Gentamicin and bone morphogenic protein-2 (BMP-2)-delivering heparinized-titanium implant with enhanced antibacterial activity and osteointegration

Abstract

Insufficient bonding of implants to bone tissues and bacterial infections lead to the failure of titanium (Ti)-based orthopedic and dental implants. The aim of this study is to develop novel Ti implants that enhance osteoblast functions, while simultaneously decreasing bacterial infections. First, the surface of pristine Ti was functionalized with heparin-dopamine by mimicking a mussel adhesion mechanism. Gentamicin sulfate (GS) and/or bone morphogenic protein-2 (BMP-2) was then sequentially immobilized to the heparinized-Ti (Hep-Ti) surface. The compositions of pristine Ti and Hep-Ti with or without gentamicin and/or BMP-2 were characterized by X-ray photoelectron spectroscopy (XPS) and the growth of Staphylococcus aureus on the substrates was assayed. Osteoblast functions of all Ti substrates were investigated by cell proliferation assays, alkaline phosphatase (ALP) activity, and calcium deposition. The results showed that the growth of bacteria on GS/Hep-Ti and GS/BMP-2/Hep-Ti was significantly lower compared to that on the pristine Ti and BMP-2/Hep-Ti. In addition, BMP-2/Hep-Ti and GS/BMP-2/Hep-Ti significantly enhanced ALP activity and calcium mineral deposition of osteoblast cells. Taken together, GS/BMP-2/Hep-Ti could achieve the dual functions of excellent antibacterial activity and osteoblast function promotion. Therefore, dual drug (antibiotics and osteoinductive protein)-eluting Ti substrates such as GS/BMP-2/Hep-Ti are a promising material for the enhanced osteointegration and implant longevity in orthopedics and dentistry.