Improving osteogenesis of PLGA/HA porous scaffolds based on dual delivery of BMP-2 and IGF-1 via a polydopamine coating

Abstract

To engineer bone tissue, an ideal biodegradable implant should be biocompatible, biodegradable, osteoinductive and osteoconductive. However, the lack of bioactivity has seriously restricted the development of biodegradable implants in bone tissue engineering. In this study, we have developed a three-dimensional porous poly(L-lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) scaffold based on the dual delivery of bone morphogenic protein 2 (BMP-2) and insulin-like growth factor 1 (IGF-1) via polydopamine (PDA) coating. The aim of this study was to improve the osteoinductivity of biodegradable implants for clinical bone repair via a PDA-assisted BMP-2 and IGF-1 surface modification strategy. Our study demonstrated that PDA layer surface modification could more efficiently immobilize BMP-2 and IGF-1 on the scaffold surfaces than physical adsorption, and the immobilized growth factor was released slowly and steadily from the scaffold in a sustained manner. MC3T3-E1 cell attachment and proliferation on IGF-1 and BMP-2-immobilized porous scaffolds were much higher than other groups. According to an in vitro osteogenesis assay, alkaline phosphatase (ALP) activity, the expression of osteogenesis-related genes and the mineralization capacity of MC3T3-E1 cells were increased by the incorporation of BMP-2 and IGF-1. In vivo, digital radiograph evaluation demonstrated that there was the most rapid healing in the defects treated with the IGF-1 and BMP-2 immobilized porous scaffold compared with the other groups eight weeks after implantation. In vitro and in vivo results of this study revealed that the PDA-assisted surface modification method can be a useful tool to graft biomolecules onto biodegradable implants, and the dual release of BMP-2 and IGF-1 could promote cell proliferation and osteogenesis differentiation. Based on the results, the surface modification strategy with growth factors has great potential for the enhancement of osteointegration of biodegradable bone implants.