Vancomycin-Loaded in situ Gelled Hydrogel as an Antibacterial System for Enhancing Repair of Infected Bone Defects

Shouye Sun,1 Qian Wang,2 Bin Zhang,3 Yutao Cui,1 Xinghui Si,4 Gan Wang,1 Jingwei Wang,1 Hang Xu,1 Baoming Yuan,1 Chuangang Peng1 1Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Otolaryngology, The First Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Spinal Surgery, The 964th Hospital of PLA Joint Logistic Support Force, Changchun, People’s Republic of China; 4Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People’s Republic of ChinaCorrespondence: Baoming Yuan, Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China, Email [email protected]: During treatment of infected bone defects, control of infection is necessary for effective bone repair, and hence controlled topical application of antibiotics is required in clinical practice. In this study, a biodegradable drug delivery system with in situ gelation at the site of infection was prepared by integrating vancomycin into a polyethylene glycol/oxidized dextran (PEG/ODEX) hydrogel matrix.Methods: In this work, PEG/ODEX hydrogels were prepared by Schiff base reaction, and vancomycin was loaded into them to construct a drug delivery system with controllable release and degradability. We first examined the microstructure, degradation time and drug release of the hydrogels. Then we verified the biocompatibility and in vitro ability of the release system. Finally, we used a rat infected bone defect model for further experiments.Results: The results showed that this antibacterial system could be completely biodegradable in vivo for 56 days, and its degradation products did not cause specific inflammatory response. The cumulative release of vancomycin from the antibacterial system was 58.3% ± 3.8% at 14 days and 78.4% ± 3.2% at 35 days. The concentration of vancomycin in the surrounding environment was about 1.2 mg/mL, which can effectively remove bacteria. Further studies in vivo showed that the antibacterial system cleared the infection and accelerated repair of infected bone defects in the femur of rats. There was no infection in rats after 8 weeks of treatment. The 3D image analysis of the experimental group showed that the bone volume fraction (BV/TV) was 1.39-fold higher (p < 0.001), the trabecular number (Tb.N) was 1.31-fold higher (p < 0.05), and the trabecular separation (Tb.Sp) was 0.58-fold higher than those of the control group (p < 0.01).Conclusion: In summary, this study clearly demonstrates that a clinical strategy based on biological materials can provide an innovative and effective approach to treatment of infected bone defects.Keywords: infected bone defects, drug delivery system, hydrogel, vancomycin