Injectable melatonin carbon dot composite hydrogel enhances anti-inflammatory and tenogenic differentiation of tendon-derived stem cells for minimally invasive treatment of Achilles tendinopathy

Achilles tendinopathy (AT), which is characterized by aseptic inflammation, is one of the most common types of tendon injury. Chronic inflammation can worsen AT progression and interfere with tendon repair, and most current anti-inflammatory treatments are associated with adverse effects. Therefore, improving the inflammatory microenvironment and promoting tenogenesis remain major challenges in AT treatment. In this study, melatonin carbon dots (MCDs) combined with an injectable porcine small intestinal submucosal hydrogel (SIS gel) were developed for the minimally invasive treatment of AT. The anti-inflammatory effects and tenogenic differentiation of tendon-derived stem cells (TDSCs) could be enhanced through the sustained release of MCDs. The results showed that MCDs were successfully prepared and that the injectable hydrogel (M-S gel), which was composed of the successfully created MCDs and the SIS hydrogel, had good biocompatibility. The M-S gel markedly promoted the migration of TDSCs. IL-6 levels in the TDSCs were inhibited while those of IL-10 levels were promoted, demonstrating that the M-S gel had excellent anti-inflammatory and regenerative potential. Animal studies indicated that the M-S gel regulated the inflammatory microenvironment and promoted Achilles tendon repair. This study shows that MCDs can enhance the anti-inflammatory and tendon regeneration capacities of injectable SIS hydrogels, offering a new minimally invasive treatment for AT.