Enhancement in sustained release of antimicrobial peptide and BMP-2 from degradable three dimensional-printed PLGA scaffold for bone regeneration

One of the goals of bone tissue engineering is to create scaffolds with well-defined, inter-connected pores, excellent biocompatibility and osteoinductive ability. Three-dimensional (3D)-printed polymer scaffold coated with bioactive peptide are an effective approach to fabricating ideal bone tissue engineering scaffolds for bone defect repair. However, the current strategy of adding bioactive peptides generally cause degradation to the polymer materials or damage the bioactivity of the biomolecules. Thus, in this study, we used a biomimetic process via poly(dopamine) coating to prepare functional 3D PLGA porous scaffolds with immobilized BMP-2 and ponericin G1 that efficiently regulate the osteogenic differentiation of preosteoblasts (MC3T3-E1) and simultaneously inhibit of pathogenic microbes, thereby enhancing biological activity. In this study, we analysed a 3D PLGA porous scaffold by scanning electron microscopy, water contact angle measurements, and materials testing. Subsequently, we examined the adsorption, release and in vitro antimicrobial activity of the 3D PLGA. Surface characterization showed that poly(dopamine) surface modification could more efficiently mediate the immobilization of BMP-2 and ponericin G1 onto the scaffold surfaces than physical adsorption, and that ponericin G1-immobilized 3D PLGA scaffolds were able to maintain long-term antibacterial activity. We evaluated the influence on cell adhesion, proliferation and differentiation by culturing MC3T3-E1 cells on different modified 3D PLGA scaffolds in vitro. The biological results indicate that MC3T3-E1 cell attachment and proliferation on BMP-2/ponericin G1-immobilized 3D PLGA scaffolds were much higher than those on other groups. Calcium deposition, and gene expression results showed that the osteogenic differentiation of cells was effectively improved by loading the 3D PLGA scaffold with BMP-2 and ponericin G1. In summary, our findings indicated that the polydopamine-assisted surface modification method can be a useful tool for grafting biomolecules onto biodegradable implants, and the dual release of BMP-2 and ponericin G1 can enhance the osteointegration of bone implants and simultaneously inhibit of pathogenic microbes. Therefore, we conclude that the BMP-2/ponericin G1-loaded PLGA 3D scaffolds are versatile and biocompatible scaffolds for bone tissue engineering.