Tetrahedral framework nucleic acids promote the proliferation and differentiation potential of diabetic bone marrow mesenchymal stem cell

Diabetes mellitus considerably affects bone marrow mesenchymal stem cells (BMSCs), for example, by inhibiting their proliferation and differentiation potential, which enhances the difficulty in endogenous bone regeneration. Hence, effective strategies for enhancing the functions of BMSCs in diabetes have far-reaching consequences for bone healing and regeneration in diabetes patients. Tetrahedral framework nucleic acids (tFNAs) are nucleic acid nanomaterials that can autonomously enter cells and regulate their behaviors. In this study, we evaluated the effects of tFNAs on BMSCs from diabetic rats. We found that tFNAs could promote the proliferation, migration, and osteogenic differentiation of BMSCs from rats with type 2 diabetes mellitus, and inhibited cell senescence and apoptosis. Furthermore, tFNAs effectively scavenged the accumulated reactive oxygen species and activated the suppressed protein kinase B (Akt) signaling pathway. Overall, we show that tFNAs can recover the proliferation and osteogenic potential of diabetic BMSCs by alleviating oxidative stress and activating Akt signaling. The study provides a strategy for endogenous bone regeneration in diabetes and also paves the way for exploiting DNA-based nanomaterials in regenerative medicine.