Smart integrated biomaterial systems for precision and optimized delivery of MSCs and their exosomes: Transforming wound healing and organ regeneration.

Mesenchymal stem cells (MSCs) and their exosome (MSCs-Exos) have been shown to be major therapeutic candidates in regenerative medicine due to their inherent capacity for modulating immune response, promoting angiogenesis, and repairing tissues. However, clinical application of MSCs and MSCs-Exos is hindered by various intrinsic barriers, such as poor survival of transplanted MSCs, quick systemic clearance of exosomes, uncontrolled release of therapeutic payloads, and loss of function in severe pathological situations, such as chronic wounds and fibrotic tissues. To overcome these limitations, recent advances have focused on the design of modern delivery systems to enhance the stability, bioavailability, and functionality of MSCs and MSCs-Exos. These platforms include responsive hydrogels, engineered nanoparticles, and multi responsive intelligent dressings that mirror protective microenvironments in general and provide controlled, long-term distribution of bioactive elements. This current review focuses on such innovative approaches that enhance regeneration results in strong preclinical models, maximize therapeutic delivery, and boost MSCs and exosome survival. Despite remarkable advancements, major obstacles still exist, such as guaranteeing biosafety, achieving scale production, and obtaining regulatory approvals. The combination of MSCs and MSCs-Exos therapies with intelligent, responsive biomaterials capable of providing antimicrobial function and active monitoring has the potential to revolutionize tissue regeneration and wound healing and make MSCs and MSCs-Exos invaluable resources in precision regenerative medicine of the future.