J Biomed Mater Res A [JOURNAL]
Sun
200 papers
Synergistic Effects of ZrO and MWCNT Duplex Coatings on TiO Nanotube Arrays for Enhanced Osteogenic, Mechanical, and Antibacterial Properties.
Swain P, Swain S, Rautray TR
J Biomed Mater Res A · 2025 Dec · PMID 41395881 · Publisher ↗
Electrochemically prepared self-organized titanium nanotube arrays have emerged as a platform of considerable interest owing to their unique structural and functional attributes, driving advances across energy, photocata...
Electrochemically prepared self-organized titanium nanotube arrays have emerged as a platform of considerable interest owing to their unique structural and functional attributes, driving advances across energy, photocatalytic, and biomedical fields. Their potential as one-dimensional biomaterials have sparked intensive research focused on their controlled fabrication, properties, surface modification, and integration into advanced biomedical technologies. Herein, zirconium dioxide and multi-walled carbon nanotubes coated titanium nanotube arrays heterostructures were fabricated using different electrolytic combinations (organic electrolyte and water-based electrolyte). Zirconium dioxide coating contributes to enhanced chemical stability and mechanical strength. In parallel, the incorporation of multi-walled carbon nanotubes not only offers increased electrical conductivity and promotes cellular interactions, facilitating osteogenic cell adhesion and proliferation, but also promotes mechanical reinforcement and antibacterial efficacy. Comprehensive physical characterizations, including X-ray diffraction, field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy, and Fourier-transform infrared spectroscopy, confirmed successful deposition and morphological uniformity of the duplex coating. In vitro biocompatibility tests using MG-63 osteoblast-like cells demonstrated excellent cytocompatibility, cell adhesion and proliferation. Additionally, water contact angle measurements and nanoscale roughness evaluations revealed considerable surface wettability and superior topography, conducive to osteogenic differentiation. These findings highlight a scalable, chemically stable, and biologically active surface strategy that poses the duplex-coated heterostructure as a next-generation platform for load-bearing implants in bone tissue engineering and regenerative medicine.
Mineralizing Elastin-Like Protein Microgels.
Sapjanskaite I, Hasan A, Rodríguez-Cabello JC … +5 more , Parmenter C, Fay MW, Fowler C, Alexander C, Mata A
J Biomed Mater Res A · 2025 Dec · PMID 41384643 · Publisher ↗
Mineralized tissues, such as bone and enamel are fundamental to the structure and function of organisms, with a complex interplay between their organic and inorganic components. Organized mineralization is crucial for bo...
Mineralized tissues, such as bone and enamel are fundamental to the structure and function of organisms, with a complex interplay between their organic and inorganic components. Organized mineralization is crucial for both the tissues of living organisms and engineered materials. Elastin-like recombinamers (ELRs) have been successfully employed in tissue engineering, primarily as macroscopic coatings and membranes capable of mediating the nucleation and growth of hierarchically ordered mineralized structures. However, their adaptation into microgels has not been previously reported. To address this gap, our study presents a simple fabrication approach to produce injectable ELR microgels that retain the capacity for organized apatite-like mineralization. Converting the ELR platform into a microgel format offers distinct advantages, including an increased surface area-to-volume ratio, tuneable particle size, and improved handling. These features broaden the material's potential applications, such as its use as minimally invasive injectable scaffolds or as bioink formulations for 3D bioprinting in hard tissue repair. Here, we report on a straightforward and reproducible water-in-oil emulsification method to fabricate injectable mineralizing ELR microgels. Following mineralization, microgels supported the growth of apatite-like crystals, achieving a mineral content of approximately 20 wt%. The hierarchical organization of the mineral phase was confirmed by SEM and TEM imaging, while FTIR and XRD analyses verified that the mineral phase corresponds to the characteristic structural parameters of hydroxyapatite. ELR microgels demonstrated low cytotoxicity, maintaining over 90% viability of human mesenchymal stem cells (hMSCs) after 14 days in culture. As a proof of concept, the osteogenic potential of ELR microgels was evaluated by assessing alkaline phosphatase (ALP) activity, which demonstrated an approximate 40% increase relative to controls at day 14, with elevated levels sustained in the presence of mineralized microgels through day 28. We envision that the versatile ELR microgel platform will offer new opportunities for its application in mineralized tissue engineering.
Bone Marrow Stromal Cells Produce Two Molecular Weight Forms of Semaphorin 3C in Response to Titanium Surface Topography That Differentially Regulate BMSCs, Osteoblasts and Osteoclasts.
Deng J, Sabalewski EL, Dennis CD … +4 more , Lotz EM, Cohen DJ, Schwartz Z, Boyan BD
J Biomed Mater Res A · 2025 Dec · PMID 41370641 · Publisher ↗
RNAseq analysis showed that human bone marrow stromal cells (BMSCs) express neurogenic factors, including semaphorins 3A and 3C (sema3A; sema3C) when grown on titanium substrates. Sema3A causes BMSCs to differentiate int...
RNAseq analysis showed that human bone marrow stromal cells (BMSCs) express neurogenic factors, including semaphorins 3A and 3C (sema3A; sema3C) when grown on titanium substrates. Sema3A causes BMSCs to differentiate into osteoblasts in vitro and promotes osseointegration in vivo, suggesting that sema3C may also contribute to peri-implant bone formation. Human BMSCs were cultured on smooth/hydrophobic (PT), microrough/hydrophobic (SLA), and microrough/hydrophilic (modSLA) Ti substrates. Production of sema3C was sensitive to surface characteristics and was mediated by integrins α2, and β1, BMP2, and Wnt5A, but not Wnt11 or sema3A. Sema3C did not affect differentiation of hBMSCs, but inhibited osteoclast differentiation and activity. Conditioned media from hBMSCs grown on modSLA reduced osteoclast differentiation of RAW264.7 cells. Blocking sema3C with anti-sema3C antibodies partially mitigated its inhibitory effect on resorption. However, sema3C did not affect macrophage polarization. Treatment of human umbilical vascular endothelial cells (HUVECs) with modSLA conditioned media increased angiogenesis at 24 h. BMSCs produced sema3C as two variants; the 95 kDa protein was stored in the ECM, whereas the 65 kDa protein was released to the media. Treatment with 65 kDa sema3C inhibited substrate-dependent osteoblastic differentiation of hBMSCs; 95 kDa sema3C had no effect. In conclusion, this study showed that BMSCs produce sema3C in a surface-dependent manner. The 65 kDa sema3C inhibits osteoblast differentiation and the 95 kDa sema3C directly inhibits osteoclastogenesis, resorption, and angiogenesis. Our findings indicate that sema3A and 3C modulate peri-implant bone formation through differential actions on multiple cell types present in the peri-implant environment to promote new bone formation.
Ibuprofen-Grafted Gelatin Hydrogel Modulates Inflammatory Response and Promotes Muscle Regeneration.
Li J, Guan X, Wu J
J Biomed Mater Res A · 2025 Dec · PMID 41370636 · Publisher ↗
Volumetric muscle loss (VML) presents a significant clinical challenge, exacerbated by the chronic inflammation and oxidative stress that impair muscle regeneration. To address this, we developed an injectable hydrogel f...
Volumetric muscle loss (VML) presents a significant clinical challenge, exacerbated by the chronic inflammation and oxidative stress that impair muscle regeneration. To address this, we developed an injectable hydrogel for muscle repair by enzymatically crosslinking gelatin covalently grafted with ibuprofen (Gel-IBU) using microbial transglutaminase (mTG). Ibuprofen was covalently grafted to gelatin via carbodiimide chemistry to obtain the Gel-IBU conjugate, which was then prepared into an injectable hydrogel by mTG crosslinking. Solubilized Gel-IBU showed good injectability and underwent sol-gel transition in the presence of mTG within 5 min at 37°C to form a hydrogel. The resulting hydrogel exhibited good adhesiveness to muscle tissue, facilitated by liquid penetration and mTG-mediated crosslinking with tissue proteins. Sustained release of IBU endowed the hydrogel with potent inflammation-modulating capacity, promoting macrophage polarization toward the anti-inflammatory M2 phenotype, suppressing pro-inflammatory cytokines, and reducing reactive oxygen species (ROS) and nitric oxide (NO) oxidative products. In a murine VML model, the Gel-IBU hydrogel effectively attenuated local inflammation and enhanced tissue regeneration, demonstrating significant promise for clinical muscle regeneration.
Silver Vanadate-Hydroxyapatite Nanofibrous Scaffolds for Enhanced Bone Regeneration and Infection Control in a Rat Tibial Defect Model.
Swidan SA, Mahdy HM, Hendawy H … +2 more , Youssry A, Abdel-Latif GA
J Biomed Mater Res A · 2025 Dec · PMID 41364830 · Publisher ↗
This study details the development of electrospun nanofibrous scaffolds composed of hydroxyapatite (HAp), polycaprolactone (PCL), and silver vanadate (AgVO) to enhance bone regeneration. AgVO and HAp were synthesized and...
This study details the development of electrospun nanofibrous scaffolds composed of hydroxyapatite (HAp), polycaprolactone (PCL), and silver vanadate (AgVO) to enhance bone regeneration. AgVO and HAp were synthesized and integrated into PCL via electrospinning. The scaffolds were characterized using Fourier-transform infrared (FTIR) spectroscopy, Raman spectroscopy, scanning electron microscopy (SEM), contact angle analysis, and antibacterial testing. A critical-size tibial defect (3 mm) was created in rats (n = 30), which were divided into three groups: control, HAp@PCL, and AgVO-HAp@PCL. Radiographic, histological, and histomorphometric assessments were conducted at 4- and 8-weeks postsurgery. The AgVO-HAp@PCL scaffolds exhibited improved hydrophilicity, homogeneous structure, and strong antibacterial activity. Cone beam computed tomography (CBCT), histological, and histomorphometry analyses revealed significantly greater bone density and organized trabecular formation in the AgVO-HAp@PCL group than in the other groups (p < 0.001). These results conclusively show that AgVO boosts scaffold bioactivity and antibacterial function, highlighting AgVO-HAp@PCL as a strong candidate for bone regeneration in dental and orthopedic uses, even with a 0.15 mm thick single scaffold layer used in this study. This multifunctional scaffold may serve as a synthetic bone graft alternative in maxillofacial reconstruction and dental surgery, particularly where infection control is critical.
Sulfonated PEDOT-Modified Decellularized Arteries as Electroactive Scaffolds for Vascular Tissue Engineering.
Brown TK, Daso R, Petersen C … +7 more , Beaumont C, Tropp J, Del Carmen A, Chao CL, Dang C, Rivnay J, Jiang B
J Biomed Mater Res A · 2025 Dec · PMID 41347858 · Publisher ↗
Electroactive biomaterials present new opportunities for "smart" vascular grafts capable of supporting tissue integration while enabling electrical stimulation, sensing, or real-time modulation of the vascular environmen...
Electroactive biomaterials present new opportunities for "smart" vascular grafts capable of supporting tissue integration while enabling electrical stimulation, sensing, or real-time modulation of the vascular environment. In this study, a conductive vascular conduit was engineered by incorporating sulfonated poly(3,4-ethylenedioxythiophene) (S'PEDOT) into extracellular matrix (ECM)-based scaffolds. Initial screening in collagen sponges identified S'PEDOT concentrations that supported biocompatibility with primary endothelial and smooth muscle cells while minimizing platelet adhesion. This strategy was then applied to decellularized rat aortas, which were functionalized with S'PEDOT and evaluated for electrical conductivity, tensile mechanics, and structural integrity. The modified grafts retained native architecture and mechanical compliance while exhibiting significantly enhanced conductivity compared to unmodified controls. In vivo biocompatibility was assessed by subcutaneous implantation in rats, followed by histological and immunohistochemical analyses. The S'PEDOT-modified grafts elicited minimal inflammatory response and preserved tissue architecture. These findings demonstrate a promising approach for integrating conductive polymers into natural scaffolds to develop electroactive vascular grafts, supporting future applications in multifunctional and responsive vascular devices.
Biomimetic Glycosaminoglycan Analog Hydrogels Inhibit Neurite Outgrowth While Supporting Neuronal Cell Viability.
Sumaya K, Segev D, Mordechai HS … +3 more , Shilo M, Sharabi M, Sivan SS
J Biomed Mater Res A · 2025 Dec · PMID 41342484 · Publisher ↗
Intervertebral disc (IVD) degeneration is a leading contributor to chronic low back pain, imposing a substantial global burden. Native IVD tissue relies on sulfated glycosaminoglycans (sGAG) to maintain hydration and mec...
Intervertebral disc (IVD) degeneration is a leading contributor to chronic low back pain, imposing a substantial global burden. Native IVD tissue relies on sulfated glycosaminoglycans (sGAG) to maintain hydration and mechanical function through fixed negative charges and associated osmotic pressure. With aging, sGAG depletion leads to matrix disorganization, dehydration, and pathological nerve ingrowth-hallmarks of disc degeneration. Synthetic GAG analog hydrogels have recently gained attention as biomimetic candidates for disc repair, owing to their structural resemblance and fixed charge density similarity to native sGAGs. Beyond their biomechanical role, these GAG analogs are hypothesized to act as neuroinhibitory barriers. In this study, we evaluated the neuroinhibitory capability of GAG analogs at varying crosslinking densities (0.5%-2%), using SH-SY5Y neuroblastoma cells. Grown on GAG analogs, neurite extension was markedly suppressed, with average neurite lengths < 10 μm, compared to 79.3 ± 55.8 and 157.1 ± 103.8 μm in control cultures. Importantly, cell viability remained high (75%-92%), irrespective of the presence of exogenous chondroitin sulfate (CS). These findings suggest that, beyond mimicking the mechanical properties of native NP, GAG analogs can also recapitulate the neuroinhibitory roles of native sGAG, underscoring their promise as therapeutic biomaterials for IVD regeneration and the prevention of pain-related nerve infiltration.
Decellularized Extracellular Matrix Produced by iPSC-Derived MSCs Promotes iPSC-MSC Proliferation and Differentiation and Regulates Secreted Factors.
Huang T, Yang M, Grant C … +4 more , Kelly K, O'Connor AJ, Kalionis B, Heath DE
J Biomed Mater Res A · 2025 Dec · PMID 41334979 · Publisher ↗
The in vitro expansion of mesenchymal stromal cells (MSCs) is essential to produce clinically relevant quantities of cells while preserving therapeutic potential. Currently, premature senescence of the MSCs during in vit...
The in vitro expansion of mesenchymal stromal cells (MSCs) is essential to produce clinically relevant quantities of cells while preserving therapeutic potential. Currently, premature senescence of the MSCs during in vitro expansion is a significant limitation that inflates costs and reduces the efficacy of treatments. Culture environments that maintain MSC properties during in vitro expansion are urgently needed. In this study, we explored the use of the decellularized extracellular matrix (dECM) deposited from different sources of MSCs for induced pluripotent stem cell (iPSC-MSC) expansion. Specifically, we compared dECMs derived from primary bone marrow (BMSCs), a placenta-derived MSC cell line (DMSC23s), and iPSC-MSCs, against conventional substrates including tissue culture plastic (TCP), collagen type I, fibronectin, and Matrigel. We demonstrated for the first time that iPSC-MSCs deposit substantially greater amounts of dECM than BMSCs and DMSC23s (35- and 2-fold, respectively). Additionally, the dECM produced by the iPSC-MSCs demonstrated superior properties in promoting MSC proliferation and lineage-specific differentiation. Furthermore, enzyme-linked immunosorbent assays revealed that dECM culture could modulate the MSC secretome. These findings suggest that iPSC-MSCs and their ECM are suitable for optimizing and upscaling the in vitro expansion of iPSC-MSCs, offering potential advantages in regenerative therapies.
Corrigendum to "Modified EBP-bFGF Targeting Endogenous Renal Extracellular Matrix Protects Against Renal Ischemia-Reperfusion Injury in Rats".
J Biomed Mater Res A · 2025 Dec · PMID 41329870 · Publisher ↗
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A Novel Strategy for Optimized Achilles Tendon Healing: DCN/Hep-Loaded Sutures.
Ye YJ, Jing ZY, Xu YF … +5 more , Hou YB, Su DB, Zhao ZX, Zhou YQ, Yin DC
J Biomed Mater Res A · 2025 Dec · PMID 41313163 · Publisher ↗
The avascular nature of tendons presents a significant challenge for postoperative healing, often resulting in complications and compromised tissue strength. This study explores a novel approach for Achilles tendon repai...
The avascular nature of tendons presents a significant challenge for postoperative healing, often resulting in complications and compromised tissue strength. This study explores a novel approach for Achilles tendon repair using a suture-based system incorporating bioactive factors. Decorin (DCN) and heparin (Hep) were selected as key biochemical factors due to their potential to modulate the tendon healing process. The optimal concentration and ratio of DCN were determined through in vitro experiments assessing their effects on tendon stem cell (TSC) proliferation and differentiation. Subsequently, Hep/DCN-loaded sutures were fabricated via electrospinning, exhibiting low immunogenicity and anti-adhesion properties. In vivo studies demonstrated enhanced collagen fibril organization and repair capacity, leading to improved tensile strength of the Achilles tendon postoperatively. These findings were confirmed through mRNA analysis and immunohistochemistry. The suture-based system established in this study not only serves as a valuable tool for investigating the molecular mechanisms underlying TSC differentiation but also holds promise as a new therapeutic strategy for clinical tendon repair applications.
Hyaluronic Acid-Chitosan Nanoparticles Encapsulating Gal-9 Alleviate Severe Acute Pancreatitis by Promoting M2 Macrophage Polarization.
Dai J, Wang X, Li S … +3 more , Chen S, Ni X, Lin M
J Biomed Mater Res A · 2025 Dec · PMID 41307175 · Publisher ↗
Severe acute pancreatitis (SAP) is a prevalent gastrointestinal disease with no effective treatment to control inflammation currently. Macrophages, particularly peritoneal macrophages (PMOs), play a pivotal role in SAP i...
Severe acute pancreatitis (SAP) is a prevalent gastrointestinal disease with no effective treatment to control inflammation currently. Macrophages, particularly peritoneal macrophages (PMOs), play a pivotal role in SAP inflammation by polarizing into M1 or M2 phenotypes, which exhibit distinct functional properties and cytokine expression profiles. Galectin-9 (Gal-9) modulates macrophage polarization, but its specific effect on PMOs in SAP remains unclear. In this study, hyaluronic acid-chitosan nanoparticles encapsulating Gal-9 (HA-CS-Gal-9 NPs) were developed for delivery. In vitro, HA-CS-Gal-9 NPs enhanced M2 marker expression and suppressed M1 markers in both naive (M0) and LPS-induced M1 macrophages. In vivo, HA-CS-Gal-9 NPs effectively delivered Gal-9, showing effective uptake by PMOs without notable toxicity, resulting in reduced IL-6, and increased IL-10 expression in PMOs. Treatment with these nanoparticles (NPs) decreased systemic pro-inflammatory cytokines, thereby alleviating pancreatitis severity. These findings demonstrate that Gal-9-loaded NPs robustly promoted M2 macrophage polarization, highlighting a promising therapeutic strategy for SAP.
Surface Functionalization of TiO With an Albumin-Teicoplanin Complex to Prevent Implant-Associated Infections.
Jagannathan C, Mansell JP
J Biomed Mater Res A · 2025 Dec · PMID 41307168 · Publisher ↗
Postoperative infection and aseptic loosening are leading causes of orthopedic implant failure, often necessitating complex and costly revision surgeries. Teicoplanin (TP), a glycopeptide antibiotic effective against met...
Postoperative infection and aseptic loosening are leading causes of orthopedic implant failure, often necessitating complex and costly revision surgeries. Teicoplanin (TP), a glycopeptide antibiotic effective against methicillin-resistant Staphylococcus aureus (MRSA), and albumin (AB), a biocompatible carrier protein, present a promising strategy for implant surface functionalization. However, previous approaches using intermediate adhesive layers have demonstrated limited antibiotic retention following physiological conditioning. This study investigates the direct functionalization of titanium dioxide (TiO) powder with an AB-TP complex to develop a stable antibacterial surface coating capable of retaining efficacy after phosphate exposure. The AB-TP complex was prepared and immobilized onto TiO powder. AB attachment kinetics and stability were assessed using the bicinchoninic acid (BCA) assay after short-term incubation, serial buffer washes, and extended conditioning. In vitro, antibacterial efficacy was evaluated against S. aureus using viable count assays and disk diffusion. Additional tests assessed TP leaching following sample conditioning. The biological response of osteoblast-like MG63 cells to AB-TP was examined to evaluate cytocompatibility and pro-osteogenic potential. AB demonstrated rapid and irreversible binding to TiO, with negligible protein loss following 10 washes or 7-day physiological buffer incubation. AB-TP-TiO completely inhibited bacterial growth (6.18-log reduction). Following phosphate conditioning, AB-TP-TiO retained antibacterial activity, with log reductions of 3.3. Disk diffusion confirmed no TP leaching from AB-TP-TiO, in contrast to TP-TiO, which exhibited significant antibiotic release and complete loss of antibacterial function post-conditioning. Treatment of MG63 with the AB-TP supported significant cell growth and increased alkaline phosphatase activity. Direct functionalization of TiO with the AB-TP complex yields a stable, durable, and antibacterial surface capable of withstanding physiological conditions. This approach bypasses the limitations of adhesive layers and demonstrates potential for application in orthopedic implant coatings.
Silver-Doped Mesoporous Bioactive Glass Nanoparticles With Core-Shell Architecture: Enhanced In Vitro Bioactivity, Antibacterial Efficacy, and Biocompatibility.
Thongnuek P, Sukparangsi W, Jomrit J … +4 more , Damrongsakkul S, Sriboonaied P, Cao C, Prasopthum A
J Biomed Mater Res A · 2025 Dec · PMID 41307167 · Publisher ↗
Orthopedic biomaterials must both prevent infection and support bone regeneration. To achieve both outcomes with bioactive glass nanoparticles (BGNs), rational nanoarchitectural design is required to decouple and tune si...
Orthopedic biomaterials must both prevent infection and support bone regeneration. To achieve both outcomes with bioactive glass nanoparticles (BGNs), rational nanoarchitectural design is required to decouple and tune silver-ion (Ag) and calcium-ion (Ca) release, balancing antibacterial efficacy with osteogenic compatibility. Herein, we synthesized four BGN types via a modified sol-gel route: solid spheres, Ag-doped solid spheres, core-shell mesoporous BGNs, and Ag-doped core-shell mesoporous BGNs. Core-shell architectures were generated by alkaline etching followed by calcium impregnation, and silver was introduced during synthesis. Comprehensive characterization (scanning/transmission electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy) confirmed homogeneous amorphous glass networks with spatially distinct Ca and Ag distributions in the mesoporous particles. Brunauer-Emmett-Teller analysis showed high-surface-area mesoporous BGNs (≈860 m/g) versus solid spheres (≈17 m/g), with markedly greater pore volume. Inductively coupled plasma mass spectrometry revealed sustained Ag and Ca release over 21 days within sub-microgram-per-milliliter levels, consistent with the core-shell design. These physicochemical features translated into superior biological performance: Ag-doped mesoporous BGNs accelerated mineralization in simulated body fluid, exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus and Escherichia coli, and supported the viability and osteogenic differentiation of human mesenchymal stem cells. In ovo biocompatibility testing found no vascular irritation in the Hen's Egg Test on the Chorioallantoic Membrane (HET-CAM). Altogether, nanostructural tuning, particularly combining mesoporosity with a core-shell architecture, can optimize ion-release behavior and biological function in BGNs, advancing multifunctional nanoglasses for regenerative and antimicrobial applications.
Recapitulating Native-Like Strain Distributions in a Tissue-Engineered Enthesis by Creating Structural, Biochemical, and Mineral Gradients.
Kim J, Boys AJ, Babmatee R … +2 more , Estroff LA, Bonassar LJ
J Biomed Mater Res A · 2025 Dec · PMID 41277704 · Publisher ↗
The incorporation of robust meniscus-to-bone interfaces into tissue-engineered menisci is critical for their clinical translation. Generating gradients in collagen fiber organization and mineral content for tissue-engine...
The incorporation of robust meniscus-to-bone interfaces into tissue-engineered menisci is critical for their clinical translation. Generating gradients in collagen fiber organization and mineral content for tissue-engineered entheses is essential for achieving native tissue-like mechanics; however, engineering such gradients remains challenging. This study presents a tissue-engineered enthesis model consisting of a fibrochondrocyte-seeded cylinder of type I collagen gel with trabecular bone plugs on both ends. Using a tri-chamber bioreactor, spatially controlled biochemical (e.g., TGF-β1 and glucose) and biomechanical stimuli were applied, generating native-like collagen fiber structure and mechanics within tissue-engineered enthesis constructs. Confocal elastography revealed a more uniform local strain distribution and reduced peak strain in the enthesis constructs cultured in a tri-chamber bioreactor compared to those in a single chamber bioreactor, likely attributed to the enhanced collagen fiber organization. To further improve the integration at the collagen-bone plug interface, we introduced partially demineralized bone plugs to the constructs. Partial demineralization improved the mechanical performance of enthesis constructs, decreasing peak strain by > 30% and strain gradients by 50%, while increasing toughness and strain at failure by 50% and 40%, respectively. Overall, these findings highlight the importance of zone-specific biochemical and biomechanical stimuli and biomimetic scaffold materials to improve tissue-engineered implants.
Poly-L-Lactic Acid Microspheres Promote Skin Rejuvenation via Enhanced Fibroblast Function.
Geara J, Luo L, Parlak O … +2 more , Sommar P, Xu Landén N
J Biomed Mater Res A · 2025 Nov · PMID 41216698 · Publisher ↗
Skin aging is marked by fibroblast decline and extracellular matrix (ECM) degradation, prompting the widespread use of poly-L-lactic acid (PLLA) dermal injectables for activating fibroblasts, stimulating neocollagenesis,...
Skin aging is marked by fibroblast decline and extracellular matrix (ECM) degradation, prompting the widespread use of poly-L-lactic acid (PLLA) dermal injectables for activating fibroblasts, stimulating neocollagenesis, and rejuvenating the skin. However, current PLLA formulations show variable efficacy and may trigger undesirable inflammatory responses. In this study, we compared two different PLLA formulations -one containing novel microspherical PLLA (PLLA-LASYNPRO) and the other containing a microflake-like PLLA -to assess their differing effects on human dermal fibroblasts and skin tissue. The results show that PLLA microspheres promote fibroblast migration, ECM synthesis, and wound contraction, while PLLA microflakes inhibit proliferation and elicit inflammatory gene expression. Transcriptomic profiling reveals that PLLA microspheres upregulate genes involved in fat cell differentiation and energy metabolism, with minimal immune activation. In contrast, PLLA microflakes trigger immune pathways and suppress regenerative signals. Importantly, each formulation induces unique long non-coding RNA (lncRNA) signatures, implicating lncRNAs in fibroblast-mediated skin remodeling. These findings highlight the novel design of PLLA microspheres as a critical determinant of their therapeutic outcome, offering a molecular basis for developing safer and more effective skin rejuvenation strategies.
Injectable Glycyrrhizic Acid Hydrogel Microspheres With Synergistic Anti-Senescence and Osteogenic Effects for Osteoporosis Therapy.
Hong Y, Liu X, Mao W … +4 more , Ma B, Chen H, Zhang X, Li D
J Biomed Mater Res A · 2025 Nov · PMID 41216672 · Publisher ↗
Osteoporosis is an age-related bone disease closely associated with the accumulation of senescent cells in the bone marrow microenvironment, a pathological feature that is not fully addressed by current biomaterial-based...
Osteoporosis is an age-related bone disease closely associated with the accumulation of senescent cells in the bone marrow microenvironment, a pathological feature that is not fully addressed by current biomaterial-based therapies. Targeting cellular senescence and its associated inflammatory microenvironment presents a promising strategy for mitigating osteoporosis progression. Glycyrrhizic acid (GA), a naturally occurring triterpenoid, has been shown to alleviate cellular senescence in various age-related disorders. Herein, injectable GA/gelatin methacrylate hydrogel microspheres (GA@GelMA) were developed using microfluidic technology to enable sustained GA release. The microspheres demonstrated multiple functionalities in vitro, including suppression of cellular senescence, induction of M1-to-M2 macrophage polarization, and enhancement of osteogenic differentiation in bone marrow stem cells (BMSCs). In an ovariectomized (OVX) mouse model of osteoporosis, local administration of GA@GelMA microspheres significantly promoted bone formation and alleviated the senescence-associated inflammatory microenvironment. These GA@GelMA microspheres provide a multifunctional strategy integrating osteogenesis promotion and senescence modulation for the treatment of osteoporosis.
Self-Assembling Synthetic Congener Collagen Mini-Fibrils With Genetically Encoded Hydroxyproline and 3,4-Dihydroxyphenylalanine for Wound Healing.
Sundarapandian A, Pachaiyappan M, Aarthy M … +5 more , Jangra S, Shanmugam G, Anandasadagopan SK, Jaganathan M, Ayyadurai N
J Biomed Mater Res A · 2025 Nov · PMID 41208082 · Publisher ↗
Collagen-like proteins (CLPs) and their congeners can form stable triple helices but show limited fibril-forming ability, restricting their application as biomaterials. To more closely replicate the structural features o...
Collagen-like proteins (CLPs) and their congeners can form stable triple helices but show limited fibril-forming ability, restricting their application as biomaterials. To more closely replicate the structural features of natural collagen, we engineered an extended CLP-CLP double domain (CLPdd) genetically encoded with Hydroxyproline (CLPdd-Hyp) and 3,4-dihydroxyphenylalanine (CLPdd-DOPA) using a genetic code expansion strategy. This study presents the first report of the dual incorporation of Hydroxyproline (Hyp) and 3,4-dihydroxyphenylalanine (DOPA) into the CLP double domain (CLPdd), yielding the variant CLPdd-HD, which exhibited significantly enhanced fibrillation, thermal stability, and biomaterial potential. Among the engineered variants, CLPdd-Hyp showed the most pronounced improvements in triple-helical structure, fibrillation behavior, wound healing efficacy, and cell adhesion highlighting its promise as a biomaterial. Biocompatibility assessments further confirmed the suitability of CLPdd variants for biomedical applications. Notably, CLPdd-HD demonstrated exceptional thermal stability and cell-adhesive properties, underscoring its potential for further optimization. This work lays a foundation for tailoring bacterial CLPs through strategic NCAA incorporation, opening new avenues for developing advanced collagen-mimetic biomaterials.
Establishment of an In Vitro Neurovascular Unit Model With Blood and Brain Components and Investigation of Its Blood-Brain Barrier.
Kole GE, Kocagoz T, Hasirci V … +1 more , Yucel D
J Biomed Mater Res A · 2025 Nov · PMID 41208081 · Publisher ↗
The neurovascular unit (NVU), including the blood-brain barrier (BBB), governs the interaction between neural tissue and blood vessels. The BBB is a highly selective interface that regulates molecular exchange between th...
The neurovascular unit (NVU), including the blood-brain barrier (BBB), governs the interaction between neural tissue and blood vessels. The BBB is a highly selective interface that regulates molecular exchange between the bloodstream and the central nervous system. This study aimed to develop a structurally relevant, multicellular in vitro NVU model integrating both vascular and brain microenvironments to evaluate BBB function. A fibrous membrane mimicking the basement membrane was fabricated via electrospinning, while a methacrylated hyaluronic acid (MeHA)-collagen hydrogel was used on the brain side. Endothelial cells (ECs) were cultured on the vascular side, and astrocytes, pericytes, and neuronal model cells were embedded within the hydrogel. The model was optimized for cell viability and endothelial monolayer formation. Cell behavior was assessed via immunocytochemistry, and barrier function was evaluated using TEER measurements and permeability assays with fluorescein, 0.4 and 20 kDa dextran, ceftriaxone, and amikacin. CD31 expression was elevated in the multicellular model, indicating improved endothelial integrity. The model achieved a TEER of 166.86 ± 5.75 Ω versus 121.70 ± 13.58 Ω cm in monoculture. Permeability to tracers was significantly reduced in the multicellular model, and ceftriaxone showed higher transport than amikacin, reflecting human BBB selectivity. This model provides a physiologically relevant platform for neurovascular research and drug screening.
Additively Manufactured Metastable-β Ti-Nb-Zr-Sn Exhibits Superior Corrosion, Semiconducting, and Cell Metabolic Properties Over Ti-6Al-4V.
Kurtz MA, Rince N, DeSantis PM … +6 more , Vuong ML, Chapagain P, Spece H, Castany P, Gloriant T, Kurtz SM
J Biomed Mater Res A · 2025 Nov · PMID 41208046 · Publisher ↗
Manufacturers frequently use Ti-6Al-4V for permanently implanted medical devices. While clinically successful, Ti-6Al-4V corrodes at modular taper interfaces in both the hip and knee. Additionally, additive manufacturing...
Manufacturers frequently use Ti-6Al-4V for permanently implanted medical devices. While clinically successful, Ti-6Al-4V corrodes at modular taper interfaces in both the hip and knee. Additionally, additive manufacturing (AM) can develop biomaterials with the potential to improve upon Ti-6Al-4V's properties. In this study, we used AM to generate Ti-Nb-Zr-Sn, comparing the admixture to classically melted Ti-Nb-Zr and wrought-annealed Ti-6Al-4V. We asked (1) how does manufacturing alter Ti-Nb-Zr biomaterial structure; (2) do resulting structural differences govern corrosion and semiconducting properties; and (3) does biomaterial chemistry and structure affect cell metabolic activity? To answer these questions, we first used scanning electron microscopy and electron backscattered diffraction to characterize microstructure. Then, we elucidated the corrosion properties and semiconducting performance in 0.1 M HO and PBS solutions. Next, we measured the cell metabolic activity after 24 and 72 h. Manufacturing profoundly altered the Ti-Nb-Zr biomaterials, with AM processes generating a columnar microstructure consisting of elongated grains. This contrasted with the equiaxed β grains of the alloy produced by melting processes. However, these structural changes had little effect on the corrosion or semiconducting properties. Additionally, both Ti-Nb-Zr-Sn and Ti-Nb-Zr exhibited increased corrosion resistance and decreased defect densities over Ti-6Al-4V in 0.1 M HO. Finally, we documented superior cell metabolic properties on polished and as-built Ti-Nb-Zr-Sn surfaces after 72 h. Combined, these results suggest an inhibitory effect of ZrO oxides on reactive oxygen species and support the continued characterization of Ti-Nb-Zr-Sn as a candidate biomaterial.
A Novel Radially Graded Hydroxyapatite-Based Composite for Bioactive Implant Interfaces.
Coskun Tas Z, Celik T, Mutlu I … +2 more , Yamanoglu R, Anguilano L
J Biomed Mater Res A · 2025 Nov · PMID 41178589 · Publisher ↗
The combination of superior mechanical properties, corrosion resistance, and biological characteristics makes Ti-6Al-4V a widely used biomaterial. However, its clinical application as an orthopedic implant is limited by...
The combination of superior mechanical properties, corrosion resistance, and biological characteristics makes Ti-6Al-4V a widely used biomaterial. However, its clinical application as an orthopedic implant is limited by its hardness and weak osseointegration capacity. This study focuses on the development of a functionally graded biomaterial that has increased bioactivity and decreased mechanical mismatch with living tissue. In this scope, a novel radially functionally graded Ti-5Mo/hydroxyapatite (HA) biocomposite was successfully fabricated via pressure-assisted sintering using a specially designed mold that enabled directional HA enrichment toward the outer surface. This architectural design addresses the persistent challenge of combining mechanical reliability with biological functionality in load-bearing implants. Comprehensive characterization was performed, including x-ray diffraction (XRD), Rietveld refinement, optical and scanning electron microscopy (SEM/EDX), atomic force microscopy (AFM), contact angle measurements, and in vitro cytotoxicity assays using L929 fibroblast cells. Mechanical behavior was assessed through Brazilian splitting, three-point bending, microhardness, and tribological testing under both dry and corrosive conditions. The biocomposite exhibited a dual-phase α + β titanium matrix and HA-derived oxides in the surface layers, with a graded increase in porosity and hardness from the core to the periphery. Mechanical tests revealed a bending modulus of 22.4 GPa, close to that of cortical bone, while the surface showed enhanced roughness, hydrophilicity (contact angle 35.3°), and corrosion resistance. In vitro results confirmed the material's biocompatibility and superior cell viability in HA-rich regions. These findings demonstrate that the developed Ti-5Mo/HA FGM offers a structurally and biologically optimized solution for orthopedic and dental implant applications.
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