Controlled release of gentamicin from gelatin/genipin reinforced beta-tricalcium phosphate scaffold for the treatment of osteomyelitis

Abstract

Infection of the bone (osteomyelitis) remains one of the most challenging problems in the field of orthopedic surgery. The limitations of systemic antibiotics administration include undesired side effects, systemic toxicity, patient discomfort, and development of bacterial resistance. In this study, we developed a bactericidal gentamicin-doped beta-tricalcium phosphate (TCP) scaffold reinforced with a gelatin/genipin hydrogel (G-TCP). Our data showed that the gentamicin-doped G-TCP had a much longer drug releasing period, while the gentamicin was completely released from pure TCP cements (B-TCP) within one day. In addition, the release profile of G-TCP exhibited an initial burst followed by a zero-order release. One standard strain, Staphylococcus aureus (S. aureus, ATCC25923) was selected to evaluate the antibacterial activity and therapeutic effect of this scaffold. G-TCP significantly inhibited growth of S. aureus both in vitro and in vivo. In a rat osteomyelitis model, osteomyelitis could be totally cured after implantation of G-TCP for three weeks. We propose that the gelatin/genipin–gentamicin TCP scaffold represents one of the promising gentamicin releasing bone scaffolds in treating osteomyelitis.