Biologically engineered protein-graft-poly(ethylene glycol) hydrogels:: A cell adhesive and plasm in-degradable biosynthetic material for tissue repair
Biologically engineered protein-graft-poly(ethylene glycol) hydrogels:: A cell adhesive and plasm in-degradable biosynthetic material for tissue repair
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DOI：
10.1021/bm015629o
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发表时间：
2002-07-01
影响因子：
6.2
通讯作者：
Hubbell, JA
中科院分区：
文献类型：
--
作者：
Halstenberg, S;Panitch, A;Hubbell, JA
为了满足伤口愈合和组织再生临床应用对生物活性材料的需求，通过重组 DNA 方法创建了一种人工蛋白质，并通过聚乙二醇二丙烯酸酯接枝进行修饰。随后含丙烯酸酯前体的光聚合产生了蛋白质接枝聚乙二醇水凝胶。该人工蛋白含有基于纤维蛋白原和抗凝血酶 III 的重复氨基酸序列，包括一个 RGD 整联蛋白结合基序、两个纤溶酶降解位点和一个肝素结合位点。二维粘附研究表明，基于纤维蛋白原序列中包含的 RGD 基序，该人工蛋白具有特定的整合素结合能力。此外，肝素与该蛋白质的抗凝血酶 III 区域强烈结合。蛋白质接枝聚乙二醇水凝胶可被纤溶酶降解，杨氏模量高达 3.5 kPa，并支持人成纤维细胞的三维生长。细胞在三个维度上的附着是由特定的细胞表面整合素与材料的 RGD 序列结合而产生的。细胞的水凝胶渗透涉及丝氨酸蛋白酶介导的基质降解，与细胞生长在时间和空间上同步。蛋白质接枝聚乙二醇水凝胶代表了一类新型多功能仿生混合材料，在作为植入物促进伤口愈合和组织再生方面具有临床应用前景。
To address the need for bioactive materials toward clinical applications in wound healing and tissue regeneration, an artificial protein was created by recombinant DNA methods and modified by grafting of poly(ethylene glycol) diacrylate. Subsequent photopolymerization of the acrylate-containing precursors yielded protein-graft-poly(ethylene glycol) hydrogels. The artificial protein contained repeating amino acid sequences based on fibrinogen and anti-thrombin III, comprising an RGD integrin-binding motif, two plasmin degradation sites, and a heparin-binding site. Two-dimensional adhesion studies showed that the artificial protein had specific integrin-binding capability based on the RGD motif contained in its fibrinogen-based sequence. Furthermore, heparin bound strongly to the protein's anti-thrombin III-based region. Protein-graft-poly(ethylene glycol) hydrogels were plasmin degradable, had Young's moduli up to 3.5 kPa, and supported three-dimensional outgrowth of human fibroblasts. Cell attachment in three dimensions resulted from specific cell-surface integrin binding to the material's RGD sequence. Hydrogel penetration by cells involved serine-protease mediated matrix degradation in temporal and spatial synchrony with cellular outgrowth. Protein-graft-poly(ethylene glycol) hydrogels represent a new and versatile class of biomimetic hybrid materials that hold clinical promise in serving as implants to promote wound healing and tissue regeneration.