Osteogenic and anti-inflammatory potential of oligochitosan nanoparticles in treating osteomyelitis

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.