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通过共价偶联到羟基上制备稳定的半乳糖化海藻酸盐微胶囊用于肝细胞应用。

Fabrication of stable galactosylated alginate microcapsules via covalent coupling onto hydroxyl groups for hepatocytes applications.

机构信息

Laboratory of Biomedical Materials Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, PR China; University of the Chinese Academy of Sciences, Beijing 100049, PR China.

Laboratory of Biomedical Materials Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, PR China.

出版信息

Carbohydr Polym. 2017 Jan 2;155:456-465. doi: 10.1016/j.carbpol.2016.08.098. Epub 2016 Aug 31.

Abstract

Galactose moieties are covalently coupled with sodium alginate to enhance liver-specific functions in microcapsules owing to the specific interaction between the galactose moieties and the asialoglycoprotein receptors (ASGPRs) of hepatocytes. In this study, galactosylated alginate (L-NH-OH-alginate) based microcapsules with desirable stability and a suitable 3D microenvironment are designed and fabricated for primary hepatocyte applications. The designed L-NH-OH-alginate is fabricated via the application of ethylenediamine grafted lactobionic acid (L-NH) onto the hydroxyl groups of sodium alginate so that the negatively charged carboxyl groups intact in L-NH-OH-alginate can effectively bond with Ca to form a stable three-dimensional gel network; a subsequent reaction with polycations forms a stable membrane of microcapsules. As a result, L-NH-OH-alginate based microcapsules exhibit an excellent mechanical stability. Moreover, with a higher degree of substitution in L-NH-OH-alginate (DS 0.41), the hepatocytes entrapped in L-NH-OH-alginate microcapsules exhibit better viability and well-maintained liver-specific functions.

摘要

半乳糖基与海藻酸钠通过共价键连接,由于半乳糖基与肝细胞的去唾液酸糖蛋白受体(ASGPRs)之间的特异性相互作用,在微胶囊中增强了肝脏特异性功能。在这项研究中,设计并制备了具有理想稳定性和合适 3D 微环境的基于半乳糖化海藻酸钠(L-NH-OH-海藻酸钠)的微胶囊,用于原代肝细胞的应用。所设计的 L-NH-OH-海藻酸钠是通过将接枝有乙二胺的乳糖酸(L-NH)应用于海藻酸钠的羟基上而制备的,以便在 L-NH-OH-海藻酸钠中保持完整的带负电荷的羧基基团能够有效地与 Ca 结合,形成稳定的三维凝胶网络;随后与多阳离子反应形成微胶囊的稳定膜。结果,基于 L-NH-OH-海藻酸钠的微胶囊表现出优异的机械稳定性。此外,随着 L-NH-OH-海藻酸钠中取代度(DS 0.41)的增加,包埋在 L-NH-OH-海藻酸钠微胶囊中的肝细胞表现出更好的活力和维持良好的肝脏特异性功能。

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