接枝改性微孔聚丙烯超滤膜的生物相容性评价

Biocompatibility of graft modified microporous polypropylene semipermeable ultrafiltration membrane

背景：生物反应器膜材料不仅具备双向物质交换、良好的理化特性,还要具有良好的生物相容性。目的：通过溶血试验、细胞毒性试验、全身急性毒性试验、热原试验、皮肤和皮内刺激试验来评价接枝改性微孔聚丙烯超滤膜（modified micropore polypropylene semipermeable ultrafiltration membrane,Modified MPP）的生物相容性。设计、时间及地点：动物实验观察。

BACKGROUND： The material of bioreactor membrane not only has the two-way exchange of materials, good physical and chemical characteristics, but also has a good biocompatibility. OBJECTIVE： To evaluate the biocompatibility of the graft modified microporous polypropylene semipermeable ultraf＇dtration membrane （MPP） by hemolysis test, cytotoxicity test, acute systemic toxicity test, thermal test, skin irritation and percutaneous stimulation test. DESIGN, TIME AND SETTING： The experimental observation of animals was performed in the Organ Transplantation Center of Ruijin Hospital Affiliated to Medical College of Shanghai Jiao Tong University （Shanghai Institute of Digestive Surgery） and the Polymers Institute of Zhejiang University from September 2005 to October 2007. MATERIALS： Fifteen adult ICR mice for general acute toxicity test were randomly divided into modified MPP group, MPP group and sodium chloride negative control group. Each group was 5 mice. Fifteen healthy adult New Zealand rabbits for the pyrogen test of modified MPP were divided into modified MPP group, MPP group and sodium chloride negative control group. Four rabbits for the skin stimulation test of modified MPP experiment were injected with modified MPP and MPP, respectively. Three rabbits for the intradermally stimulation test were injected with modified MPP leaching liquor, MPP leaching liquor and sodium chloride diffusion medium, respectively. METItODS： The experiment adopted the microporous polypropylene ultrafiltration plane films （its aperture was 0.2 1~ m and the cut-off of its molecule was Mr 50 000-100 000） for the models. Photochemical graft polymerization modification technology was used to graft hydrophilic acrylamide group through chemical bonds on MPP surface and succeeded in building a new bioreactor membrane of bioartificial liver, graft modified MPP. The biocompatibility of modified MPP was evaluated by hemolysis test, cytotoxicity test, acute systemic toxicity test, thermal test, skin irritation and percutaneous stimulation test. MAIN OUTCOME MEASURES： Whether the experimental results of hemolysis, cytotoxicity, general acute toxicity, pyrogen, skin irritation and intradermally stimulus of modified MPP were consistent with the relevant standards of biomedical materials or not. RESULTS： The hemolytic rate of modified MPP was 1.90% （〈 5%）, which showed that modified MPP did not lead to hemolysis. The leaching liquor of modified MPP had no significant inhibition on the proliferative activity of L929 cells. At 24, 48 and 72 hours after injection, no mice death, no significant changes in body weight, and no acute systemic toxicity were observed, such as ptosis, dyspnea, cyano＇sis, abdominal stimulation, diarrhea, decreased movement and tremor. In rabbit pyrogen test, the body temperature changed in a range from -0.2 to 0.4, the average increasing temperature of each rabbit was less than 0.6 ~C and the sum increase of three rabbits was 0.0-0.4, all of groups were less than 1.4 ~, which was consistent with the evaluation criteria of biomedical materials without pyrogen. Modified MPP group had only one case of very slight erythema, its integral was l, its primary stimulation index was 0.25 （〈0.4）, the primary stimulation index of percutaneous stimulation test was 0.2, the average primary stimulation index was 0.068, the above results were less than 0.4, which indicated that modified MPP had no skin irritation. CONCLUSION： Modified MPP has no haemolyt/cus, cytotoxicity, pyrogenicity or skin stimulus sensitization, and it shows good biocompatibility by photochemical graft acrylamide on the surface of MPP.