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Journal Of Functional Biomaterials[JOURNAL]

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Synergistic Liposomal Delivery of Ibrexafungerp Citrate and Marine-Sourced Silver Nanoparticles for Effective Management of Vulvovaginal Candidiasis.

Shyam Sundar P, Patil UKS, Sarjerao TP … +6 more , Bhinge SD, Galatage ST, Sambamoorthy U, Kadam RJ, Solomon VR, Manjappa AS

J Funct Biomater · 2026 Jun · PMID 42346681 · Full text

BACKGROUND: Increasing antifungal resistance, poor mucosal retention, and systemic side effects limit the effectiveness of currently available drugs. This study explores a novel topical nanotherapeutic approach for the t... BACKGROUND: Increasing antifungal resistance, poor mucosal retention, and systemic side effects limit the effectiveness of currently available drugs. This study explores a novel topical nanotherapeutic approach for the targeted treatment of vulvovaginal candidiasis (VVC), employing green-synthesized silver nanoparticles (AgNPs) derived from (AN) and incorporating ibrexafungerp citrate (IBC) into a liposomal formulation. METHODS: AgNPs were biosynthesized using AN extract and characterized. Liposomes were prepared by thin-film hydration, and optimised using Central Composite design and characterized and optimized. Optimised liposomes, co-loaded with IBC and AN-AgNPs, were incorporated into a Carbopol-CMC-based topical gel. RESULTS: FTIR shifts in the -OH (3332.31 cm) and carbonyl (1636.87 cm) bands with reduced intensity confirmed their involvement in Ag reduction and nanoparticle surface coordination, while the persistence of the 1015 cm band indicated the role of polysaccharides in capping and stabilizing the AN-AgNP. Characterization of the optimized liposomes (IBCL-11) revealed a particle size of 127.2 nm, a zeta potential of -43.8 mV, and a polydispersity index (PDI) of 0.35. Transmission Electron Microscopy (TEM) confirmed the presence of intact, spherical vesicles, while Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD) validated the molecular dispersion and amorphous characteristics of the films. In vitro evaluations of the IBC liposomal gel demonstrated a sustained drug release of 72.6% over 24 h, alongside enhanced drug penetration across all skin layers. Antifungal assays highlighted the formulation's potent efficacy, yielding Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) values below 1 µg/mL. Furthermore, the treatments exhibited strong anti-biofilm properties; at MIC and MBC levels, AN-AgNPs achieved biofilm reductions of 45.27 ± 3.16% and 27.62 ± 2.13%, respectively, whereas IBCL-11 produced reductions of 34.25 ± 2.43% and 16.28 ± 1.72%. CONCLUSION: Ultimately, this study successfully developed an eco-friendly liposomal formulation co-loaded with AN-AgNPs and IBC, offering a promising and targeted therapeutic approach for the treatment of vulvovaginal candidiasis.

Influence of Printing Parameters and Nozzle Diameter on the Effective Microarchitecture and Compressive Modulus of Gyroid PCL Scaffolds.

González J, Flores ME, Uzcátegui LM … +1 more , Martínez G

J Funct Biomater · 2026 Jun · PMID 42346680 · Full text

Three-dimensional scaffolds based on triply periodic minimal surfaces (TPMSs) have attracted growing interest in bone tissue engineering because of their high interconnectivity and ability to combine high porosity with m... Three-dimensional scaffolds based on triply periodic minimal surfaces (TPMSs) have attracted growing interest in bone tissue engineering because of their high interconnectivity and ability to combine high porosity with mechanical integrity. However, in fused deposition modeling (FDM), printed architecture may systematically deviate from the nominal design, thereby affecting structural fidelity and mechanical performance. This study investigated the influence of FDM processing parameters and nozzle diameter on the effective microarchitecture and compressive elastic modulus of polycaprolactone (PCL) gyroid scaffolds. First, a Taguchi L18 design was used to evaluate the effects of extrusion temperature, printing speed, and flow rate on pore size for two nozzle diameters (0.4 and 0.3 mm). In a second experimental stage, prismatic specimens fabricated at three nominal porosity levels were compression-tested to determine the elastic modulus (E), and measured porosity (ϕ) was quantified by densimetric measurements. A systematic mismatch was observed between the nominal design and the printed scaffold architecture, with both pore size and measured porosity consistently lower than their intended values. The dominant process parameter associated with pore-size variability was nozzle-specific: extrusion temperature contributed most for the 0.4 mm nozzle, whereas printing speed contributed most for the 0.3 mm nozzle. In compression, E decreased with increasing measured porosity, and statistical analysis showed that the E-ϕ relationship was nozzle-dependent. Overall, these findings support a process-structure-property interpretation based on the effective printed microarchitecture rather than on nominal design parameters alone. The experimental stiffness ranges obtained here also provide an exploratory mechanical contextualization relative to reported trabecular bone domains, without implying site-specific scaffold selection.

Enhanced Osteogenic Differentiation of Primary Human Osteoporotic Osteoblasts on a Roughened Titanium Surface by Vitamin K2 and Vitamin D3 Compared to the Differentiation Behaviour of Primary Healthy Human Osteoblasts.

Tscheu K, Schultz K, Suschek CV … +1 more , Maus U

J Funct Biomater · 2026 Jun · PMID 42346679 · Full text

The number of patients who require endoprosthetic treatment related to osteoporosis has increased in recent years. Vitamin D3 supplementation has long been standard practice in osteoporosis treatment, while vitamin K2 ha... The number of patients who require endoprosthetic treatment related to osteoporosis has increased in recent years. Vitamin D3 supplementation has long been standard practice in osteoporosis treatment, while vitamin K2 has gained importance. Using our in vitro model, we compared the osteogenic behaviour of primary healthy human osteoblasts (hOBs) and primary osteoporotic human osteoblasts (hopOBs) under unchanged conditions, with vitamin K2, vitamin D3 and the combined addition. Fluorescence microscopy examinations on a plastic surface and a rough titanium surface structure revealed morphological differences. A quantitative analysis of mineralisation and differentiation was performed using an alizarin red S assay and analysis of alkaline phosphatase activity. It was shown that the hopOBs behave differently morphologically on the titanium surface, while hopOBs are particularly noticeable due to the higher number of cell-cell interactions with vitamin K2. The rough surface led to more pronounced mineralisation of the hopOBs. This effect was pronounced under vitamin K2. Vitamin D3 had an effect in the initial phase of hopOB differentiation. Overall, vitamin K2 had a greater influence on the mineralisation of hopOBs than expected. It must be assumed that vitamin K2 plays a significantly greater role in the metabolism of hopOBs than previously assumed.

The Effect of Er:YAG Laser Biomodification of the Implant Site Surface on Osseointegration: A Randomized Controlled Clinical Study.

Kanazirski N, Neychev D, Kanazirska P … +1 more , Miteva-Katrandzhieva T

J Funct Biomater · 2026 Jun · PMID 42346678 · Full text

: Er:YAG laser (λ = 2940 nm) biomodification of the implant osteotomy site removes the smear layer after rotary preparation and may enhance bone-implant contact. This randomized controlled clinical study evaluated implan... : Er:YAG laser (λ = 2940 nm) biomodification of the implant osteotomy site removes the smear layer after rotary preparation and may enhance bone-implant contact. This randomized controlled clinical study evaluated implant stability dynamics following Er:YAG laser biomodification using resonance frequency analysis (RFA). Ninety patients were randomized 1:1 into a case group ( = 45; rotary osteotomy + Er:YAG biomodification; 400 mJ, 17 Hz) and a control group ( = 45; rotary osteotomy alone). Implant stability quotient (ISQ) was measured by RFA in vestibulo-oral (VO) and mesiodistal (MD) directions at placement, days 10, 20, 30, and month 3. The case group showed significantly higher ISQ values at all time points in both directions (-test, < 0.05). Repeated measures ANOVA revealed a significant time × group interaction in the MD direction (F = 14.461, < 0.001, partial η = 0.341). Primary VO ISQ: 75.04 ± 4.27 (cases) vs. 72.29 ± 3.38 (controls); primary MD ISQ: 76.49 ± 4.29 vs. 72.89 ± 2.29. The proportion achieving ISQ ≥ 70 was consistently higher in the case group. Er:YAG laser biomodification combined with rotary osteotomy yields higher, more stable ISQ values throughout early healing in mandibular D2/D3 bone, potentially supporting shorter healing intervals and early loading in selected clinical situations.

Scaffold-Based Biomaterials for Periodontal Regeneration in Periodontitis: A Systematic Review and Meta-Analysis.

Beresescu FG, Mucenic S, Monea A … +2 more , Bors A, Beresescu L

J Funct Biomater · 2026 Jun · PMID 42346677 · Full text

BACKGROUND: Periodontitis is characterized by loss of the periodontal ligament, cementum, and alveolar bone. Scaffold-based biomaterials are intended to provide a three-dimensional framework for periodontal wound stabili... BACKGROUND: Periodontitis is characterized by loss of the periodontal ligament, cementum, and alveolar bone. Scaffold-based biomaterials are intended to provide a three-dimensional framework for periodontal wound stabilization and tissue regeneration, but their incremental clinical benefit over conventional regenerative therapy remains uncertain. This systematic review and meta-analysis evaluated scaffold-based periodontal regenerative procedures for probing depth (PD) reduction, clinical attachment level (CAL) gain, and radiographic defect fill compared with conventional treatment. METHODS: Original randomized controlled trials published from January 2020 to 1 March 2026 were searched in MEDLINE (Ovid), Embase, CENTRAL, and Web of Science, screened in Rayyan, and meta-analyzed in RevMan v5.4. Certainty was evaluated using GRADE. RESULTS: Thirty-one studies were included. Scaffold-based interventions produced statistically significant but clinically modest PD reductions at 6 months (MD = -0.27 mm; 95% CI: -0.43 to -0.10; = 0.001; I = 34%) and 12 months (MD = -0.21 mm; 95% CI: -0.41 to -0.01; = 0.04; I = 22%), but not at 24 months. The overall PD effect was small (MD = -0.26 mm; < 0.0001). CAL gain was not significant at 6 or 12 months but was significant at 24 months (MD = 1.00 mm; < 0.0001; I = 0%). Defect fill improved at 12 months (MD = 0.51 mm; = 0.02) but not at 6 months. Subgroup and meta-regression analyses did not identify significant effects of scaffold type or PRF/PRP enrichment ( > 0.05). CONCLUSIONS: Scaffold-based biomaterials may provide limited, time-dependent clinical and radiographic benefits as adjuncts to conventional periodontal regenerative therapy. The evidence remains constrained by heterogeneous interventions, modest effect sizes, low-to-very-low certainty for several outcomes, and a paucity of histologic confirmation of true periodontal regeneration.

Individual, High-Precision 3D Mandibular Model for Finite Element Analysis of Three-Unit Bridges: A Biomechanical Pilot Study.

Pelsőczi-Kovács I, Deák B, Papp K … +1 more , Piros AI

J Funct Biomater · 2026 Jun · PMID 42346676 · Full text

Tooth-supported fixed partial dentures (FPDs) exhibit complex biomechanical behaviour because occlusal loads are transferred through the periodontal ligament (PDL) and heterogeneous mandibular bone. This pilot study aime... Tooth-supported fixed partial dentures (FPDs) exhibit complex biomechanical behaviour because occlusal loads are transferred through the periodontal ligament (PDL) and heterogeneous mandibular bone. This pilot study aimed to develop a patient-specific NURBS-based finite element analysis (FEA) workflow for anatomically realistic mandibular reconstruction and to evaluate the biomechanical effect of geometric simplification in tooth-supported FPD simulations. Cone beam computed tomography data from a single subject were segmented and reconstructed into a layered three-dimensional model of the mandible and dentition, including cortical bone, cancellous bone, teeth, and PDL. A high-fidelity reference model (V0) and four simplified variants (V1-V4) were analysed under static 500 N loads applied at 0° and 30°. The reference model yielded a maximum von Mises stress of 507 MPa and a peak displacement of 0.74 mm, with stress concentrations consistently localised at the retainer-pontic connector region. Inclusion of the PDL markedly affected the mechanical response, doubling denture displacement in simplified comparative models. Among the simplified configurations, V4, which preserved cortical morphology and PDL representation while omitting detailed trabecular architecture, showed the closest agreement with the reference model, with mean deviations of 6.1% and 5.8% under the two loading conditions, respectively. These findings suggest that patient-specific NURBS-FEA modelling provides a robust framework for biomechanical assessment of tooth-supported FPDs, while controlled simplification may improve computational efficiency without substantially compromising accuracy under static loading conditions.

Physicochemical Stability of Dentin-Derived Biomaterials During Long-Term Storage.

Dłucik R, Scoglio A, Puzzolo D … +5 more , Testagrossa B, Alibrandi A, Toscano A, Orzechowska-Wylęgała B, Acri G

J Funct Biomater · 2026 Jun · PMID 42346675 · Full text

Dentin-derived biomaterials are hierarchical collagen-mineral composites increasingly used as bio-based scaffolds for bone regeneration. However, the effect of prolonged storage of extracted teeth on their physicochemica... Dentin-derived biomaterials are hierarchical collagen-mineral composites increasingly used as bio-based scaffolds for bone regeneration. However, the effect of prolonged storage of extracted teeth on their physicochemical integrity remains unclear. This study evaluated the stability of dentin-derived biomaterials following long-term refrigerated storage (up to six years) using Raman spectroscopy. Extracted human teeth were processed using three preparation systems (BonMaker, Tooth Transformer, and Smart Dentin Grinder), and Raman-derived indices describing mineral and collagen structure were compared with freshly extracted controls. No time-dependent changes were observed in mineral crystallinity, carbonate substitution, or collagen-related parameters, indicating preservation of the collagen-mineral interface during storage. In contrast, the observed differences were primarily associated with processing pathways. Tooth Transformer and Smart Dentin Grinder exhibited Raman profiles closely resembling native dentin, whereas BonMaker showed reduced mineral content and altered mineral-matrix balance consistent with its demineralization protocol. These findings demonstrate that dentin behaves as a structurally stable hierarchical composite, reflecting intrinsic structural organization that limits physicochemical degradation over time. Long-term storage does not compromise dentin integrity, supporting its use as a reliable source of biomaterial for regenerative applications and future tooth banking strategies.

Evaluation of the Effects of Implants with Different Geometries on the Inferior Alveolar Nerve Under Occlusal Stresses.

Karahan D, Çinar İÇ

J Funct Biomater · 2026 Jun · PMID 42346674 · Full text

Dental implant placement in the posterior mandible can be challenging due to the presence of the inferior alveolar nerve (IAN). Biomechanical factors related to implant design and loading may also influence nerve compres... Dental implant placement in the posterior mandible can be challenging due to the presence of the inferior alveolar nerve (IAN). Biomechanical factors related to implant design and loading may also influence nerve compression. This study aimed to investigate the influence of implant geometry, diameter, length, and implant-canal distance on IAN pressure. Dental implants with two geometries (tapered and cylindrical), two lengths (8 and 12 mm), and two diameters (3.3 and 4.1 mm) were virtually positioned at three implant-canal distances (0.5, 1.0, and 1.5 mm). A total of 24 finite element models were generated. Functional occlusal loading was simulated using a 300 N vertical force and a 100 N oblique force applied at a 45° angle. The resulting IAN pressure values were determined. The implant diameter affected IAN pressure, with 3.3 mm implants yielding higher values than 4.1 mm implants. Longer implants exhibited lower pressure values than shorter implants. Cylindrical implants generated higher pressure than tapered implants. Increasing the implant-canal distance from 0.5 to 1.5 mm reduced nerve pressure. Vertical loading yielded higher pressure values than oblique loading. The implant-canal distance was the primary factor influencing IAN pressure. Implant diameter and geometry had secondary effects, whereas implant length had a limited influence. These findings highlight the importance of implant planning and design selection to reduce load transfer to the IAN.

Targeting Biofilms in Chronic Wounds: Emerging Strategies with Antimicrobial Nanocomposites.

Guerrero-Rodriguez ID, Nguyen CM, Nguyen KT … +1 more , Soto-Garcia L

J Funct Biomater · 2026 Jun · PMID 42346673 · Full text

Chronic wounds present a significant challenge to healthcare systems globally, affecting approximately 1% of the population and severely impacting their quality of life. Biofilm development occurs in approximately 90% of... Chronic wounds present a significant challenge to healthcare systems globally, affecting approximately 1% of the population and severely impacting their quality of life. Biofilm development occurs in approximately 90% of chronic wounds, contributing to an increased prevalence of polymicrobial infections. Currently, there is a large quantity of antimicrobial topical treatments, dressings, and advanced therapies. However, many of them are hindered by the complex biofilm environment, antibiotic resistance, and/or host tissue toxicity. Furthermore, conventional treatments such as debridement, systemic/local antibiotics, and negative-pressure therapy are often ineffective at eradicating biofilms and fostering optimal healing conditions. Nanomedicine approaches have shown promising potential to address the limitations of current treatments. In this review, we discuss the pathophysiology of chronic wounds, the role of biofilms, microenvironmental changes, current treatments and their limitations, and nanocomposite-based strategies to eradicate biofilms and resolve chronic wounds.

Advances in GelMA Hydrogel-Enabled Angiogenic-Osteogenic Coupling: From Structural Programming to Exogenous Cue Synergy.

Hu C, Zhang M, Jiang H … +8 more , Qu Y, Meng Q, Tian J, Zhang H, Yang Z, Lin Z, Xing B, Zhang P

J Funct Biomater · 2026 Jun · PMID 42346672 · Full text

Vascular-osteogenic coupling plays a central regulatory role in bone regeneration, but it is frequently impaired under pathological conditions, including aging, ischemia, and chronic inflammation, which compromises effic... Vascular-osteogenic coupling plays a central regulatory role in bone regeneration, but it is frequently impaired under pathological conditions, including aging, ischemia, and chronic inflammation, which compromises efficient bone repair. Gelatin methacryloyl (GelMA) hydrogels, which combine extracellular matrix-like bioactivity, adjustable mechanical properties, and compatibility with three-dimensional biomanufacturing, have become a widely used material platform for vascularized bone regeneration. From the perspective of vascular-osteogenic coupling, this review reframes and synthesizes GelMA-based approaches for vascularized bone regeneration, grouping existing strategies into three categories: (i) intrinsic material design, in which pore architecture, microchannels, dynamic networks, and interfacial functionalization are used to guide vascular ingrowth; (ii) exogenous bioactive delivery, involving growth factors, extracellular vesicles, cells, and inorganic ions to enhance vascularization; and (iii) smart responsive strategies, including ROS/pH-responsive systems, sequential release, and external stimulation, which aim to recapitulate the evolving microenvironment during bone repair. This review further compares these strategies in terms of evidence level, reproducibility, and translational potential. Exogenous delivery systems currently have the strongest preclinical support, but issues related to dose standardization, burst release, and long-term safety remain unresolved. Intrinsic material programming is less extensively studied, yet may be more compatible with manufacturing consistency, sterilization, and engineering translation. Most stimuli-responsive systems, by contrast, remain largely at the small-animal or proof-of-concept stage. Future GelMA-based systems should therefore shift from increasing functional complexity toward improving predictability, reproducibility, and clinical feasibility. Compositionally defined and structurally controllable GelMA composites that integrate vascular regulation with mechanical support may provide a more realistic path for vascularized bone regeneration.

Histomorphometric Evaluation of Non-Thermal Plasma-Treated Xenogenic Bone Graft for Enhanced Bone Regeneration in a Rabbit Calvarial Defect Model.

Choi H, Moon YS, Kim HG … +1 more , Sohn DS

J Funct Biomater · 2026 Jun · PMID 42346671 · Full text

When placing dental implants, xenografts are most commonly used clinically to compensate for the insufficient bone volume of patients. However, xenografts have limitations including low osteoinductive capacity and prolon... When placing dental implants, xenografts are most commonly used clinically to compensate for the insufficient bone volume of patients. However, xenografts have limitations including low osteoinductive capacity and prolonged healing time. This study aimed to determine whether non-thermal plasma treatment could enhance the regenerative performance of bovine cancellous bone graft (SANTA-OSS) in a rabbit calvarial defect model. Twenty-four adult male New Zealand white rabbits received bilateral 8 mm critical-size calvarial defects. One defect was filled with untreated SANTA-OSS (control) and the contralateral defect with plasma-treated SANTA-OSS using the ACTILINK™ Reborn device. Animals were sacrificed at 2, 4, and 8 weeks ( = 8 per group) for histomorphometric analysis. The plasma-treated group showed significantly higher new bone area (14.12 ± 0.69%, 18.93 ± 0.68%, and 32.72 ± 0.61% at 2, 4, and 8 weeks) than the control at all time points ( < 0.05). In addition, the experimental group exhibited accelerated graft resorption, larger bone marrow area, greater blood vessel area, and more TRAP-positive osteoclasts compared with the control ( < 0.05). Within the limitations of this study, non-thermal plasma treatment significantly enhanced new bone formation and promoted favorable graft remodeling, while also accelerating graft resorption, increasing bone marrow area, and improving vascularization. These findings suggest that simple chairside plasma activation can improve the regenerative performance of xenografts.

Clinical and Radiographic Outcomes of Locking-Plate Fixation Augmented with a Porous Hydroxyapatite Bone Substitute for Proximal Humerus Fractures: A Retrospective Cohort Study with 12-Month Follow-Up.

Saracco A, Massari L, Amadio M … +2 more , Menin R, Caruso G

J Funct Biomater · 2026 Jun · PMID 42346670 · Full text

BACKGROUND: Evidence on the role of synthetic biomimetic bone substitutes in the surgical management of proximal humerus fractures remains limited. This study aimed to evaluate the clinical, radiographic, and safety outc... BACKGROUND: Evidence on the role of synthetic biomimetic bone substitutes in the surgical management of proximal humerus fractures remains limited. This study aimed to evaluate the clinical, radiographic, and safety outcomes of a porous hydroxyapatite bone substitute used as an adjunct to locking-plate fixation in proximal humerus fractures with metaphyseal bone loss. METHODS: We performed a retrospective comparative cohort study including 45 patients treated with locking-plate fixation and porous hydroxyapatite scaffold augmentation and 40 comparable control patients treated with locking-plate fixation without scaffold augmentation. Patients were evaluated clinically and radiographically at 1, 3, 6, and 12 months after surgery. Functional outcome was assessed with the Constant-Murley Score (CMS), and pain was assessed using the Visual Analogue Scale (VAS). Longitudinal changes over time were analyzed using mixed-effects models for repeated measures. RESULTS: CMS improved progressively over follow-up, whereas VAS pain scores decreased significantly over time. No cases of device migration or radiographic resorption were observed during follow-up. Adverse events were recorded, but no complication was considered directly attributable to the implanted biomaterial. Functional recovery and pain reduction followed a similar trajectory in both groups, with no significant group-by-time interaction. CONCLUSIONS: In this retrospective series, graft augmentation with a porous hydroxyapatite scaffold during locking-plate fixation of proximal humerus fractures with bone void was associated with progressive functional improvement and pain reduction, without evident device-related safety concerns. Owing to the retrospective, non-randomized design, limited sample size, potential selection bias, and incomplete follow-up in part of the cohort, these findings should be interpreted as supportive of feasibility and short- to mid-term safety rather than as definitive evidence of biomaterial efficacy. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Research Progress and Translational Perspectives of Piezoelectric Materials in Dental Implant Surface Engineering.

Cao X, Hu J, Pang Q … +3 more , Jiang Q, Chen S, Luo B

J Funct Biomater · 2026 Jun · PMID 42346669 · Full text

The long-term stability of dental implants is limited by multiple factors, including peri-implant infection, impaired osseointegration, and poor soft tissue sealing. Compared with conventional passive surface modificatio... The long-term stability of dental implants is limited by multiple factors, including peri-implant infection, impaired osseointegration, and poor soft tissue sealing. Compared with conventional passive surface modification strategies, piezoelectric materials can convert mechanical energy into local electrical signals under occlusal loading, cell traction, or ultrasonic stimulation. With the aid of defect engineering, heterostructure construction, and co-catalytic design, these materials can also induce the generation of reactive oxygen species and reactive nitrogen species, thereby enabling on-demand antibacterial activity. This review systematically summarizes the bioelectric basis of bone tissue and clarifies how piezoelectricity and piezocatalysis may be used in dental implant surface engineering. Their applications are discussed in terms of antibiofilm and antibacterial activity, osteogenesis and osseointegration, osteoimmunomodulation, soft tissue healing, and temporally programmed therapy. In addition, this review also discusses issues that remain unresolved, such as polymer-based composite systems, realistic activation windows, evaluation standards, device-material integration, and multi-omics validation. Overall, piezoelectric surface engineering is evolving from a single osteogenesis-oriented strategy into an integrated platform that coordinates infection control, immune remodeling, and osseointegration. However, the actual effectiveness of its clinical application still needs to be determined through more rigorous mechanism analysis, long-term stability assessment, biosafety assessment, and standardized preclinical research.

The Influence of Mechanical and Microstructural Characteristics on the Durability of a Femoral Implant Made of Different Alloys.

Panfilov I, Sadyrin E, Nikolaev A … +6 more , Antipov P, Vasiliev A, Vilkovyskiy I, Pantiulin A, Ananova O, Meskhi B

J Funct Biomater · 2026 Jun · PMID 42346668 · Full text

The long-term success of orthopedic implants is fundamentally dependent on the synergy between mechanical performance and biological integration. Thus, a comprehensive investigation of both mechanical characteristics and... The long-term success of orthopedic implants is fundamentally dependent on the synergy between mechanical performance and biological integration. Thus, a comprehensive investigation of both mechanical characteristics and microstructural parameters is essential for the development of reliable implant systems in hip arthroplasty, both in human medicine and veterinary practice. The present study provides a detailed analysis of the mechanical properties, microstructure, and chemical composition of a Ti-6Al-4V-based femoral implant using nanoindentation, scanning electron and optical microscopy, and energy-dispersive X-ray spectroscopy. Then, using finite element analysis, the influence of Young's modulus on the stress-strain state of the endoprosthesis was evaluated. Dynamic loading conditions were considered by analyzing an impact on a cantilever beam, simulating an animal's jump onto a supporting limb. For reliable numerical simulation, the model geometry was constructed utilizing computed X-ray microtomography. The numerical simulations were performed for three material cases: reference Ti-6Al-4V, experimentally characterized Ti-6Al-4V (with properties determined by nanoindentation), and CoCrMo alloy, which is also widely used in endoprosthetic applications. The influence of the founded mechanical characteristics on the stress-strain state of the prostheses was assessed. In particular, the results indicate that under dynamic loading conditions, the load-bearing capacity of CoCrMo is lower by approximately 30% and 21% compared to the reference and experimentally characterized Ti-6Al-4V, respectively.

Effects and Properties of Deproteinizing Methods in Dentin: A Comprehensive Narrative Review.

Belmar da Costa M, Mano Azul A, Sauro S … +1 more , Delgado AHS

J Funct Biomater · 2026 Jun · PMID 42346667 · Full text

Dentin deproteinization strategies are being revisited as adjunctive approaches to reduce technique sensitivity, improve monomer infiltration to mineralized dentin, and enhance the longevity of resin-dentin interfaces. T... Dentin deproteinization strategies are being revisited as adjunctive approaches to reduce technique sensitivity, improve monomer infiltration to mineralized dentin, and enhance the longevity of resin-dentin interfaces. This organized narrative review critically summarizes the chemistry, kinetics, biological considerations, and clinical translatability of agents used for smear-layer deproteinization or post-etching deproteinization. Searches of PubMed/MEDLINE, Scopus, and LILACS up to October 2025 were used to identify evidence on oxidizing irrigants (sodium hypochlorite/hypochlorous acid, calcium hypochlorite, peracetic acid, chlorine dioxide), enzymatic proteolysis treatments (bromelain, papain, trypsin/pepsin, and GAG-targeting enzymes), physical approaches (heat and lasers), and post-oxidizer reducing/antioxidant strategies. Oxidizers provide the fastest and most surface-verified organic removal, but their clinical value is limited by concentration- and time-dependent oxidative carry-over, which interferes with free-radical polymerization. Enzymes offer a more selective route, although their support is driven largely by bond strength and morphological outcomes rather than direct surface-chemical confirmation. Heat remains a proof-of-principle method rather than a clinical option, whereas laser protocols are highly parameter-sensitive. Overall, deproteinization should be interpreted through a combined framework of surface chemistry, adhesive compatibility, aging behavior, biosafety, and chairside feasibility. Current evidence supports cautious, protocol-specific development rather than routine clinical adoption, with priority given to clinically realistic time-dose windows and paired surface/aging outcomes.

The Influence of Ageing and Hydrothermal Fatigue (Thermocycling) on Degradation and Fracture Toughness of Light-Cured and Hybrid Resin-Based Nanocomposites (RBCs).

Pieniak D, Niewczas AM, Walczak A … +3 more , Selech J, Czarnecka-Komorowska D, Matijošius J

J Funct Biomater · 2026 Jun · PMID 42346666 · Full text

The aim of this study was to evaluate the influence of artificial saliva ageing and cyclic hydrothermal loading on the mechanical properties of dental composite materials. Two commercial composites (Filtek Z550 and Filte... The aim of this study was to evaluate the influence of artificial saliva ageing and cyclic hydrothermal loading on the mechanical properties of dental composite materials. Two commercial composites (Filtek Z550 and Filtek Ultimate Flow) and two experimental materials representing flow-type and hybrid composites were investigated. SENB specimens were prepared in accordance with ASTM E399, together with flat specimens intended for impact strength testing using the Dynstat method. All samples were aged in artificial saliva for approximately one month at 37 ± 1 °C, and subsequently, half of the specimens were subjected to thermocycling in the temperature range of 10-65 °C for 10,000 cycles. Static mechanical tests, including three-point bending (TFS), biaxial flexural strength (BFS), and compression strength (CS), were performed before and after thermocycling. In addition, impact strength and fracture toughness expressed by the stress intensity factor K were determined. The results were analyzed in terms of the residual work of fracture (WOF), while the durability of the materials was evaluated using Weibull distribution parameters. The experimental analysis was complemented by SEM observations of the microstructure. The obtained results demonstrated a pronounced deterioration of mechanical properties after hydrothermal loading. The average impact strength after artificial saliva ageing reached 11.69 J/mm for Filtek Z550, 11.57 J/mm for Ex-hyb(P), 16.39 J/mm for Filtek Ultimate Flow, and 10.27 J/mm for Ex-flow(P), whereas after thermocycling, these values decreased to 5.38 J/mm, 8.86 J/mm, 4.55 J/mm, and 4.39 J/mm, respectively. A similar trend was observed for the fracture toughness parameter KIC, which decreased considerably after thermocycling for all investigated materials. The analysis of the residual work of fracture revealed the influence of thermocycling on the energy-related parameters of the composites. In the case of TFS, the average WOF decreased, among others, from 13.65·10 J to 1.90·10 J for Filtek Ultimate Flow and from 4.76·10 J to 2.37·10 J for Filtek Z550. For BFS, a noticeable decrease in WOF was also observed, particularly for Ex-flow(P) and Filtek Ultimate Flow. In the compression tests (CS), the changes were less unambiguous, and some materials exhibited an increase in WOF after thermocycling. Furthermore, changes in the scale and shape parameters of the Weibull distribution were identified, indicating degradation of composite durability under hydrothermal loading. The results confirmed that cyclic hydrothermal loading exerts a greater influence on impact strength and fracture toughness than on static flexural strength. While all investigated materials exhibited degradation, the extent of changes was material-dependent, and compression behaviour showed non-uniform responses. Weibull analysis confirmed reduced reliability and increased heterogeneity of the composites after ageing, indicating that hydrothermal fatigue is a dominant factor governing long-term mechanical deterioration of dental resin-based composites.

Alkaline Ozonation-Induced TiO Nanoscaffold on Titanium Alloy for Surface-Mediated Osteogenic Guidance.

Winiecki M, Krawczyk P, Reczyńska-Kolman K … +3 more , Pudełko-Prażuch I, Pamuła E, Trzcinski M

J Funct Biomater · 2026 Jun · PMID 42346665 · Full text

Numerous surface modification strategies, particularly nanoengineering approaches, have been explored to tailor the physicochemical and topographical properties of titanium surfaces in order to enhance osteogenic respons... Numerous surface modification strategies, particularly nanoengineering approaches, have been explored to tailor the physicochemical and topographical properties of titanium surfaces in order to enhance osteogenic responses at the implant interface. In this study, we propose an alkaline ozonation strategy as a novel approach to generate nanostructured TiO layers on Ti-6Al-4V alloy surfaces. Titanium discs were treated in a 6 M KOH solution under continuous bubbling of ozone, allowing the formation of reactive oxygen species (ROS) responsible for oxidative surface restructuring. Scanning electron microscopy (SEM) revealed the formation of a homogeneous three-dimensional TiO nanonetwork composed of intertwined nanofibers. X-ray photoelectron spectroscopy (XPS) confirmed the oxidative reconstruction of the Ti alloy surface. The fraction of Ti species characteristic of TiO increased markedly from 44.2 at% to 92.2 at%, accompanied by a strong reduction in Ti (from 40.2 at% to 5.8 at%) and Ti (from 15.7 at% to 2.1 at%). Concomitantly, lattice oxygen associated with Ti-O-Ti bonding increased from 48 at% to 78 at% as deduced from the O 1s signal, while the surface carbon content decreased from 48 at% to 18 at%. The modification induced a pronounced increase in surface hydrophilicity, with the water contact angle decreasing from 85° to 32° and the surface free energy increasing from 40.8 mJ/m to 69.8 mJ/m. In vitro studies demonstrated good cytocompatibility and enhanced osteogenic differentiation of human mesenchymal stem cells, with twice as much alkaline phosphatase activity after 14 days and mineralization of the extracellular matrix after 28 days than those on TCPS, and also significantly higher than those on the nonmodified Ti alloy control. These findings indicate that the generated three-dimensional TiO nanonetwork acts as a surface-confined nanoscaffold providing nanoscale cues that promote osteogenic cell responses on titanium implant surfaces.

Human BMP4 mRNA Encapsulated in Lipid Nanoparticle for Bone and Articular Cartilage Repair in Aged Mice.

Gao X, Xiao Z, Huard M … +9 more , Nakayama K, Cummings A, Force BS, Li H, Mancino C, Cooke JP, Taraballi F, Philippon MJ, Huard J

J Funct Biomater · 2026 Jun · PMID 42346664 · Full text

Segmental bone defects and age-related osteoarthritis (OA) are clinically challenging in terms of treatment. Although preclinical studies have demonstrated efficacy for bone defect healing and OA using ex vivo gene thera... Segmental bone defects and age-related osteoarthritis (OA) are clinically challenging in terms of treatment. Although preclinical studies have demonstrated efficacy for bone defect healing and OA using ex vivo gene therapy or biomaterial sustained-release delivery, few such treatments have translated into clinical therapies due to safety concerns. Bone morphogenetic proteins belong to the transforming growth factor β (TGFβ) superfamily and are effective in bone and cartilage regeneration/repair. Among BMPs, BMP4 is not only effective in promoting bone and cartilage repair but also promotes stem cell renewal potential and exhibits anti-aging effects. Therefore, the aim of this study is to investigate whether human BMP4 mRNA encapsulated in lipid nanoparticles (hBMP4 mRNA/LNP) can promote bone and cartilage repair. In vitro data demonstrated that hBMP4 mRNA/LNP-treated human MSCs secreted BMP4 protein, as detected by ELISA, and enhanced osteogenic differentiation. In vivo results demonstrated that hBMP4 mRNA/LNP at a 50 µg dose promoted limited new bone formation only at 2 weeks after creation of defect in critical-sized calvarial bone defects in aged mice when delivered using fibrin sealant hydrogel, as revealed by micro-CT and histology. However, intra-articular injection (IA) of lower doses (2.5 and 5 µg) in aged mice knee joints prevented cartilage loss, as demonstrated by micro-CT; decreased OARSI histology scores; and improved cartilage-specific matrix COL2. hBMP4 mRNA/LNP at a 5 μg dose significantly increased SOX9 cells per normalized cartilage area as well as the percentage of SOX9 cells in the cartilage area. hBMP4 mRNA/LNP treatment showed a trend of pain alleviation and did not change serum hyaluronic acid levels. In conclusion, human BMP4 mRNA encapsulated in lipid nanoparticles improved cartilage repair and delayed cartilage degeneration in aged mice, while having a limited effect on bone healing, even at a higher dosage. These results suggest that hBMP4 mRNA encapsulated with lipid nanoparticles represents a promising treatment for age-related OA.

Convergence and Reducibility as Transferability Filters in Biomimetic Design.

Polašek O

J Funct Biomater · 2026 Jun · PMID 42346663 · Full text

Biomimetic design is often justified by the claim that evolution has refined biological systems under severe selective pressure; however, this claim is incomplete. Evolution does not produce optimal solutions, but constr... Biomimetic design is often justified by the claim that evolution has refined biological systems under severe selective pressure; however, this claim is incomplete. Evolution does not produce optimal solutions, but constrained trade-off resolutions. The translational question is therefore not whether a biological system performs the desired function, but whether the functional principle can survive separation from the system that produced it. Convergent evolution, where distantly related lineages independently arrive at similar solutions to the same functional problem, raises the probability that such solutions reflect physical or chemical constraints, which are stronger candidates for transfer into biomaterial design. Lineage-isolated solutions require a different test, namely whether the function reduces to a feature that can be reproduced outside the source organism. The argument is demonstrated through a convergence × reducibility matrix and an ex natura protocol from a biological phenomenon to a testable biomaterial claim. Biomimetics earns its place not as a universal design doctrine, but in those situations where evolutionary trade-off resolutions can survive translation into safe and manufacturable biomaterials.

Acid-Induced Surface Degradation of Metallic Biomaterials: Alloy-Dependent Behavior and Implications for Surface Functionality.

Niklai R, Szabó P, Kopniczky J … +6 more , Dergez T, Kolarovszki B, Kada O, Nagy Á, Turzó K, Frank D

J Funct Biomater · 2026 Jun · PMID 42346662 · Full text

Metallic biomaterials are frequently exposed to chemically aggressive environments that may compromise surface integrity and corrosion resistance. Acidic media containing organic acids represent a relevant challenge for... Metallic biomaterials are frequently exposed to chemically aggressive environments that may compromise surface integrity and corrosion resistance. Acidic media containing organic acids represent a relevant challenge for metallic systems, as they can destabilize passive oxide layers and promote surface degradation processes. The present in vitro study investigated acid-induced surface alterations in four commercially relevant orthodontic alloys-nickel-titanium (NiTi), copper-nickel-titanium (CuNiTi), titanium-molybdenum alloy (TMA), and stainless steel-as representative metallic biomaterials. Specimens were exposed to two commercially available acidic beverages with distinct pH conditions, followed by analysis of surface morphology, roughness, and elemental composition using atomic force microscopy (AFM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). The results demonstrated pronounced alloy-dependent differences in degradation behavior. Stainless steel and TMAs exhibited significant increases in surface roughness and morphological alterations, whereas NiTi-based alloys showed comparatively stable surface characteristics. Elemental analysis revealed material-specific compositional variations, suggesting selective surface modification processes under acidic exposure. These differences can be attributed to variations in alloy composition, microstructure, and the stability of passive oxide layers, which collectively govern corrosion resistance in metallic systems. The findings provide insight into acid-induced degradation mechanisms in metallic biomaterials and highlight the importance of material-dependent corrosion behavior under chemically aggressive conditions. These observations may have implications for surface-mediated biological responses and long-term functional performance of metallic biomaterials.
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