Journal of Functional Biomaterials

21 pages, 5460 KB

Open AccessArticle

ZrO₂ Ceramic without and with Fullerene C₆₀ Films: In Vitro Direct-Contact Model Using E. coli and S. aureus Bacteria

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

J. Funct. Biomater. 2026, 17(4), 206; https://doi.org/10.3390/jfb17040206 - 21 Apr 2026

Viewed by 1904

Abstract

Zirconia is known as a strong and bioinert load-bearing material for dental implants. It typically exhibits no antibacterial activity. Inflammation is a crucial problem for dental implant surgery: about 3–5% of all dental implants experience inflammation. This study demonstrates that either fullerene C [...] Read more.

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

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

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14 pages, 14338 KB

Open AccessArticle

Recombinant Human SLPI Surface Functionalization Enhances Early Osseointegration and Biomechanical Stability of Titanium Implants in Rat Model

by Wannapat Chouyratchakarn, Burin Boonsri, Surasak Tangkamonsri, Watchara Thepsupa, Chayarop Supanchart and Sarawut Kumphune

J. Funct. Biomater. 2026, 17(4), 205; https://doi.org/10.3390/jfb17040205 - 20 Apr 2026

Viewed by 1604

Abstract

Titanium and its alloys are used in dental and orthopedic implants. However, long-term stability remains a clinical challenge. To overcome this limitation, surface modification has been investigated to improve surface properties. Our previous study demonstrated that the immobilization of secretory leukocyte protease inhibitor [...] Read more.

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

(This article belongs to the Section Bone Biomaterials)

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18 pages, 11756 KB

Open AccessArticle

Microstructure-Dependent Rotational Wear of Dental Glass-Ceramics Under Low Humidity

by Estíbaliz Sánchez-González, Fernando Rodríguez-Rojas and Oscar Borrero-López

J. Funct. Biomater. 2026, 17(4), 204; https://doi.org/10.3390/jfb17040204 - 20 Apr 2026

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Abstract

Background: The wear resistance of modern commercial glass-ceramic materials used in dental prostheses was investigated under cyclic contact conditions that included a rotational component. This loading mode has been largely overlooked in conventional in vitro wear testing, yet may be clinically relevant [...] Read more.

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

(This article belongs to the Section Dental Biomaterials)

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24 pages, 5670 KB

Open AccessReview

4D Printing in Biomedical Implants and Functional Healthcare Devices

by Muhammad Shafiq and Liaqat Zeb

J. Funct. Biomater. 2026, 17(4), 203; https://doi.org/10.3390/jfb17040203 - 20 Apr 2026

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Abstract

Four-dimensional (4D) printing integrates additive manufacturing with stimuli-responsive materials to fabricate biomedical implants and functional healthcare devices that undergo programmed, time-dependent changes in shape or function. Unlike static 3D-printed constructs, 4D-printed systems can respond to clinically relevant stimuli such as temperature, hydration, pH, [...] Read more.

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

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

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27 pages, 5309 KB

Open AccessArticle

Cotton-Type Nanofiber Guided Pathway Engineering Enables Rapid Tissue Integration and Accelerated Bone Regeneration in Mineral Powder-Based Bone Grafts

by Subin Park, Siphesihle Cassandra Nonjola, Jeong In Kim and Soonchul Lee

J. Funct. Biomater. 2026, 17(4), 202; https://doi.org/10.3390/jfb17040202 - 20 Apr 2026

Viewed by 1585

Abstract

Mineral powder–based bone grafts exhibit excellent osteoconductivity; however, their clinical efficacy is often compromised by insufficient early-stage tissue ingrowth, leading to particle aggregation and pocket formation within the defect site during the initial healing phase. Here, we report a cotton-type nanofiber-guided mineral graft [...] Read more.

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

(This article belongs to the Special Issue Functional Scaffolds for Hard Tissue Engineering and Surgery)

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23 pages, 3916 KB

Open AccessArticle

How Bioactive Glass S53P4 Kills Bacteria

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

J. Funct. Biomater. 2026, 17(4), 201; https://doi.org/10.3390/jfb17040201 - 19 Apr 2026

Viewed by 1575

Abstract

Bioactive glass (BAG) S53P4 is a clinically approved bone substitute with antibacterial, osteoconductive and osteostimulatory properties. Its antibacterial effect is associated with ion release, local pH elevation and osmolality, but the precise biochemical and biophysical mode-of-action is unclear. This study investigates the antibacterial [...] Read more.

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

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

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17 pages, 6987 KB

Open AccessArticle

Nanotopography-Mediated Mechanotransduction Enhances hBMSCs Adhesion on TiO₂ Nanotubes

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

J. Funct. Biomater. 2026, 17(4), 200; https://doi.org/10.3390/jfb17040200 - 19 Apr 2026

Viewed by 1631

Abstract

Titanium and its alloys are widely used for orthopedic implants, but their intrinsic bioinertness may hinder osseointegration. In this study, titanium dioxide nanotube (TNT) arrays were fabricated on Ti-6Al-4V scaffolds via anodization, and their effects on the adhesion behavior of human bone marrow [...] Read more.

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

(This article belongs to the Special Issue Metals and Alloys for Biomedical Applications (2nd Edition))

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16 pages, 16204 KB

Open AccessArticle

ATP-Responsive Bimetallic Metal–Organic Frameworks Amplify Oxidative Stress in the Tumor Microenvironment for Synergistic Chemo-Immunotherapy

by You Li, Wenxin Zhang, Zitao Xu, Shixin Ma, Yufei Xiong, Li Yu, Huiling Gao, Yang Shu and Teng Fei

J. Funct. Biomater. 2026, 17(4), 199; https://doi.org/10.3390/jfb17040199 - 19 Apr 2026

Viewed by 1634

Abstract

Metal ion-based chemo-immunotherapy is often limited by rigid intracellular metal homeostasis, insufficient reactive oxygen species (ROS) accumulation, and an immunosuppressive tumor microenvironment (TME). To overcome these limitations, we engineered an ATP-responsive, core–shell bimetallic nanoreactor (Cu/ZIF@PDA, termed CZP) featuring a precisely controlled ~25 nm [...] Read more.

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

(This article belongs to the Section Biomaterials for Cancer Therapies)

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13 pages, 2720 KB

Open AccessArticle

Bone Compatibility of Experimental Ti–Ag and Ti–Cu Alloy Dental Implants in a Beagle Dog Model

by Yasumitsu Ohtsuka, Taichi Tenkumo, Masatoshi Takahashi, Yasuhiro Nakanishi, Hiroaki Takebe and Takashi Nezu

J. Funct. Biomater. 2026, 17(4), 198; https://doi.org/10.3390/jfb17040198 - 18 Apr 2026

Viewed by 1544

Abstract

Titanium–silver (Ti–Ag) and titanium–copper (Ti–Cu) alloys have been developed to improve the mechanical properties and machinability of titanium (Ti) for dental applications while maintaining corrosion resistance comparable to that of pure Ti. Herein, cylindrical dental implants composed of experimental Ti–20Ag, Ti–30Ag, Ti–5Cu, and [...] Read more.

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

(This article belongs to the Special Issue Functional Dental Materials for Orthodontics and Implants)

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14 pages, 1370 KB

Open AccessTechnical Note

Personalized 3D-Printed Hybrid PDMS and PEEK Implants for Revisional Orbitomaxillary Reconstruction: A Translational Case-Based Technical Note

by Goran Marić, Darko Solter, Blanka Doko Mandić, Jelena Škunca Herman, Zoran Vatavuk, Damir Godec, Davor Vagić and Alan Pegan

J. Funct. Biomater. 2026, 17(4), 197; https://doi.org/10.3390/jfb17040197 - 18 Apr 2026

Viewed by 1536

Abstract

The reconstruction of complex orbitomaxillary defects requires biomaterials that can simultaneously provide structural stability, biocompatibility, and accurate restoration of facial volume and contour. While rigid polymers such as polyetheretherketone (PEEK) offer reliable mechanical support, they do not adequately replicate the viscoelastic behavior of [...] Read more.

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

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

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13 pages, 938 KB

Open AccessArticle

Acellular Dermal Matrix (WITHderm^®) Spacer Grafts for the Prevention of Lower Eyelid Ectropion After Subciliary Approaches in Facial Fracture Surgery: A Preliminary Study

by Wooseob Kim, Eun A. Jang and Kyu Nam Kim

J. Funct. Biomater. 2026, 17(4), 196; https://doi.org/10.3390/jfb17040196 - 18 Apr 2026

Viewed by 1462

Abstract

Background/Objectives: The subciliary approach offers excellent exposure for orbital and zygomaticomaxillary complex fracture repair but is associated with a relatively high risk of postoperative lower eyelid ectropion. This study evaluated the preventive efficacy of an acellular dermal matrix (ADM; WITHderm^®) spacer [...] Read more.

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

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

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13 pages, 2777 KB

Open AccessArticle

Comparative Cytocompatibility and Oxidative Stress Analysis of Green-Synthesized Nano-Silver Fluoride and Silver Diamine Fluoride in Human Gingival Fibroblasts

by Antonia P. Palankalieva, Iva D. Stoykova, Milen I. Georgiev and Ani B. Belcheva

J. Funct. Biomater. 2026, 17(4), 195; https://doi.org/10.3390/jfb17040195 - 17 Apr 2026

Viewed by 1683

Abstract

Silver diamine fluoride (SDF) is widely used in pediatric dentistry for caries arrest; however, concerns exist regarding its cytotoxicity. Green-synthesized nano-silver fluoride (NSF) is a potential alternative to SDF, offering antimicrobial efficacy with improved biocompatibility. This study aimed to evaluate the in vitro [...] Read more.

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

(This article belongs to the Special Issue Biomaterials for Management of Dental Caries and Periodontal Disease)

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16 pages, 3363 KB

Open AccessArticle

Accuracy of Static Computer-Aided Implant Surgery: A Clinical Comparison of Tooth-, Bone-, and Mucosa-Supported Surgical Guides

by Igor Smojver, Roko Bjelica, Marko Vuletić, Luka Stojić, Vlatka Njari Galić and Dragana Gabrić

J. Funct. Biomater. 2026, 17(4), 194; https://doi.org/10.3390/jfb17040194 - 17 Apr 2026

Viewed by 1544

Abstract

The accuracy of static computer-aided implant surgery (s-CAIS) is fundamental for predictable clinical outcomes. The objective of this study was to evaluate the influence of different guide-support modalities on the linear and angular accuracy of implant placement. In this retrospective clinical investigation conducted [...] Read more.

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

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

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22 pages, 3487 KB

Open AccessArticle

Synthesis and Characterization of Modified Chitosan Materials with Assessment of Their Antibacterial and Antiviral Activities

by Dhouha Bouzir, Adel Elamri, Khmais Zdiri, Mohamed Hamdaoui, Christelle Delaite, Abdelaziz Lallam and Omar Anis Harzallah

J. Funct. Biomater. 2026, 17(4), 193; https://doi.org/10.3390/jfb17040193 - 17 Apr 2026

Viewed by 1096

Abstract

Modified chitosan (Cs) derivatives were synthesized and evaluated as potential antibacterial and antiviral coatings of medical protective equipment (facial masks, gloves, …). Quaternized chitosan (HTCC) and chitosan–silver nanocomposites (Ag/Cs) were successfully prepared, with structural characterization confirming efficient quaternization and uniform incorporation of silver [...] Read more.

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

(This article belongs to the Special Issue Innovative Approaches to Antimicrobial and Antiviral Functionalization of Textile Materials)

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18 pages, 2844 KB

Open AccessArticle

Setting Characteristics, Solubility, Bioactivity and Interaction with Dentin of Four Calcium Silicate-Based Endodontic Sealers

by Areti Dimitra Vrochari, Anastasia Agrafioti, Maria Dimitriadi and George Eliades

J. Funct. Biomater. 2026, 17(4), 192; https://doi.org/10.3390/jfb17040192 - 17 Apr 2026

Viewed by 426

Abstract

The aim of this study was to evaluate setting time, hardness, solubility, bioactivity and interaction with dentin of four calcium silicate-based sealers (CSBS). Three single-phase CSBS (AH Plus Bioceramic/AHB, CeraSeal/CSL, TotalFill BC/TFL), one powder/liquid CSBS (BioRoot RCS/BRT) and an epoxy control (AH Plus [...] Read more.

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

(This article belongs to the Section Dental Biomaterials)

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1 pages, 133 KB

Open AccessCorrection

Correction: Petropoulou et al. Conversion and Tack-Curing of Light-Cured Veneer Luting Agents. J. Funct. Biomater. 2025, 16, 307

by Aikaterini Petropoulou, Maria Dimitriadi, Spiros Zinelis, Ioannis Papathanasiou and George Eliades

J. Funct. Biomater. 2026, 17(4), 191; https://doi.org/10.3390/jfb17040191 - 15 Apr 2026

Viewed by 220

Abstract

In the original publication [...] Full article

(This article belongs to the Section Dental Biomaterials)

20 pages, 2967 KB

Open AccessArticle

Using Citric-Acid-Based Anodization to Form Magnesium-Doped Carbonated Apatite-Containing Oxides on Solid and 3D-Printed Titanium Substrates

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

J. Funct. Biomater. 2026, 17(4), 190; https://doi.org/10.3390/jfb17040190 - 14 Apr 2026

Viewed by 414

Abstract

With increasing life expectancy and an aging global population, the demand for orthopedic and dental implants is increasing. Recently developed, citric-acid-based anodization processes facilitate the production of more bioactive oxide layers by incorporating important bone minerals such as Ca, P, and Mg and [...] Read more.

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

(This article belongs to the Special Issue Drug- and Ion-Releasing Implants)

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20 pages, 11367 KB

Open AccessArticle

Design and Development of Teixobactin Analog-Loaded Magnetic Nanocomposites for Biofilm Destruction and Pathogen Elimination

by Huaxiang Lei, Ye Liang, Xuechen Li, Xiaojing Huang, Chengfei Zhang and Ting Zou

J. Funct. Biomater. 2026, 17(4), 189; https://doi.org/10.3390/jfb17040189 - 13 Apr 2026

Viewed by 283

Abstract

Although teixobactin, a promising cyclic undecadepsipeptide, exhibits efficacy against Gram-positive bacteria due to its novel mode of action and low potential for resistance, its clinical application is limited by two key shortcomings: ineffectiveness against Gram-negative bacteria and poor penetration of the protective extracellular [...] Read more.

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

(This article belongs to the Section Antibacterial Biomaterials)

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24 pages, 13960 KB

Open AccessArticle

Evaluation of Post-Processing Time’s Influence on Biocompatibility of 3D-Printed Denture Base Resins

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

J. Funct. Biomater. 2026, 17(4), 188; https://doi.org/10.3390/jfb17040188 - 12 Apr 2026

Viewed by 492

Abstract

In the continuous development of additive technologies and light-sensitive resins, the biological performance of 3D-printed resins is strongly dependent on photopolymerization efficiency and post-processing conditions. This study evaluated the effect of post-curing duration on the cellular response to two denture base resins using [...] Read more.

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

(This article belongs to the Section Dental Biomaterials)

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24 pages, 4530 KB

Open AccessArticle

Granulate-to-Filament: An Extrusion-Mixed PLA–Human Bone Material System for 3D-Printed Bone Scaffolds

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

J. Funct. Biomater. 2026, 17(4), 187; https://doi.org/10.3390/jfb17040187 - 11 Apr 2026

Viewed by 472

Abstract

Fused filament fabrication (FFF) enables patient-specific scaffolds for critical-size bone defects, but most filaments are bioinert and difficult to functionalize at high particulate loadings due to segregation, agglomeration, clogging, and diameter instability. We developed a mechanism-guided extrusion toolkit to stabilize polylactic acid (PLA) [...] Read more.

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

(This article belongs to the Special Issue Translational Biomedical Devices and Biomaterials: Bridging Biology, Engineering and Medicine)

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17 pages, 3087 KB

Open AccessArticle

Bone Regeneration After Maxillary Sinus Augmentation with Allogeneic and Xenogeneic Biomaterials with Adjunctive Photobiomodulation: Histological and Radiological Secondary Outcomes of a Randomized Clinical Trial

by Sebastian Dominiak, Aleksandra Piotrowska, Marzena Dominiak, Tomasz Gedrange, Piotr Dzięgiel, Alicja Baranowska, Michał Ciszyński, Jakub Hadzik and Paweł Kubasiewicz-Ross

J. Funct. Biomater. 2026, 17(4), 186; https://doi.org/10.3390/jfb17040186 - 10 Apr 2026

Viewed by 380

Abstract

Background: Atrophy of the alveolar ridge in the posterior maxilla often requires sinus floor elevation prior to implant placement. Photobiomodulation using low-level laser therapy (LLLT) has been suggested as a supportive approach for bone healing, although data based on histological evaluation are still [...] Read more.

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

(This article belongs to the Special Issue New Biomaterials in Periodontology and Implantology)

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20 pages, 4154 KB

Open AccessArticle

Potentiation of a Porous Silicon Therapeutic Vaccine in Colorectal Cancer via Oxaliplatin-Mediated Regulation of Myeloid-Driven Immunosuppression

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

J. Funct. Biomater. 2026, 17(4), 185; https://doi.org/10.3390/jfb17040185 - 10 Apr 2026

Viewed by 461

Abstract

Although immunotherapy has shown great promise in treating various types of cancer, advanced tumors are often refractory due to a highly immunosuppressive tumor microenvironment (TME). We previously engineered a cancer therapeutic vaccine platform, µGCVax, by co-loading tumor antigen peptides, STING and TLR9 agonists [...] Read more.

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

(This article belongs to the Special Issue Functional Porous Materials for Biomedical Applications)

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41 pages, 3003 KB

Open AccessReview

Advances and Challenges in Tissue Engineering: Biomaterials, Cellular Strategies, and Clinical Applications

by Rosana Farjaminejad, Samira Farjaminejad, Franklin Garcia-Godoy, Anand Marya, Ludovica Nucci and Abdolreza Jamilian

J. Funct. Biomater. 2026, 17(4), 184; https://doi.org/10.3390/jfb17040184 - 10 Apr 2026

Viewed by 460

Abstract

Tissue engineering integrates concepts from medicine, biology, and engineering to create living constructs capable of repairing, replacing, or supporting damaged tissues. This multidisciplinary field relies on the interplay between biomaterials, cellular sources, and bioactive signaling to achieve functional tissue regeneration. This review provides [...] Read more.

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

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

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27 pages, 8951 KB

Open AccessArticle

Comparative Late Effects of Hemostatic Biomaterials on Wound Healing at 14 and 30 Days: An In Vivo Animal Study

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

J. Funct. Biomater. 2026, 17(4), 183; https://doi.org/10.3390/jfb17040183 - 9 Apr 2026

Viewed by 472

Abstract

Hemostatic biomaterial agents are widely used during surgery and trauma care to control bleeding, yet their effects on wound healing remain incompletely understood. This study evaluated the impact of oxidized non-regenerated cellulose (ONRC), oxidized regenerated cellulose (ORC), and a gelatin-based hemostat (GELA) on [...] Read more.

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

(This article belongs to the Special Issue Biomaterials for Hemostasis and Wound Healing Applications)

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22 pages, 1009 KB

Open AccessReview

Biological Effects on S-PRG: An Integrative Review

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

J. Funct. Biomater. 2026, 17(4), 182; https://doi.org/10.3390/jfb17040182 - 9 Apr 2026

Viewed by 452

Abstract

Advances in dental material science over recent decades have significantly improved the mechanical, physical, esthetic, and adhesive properties of restorative systems. As clinical performance and durability have reached high standards, research has progressively shifted from purely mechanical replacement toward the development of bioactive [...] Read more.

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

(This article belongs to the Section Dental Biomaterials)

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23 pages, 20628 KB

Open AccessArticle

Osteogenic and Anti-Inflammatory Effects of Strontium-Loaded Polydopamine on Micro-Arc Oxidized Titanium Surfaces

by Yiming Yang, Rongpu Liu, Yuqi Zhou, Lingjun Yuan, Zhenxia Li, Qian Liao and Bing Fang

J. Funct. Biomater. 2026, 17(4), 181; https://doi.org/10.3390/jfb17040181 - 7 Apr 2026

Viewed by 597

Abstract

Titanium implants are widely used in orthopedic and dental fields but often face challenges such as insufficient osseointegration and peri-implant inflammation. While Strontium (Sr) possesses potent bioactive properties, achieving its controlled delivery at the implant-tissue interface remains technically challenging. To address this, we [...] Read more.

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

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

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21 pages, 20623 KB

Open AccessArticle

Development and Ex Vivo Evaluation of a Thermoreversible Silver Nanoparticle-Loaded Gel as a Biocompatible Intracanal Medicament

by Shih-Min Hsia, Ming-Gene Tu, Wen-Hao Yang, Tong-Hong Wang, Yin-Hwa Shih and Tzong-Ming Shieh

J. Funct. Biomater. 2026, 17(4), 180; https://doi.org/10.3390/jfb17040180 - 6 Apr 2026

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Abstract

Inspired by their biocompatibility and thermoreversible gelation—transitioning from room temperature liquids to body temperature gels—Pluronic hydrogels were employed in this study to optimize intracanal penetration and ensure medicament stability. We developed a silver nanoparticle (AgNP)-loaded Pluronic gel (AgNPs-P-gel) as a biocompatible, easily removable [...] Read more.

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

(This article belongs to the Topic Clinical and Experimental Research in Dentistry and Bioactive Materials, 2nd Edition)

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17 pages, 14168 KB

Open AccessArticle

Structure and Mechanical Properties of Ti-38Zr-(8-10)Nb (at. %) Alloys for Medical Use

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

J. Funct. Biomater. 2026, 17(4), 179; https://doi.org/10.3390/jfb17040179 - 3 Apr 2026

Viewed by 355

Abstract

The research described in this article is a continuation of a series of studies on biocompatible materials, focused on finding the optimal alloy composition and heat treatment regimes. The use of materials with a low Young’s modulus ensures the long-term safety of the [...] Read more.

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

(This article belongs to the Section Bone Biomaterials)

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38 pages, 3976 KB

Open AccessReview

Multiscale Interface Engineering for Orthopedic and Dental Implants: A Review

by Fiza Ashraf and Ataf Ali Altaf

J. Funct. Biomater. 2026, 17(4), 178; https://doi.org/10.3390/jfb17040178 - 3 Apr 2026

Viewed by 769

Abstract

Multiscale interface engineering has influenced the engineering of orthopedic and dental implants through the integration of macroscale architecture, micro-textured surfaces and nanoscale bio-cues. These characteristics help to increase mechanical stability and support early biological responses, as well as increase resistance to microbial colonization. [...] Read more.

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

(This article belongs to the Special Issue New Biomaterials in Periodontology and Implantology)

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22 pages, 10104 KB

Open AccessArticle

Biomimetic Chitosan/Polyvinyl Alcohol–Glycerol Scaffolds Inspired by Porcupine Quills for Segmental Bone Defect Repair

by Jingwen Yang, Zihao Zhao, Zengtao Song, Lei Cao, Xifan Mei and Xing Zhang

J. Funct. Biomater. 2026, 17(4), 177; https://doi.org/10.3390/jfb17040177 - 3 Apr 2026

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Abstract

Segmental bone defects are large, non-healing injuries characterized by insufficient structural support and limited bioactivity, posing a significant clinical challenge. In this study, we developed biomimetic chitosan/polyvinyl alcohol–glycerol (CS/PG) scaffolds inspired by porcupine quills, which were fabricated via fused deposition modeling and unidirectional [...] Read more.

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

(This article belongs to the Section Bone Biomaterials)

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J. Funct. Biomater., Volume 17, Issue 4 (April 2026) – 48 articles

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