INTRODUCTION: In grade III open fractures, therate of infection can be as high as 30%. Protection against infection can be achieve by delivering high concentrations of antibiotics locally using antibiotic loaded biomaterials (ALBs). However, to date commercial available ALBs cannot be introduced easily into complex wound fracture. Thus, a flowing thermo-responsive hydrogel might be beneficial over conventional ALBs. In this study, a hyaluronic acid-poly(N-isopropylacrylamide) (HApN) hydrogel loaded gentamicin was synthesised and characterized in vitro. Furthermore, the ability of the HApN loaded with gentamicin to prevent infection in and its influence the bone healing was investigated in an in vivo model.
MATERIALS & METHODS: A thermo-responsive hyaluronic acid derivative (hyaluronic acid- poly(N-isopropylacrylamide) (HApN)) was prepared by a direct amidation reaction between the tetrabutyl ammonium (TBA) salt of hyaluronic acid and amine-terminated poly(N-isopropylacrylamide) (pN). The degree of grafting, molecular weight and gelation properties of this gel were characterized, and the composition was loaded with gentamicin. The rheological- and release properties of this gentamicin-loaded HApN composition were tested in vitro and its efficacy in preventing infection was tested in a rabbit model of osteosynthesis contaminated with Staphylococcus aureus (ter Boo et al., 2016). Non-infected control (n=10) and non-infected with HApN (n=10) did not receive a bacterial inoculum, whereas rabbits belonging to infected control (n=10) and infected + HApN + Genentamicin (n=10) received a bacterial inoculum after creation of the osteotomy.
RESULTS: The gentamicin-loaded-HApN composition was able to prevent bacterial colonization of the implant site as shown by quantitative bacteriology at 1 and 4 weeks. This finding was supported by histopathological evaluation of the humeri samples where no bacteria were found in the stained sections. The HApN did not impede bone healing as shown non-destructive four-point bending test.
CONCLUSION: Gentamicin-loaded HApN hydrogel effectively prevents infection in a complex wound, simulating a contaminated fracture treated with plating osteosynthesis without impeding of the bone healing.