Abstract
Articular cartilage's avascular and aneural nature severely limits its intrinsic regenerative capacity, making injuries and degenerative diseases like osteoarthritis a significant clinical challenge. This review comprehensively examines the paradigm shift towards regenerative medicine strategies, focusing on the integration of the natural polyphenol curcumin into advanced cartilage tissue engineering. While curcumin possesses potent multi-modal therapeutic properties-including anti-inflammatory, antioxidant, anti-catabolic, and chondroprotective effects-its clinical translation is hindered by poor bioavailability and rapid metabolism. We explore innovative biomaterial-based solutions to these limitations, detailing the development of sophisticated DDSs such as nanoparticles, hydrogels (e.g., chitosan, gelatin methacrylate), and synthetic scaffolds (e.g., PCL, PLGA) that enable targeted, sustained release. The review critically analyzes the transition from conventional surgical techniques to emerging therapies like MSC-based treatments, gene therapy, and 3D-bioprinted constructs. Furthermore, we synthesize compelling clinical evidence demonstrating that bioavailable curcumin formulations (e.g., Meriva(®), Theracurmin(®)) significantly improve pain, stiffness, and functional scores in OA and RA patients. By bridging cutting-edge biomaterial science with the ancient therapeutic wisdom of curcumin, this review highlights a promising frontier in restoring joint integrity and offers a critical roadmap for future research in combinatorial regenerative approaches.