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与定制的类弹性蛋白聚合物进行酶交联的胶原蛋白支架的体外表征

In vitro characterization of a collagen scaffold enzymatically cross-linked with a tailored elastin-like polymer.

作者信息

Garcia Yolanda, Hemantkumar Naik, Collighan Russell, Griffin Martin, Rodriguez-Cabello Jose Carlos, Pandit Abhay

机构信息

Department of Anatomy, National University of Ireland Galway, Galway, Ireland.

出版信息

Tissue Eng Part A. 2009 Apr;15(4):887-99. doi: 10.1089/ten.tea.2008.0104.

DOI:10.1089/ten.tea.2008.0104
PMID:18976154
Abstract

Collagen, the main structural component of the extracellular matrix (ECM), provides tensile stiffness to different structures and organs against rupture. However, collagen tissue-engineered implants are hereto still lacking in mechanical strength. Attempts to create stiffer scaffolds have resulted in increased brittleness of the material, reducing the versatility of the original component. The hypothesis behind this research is that the introduction of an elastic element in the scaffold will enhance the mechanical properties of the collagen-based scaffolds, as elastin does in the ECM to prevent irreversible deformation. In this study, an elastin-like polymer (ELP) designed and synthesized using recombinant DNA methodology is used with the view to providing increased proteolytic resistance and increased functionality to the scaffolds by carrying specific sequences for microbial transglutaminase cross-linking, endothelial cell adhesion, and drug delivery. Evaluation of the effects that cross-linking ELP-collagen has on the physicochemical properties of the scaffold such as porosity, presence of cross-linking, thermal behavior, and mechanical strength demonstrated that the introduction of enzymatically resistant covalent bonds between collagen and ELP increases the mechanical strength of the scaffolds in a dose-dependent manner without significantly affecting the porosity or thermal properties of the original scaffold. Importantly, the scaffolds also showed selective behavior, in a dose (ELP)-dependent manner toward human umbilical vein endothelial cells and smooth muscle cells when compared to fibroblasts.

摘要

胶原蛋白是细胞外基质(ECM)的主要结构成分,可为不同结构和器官提供抗破裂的拉伸刚度。然而,迄今为止,胶原蛋白组织工程植入物的机械强度仍然不足。制造更硬支架的尝试导致材料脆性增加,降低了原始组件的通用性。本研究背后的假设是,在支架中引入弹性元件将增强基于胶原蛋白的支架的机械性能,就像弹性蛋白在ECM中防止不可逆变形一样。在本研究中,使用重组DNA方法设计和合成的类弹性蛋白聚合物(ELP)被用于通过携带用于微生物转谷氨酰胺酶交联、内皮细胞粘附和药物递送的特定序列,为支架提供更高的抗蛋白水解性和增加功能性。对交联ELP-胶原蛋白对支架的物理化学性质(如孔隙率、交联的存在、热行为和机械强度)的影响的评估表明,在胶原蛋白和ELP之间引入抗酶共价键以剂量依赖的方式增加了支架的机械强度,而不会显著影响原始支架的孔隙率或热性质。重要的是,与成纤维细胞相比,支架还以剂量(ELP)依赖的方式对人脐静脉内皮细胞和平滑肌细胞表现出选择性行为。

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