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巯基化聚(2-羟乙基甲基丙烯酸酯)水凝胶作为一种可降解的生物相容性支架用于组织工程。

Thiolated poly(2-hydroxyethyl methacrylate) hydrogels as a degradable biocompatible scaffold for tissue engineering.

机构信息

Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, 162 06 Prague 6, Czech Republic.

Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, 162 06 Prague 6, Czech Republic.

出版信息

Mater Sci Eng C Mater Biol Appl. 2021 Dec;131:112500. doi: 10.1016/j.msec.2021.112500. Epub 2021 Oct 19.

Abstract

Research of degradable hydrogel polymeric materials exhibiting high water content and mechanical properties resembling tissues is crucial not only in drug delivery systems but also in tissue engineering, medical devices, and biomedical-healthcare sensors. Therefore, we newly offer development of hydrogels based on poly(2-hydroxyethyl methacrylate-co-2-(acetylthio) ethyl methacrylate-co-2-methacryloyloxyethyl phosphorylcholine) [P(HEMA-ATEMA-MPC)] and optimization of their mechanical and in vitro and in vivo degradability. P(HEMA-ATEMA-MPC) hydrogels differed in chemical composition, degree of crosslinking, and starting molar mass of polymers (15, 19, and 30 kDa). Polymer precursors were synthesized by a reversible addition fragmentation chain transfer (RAFT) polymerization using 2-(acetylthio)ethyl methacrylate containing protected thiol groups, which enabled crosslinking and gel formation. Elastic modulus of hydrogels increased with the degree of crosslinking (Slaughter et al., 2009) [1]. In vitro and in vivo controlled degradation was confirmed using glutathione and subcutaneous implantation of hydrogels in rats, respectively. We proved that the hydrogels with higher degree of crosslinking retarded the degradation. Also, albumin, γ-globulin, and fibrinogen adsorption on P(HEMA-ATEMA-MPC) hydrogel surface was tested, to simulate adsorption in living organism. Rat mesenchymal stromal cell adhesion on hydrogels was improved by the presence of RGDS peptide and laminin on the hydrogels. We found that rat mesenchymal stromal cells proliferated better on laminin-coated hydrogels than on RGDS-modified ones.

摘要

研究具有高含水量和类似组织机械性能的可降解水凝胶聚合材料不仅在药物输送系统中至关重要,而且在组织工程、医疗器械和生物医学保健传感器中也是如此。因此,我们新提供了基于聚(2-羟乙基甲基丙烯酸酯-co-2-(乙酰巯基)乙基甲基丙烯酸酯-co-2-甲基丙烯酰氧乙基膦酰胆碱)[P(HEMA-ATEMA-MPC)]的水凝胶的开发,并对其机械性能和体外及体内降解性进行了优化。P(HEMA-ATEMA-MPC)水凝胶在化学组成、交联度和聚合物的起始摩尔质量(15、19 和 30 kDa)方面有所不同。聚合物前体是通过可逆加成-断裂链转移(RAFT)聚合合成的,使用含有保护巯基的 2-(乙酰巯基)乙基甲基丙烯酸酯,这使其能够交联和形成凝胶。水凝胶的弹性模量随交联度的增加而增加(Slaughter 等人,2009)[1]。分别使用谷胱甘肽和皮下植入水凝胶在体内进行体外和体内控制降解的验证。我们证明了具有更高交联度的水凝胶会延迟降解。此外,还测试了 P(HEMA-ATEMA-MPC)水凝胶表面对白蛋白、γ-球蛋白和纤维蛋白原的吸附,以模拟在活体内的吸附。水凝胶表面存在 RGDS 肽和层粘连蛋白可提高大鼠间充质基质细胞的黏附性。我们发现大鼠间充质基质细胞在涂有层粘连蛋白的水凝胶上的增殖优于 RGDS 修饰的水凝胶。

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