1 Department of Biomedical Engineering, Case Western Reserve University , Cleveland, Ohio.
Tissue Eng Part A. 2014 Feb;20(3-4):864-73. doi: 10.1089/ten.TEA.2013.0050. Epub 2014 Jan 9.
We report on a biomimetic scaffold as a model system to evaluate smooth muscle cell (SMC) migration in three dimensions. To accomplish this, bio-inert poly (ethylene glycol) (PEG)-based hydrogels were designed as the scaffold substrate. To mimic properties of the extracellular matrix, cell-adhesive peptide (GRGDSP) derived from fibronectin and collagenase-sensitive peptide (GPQGIAGQ) derived from collagen type I were incorporated into the PEG macromer chain. Copolymerization of the biomimetic macromers results in the formation of bioactive PEG hydrogels with cell adhesivity and biodegradability. By utilizing these biomimetic scaffolds, we studied the effect of adhesive ligand concentration, proteolysis, and network cross-linking density on cell migration. Our results showed that three-dimensional SMC migration has a biphasic dependence on adhesive ligand density, and both adhesive and collagenase-sensitive peptides were required for cell migration to occur. Furthermore, network cross-linking density was shown to dramatically influence the behavior of cell migration in the hydrogels.
我们报告了一种仿生支架作为模型系统,以评估平滑肌细胞(SMC)在三维空间中的迁移。为此,设计了生物惰性聚(乙二醇)(PEG)基水凝胶作为支架基质。为了模拟细胞外基质的特性,将来源于纤连蛋白的细胞黏附肽(GRGDSP)和来源于胶原蛋白 I 的胶原酶敏感肽(GPQGIAGQ)整合到 PEG 大分子链中。仿生大分子的共聚导致具有细胞黏附性和生物可降解性的生物活性 PEG 水凝胶的形成。通过利用这些仿生支架,我们研究了黏附配体浓度、蛋白水解和网络交联密度对细胞迁移的影响。结果表明,SMC 的三维迁移对黏附配体密度具有双相依赖性,并且细胞迁移需要黏附肽和胶原酶敏感肽。此外,网络交联密度被证明极大地影响了细胞在水凝胶中的迁移行为。