School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Mater Sci Eng C Mater Biol Appl. 2022 Apr;135:112681. doi: 10.1016/j.msec.2022.112681. Epub 2022 Jan 26.
Osteomyelitis is commonly developed via hematogenous spreading or direct inoculation of bacteria from orthopedics trauma. Pathogens-induced bone destruction impedes the penetration of antibiotics to the infection site, and the severe inflammation further compromises the traditional treatment outcome. In this work, vancomycin-loaded oligochitosan nanoparticles (Van-NPs) with antibacterial, antibiofilm, antioxidant as well as bone regenerative properties are prepared using sodium tripolyphosphate (TPP) as a crosslinker, and employed for the treatment of osteomyelitis. Van-NPs exhibit strong interactions with dissociative S. aureus and biofilms due to the positive zeta potential, the additional effect between vancomycin (Van) and oligochitosan (OCS) further contributes to an enhanced antibacterial and antibiofilm outcome. The in vitro osteogenic differentiation of rBMSCs is facilitated by the antioxidant ability of Van-NPs and the TPP-induced activation of ERK1/2 and p38 signaling pathways. Moreover, the combination of Van-NPs with PLGA-PEG-PLGA gel (Gel/Van-NPs) achieves successful localized treatment of osteomyelitis in terms of enhanced bacteria elimination, inflammatory modulation, and accelerated bone regeneration. Therefore, Gel/Van-NPs may serve as a promising biomaterial for the optimal treatment of osteomyelitis.
骨髓炎通常是通过血源性播散或骨科创伤直接接种细菌引起的。病原体引起的骨破坏阻碍了抗生素渗透到感染部位，严重的炎症进一步影响了传统的治疗效果。在这项工作中，使用三聚磷酸钠（TPP）作为交联剂，制备了具有抗菌、抗生物膜、抗氧化和骨再生特性的载万古霉素低聚壳聚糖纳米颗粒（Van-NPs），并用于治疗骨髓炎。Van-NPs 由于具有正 zeta 电位，与游离的金黄色葡萄球菌和生物膜之间具有很强的相互作用，万古霉素（Van）和低聚壳聚糖（OCS）之间的附加作用进一步增强了抗菌和抗生物膜效果。Van-NPs 的抗氧化能力和 TPP 诱导的 ERK1/2 和 p38 信号通路的激活促进了 rBMSCs 的体外成骨分化。此外，将 Van-NPs 与 PLGA-PEG-PLGA 凝胶（Gel/Van-NPs）结合，可通过增强细菌消除、炎症调节和加速骨再生来实现骨髓炎的局部治疗。因此，Gel/Van-NPs 可能是治疗骨髓炎的一种很有前途的生物材料。
