Biodegradable Cryo-Self-Assembled Silk Fibroin Sponge for Enzyme-Responsive Exosome Delivery to Enhance Tendon Regeneration

The utilization of biological therapeutic agents in the treatment of tendon injuries represents a promising avenue, with particular attention drawn to adipose mesenchymal stem-cell-derived exosomes (ADSCs-exos) owing to their pivotal role in regenerative medicine. Identifying a therapeutic strategy to prolong exosome retention at the injury site for effective tendon repair remains challenging. In this study, we explored the potential of ADSC-exosomes in vitro, demonstrating their ability to promote the behavior of tendon stem/progenitor cells (TSPCs). Additionally, we designed a fibroin (SF) sponge as a biodegradable platform for enzyme-responsive exosome delivery. Subsequently, we used biodegradable SF sponges to deliver ADSC exosomes into the patellar tendon defect in rats. The results showed that, in vivo, exosomes were gradually released from the SF sponges, remained in the defect area for an extended period, and exerted functional benefits locally. These findings were supported by the upregulation of tendon-associated protein expression and improved mechanical properties observed in the in vivo specimens. In summary, we substantiated the advantageous role of ADSCs-exos in facilitating tendon regeneration. Moreover, the utilization of a SF-exos sponge delivery system emerged as an efficacious local treatment strategy for exosome delivery. These findings hold promise for the future application of exosomes in innovative therapies tailored to address tendon injuries.