{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:28:36Z","timestamp":1788629316293,"version":"build-2803163510"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["3\/1\/2\/2\/Ortho\/2022\/NCD-1"],"award-info":[{"award-number":["3\/1\/2\/2\/Ortho\/2022\/NCD-1"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007855","name":"Central Leather Research Institute","doi-asserted-by":"publisher","award":["OLP- 2403"],"award-info":[{"award-number":["OLP- 2403"]}],"id":[{"id":"10.13039\/501100007855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Trauma, aging, arthritis, and sports injuries are provoking conditions of osteochondral defects (OCDs). If left untreated, these conditions may affect millions and create a significant socio-economic burden. Repair of osteochondral tissue poses significant challenges owing to its lack of vascularization and intricate zonal architecture, which includes both subchondral bone and superficial cartilage layers. This study aims to fabricate a biomimetic bilayer scaffold for osteochondral defect regeneration, emphasizing the restoration of both chondral and subchondral regions. The subchondral layer was prepared with an inorganic phase (hydroxyapatite and graphene oxide [HAP\u2013GO]), while the cartilage layer was constructed with an organic phase (collagen type I and fibrin [COL\u2013F]) to replicate the native extracellular matrix (ECM) of osteochondral tissue. Structural and physicochemical characterization of the bilayer scaffold demonstrated an integrated layer with appropriate pore sizes, high porosity, and optimal mechanical strength. In vitro evaluations exhibited high biocompatibility and cellular adhesion. Furthermore, the osteoinductive and chondroinductive potential of the scaffold\u2019s bone and chondral layers were evaluated at cellular and molecular levels. In vivo studies in a rat model showed significant osteochondral defect regeneration after 12 weeks, evidenced by complete defect closure through macroscopic analysis, X-ray, and microcomputed tomography. Histological and immunohistochemical analyses confirmed collagen and glycosaminoglycan deposition, supporting initial bone and chondral tissue formation. The enhanced healing potential of this cell-free bilayer scaffold suggests it is a promising biomaterial for osteochondral regeneration.<\/jats:p>","DOI":"10.1021\/acsabm.5c01784","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T13:23:26Z","timestamp":1761830606000},"page":"10456-10471","source":"Crossref","is-referenced-by-count":3,"title":["Engineered Composite\nBilayer Scaffold with Functional\nOsteogenic and Chondrogenic Potential to Repair Articular Cartilage\nDefect"],"prefix":"10.1021","volume":"8","author":[{"given":"Srinivetha","family":"Pathmanapan","sequence":"first","affiliation":[{"name":"Council of Scientific and Industrial Research (CSIR) , , Adyar , ,","place":["Chennai, India, 600020"]},{"name":"Anna University , , ,","place":["Chennai, India, 600020"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwathi","family":"Vijayalekha","sequence":"additional","affiliation":[{"name":"B.S. Abdur Rahman Crescent Institute of Science and Technology , , ,","place":["Chennai, Tamil Nadu, India, 600048"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok Kumar","family":"Pandurangan","sequence":"additional","affiliation":[{"name":"B.S. Abdur Rahman Crescent Institute of Science and Technology , , ,","place":["Chennai, Tamil Nadu, India, 600048"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7333-6344","authenticated-orcid":true,"given":"Niraikulam","family":"Ayyadurai","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research (CSIR) , , Adyar , ,","place":["Chennai, India, 600020"]},{"name":"Academy of Scientific and Innovative Research (AcCSIR) , ,","place":["Ghaziabad, India, 201 002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-005X","authenticated-orcid":true,"given":"Suresh Kumar","family":"Anandasadagopan","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research (CSIR) , , Adyar , ,","place":["Chennai, India, 600020"]},{"name":"Academy of Scientific and Innovative Research (AcCSIR) , ,","place":["Ghaziabad, India, 201 002"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"2026072914071864900_cit1","doi-asserted-by":"publisher","first-page":"812383","DOI":"10.3389\/fbioe.2021.812383","article-title":"Scaffold-Based\nTissue Engineering Strategies for Osteochondral Repair","volume":"9","author":"Fu","year":"2022","journal-title":"Front. 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Cartil."},{"issue":"4","key":"2026072914071864900_cit4","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1021\/acs.biomac.9b00043","article-title":"Thermosensitive\nHydrogels as Scaffolds for Cartilage Tissue Engineering","volume":"20","author":"Zhang","year":"2019","journal-title":"Biomacromolecules"},{"key":"2026072914071864900_cit5","doi-asserted-by":"publisher","first-page":"5189","DOI":"10.12659\/MSM.904082","article-title":"Repair of\nOsteochondral Defects in a Rabbit Model Using Bilayer Poly (Lactide-co-Glycolide)\nScaffolds Loaded with Autologous Platelet Rich Plasma","volume":"23","author":"Zhang","year":"2017","journal-title":"Med. Sci. Monit."},{"issue":"11","key":"2026072914071864900_cit6","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1016\/j.joca.2019.07.002","article-title":"Clinical,\nhumanistic, and economic\nburden of osteoarthritis among noninstitutionalized adults in the\nUnited States","volume":"27","author":"Zhao","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"2026072914071864900_cit7","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1007\/s11431-020-1597-4","article-title":"A biomimetic bi-layered\ntissue engineering scaffolds for osteochondral defects repair","volume":"64","author":"Liu","year":"2021","journal-title":"Sci. China: Technol. Sci."},{"issue":"6","key":"2026072914071864900_cit8","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1007\/s10439-010-0038-y","article-title":"Bioactive stratified polymer ceramic-hydrogel\nscaffold for integrative\nosteochondral repair","volume":"38","author":"Jiang","year":"2010","journal-title":"Ann. Biomed. 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Mater."},{"key":"2026072914071864900_cit25","doi-asserted-by":"publisher","first-page":"599","DOI":"10.3390\/polym13040599","article-title":"Collagen Type I Biomaterials as Scaffolds\nfor Bone Tissue Engineering","volume":"13","author":"Rico-Llanos","year":"2021","journal-title":"Polymers"},{"issue":"17","key":"2026072914071864900_cit26","doi-asserted-by":"publisher","first-page":"9879","DOI":"10.3390\/ijms23179879","article-title":"Physical, Mechanical, and Biological\nProperties of Fibrin Scaffolds for Cartilage Repair","volume":"30","author":"Rojas-Murillo","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2026072914071864900_cit27","doi-asserted-by":"publisher","first-page":"102251","DOI":"10.1016\/j.nano.2020.102251","article-title":"Fibrin hydrogel incorporated with\ngraphene oxide functionalized nanocomposite scaffolds for bone repair\n- In vitro and in vivo study","volume":"29","author":"Pathmanapan","year":"2020","journal-title":"Nanomed. Nanotechnol.\nBiol. Med."},{"key":"2026072914071864900_cit28","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.ijbiomac.2019.04.113","article-title":"Development of a\nnanocomposite scaffold of gelatin-alginate-graphene\noxide for bone tissue engineering","volume":"133","author":"Purohit","year":"2019","journal-title":"Int. J. Biol.\nMacromol."},{"issue":"1","key":"2026072914071864900_cit29","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1515\/bmc-2020-0017","article-title":"Graphene Oxide:\nA Promising Material for Regenerative Medicine and Tissue Engineering","volume":"11","author":"Maleki","year":"2020","journal-title":"Biomol. 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Sci."},{"key":"2026072914071864900_cit32","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1016\/j.ijbiomac.2020.09.212","article-title":"Polymeric scaffold of Gallic acid\nloaded chitosan nanoparticles infused with collagen-fibrin for wound\ndressing application","volume":"165","author":"Kaparekar","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"2026072914071864900_cit33","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.jmst.2013.10.011","article-title":"Synthesis and characterization\nof nano-hydroxyapatite\npowder using wet chemical precipitation reaction","volume":"30","author":"Abidi","year":"2014","journal-title":"J. Mater. Sci. Technol."},{"key":"2026072914071864900_cit34","doi-asserted-by":"publisher","first-page":"108947","DOI":"10.1016\/j.matdes.2020.108947","article-title":"Biphasic fish\ncollagen\nscaffold for osteochondral regeneration","volume":"195","author":"Zhou","year":"2020","journal-title":"Mater.\nDes."},{"key":"2026072914071864900_cit35","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.biomaterials.2018.01.056","article-title":"Gradient nano-engineered\nin situ forming composite\nhydrogel for osteochondral regeneration","volume":"162","author":"Radhakrishnan","year":"2018","journal-title":"Biomaterials"},{"issue":"10","key":"2026072914071864900_cit36","doi-asserted-by":"publisher","first-page":"2300815","DOI":"10.1002\/adem.202300815","article-title":"Hyaluronic\nAcid-based Cell-free Composite Scaffold\nPromotes Osteochondral Repair In Vitro by Upregulating Osteogenic-\nand Chondrogenic-Specific Gene Expressions","volume":"26","author":"Pathmanapan","year":"2024","journal-title":"Adv. Eng. Mater."},{"key":"2026072914071864900_cit37","doi-asserted-by":"publisher","first-page":"5077","DOI":"10.3390\/ijms20205077","article-title":"Graphene Oxide\nEnhances Chitosan-Based 3D Scaffold Properties for Bone Tissue Engineering","volume":"20","author":"Dinescu","year":"2019","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"2026072914071864900_cit38","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1002\/jbm.a.36555","article-title":"Electroactive\ngraphene oxide-incorporated collagen assisting vascularization for\ncardiac tissue engineering","volume":"107","author":"Norahan","year":"2019","journal-title":"J. Biomed. 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Macromol."},{"key":"2026072914071864900_cit44","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s40204-019-0113-x","article-title":"Fabrication\nof biocompatible porous\nscaffolds based on hydroxyapatite\/collagen\/chitosan composite for\nrestoration of defected maxillofacial mandible bone","volume":"8","author":"Rahman","year":"2019","journal-title":"Prog. Biomater."},{"key":"2026072914071864900_cit45","doi-asserted-by":"publisher","first-page":"629270","DOI":"10.3389\/fbioe.2021.629270","article-title":"Effect of Pore Size\non Cell Behavior Using Melt Electrowritten Scaffolds","volume":"9","author":"Han","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"issue":"Pt 1","key":"2026072914071864900_cit46","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.msec.2016.08.027","article-title":"A new bi-layered\nscaffold for osteochondral tissue\nregeneration: In vitro and in vivo preclinical investigations","volume":"70","author":"Sartori","year":"2017","journal-title":"Mater. Sci. Eng., C"},{"key":"2026072914071864900_cit47","doi-asserted-by":"publisher","first-page":"4314","DOI":"10.1557\/s43578-023-01145-z","article-title":"Biomimetic scaffold\ndevelopment for bone tissue engineering: Crosslinking graphene with\ncollagen to enhance mechanical strength, conductivity, and porous\nstructure","volume":"38","author":"Rebecca","year":"2023","journal-title":"J. Mater. 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