Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town, Department of Health Sciences, Cape Town, South Africa.
Biomaterials. 2013 Sep;34(28):6797-803. doi: 10.1016/j.biomaterials.2013.05.057. Epub 2013 Jun 15.
Extracellular mimetic hydrogels formed from peptide crosslinkers and polyethylene glycol monomers permit cell-controlled invasion. The use of matrix metalloproteinase specific peptides might further allow for selective control of different cell-type invasion. In this study, the invasion of fibroblasts and vascular smooth muscle cells (VSMC) into hydrogels polymerised with either a peptide generally permissive for matrix metalloproteinase (MMP) degradation or peptides preferentially cleaved by MMP-14 or MMP-9 enzymes were compared. The two cell-types invaded the MMP permissive hydrogel equally. However, invasion of VSMC into MMP-14 selective peptide crosslinked hydrogels was diametrically opposite in nature to that of fibroblasts whereby VSMC showed a two-fold increase into these hydrogels relative to that observed in permissive hydrogels whilst fibroblasts had a relative two-fold decrease (p < 0.01). These findings are suggestive that invasion and growth of different cell-types in engineered synthetic extracellular matrix mimics may be controlled selectively by the choice of protease specific peptide crosslinker and this could have general utility in tissue regenerative and engineering approaches.
由肽交联剂和聚乙二醇单体形成的细胞外模拟水凝胶允许细胞控制入侵。使用基质金属蛋白酶特异性肽可能进一步允许对不同细胞类型的入侵进行选择性控制。在这项研究中，比较了成纤维细胞和血管平滑肌细胞（VSMC）侵入用一般允许基质金属蛋白酶（MMP）降解的肽或优先由 MMP-14 或 MMP-9 酶切割的肽聚合的水凝胶。两种细胞类型均均等侵入 MMP 允许的水凝胶。然而，VSMC 侵入 MMP-14 选择性肽交联水凝胶的性质与成纤维细胞完全相反，VSMC 在这些水凝胶中的侵入是在允许水凝胶中观察到的两倍，而成纤维细胞的相对侵入则降低了两倍（p < 0.01）。这些发现表明，在工程合成细胞外基质模拟物中不同细胞类型的入侵和生长可以通过选择蛋白酶特异性肽交联剂来选择性控制，这可能在组织再生和工程方法中有广泛的应用。
