Hudalla Gregory A, Murphy William L
Department of Biomedical Engineering, University of Wisconsin, 5009 Wisconsin Institutes of Medical Research, 1111 Highland Ave. Madison, WI 53705 (USA).
Adv Funct Mater. 2011 May 24;21(10):1754-1768. doi: 10.1002/adfm.201002468.
Growth factor activity is localized within the natural extracellular matrix (ECM) by specific non-covalent interactions with core ECM biomolecules, such as proteins and proteoglycans. Recently, these interactions have inspired us and others to develop synthetic biomaterials that can non-covalently regulate growth factor activity for tissue engineering applications. For example, biomaterials covalently or non-covalently modified with heparin glycosaminoglycans can augment growth factor release strategies. In addition, recent studies demonstrate that biomaterials modified with heparin-binding peptides can sequester cell-secreted heparin proteoglycans and, in turn, sequester growth factors and regulate stem cell behavior. Another set of studies show that modular versions of growth factor molecules can be designed to interact with specific components of natural and synthetic ECMs, including collagen and hydroxyapatite. In addition, layer-by-layer assemblies of GAGs and other natural polyelectrolytes retain growth factors at a cell-material interface via specific non-covalent interactions. This review will detail the various bioinspired strategies being used to non-covalently localize growth factor activity within biomaterials, and will highlight in vivo examples of the efficacy of these materials to promote tissue regeneration.
生长因子活性通过与核心细胞外基质生物分子（如蛋白质和蛋白聚糖）的特定非共价相互作用，定位于天然细胞外基质（ECM）中。最近，这些相互作用启发我们及其他研究人员开发出可通过非共价方式调节生长因子活性的合成生物材料，用于组织工程应用。例如，用肝素糖胺聚糖进行共价或非共价修饰的生物材料可增强生长因子释放策略。此外，最近的研究表明，用肝素结合肽修饰的生物材料可螯合细胞分泌的肝素蛋白聚糖，进而螯合生长因子并调节干细胞行为。另一组研究表明，可设计生长因子分子的模块化版本，使其与天然和合成ECM的特定成分（包括胶原蛋白和羟基磷灰石）相互作用。此外，糖胺聚糖和其他天然聚电解质的层层组装通过特定的非共价相互作用，将生长因子保留在细胞 - 材料界面处。本综述将详细介绍用于在生物材料中非共价定位生长因子活性的各种受生物启发的策略，并将重点介绍这些材料在促进组织再生方面功效的体内实例。
