A Di-aptamer-functionalized scaffold promotes bone regeneration by facilitating the selective retention of MSCs and EPCs and then promoting crosstalk between osteogenesis and angiogenesis

The crosstalk between osteogenesis and angiogenesis plays an important role in promoting the formation of a microenvironment that supports bone regeneration. This suggests that the retention of endogenous osteogenic and angiogenic cells in the bone defect area can promote tissue-engineered bone (TEB) osteogenesis and cell–cell interactions. In this study, a Di-Aptamer-functionalized HA/β-TCP (Di-Aptamer-H/T) scaffold was prepared by sequential modification of APTES and sulfo-SMCC and connected with aptamer HM69 and EPC1. We confirmed that aptamers HM69 and EPC1 can specifically identify mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), respectively. This process triggers the expression of adhesion-related genes in these cells and allows these cells to selectively stay coupled to Di-Aptamer-H/T. The osteogenic differentiation ability of MSCs treated with Di-Aptamer-H/T in vitro was significantly increased. Similarly, the ability of Di-Aptamer-H/T-treated EPCs to form blood vessels was also enhanced. Notably, the osteogenic and angiogenic abilities of cocultured MSCs and EPCs treated with the Di-Aptamer-H/T scaffold were significantly better than those of cells cultured individually. In vivo, the results of micro-CT angiography, H&E staining, Masson's staining and histochemical staining further confirmed that Di-Aptamer-H/T formed new bones and vessels more readily than those treated with a single aptamer linked to HA/β-TCP or with HA/β-TCP alone. In brief, our study demonstrated that crosstalk between osteogenesis and angiogenesis is promoted by the Di-Aptamer-H/T scaffold, which serves as a potential treatment strategy for bone defects and can improve outcomes.