Abstract

BackgroundA novel injectable cement composed of chitosan-bonded borate bioactive glass (BG) particles was evaluated as a carrier for local delivery of vancomycin in the treatment of osteomyelitis in a rabbit tibial model.Materials and MethodsThe setting time, injectability, and compressive strength of the borate BG cement, and the release profile of vancomycin from the cement were measured in vitro. The capacity of the vancomycin-loaded BG cement to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in rabbit tibiae in vivo was evaluated and compared with that for a vancomycin-loaded calcium sulfate (CS) cement and for intravenous injection of vancomycin.ResultsThe BG cement had an injectability of >90% during the first 3 minutes after mixing, hardened within 30 minutes and, after hardening, had a compressive strength of 18±2 MPa. Vancomycin was released from the BG cement into phosphate-buffered saline for up to 36 days, and the cumulative amount of vancomycin released was 86% of the amount initially loaded into the cement. In comparison, vancomycin was released from the CS cement for up 28 days and the cumulative amount released was 89%. Two months post-surgery, radiography and microbiological tests showed that the BG and CS cements had a better ability to eradicate osteomyelitis when compared to intravenous injection of vancomycin, but there was no significant difference between the BG and CS cements in eradicating the infection. Histological examination showed that the BG cement was biocompatible and had a good capacity for regenerating bone in the tibial defects.ConclusionsThese results indicate that borate BG cement is a promising material both as an injectable carrier for vancomycin in the eradication of osteomyelitis and as an osteoconductive matrix to regenerate bone after the infection is cured.

Highlights

  • Curing osteomyelitis presents a clinical challenge because once infection has entered bone, it is difficult to treat

  • The vancomycin-loaded cement had a compressive strength of 18.262.3 MPa; upon immersion of the cement in phosphate buffered saline (PBS), the strength decreased to 15.061.8 MPa after 1 day and more gradually thereafter, to 12.261.8 MPa after 7 days (Fig. 2)

  • scanning electron microscope (SEM) of the surface of the hardened vancomycin-loaded bioactive glass (BG) cement showed a heterogeneous microstructure with some pores, which might be caused by bubbles produced during the mixing process (Fig. 3a)

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Summary

Introduction

Curing osteomyelitis (bone infection) presents a clinical challenge because once infection has entered bone, it is difficult to treat. Poly(methyl methacrylate) (PMMA), calcium sulfate (CaSO4), calcium phosphate ceramics such as hydroxyapatite (HA) and beta-tricalcium phosphate (b-TCP), and biodegradable polymers, synthetic or natural, such as poly(lactic acid) poly (glycolic acid), and their copolymers, collagen and chitosan) have been widely studied or used as carriers for local drug delivery [4,5]. Those carriers have limitations such as bioinertness (e.g., PMMA) or inadequate degradation rate (e.g., HA), poor osteoconductivity, rapid antibiotic elution rate, transient cytotoxicity, and low strength [6,7]. A novel injectable cement composed of chitosan-bonded borate bioactive glass (BG) particles was evaluated as a carrier for local delivery of vancomycin in the treatment of osteomyelitis in a rabbit tibial model

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