Cell-responsive hydrogel for encapsulation of vascular cells.
Cell-responsive hydrogel for encapsulation of vascular cells.
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DOI：
10.1016/j.biomaterials.2009.04.057
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发表时间：
2009-09
期刊：
影响因子：
14
通讯作者：
Langer, Robert
中科院分区：
文献类型：
--
作者：
Kraehenbuehl, Thomas P.;Ferreira, Lino S.;Zammaretti, Prisca;Hubbell, Jeffrey A.;Langer, Robert
关键词：
研究了一种人工合成的基质金属蛋白酶反应的聚乙二醇基水凝胶作为血管细胞和小分子生物活性多肽胸腺素β4(TP4)的生物活性共包裹系统的体外潜力。我们发现，T-β-4在这种生物活性基质中的物理掺入为人脐静脉内皮细胞的黏附、存活、迁移和组织创造了一个三维(3D)环境。与未包裹Tβ4的凝胶相比，包裹T Tp4的凝胶可显著提高内皮细胞的存活率，并显著上调血管内皮细胞钙粘素和血管生成素2的表达，而von Willebrand因子则显著下调。T-β-4的掺入可显著增加微囊化脐静脉内皮细胞分泌MMP2和MMP9。当β-2和MMP9酶触发释放时，凝胶作为受控的T-MMP4释放系统。此外，Tβ4促进血管内皮细胞在聚乙二醇水凝胶上的附着和诱导血管样网络的形成。因此，这些对基质金属蛋白酶反应的聚乙二醇水凝胶可以作为血管细胞的受控共包埋系统和生物活性因子，用于缺血组织的原位再生。
The in vitro potential of a synthetic matrix metalloproteinase (MMP)-responsive polyethylene glycol) (PEG)-based hydrogel as a bioactive co-encapsulation system for vascular cells and a small bioactive peptide, thymosin β4 (Tp4), was examined. We show that the physical incorporation of Tβ4 in this bioactive matrix creates a three-dimensional (3D) environment conducive for human umbilical vein endothelial cell (HUVEC) adhesion, survival, migration and organization. Gels with entrapped Tβ4 increased the survival of HUVEC compared to gels without Tp4, and significantly up-regulated the endothelial genes vascular endothelial-cadherin and angiopoietin-2, whereas von Willebrand factor was significantly down-regulated. Incorporation of Tβ4 significantly increased MMP-2 and MMP-9 secretion of encapsulated HUVEC. The gel acts as a controlled Tβ4-release system, as MMP-2 and MMP-9 enzymes trigger the release. In addition, Tβ4 facilitated HUVEC attachment and induced vascular-like network formation upon the PEG-hydrogels. These MMP-responsive PEG-hydrogels may thus serve as controlled co-encapsulation system of vascular cells and bioactive factors for in situ regeneration of ischemic tissues.
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