Resveratrol-loaded co-axial electrospun poly(ε-caprolactone)/chitosan/polyvinyl alcohol membranes for promotion of cells osteogenesis and bone regeneration

Abstract

The guided bone regeneration (GBR) membranes currently used in clinics are usually compromised by their limited osteogenic induction potential. In this study, we fabricate a core-shell poly(ε-caprolactone)/chitosan/polyvinyl alcohol (PCL/CS/PVA) GBR membrane with different amount of resveratrol (RSV), endowing the PCL/CS/PVA GBR membrane with superior osteogenic induction ability, which was not attained by the regular GBR membrane. The prepared GBR membranes were characterized by scanning electron microscopy, transmission electron microscopy, and CCK-8 and live-dead staining assays, and their osteogenic induction ability was evaluated using Col-I immunofluorescence staining, micro-computed tomography, haematoxylin and eosin staining and immunohistochemical staining. Results of the in vitro release experiment confirmed that the membranes exhibited a continuous RSV release profile for 15 days. Furthermore, the cumulative releasing of RSV was increased from 39.68 ± 2.09 μg to 65.8 ± 2.91 μg with increasing contents of RSV from 0.1 % to 0.5 % (w/v) in the core layer of GBR membranes. In particular, the PCL/CS/PVA GBR membrane loading with 0.5 % RSV most efficiently release RSV in a sustained and controlled manner, which significantly induced osteogenic differentiation of pre-osteoblasts in vitro and bone regeneration in vivo. Based on the in vivo histological findings, newly formed bone tissues with 82.46 ± 9.86 % BV/TV and 0.70 ± 0.07gcm−3 BMD were generated in the defect sites treated by the GBR membrane loaded with 0.5 % RSV, which were the largest values among those for all three groups after 12 weeks of post implantation. Overall, the PCL/CS/PVA GBR membrane loaded with 0.5 % RSV has significant potential for bone regeneration.