Injectable Butyl Glycidyl Ether‐Modified Methylcellulose Thermosensitive Hydrogel for Topical Delivery of Vancomycin Hydrochloride in the Treatment of Osteomyelitis

Osteomyelitis (OM) is caused by the entry of septic cells into bone tissue. Due to systemic antibiotic side effects and drug resistance, local administration is a strategy for treating OM. In this study, a biodegradable, injectable thermosensitive hydrogel containing vancomycin hydrochloride (VA) was developed to reduce drug resistance and prolong the therapeutic efficacy of Staphylococcus aureus by sustained topical delivery of VA. VA was loaded into an injectable butyl glycidyl ether-modified methylcellulose hydrogel (MC-BGE), and VA-loaded MC-BGE hydrogel (VA@MC-BGE) was obtained. The gelation time of VA@MC-BGE at 37°C was approximately 10 min. In vitro, the hydrogel released ~40% of its VA payload within the first 4 days, followed by a sustained release that reached 91.0% cumulative release by Day 28. During this period, mass-loss measurements showed ~67% degradation of the hydrogel. The in vitro study showed that the VA@MC-BGE had stronger antimicrobial activity against S. aureus for at least 7 days and could reduce the cytotoxicity of VA with high osteoblast viability (> 85%) over 72 h. VA@MC-BGE inhibited S. aureus infection and improved inflammation and oxidative stress in osteoblasts. The in vivo study showed that the hydrogel was able to degrade gradually in vivo and that only a small amount of hydrogel remained at 28 days. The hydrogel was also not significantly toxic to major organs. In an OM rat model, injecting the VA@MC-BGE into the site of tibial infection in rats further reduced bone infection and improved bone regeneration compared to free VA. In conclusion, in situ thermosensitive MC-BGE hydrogels encapsulating VA have slow-release properties and good biocompatibility, which are promising for the treatment of OM.