Cytocompatibility evaluation of amphiphilic, thermally responsive and chemically crosslinkable macromers for in situ forming hydrogels
Cytocompatibility evaluation of amphiphilic, thermally responsive and chemically crosslinkable macromers for in situ forming hydrogels
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DOI：
10.1016/j.biomaterials.2009.05.029
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发表时间：
2009-09-01
期刊：
影响因子：
14
通讯作者：
Mikos, Antonios G.
中科院分区：
文献类型：
--
作者：
Klouda, Leda;Hacker, Michael C.;Mikos, Antonios G.
考察了两亲性、热响应性和化学可交联性大分子聚合物的体外细胞相容性。以不同摩尔比、不同相对分子质量和较低临界溶解温度的季戊四醇二丙烯酸酯单硬脂酸酯、N-异丙基丙烯酰胺、丙烯酰胺和丙烯酸羟乙酯为原料，合成了与大鼠成纤维细胞相容的大分子聚合物。在与分子量约为1500-3000 Da的大分子单体孵育24小时后，观察到ALL的细胞存活率超过60%，大多数制剂的细胞存活率超过80%。用(甲基)丙烯酸酯基团对大分子单体进行化学修饰对细胞存活率有时间和剂量依赖性的影响。(甲基)丙烯酸化程度较低的未交联大分子单体可使细胞存活率在长达6小时的时间内保持在60%以上。(甲基)临界溶液温度(LCST)较低的丙烯酸类大分子聚合物更接近生理温度，可获得较高的细胞存活率，而不是具有较低的临界溶液温度(LCST)。数据表明，当(甲基)丙烯酸酯大分子单体组装成物理凝胶时，它们的细胞毒性就会降低。凝胶相分离后，细胞毒性增加。这项研究提供了使原位形成水凝胶系统的细胞能够被有效包裹的参数的信息。(C)2009爱思唯尔有限公司。保留所有权利。
The cytocompatibility of amphiphilic, thermoresponsive and chemically crosslinkable macromers was examined in vitro. Macromers synthesized from pentaerythritol diacrylate monostearate, N-isopropylacrylamide, acrylamide and hydroxyethyl acrylate in different molar ratios and with varying molecular weights and lower critical solution temperatures were evaluated for cytocompatibility with rat fibroblasts. Cell viabilities of over 60% for all and over 80% for most formulations were observed after 24-h incubation with macromers with molecular weights in the range of approximately 1500-3000 Da. The chemical modification of the macromers with a (meth)acrylate group was shown to have a time- and dose-dependent effect on cell viability. Uncrosslinked macromers with lower degrees of(meth)acrylation allowed for cell viability of over 60% for up to 6 h. (Meth)acrylated macromers with lower critical solution temperature (LCST) closer to physiological temperature allowed for higher cell viabilities as opposed to those with lower LCST. The data suggest that when the (meth)acrylated macromers are assembled into a physical gel, their cytotoxicity is diminished. After gel phase separation, cytotoxicity increased. This study gives information on the parameters that enable viable cell encapsulation for in situ forming hydrogel systems. (C) 2009 Elsevier Ltd. All rights reserved.