Endothelial cells-derived Exosomes-based Hydrogel Improved Tendinous Repair via anti- inflammatory and Tissue Regeneration-promoting Properties

Abstract Tendon injuries are common orthopedic ailments with a challenging healing trajectory, especially prominent in cases like Achilles tendon afflictions. The healing trajectory of tendon injuries is often suboptimal, leading to scar formation and functional impairment due to inherent low metabolic activity and vascularization of tendon tissue. The pressing need for effective interventions has led to exploring biomaterials to augment tendon healing. However, tissue engineering approaches face hurdles in optimizing tissue scaffolds and nanomedical strategies. To navigate these challenges, we innovated an injectable hydrogel amalgamated with Human Umbilical Vein Endothelial Cells derived exosomes (HUVECs-Exos) aiming for enhanced tendon repair. Employing this concoction in a rat Achilles tendon injury model, both in vivo and in vitro explorations were conducted, unveiling augmented mechanical fortitude, modulated inflammation, stimulated tendon regeneration, and expedited functional recuperation. Extensive in vivo assessments entailed histological and behavioral evaluations. Mechanically, HUVECs-Exos modulated the cellular behavior of macrophages and tendon-derived stem cells (TDSCs) by inhibiting inflammation-related pathways and promoting proliferation-related pathways. Our findings delineate that the HUVECs-Exos epitomized a viable bioactive medium for tendon restoration, heralding a promising avenue for clinical amelioration of tendon injuries.