Abstract

Failure of poly(aryl ether ketone) (PAEK) bone implants results mainly from poor osteogenesis and bacterial infection. One promising strategy for enhancing osteointegration involves developing a bioactive surface of PAEK implants through chemical modification. Poly(phthalazinone ether nitrile ketone) (PPENK) is considered a potential PAEK bone implant because it possesses mechanical properties similar to those of natural bone and its cyano group has high reactivity which provides a surface modification strategy. In this work, recombinant human bone morphogenetic protein-2 (rhBMP-2) and newly synthesized cationic antimicrobial polypeptides (AMPs) were chemically conjugated to a PPENK substrate surface to enhance osteogenic and antibacterial activities. The molecular structures of AMP-1 and AMP-2 containing PEG segments were confirmed by nuclear magnetic resonance spectroscopy. The surface roughness of each substrate was reduced by rhBMP-2 and AMP immobilization. In situ, real-time quartz crystal microbalance with dissipation studies revealed that the loading amount increased with the successive immobilization of rhBMP-2 and AMPs. In vitro antibacterial assay confirmed that the AMP-modified PPENK surfaces provided an effective antibacterial effect and the number of residential bacteria remaining on the substrate was reduced by the PEG segments in AMP-2. In vitro osteogenic properties of the rhBMP-2-modified PPENK surface presented favorable cytocompatibility and osteo-inductive activity. In vivo studies confirmed that the rhBMP-2 and AMP immobilization led to decrease amounts of fibrous tissues around the implant and improved bone regeneration. This study provides a strategy for surface modification that enhances the antibacterial and osteogenic activities to develop a bone implant material with considerable potential for clinical application.