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首页> 外文期刊>Acta biomaterialia >FGF-1 and proteolytically mediated cleavage site presentation influence three-dimensional fibroblast invasion in biomimetic PEGDA hydrogels
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FGF-1 and proteolytically mediated cleavage site presentation influence three-dimensional fibroblast invasion in biomimetic PEGDA hydrogels

机译：FGF-1和蛋白水解介导的裂解位点表达影响仿生PEGDA水凝胶中三维成纤维细胞的侵袭

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摘要

Controlled scaffold degradation is a critical design criterion for the clinical success of tissue-engineered constructs. Here, we exploited a biomimetic poly(ethylene glycol) diacrylate (PEGDA) hydrogel system immobilized with tethered YRGDS as the cell adhesion ligand and with either single (SSite) or multiple (MSite) collagenase-sensitive domains between crosslinks, to systematically study the effect of proteolytic cleavage site presentation on hydrogel degradation rate and three-dimensional (3-D) fibroblast invasion in vitro. Through the incorporation of multiple collagenase-sensitive domains between cross-links, hydrogel degradation rate was controlled and enhanced independent of alterations in compressive modulus. As compared to SSite hydrogels, MSite hydrogels resulted in increased 3-D fibroblast invasion in vitro, which occurred over a wider range of compressive moduli. Furthermore, encapsulated soluble acidic fibroblast growth factor (FGF-1), a potent mitogen during processes such as vascularization and wound healing, was incorporated into SSite and MSite PEGDA scaffolds to determine its in vitro potential on fibroblast cell invasion. Hydrogels containing soluble FGF-1 significantly enhanced 3-D fibroblast invasion in a dose-dependent manner within the different types of PEG matrices investigated over a period of 15 days. The methodology presented provides flexibility in designing PEG scaffolds with desired mechanical properties, but with increased susceptibility to proteolytically mediated degradation. These results indicate that effective tuning of initial matrix stiffness and hydrogel degradation kinetics plays a critical role in effectively designing PEG scaffolds that promote controlled 3-D cellular behavior and in situ tissue regeneration.
机译：受控的支架降解是组织工程构建体临床成功的关键设计标准。在这里，我们开发了一种仿生聚乙二醇二丙烯酸酯（PEGDA）水凝胶系统，该系统以束缚YRGDS作为细胞粘附配体，并在交联之间具有单个（SSite）或多个（MSite）胶原酶敏感域，从而系统地研究了这种效果裂解位点的表达对体外水凝胶降解速率和三维（3-D）成纤维细胞侵袭的影响通过在交联之间引入多个胶原酶敏感域，水凝胶降解速率得到控制和增强，而与压缩模量的变化无关。与SSite水凝胶相比，MSite水凝胶在体外导致3-D成纤维细胞侵袭的增加，这种侵袭发生在更宽的压缩模量范围内。此外，将包囊的可溶性酸性成纤维细胞生长因子（FGF-1），即血管生成和伤口愈合等过程中的有力促分裂原，掺入SSite和MSite PEGDA支架中，以确定其体外对成纤维细胞侵袭的潜力。在15天的时间内研究的不同类型的PEG基质中，含有可溶性FGF-1的水凝胶以剂量依赖的方式显着增强了3-D成纤维细胞的侵袭。提出的方法为设计具有所需机械性能但对蛋白水解介导的降解的敏感性增加的PEG支架提供了灵活性。这些结果表明，有效调节初始基质刚度和水凝胶降解动力学在有效设计可促进受控3D细胞行为和原位组织再生的PEG支架中起着关键作用。

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