Smart functionalized cartilage repair microspheres: Concepts and applications

Cartilage has a limited intrinsic capacity for self-repair, causing injuries to progress into degenerative disorders. Current conservative and surgical treatments offer only partial benefits and are often hindered by poor tissue quality, limited durability, and procedural invasiveness. Functionalized microspheres have recently gained attention in cartilage repair due to their biocompatibility, injectability, structural versatility, and ability to achieve controlled therapeutic delivery. Evolving from passive carriers to smart, bioactive platforms, these microspheres can modulate the local regenerative microenvironment through programmable release, structural engineering, and responsive functionalities. This review summarizes the structure and degeneration of articular cartilage and the cartilaginous endplate, introduces major microsphere fabrication techniques and biomaterial choices, and highlights emerging strategies for functionalization. We further discuss structural innovations that enhance therapeutic outcomes and examine the translational potential of microspheres as precise and multifunctional smart microtissues for personalized cartilage regeneration.