Functional engineering of adipose-derived stem cell exosomes and its application in soft tissue regeneration

Adipose-derived stem cell exosomes are increasingly recognized as promising cell-free mediators for soft tissue repair because of their favorable biocompatibility, low immunogenicity, and broad paracrine activity. By transferring regulatory RNAs, proteins, lipids, and other bioactive molecules, they participate in key regenerative processes, including angiogenesis, immune modulation, extracellular matrix remodeling, and cellular proliferation. However, native adipose-derived stem cell exosomes still face important translational limitations, including limited targeting specificity, variable cargo composition, rapid clearance, and insufficient retention at injured sites.

Recent advances in exosome engineering provide new opportunities to enhance the regenerative performance of adipose-derived stem cell exosomes. Function-oriented strategies include parental-cell preconditioning, genetic engineering, direct cargo loading, surface modification, and biomaterial-assisted delivery. These approaches can enrich therapeutic cargos, improve lesion-specific targeting, prolong local retention, and enable sustained or microenvironment-responsive release. Current applications are mainly concentrated in wound healing, muscle repair, and adipose tissue regeneration or fat grafting, while tendon-to-bone healing and peripheral nerve repair represent emerging areas with growing preclinical evidence. This review summarizes the biological basis, engineering strategies, application scenarios, and translational challenges of engineered adipose-derived stem cell exosomes in defined soft tissue regenerative settings.

Although engineered adipose-derived stem cell exosomes show encouraging potential for soft tissue regeneration, clinical translation remains at an early stage. Future development should focus on mechanism-guided cargo design, precise targeting, responsive delivery systems, standardized characterization, and clinically scalable production. These advances may support the development of next-generation cell-free therapies for specific soft tissue repair indications.