[Injectable borate glass/chitosan composite as drug carrier for treatment of chronic osteomyelitis].
OBJECTIVE
To evaluate the characterization, biocompatibility in vitro and in vivo, and antimicrobial activity of an injectable vancomycin-loaded borate glass/chitosan composite (VBC) so as to lay the foundation for its further clinical application.


METHODS
The solid phase of VBC was constituted by borate glass and vancomycin, liquid phase was a mixture of chitosan, citric acid, and glucose with the proportion of 1 : 10 : 20. Solid phase and liquid phase was mixed with the ratio of 2 : 1. Vancomycin-loaded calcium sulfate (VCS) was produced by the same method using calcium sulfate instead of borate glass and saline instead of chitosan, as control. High performance liquid chromatography was applied to detect the release rate of antibiotics from VBC and VCS, and minimum inhibitory concentration (MIC) was tested by using an antibiotic tube dilution method. The structure of the VBC and VCS specimens before and 2, 4, 8, 16, and 40 days after immersion in D-Hank's was examined by scanning electron microscopy, and the phase composition of VBC was analysed by X-ray diffraction after soaked for 40 days. Thirty-three healthy adult New Zealand white rabbits (weighing, 2.25-3.10 kg; male or female) were used to establish the osteomyelitis models according to Norden method. After 4 weeks, the models of osteomyelitis were successfully established in 28 rabbits, and they were randomly divided into 4 groups (groups A, B, C, and D). In group A (n=8), simple debridement was performed; in groups B and C (n=8), defect was treated by injecting VCS or VBC after debridement; and in group D (n=4), no treatment was given. The effectiveness of treatment was assessed using radiological and histological techniques after 2 months.


RESULTS
The releases of vancomycin from VBC lasted for 30 days; the release rate of vancomycin reached 75% at the first 8 days, then could reached more than 90%. The releases of vancomycin from VCS lasted only for 16 days. The MIC of VBC and VCS were both 2 microg/mL. The VCS had a smooth glass crystal surface before immersion, however, it was almost degradated after 4 days. The fairly smooth surface of the VBC pellet became more porous and rougher with time, X-ray diffraction analysis of VBC soaked for 40 days indicated that the borate glass had gradually converted to hydroxyapatite. After 2 months, the best result of treatment was observed in group C, osteomyelitis symptoms disappeared. The X-ray scores of groups A, B, C, and D were 3.50 +/- 0.63, 2.29 +/- 0.39, 2.00 +/- 0.41, and 4.25 +/- 0.64, respectively; Smeltzer scores were 6.00 +/- 0.89, 4.00 +/- 0.82, 3.57 +/- 0.98, and 7.25 +/- 0.50, respectively. The scores were significantly higher in group D than in groups A, B, and C (P < 0.05), and in group A than in groups B and C (P < 0.05). The scores were higher in group B than in group C, but no significant difference was found (P > 0.05).


CONCLUSIONS
The VBC is effective in treating chronic osteomyelitis of rabbit by providing a sustained release of vancomycin, in addition to stimulating bone regeneration, so it may be a promising biomaterial for treating chronic osteomyelitis.
Department of Orthopedics, the Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, 200233.
Cunju
C
Zhao
Xinfu
X
Wang
Changqing
C
Zhang
Xu
X
Cui
Weitao
W
Jia
Wenchan
W
Huang
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry; D001881:Borates / Q000737:chemistry*; D002133:Calcium Sulfate / Q000737:chemistry / Q000627:therapeutic use; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D005898:Glass / Q000737:chemistry; D007267:Injections; D008297:Male; D008422:Materials Testing; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy; D014640:Vancomycin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D014961:X-Ray Diffraction
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D001881:Borates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D014640:Vancomycin; D048271:Chitosan; D002133:Calcium Sulfate