Bmscs loaded exosome hydrogel promotes the repair of rotator cuff injury in rats in vivo

To explore whether the hydrogels loaded with bone marrow mesenchymal stem cell-derived exosomes can facilitate the repair and regeneration of tendons in rats with acute rotator cuff injury through regulating transforming growth factor-beta1 (TGF-β1). After the extraction and identification of mesenchymal stem cell-derived exosomes, 60 male Sprague-Dawley rats were randomly divided into five groups (n = 12 per group): control (untreated), repair-alone, GelMA (hydrogel only), BMSC-Exos (hydrogel + BMSC-Exos), and BMSC-Exos + TGF-β1 inhibited (hydrogel + BMSC-Exos + TGF-β1 inhibitor P144). An acute rotator cuff injury repair model was established in the left shoulder joint of the rats, and different treatments were administered to the rats according to the groups. Six weeks later, the rats in each group were sacrificed, and HE staining, Masson staining, Sirius Red staining, biomechanical tests, and PCR detection were carried out. BMSC-Exos were successfully isolated and characterized. Biomechanical tests showed that the BMSC-Exos group exhibited significantly higher maximum failure load and stiffness compared with the repair-alone, GelMA, and BMSC-Exos + TGF-β1 inhibited groups (all P < 0.05), reaching levels similar to the normal control. Histological scoring revealed that the BMSC-Exos group had better collagen fiber continuity, parallelism, density, and fewer inflammatory cells and blood vessels at the tendon-bone interface. Gene expression analysis demonstrated that the BMSC-Exos group significantly upregulated the mRNA levels of ColⅠ, ColⅢ, Scx, and α-SMA compared with the other experimental groups (all P < 0.05). The hydrogels loaded with mesenchymal stem cell-derived exosomes can enhance the repair and regeneration of tendons in rat shoulder cuff injuries through TGF-β1.