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Experimental Research On Anti-infectious Tissue Engineered Bone

Posted on:2005-08-22Degree:MasterType:Thesis
Country:ChinaCandidate:L BiFull Text:PDF
GTID:2144360122490175Subject:Surgery
Abstract/Summary:PDF Full Text Request
Open fracture or bone defect after trauma is frequently encountered in peace and wartime. It is difficult to make a successful bone graft and control infection at the same time. When the gentamycin-PMMA chains were used clinically, local drug delivery system (LDDS) has been regarded as a good way to cure bone and soft tissue infections. But pure gentamycin-PMMA chains can be used only to control local infection, and for patients with bone defect, the traditional treatment is controlling infection at first stage and making bone graft at second stage. In this experimental study, RBX (reconstituted bone xenograft) is used as core carrier, which is combined with clindamycin , rifampicin and ciprofloxacin, respectively, to prepare anti - infectious tissue engineered bone (AITE-Bone). Then, the osteoinductive ability of AITE-Bone, the release of antibiotics from the LDDS in vivo and their ability to repair rabbit contaminated segmental defects were investigated and measured.Part I: Osteoinductive ability of AITE-BoneObjective: To observe the osteoinductive ability of AITE-Bone. Method: A pellet of the three kinds of AITE - Bone (combined with clindamycin , rifampicin and ciprofloxacin , respectively ),RBX-G-LDDS (RBX combined with gentamycin) and RBX alone (as positive controls) were implanted into mice right muscle pouch, respectively. The left one was left empty (as negative control) . The implants were harvested after 1, 2, 4 weeks. The results were evaluated grossly, by radiology, histology and ALP (alkaline phosphatase) test. Results: Combined with clindamycin, rifampicin and ciprofloxacin, the AITE-Bones still had perfect osteoinductive ability as in positive controls. There was no osteoinductive ability found in negative control. Conclusion: At certain concentration (40 mg/ml), the clindamycin, rifampicin and ciprofloxacin do not have an inhibitive effect on the osteoinductive ability of AITE-Bone. Part II: Antibiotics Released from AITE-Bone in vivo Objective: To observe the releasing character of antibiotics from AITE-Bone in vivo. Method: A pellet of the three kinds of AITE -Bone (combined with clindamycin, rifampicin and ciprofloxacin, respectively ) was implanted into mice right muscle pouches in vivo, respectively. Then the amount of antibiotics released into blood and the surrounding soft tissue were measured at set time points by K-B (Kirby-Bauer) disc diffusion technique on Mueller-Hinton agar. Results: (1) The initial phase of rapid release of antibiotics lasted for 72 hours in vivo which was followed by a second phase of sustained but gradually declining stage of drug release. ( 2) Effective release of AITE-Bone lasted stably for at least 3 weeks in vivo. Even 3 weeks later, the local drug concentrations were much higher than the MIC (minimal inhibitory concentration ) of common pathogenic germs in bone diseases. (3) On the contrary, the blood drug concentrations were much lower, even under the safe of concentrations. Conclusion: Used locally, the AITE - Bone can maintain effective bacterial inhibitory concentration locally and safeconcentration in blood.Part III: AITE -Bone used for primary bone grafting to repair rabbit contaminated segmental defect.Objective: To observe the ability of AITE -Bone repairing rabbit contaminated segmental defect at first period. Method: A proximal radial defect (length 15 mm ) in rabbit model was made and 0.2 ml staphylococcus aureus (5x106 CFU / mDwas injected into the defect. Pellet of AITE -Bone (combined with clindamycin)were implanted in group A, pellets of RBX were implanted in group B in conjunction with intramuscular clindamycin for 5 days (5 mg / kg weight), and pellets of RBX in group C. Results were observed by gross, radiological, bacteriological evaluation and histologically, comparing the 3 groups with regard to the beneficial effect of the above procedures in preventing infection. Results: (1) At 2 weeks, the wound of group A healed completely, while the wound of group B healed poorly, there was pus secretion exuding...
Keywords/Search Tags:tissue engineering, clindamycin, rifampicin, ciprofloxacin, Local drug delivery system
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