were further assessed in terms of bioactivity by immersion in simulated body fluid (SBF), antibacterial activity, and in vitro cellular response. The results confirmed that copper doping enhanced antibacterial properties, while maintaining favorable biological behavior. Comparative analysis revealed differences between the two synthesis methods, with sol–gel providing more homogeneous structures and combustion leading to highly porous morphologies. These findings highlight copper-doped silicate scaffolds as promising candidates for bone tissue regeneration, combining architectural integrity with biological functionality. Full article

(This article belongs to the Special Issue The 15th Anniversary of JFB—Innovative Biomaterials for Tissue Engineering: Regeneration of Soft and Hard Tissues)

► Show Figures

Figure 1

22 pages, 5937 KB

Open AccessArticle

Hydrophobic pp-HMDSO Coating for Three-Dimensional Cell Culture

by Marina Rakhmanova, Anastasia Leonteva, Maxim Chagin, Evgeniya Ermakova, David Sergeevichev, Vladimir Richter, Marina Kosinova and Anna Nushtaeva

J. Funct. Biomater. 2026, 17(7), 334; https://doi.org/10.3390/jfb17070334 - 9 Jul 2026

Viewed by 627

Abstract

The interaction of biomaterial surface with cells is a pivotal factor in tissue engineering and three-dimensional (3D) modeling. This paper presents an approach to modifying polystyrene surface by plasma-enhanced chemical vapor deposition of thin plasma-polymerized hexamethyldisiloxane (pp-HMDSO) films to enhance biocompatibility and stimulate [...] Read more.

The interaction of biomaterial surface with cells is a pivotal factor in tissue engineering and three-dimensional (3D) modeling. This paper presents an approach to modifying polystyrene surface by plasma-enhanced chemical vapor deposition of thin plasma-polymerized hexamethyldisiloxane (pp-HMDSO) films to enhance biocompatibility and stimulate the formation of 3D cellular structures. The coatings were characterized by SEM, EDS, XPS, FTIR, AFM, contact angle measurements, and surface free energy (SFE) analysis. A hydrophobic surface initiates 3D structure formation by ensuring uniform cell repulsion and stimulating intercellular interactions. Biological evaluation was performed on U-87 MG (glioblastoma) and HMC3 (microglia) cell lines. For U-87 MG, the pp-HMDSO layer proved critical: cell death and atypical adhesion occurred on untreated plastic, whereas stable spheroids formed on the modified surface. HMC3 cells formed small spheroids even on unmodified surfaces, but on pp-HMDSO coatings, the process was more intense and the structures more uniform due to surface hydrophobicity. These results demonstrate the potential of plasma-polymerized HMDSO films as a scalable platform for creating biomaterials with controlled properties for 3D culturing. Full article

(This article belongs to the Special Issue Surface Coating, Functionalization, and Characterization of Cell- and Tissue-Based Biomaterials)

► Show Figures

Figure 1

17 pages, 19305 KB

Open AccessArticle

Remineralization of Artificial Caries-like Lesions in Permanent Enamel by MI Paste One: Comparative Physicochemical Outcomes and In Vitro Resistance to Secondary Demineralization

by Najla F. Alsayari, Sarah S. Al-Angari, Latifa A. Alhowaish, Abdulaziz S. Alangari, Raman Bedi, Ayman M. Sulimany and Maha A. Alsarheed

J. Funct. Biomater. 2026, 17(7), 333; https://doi.org/10.3390/jfb17070333 - 9 Jul 2026

Viewed by 677

Abstract

Background: Patients with White spot lesions (WSLs) are seeking minimally invasive remineralizing treatment. While fluoride is the gold standard of non-invasive caries therapy, its remineralizing impact is predominantly superficial. MI Paste One (MIP-1) combines casein phosphopeptide–amorphous calcium phosphate (CPP–ACP) with 1100 ppm fluoride. [...] Read more.

Background: Patients with White spot lesions (WSLs) are seeking minimally invasive remineralizing treatment. While fluoride is the gold standard of non-invasive caries therapy, its remineralizing impact is predominantly superficial. MI Paste One (MIP-1) combines casein phosphopeptide–amorphous calcium phosphate (CPP–ACP) with 1100 ppm fluoride. This in vitro study aimed to assess the effect of MIP-1 compared with other agents. Methods: Enamel slabs were demineralized to create a caries-like lesion and randomized into five groups (n = 10): G1, WSL/artificial saliva (AS) (negative control); G2, deionized water brushing; G3, fluoridated toothpaste brushing; G4, MIP-1 brushing; G5, topical MI Paste application. Color change (ΔE), gloss (GU), microhardness (VHN), roughness (Ra), and surface topography (SEM) were assessed at four time points: baseline, first demineralization, treatment, and second demineralization. Results: All active agents improved microhardness after treatment. After secondary demineralization, G4 achieved the highest hardness, significantly superior to G3 (p = 0.016). G5 occupied a statistically intermediate position. CPP–ACP-containing agents (G4, G5) achieved color improvement that was significantly superior to controls. Conclusions: MIP-1 outperformed fluoride toothpaste in resisting secondary demineralization of permanent enamel WSLs. CPP–ACP made a measurable independent contribution to demineralization resistance in permanent enamel. These findings highlight the need for further clinical investigation of MIP-1. Full article

(This article belongs to the Section Dental Biomaterials)

► Show Figures

Figure 1

17 pages, 8126 KB

Open AccessArticle

Implants in Adolescents: Clinical Outcomes After Growth-Pattern-Adapted Implant Placement

by Felix Tetsch, Milan Stoilov, Dominik Kraus, Michael Marder, Jan Tetsch and Norbert Enkling

J. Funct. Biomater. 2026, 17(7), 332; https://doi.org/10.3390/jfb17070332 - 9 Jul 2026

Viewed by 637

Abstract

(1) Background: Dental implants in adolescents remain controversial. This retrospective study aimed to evaluate the esthetic outcome of implants placed during adolescence using a growth-pattern-adapted concept, with implant survival, peri-implant health, and patient satisfaction as secondary outcomes. (2) Materials and methods: Primary implant [...] Read more.

(1) Background: Dental implants in adolescents remain controversial. This retrospective study aimed to evaluate the esthetic outcome of implants placed during adolescence using a growth-pattern-adapted concept, with implant survival, peri-implant health, and patient satisfaction as secondary outcomes. (2) Materials and methods: Primary implant survival was retrospectively evaluated based on treatment records in 305 patients (612 implants) affected by tooth loss or congenital tooth agenesis. A subgroup of 68 anterior maxillary implants (50 patients, mean age at implantation: 16.2 ± 2.3 years; range: 12–20) were clinically re-examined after a mean follow-up of 92.4 ± 61.2 months (range: 36–288). (3) Results: Primary implant survival was 93.8% overall (tooth loss: 97.7%; tooth agenesis: 92.3%). The clinical follow-up cohort showed no cases of peri-implantitis and patient satisfaction was high. Anterior maxillary implants demonstrated favorable esthetic outcomes (Pink Esthetic Score [PES]: 12.0 ± 1.1), with females exhibiting significantly higher scores than males. Vertical discrepancies between the implant crown and the contralateral tooth were observed in 41.2% of implants (infraocclusion: 32.4%; supraocclusion: 8.8%). They were significantly associated with tooth loss, non-mesofacial growth patterns and younger age at implantation, without significant influence on PES. (4) Conclusions: The growth-pattern-adapted implant placement met the predefined esthetic threshold and resulted in high primary implant survival, stable peri-implant health, and high satisfaction, supporting its feasibility for anterior maxillary implant placement during adolescence. Full article

(This article belongs to the Special Issue Advanced Biomaterials and Oral Implantology—3rd Edition)

► Show Figures

Graphical abstract

19 pages, 940 KB

Open AccessReview

Natural Polymers in Guided Bone Regeneration (GBR)

by Anca Fratila, Diana Marian, Alexandru Petre, Anca Hermenean and Ioana Lile

J. Funct. Biomater. 2026, 17(7), 331; https://doi.org/10.3390/jfb17070331 - 7 Jul 2026

Viewed by 813

Abstract

Guided Bone Regeneration (GBR) is a pivotal technique in dental and orthopedic applications for regenerating bone in areas of deficiency. Natural polymers such as collagen, chitosan, alginate, and gelatin have emerged as essential materials in GBR due to their biocompatibility, biodegradability, and bioactivity. [...] Read more.

Guided Bone Regeneration (GBR) is a pivotal technique in dental and orthopedic applications for regenerating bone in areas of deficiency. Natural polymers such as collagen, chitosan, alginate, and gelatin have emerged as essential materials in GBR due to their biocompatibility, biodegradability, and bioactivity. These polymers not only provide a scaffold for bone regeneration but also support cellular adhesion, proliferation, and differentiation. Despite their benefits, challenges such as variable degradation rates, insufficient mechanical strength, and limited bioactivity hinder their optimal clinical use. To address these limitations, ongoing research focuses on enhancing the properties of natural polymers. Composite materials combining fast- and slow-degrading polymers are being developed to achieve consistent degradation rates. Surface modifications, including nanoscale texturing and growth factor coatings, are improving bioactivity. Nanotechnology further enhances the structural and therapeutic potential of GBR materials, while advancements in 3D bioprinting enable the creation of customized scaffolds with precise architecture. These innovations aim to bridge the gap between biological compatibility and clinical functionality, making natural polymers more adaptable and effective in GBR. This review highlights the mechanisms, challenges, and advancements in natural polymers for GBR, emphasizing their potential to transform bone regeneration into a more reliable and patient-centered approach. Full article

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

► Show Figures

Figure 1

14 pages, 8304 KB

Open AccessArticle

Partially Demineralized Acellular Bovine Bone Matrix Supports for Bone Healing In Vivo

by Cuc Bui, Quan Minh To, My Thi Ngoc Nguyen, Thuan Minh Le, Triet Minh Tran, Lam Nguyen Le, Duc Hoang Minh Bui, Lam Van Nguyen and Ha Le Bao Tran

J. Funct. Biomater. 2026, 17(7), 330; https://doi.org/10.3390/jfb17070330 - 6 Jul 2026

Viewed by 804

Abstract

Acellular bone matrix, with its natural extracellular matrix components, has been considered a potential alternative platform for bone grafting. Our study focused on fabricating acellular bovine bone matrix (ABBM) and evaluating its in vitro characteristics and in vivo effect on bone repair. The [...] Read more.

Acellular bone matrix, with its natural extracellular matrix components, has been considered a potential alternative platform for bone grafting. Our study focused on fabricating acellular bovine bone matrix (ABBM) and evaluating its in vitro characteristics and in vivo effect on bone repair. The bovine cancellous bone was subjected to ABBM preparation, which included partial demineralization and decellularization processing. The effects of the ABBM on human bone marrow-derived stem cells (hBMSCs) were evaluated, including viability, migration, attachment, and proliferation. A rabbit bone defect model was implanted with ABBM and histologically assessed for bone healing. The acellular properties were determined by the absence of nuclear material and the accepted minimum residual DNA content. An in vitro study indicated the ABBM’s positive effect on the migration of hBMSCs. ABBM was also demonstrated to support hBMSC attachment and proliferation. In vivo testing was performed in rabbits with a cranial bone defect, which showed complete bone healing after 8 weeks of grafting with ABBM. Overall, the fabricated ABBM demonstrated in vitro and in vivo biocompatibility and effective support for bone healing in vivo, and therefore represents a potential xenogeneic biomaterial for bone tissue repair. Full article

(This article belongs to the Special Issue Biomaterials for Wound Healing and Tissue Repair)

► Show Figures

Figure 1

24 pages, 1412 KB

Open AccessReview

Functional Adhesives for a Restorative Future

by Andreas Katsonis, Monica Silvia Tatarciuc, Anca Mihaela Vitalariu, Roxana Ionela Vasluianu, Jamal Al-Ashkar, Catalina Holban Cioloca, Andrea-Simoni Katsoni, Panagiotis Perperidis, Irina Gradinaru, Adina Oana Armencia and Ovidiu Stamatin

J. Funct. Biomater. 2026, 17(7), 329; https://doi.org/10.3390/jfb17070329 - 6 Jul 2026

Viewed by 612

Abstract

Cementation of indirect restorations has undergone a profound change over the past century, evolving from a philosophy of purely mechanical cementation to sophisticated biomaterials science based on adhesion. The aim of this narrative review is to provide essential context for understanding contemporary clinical [...] Read more.

Cementation of indirect restorations has undergone a profound change over the past century, evolving from a philosophy of purely mechanical cementation to sophisticated biomaterials science based on adhesion. The aim of this narrative review is to provide essential context for understanding contemporary clinical decision-making. A key aspect is the structural and compositional characteristics of enamel and dentin as bonding substrates, underlining why enamel remains the gold standard, while dentin continues to present significant challenges. The synthesis is based on evidence of adhesive strategies for the four main classes of contemporary restorative materials, such as glass-ceramics (lithium disilicate and leucite), polycrystalline zirconia, resin-matrix ceramics (hybrid ceramics), and indirect composites. Each material was detailed in terms of surface penetration (e.g., hydrofluoric acid etching and air abrasion), chemical coupling (e.g., silanization and MDP-based primers), and appropriate resin cement selection (light-cured, dual-cured, or self-adhesive). A step-by-step clinical protocol is synthesized based on current evidence, integrating critical techniques such as immediate dentin sealing and optimized polymerization. This review concludes that while adhesive resin cements provide predictable long-term results, significant challenges remain, guiding future clinical research and innovation. Full article

(This article belongs to the Section Dental Biomaterials)

► Show Figures

Figure 1

12 pages, 1646 KB

Open AccessArticle

Soft Tissue Healing After Post-Extractive Alveolar Ridge Reconstruction Using a Magnesium Membrane-Based Regenerative Approach: A Preliminary Study

by Ilham Mounssif, Claudio Mazzotti, Valentina Bentivogli, Francesco Bondi, Diego Bianchelli, Matteo Sangiorgi, Giovanni Zucchelli and Martina Stefanini

J. Funct. Biomater. 2026, 17(7), 328; https://doi.org/10.3390/jfb17070328 - 6 Jul 2026

Viewed by 721

Abstract

Post-extractive alveolar ridge reconstruction with resorbable barrier membranes aims to preserve ridge dimensions and support future implant placement, yet evidence on soft tissue healing with magnesium-based membranes remains limited. This prospective observational pilot study evaluated mucosal healing following alveolar ridge reconstruction using a [...] Read more.

Post-extractive alveolar ridge reconstruction with resorbable barrier membranes aims to preserve ridge dimensions and support future implant placement, yet evidence on soft tissue healing with magnesium-based membranes remains limited. This prospective observational pilot study evaluated mucosal healing following alveolar ridge reconstruction using a resorbable pure magnesium membrane (NOVAMag^®) combined with a xenogeneic bone graft and a collagen dermal matrix overlay in five consecutively enrolled patients. Soft tissue healing was assessed with the Wound Healing Index (WHI) at 7, 14, 30, 90, and 180 days postoperatively. Secondary outcomes included postoperative pain (VAS) and oral health-related quality of life (OHIP-14) at 7 days. Mean WHI scores progressed from 4.4 ± 0.8 at day 7 to 4.8 ± 0.4 at day 14, with complete excellent healing (WHI 5.0 ± 0.0) achieved in all patients by day 90 and maintained through day 180. One case of partial wound dehiscence resolved spontaneously without infection or graft loss. Mean VAS was 1.86 ± 1.89 cm, and mean OHIP-14 was 20.8 ± 5.23, indicating limited and transient patient-reported impact. These preliminary findings support the clinical feasibility of the NOVAMag^® membrane as part of a combined regenerative approach in post-extractive ridge reconstruction and warrant validation in larger controlled trials. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Oral Rehabilitation)

► Show Figures

Figure 1

21 pages, 24047 KB

Open AccessArticle

Balancing Osseointegration and Infection Control: The Role of Titanium Surface Topography in Peri-Implant Biology

by Simina Angela Lăcrimioara Iușan, Dana-Gabriela Feștilă, Ioana-Codruța Mirică, Giorgiana Corina Mureșan, Bianca-Nausica Petrescu, Olga Sorițău, Carmen Costache, Dan-Alexandru Toc, Otilia Andercou, Maria Aluaș, Simion Bran, Dragoș Budei, Silviu Albu and Ondine Patricia Lucaciu

J. Funct. Biomater. 2026, 17(7), 327; https://doi.org/10.3390/jfb17070327 - 6 Jul 2026

Viewed by 530

Abstract

Background: Peri-implant infections remain a major cause of dental implant failure, largely due to bacterial adhesion and biofilm formation on implant surfaces. This study aimed to investigate how surface topography influences bacterial colonisation and osteoblastic response. Methods: Titanium discs with machined (Ma), sandblasted, [...] Read more.

Background: Peri-implant infections remain a major cause of dental implant failure, largely due to bacterial adhesion and biofilm formation on implant surfaces. This study aimed to investigate how surface topography influences bacterial colonisation and osteoblastic response. Methods: Titanium discs with machined (Ma), sandblasted, large-grit, and acid-etched (SLA), and nanostructured (Nano) surfaces were prepared, sterilised, and seeded with pre-differentiated dental follicle mesenchymal stem cells. Co-cultures with Enterococcus faecalis (E. faecalis) and Streptococcus oralis (S. oralis) were established under CO₂-free conditions, and cell–bacteria interactions were evaluated using fluorescence microscopy and quantitative image analysis. Results: Nano surfaces showed the highest osteoblastic adhesion and viability, while significantly reducing bacterial proliferation and biofilm formation compared with Ma and SLA surfaces. The sequence of colonisation influenced cell–bacteria dynamics, with early cell attachment limiting subsequent bacterial adhesion. Conclusions: Nano titanium surfaces may offer a dual benefit by promoting osseointegration while limiting bacterial adhesion. These findings support their potential use as surface modifications to reduce peri-implant infection risk and improve long-term implant success. Full article

(This article belongs to the Special Issue Antibacterial Biomaterials for Medical Applications)

► Show Figures

Figure 1

18 pages, 5421 KB

Open AccessArticle

Enhanced Antibacterial Activity of Artemisia absinthium Extract Containing Artemisinin and Polyphenols Loaded into Mesoporous Silica Calcium- and Cerium-Doped Nanoparticles

by Ioannis Tsamesidis, Georgia K. Pouroutzidou, Athanasios Christodoulou, Dimitrios Gkiliopoulos, Dionysia Amanatidou, Styliani Axypolitou, Maria Bousnaki, Georgia Michailidou, Dimitrios Bikiaris, Phaedra Eleftheriou, Maria Chatzidimitriou, Sotirios Kalfas and Eleana Kontonasaki

J. Funct. Biomater. 2026, 17(7), 326; https://doi.org/10.3390/jfb17070326 - 6 Jul 2026

Viewed by 646

Abstract

Background: Artemisia absinthium (A. absinthium) is a perennial plant valued for its antibacterial, antioxidant, and anti-inflammatory properties, exhibiting broader therapeutic potential. Given the need to deliver low doses of A. absinthium extract, mesoporous silica nanoparticles have attracted considerable attention as promising [...] Read more.

Background: Artemisia absinthium (A. absinthium) is a perennial plant valued for its antibacterial, antioxidant, and anti-inflammatory properties, exhibiting broader therapeutic potential. Given the need to deliver low doses of A. absinthium extract, mesoporous silica nanoparticles have attracted considerable attention as promising nanocarriers due to their distinctive physical and chemical properties. Methods: Physicochemical characterization of the materials was performed and biological assays were conducted to investigate the ROS, antibacterial and antioxidant activity of A. absinthium extract encapsulated within cerium- and calcium-doped mesoporous silica nanoparticles (MNSiCaCe) against both aerobic and anaerobic bacteria. Results: FTIR, SEM, and BET analysis confirmed successful synthesis of the MNSiCaCe. Phytochemical profiling of Artemisia absinthium extract using HPLC revealed the presence of artemisinin and a rich composition of phenolic and flavonoid constituents, with a total phenolic content of 182 ± 3.6 mg GAE/100 g dry plant material and a total flavonoid content of 42.5 ± 0.6 mg QE/100 g. Quantitative drug loading profiling demonstrated that while plain MNSi nanocarriers achieved a loading capacity of 16.96%, the MNSiCaCe enhanced this threshold to 43.11%. The in vitro controlled-release kinetics exhibited a highly prolonged and slow-release profile of the MNSiCaCe. The materials demonstrated excellent hemocompatibility and high mitochondrial activity with human periodontal ligament cells (hPDLCs). Elevated ROS generation was observed under conditions where antibacterial activity was most pronounced. While the artemisinin-doped nanoparticles showed notable antibacterial effects, the complete Artemisia absinthium-loaded nanoparticles achieved a significantly greater reduction in bacterial viability probably due to the synergistic interaction between artemisinin and the extract’s rich polyphenol profile. Conclusions: These findings highlight MNSiCaCe as a promising and safe nanocarrier system for drug delivery, with strong antibacterial potential, offering valuable applications in antibacterial therapies. Full article

(This article belongs to the Special Issue Antibacterial Biomaterials for Medical Applications)

► Show Figures

Figure 1

26 pages, 2002 KB

Open AccessReview

Polymer Microneedles for Localized Drug Delivery in Musculoskeletal Tissue Regeneration

by Seihyun Park, Dohee Kim, Hongyoon Kim, Inseon Kim and Seunghun S. Lee

J. Funct. Biomater. 2026, 17(7), 325; https://doi.org/10.3390/jfb17070325 - 6 Jul 2026

Viewed by 815

Abstract

Musculoskeletal (MSK) disorders—osteoporosis, osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, tendinopathy, and skeletal muscle injury—contribute the largest share of years lived with disability worldwide. Conventional therapy relies on systemic dosing or repeated intra-articular and peri-tissue injections, which suffer from off-target toxicity, poor lesional bioavailability, [...] Read more.

Musculoskeletal (MSK) disorders—osteoporosis, osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, tendinopathy, and skeletal muscle injury—contribute the largest share of years lived with disability worldwide. Conventional therapy relies on systemic dosing or repeated intra-articular and peri-tissue injections, which suffer from off-target toxicity, poor lesional bioavailability, and low adherence. Polymer microneedles (MNs)—micron-scale projections of biodegradable, dissolving, hydrogel-forming, or composite polymers—have rapidly matured into a versatile platform for minimally invasive, spatially localized, and temporally programmable delivery of small molecules, biologics, nucleic acids, extracellular vesicles, and cells to MSK tissues. This review synthesizes 2018–2026 advances in polymer MN systems engineered specifically for MSK regeneration. We classify dominant polymer chemistries and MN architectures; map fit-for-purpose across bone, cartilage, joint, intervertebral disc, tendon, and skeletal muscle; and survey “smart” MN designs that exploit reactive oxygen species, pH, mechanical, triboelectric, optogenetic, and ultrasonic triggers. We close with a concise conclusion and forward perspective that identifies the key design levers—hybrid MN–scaffold combination products, stimuli-responsive platforms tuned to the MSK micro-environment, and cell- and EV-loaded formats—most likely to have clinical impact. Full article

(This article belongs to the Special Issue Polymers for Drug Delivery and Drug Release Systems)

► Show Figures

Graphical abstract

10 pages, 4226 KB

Open AccessCommunication

Assessment of Creativity Potential of a 3DGAN in Implant Crown Design: A Proof-of-Concept Study

by Aleksandar Naydenov, Todor Uzunov, Dimitar Kirov and Georgi Kostadinov

J. Funct. Biomater. 2026, 17(7), 324; https://doi.org/10.3390/jfb17070324 - 5 Jul 2026

Viewed by 872

Abstract

Digital dentistry increasingly relies on artificial intelligence (AI) to automate restorative design. However, the ability of generative networks to produce multiple geometrically distinct outputs for the same prosthetic field remains insufficiently evaluated. This study assessed repeated-output geometric variability in a previously developed three-dimensional [...] Read more.

Digital dentistry increasingly relies on artificial intelligence (AI) to automate restorative design. However, the ability of generative networks to produce multiple geometrically distinct outputs for the same prosthetic field remains insufficiently evaluated. This study assessed repeated-output geometric variability in a previously developed three-dimensional generative adversarial network (3DGAN) for screw-retained implant crown design as a preliminary indicator of potential generative diversity. Nine AI-generated implant crown designs were analyzed, consisting of three independently generated crowns for each of three different prosthetic fields. Within each set, the crowns were superimposed and compared using “MeshLab”. Mean Hausdorff distance (HD), maximum HD, and root mean square (RMS) values were recorded, with 0.05 model units used as the threshold for identifying insufficient morphological variation. The overall mean HD was 3.32 model units, the mean maximum HD was 16.18 model units, and the mean RMS value was 4.40 model units. No pairwise comparison showed values equal to or below 0.05 model units. In conclusion, the investigated 3DGAN demonstrated preliminary evidence of geometric output variability compatible with potential generative diversity. Full article

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

► Show Figures

Figure 1

17 pages, 11314 KB

Open AccessArticle

Guiding of Cell Migration over Sloped Steps Using TiO_x Arrowhead Patterns

by Yijun Cheng, Chang Liu and Stella W. Pang

J. Funct. Biomater. 2026, 17(7), 323; https://doi.org/10.3390/jfb17070323 - 5 Jul 2026

Viewed by 538

Abstract

Cell migration is a fundamental biological process regulated by interactions between cells and extracellular matrix. Although topographical cues are known to influence cell behaviors, directional migration across three-dimensional (3D) sloped steps remains poorly understood. Here, 3D sloped steps with patterned TiO_x surfaces [...] Read more.

Cell migration is a fundamental biological process regulated by interactions between cells and extracellular matrix. Although topographical cues are known to influence cell behaviors, directional migration across three-dimensional (3D) sloped steps remains poorly understood. Here, 3D sloped steps with patterned TiO_x surfaces were fabricated to investigate topography-guided cell migration in complex 3D microenvironments. The ultrathin TiO_x layers were patterned along the bottom, sidewall, and top regions of the steps, providing continuous guidance during cell migration up or down the steps. MC3T3-E1 cells were confined to the patterned regions and exhibited contact-guided migration along the asymmetrical arrowhead patterns. Forward and reverse arrowheads were introduced to evaluate the effect of geometrical asymmetry on cell migration directionality. Forward arrowheads preferentially guided cells from the bottom to the top of steps, whereas reverse arrowheads promoted migration down the steps, demonstrating reversible control of cell migration direction through arrowhead orientation. Analysis of cell morphology revealed that ultrathin TiO_x topographies influenced lamellipodia orientation and cell adhesion, providing mechanistic insights into geometry-mediated control of cell migration direction. These findings demonstrate that guiding pattern asymmetry can be used to regulate the speed and directionality of cell migration across sloped steps, which can be applied to control cell migration behaviors on engineered 3D platforms. Full article

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

► Show Figures

Figure 1

Journal Menu

Journal Browser

J. Funct. Biomater., Volume 17, Issue 7 (July 2026) – 43 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI