Gentamicin-loaded borate bioactive glass eradicates osteomyelitis due to Escherichia coli in a rabbit model.

The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus Escherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated in vitro and in vivo for the treatment of osteomyelitis induced by Escherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli.

Bioactive borate glass promotes the repair of radius segmental bone defects by enhancing the osteogenic differentiation of BMSCs.

Bioactive borate glass (BG) has emerged as a promising alternative for bone regeneration due to its high osteoinductivity, osteoconductivity, compressive strength, and biocompatibility. However, the role of BG in large segmental bone repair is unclear and little is known about the underlying mechanism of BG's osteoinductivity. In this study, we demonstrated that BG possessed pro-osteogenic effects in an experimental model of critical-sized radius defects. Transplanting BG to radius defects resulted in better repair of bone defects as compared to widely used ß-TCP. Histological and morphological analysis indicated that BG significantly enhanced new bone formation. Furthermore, the degradation rate of the BG was faster than that of ß-TCP, which matched the higher bone regeneration rate. In addition, ions from BG enhanced cell viability, ALP activity, and osteogenic-related genes expression. Mechanistically, the critical genes Smad1/5 and Dlx5 in the BMP pathway and p-Smad1/5 proteins were significantly elevated after BG transplantation, and these effects could be blocked by the BMP/Smad specific inhibitor. Taken together, our findings suggest that BG could repair large segmental bone defects through activating the BMP/Smad pathway and osteogenic differentiation in BMSCs.

[Vancomycin-loaded bioactive borate glass for treatment of chronic osteomyelitis in rabbits].

OBJECTIVE: Bioactive borate glass (BG) has good biocompatibility and biodegradation. To investigate the feasibility of bioactive borate glass as a carrier of the antibiotic controlled-releasing by implanting vancomycin-loaded BG (VBG) into the focus of tibia chronic osteomyelitis after debridement. METHODS: VBG and vancomycin-loaded calcium sulfate (VCS) were prepared with a vancomycin content of 80 mg/g. Sixty-five New Zealand white rabbits, weighing 2.12-3.91 kg (mean, 2.65 kg), were used. The tibia chronic osteomyelitis rabbit models were established by injecting methicillin-resistant Staphylococcus aureus (MRSA, 0.1 mL, 1 x 10(9) cfu/mL) into the right tibia of 65 rabbits. After 3 weeks of injection, 54 rabbits of successful models were randomly divided into groups A (n=11), B (n=11), C (n=16), and D (n=16). Simple debridement was performed in group A; BG, VCS, and VBG were implanted into the infection sites of groups B, C, and D respectively after thorough debridement. A sample of the debrided tissues was harvested for bacterial examination. The vancomycin serum levels were determined in groups C and D at 1, 2, 4, 10, 24, and 48 hours after operation. The boron serum levels were determined in groups B and D at 10, 24, 48, 72, and 120 hours after operation. After 8 weeks, the effectiveness was assessed radiographically, bacteriologically, and histopathologically. RESULTS: Ten rabbits died after operation. No vancomycin was detected in group C; the vancomycin level increased gradually, reached the highest level at 4 hours after operation, and then decreased rapidly in group D. No boron was detected in group B; the boron reached the highest serum level at 10 hours after operation, and then decreased gradually in group D. At 8 weeks, calcium sulfate degraded in group C; BG degraded partially in group D; and no obvious degradation was observed in group B. The repair effect was better in group D than in group C. There was no significant difference in radiograph scoring between groups A, B, C and D (P > 0.05) before operation, but there was significant difference between group D and groups A, B, C (P < 0.05) at 8 weeks after operation. The bacterial culture showed that all the MRSA results were positive in 4 groups. At 8 weeks, the negative rates of MRSA examination were 36.36%, 18.18%, 73.33%, and 81.25% respectively in groups A, B, C, and D, showing significant differences between group D and groups A, B (P < 0.05). The histopathological observation showed that a large number of new bones formed and no foreign body reaction occurred in group D. The histopathologic scores of groups A, B, C, and D were 6.45 +/- 3.62, 7.55 +/- 3.36, 4.27 +/- 2.91, and 3.81 +/- 3.04 respectively, showing significant differences between group D and groups A, B, and between group C and group B (P < 0.05). CONCLUSION: VBG can improve the repair of bone defect in the treatment of chronic osteomyelitis.

Novel borate glass/chitosan composite as a delivery vehicle for teicoplanin in the treatment of chronic osteomyelitis.

Composite materials composed of borate bioactive glass and chitosan (designated BGC) were investigated in vitro and in vivo as a new delivery system for teicoplanin in the treatment of chronic osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA). In vitro, the release of teicoplanin from BGC pellets into phosphate-buffered saline (PBS), as well as its antibacterial activity, were determined. The compressive strength of the pellets was measured after specific immersion times, and the structure of the pellets was characterized using scanning electron microscopy and X-ray diffraction. In vivo, the tibial cavity of New Zealand White rabbits was injected with MRSA strain to induce chronic osteomyelitis, treated by debridement after 4weeks, implanted with teicoplanin-loaded BGC pellets (designated TBGC) or BGC pellets, or injected intravenously with teicoplanin. After 12weeks' implantation, the efficacy of the TBGC pellets for treating osteomyelitis was evaluated using hematological, radiological, microbiological and histological techniques. When immersed in PBS, the TBGC pellets provided a sustained release of teicoplanin, while the surface of the pellets was converted to hydroxyapatite (HA). In vivo, the best therapeutic effect was observed in animals implanted with TBGC pellets, resulting in significantly lower radiological and histological scores, a lower positive rate of MRSA culture, and an excellent bone defect repair, without local or systemic side effects. The results indicate that TBGC pellets are effective in treating chronic osteomyelitis by providing a sustained release of teicoplanin, in addition to participating in bone regeneration.

Treatment of osteomyelitis and repair of bone defect by degradable bioactive borate glass releasing vancomycin.

The effectiveness of a degradable and bioactive borate glass has been compared with the clinically used calcium sulfate in the treatment of osteomyelitis of rabbits, as a carrier for vancomycin. The bone infections were induced in the tibias of 65 rabbits by injecting methicillin-resistant Staphylococcus aureus (MRSA). After 3 weeks, these rabbits were distributed into 4 groups and treated by debridement. Pure borate glass (BG), vancomycin-loaded calcium sulfate (VCS) and vancomycin-loaded borate glass (VBG) were implanted into the infection sites of groups 2 to 4 respectively. After 8 weeks, the effectiveness of treatment was assessed radiographically, bacteriologically, and histopathologically. The results showed that the negative rates of MRSA examination for rabbits were 36.36%, 18.18%, 73.33% and 81.25% respectively for groups 1 to 4. Significant differences were observed radiographically, bacteriologically, and histopathologically between groups 1 and 4, groups 2 and 3, and between groups 2 and 4. The best result of treatment was observed in group 4. Radiographically, VBG was found to be mostly reabsorbed and replaced by lots of new bones, whereas, VCS was completely reabsorbed and replaced by modest new bones. Histopathologically, there were lots of newly formed bones around VBG without any foreign body response, and only modest new bones around VCS with obvious foreign body response. VBG proved to have excellent biocompatibility and to be very effective in eradicating osteomyelitis and simultaneously stimulating bone regeneration, avoiding the disadvantages of VCS.