Chitosan-exosome synergy: Advanced cell-free scaffold approaches for bone tissue engineering

Bone regeneration and repair, which are hampered by fractures, bone diseases, and trauma, require innovative therapeutic strategies in the field of regenerative medicine. Conventional treatments, such as the use of autologous and allogeneic bone grafts and metal implants, are the primary modalities for bone augmentation in clinical practice; however, they exhibit various limitations. To overcome these limitations, new paradigms, such as exosome-based therapies using chitosan scaffolds, exhibit significant potential for bone tissue engineering. Exosomes, which serve as cell-free therapeutic agents, promote immunomodulation, angiogenesis, and osteogenesis. Moreover, the distinct structural and functional properties of chitosan facilitate efficient exosome loading and sustained release, exerting localized and prolonged regenerative effects crucial for bone repair. Advanced scaffold modification and exosome mimetic integration are other innovative strategies to promote osteogenesis and vascularized bone regeneration. Focusing on these novel approaches, this review highlights chitosan-exosome scaffolds as transformative platforms for bone tissue engineering, providing new avenues for effective and targeted bone regeneration and repair.