Dual-functional borosilicate glass (BSG) delivery implant for osteomyelitis treatment and bone regeneration

Abstract

<p>Effective treatment of osteomyelitis remains to be clinical challenge due to the recurrent and persistent nature of the disease. Studies have shown that borate glasses can serve as implants for local drug delivery in treating osteomyelitis, as well as aid in regenerating bone defects in vivo. However, both the kinetics of drug release from borate glass-based implants and the underlying molecular mechanism for promoting bone regeneration remain unclear. Here, delivery implants with varying amounts of antibiotics were fabricated by encapsulating gentamicin sulfate (GS) into a chitosan glue and applying it to borosilicate glass (BSG). Upon immersion in phosphate buffered saline (PBS), delivery implants degraded and converted into hydroxyapatite (HA). All delivery implants released GS sustainably over a period of around 25 days in both PBS and K2HPO4 solutions and displayed efficacious inhibition of E. coli and S. aureus in vitro. GS release occurred through diffusion for inhibition whereby Fickian diffusion was revealed to be the predominant release kinetic. Ions (B, Ca, P and Si) released from BSG supported the proliferation, differentiation, osteogenic gene expression and protein secretion of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. When implanted in a rabbit tibial osteomyelitis model, osteomyelitis in the experimental group with delivery implants was effectively cured. Meanwhile, delivery implants have significant osteogenesis-promoting effects after implantation time of 12-weeks in vivo. Implantation of BSG-based drug delivery implants developed in this study may provide a promising method for treating osteomyelitis as well as for facilitating efficient bone regeneration.</p>