Controlled release of adenosine from core-shell nanofibers to promote bone regeneration through STAT3 signaling pathway

Adenosine (Ade) has been identified to stimulate bone formation. However, the use of Ade is severely limited by the accompanying side effects and its very short half-life in vivo. This study aimed to fabricate an efficient drug-delivery system to reduce the undesirable side effects and enable the clinical application of Ade for treating large bone defects. The fabricated poly(ε-caprolactone) (PCL)/Ade-polyvinyl alcohol (PVA)(0.3/0.4) nanofibrous mats with 0.3:0.4 (w/w) ratio of Ade and PVA showed a sustained and controlled release of Ade and facilitated the osteogenic differentiation of bone mesenchymal progenitor cells (BMSCs). A larger amount of newly formed bone was observed in vivo in the cranial defects of the PCL/Ade-PVA(0.3/0.4) group compared with those of the non-loaded PCL/PVA nanofibrous mats at 4 and 8 weeks after surgery. Moreover, it is the first time to confirm that Ade mediates the osteogenesis of rat BMSCs through the STAT3 signaling pathway and restrains the osteoclastogenesis of rat bone-marrow macrophages (BMMs). These results suggested that this coaxial drug-delivery system loaded with Ade provided a promising and clinically relevant platform to controlled-release Ade and address large bone defects.