A biodegradable antibiotic-eluting PLGA nanofiber-loaded deproteinized bone for treatment of infected rabbit bone defects.
We fabricated a biodegradable antibiotic-eluting poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (ANDB) scaffold that provided sustained delivery of vancomycin to repair methicillin-resistant Staphylococcus aureus bone defects. To fabricate the biodegradable ANDB, poly(d,l)-lactide-co-glycolide and vancomycin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propano. The solution was then electrospun to produce biodegradable antibiotic-eluting membranes that were deposited on the surface of bovine deproteinized cancellous bone. We used scanning electron microscopy to determine the properties of the scaffold. Both elution and high-performance liquid chromatography assays were used to evaluate the in vitro vancomycin release rate from the ANDB scaffold. Three types of scaffolds were co-cultured with bacteria to confirm the in vitro antibacterial activity. The infected bone defect rabbit model was induced by injecting 10(7) colony forming units of a methicillin-resistant Staphylococcus aureus strain into the radial defect of rabbits. Animals were then separated into treatment groups and implanted according to the following scheme: ANDB scaffold in group A, poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (NDB) scaffold with intravenous (i.v.) vancomycin in group B, and NDB scaffold alone in group C. Treatment efficacy was evaluated after eight weeks using radiological, microbiological, and histological examinations. In vitro results revealed that biodegradable ANDB scaffolds released concentrations of vancomycin that were greater than the minimum inhibitory concentration for more than four weeks. Bacterial inhibition tests also confirmed antibacterial efficacy lasted for approximately four weeks. Radiological and histological scores obtained in vivo revealed significant differences between groups A, B and C. Importantly, group A had significantly lower bacterial load and better bone regeneration when compared to either group B or C. Collectively, these results show that our fabricated ANDB scaffolds possess: (1) effective bactericidal activity against methicillin-resistant Staphylococcus aureus, (2) the ability to promote site-specific bone regeneration, and (3) the potential for use in the treatment of infected bone defects.
Department of Orthopaedic Surgery, Orthopaedic Center of PLA, Affiliated Southeast Hospital of Xiamen University, Zhangzhou, PR China.
Jianting
J
Gao
Department of Orthopaedic Surgery, Orthopaedic Center of PLA, Affiliated Southeast Hospital of Xiamen University, Zhangzhou, PR China.
Guofeng
G
Huang
Department of Orthopaedic Surgery, Orthopaedic Center of PLA, Affiliated Southeast Hospital of Xiamen University, Zhangzhou, PR China.
Guojun
G
Liu
Department of Orthopaedic Surgery, Orthopaedic Center of PLA, Affiliated Southeast Hospital of Xiamen University, Zhangzhou, PR China.
Yan
Y
Liu
Department of Orthopaedic Surgery, Orthopaedic Center of PLA, Affiliated Southeast Hospital of Xiamen University, Zhangzhou, PR China.
Qi
Q
Chen
Department of Biomaterials, College of Materials, Xiamen University, Xiamen, PR China.
Lei
L
Ren
Department of Orthopaedic Surgery, Orthopaedic Center of PLA, Affiliated Southeast Hospital of Xiamen University, Zhangzhou, PR China 543593466@qq.com.
Changqing
C
Chen
Department of Orthopaedic Surgery, Orthopaedic Center of PLA, Affiliated Southeast Hospital of Xiamen University, Zhangzhou, PR China xwzy669@163.com.
Zhenqi
Z
Ding
D020341:Absorbable Implants; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D058491:Bacterial Load; D001850:Bone Diseases, Infectious / Q000188:drug therapy*; D001861:Bone Regeneration; D001842:Bone and Bones / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D019344:Lactic Acid / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D057139:Nanofibers / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D011897:Random Allocation; D054457:Tissue Scaffolds / Q000737:chemistry*; D014640:Vancomycin / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D014640:Vancomycin
Vancomycin; electrospinning; infected bone defect; nanofiber-membrane; scaffold