Scaffold Mediated Delivery of Kartogenin for Replenishing Cartilage Defects: A Scoping Review on Recent Trends and Future Frontiers

The progressive deterioration of cartilage tissues ultimately results in joint pain and dysfunction, which is clinically recognized as osteoarthritis (OA). Kartogenin (KGN), a heterocyclic molecule, has been identified as a promising chondrogenic and chondroprotective drug candidate, as it mimics the natural ligands involved in cell signaling and differentiation. The standalone effectiveness of KGN is often hindered by its own physical and chemical properties (hydrophobicity and short retention), therefore combining KGN with a suitable carrier biomaterial is often desirable to improve its bioavailability. Various biomaterials have been functionalized with KGN using different fabrication strategies, such as hydrogels, three-dimensional (3D) bioprinting, electrospinning, and scaffold engineering, to promote effective cartilage regeneration. The purpose of this review is to provide a comprehensive overview of promising approaches used in the delivery of KGN, either as a standalone therapeutic molecule or in combination with biomaterials to augment cartilage repair, particularly in the context of OA. A special emphasis on the biomaterial functionalization with KGN in terms of synthesis, structure, function and applications have been discussed elaborately. Finally, this review will summarize and document a handful of insights about the potential benefits, limitations and future prospects of KGN functionalized biomaterials in cartilage repair and regeneration.