海藻酸-壳聚糖-聚乙烯乙二醇微囊生物相容性的研究

目的比较海藻酸-壳聚糖-聚乙烯乙二醇微囊(ACP微囊)和海藻酸-聚赖氨酸-海藻酸微囊(APA微囊)的生物相容性。方法(1)两种微囊(50、100和200个)与健康人血清共浴，检测微囊对补体的激活程度。(2)1000个APA和ACP微囊分别植入Wistar大鼠的腹腔，4d和3周时统计取出的微囊数和微囊的纤维化率。(3)Wistar大鼠胰岛用ACP微囊和APA微囊包裹，分别贯续置于含3.3mmol/L和16.7mmol/L葡萄糖的Hank's溶液中培养，测定培养液中胰岛素的浓度。结果(1)ACP微囊组残余补体活性高于APA微囊组。(2)4d时，ACP和APA微囊的取出数分别是845.0±40.4和807.6±45.7(P>0.05)，囊周纤维化率分别是16.40%和65.68%(P<0.05)；3周时两种微囊的取出数分别为715.0±133.0和367.5±105.6(P<0.05)，囊周纤维化率为27.8%和83.9%(P<0.05)。(3)在含3.3mmol/L葡萄糖的Hank's液中，未微囊胰岛组、APA和ACP微囊化胰岛组的胰岛素浓度分别是(123.48±4.70)mIU/L、(110.11±12.18)mIU/L和(110.90±11.95)mIU/L，当葡萄糖浓度为16.7mmol/L时，胰岛素浓度分别是(754.75±13.81)mIU/L、(689.30±27.71)mIU/L和(684.28±70.10)mIU/L。结论海藻酸-壳聚糖-聚乙烯乙二醇微囊的生物相容性要优于海藻酸-聚赖氨酸-海藻酸微囊，前者更适合应用于微囊化胰岛移植。

Study on biocompatibility of alginate-chitosan-polyethyleneglycol microcapsules

Objective　To compare the biocompatibility of the alginate-polylysine-alginate (APA) microcapsule and the alginate-chitosan-polyethyleneglycol (ACP) microcapsule. Methods　50, 100 and 200 of both APA and ACP microcapsule were co-cultured with human serum and the ability of complement activation of both microcapsules recorded. 1000 ACP microcapsules and 1000 APA microcapsules were implanted into the peritoneal cavity of wister rats respectively and retrieved at 4th day and 3rd week after implantation. The number of retrieved microcapsules and percentage of microcapsules with pericapsular fibrosis were recorded. Isolated rat islets were microencapsulated with ACP microencapsulates and APA microcapsulates. The contents of secreted insulin were measured when both encapsulated islets were serially cultured in Hank's solution containing 3.3 mmol/L and 16.7 mmol/L glucose respectively. The unencapsulated islets served as control. Results　Four days after implantation, the number of retrieved ACP and APA microcapsules were 845.0±40.4 and 807.6±45.7 respectively, while the percentage of microcapsules with pericapsular fibrosis was 16.40 % and 65.68 % respectively (P<0.05). Three weeks after implantation, the number of retrieved ACP and APA microcapsules were 715.0±133.0 and 367.5±105.6 respectively (P<0.05), while the percentage of ACP and APA microcapsules with pericapsular fibrosis was 27.8 % and 83.9 % respectively (P<0.05). The residual complement activity of human serum was much higher in the ACP activation group. As with unencapsulated islets, the ACP microencapsulated islets maintained the ability of constitutional insulin secretion and stimulated secretion when challenged with high concentration glucose. No significant difference was observed among groups. Conclusion　The ACP microcapsules possess better biocompatibility than APA microcapsules.