β-tricalcium phosphate/gelatin composite scaffolds incorporated with gentamycin-loaded chitosan microspheres for infected bone defect treatment

Abstract

The repair of infected bone defects remains a clinical challenge. Staphylococcus aureus is a common pathogenic micro-organism associated with such infections. Gentamycin (GM) is a broad spectrum antibiotic that can kill S. aureus in a dose-dependent manner. However, the systemic administration of antibiotics may lead to drug resistance and gut dysbiosis. In this work, we constructed β-tricalcium phosphate/gelatin composite scaffolds incorporated with gentamycin-loaded chitosan microspheres (CMs(GM)-β-TCP/gelatin composite scaffolds), which helped optimize the local GM release in the infected defect areas and enhance bone regeneration. The cumulative release curves showed that both microspheres and composite scaffolds reached a sustained slow-release phase after the initial rapid release, and the latter further stabilized the initial drug release rate. The release curve of CMs(GM)-β-TCP/gelatin composite scaffolds reached a plateau after 24 h, and the cumulative release reached 41.86% during this period. Moreover, the combination of β-TCP and gelatin mimicked bone composition and were able to provide the requisite mechanical strength (0.82 ± 0.05 MPa) during the first phase of bone generation. The inner structure of the scaffold was arranged in the shape of interconnected pores, and presented a porosity level of 16%. The apertures were uniform in size, which was beneficial for cell proliferation and material transportation. Macroscopic observation and histological analysis showed that CMs(GM)-β-TCP/gelatin composite scaffolds fused with bone tissues, and new tissues were formed in defect areas without any infection. This new composite scaffold may be a promising repair material for treating infected bone defects.