Tetrahedral framework nucleic acids promote the biological functions and related mechanism of synovium-derived mesenchymal stem cells and show improved articular cartilage regeneration activity in situ.

Many recent studies have shown that joint-resident mesenchymal stem cells (MSCs) play a vital role in articular cartilage (AC) in situ regeneration. Specifically, synovium-derived MSCs (SMSCs), which have strong chondrogenic differentiation potential, may be the main driver of cartilage repair. However, both the insufficient number of MSCs and the lack of an ideal regenerative microenvironment in the defect area will seriously affect the regeneration of AC. Tetrahedral framework nucleic acids (tFNAs), notable novel nanomaterials, are considered prospective biological regulators in biomedical engineering. Here, we aimed to explore whether tFNAs have positive effects on AC in situ regeneration and to investigate the related mechanism. The results of in vitro experiments showed that the proliferation and migration of SMSCs were significantly enhanced by tFNAs. In addition, tFNAs, which were added to chondrogenic induction medium, were shown to promote the chondrogenic capacity of SMSCs by increasing the phosphorylation of Smad2/3. In animal models, the injection of tFNAs improved the therapeutic outcome of cartilage defects compared with that of the control treatments without tFNAs. In conclusion, this is the first report to demonstrate that tFNAs can promote the chondrogenic differentiation of SMSCs in vitro and enhance AC regeneration in vivo, indicating that tFNAs may become a promising therapeutic for AC regeneration.