Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
Biomaterials. 2010 Apr;31(10):2836-47. doi: 10.1016/j.biomaterials.2009.12.050. Epub 2010 Jan 21.
Our research is focused on the design of hydrogel biomaterials that can be used for 3-D cell encapsulation and tissue engineering. In this study, our goal was to engineer a temperature-responsive biomaterial to possess bioactive properties using polymer and protein chemistry, and at the same time provide the biomaterial with susceptibility to cell-mediated remodeling. Toward this goal, we developed a biomimetic material that can harness the bioactive properties of fibrinogen and the unique structural properties of PluronicF127. PluronicF127 is a synthetic block copolymer that exhibits reverse thermal gelation (RTG) in response to small changes in ambient temperature. We conjugated fibrinogen to Pluronic)F127 to create a biosynthetic precursor with tunable physicochemical properties based on the relationship between the two constituents. A hydrogel matrix was formed from the fibrinogen-F127 adducts by free-radical polymerization using light activation (photo-polymerization). These materials displayed a reversible temperature-induced physical sol-gel transition and an irreversible light-activated chemical cross-linking. The susceptibility of this hydrogel biomaterial to protease degradation and consequent cell-mediated remodeling was controlled by the PluronicF127 constituent. The protein-based material also conveyed inductive signals to cells through bioactive sites on the fibrinogen backbone, as well as through structural properties such as the matrix modulus. We apply these materials as a tissue engineering hydrogel scaffold for 3-D in vitro culture of dermal fibroblasts in order to gain a better understanding of how the material bioactivity and matrix properties can independently affect cell morphology and remodeling.
我们的研究集中于水凝胶生物材料的设计,这些材料可用于 3D 细胞包封和组织工程。在这项研究中,我们的目标是通过聚合物和蛋白质化学工程来设计一种对温度响应的生物材料,使其具有生物活性,并同时使生物材料易于细胞介导的重塑。为此,我们开发了一种仿生材料,它可以利用纤维蛋白原的生物活性特性和 PluronicF127 的独特结构特性。PluronicF127 是一种合成嵌段共聚物,可响应环境温度的微小变化发生反向热凝胶化 (RTG)。我们将纤维蛋白原与 PluronicF127 缀合,根据两种成分之间的关系,创建一种具有可调理化性质的生物合成前体。纤维蛋白原-F127 加合物通过自由基聚合用光激活(光聚合)形成水凝胶基质。这些材料显示出可逆的温度诱导的物理溶胶-凝胶转变和不可逆的光激活的化学交联。这种水凝胶生物材料对蛋白酶降解和随后的细胞介导重塑的敏感性由 PluronicF127 成分控制。基于纤维蛋白原骨架上的生物活性位点以及基质模量等结构特性,该蛋白基材料还向细胞传递诱导信号。我们将这些材料用作组织工程水凝胶支架,用于体外培养真皮成纤维细胞的 3D 培养,以更好地了解材料的生物活性和基质特性如何独立影响细胞形态和重塑。