J Biomed Mater Res A [JOURNAL]
Sun
200 papers
Uniaxial Tensile Tests and Digital Image Correlation Analysis for the Mechanical Characterization of Human Fascia Lata Under Different Decellularization Treatments.
Demontis F, Loi G, Mazzotti E … +9 more , Rodriguez Reinoso M, Vecchio F, Faini AC, Leone A, Camusso E, Genzano Besso F, Surace C, Lacidogna G, Scaramozzino D
J Biomed Mater Res A · 2025 Nov · PMID 41159263 · Publisher ↗
Fascia lata (FL) is frequently employed as a grft source in reconstructive surgery. To minimize unwanted responses from the host immune system, several decellularization treatments have been proposed. Effective treatment...
Fascia lata (FL) is frequently employed as a grft source in reconstructive surgery. To minimize unwanted responses from the host immune system, several decellularization treatments have been proposed. Effective treatments should aim at avoiding the deterioration of the physical and mechanical properties of the implanted tissue. In this work, we carried out a mechanical characterization of FL specimens from human dead donors, both in their native-physiological condition and upon decellularization with three commonly used detergents, t-octyl-phenoxypolyethoxyethanol (Triton X-100), sodium dodecyl sulfate (SDS), and tri-n-butyl phosphate (TnBP). Uniaxial tensile tests were used to characterize the elastic stiffness and ultimate stresses of the tissue, and Digital Image Correlation (DIC) was applied to monitor the strain evolutions and meso-mechanical deformation responses. None of the investigated decellularization protocols was found to lead to a significant deterioration of the FL mechanical properties, suggesting the applicability of these chemical treatments for graft preparation and usage in clinical practice. The application of DIC also allowed us to get a first estimate of the FL Poisson ratio as well as to draw attention to the inhomogeneity of strain distributions, suggesting that the use of average engineering strains can lead to an oversimplification of the actual deformation field.
Adipose-Derived Stem Cell-Loaded Fish-GelMA/CMC Hydrogel Accelerates Wound Healing via Macrophage Polarization Suppression and Promoting Angiogenesis.
Xue X, Xue H, Lu R … +1 more , Ji J
J Biomed Mater Res A · 2025 Nov · PMID 41147636 · Publisher ↗
Extensive cutaneous injuries with impaired regenerative capacity present substantial risks to both public health and socioeconomic systems. Current skin substitutes remain inadequate in fully replicating native tissue ar...
Extensive cutaneous injuries with impaired regenerative capacity present substantial risks to both public health and socioeconomic systems. Current skin substitutes remain inadequate in fully replicating native tissue architecture and physiological functionality. While fish skin-derived gelatin-methacrylate (F-GelMA) serves as a principal scaffold material in vitro skin models, it has weak mechanical properties and limited mechanical strength, which necessitates supplementation with viscosity-enhancing additives. We created functional in vitro 3D extracellular matrix mimics with composite hydrogels based on F-GelMA and the thickener carboxymethyl cellulose (CMC). The physicochemical properties and bioactivity of the hydrogel scaffolds were assessed through testing their rheological properties, swelling behavior, degradation characteristics, and biocompatibility. It was discovered that the F-GelMA/CMC hydrogel bioscaffold loaded with adipose-derived stem cells (ADSCs) expedited wound healing by facilitating wound re-epithelialization, enhancing wound collagen formation, accelerating the deposition of myofibroblasts at the wound site, promoting angiogenesis, stimulating the proliferation and differentiation of keratinocytes, and suppressing skin wound inflammation.
Conjugation of Proangiogenic Peptide to Enhance a Soft Tissue Bioink.
Christensen AP, Fisher JP
J Biomed Mater Res A · 2025 Nov · PMID 41147605 · Full text
Acellular methods are needed to vascularize 3D-printed tissue-engineered constructs for faster clinical translation. One method is to create bioactive materials that encourage migration and network formation of a patient...
Acellular methods are needed to vascularize 3D-printed tissue-engineered constructs for faster clinical translation. One method is to create bioactive materials that encourage migration and network formation of a patient's own cells. This study utilizes QK peptide, which replicates a binding sequence of vascular endothelial growth factor. This peptide has previously shown to maintain bioactivity when modified with an acrylate group and covalently bound to gelatin methacrylate (GelMA). However, this binding interferes with the crosslinking of the hydrogel matrix, requiring characterization of the modified material. We investigated how binding QK peptide impacts GelMA crosslinking and material properties. A factorial design was employed to investigate the relationships between GelMA concentration, GelMA degree of substitution, and QK peptide concentration. These experiments were used to inform a rheology study, where the impact of QK peptide on crosslinking was investigated over a range of photocrosslinking times. We then investigated the printability of QK-GelMA bioink using rheology and a filament collapse test. The bioactivity induced by the peptide on the hydrogel surface was evaluated using endothelial cell network formation. QK peptide impacted key GelMA characteristics, including swelling behavior, mesh size, and storage modulus, potentially through inhibition of temperature-induced chain entanglement. While bound QK peptide impacts GelMA bioink at the nanoscale, QK-GelMA bioinks maintain high print fidelity and increase endothelial network formation on the surface of the hydrogel. The addition of QK peptide increases the vascularization potential of 3D-printed tissue-engineered constructs.
Silver (I) and Silver (II) Oxide Films for Biomedical Implants: Synthesis, Stability, Ion Release, and Antibacterial Efficacy.
Akantibila M, Maurer H, Urban M … +10 more , DiSpirito S, Torres J, Muhamed A, Harris J, Bharath A, Green R, Scabarozi TH, Caputo GA, Carabetta VJ, Hettinger JD
J Biomed Mater Res A · 2025 Nov · PMID 41144936 · Publisher ↗
Coatings of silver compounds with higher dissolution rates than metallic silver offer a promising approach for delivering Ag ions to prevent medical implant device-associated infections. In this study, we investigate the...
Coatings of silver compounds with higher dissolution rates than metallic silver offer a promising approach for delivering Ag ions to prevent medical implant device-associated infections. In this study, we investigate the synthesis and characterization of single-phase, silver (I) oxide (AgO) and silver (II) oxide (AgO) for potential antimicrobial applications. The synthesis of these materials leverages the higher stability of AgO in comparison to AgO. The formation of AgO requires a low landing energy of the adatoms, achieved through gas phase scattering and rapid quenching when landing. Alternatively, higher landing energies cause re-sputtering of oxygen, which favors the formation of AgO. Higher chamber pressures during deposition increase the number of inelastic collisions, thereby reducing the energy of the adatoms influencing phase formation. A combination of energy dispersive spectroscopy, microstructural imaging, X-ray diffraction (XRD), and high-temperature XRD confirms this result. To evaluate antimicrobial potential, silver ion release (elution) was measured in water, Luria-Bertani broth, and tryptic soy broth. Elution rates were highest in water, but in all media, both oxides elute significantly more Ag ions than metallic silver coatings. Antimicrobial assays clearly show potent and broad-spectrum activity of silver oxides against both clinical and multidrug-resistant bacteria, confirming their potential as effective antimicrobial coatings for implanted devices.
Flavonoid-Enriched Solanum mauritianum Leaf Extract/PU/PCL Composite Attenuates Ang II-Induced Inflammation in Cardiomyocytes and Enhances Cell Adhesion.
Karanath-Anilkumar A, Sadiq M, Ganesan S … +3 more , Bose N, Rajappan K, Munuswamy-Ramanujam G
J Biomed Mater Res A · 2025 Nov · PMID 41144924 · Publisher ↗
Inflammatory disorders like cardiovascular diseases remain a major global health concern, with oxidative stress and chronic inflammation playing critical roles in disease progression. This study presents a PU/PCL composi...
Inflammatory disorders like cardiovascular diseases remain a major global health concern, with oxidative stress and chronic inflammation playing critical roles in disease progression. This study presents a PU/PCL composite functionalized with flavonoid-enriched Solanum mauritianum leaf extract (SL). Incorporation of SL into PU/PCL enhanced its hydrophilicity, oxidative stability, and anti-inflammatory properties, while enabling sustained drug release without adverse in vitro toxicity. PU/PCL/SL was fabricated using a phase inversion technique and characterized to confirm strong molecular interactions, improved thermal stability, and a porous structure that facilitated controlled release. The composite exhibited potent antioxidant and anti-inflammatory activity. PU/PCL/SL showed biocompatibility to H9c2 cardiomyocytes and Peripheral Blood Mononuclear Cells, while confocal imaging demonstrated enhanced cellular adhesion of H9c2 to PU/PCL/SL. Flow cytometry confirmed the ability of the biomaterial to reduce intracellular ROS. PU/PCL/SL was able to significantly downregulate TNF-α, IL-6, IL-1β, and TLR4 in AngII-activated cardiomyocytes. This highlighted the material's potential as an immunomodulator that can target inflammation. Collectively, these results demonstrate the successful fabrication of a flavonoid-functionalized PU/PCL composite with improved physicochemical properties, sustained release capability, and strong biological relevance through biocompatibility and immunomodulatory activity. Together, these findings position PU/PCL/SL as an advanced multifunctional biomaterial with promising applications in cardiovascular disease.
Exogenous Extracellular Matrix in an Environmentally-Mediated In Vitro Model for Cardiac Fibrosis.
Pachter N, Allen K, Hookway TA
J Biomed Mater Res A · 2025 Nov · PMID 41128360 · Publisher ↗
Few clinical solutions exist for cardiac fibrosis, creating the need for a tunable in vitro model to better understand fibrotic disease mechanisms and screen potential therapeutic compounds. Here, we combined cardiomyocy...
Few clinical solutions exist for cardiac fibrosis, creating the need for a tunable in vitro model to better understand fibrotic disease mechanisms and screen potential therapeutic compounds. Here, we combined cardiomyocytes, cardiac fibroblasts, and exogenous extracellular matrix (ECM) proteins to create an environmentally mediated in vitro cardiac fibrosis model. Cells and ECM were combined into 2 types of cardiac tissues-aggregates and tissue rings. The addition of collagen I had a drastic negative impact on aggregate formation, but ring formation was not as drastically affected. In both tissue types, collagen and other ECM did not severely affect contractile function. Histological analysis showed direct incorporation of collagen into tissues, indicating that we can directly modulate the cells' ECM environment. This modulation affects tissue formation and distribution of cells, indicating that this model provides a useful platform for understanding how cells respond to changes in their extracellular environment and for potential therapeutic screening.
Characterizing Piezoelectric-Blended Polydimethylsiloxane for Use as a Mechanoelectrical Responsive Cell Culture Substrate.
Applequist AP, Cordes LD, Ferreira LA … +1 more , Balachandran K
J Biomed Mater Res A · 2025 Nov · PMID 41128299 · Publisher ↗
In this study, we developed a piezoelectric-polydimethylsiloxane (pz-PDMS) composite by blending poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) with PDMS to create a biocompatible, mechanoelectrical respons...
In this study, we developed a piezoelectric-polydimethylsiloxane (pz-PDMS) composite by blending poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) with PDMS to create a biocompatible, mechanoelectrical responsive material. The pz-PDMS was synthesized with varying piezoelectric concentrations (0%, 1%, 3%, and 5%) and characterized for visual properties, mechanical properties, mechanoelectrical sensitivity, and biocompatibility. Compression testing showed no significant change in mechanical strength with the addition of piezoelectric particles, while mechanolectrical sensitivity testing revealed a non-linear increase in voltage response, with 5% pz-PDMS producing the highest sensitivity. Fatigue testing demonstrated no change in sensitivity after 7 days of cyclic displacement. Additionally, microcantilever experiments demonstrated the high fidelity of the 5% pz-PDMS to mechanical deformation. In parallel, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes cultured on both 0% pz-PDMS and 5% pz-PDMS substrates exhibited comparable cell viability, attachment, and maturation, as confirmed by MTS assays and immunofluorescence imaging. The results suggest that 5% pz-PDMS offers a promising platform for bioelectronic applications, combining piezoelectric functionality with long-term biocompatibility.
In Vitro Oxidative Degradation of Hydroxyapatite Biopolymer Nanocomposites and the Resulting Consequences on Their Mechanical Performance.
Diederichs EV, Mondal D, Willett TL
J Biomed Mater Res A · 2025 Nov · PMID 41128290 · Publisher ↗
Development of synthetic biomaterials for skeletal reconstruction has progressed rapidly, driven partly by demand to reduce dependency on allografts. One class of materials, biopolymer nanocomposites, has shown promise w...
Development of synthetic biomaterials for skeletal reconstruction has progressed rapidly, driven partly by demand to reduce dependency on allografts. One class of materials, biopolymer nanocomposites, has shown promise when combined with additive manufacturing for these applications. The driving goal for the development of 3D-printable biopolymer nanocomposites composed of methacrylated monomers (triglycerides and triethylene glycol) and hydroxyapatite (HA) is to produce structurally robust and degradable customizable grafts. These materials must be able to withstand the loading conditions found in vivo while allowing for degradation and remodeling processes. This study focused on the degradation potential of previously developed HA-containing biopolymer nanocomposites and the resulting consequences of degradation on their mechanical performance. One of the means to study a material's in vivo degradation performance is to assess its susceptibility to oxidative degradation, as oxidation is naturally occurring in cell metabolism, inflammatory responses, and osteoclast resorption. Two in vitro models of oxidative degradation were trialed: aqueous solutions of either hydrogen peroxide or neutral hypochlorous acid. Hypochlorous acid was shown to be a useful in vitro assessment for the degradation potential of biomaterials to different reactive oxygen species. The biopolymer nanocomposites were clearly susceptible to oxidative degradation, demonstrating significant changes in mass and surface morphology. Mechanical performance was reduced under these testing conditions. This was attributed to three main factors: swelling and water absorption effects, chemical modifications, and loss of structure. Overall, this study provides insights into the effects of oxidative degradation on biomaterial functionality and highlights the importance of exploring relevant physiological effects on mechanical properties when developing biomaterials.
Electro-Actuation of a Smart Hydrogel Compatible With 3D Printing.
Mikalef G, Schofield Z, Moxon SR … +6 more , Robinson TE, Chu HO, Nugent PF, Baiocco D, Esteban PP, Grover LM
J Biomed Mater Res A · 2025 Oct · PMID 41088848 · Publisher ↗
Hydrogels that can change shape on the application of an electric field are receiving increasing attention due to their potential to fulfill a range of functions in biomedicine, including the controlled release of therap...
Hydrogels that can change shape on the application of an electric field are receiving increasing attention due to their potential to fulfill a range of functions in biomedicine, including the controlled release of therapeutic agents or the creation of replacements for contractile tissues. In this manuscript, a novel electroactive polymer was reported based on the copolymerisation of 2-acrylamido-2-methylpronane sulfonic acid and poly(ethylene glycol) diacrylate (AMPS-co-PEGDA), via free radical polymerization using UV light. It was shown that to enable curing and the production of a material that could repeatably actuate without cracking, 900 mJ/cm (at 365 nm) of UV exposure was optimal. Further increasing the curing time resulted in the production of a brittle material that cracked following actuation, preventing multiple actuations from occurring. The polymer that was cured for 900 mJ/cm was shown to be non-cytotoxic to dermal fibroblast cells, showing potential in biomedical applications. Furthermore, it was shown that the optimized polymer could be structured using a process of suspended 3D printing, allowing for the manufacture of complex, electro-actuatable geometries. Processing in an agarose supporting bed resulted in a reduction in the Young's modulus of the printed polymer and an associated greater degree of bending. These results demonstrate that the optimized (AMPS-co-PEGDA) polymer is a promising electroactive material with tuneable properties and complex geometries, suitable for advanced biomedical applications.
Dynamic Loading Does Not Interfere With the Initial Repopulation of Decellularized Tendons: An Ex Vivo Study.
Spierings J, Abinzano F, Salzer E … +4 more , Bulsink J, Janssen R, Ito K, Foolen J
J Biomed Mater Res A · 2025 Oct · PMID 41088847 · Publisher ↗
Rupture of the anterior cruciate ligament (ACL) is a common injury resulting in joint instability. Tendon autografts, the gold standard to reconstruct a ruptured ACL, contain dead or dying cells upon implantation that ca...
Rupture of the anterior cruciate ligament (ACL) is a common injury resulting in joint instability. Tendon autografts, the gold standard to reconstruct a ruptured ACL, contain dead or dying cells upon implantation that can initiate early localized catabolic and inflammatory events. This is hypothesized to contribute to detrimental remodeling, which may compromise graft stability and increase the risk of rupture. To address this, we propose using decellularized grafts. However, the cells used to reseed decellularized tendons cannot be detected anymore in vivo, potentially due to the dynamic loading conditions. Therefore, the repopulation efficiency of decellularized tendons under dynamic load was investigated using a custom developed bioreactor. As a proof of concept, human gracilis tendons were decellularized and reseeded with human dermal fibroblasts and cultured for 7 days dynamically (2%-6% strain at 1 Hz for 7 h a day) or statically. Thereafter, the viability and infiltration ability of the reseeded cells were assessed. The loading protocol used in this study demonstrated that the bioreactor could measure the transient response of tendon mechanical behavior and could detect changes in mechanical properties over time. The application of dynamic load to reseeded decellularized tendons had no significant effect on cell adhesion, viability, cell metabolism, and infiltration. In both loading groups, cell infiltration was localized rather than globally observed. As bioreactors can serve as an in vitro or ex vivo model to potentially predict in vivo outcomes, this bioreactor shows promising potential for future ACL graft research.
In Vitro Assessment and Preliminary In Vivo Characterization of Innovative Hybrid Materials for Biomedical Applications.
Todesco M, Luisetto R, Casarin M … +11 more , Simoni E, Penzo D, Sandrin D, Modesti M, Astolfi L, Albertin G, Romanato F, Marchesan M, Gerosa G, Fontanella CG, Bagno A
J Biomed Mater Res A · 2025 Oct · PMID 41069216 · Publisher ↗
Hybrid materials are gaining increasing attention for several applications since they properly combine biological and synthetic components, leveraging the advantages of both; thus, these materials can integrate with the...
Hybrid materials are gaining increasing attention for several applications since they properly combine biological and synthetic components, leveraging the advantages of both; thus, these materials can integrate with the host organism to support proper functions, offering new promising solutions, especially in the biomedical field. In this study, we developed hybrid membranes by combining decellularized porcine pericardium with a commercial polycarbonate urethane, available in two formulations: without (AR) and with microsilica particles (AR-LT). These membranes were characterized through chemical and physical analyses; their cytocompatibility was assessed in vitro via direct contact tests, and their biocompatibility was checked in vivo by implanting the materials in a subdermal pouch in a rat animal model. Three kinds of mechanical tests have been performed to check different mechanical features: tensile test to rupture, to measure the mechanical resistance in terms of elastic modulus, failure strain (FS), and ultimate tensile strength (UTS); cyclic tests to assess the effects of repetitive loadings on the mechanical resistance; and stress-relaxation tests to assess the time-dependent behavior. The physicochemical analyses demonstrated that the two components well adhere to each other, with traces of the polymer on the pericardial side of the membranes. Considering mechanical response, coupling pericardium with the polymer causes a reduction of FS and UTS compared to the individual components. Hybrid materials show a viscoelastic behavior while loading cycles do not cause significant changes in their tensile resistance. In vitro tests showed no cytotoxic effects, with cell proliferation observed for up to 7 days. In vivo, 8 weeks after implantation, the hybrid membranes exhibited better integration with host tissue compared to the polymer alone (control), and the polymeric component did not show any sign of degradation. The improved integration was demonstrated by increased neovascularization around the implant, reduced fibrotic capsule thickness, lower expression of interleukin-6 (IL-6), and stable body weight of the rats throughout the experiment. This study highlights the potential of the hybrid membranes for tissue engineering applications, combining favorable biocompatibility and adequate mechanical features.
Modulating Hydrogel Stiffness Through Light-Based 3D Printing to Mimic Cardiac Fibrosis and Cardiomyocyte Dysfunction Using hiPSC-Derived Cells.
Sohn S, Momtahan N, Stevens LM … +6 more , Han J, Liu Y, Kiker MT, Recker EA, Page ZA, Zoldan J
J Biomed Mater Res A · 2025 Oct · PMID 41055580 · Publisher ↗
The human heart's limited regenerative capacity is a significant barrier to addressing cardiovascular disease (CVD). This is particularly true for cardiac fibrosis, a form of CVD wherein the wound healing process has gon...
The human heart's limited regenerative capacity is a significant barrier to addressing cardiovascular disease (CVD). This is particularly true for cardiac fibrosis, a form of CVD wherein the wound healing process has gone awry. In cardiac fibrosis, excessive scar tissue formation due to dysregulated remodeling of the heart's extracellular matrix (ECM) results in increased stiffness that reduces cardiac output and can lead to heart failure. This dysregulated ECM deposition is driven by activated cardiac fibroblasts, where cell substrate stiffness is known to play a role in cardiac fibroblast activation. New preclinical models that accurately recapitulate the behavior of activated cardiac fibroblasts are needed to better understand and treat cardiac fibrosis. To this end, we describe a model wherein human induced pluripotent stem cell (hiPSC)-derived cardiac fibroblasts (HCFs) are cultured on 3D printed hydrogels of tunable stiffness, fabricated using dosage-controlled digital light processing (DLP). We demonstrate that our model can induce HCF activation in the absence of TGFβ, a key mediator of fibroblast activation, surpassing the activation levels seen with HCFs activated with TGFβ on protein-coated tissue culture plates. Furthermore, combining stiffer hydrogels with TGFβ recapitulates fibroblast activation similar to what is observed in native cardiac tissue. Lastly, by indirectly coculturing HCFs seeded and activated on these stiff hydrogels with hiPSC-derived cardiomyocytes, we demonstrate that the activated HCFs in our cardiac fibrosis model can impair cardiomyocyte function, mimicking the deleterious effects of cardiac fibrosis.
GelMA Hydrogel Encapsulating iPSC-Derived Human Spinal Cord Organoids Enhances Neural Regeneration and Restores Motor Function in Rat Spinal Cord Injury.
Li Y, Gu Y, Wang Z … +6 more , Wang Y, Jiang S, Wang K, Zheng Y, Feng R, Yang M
J Biomed Mater Res A · 2025 Oct · PMID 41051068 · Publisher ↗
Spinal cord injury (SCI) severely compromises neural regeneration due to limited intrinsic repair capacity. Combining induced pluripotent stem cell (iPSC)-derived organoids with biomaterial scaffolds offers a promising r...
Spinal cord injury (SCI) severely compromises neural regeneration due to limited intrinsic repair capacity. Combining induced pluripotent stem cell (iPSC)-derived organoids with biomaterial scaffolds offers a promising regenerative strategy. This study investigated the therapeutic potential of human spinal cord organoids (hSCOs) encapsulated within gelatin methacryloyl (GelMA) hydrogel for SCI repair. hSCOs were generated from iPSCs via stage-specific patterning (dorsoventral inhibition followed by retinoic acid/SAG-induced motor neuron specification) and encapsulated in GelMA hydrogel. The therapeutic efficacy of hSCOs/GelMA composites was evaluated in a rat T10 contusion SCI model (n = 6/group: Sham, SCI, GelMA-only, GelMA+hSCOs). Functional recovery was assessed weekly for 4 weeks using Basso-Beattie-Bresnahan (BBB) locomotor scores and inclined plane tests. Histological (H&E, Nissl) and immunofluorescence analyses (Tuj1, GFAP, NF200, CD68) quantified tissue repair, neuronal regeneration, astrogliosis, and neuroinflammation at the lesion site. hSCOs expressed key spinal cord markers (OLIG2, NKX6.1, Tuj1, Islet1) and maintained high viability within GelMA hydrogels. Implantation of GelMA+hSCOs composites significantly enhanced functional recovery (improved BBB scores and inclination angles) and reduced lesion volume compared to both SCI and GelMA-only controls. Immunofluorescence revealed that GelMA+hSCOs treatment promoted neuronal integration (increased density of Tuj1 neurons and NF200 neurofilaments), attenuated astrogliosis (reduced GFAP scarring), and suppressed neuroinflammation (decreased CD68 macrophages) at the injury epicenter relative to control groups. The integration of iPSC-derived hSCOs with GelMA hydrogel significantly promotes structural and functional recovery after SCI by facilitating neuronal survival and integration, mitigating glial scar formation, and modulating the inflammatory response. This combinatorial organoid-hydrogel approach demonstrates substantial translational potential for neural repair strategies.
Decellularised Cartilage-Based Hydrogels Functionalised With Chondroitin Sulphate and Quercetin: The Impact on Chondrogenesis.
Rosa NDS, Neves N, Gelinsky M … +3 more , Santos SG, Bernhardt A, Barbosa MA
J Biomed Mater Res A · 2025 Oct · PMID 41039807 · Publisher ↗
Tissue engineering and regenerative medicine approaches are being actively developed for degenerative disorders, including osteoarthritis (OA). Decellularized matrix (dECM) is a promising biomaterial; however, glycosamin...
Tissue engineering and regenerative medicine approaches are being actively developed for degenerative disorders, including osteoarthritis (OA). Decellularized matrix (dECM) is a promising biomaterial; however, glycosaminoglycan (GAG) loss during decellularization limits its chondrogenic potential. In this study, we aimed to overcome this by developing a dECM hydrogel originating from cartilage, functionalized with the GAG chondroitin sulphate (CS), to replenish those originally depleted and incorporating quercetin to enhance hydrogel properties and chondrogenesis. An optimized decellularization protocol efficiently removed DNA, but with a significant loss of GAGs (73%). After dECM solubilization, functionalization with CS or aldehyde modified CS (mCS) was performed. CS-functionalized hydrogels maintained low stiffness compared to non-functionalized hydrogel, while 0.2 mg/mL mCS hydrogels exhibited significantly slower gelation kinetics. To aid the hydrogel's chondrogenic ability, a novel approach using quercetin was investigated. Incorporation of 0.3 mg/mL quercetin in 0.4 mg/mL mCS-functionalized hydrogels resulted in increased gel stiffness. The impact on cell viability and chondrogenic differentiation was evaluated. Results showed similar cell viability in dECM and CS-functionalized hydrogels at 1 and 3 days of culture, with no significant changes in gene expression of chondrogenic and hypertrophic genes. In quercetin-containing hydrogels, the viability of human dermal fibroblasts was not significantly different from non-functionalized hydrogels, while human chondrocytes showed a significant upregulation of collagen type II, with 6.6- and 2.2-fold increases for 0.15 and 0.3 mg/mL quercetin, respectively. These results provide an initial proof-of-concept for dECM functionalization strategies that restore lost CS while incorporating quercetin, creating a microenvironment favorable for cartilage repair.
Triamcinolone Acetonide (TCA)-Loaded Biodegradable Microspheres Improve Therapeutic Outcomes in Thyroid-Associated Ophthalmopathy (TAO) by Reducing Fibrosis and Adipogenesis.
Xie B, Xiong W, Zhang F … +3 more , Cao J, Chenzhao C, Chen X
J Biomed Mater Res A · 2025 Oct · PMID 41036639 · Publisher ↗
Thyroid-associated ophthalmopathy (TAO) is an inflammatory orbital disease linked to thyroid dysfunction, leading to fibrosis and adipogenesis, which compromise visual acuity and quality of life. Triamcinolone acetonide...
Thyroid-associated ophthalmopathy (TAO) is an inflammatory orbital disease linked to thyroid dysfunction, leading to fibrosis and adipogenesis, which compromise visual acuity and quality of life. Triamcinolone acetonide (TCA) is effective in managing inflammation; however, it is limited by delivery challenges and side effects. This study evaluates TCA-loaded biodegradable microspheres (TCA@MS) as a controlled-release system to improve TCA's therapeutic efficacy in TAO. It was hypothesized that TCA@MS would enhance drug uptake, reduce fibrosis, and inhibit adipogenesis in TAO models. The TCA@MS was prepared and characterized for drug loading and release, showing 95% release within 7 days. The average diameter of TCA@MS is approximately 365 nm. The TCA@MS demonstrated a drug loading efficiency of approximately 10% and an encapsulation efficiency of around 55%. In vitro, TCA@MS enhanced TCA uptake, reduced fibrosis marker levels, and inhibited adipogenic differentiation in transforming growth factor beta 1 (TGF-β1)-induced human orbital fibroblasts (OFs). In vivo, TCA@MS intraorbital injection treatment of TAO mice decreased adipose tissue, inflammatory cell infiltration, and collagen deposition more effectively than free TCA intraorbital injection treatment. The fibrosis (CTGF, collagen I), proliferative marker (ki-67), and adipogenesis markers (PPARγ) were also downregulated by TCA@MS treatment in TAO mice. These findings suggest that TCA@MS offers a promising delivery system for localized treatment of TAO, providing sustained therapeutic effects with reduced adverse outcomes.
Biochemical and Biophysical Properties of Extracellular Matrix Nanofibers Modulate iPSC-Derived Human Hepatocyte Maturation.
Yuan Y, Madruga LC, Cotton KY … +2 more , Kipper MJ, Khetani SR
J Biomed Mater Res A · 2025 Oct · PMID 41036615 · Publisher ↗
Human liver models grown in the lab are used for testing drug metabolism and toxicity, studying liver diseases, and developing new therapies. Induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) prov...
Human liver models grown in the lab are used for testing drug metabolism and toxicity, studying liver diseases, and developing new therapies. Induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) provide a renewable alternative to scarce primary human hepatocytes (PHHs), but they remain functionally immature compared to adult liver cells. The extracellular matrix (ECM) is a key regulator of liver cell behavior, yet how its biochemical makeup, stiffness, and structural organization work together to influence HLC maturation is not well understood. Here, we engineered electrospun nanofibers from collagen I, chitosan, porcine liver ECM (PLECM), and blends of these materials. Over 3 weeks of differentiation, HLCs cultured on ECM nanofibers showed more advanced functional maturation than those grown on standard Geltrex-coated substrates. Importantly, chitosan/collagen nanofibers promoted greater HLC function than either hydrogels of similar stiffness or proteins adsorbed to glass, highlighting the importance of nanoscale topography. By contrast, stiffer polyvinyl alcohol nanofibers of comparable size failed to enhance HLC maturation, a result linked to higher nuclear activity of the mechanosensor Yes-associated protein 1 (YAP). These findings demonstrate that ECM nanofibers drive more mature iPSC-HLCs and advance the development of predictive human liver models for drug discovery, disease modeling, and regenerative medicine.
Biodegradable Piezoelectric Zinc Oxide Composite Scaffolds Affect Mesenchymal Stem Cell Osteochondral Differentiation Under Mechanical Loading.
Khader A, Limaye A, Arinzeh TL
J Biomed Mater Res A · 2025 Oct · PMID 41024652 · Publisher ↗
Bone and cartilage tissue have known piezoelectric properties, which means the tissues can generate electrical activity in response to mechanical deformation. Piezoelectricity may be an important physical cue for regener...
Bone and cartilage tissue have known piezoelectric properties, which means the tissues can generate electrical activity in response to mechanical deformation. Piezoelectricity may be an important physical cue for regenerating tissues. However, biodegradable, biocompatible piezoelectric materials that can be used as tissue engineering scaffolds are limited. In this study, a biodegradable, piezoelectric scaffold was developed where zinc oxide (ZnO), which has known piezoelectric properties, was fabricated into a 3-D fibrous scaffold consisting of polycaprolactone (PCL), a slow-degrading biopolymer, with embedded ZnO nanoparticles (10 wt.%). The ZnO-PCL scaffold was then corona poled in order to improve its piezoelectric activity. The d piezoelectric coefficient was 0.21 + 0.05 pC/N for poled ZnO-PCL scaffold. ZnO-PCL and ZnO-PCL-poled composite scaffolds were investigated for promoting human mesenchymal stem cell (MSC) growth and differentiation while subjected to physiological loading without inductive factors in the culture media. Comparisons were made with a PCL control scaffold. Under dynamic compression conditions, the ZnO-PCL group had higher cell growth and promoted chondrogenic differentiation as demonstrated by significantly higher collagen type II and GAG production and gene expression for Sox-9 as compared to PCL control and ZnO-PCL-poled scaffolds, whereas MSCs on ZnO-PCL-poled scaffolds underwent osteogenic differentiation as indicated by significantly higher collagen type I and VEGF-A production. Cells on ZnO-PCL-poled scaffolds also had alkaline phosphatase activity, although not significantly different from the PCL control and ZnO-PCL groups. This study demonstrates ZnO composite scaffolds hold promise as a tissue engineering strategy for osteochondral tissue engineering.
Mechanisms of Osteoblast-Like Cells and Bacterial Responses to Copper in Titanium-Copper Alloys.
Khalid J, Stephen AS, Rawlinson SCF … +1 more , Allaker RP
J Biomed Mater Res A · 2025 Oct · PMID 41024645 · Publisher ↗
Titanium-copper (Ti-Cu) alloys are gaining attention for their dual functionality in promoting osteogenesis while providing antimicrobial protection, making them ideal candidates for dental and orthopedic implants. Coppe...
Titanium-copper (Ti-Cu) alloys are gaining attention for their dual functionality in promoting osteogenesis while providing antimicrobial protection, making them ideal candidates for dental and orthopedic implants. Copper's ability to enhance bone cell activity and inhibit bacterial growth could help address two critical challenges: successful osseointegration and the prevention of peri-implant infections. This study investigated the cellular and molecular mechanisms by which copper, when incorporated into titanium alloys, stimulates both pro-osteogenic behavior and inhibits bacterial viability. MG-63 osteoblast-like cells were cultured on Ti-5Cu alloy surfaces, and osteogenic activity was assessed through alkaline phosphatase (ALP) activity, collagen deposition, and mineralization assays. Gene expression analysis using qPCR and protein expression via band densitometry provided insights into key pathways, including copper homeostasis and bone matrix formation. The antimicrobial effects of Ti-5Cu were evaluated against common pathogens such as Escherichia coli and Staphylococcus aureus, as well as oral bacteria such as Streptococcus oralis and Fusobacterium nucleatum. Bacterial gene expression was analyzed using qPCR and RNA sequencing. Osteoblast-like cells cultured on Ti-5Cu surfaces showed enhanced ALP activity, increased collagen production, and significant gene upregulation of RUNX2, Osteonectin, Alkaline phosphatase, and BMP-2, driving bone matrix formation. Copper homeostasis proteins, such as CTR1 and ATP7A/ATP7B, were modulated to prevent cytotoxicity while supporting osteogenesis. Ti-5Cu alloys also exhibited broad-spectrum antimicrobial effects, significantly reducing bacterial viability. In S. oralis, stress response genes, CsoR and SOD, were upregulated in response to copper exposure, indicating oxidative stress and disruption of copper homeostasis. Transcriptome analysis found that the alloys induce oxidative stress and disrupt metal homeostasis in commensal bacteria such as S. oralis and Actinomyces naeslundii. The study demonstrates that Ti-5Cu alloys effectively promote osteoblast differentiation and mineralization while preventing bacterial colonization through copper-induced stress responses. These findings support the potential of Ti-5Cu alloys for clinical applications, particularly in dental implants, where both regenerative bone formation and infection prevention are critical for long-term success.
Carrier-Free Nanomaterials Simultaneously Combat Infection and Inflammation for Enhanced Diabetic Wound Healing.
Wang K, Zhang J, Han B … +5 more , Xu Y, Xu J, Yuan F, Wang L, Zhu J
J Biomed Mater Res A · 2025 Oct · PMID 40999652 · Publisher ↗
Diabetic wound ulcers, characterized by chronic infection and persistent inflammation, significantly impair patient quality of life and present substantial socioeconomic burdens. Traditional therapeutic strategies freque...
Diabetic wound ulcers, characterized by chronic infection and persistent inflammation, significantly impair patient quality of life and present substantial socioeconomic burdens. Traditional therapeutic strategies frequently encounter challenges, including antibiotic resistance, systemic side effects, and inadequate control over localized inflammation. We herein developed novel carrier-free nanoparticles (CeCur NPs) by self-assembling chlorin e6 (Ce6) and curcumin, achieving simultaneous photodynamic antibacterial activity and sustained anti-inflammatory effects. CeCur NPs exhibited effective and synergetic anti-bacteria and anti-inflammation both in vitro and in vivo. Comprehensive biosafety evaluations further confirmed the excellent biocompatibility of CeCur NPs, underscoring their potential as a promising therapeutic strategy for accelerating diabetic wound healing.
Field-Emitted Silver Ions at Atmospheric Pressure: Antibacterial Activity and Penetration Into Artificial Skin.
Daiko Y, Akiyama M, Matsuoka K … +2 more , Urushihara D, Obata A
J Biomed Mater Res A · 2025 Oct · PMID 40994255 · Publisher ↗
Silver (Ag) ions are field-emitted under atmospheric pressure from a sharpened Ag ion-conductive glass by applying a high voltage. This study investigates the antibacterial efficacy of emitted Ag ions. When Ag ions are i...
Silver (Ag) ions are field-emitted under atmospheric pressure from a sharpened Ag ion-conductive glass by applying a high voltage. This study investigates the antibacterial efficacy of emitted Ag ions. When Ag ions are irradiated onto hydroxyapatite (HAP) for 5 min, an antibacterial effect against Escherichia coli is clearly observed. Furthermore, Ag ion irradiation directly into the E. coli suspension results in a significant reduction in viable E. coli after 24 h of incubation, compared to immediately after ion irradiation. Although Ag ions are expected to rapidly lose energy upon collision with air molecules, penetration exceeding 100 μm into the hydrated agar gel is confirmed. When Ag ions are irradiated onto the surface of an artificial skin (3D reconstructed human epidermis model), fungal cells located beneath the skin are successfully eliminated. These results demonstrate, for the first time, that field-emitted Ag ions under atmospheric conditions exhibit potent antimicrobial activity.
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