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Effects of the tetrahedral framework nucleic acids on the skeletal muscle regeneration in vitro and in vivo

The challenges associated with muscle degenerative diseases and volumetric muscle loss (VML) emphasizes the prospects of muscle tissue regeneration. Especially, it is essential to maintain the stemness and self-renewal of myoblasts for generating an adequate number of cells as quickly as possible, which highlights the importance of the quantity and quality of myoblasts. However, changes in aged cellular status are gradually manifested due to decline in muscle repair capacity. Currently, in the absence of a satisfactory approach to maintain muscle regeneration capacity, the discovery of drugs for promoting myoblast activity in muscle regeneration remains the goal of experimental research. Tetrahedral framework nucleic acids (tFNAs) can regulate various biological behaviors of cells, including proliferation and migration, which imply a great potential in tissue engineering. In the present study, we investigated the effects of tFNAs on proliferation, autophagy regulation, stemness maintenance, and associated potential mechanism of myoblasts, and their skeletal muscle repairment in vivo. Our results revealed that tFNAs promoted the proliferation of myoblasts via the Wnt/β-catenin signal pathway. Moreover, the autophagy level of myoblasts was upregulated and the stemness was also maintained upon exposure to tFNAs. Further, the animal experiments demonstrated that tFNAs could accelerate skeletal muscle regeneration in acute muscle injury. Therefore, a new idea for enhancing myoblast activity and promoting skeletal muscle regeneration based on the application of tFNAs is provided.