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Journal Of Functional Biomaterials[JOURNAL]

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Polyherbal-Mediated Synthesis of Copper Nanoparticles Using and : Cytotoxicity, Antioxidant Effect, and Antibacterial Potential Against Healthcare-Associated Pathogens.

Vijayakumar G, Raja A, Ganesan S … +4 more , Senthil TS, Kandasamy J, Senthil Kumaran P, Rangarajulu SK

J Funct Biomater · 2026 Apr · PMID 42042276 · Full text

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

Physicochemical Characterization of a Strontium Silicate-Based Root Canal Sealer Compared with Two Conventional Sealers.

Alsofi L

J Funct Biomater · 2026 Apr · PMID 42042275 · Full text

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

Additive vs. Subtractive Manufacturing of Zirconia: Influence on Surface Properties, Cell Viability, and Adhesion.

Kalyoncuoğlu ÜT, Baysal N, Akca G … +2 more , Ayyıldız S, Yilmaz B

J Funct Biomater · 2026 Apr · PMID 42042274 · Full text

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

Protein-Encoding Chemically Modified mRNAs for Musculoskeletal Tissue Regeneration and Repair.

Force BS, Gao X, Huard J

J Funct Biomater · 2026 Apr · PMID 42042273 · Full text

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

Development of Extracellular Matrix-Retaining Mesenchymal Stromal Cell Fibers for Novel Endovascular Regenerative Therapy for Aortic Disease.

Fukushima S, Teng L, Koizumi M … +5 more , Hasegawa-Ogawa M, Ohta H, Iwai R, Okano HJ, Ohki T

J Funct Biomater · 2026 Apr · PMID 42042272 · Full text

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

Effect of Implant Surface Decontamination Procedures on Surface Morphology-In Vitro Study.

Özay F, Ersanlı S

J Funct Biomater · 2026 Apr · PMID 42042271 · Full text

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

Characterization of Shells as Marine-Derived Bioceramics: Microstructural and Biological Insights for Tissue Engineering Applications.

Millán C, Benjumeda-Wijnhoven I, Contreras Raggio JI … +7 more , Muñoz A, Muñoz-Brautigam I, Álamos MF, Lardies MA, Santibañez JF, Lagos NA, Vivanco JF

J Funct Biomater · 2026 Apr · PMID 42042270 · Full text

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

Biological Impact of Extrusion Bioprinting Nasoseptal Chondrocytes for Tissue Engineering Applications.

Jovic TH, Roberts J, Zhao F … +2 more , Doak SH, Whitaker IS

J Funct Biomater · 2026 Apr · PMID 42042269 · Full text

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

Amine-Reactive Augmentation of Silk Fibroin Mats for Increasing Cargo Retention Capabilities.

Charles KL, Xing Y, Otto EL … +4 more , Ren X, Campbell PG, Vorp DA, Weinbaum JS

J Funct Biomater · 2026 Mar · PMID 42042268 · Full text

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

Comparison of Adhesive Strategies with Different Etching Approaches on the Clinical Performance of Restorations in Non-Carious Cervical Lesions: A Systematic Review and Network Meta-Analysis.

Chaple Gil AM, Pereda Vázquez L, Santiesteban Velázquez M … +1 more , Menéndez JJ

J Funct Biomater · 2026 Mar · PMID 42042267 · Full text

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

Sterilization-Induced Property Changes in FDM-Printed Carbon Fiber-Reinforced Polycarbonate for Medical Device Applications.

Remache A, Pavon W, Vinueza OJ … +3 more , Chicaiza J, Fuentes JM, Cadena H

J Funct Biomater · 2026 Mar · PMID 42042266 · Full text

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

Surface-Activated Zirconia Nanotubes with UV-Assisted Mg Deposition: Novel Bioinstructive Implants.

Raghu SNV, Badran Y, Periyannan S … +1 more , Killian MS

J Funct Biomater · 2026 Mar · PMID 41893214 · Full text

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

The Effect of Surface Pretreatments on the Bond Strength of Hybrid CAD/CAM with Composite Elevation.

Fildisi MA, Oglakci Ozkoc B, Ozduman ZC … +1 more , Eliguzeloglu Dalkilic E

J Funct Biomater · 2026 Mar · PMID 41893213 · Full text

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

Heparin-Based Biomaterials for Sustained Release of Growth Factors for Bone Tissue Engineering and Regeneration.

Nakayama K, Gao X, Force BS … +2 more , Philippon MJ, Huard J

J Funct Biomater · 2026 Mar · PMID 41893212 · Full text

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

A Borophosphate Glass Doped with Cobalt Oxide Improves Skeletal Muscle Structure and Function in Myopathic Mice.

Kendra JA, Naman AG, Blatt RL … +4 more , Zingariello CD, Brow RK, Segal SS, Morton AB

J Funct Biomater · 2026 Mar · PMID 41893211 · Full text

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

Hyaluronic Acid as an Adjunctive Therapy in Periodontal and Dental Treatment of Medically Compromised Patients: A Narrative Review.

Eliezer M, Christodorescu R, Belova A … +4 more , Rusu D, Milicescu S, Cohen M, Stratul SI

J Funct Biomater · 2026 Mar · PMID 41893210 · Full text

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

Amino-Modified Mesoporous Bioactive Glass Adsorbed with Osteopontin Enhances Osteogenic Differentiation and Matrix Mineralization via the Erk1/2 Signaling Pathway.

Yang Y, Lin K, Zhou Z … +5 more , Liu L, Liu L, Liu H, Mao H, Wang X

J Funct Biomater · 2026 Mar · PMID 41893209 · Full text

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

Green Palladium Nanoparticles: Mechanism of Synthesis and Biomedical Application.

Mikhailova EO

J Funct Biomater · 2026 Mar · PMID 41893208 · Full text

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

A Flexible and Thermally Uniform TiO/Ag/SiO Transparent Heater for Skin-Integrated Applications.

Jo J, Kang G, Lee C … +2 more , Vo TTB, Choi D

J Funct Biomater · 2026 Mar · PMID 41893207 · Full text

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

Acute Oroantral Communication Closure: Resorbable Collagen Membrane vs. Buccal Advancement Flap Outcomes: A Clinical Trial.

Balicz A, Szurko A, Jędzierowska M … +6 more , Kiełboń A, Wójcik S, Adamczyk J, Starosta M, Fiegler-Rudol J, Morawiec T

J Funct Biomater · 2026 Mar · PMID 41893206 · Full text

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