Osteogenic and angiogenic dual small molecule loaded chitosan nanoparticles for vascularized bone regeneration

In recent years, the preference for small molecules has increasingly overshadowed growth factors. In this study, an osteogenic factor, DIPQUO, and an angiogenic factor, a VEGF inducer, GS4012, were encapsulated in chitosan nanoparticles (NPs) to provide vascularized bone regeneration. The encapsulation efficiencies of DIPQUO and GS4012 were 79% and 75%, respectively. The release profiles were 69% and 41% within the first 3 h, followed by 13 days to complete the release of all materials. The synthesis of NPs was validated via FT-IR analysis, while their thermal properties were assessed via Differential scanning calorimetry (DSC). For in vitro osteogenesis, mesenchymal stem cells isolated from rat bone marrow were investigated by MTS, ALP, and various histological stains (H&E, alizarin red, and von Kossa). In the context of angiogenesis, endothelial cells derived from the peripheral blood of rats were isolated, characterized, and their capabilities to migrate and form vessels assessed. This study demonstrated that two different small molecules act synergistically to enable bone differentiation and may contribute to vascularized bone regeneration.