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一种用于药物递送和组织工程的可注射、原位酶促凝胶化的明胶衍生物。

An injectable, in situ enzymatically gellable, gelatin derivative for drug delivery and tissue engineering.

作者信息

Sakai Shinji, Hirose Keisuke, Taguchi Kenichi, Ogushi Yuko, Kawakami Koei

机构信息

Department of Chemical Engineering, Kyushu University, Motooka, Nishi-ku, Fukuoka, Japan.

出版信息

Biomaterials. 2009 Jul;30(20):3371-7. doi: 10.1016/j.biomaterials.2009.03.030. Epub 2009 Apr 5.

Abstract

A phenolic hydroxyl group was incorporated into gelatin, using aqueous-phase carbodiimide activation chemistry, to obtain in situ gellable and injectable protein-based materials for drug delivery and tissue engineering applications. By this means, gelatin derivatives that were gellable via a peroxidase-catalyzed reaction were obtained. The enzymatically cross-linked gelatin gels did not melt at 37 degrees C and showed tunable proteolytic degradability. The time necessary for gelation decreased with increasing content of the phenolic hydroxyl (Ph) group, peroxidase concentration and decreasing H(2)O(2) concentration. Resistance to gel compression also depended on the content of Ph groups, with the gel containing the lowest Ph group content showing the greatest resistance to compression. We encapsulated L929 fibroblast cells in gelatin gels under conditions that induced gelation in about 10 s. The encapsulated cells showed about 95% viability. In addition, L929 cells seeded on the gels showed the same growth profiles as those seeded on an unmodified gelatin-coated dish. Subcutaneous rodent injection experiments demonstrated successful in situ formation of gels at the injected site.

摘要

利用水相碳二亚胺活化化学方法将酚羟基引入明胶中,以获得用于药物递送和组织工程应用的可原位凝胶化且可注射的蛋白质基材料。通过这种方式,获得了可通过过氧化物酶催化反应凝胶化的明胶衍生物。酶促交联的明胶凝胶在37℃下不会熔化,并显示出可调节的蛋白水解降解性。凝胶化所需的时间随着酚羟基(Ph)基团含量的增加、过氧化物酶浓度的增加和过氧化氢浓度的降低而减少。凝胶的抗压性也取决于Ph基团的含量,Ph基团含量最低的凝胶表现出最大的抗压性。我们在约10秒内诱导凝胶化的条件下将L929成纤维细胞封装在明胶凝胶中。封装的细胞显示出约95%的活力。此外,接种在凝胶上的L929细胞显示出与接种在未修饰的明胶包被培养皿上的细胞相同的生长曲线。皮下啮齿动物注射实验证明在注射部位成功原位形成了凝胶。

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