The role of ECM proteins and protein fragments in guiding cell behavior in regenerative medicine
The role of ECM proteins and protein fragments in guiding cell behavior in regenerative medicine
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DOI：
10.1016/j.biomaterials.2011.02.027
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发表时间：
2011-06-01
期刊：
影响因子：
14
通讯作者：
Barker, Thomas H.
中科院分区：
文献类型：
--
作者：
Barker, Thomas H.
用于再生医学组织工程的生物材料设计的前景是基于指导或引导特定和高度协调的细胞行为的基本能力，这些细胞行为最终导致生理功能组织和器官的产生。迄今为止，我们的努力主要集中在移植和介绍短合成肽的正当理由。短肽能够进行高水平的控制，可以在GMP指导下以高度可再现的方式相对容易地制造，并且容易被修饰以使其能够与用于生物材料移植的许多当前和新兴的化学物质整合。然而，虽然细胞外基质（ECM）衍生肽已证明其最初目的是促进细胞粘附，但它们普遍缺乏特异性且受体结合亲和力显着降低，这已被证明不利于调节组织再生所需的高度特异性和整合过程。与粘附肽不同，天然ECM通过支持环境敏感性和细胞依赖性整联蛋白特异性和结合亲和力而显示出与细胞的复杂相互作用。此外，ECM蛋白上的粘附配体显示出微调和进化定向的空间周期性，其通过机械和化学修饰动态控制。如果生物材料设计要实现其承诺，这些和其他来自基质生物学的新兴概念需要我们的注意。在这里，我们负责辩论的声明“使用短的合成粘附肽，如RGD，是最好的方法在设计的生物材料，指导细胞行为的再生医学组织工程”。在这篇主要观点论文中，我将重点关注天然ECM蛋白和蛋白片段的各个方面，这些蛋白和蛋白片段已被证明很难（如果不是不可能的话）在基于肽的系统中重现。虽然这代表了反对使用肽本身的论点，但它也可以被视为概述了生物材料领域的挑战和机遇。(C)2011爱思唯尔有限公司保留所有权利。
The promise of biomaterials design for regenerative medicine tissue engineering is predicated on the fundamental ability to direct or guide specific and highly coordinated cellular behaviors that culminate in the creation of physiologically functional tissues and organs. To date, our efforts have focused primarily on the grafting and presentation of short synthetic peptides with just cause. Short peptides are capable of high levels of control, can be manufactured relatively easily in a highly reproducible manner under GMP guidelines and are readily modified to enable their integration with numerous current and emerging chemistries for biomaterials grafting. However, while extracellular matrix (ECM)-derived peptides have demonstrated their initial purpose of promoting cell adhesion, their general lack of specificity and significantly decreased receptor binding affinities have proven detrimental in attempts to regulate highly specific and integrated processes necessary for tissue regeneration. Unlike adhesion peptides, the natural ECM displays a complex interplay with cells by supporting environmentally sensitive and cell dependent integrin specificity and binding affinity. Furthermore, the adhesion ligands on ECM proteins display a finely tuned and evolutionarily directed spatial periodicity, of which is dynamically controlled through both mechanical and chemical modifications. These and other emerging concepts from matrix biology require our attention if biomaterials design is to fulfill its promise. Here, we are charged with debating the statement 'The use of short synthetic adhesion peptides, like RGD, is the best approach in the design of biomaterials that guide cell behavior for regenerative medicine tissue engineering'. In this Leading Opinion Paper I will focus on aspects of natural ECM proteins and protein fragments that have proven difficult, if not impossible to date, to recapitulate in peptide-based systems. While this represents an argument against the use of peptides per se, it might also be viewed as outlining the challenges and opportunities for the biomaterials field. (C) 2011 Elsevier Ltd. All rights reserved.