Thermosensitive vancomycin@PLGA-PEG-PLGA/HA hydrogel as an all-in-one treatment for osteomyelitis

Abstract

Osteomyelitis is a difficult-to-treat infectious disease. Treatment, which includes controlling the infection and removing necrotic tissues, is challenging. Considering the side effects and drug resistance of systemic antibiotics, local drug delivery systems are being explored. Antibiotic-loaded bone cement is the main treatment strategy; however, it has several disadvantages. Thus, based on its thermosensitive gelation properties, poly(D, L-lactide-co-glycolide)–poly(ethylene glycol)–poly(D, L-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymer was used as a sustained-release drug carrier by calibrating its synthesis parameters. We prepared and characterized vancomycin@PLGA-PEG-PLGA/hydroxyapatite (HA) thermosensitive hydrogel with an LA/GA ratio of 15:1. The rheological characteristics, sol–gel phase-transition properties, and critical micelle concentration value of the PLGA-PEG-PLGA/HA complex confirmed that it undergoes a temperature-sensitive sol–gel phase transition. Furthermore, the HA in the composite increased the storage modulus of the system. FT-IR, XRD, and TEM findings showed that HA could be dispersed uniformly in the PLGA-PEG-PLGA polymer. Moreover, HA neutralized acidity during polymer degradation, improving in vitro cytocompatibility. In vitro and in vivo antibacterial experiments showed that the composite sustained-release system exhibited good bone repair characteristics owing to its efficacy in infection treatment. Therefore, vancomycin@PLGA-PEG-PLGA/HA allows sustained release of antibiotics and promotes bone tissue repair, showing potential for wide clinical applicability.