Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15211-6. doi: 10.1073/pnas.1006442107. Epub 2010 Aug 9.
We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.
在这里，我们展示了一种心脏组织工程策略，该策略解决了细胞的组织化、与宿主心肌的整合以及构建心脏肌肉功能结构的定向线索等问题。微模板被用于将聚（2-羟乙基甲基丙烯酸酯-共-甲基丙烯酸）水凝胶塑造成具有驱动心脏组织整合的结构的组织工程支架。该构建物包含平行的通道，以组织心肌细胞束，由微米级的、球形的、相互连接的孔支撑，这些孔增强了血管生成，同时减少了瘢痕形成。表面修饰的支架被接种了人胚胎干细胞来源的心肌细胞，并在体外培养。心肌细胞在支架中存活并增殖了 2 周，达到了成年心脏的密度。具有 30-40 微米孔径的细胞外支架的心脏植入显示出血管生成和减少的纤维化反应，同时伴随着巨噬细胞表型向 M2 状态的转变。这项工作通过在支架中为心肌细胞和基质提供离散的隔室，增强了血管生成和整合，同时控制炎症反应，为空间控制的心脏组织工程奠定了基础。
