A Mesoporous Silica-loaded Multi-functional Hydrogel Enhanced Tendon Healing via Immunomodulatory and pro-regenerative Effects.

Tendon injuries are pervasive orthopedic injuries encountered by the general population. Nonetheless, recovery after severe injuries such as Achilles tendon injury is limited. Consequently, there is a pressing need to devise interventions, including biomaterials, that foster tendon healing. Regrettably, tissue engineering treatments have faced obstacles in crafting appropriate tissue scaffolds and efficacious nanomedical approaches. To surmount these hurdles, we have pioneered an innovative injectable hydrogel (CP@SiO2 ), comprising puerarin and chitosan through in situ self-assembly, while concurrently delivering mesoporous silica nanoparticles for tendon healing. In our research, we employed CP@SiO2 hydrogel for the treatment of Achilles tendon injuries, conducting extensive in vivo and in vitro experiments to evaluate its efficacy. Our results show that CP@SiO2 hydrogel significantly promotes the proliferation and differentiation of tendon-derived stem cells. BrdU assay results indicated a 12% increase in cell growth rate compared to gel treatment. Additionally, PCR results showed an increase in the expression of genes related to tendon differentiation and stemness maintenance. Moreover, the hydrogel effectively mitigated inflammation by promoting M2 polarization and inhibiting M1 polarization, thus alleviating macrophage-induced inflammation. The hydrogel also accelerated the recovery of injured tendon function; biomechanical assessments revealed that at 28 days post-operation, the load-to-failure ratio of tendons in the CP@SiO2 group was 53.28N, surpassing the 32.06N of the model group. Furthermore, we conducted a comprehensive in vivo evaluation using a tendon injury model, which included detailed histological analysis and behavioral observations. Our findings indicate that this multifaceted injectable CP@SiO2 hydrogel constitutes a suitable bioactive material for tendon repair and presents a promising new strategy for the clinical management of tendon injuries. This article is protected by copyright. All rights reserved.