| Complications such as osteomyelits, fracture non-union or delayed union often occurred during the treatment of open fracture caused by war injury or high energy injury, which make the treatment of fracture troublesome with a long curative period , and the curative result is usually dissatisfactory. Such clinical problems have been challenging dilemma for orthopaedic surgeon. The routine methods including general antibiotic use and implantation of PMMA-antibiotic composite have some disadvantage. The optimal plan may be implantation of a kind of bone graft substitute -antibiotic composite materials into the wound which can deliver antibiotic to treat bone infection and repair the bone defect simultaneously.Calcium sulfate is a kind of good bone graft substitute because of its excellent biocompatibility, biodegradation and osteo-conductivity, application of calcium sulfate can also avoid the side effects caused by using allograft bone or xenographic bone. A kind of commercial calcium sulfate which is carefully processed and purified named osteoset and tobramycin-impregnated calcium sulfate named Osteoset-T has been widely used in clinical practice in the united state and other countries. But research related with surgical grade calcium sulfate is rare in our country, and to our knowledge research related with antibiotic-carried calcium sulfate has not been found in our country.CCaS, a new kind of calcium sulfate has been carefully processed in our institute, its characteristics is similar to Osteoset. Based on the result of previous study, the aim of this study is to develop CaS/GM and CaS/PLA/GM, two kind of local biodegradable antibiotic delivery system which use CCaS or CCaS/PLA composite as antibiotic vehicle, and to do research on the following items,Physico-chemical property of the system, biocompatibility, feature of antibiotic release in vitro and the validity of preventing bone infection of the antibiotic delivery system. The feasibility of the CCaS used as antibiotic vehicle and clinical application of the antibiotic laden calcium sulfate is also explored in this study.PurposeTo develop bone-implanted local antibiotic delivery system, CaS/GM and CaS/PLA/GM, and to do research on the constructive characteristics, biocompatibility, degradable feature, characteristics of antibiotic elution in vitro and validity of preventing bone infection of both antibiotic delivery systems.Materials and methods(1) Development and analysis of the local antibiotic delivery system, CaS/GM and CaS/PLA/GM. To develop CaS/GM of different ratio of gentmycin and CaS/PLA/GM with different content of GM , CaS and PLA . And to analysis the physical and biomechanical characteristic, feature of constitute of the delivery system, and to have an initial exploration of its degradable property in vitro.(2) Evaluation of biocompatibility and safety of local antibiotic delivery system. According to ISO 10993-5 and GB/T 16886-1 standards, haemolysis test, cytotoxicity test by MTT method, pyrogenic test, and intramusculary implanting test has been performed.(3) Test of antibiotic delivery system In vitro. The study of antibiotic elution in vitro was performed in container filled with 6 ml PBS fluid, similar to the wound environment. The release amount of antibiotic at different time and the total amount of antibiotic released from the pellets of different type of delivery system was calculated, the antibiotic release characteristic was analysised. Also the bioassay of antibacterial activity of the eluted antibiotic was assessed by the zone of inhibition of bacterial growth using the Kirby-Bauer diffusion disc technique.(4) The experimental study preventing bone infection of the contaminated wound for CaS/GM CaS/PLA/GM. The validity of preventing bone infection ofantibiotic delivery system by implanting them into the local contaminated wound in rabbit proximal tibia was evaluated.Result(1) Development and analysis of the local antibiotic delivery system, CaS/GM and CaS/PLA/GM. The major constituent of antibiotic delivery system is calcium sulphate dihydrate, both of them have some degree of porosity and initial anti-compressive strength; CaS is encapsulated by PLA in CaS/PLA/GM system, the degradable rate of CaS/PLA/GM is slower than that of CaS/GM.(2) Evaluation of biocompatibility and safety of local antibiotic delivery system. The rate of haemolysis was 2.02 percent for CaS/GM and 3.07 percnt for CaS/PLA/GM, both were smaller than the positive standard for hamolysis. Both antibiotic systems had no toxicity to mesenchymal cell proliferations. The body temperature had no significant changes in pyrogenic test. Therefore, both antibiotic systems are biocompatible and safety. They both answer the demands of medical biomaterials.(3) Test of antibiotic delivery system In vitro: Method applying HPLC-ELSD to detect gentamycin is reliable and reproducibility, release of gentamycin can last for 4 to 5 weeks, gentamycin concentration of eluted fluid of CaS/GM at 28th day or CaS/PLA/GM at 35th day is bigger than MIC of gentamycin. The eluted gentamycine at 4 or 5 weeks still can inhibit ATCC29523 growing. The more gnetamycin the pellet contains, the more amount it release. The effective release time of CaS/GM is longer than that of CaS/PLA/GM., especially the type of gentamycin content 5% and PLA content 25%. The antibiotic release time and release amount of CaS/GM and CaS/PLA/GM is superior to that of PMMA/GM composite.(4) The experimental study preventing bone infection of the contaminated wound for CaS/GM CaS/PLA/GM.: there is no bone infection occurred in the rabbit in the experimental group, on the contrary all rabbit developed into osteomyelitis in the control group.Conclusion1. The major constituent of both local antibiotic delivery system is calcium sulfate dihydryte, both antibiotic delivery system have some degree of porosity and anti-compressive strength, so both of them are suit for drug release and bone implantation.2. Both antibiotic delivery systems are biocompatible and degradable, the degradation time of CaS/PLA/GM is longer than that of CaS/PLA/GM In vitro.3. The local antibiotic delivery system can release antibiotic for 4 to 5 weeks, the release time of CaS/PLA/GM is longer than that of CaS/GM. The release of antibiotic is relatively complete for the developed antibiotic delivery system. Gentamycin is heat stable, the anti-bacteria activity of the eluted gentamycin can last for 4-5 weeks.4. The local antibiotic delivery system can prevent bone infection occurring in open contaminated bone wound, and it does not hamper the repair of bone defect.5. CCaS and CCaS/PLA composite are suitable for antibiotic vehicle.
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