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We developed a bilayer scaffold using fish collagen extracted from <jats:styled-content style=\"fixed-case\"><jats:italic>Catla catla<\/jats:italic><\/jats:styled-content> skin to overcome the limitations of conventional biomaterials, such as mammalian collagen and synthetic polymers, which often suffer from immunogenic risks, poor bioactivity, or inadequate structural integration. The scaffold is comprised of collagen\/fibrin (CC\/FIB) for the articular cartilage layer and collagen\/sodium citrate\/hydroxyapatite (CC\/NAC\/HAP) for the subchondral bone layer, which is cross\u2010linked with citric acid. Physicochemical characterization confirmed scaffold integration, enhanced thermal stability, and a porous architecture. The scaffold demonstrated optimal porosity (63.12%), degradation (62.08% over 28\u2009days), superior swelling potential, and enhanced bio\u2010mineralization in simulated body fluid. In\u00a0vitro studies using MG\u201063 osteoblast\u2010like cells and MC3T3\u2010E1 cells showed high biocompatibility, increased alkaline phosphatase activity, and enhanced calcium deposition (33.73\u2009\u00b1\u20090.53\u2009\u03bcg\/mg of protein at 21\u2009days). Gene expression analysis revealed upregulation of osteogenic (<jats:italic>COL I<\/jats:italic> ~23\u2010fold, <jats:italic>RUNX\u20102<\/jats:italic> ~15\u2010fold, <jats:italic>OCN<\/jats:italic> ~8\u2010fold) and chondrogenic (<jats:italic>COL II<\/jats:italic> ~12\u2010fold, <jats:italic>SOX\u20109<\/jats:italic> ~10\u2010fold, <jats:italic>ACAN<\/jats:italic> ~6\u2010fold) markers, confirming osteochondral regeneration potential. In\u00a0vivo studies involving the implantation of 3\u2009mm femoral trochlear OCDs in albino Wistar rats (<jats:italic>n<\/jats:italic>\u2009=\u20093 per group) resulted in substantial bone and cartilage regeneration, with complete defect closure by 12\u2009weeks. Radiographic and histological assessments at 4, 8, and 12\u2009weeks confirmed well\u2010organized osteochondral repair, demonstrating superior regenerative capability compared to control groups. This study establishes the novelty of the fish collagen\u2010based bilayer scaffold as a promising candidate for osteochondral tissue engineering, supporting effective cartilage and subchondral bone regeneration in OCD treatment.<\/jats:p>","DOI":"10.1002\/jbm.a.37977","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T08:26:22Z","timestamp":1755159982000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fish Collagen\u2010Based Bilayer Composite Scaffold Functionalized With Fibrin\/Hydroxyapatite\/Sodium Citrate for Osteochondral Tissue Engineering\u2014In Vitro and\u00a0In\u00a0Vivo Studies"],"prefix":"10.1002","volume":"113","author":[{"given":"Ashwathi","family":"Vijayalekha","sequence":"first","affiliation":[{"name":"School of Life Sciences B.S. 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