Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering
Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering
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DOI：
10.1016/j.biomaterials.2007.03.027
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发表时间：
2007-09-01
期刊：
影响因子：
14
通讯作者：
Lutolf, Matthias P.
中科院分区：
文献类型：
--
作者：
Ehrbar, Martin;Rizzi, Simone C.;Lutolf, Matthias P.
以细胞为导向的人工细胞外基质的分子工程是控制细胞行为和实现复杂的组织形成和再生过程的有力手段。这项工作报告了一种新的方法，通过在合成类似物中重述生物聚合物纤维蛋白的交联化学和生物分子特征来制备这种智能生物材料。我们使用激活的凝血酶转谷氨酰胺酶XIIIA将细胞黏附配体和工程生长因子蛋白定点偶联到多臂聚乙二醇大分子上，在同一酶催化的反应中同时形成蛋白水凝胶网络。生长因子蛋白在细胞来源的凝胶蛋白降解时被定量地结合和释放。无论是在体外还是在体内，原始基质细胞都可以侵入并蛋白水解性地重塑这些网络。这些杂化网络的合成简便性和设计其物理化学和生物活性特性的潜力使其成为组织工程中纤维蛋白的临时药物输送平台的真正替代品。(C)2007爱思唯尔有限公司。保留所有权利。
The molecular engineering of cell-instructive artificial extracellular matrices is a powerful means to control cell behavior and enable complex processes of tissue formation and regeneration. This work reports on a novel method to produce such smart biomaterials by recapitulating the crosslinking chemistry and the biomolecular characteristics of the biopolymer fibrin in a synthetic analog. We use activated coagulation transglutaminase factor XIIIa for site-specific coupling of cell adhesion ligands and engineered growth factor proteins to multiarm poly(ethylene glycol) macromers that simultaneously form proteolytically sensitive hydrogel networks in the same enzyme-catalyzed reaction. Growth factor proteins are quantitatively incorporated and released upon cell-derived proteolytic degradation of the gels. Primary stromal cells can invade and proteolytically remodel these networks both in an in vitro and in vivo setting. The synthetic ease and potential to engineer their physicochemical and bioactive characteristics makes these hybrid networks true alternatives for fibrin as provisional drug delivery platforms in tissue engineering. (c) 2007 Elsevier Ltd. All rights reserved.