Bilayer pifithrin-α loaded extracellular matrix/PLGA scaffolds for enhanced vascularized bone formation

Small intestinal submucosa extracellular matrix (SIS-ECM) composite materials are catching eyes in tissue engineering but have been rarely studied in bone repair. In this study, we developed the unique bilayer bone scaffolds by assembling decellularized SIS-ECM and poly(lactic-co-glycolic acid) (PLGA) nanofibers through the electrospinning technique. To strengthen the bioactivity of the scaffolds, pifithrin-alpha (PFT alpha), a p53 inhibitor that can reduce the repressive function of p53 in osteogenesis, was preloaded in the PLGA electrospinning solution. We found that the resultant SIS-ECM/PLGA/PFT alpha scaffolds exhibited porous morphology, good biocompatibility, and enhanced osteoinductivity. Specifically, the SIS-ECM/PLGA/PFT alpha scaffolds could promote the osteogenic differentiation and mineralization of the preosteoblasts MC3T3-E1 in a PFT alpha does dependent manner in vitro. Furthermore, the SIS-ECM/PLGA/PFT alpha scaffolds were better than the pure SIS-ECM and SIS-ECM/PLGA scaffolds in terms of vessel and new bone tissue formation after 4 weeks post-implantation in vivo. These overall findings indicated that the bilayer PFT alpha loaded SIS-ECM/PLGA scaffolds facilitated vascularized bone regeneration, showing promising potential for bone tissue engineering.