Gelatin-methacrylate microspheres loaded with tendon-derived stem cells facilitate tendinopathy healing

Tendon injuries are very common in orthopedic practice and can lead to constant pain, disability, and huge financial burden on society. Gelatin methacrylate (GelMA) and tendon-derived stem cells (TDSCs) may be helpful for the treatment of chronic micro-injury disease of the tendons. In vitro, GelMA microspheres were physically evaluated and assessed for their biological effects on TDSCs, including adhesion, proliferation, and ability to differentiate into tendons, and were also analyzed by sequencing at the RNA level and validated for relevant signaling pathways. A rat Achilles tendon microinjury model was used to evaluate the effect of GelMA microspheres combined with TDSCs on tendon repair. GelMA microspheres promoted adhesion, proliferation, and early tendinous differentiation of TDSCs. TDSCs were able to secrete large amounts of extracellular matrix and activate RAS/ERK signaling in the GelMA microenvironment. In vivo, injection of TDSCs-loaded GelMA microspheres promoted repair of Achilles tendon microinjury. GelMA microspheres and TDSCs synergistically promote Achilles tendon regeneration with the involvement of the RAS/ERK signaling pathway.