Journal of biomedical materials research. Part A最新文献

{"title":"The PLLA/Gel@BBR 3D Nanoscaffold Protects Hair Cells From Neomycin Damage by Reducing Oxidative Stress","authors":"Xianxia Li,&nbsp;Mengyu Chen,&nbsp;Yue Peng,&nbsp;Wanru Zhai,&nbsp;Yingjie Wang,&nbsp;Yiyin Pan,&nbsp;Xiangxin Lou","doi":"10.1002/jbm.a.70170","DOIUrl":"https://doi.org/10.1002/jbm.a.70170","url":null,"abstract":"<div>\u0000 \u0000 <p>Sensorineural hearing loss (SNHL) is the most prevalent form of hearing impairment observed in clinical practice. The primary pathological characteristic of this condition is the irreversible damage to the cochlear hair cells (HCs) and the associated spiral ganglion neurons (SGNs). Since HCs in the mammalian inner ear lack intrinsic regenerative capacity, damage to these cells often results in irreversible hearing loss. In recent years, two-dimensional (2D) culture systems have made substantial progress in supporting the regeneration of auditory cells. However, the regenerated HCs in these 2D systems fail to develop fully mature, functional stereociliary bundles and do not form synaptic connections with SGNs. As a result, they cannot achieve true physiological restoration of hearing. Therefore, the development of three-dimensional (3D) systems that replicate the inner ear microenvironment is essential for investigating therapeutic methods against SNHL. In this study, we aim to prepare 2D electrospun nanofiber membranes using electrospinning technology, and then these 2D nanofiber membranes were successfully converted into 3D PLLA/Gel@BBR nanoscaffolds via freeze-drying. We subsequently assessed the effects of the inner ear organoid on HC growth and neomycin (Neo)-induced ototoxicity. Our findings indicate that the inner ear organoid effectively mimics the physiological microenvironment of the genuine organ of Corti in the inner ear. This inner ear organoid can facilitate drug sustained-release and protect damaged auditory cells from ototoxic damage. This research offers promising insights for developing innovative strategies to protect auditory cells and treat SNHL.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Modification of Collagen Hydrogels Using UVA-Riboflavin Crosslinking and Silk Fibroin Incorporation to Enhance Mechanical Properties, Stability, and Printability","authors":"Nithyashri Muthu Vijayan,&nbsp;Diya Pillai Babu,&nbsp;Beste Caner,&nbsp;Rohin Shyam,&nbsp;Arunkumar Palaniappan,&nbsp;Vipuil Kishore","doi":"10.1002/jbm.a.70165","DOIUrl":"10.1002/jbm.a.70165","url":null,"abstract":"<p>Type I collagen is a biomaterial of preferred choice due to its biocompatibility, biodegradability, and ability to support cell adhesion and proliferation. However, the use of collagen hydrogels in tissue engineering (TE) is limited due to poor mechanical properties and low stability. This study introduces a novel dual-modification strategy to enhance collagen properties by combining UVA-mediated riboflavin/sodium persulfate (RF/SPS) photocrosslinking with the incorporation of unsonicated silk fibroin (SF), an approach not previously reported. Collagen hydrogels were fabricated in four variations: uncrosslinked collagen (UXL-C), UVA-mediated RF/SPS photocrosslinked collagen (XL-C), SF incorporated UVA-RF/SPS photocrosslinked collagen using two different collagen:SF ratios (XL-CS 1:1 w/w) and (XL-CS 1:2 w/w). Mechanical testing and stability results showed that combining UVA-RF/SPS photocrosslinking and SF incorporation significantly enhanced (<i>p</i> &lt; 0.05) the compressive modulus and increased mass-retention of collagen hydrogels suggesting that the addition of unsonicated SF improves the mechanical properties and stability of photochemically crosslinked collagen hydrogels. All hydrogel compositions exhibit shear-thinning behavior demonstrating applicability for extrusion-based 3D printing via Freeform Reversible Embedding of Suspended Hydrogels (FRESH)-based methodology. 3D printed SF-incorporated collagen constructs showed improved shape fidelity compared to constructs printed with collagen-only inks. In vitro cell culture studies revealed that all hydrogel formulations supported cell viability and metabolic activity over 7 days of culture. Together, these findings demonstrate that combining UVA-mediated RF/SPS photocrosslinking and unsonicated SF incorporation is a viable strategy to improve the mechanical properties, stability, and printability of collagen hydrogels for biomedical and TE applications.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin B6 Modification of Bovine Pericardial Bioprosthetic Heart Valve Leaflets Promotes Blood Outgrowth Endothelial Cell Adhesion","authors":"Tina E. Thomas,&nbsp;Sachin Aryal,&nbsp;Andrey Zakharchenko,&nbsp;Alexis Martinez,&nbsp;Stanley J. Stachelek,&nbsp;Giovanni Ferrari,&nbsp;Robert J. Levy","doi":"10.1002/jbm.a.70175","DOIUrl":"10.1002/jbm.a.70175","url":null,"abstract":"<div>\u0000 \u0000 <p>Bioprosthetic heart valves (BHV), typically fabricated from glutaraldehyde-fixed bovine pericardium (BP), are the most common type of replacement for patients with severe heart valve disease. Despite being preferred, BHV are limited in durability due to structural valve degeneration (SVD), which occurs due to leaflet calcification and non-calcific mechanisms including advanced glycation end product (AGE) accumulation and serum protein infiltration. Another limitation of BHV is characteristically they do not endothelialize, even after years of implantation. Previously we showed pretreating BP with Pyridoxamine (PYR), a vitamer of vitamin B6, effectively mitigated AGE accumulation in vitro and in vivo. The present studies investigated the effect of PYR pretreated BHV on endothelial cell-material interactions, using bone marrow origin human blood outgrowth endothelial cells (BOEC) as a model cell type; the hypothesis was PYR pretreatment would provide a more favorable surface for endothelialization compared to glut-fixed BP. Static studies compared untreated BP versus PYR-BP to examine the effect on cell adhesion; PYR-BP had significantly more BOEC adhered than untreated BP measured by Alamar blue assays. PYR pretreatment under non-AGE and model AGE conditions were also investigated via static and high shear studies. PYR pretreated collagen coated-glutaraldehyde fixed slides significantly increased BOEC attachment over time under AGE and non-AGE conditions. Under arterial shear levels, PYR pretreatment increased BOEC retention compared to untreated slides under non-AGE and AGE conditions. In conclusion, PYR pretreated BP or model, thin-layer collagen surfaces promote endothelial cell attachment and reduced cytotoxicity under static and shear conditions, with or without AGE presence.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Porosity and Stiffness of Articular Cartilage Extracellular Matrix Derived Scaffolds Modulate Chondrogenesis of Mesenchymal Stromal Cells","authors":"Giovanni Gonnella,&nbsp;Tosca Roncada,&nbsp;Daniel J. Kelly","doi":"10.1002/jbm.a.70153","DOIUrl":"10.1002/jbm.a.70153","url":null,"abstract":"<p>Articular cartilage (AC) regeneration remains a major challenge in musculoskeletal tissue engineering. Cartilage extracellular matrix (ECM)-derived scaffolds have shown promise as tissue-specific biomaterials, but the extent to which the fabrication process can be tuned to modulate scaffold pore architecture and mechanics and how this might influence the chondrogenic differentiation of mesenchymal stromal/stem cells (MSCs) remains incompletely defined. The aim of this study was to develop solubilized porcine AC-ECM scaffolds with controlled differences in pore size and matrix stiffness, and to evaluate how these factors regulate chondrogenesis of MSCs. Scaffolds with different pore sizes were fabricated by modifying the freezing cycle during lyophilization through the inclusion of an annealing step, while scaffold stiffness was varied by adjusting the AC-ECM concentration from 10 (1% ECM) to 50 mg/mL (5% ECM). Incorporation of an annealing step led to a ~2.5-fold increase in the mean scaffold pore size and was associated with improved construct elasticity and greater early cellular penetration. Increasing the AC-ECM concentration increased scaffold stiffness, with the ramp modulus increasing from approximately 5 kPa in the 1% scaffolds to approximately 60 kPa in the 5% scaffolds. All scaffold groups supported cartilage-matrix deposition during chondrogenic culture. Higher ECM concentrations were associated with greater total collagen accumulation, while the stiffest 5% scaffolds supported increased Type X collagen staining relative to the softer scaffolds. The expression of key chondrogenic genes <i>SOX9</i>, <i>ACAN</i>, and <i>COL2A1</i> was higher in the 2% scaffolds compared to 5% scaffolds, while the expression of the hypertrophic marker <i>COL10A1</i> was higher in the 5% scaffolds. In summary, scaffold processing provided a practical means to tune pore architecture and bulk mechanical behavior in solubilized AC-ECM scaffolds, and these differences were associated with changes in cell distribution and phenotype. These findings can potentially be leveraged to engineer scaffolds supportive of zonal cartilage tissue engineering or for osteochondral defect repair.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Hydrogel Microenvironment Density Effects on Mechanotransduction In Vitro and Bone Regeneration In Vivo","authors":"Sofia M. Vignolo,&nbsp;Daniela M. Roth,&nbsp;May A. A. Fraga,&nbsp;Lillian Wu,&nbsp;Jameson A. Cosgrove,&nbsp;Avathamsa Athirasala,&nbsp;Angela S. P. Lin,&nbsp;Robert E. Guldberg,&nbsp;Luiz E. Bertassoni","doi":"10.1002/jbm.a.70163","DOIUrl":"10.1002/jbm.a.70163","url":null,"abstract":"<div>\u0000 \u0000 <p>For bone regeneration, matrix density is a critical determinant of scaffold performance, influencing both mechanical stiffness and biological accessibility, that is, how readily cells interact with and remodel the matrix. Here, we investigated how collagen matrix densification modulates stem cell mechanosensing in vitro and bone healing outcomes in vivo using density-tunable collagen microgels. Centrifugation-based collagen densification produced a sixfold increase in stiffness and a compact fibrillar architecture that enhanced early mechanosensitive signaling in human mesenchymal stem cells, including YAP1 and Piezo1 upregulation, reaching levels comparable to biochemical osteoinduction. In vivo, low- and high-density microgels increased bone formation relative to untreated defects, though low-density constructs supported more uniform and volumetric regeneration. Despite these differences in bone volume, bone mineral density and histological maturity were comparable across all groups, while complete bridging was observed only with autologous bone grafts. Our findings demonstrate that matrix densification promotes early mechanotransductive priming, but the microgel format did not achieve full regeneration for either gel group, suggesting that effective bone healing likely requires balancing mechanical stimulation with sufficient biological accessibility. Designing scaffolds with controlled density and adaptive mechanical properties may create dynamically permissive environments that support both early mechanosensing and late-stage remodeling for functional bone repair.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication and Characterization of Bioengineered Sandwich Model Scaffold for Urethral Stricture Reconstruction","authors":"Parvin Mohammadi,&nbsp;Mina Habibizadeh,&nbsp;Zhila Izadi,&nbsp;Kamran Mansouri,&nbsp;Mahmoudreza Moradi","doi":"10.1002/jbm.a.70166","DOIUrl":"10.1002/jbm.a.70166","url":null,"abstract":"<div>\u0000 \u0000 <p>Urethral stricture remains a challenging clinical condition, particularly in patients with long or complex defects where suitable donor tissue is limited. Tissue engineering offers a promising alternative through the development of biomimetic scaffolds capable of restoring urethral structure and function. In this study, we fabricated a sandwich nanofibrous scaffold based on polyglycolic acid (PGA) and decellularized urethral extracellular matrix (uECM) using a sandwich design (uECM/PGA/uECM) and compared it with PGA and mix (PGA–uECM) scaffolds. Successful decellularization was confirmed by histological and molecular analyses, demonstrating effective removal of cellular components while preserving ECM architecture. Structural characterization revealed high porosity, enhanced hydrophilicity, favorable swelling behavior, and controlled degradation in ECM-containing scaffolds. The uECM/PGA/uECM construct exhibited superior mechanical strength while maintaining suitable elasticity for urethral applications. Biological evaluation showed significantly improved endothelial cell adhesion, cell viability, and migration in ECM-integrated scaffolds compared with PGA alone. In vivo implantation demonstrated excellent biocompatibility, absence of adverse inflammatory responses, and evident neovascularization. Overall, the sandwich uECM/PGA/uECM scaffold combines mechanical stability with bioactive functionality, highlighting its potential as a promising candidate for urethral tissue regeneration.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Cytotoxicity of Commercial Materials for Additive Manufacturing of Soft Tissues","authors":"Amal Shabazz,&nbsp;Julia Fitlin,&nbsp;Henry Orozco-Contreras,&nbsp;Cassandra Nti,&nbsp;William Pieper Holeman,&nbsp;Stephen Farias,&nbsp;John P. Fisher","doi":"10.1002/jbm.a.70169","DOIUrl":"10.1002/jbm.a.70169","url":null,"abstract":"<p>The rapid growth of additive manufacturing technologies continues to drive the commercial development of standardized materials to streamline the process. Despite the growing range of available materials, few still achieve a balance between flexibility and biocompatibility. Here, we evaluated the cytotoxicity of Formlabs Biomed Elastic 50A, Biomed Flexible 80A, and Biomed Durable resin using normal human dermal fibroblasts and human mesenchymal stromal cells. The sol fraction of the crosslinked and uncrosslinked materials was measured to determine the amount of leachable components in the polymer network. Following ISO 10993-5 guidelines, cytotoxicity was evaluated through direct, indirect, or extract testing for 24 h. All three materials did not elicit a cytotoxic response when assessed through fluorescence imaging and LDH assay. In each test, cells showed similar viability as cells cultured with a known noncytotoxic control, polycaprolactone, and showed significantly higher viability compared to a cytotoxic control, a polyurethane film containing 0.1% zinc diethyldithiocarbamate (ZDEC). Post-processing parameters were shown to minimize the effects of cytotoxicity when post-treated with an isopropyl alcohol wash, UV post-curing, or ethanol sterilization. Overall, the Formlabs Biomed Elastic 50A, Biomed Flexible 80A, and Biomed Durable resins were shown to exhibit minimal cytotoxicity after printing and post-processing. Further, the presented findings can be adapted to standardize in vitro testing of a wide range of commercial photocurable resins for tissue-interfacing parts.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.70169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Paquinimod-Loaded Implants to Modulate the Foreign Body Response","authors":"Cole Weber,&nbsp;Isabel Vanderzee,&nbsp;Sonja Danon,&nbsp;Meijuan Lin,&nbsp;Shivanie Kodikalla,&nbsp;Aaron H. Morris","doi":"10.1002/jbm.a.70168","DOIUrl":"10.1002/jbm.a.70168","url":null,"abstract":"<p>The foreign body response (FBR) is an immune reaction from the host to any foreign material that makes it beyond barrier tissues, resulting in the recruitment of immune cells and fibroblasts. The FBR to medical implants can lead to degradation and encapsulation, affecting their efficacy, lifespan, and safety. A key protein involved in myriad inflammatory responses is S100A9, inducing inflammatory cytokine secretion and leukocyte chemotaxis. Inspired by recent studies indicating that inhibiting systemic S100A9 in mice results in a diminished FBR, we have identified S100A9 as a potential locally-targetable molecule to reduce FBR. Paquinimod is a potential candidate for local drug delivery, as it is an experimentally available S100A9 inhibitor that has been investigated in autoimmunity and fibrotic disease. We first investigated paquinimod's effects on neutrophil and macrophage cell lines in vitro and found reduced inflammatory cytokine expression. To leverage these effects of paquinimod and assess its ability to mitigate the FBR, we created wet-spun PCL fibrous scaffolds loaded with varied doses of paquinimod. With these scaffolds, we demonstrate successful loading and release of paquinimod, with higher loading leading to decreased cell invasion and reduced deposition of collagen. These findings suggest paquinimod-mediated inhibition of S100A9 activity can modulate inflammation in the FBR through decreased cytokine release and cell recruitment and identify S100A9 as a promising target to locally mediate the FBR to medical implants.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.70168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cascade Catalytic Nanozyme Amplifies Ferroptosis Immunotherapy in Bladder Cancer","authors":"Hongbo Luo,&nbsp;Xiaolong Liu,&nbsp;Yang Du","doi":"10.1002/jbm.a.70164","DOIUrl":"10.1002/jbm.a.70164","url":null,"abstract":"<div>\u0000 \u0000 <p>Immune checkpoint inhibitors have shown limited efficacy in bladder cancer due to the immunosuppressive tumor microenvironment. To address this challenge, we developed a β-lapachone-loaded iron-based carbon nanozyme (C-MIL@Lapa) that synergistically induces ferroptosis and immunogenic cell death (ICD). Carbonized MIL-100(Fe) (C-MIL) serves as both a drug carrier and a nanozyme with dual peroxidase and glutathione oxidase activities. In tumor cells, β-lapachone generates endogenous H₂O₂ via NQO1-mediated redox cycling, which is then converted into cytotoxic hydroxyl radicals by C-MIL. This cascade reaction causes glutathione depletion and lipid peroxidation, leading to ferroptosis. Meanwhile, ferroptotic cell death releases damage-associated molecular patterns that trigger ICD, activating dendritic cells and CD8⁺ T cell-mediated antitumor immunity. In vitro and in vivo results demonstrated that C-MIL@Lapa significantly inhibited bladder cancer growth and remodeled the tumor immune microenvironment. This work provides a nanozyme-based strategy for synergistic ferroptosis-immunotherapy of bladder cancer with promising clinical potential.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of Probiotic-Based Multifunctional Hydrogels Capable of Carrying Oxygen and Anti-Inflammatory Drugs and Their Effect on Cell Viability Under Hypoxic Conditions","authors":"Ulvi Suleymanzade,&nbsp;Yağmur Damla Demir,&nbsp;Dilek Tepeli,&nbsp;Tuğba Ezgi Şahin,&nbsp;Nermin Seda Kehr","doi":"10.1002/jbm.a.70150","DOIUrl":"10.1002/jbm.a.70150","url":null,"abstract":"<p>Hypoxia and chronic inflammation have an interdependent relationship, as they stimulate each other. Under inflammation, hypoxia occurs in tissues and under hypoxia, transcription factors induce overproduction of pro-inflammatory cytokines, causing the chronic inflammatory process. There are very few studies that combine O₂ with anti-inflammatory agents to simultaneously reduce the effects of hypoxia and inflammation. However, despite the important role of probiotic metabolites in regulating pro-inflammatory cytokines, none of these studies have addressed the combined use of O₂, anti-inflammatory agents, and probiotic metabolites to effectively inhibit the harmful effects of hypoxia and inflammation. In this context, we report a biomaterial (GA-^RutPMOF-CAP) consisting of a GelMA-Alginate (GA) hydrogel matrix incorporating rutin-loaded, perfluorocarbon-functionalized periodic mesoporous organosilica (^RutPMOF) nanoparticles and probiotic-loaded alginate microcapsules (CAP), capable of delivering sustained O₂, probiotic-derived metabolites, and pH-sensitive anti-inflammatory drug release. GA-^RutPMOF-CAP, which provides approximately 90% release of the anti-inflammatory drug (Rut) at pH 6.0, &gt; 5% O₂ release within the first 5 days under hypoxic conditions, and release of probiotic metabolites over a 7-day incubation period. GA-^RutPMOF-CAP does not increase the production of reactive oxygen species (ROS) during 1 and 7 day incubation periods under hypoxic conditions. Furthermore, GA-^RutPMOF-CAP supports cell viability under hypoxia and promotes a decrease in TNF-α levels under LPS-stimulated normoxic conditions; this demonstrates that GA-^RutPMOF-CAP has beneficial effects on cells under inflammatory-like conditions.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}