Abstract：
The conventional treatment of osteomyelitis with antibiotic-loaded nondegradable polymethylmethacrylate (ATB-PMMA) beads has certain limitations, including impeded bone reconstruction and the need for secondary surgery. To overcome this challenge, this study aimed to develop and characterize an injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel (VC-SF/MC-CAPs). The VC-SF/MC-CAPs solution can be easily administered at room temperature with a low injectability force of ≤30 N and a high vancomycin (VC) content of ~96%. Additionally, at physiological temperature (37 °C), the solution could transform into a rigid hydrogel within 7 minutes. In vitro drug release performed under both physiological (pH 7.4) and infection conditions (pH 4.5) revealed a prolonged release pattern of VC-SF/MC-CAPs following the Peppas-Sahlin kinetic model. In addition, the released VC from VC-SF/MC-CAPs hydrogels exhibited antibacterial activity against Staphylococcus aureus for a period exceeding 35 days, as characterized by the disk diffusion assay. Furthermore, at pH 7.4, the VC-SF/MC-CAPs demonstrated >60% degradation within 35 days. Importantly, when exposed to physiological pH conditions, CAPs are transformed into bioactive hydroxyapatite, which benefits bone formation. Therefore, VC-SF/MC-CAPs showed significant potential as a local drug delivery system for treating osteomyelitis.
摘要：
用负载抗生素的不可降解聚甲基丙烯酸甲酯（ATB-PMMA）珠治疗骨髓炎有一定的局限性，包括阻碍骨重建和二次手术的需要。为了克服这一挑战，这项研究旨在开发和表征可注射的万古霉素负载丝素蛋白/甲基纤维素含磷酸钙基原位热敏水凝胶（VC-SF/MC-CAPs）。VC-SF/MC-CAPs溶液可以在室温下轻松施用，注射力≤30N，万古霉素（VC）含量高，约96％。此外,在生理温度（37°C）下，该溶液可以在7分钟内转变为刚性水凝胶。在生理条件（pH7.4）和感染条件（pH4.5）下进行的体外药物释放表明，按照Peppas-Sahlin动力学模型，VC-SF/MC-CAPs的释放模式延长。此外,VC-SF/MC-CAPs水凝胶释放的VC对金黄色葡萄球菌表现出超过35天的抗菌活性，以圆盘扩散测定为特征。此外，在pH7.4下,VC-SF/MC-CAP在35天内表现出>60%的降解。重要的是,当暴露于生理pH条件时，CAPs转化为生物活性羟基磷灰石，有利于骨骼形成。因此,VC-SF/MC-CAP显示出作为治疗骨髓炎的局部药物递送系统的巨大潜力。
