Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People's Republic of China.
Department of Otolaryngology, The First Hospital of Jilin University, Changchun, People's Republic of China.
Int J Nanomedicine. 2024 Oct 11;19:10227-10245. doi: 10.2147/IJN.S448876. eCollection 2024.
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.
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.
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 ( < 0.001), the trabecular number (Tb.N) was 1.31-fold higher ( < 0.05), and the trabecular separation (Tb.Sp) was 0.58-fold higher than those of the control group ( < 0.01).
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.
在治疗感染性骨缺损时，控制感染对于有效的骨修复是必要的，因此在临床实践中需要对局部应用抗生素进行控制。本研究通过将万古霉素整合到聚乙二醇/氧化葡聚糖（PEG/ODEX）水凝胶基质中，制备了一种在感染部位原位凝胶化的可生物降解药物输送系统。
在这项工作中，PEG/ODEX 水凝胶通过席夫碱反应制备，万古霉素被加载到其中，构建了一种具有可控释放和可降解性的药物输送系统。我们首先检查了水凝胶的微观结构、降解时间和药物释放。然后验证了释放系统的生物相容性和体外能力。最后，我们使用大鼠感染性骨缺损模型进行了进一步的实验。
结果表明，这种抗菌系统在体内可完全生物降解，56 天内降解产物不会引起特异性炎症反应。抗菌系统中万古霉素的累积释放率在 14 天为 58.3%±3.8%，在 35 天为 78.4%±3.2%。周围环境中万古霉素的浓度约为 1.2mg/mL，可以有效去除细菌。进一步的体内研究表明，抗菌系统清除了感染并加速了大鼠股骨感染性骨缺损的修复。治疗 8 周后，大鼠无感染。实验组的 3D 图像分析显示，骨体积分数（BV/TV）提高了 1.39 倍（<0.001），骨小梁数量（Tb.N）提高了 1.31 倍（<0.05），骨小梁间隔（Tb.Sp）降低了 0.58 倍（<0.01），与对照组相比。
综上所述，本研究清楚地表明，基于生物材料的临床策略可以为治疗感染性骨缺损提供一种创新而有效的方法。
