{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:53:22Z","timestamp":1792688002580,"version":"4.5.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>\n                    Chronic kidney disease (CKD) and the limited availability of donor organs continue to drive the need for advanced biomaterial systems for renal tissue engineering and\n                    <jats:italic>in vitro<\/jats:italic>\n                    kidney modeling. However, reproducing the spatial complexity and compartmentalized organization of native renal tissue remains a significant challenge. In this study, a compartmentalized silk fibroin (SF)-reinforced gelatin methacrylate (GelMA) hydrogel platform with spatially defined architectures inspired by renal tissue organization was developed. Initially, SF-reinforced GelMA hydrogels with tunable stiffness were fabricated by varying the concentration of the hydroxyethyl methacrylate (HEMA) crosslinker, while SF was incorporated at concentrations of 25\u00a0mg\/mL and 50\u00a0mg\/mL to systematically modulate the physicochemical properties of the hydrogels. The resulting formulations were characterized through degradation and swelling analyses, along with preliminary\n                    <jats:italic>in vitro<\/jats:italic>\n                    cytocompatibility studies. Degradation studies demonstrated that low-stiffness hydrogels exhibited more controlled degradation behavior compared to high-stiffness formulations, particularly at higher SF concentrations, indicating improved structural stability. Swelling analysis revealed that all hydrogel groups supported fluid uptake, with hydrogels containing 25\u00a0mg\/mL SF exhibiting comparatively stable swelling and degradation profiles.\n                    <jats:italic>In vitro<\/jats:italic>\n                    studies confirmed that all scaffold formulations supported cellular attachment and exhibited non-toxic behavior. Based on the optimized hydrogel formulation, a two-zone compartmentalized platform was subsequently developed consisting of a central triangular-patterned region inspired by the renal medulla and a surrounding honeycomb-patterned region representing the renal cortex. Confocal imaging demonstrated spatial organization of L929 fibroblasts within the patterned hydrogel architecture, while depth-coded three-dimensional confocal imaging of nuclei-stained renal proximal tubular epithelial cells (RPTECs) at days 1, 3, and 5 enabled visualization of cell localization within the engineered patterned regions. Collectively, this study demonstrates the feasibility of developing a compartmentalized SF\u2013GelMA hydrogel platform with tunable material properties and spatially organized architectures inspired by renal tissue organization. The platform provides a promising foundation for future studies involving kidney-specific cell populations and region-specific renal tissue engineering applications.\n                  <\/jats:p>","DOI":"10.3389\/fbioe.2026.1876387","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:41:01Z","timestamp":1784785261000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of a compartmentalized silk fibroin\u2013reinforced GelMA hydrogel platform for kidney-inspired tissue engineering"],"prefix":"10.3389","volume":"14","author":[{"given":"Amrita","family":"Natarajan","sequence":"first","affiliation":[{"name":"Laboratory for Polymeric Biomaterials, Department of Biomedical and Mechanical Engineering, Alabama State University","place":["Montgomery, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghasilia","family":"Stewart","sequence":"additional","affiliation":[{"name":"Laboratory for Polymeric Biomaterials, Department of Biomedical and Mechanical Engineering, Alabama State University","place":["Montgomery, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Sudha","sequence":"additional","affiliation":[{"name":"Laboratory for Polymeric Biomaterials, Department of Biomedical and Mechanical Engineering, Alabama State University","place":["Montgomery, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick","family":"Dean","sequence":"additional","affiliation":[{"name":"Laboratory for Polymeric Biomaterials, Department of Biomedical and Mechanical Engineering, Alabama State University","place":["Montgomery, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineeth M.","family":"Vijayan","sequence":"additional","affiliation":[{"name":"Laboratory for Polymeric Biomaterials, Department of Biomedical and Mechanical Engineering, Alabama State University","place":["Montgomery, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"123349","DOI":"10.1016\/j.biomaterials.2025.123349","article-title":"Tuneable gelatin methacryloyl (GelMA) hydrogels for the directed specification of renal cell types for hiPSC-derived kidney organoid maturation","volume":"322","author":"Clerkin","year":"2025","journal-title":"Biomaterials"},{"key":"B2","doi-asserted-by":"publisher","first-page":"031509","DOI":"10.1063\/5.0046076","article-title":"The effects of surface topography modification on hydrogel properties","volume":"5","author":"Cui","year":"2021","journal-title":"APL Bioeng."},{"key":"B3","doi-asserted-by":"publisher","first-page":"pgae289","DOI":"10.1093\/pnasnexus\/pgae289","article-title":"Spatial regulation of substrate adhesion directs fibroblast morphotype and phenotype","volume":"3","author":"D\u2019Urso","year":"2024","journal-title":"PNAS Nexus"},{"key":"B4","doi-asserted-by":"publisher","first-page":"134834","DOI":"10.1016\/j.ijbiomac.2024.134834","article-title":"Bioactive silk fibroin hydrogels: unraveling the potential for biomedical engineering","volume":"278","author":"Fern\u00e1ndez-Gonz\u00e1lez","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"109842","DOI":"10.1016\/j.eurpolymj.2020.109842","article-title":"Tuning the conformation and mechanical properties of silk fibroin hydrogels","volume":"134","author":"Johari","year":"2020","journal-title":"Eur. Polym. J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"127882","DOI":"10.1016\/j.ijbiomac.2023.127882","article-title":"Fundamental properties of smart hydrogels for tissue engineering applications: a review","volume":"254","author":"Khan","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1007\/s10856-021-06542-6","article-title":"Fabrication and characterization of an antibacterial chitosan\/silk fibroin electrospun nanofiber loaded with a cationic peptide for wound-dressing application","volume":"32","author":"Khosravimelal","year":"2021","journal-title":"J. Mater Sci. Mater Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e2103526","DOI":"10.1002\/advs.202103526","article-title":"Kidney decellularized extracellular matrix enhanced the vascularization and maturation of human kidney organoids","volume":"9","author":"Kim","year":"2022","journal-title":"Adv. Sci. (Weinh)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"671402","DOI":"10.3389\/fcell.2021.671402","article-title":"Organ-specific branching morphogenesis","volume":"9","author":"Lang","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"100399","DOI":"10.1016\/j.medntd.2025.100399","article-title":"Effects of silk fibroin incorporation on the mechanical properties and osteogenic activity of bone repair materials","volume":"28","author":"Liu","year":"2025","journal-title":"Med. Nov. Technol. Devices"},{"key":"B11","doi-asserted-by":"publisher","first-page":"114","DOI":"10.4252\/wjsc.v16.i2.114","article-title":"Human pluripotent stem cell-derived kidney organoids: current progress and challenges","volume":"16","author":"Long","year":"2024","journal-title":"World J. Stem Cells"},{"key":"B12","doi-asserted-by":"publisher","first-page":"431","DOI":"10.3390\/gels9050431","article-title":"Application of silk-fibroin-based hydrogels in tissue engineering","volume":"9","author":"Lyu","year":"2023","journal-title":"Gels"},{"key":"B13","doi-asserted-by":"publisher","first-page":"554","DOI":"10.3390\/bioengineering9100554","article-title":"A concise review on electrospun scaffolds for kidney tissue engineering","volume":"9","author":"Miranda","year":"2022","journal-title":"Bioeng. (Basel)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1444986","DOI":"10.3389\/fbioe.2024.1444986","article-title":"Optimizing scaffold pore size for tissue engineering: insights across various tissue types","volume":"12","author":"Mukasheva","year":"2024","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"908","DOI":"10.3390\/gels11110908","article-title":"Silk fibroin-derived smart living hydrogels for regenerative medicine and organoid engineering: bioactive, adaptive, and clinically translatable platforms","volume":"11","author":"Mushtaq","year":"2025","journal-title":"Gels"},{"key":"B16","doi-asserted-by":"publisher","first-page":"114099","DOI":"10.1016\/j.colsurfb.2024.114099","article-title":"3D printing assisted surface patterning process on acrylated hydrogels for contact guidance of fibroblasts","volume":"242","author":"Natarajan","year":"2024","journal-title":"Colloids Surfaces B Biointerfaces"},{"key":"B17","doi-asserted-by":"publisher","first-page":"53343","DOI":"10.1021\/acsami.5c16374","article-title":"3D surface-patterned hyaluronic acid hydrogels: customizable platforms for enhanced chondrogenic differentiation and organized production of a specific hyaline cartilage extracellular matrix","volume":"17","author":"Natarajan","year":"2025","journal-title":"ACS Appl. Mater Interfaces"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1273923","DOI":"10.3389\/fcell.2023.1273923","article-title":"Harnessing mechanobiology for kidney organoid research","volume":"11","author":"Nauryzgaliyeva","year":"2023","journal-title":"Front. Cell Dev. Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"23018","DOI":"10.1038\/s41598-024-73735-8","article-title":"A systematic review and quality assessment of economic evaluations of kidney replacement therapies in end-stage kidney disease","volume":"14","author":"Nyokabi","year":"2024","journal-title":"Sci. Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3893","DOI":"10.1021\/acsbiomaterials.5c00286","article-title":"Silk Fibroin\/gelMA-based hydrogels as a platform for tissue adhesives and tissue engineering","volume":"11","author":"Patel","year":"","journal-title":"ACS Biomater. Sci. Eng."},{"key":"B21","doi-asserted-by":"publisher","first-page":"56606","DOI":"10.1007\/s11356-022-19833-4","article-title":"Silk fibroin: a promising bio-material for the treatment of heavy metal-contaminated water, adsorption isotherms, kinetics, and mechanism","volume":"29","author":"Pilley","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1476510","DOI":"10.3389\/fbioe.2024.1476510","article-title":"Effective and new technologies in kidney tissue engineering","volume":"12","author":"Rayat Pisheh","year":"2024","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"5706","DOI":"10.1039\/d3bm00255a","article-title":"Renal tissue engineering for regenerative medicine using polymers and hydrogels","volume":"11","author":"Syed Mohamed","year":"2023","journal-title":"Biomater. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"822","DOI":"10.3390\/polym17060822","article-title":"Extracellular matrix stiffness: mechanotransduction and mechanobiological response-driven strategies for biomedical applications targeting fibroblast inflammation","volume":"17","author":"Tiskratok","year":"2025","journal-title":"Polym. (Basel)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"75","DOI":"10.22306\/atec.v11i2.272","article-title":"Hydrogels as bioactive scaffolds in biomedical engineering","volume":"11","author":"Trebunova","year":"2025","journal-title":"Acta Tecnol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41378-025-01141-9","article-title":"Strategies to control cellular spatial organization in microphysiological systems","volume":"12","author":"Truong","year":"2026","journal-title":"Microsyst. Nanoeng."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e00429","DOI":"10.1016\/j.bprint.2025.e00429","article-title":"Impact of polymer degradation on cellular behavior in tissue engineering","volume":"50","author":"Umemori","year":"2025","journal-title":"Bioprinting"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1472361","DOI":"10.3389\/fphar.2024.1472361","article-title":"Recent advances in extracellular matrix manipulation for kidney organoid research","volume":"15","author":"Wang","year":"2024","journal-title":"Front. Pharmacol."}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2026.1876387\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:41:02Z","timestamp":1784785262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2026.1876387\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":28,"alternative-id":["10.3389\/fbioe.2026.1876387"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2026.1876387","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"article-number":"1876387"}}