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用于原位形成水凝胶的两亲性、热响应性和可化学交联大分子单体的细胞相容性评估

Cytocompatibility evaluation of amphiphilic, thermally responsive and chemically crosslinkable macromers for in situ forming hydrogels.

作者信息

Klouda Leda, Hacker Michael C, Kretlow James D, Mikos Antonios G

机构信息

Department of Bioengineering, Rice University, MS-142, P.O. Box 1892, Houston, TX 77251-1892, USA.

出版信息

Biomaterials. 2009 Sep;30(27):4558-66. doi: 10.1016/j.biomaterials.2009.05.029. Epub 2009 Jun 9.

Abstract

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.

摘要

在体外检测了两亲性、热响应性和可化学交联的大分子单体的细胞相容性。对由季戊四醇二丙烯酸单硬脂酸酯、N-异丙基丙烯酰胺、丙烯酰胺和丙烯酸羟乙酯以不同摩尔比合成的、具有不同分子量和较低临界溶液温度的大分子单体,评估其与大鼠成纤维细胞的细胞相容性。在用分子量约为1500 - 3000 Da的大分子单体孵育24小时后,观察到所有配方的细胞活力均超过60%,大多数配方的细胞活力超过80%。结果表明,用(甲基)丙烯酸酯基团对大分子单体进行化学修饰对细胞活力具有时间和剂量依赖性影响。具有较低(甲基)丙烯酸化程度的未交联大分子单体在长达6小时内可使细胞活力超过60%。与较低临界溶液温度(LCST)的大分子单体相比,LCST更接近生理温度的(甲基)丙烯酸化大分子单体具有更高的细胞活力。数据表明,当(甲基)丙烯酸化大分子单体组装成物理凝胶时,其细胞毒性会降低。凝胶相分离后,细胞毒性增加。本研究提供了有关参数的信息,这些参数有助于原位形成水凝胶系统时实现活细胞包封。

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