Department of Orthopaedic Surgery, Loma Linda University School of Medicine, Loma Linda, California, USA.
Department of Pharmaceutical Sciences, Loma Linda University School of Pharmacy, Loma Linda, California, USA.
J Orthop Res. 2021 Feb;39(2):365-375. doi: 10.1002/jor.24919. Epub 2020 Dec 2.
The objective of this study was to develop a novel microcomposite implant to be used in the treatment of osteomyelitis following total joint arthroplasty, with the dual purpose of releasing high local concentrations of antibiotic to eradicate the infection while providing adequate mechanical strength to maintain the dynamic or static spacer. Vancomycin-loaded microcomposite implants were fabricated by incorporating drug-loaded microparticles comprised of mesoporous silica into commonly employed polymethylmethacrylate (PMMA) bone cement, to yield a final drug loading of 10% w/w. In vitro release kinetics at 37°C were monitored by reverse-phase high-performance liquid chromatography, and compared to the release kinetics of current therapy implants consisting of drug alone incorporated at 10% w/w directly into PMMA bone cement. Results demonstrated a sevenfold improvement in the elution profile of microcomposite systems over current therapy implants. In vivo delivery of vancomycin to bone from microcomposite implants (70% of payload) was significantly higher than that from current therapy implants (approx. 22% of payload) and maintained significantly higher bone concentrations for up to 2 weeks duration. The elastic modulus showed no statistical difference between microcomposite implants and current standard therapy implants before drug elution, and maintenance of acceptable strength of microcomposite implants postdrug elution. These results demonstrate that we have developed a novel microcomposite spacer that will release continuously high antibiotic concentrations over a prolonged period of time, offering the possibility to eliminate infection and avoid the emergence of new resistant bacterial strains, while maintaining the requisite mechanical properties for proper space maintenance and joint fixation.
本研究的目的是开发一种新型微复合植入物，用于治疗全关节置换术后骨髓炎，其双重目的是释放高浓度的局部抗生素以消除感染，同时提供足够的机械强度以维持动态或静态间隔物。载万古霉素的微复合植入物是通过将载药微颗粒掺入常用的聚甲基丙烯酸甲酯（PMMA）骨水泥中制成的，最终药物负载量为 10wt%。在 37°C 下通过反相高效液相色谱法监测体外释放动力学，并与当前治疗植入物（将药物单独掺入 10wt%直接掺入 PMMA 骨水泥中）的释放动力学进行比较。结果表明，微复合体系的洗脱曲线比当前治疗植入物提高了七倍。从微复合植入物向骨中输送万古霉素（达payload 的 70%）明显高于当前治疗植入物（达payload 的约 22%），并且在长达 2 周的时间内保持明显更高的骨浓度。在药物洗脱之前，微复合植入物与当前标准治疗植入物的弹性模量没有统计学差异，并且药物洗脱后微复合植入物的强度保持可接受。这些结果表明，我们已经开发出一种新型的微复合间隔物，它可以在较长时间内持续释放高浓度的抗生素，有可能消除感染并避免新的耐药菌菌株的出现，同时保持适当的空间维持和关节固定所需的机械性能。
