Hana Macková , Helena Hlídková , Zhansaya Kaberova , Vladimír Proks , Jan Kučka , Vitalii Patsula , Miroslav Vetrik , Olga Janoušková , Bohumila Podhorská , Ognen Pop-Georgievski , Šárka Kubinová , Daniel Horák
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引用次数: 6
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.
研究具有高含水量和类似组织的机械性能的可降解水凝胶聚合物材料不仅在药物输送系统中,而且在组织工程、医疗设备和生物医疗保健传感器中都至关重要。因此,我们提出了基于聚(2-甲基丙烯酸羟乙基-co-2-(乙酰硫)甲基丙烯酸乙基-co-2-甲基丙烯酰氧乙基磷酸胆碱)[P(HEMA-ATEMA-MPC)]的水凝胶的开发,并优化了其机械降解性和体内外降解性。P(HEMA-ATEMA-MPC)水凝胶在化学成分、交联程度和聚合物的起始摩尔质量(15、19和30 kDa)方面存在差异。聚合物前驱体采用可逆加成裂解链转移(RAFT)聚合法制备,以含保护巯基的2-(乙酰硫)甲基丙烯酸乙酯为原料,实现交联和凝胶形成。水凝胶的弹性模量随着交联程度的增加而增加(Slaughter et al., 2009)[1]。采用谷胱甘肽和皮下植入水凝胶分别在大鼠体内和体外控制降解。结果表明,交联度较高的水凝胶可以延缓降解。同时,测试白蛋白、γ-球蛋白和纤维蛋白原在P(HEMA-ATEMA-MPC)水凝胶表面的吸附,模拟生物体内的吸附。RGDS肽和层粘连蛋白的存在可改善大鼠间充质间质细胞对水凝胶的粘附。我们发现大鼠间充质间质细胞在层粘连蛋白包被的水凝胶上比在rgds修饰的水凝胶上增殖得更好。
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