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具有内皮细胞活性的抗血栓形成的柠檬酸交联明胶。

An antithrombogenic citric acid-crosslinked gelatin with endothelialization activity.

机构信息

Biomaterials Unit, Nano-bio field, Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.

出版信息

Adv Healthc Mater. 2012 Sep;1(5):573-81. doi: 10.1002/adhm.201200001. Epub 2012 Jul 6.

Abstract

A novel citric acid-crosslinked gelatin matrix with endothelialization activity and anti-adhesive properties for platelets is prepared. The matrix is characterized using an endothelial cell culture and an antithrombogenic activity test. The number of endothelial cells cultured on the surface of the trisuccinimidyl citrate (TSC)-crosslinked gelatin increases as the concentration of TSC increases to 20 mM, and then decreases with further increases in TSC concentration. Compared with glutaraldehyde-crosslinked gelatin, platelet number and fibrin network formation on the TSC-crosslinked gelatin are minimal at high TSC concentration. The biocompatibility of the matrix is evaluated by bioluminescence imaging. This indicates that the inflammation reaction of the TSC-crosslinked gelatin is lower than that of glutaraldehyde-crosslinked gelatin. Physicochemical analysis of TSC-crosslinked gelatin with different TSC concentrations shows that the high concentration of the cell adhesion sequence, arginine-glycine-aspartic acid, contributes to the promotion of endothelial cell adhesion and subsequent endothelial cell growth. Analysis of the carboxyl groups in the TSC-crosslinked gelatin showed that the antithrombogenic activity is due to the increased negative charge derived from the hydrolyzed active ester groups of TSC. These findings show that TSC-crosslinked gelatin has the potential for use in biomedical devices in contact with blood, such as stents, artificial blood vessels, and artificial heart valves.

摘要

一种具有内皮细胞活性和抗血小板黏附特性的新型柠檬酸交联明胶基质被制备。使用内皮细胞培养和抗血栓形成活性测试对该基质进行了表征。在三(2-羧乙基)异氰尿酸酯(TSC)交联明胶表面培养的内皮细胞数量随着 TSC 浓度增加到 20mM 而增加,然后随着 TSC 浓度的进一步增加而减少。与戊二醛交联明胶相比,在高 TSC 浓度下,血小板数量和 TSC 交联明胶上的纤维蛋白网络形成最小。通过生物发光成像评估了基质的生物相容性。这表明 TSC 交联明胶的炎症反应低于戊二醛交联明胶。对不同 TSC 浓度的 TSC 交联明胶进行的物理化学分析表明,高浓度的细胞黏附序列精氨酸-甘氨酸-天冬氨酸有助于促进内皮细胞黏附和随后的内皮细胞生长。对 TSC 交联明胶中的羧基进行分析表明,抗血栓形成活性是由于 TSC 的水解活性酯基团产生的负电荷增加所致。这些发现表明,TSC 交联明胶有可能用于与血液接触的生物医学设备,如支架、人工血管和人工心脏瓣膜。

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