Cell- and Tissue-Derived Extracellular Matrix-Based Approaches for Osteochondral Repair and Regeneration

Osteochondral (OC) tissue comprises a complex, multilayered structure integrating avascular hyaline cartilage, calcified cartilage, and subchondral bone, each with distinct biochemical compositions and mechanical roles critical to joint function. The superficial hyaline cartilage provides a smooth, load-bearing surface, while the underlying calcified cartilage and subchondral bone offer structural support and mechanical stability. Damage to this interface presents a significant clinical chal-lenge, largely due to cartilage’s poor intrinsic healing capacity, limited chondrocyte proliferation, and the biomechanical complexity of the cartilage–bone junction. Traditional treatments such as marrow stimulation, autologous chondrocyte implan-tation, and osteochondral grafting offer only partial and often temporary relief. These approaches frequently result in fibrocartilage formation and inadequate restoration of tissue architecture, which can ultimately lead to joint degeneration and osteoarthritis. In response, tissue engineering strategies employing decellularized extracellular matrix (dECM) materials have gained increasing attention from researchers as promising alternatives. dECM scaffolds derived either from tissues or produced by cultured cells provide biologically instructive environments that support cell adhe-sion, infiltration, and differentiation. Tissue-derived dECM retains native extracellu-lar components and microarchitecture, while cell-derived dECM allows for design flexibility and tunability to meet specific regenerative needs. Both are recognized for their ability to guide endogenous repair without reliance on exogenous growth factors. Recent advances in tissue-and cell-derived dECM scaffolds, hydrogels, andnanofibrillar compositesarereviewedherein,withafocusonbiomaterialdesigns that integrate structural mimicry and bioactive signaling. These approaches support stem cell–driven regeneration and enhance osteochondral repair outcomes. Collec-tively, dECM platforms represent a versatile, biologicallyrelevant,andincreasinglytranslationalstrategyforaddressingthepersistentchallengesofosteochondraldefectrepair.