Biocompatibility of human hepatocyte/microporous polypropylene hybridization / 中国组织工程研究

ABSTRACT

BACKGROUND: Membrane materials of bioreactor have exchange of substance and good physiochemical characteristics as well as good biocompatibility.OBJECTIVE: To evaluate the biocompatibility of interface of human hepatocyte/microporous polypropylene, i.e. graft modified microporous polypropylene semipermeable ultrafiltration membrane (MPP).DESIGN, TIME AND SETTING: Animal observation was performed at the Organ Transplantation Center, Ruijin Hospital of Shanghai Jiao Tong University Medical School and Polymers Institute of Zhejiang University between September 2005 and October 2007.MATERIALS The microporous polypropylene ultrafiltration plane thin membranes, 0.2 μm diameter, M<,r> 50 000-100 000 molecular blockage, were used. Photochemical graft polymerization modification technique was adopted to graft hydrophilic acrylamide group through chemical bonds on MPP surface and succeeded in constructing an interface of human hepatocyte/microporous polypropylene, i.e. bioreactor membrane of bioartificial liver, graft modified MPP.METHODS: The biocompatibility of modified MPP was evaluated by hemolysis test, cytotoxicity test, acute systemic toxicity test, pyrogen test, skin sensitization and percutaneous stimulation test according to the requirements and biological evaluation criteria of medical device of ISO10993-11992.MAIN OUTCOME MEAURES The experimental results of hemolysis, cytotoxicity, general acute toxicity, pyrogen, skin sensitization and percutaneous stimulation of modified MPP.RESULTS: The hemolytic rate of modified MPP was 1.90% (<5%), which showed that modified MPP did not lead to hemolysis. The extract solution of modified MPP exhibited no significant inhibition on the proliferative activity of L929 cells. At 24, 48 and 72 hours after MPP injection, no mice death, significant changes in body mass, or acute systemic toxicity were observed, such as ptosis, dyspnea, eyanosis, abdominal stimulation, diarrhea, decreased movement or tremor. In rabbit pyrogen test, the body temperature changed in a range from -0.2 to 0.4, which was consistent with the evaluation criteria of biomedical materials without pyrogen. Only one case was found with very slight erythema in skin sensitization test; its integral was 1 and primary stimulation index was 0.25 (<0.4), and the primary stimulation index of percutaneous stimulation test was 0.2; the average primary stimulation index was 0.068, indicating that modified MPP had no skin irritation.CONCLUSION: Modified MPP has no haemolytieus, cytotoxicity, pyrogenicity or skin sensitization, suggesting good biocompatibility by photochemical graft acrylamide on the surface of MPP.