Chitosan microcarriers loaded with functional drug for stimulating osteogenesis and angiogenesis in vitro.

Abstract

Angiogenesis-osteogenesis coupling plays important roles in bone regeneration; therefore, biomaterials capable of stimulating both osteogenesis and angiogenesis show significant influence in bone repair. Herein, chitosan (CS) microcarriers loaded with functional drug dimethyloxalylglycine (DMOG) were prepared using the emulsion phase separation and impregnation method for stimulating osteogenesis and angiogenesis. FTIR and zeta potential analyses confirmed successful DMOG loading into CS microcarriers, primarily through physical adsorption, particularly hydrogen-bond interaction. As the impregnation concentration of DMOG increased, the amounts of DMOG loaded into the microcarriers increased, while the drug encapsulation efficiency decreased. All microcarriers, ranging in size from 200 to 400 μm, revealed quasi-spherical shapes and an interconnected porous structure with pore sizes mainly between 15 and 30 μm, suitable for cell attachment and proliferation. The introduction of DMOG increased the residues of the microcarriers during thermogravimetric analysis. CS/DMOG microcarriers exhibited sustained drug release (for >19 days) and good degradation ability. Furthermore, CS/DMOG microcarriers supported stem cell adhesion and proliferation. They also enhanced stem cell osteogenesis verified by strengthening alkaline phosphatase expression and mineralization. Moreover, they promoted angiogenesis, as evidenced by stimulating endothelial cell migration and tube formation. These results suggest that CS/DMOG microcarriers have the potential to be used for bone tissue regeneration.