Gelatin Methacrylate Loaded with Adipose-Derived Mesenchymal Stem Cell Exosomes Promotes High-Quality Healing of Injured Tendon by Activating Both SMAD1/5/9 and SMAD2/3

Adipose-derived mesenchymal stem cell exomes (ADSC-Exos) have become a new therapeutic target in biomedical field owing to their important role in regenerative medicine. However, the role of ADSC-Exos in tendon repair has not yet been evaluated. In this study, we explored a new treatment method for tendon injury, combining exosome therapy with local targeting of biohydrogel. We found ADSC-Exos could be absorbed by tendon stem cells (TSCs) and promoted the proliferation, migration, and tenogenic differentiation of the TSCs, which may have depended on the activation of the Smad2/3 and Smad1/5/9 pathways. Furthermore, gelatin methacrylate (GelMA) loaded with ADSC-Exos could promote initial healing of tendons and normalize tendon structure. Overall, we demonstrated that ADSC-Exos contributed to tendon regeneration and that ADSC-Exos–loaded GelMA was able to promote high-quality healing after tendon injury. This study provides proof of concept of a new idea for treating tendon injuries.