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首页> 外文期刊>Journal of biomedical materials research, Part A >Tuning composition and architecture of biomimetic scaffolds for enhanced matrix synthesis by murine cardiomyocytes
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Tuning composition and architecture of biomimetic scaffolds for enhanced matrix synthesis by murine cardiomyocytes

机译：调整仿生支架的组成和结构以增强鼠心肌细胞的基质合成

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摘要

A major onset of heart failure is myocardial infarction, which causes the myocardium to lose cardiomyocytes and transform into a scar tissue. Since mammalian infarcted cardiac tissue has a limited ability to regenerate, alternative strategies including implantation of tissue-engineered scaffolds at the site of damaged myocardium have been explored. The goal is to enable in situ cardiac reconstruction at the injured myocardium site, replace the lost cardiomyocytes, deliver the required biomolecules, and remodel the extracellular matrix (ECM). ECM synthesis and deposition by cardiomyocytes within such scaffolds remains categorically unexplored. Here, we investigated the survival, ECM synthesis and deposition, and matrix metalloproteinases (MMPs) release by cardiomyocytes within three-dimensional (3D) substrates. Rat cardiomyocytes were cultured for three weeks within two structurally different substrates: 3D collagen hydrogels or polycaprolactone (PCL) nanofibrous scaffolds. The concentration and composition of the hydrogels was varied, while PCL nanofibers were surface-modified with various ECM proteins. Results showed that myocyte attachment and survival was higher within collagen hydrogels, while myocyte alignment and beating was noted only within PCL scaffolds. Total protein synthesis by myocytes within PCL scaffolds was significantly higher compared to that within collagen hydrogels, although more protein was deposited as matrix within hydrogels. Significant ECM synthesis and matrix deposition, TIMP-1, and MMP release were noted within modified collagen hydrogels and PCL nanofiber scaffolds. These results were qualitatively confirmed by imaging techniques. Results attest to the prominent role of scaffold composition and architecture in influencing cardiomyocyte phenotype, matrix synthesis and cytokines release, with significant applications in cardiac tissue remodeling strategies. (C) 2014 Wiley Periodicals, Inc.
机译：心力衰竭的主要发作是心肌梗塞，它导致心肌细胞丢失心肌细胞并转化为疤痕组织。由于哺乳动物梗塞的心脏组织再生能力有限，因此已经探索了包括在受损的心肌部位植入组织工程支架的替代策略。目的是在受损的心肌部位进行原位心脏重建，更换丢失的心肌细胞，输送所需的生物分子，并重塑细胞外基质（ECM）。此类支架中心肌细胞的ECM合成和沉积仍未明确分类。在这里，我们研究了三维（3D）基质内心肌细胞的存活，ECM合成和沉积以及基质金属蛋白酶（MMP）释放。将大鼠心肌细胞在两种结构不同的底物中培养3周：3D胶原水凝胶或聚己内酯（PCL）纳米纤维支架。水凝胶的浓度和组成各不相同，而PCL纳米纤维则通过各种ECM蛋白进行了表面修饰。结果显示，胶原蛋白水凝胶中的心肌细胞附着和存活率更高，而仅在PCL支架中才注意到心肌细胞的排列和跳动。尽管更多的蛋白质以基质形式沉积在水凝胶中，但PCL支架中的心肌细胞的总蛋白质合成水平明显高于胶原水凝胶。在改性胶原蛋白水凝胶和PCL纳米纤维支架中发现了重要的ECM合成和基质沉积，TIMP-1和MMP释放。通过成像技术定性地证实了这些结果。结果证明了支架组成和结构在影响心肌细胞表型，基质合成和细胞因子释放方面的重要作用，并在心脏组织重塑策略中有重要应用。 （C）2014威利期刊公司

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