In vitro and in vivo investigation of PLA/PCL scaffold coated with metformin-loaded gelatin nanocarriers in regeneration of critical-sized bone defects

The effects of local delivery of metformin (MET) in osteogenic differentiation and healing of the critical sized-calvarial bone defect was evaluated in vitro and in vivo. MET loaded gelatin nanocarriers (MET/GNs) were papered, using the nanoprecipitation method. The poly caprolactone-poly (L-lactic) acid hybrid scaffold (PCL/PLA) was then coated by MET/GNs and characterized by different methodologies. The fabricated scaffolds were implanted into the critical sized-calvarial bone defects and resulted in significant enhanced new bone formation and bone healing in comparison to those of the control ones. Our results suggest that MET increased the expression level of the osteogenic and angiogenic genes; these were confirmed by in vivo results via the local sustained delivery of MET.275