Stanford University, Department of Pediatrics, 300 Pasteur Dr., Stanford, CA 94305, USA.
Biomaterials. 2013 Dec;34(36):9048-55. doi: 10.1016/j.biomaterials.2013.08.017. Epub 2013 Aug 30.
Regeneration of the damaged myocardium is one of the most challenging fronts in the field of tissue engineering due to the limited capacity of adult heart tissue to heal and to the mechanical and structural constraints of the cardiac tissue. In this study we demonstrate that an engineered acellular scaffold comprising type I collagen, endowed with specific physiomechanical properties, improves cardiac function when used as a cardiac patch following myocardial infarction. Patches were grafted onto the infarcted myocardium in adult murine hearts immediately after ligation of left anterior descending artery and the physiological outcomes were monitored by echocardiography, and by hemodynamic and histological analyses four weeks post infarction. In comparison to infarcted hearts with no treatment, hearts bearing patches preserved contractility and significantly protected the cardiac tissue from injury at the anatomical and functional levels. This improvement was accompanied by attenuated left ventricular remodeling, diminished fibrosis, and formation of a network of interconnected blood vessels within the infarct. Histological and immunostaining confirmed integration of the patch with native cardiac cells including fibroblasts, smooth muscle cells, epicardial cells, and immature cardiomyocytes. In summary, an acellular biomaterial with specific biomechanical properties promotes the endogenous capacity of the infarcted myocardium to attenuate remodeling and improve heart function following myocardial infarction.
心肌损伤的再生是组织工程领域最具挑战性的前沿之一,这是由于成年心脏组织的愈合能力有限,以及心脏组织的力学和结构限制。在这项研究中,我们证明了一种由 I 型胶原组成的工程化去细胞支架,具有特定的生理机械性能,在心肌梗死后用作心脏补片时可改善心脏功能。在左前降支结扎后,立即将补片移植到成年鼠的梗死心肌上,并通过超声心动图、血流动力学和组织学分析在梗死后 4 周监测生理结果。与未经治疗的梗死心脏相比,携带补片的心脏保持了收缩功能,并在解剖和功能水平上显著保护心脏组织免受损伤。这种改善伴随着左心室重构的减弱、纤维化的减少以及梗死区内相互连接的血管网络的形成。组织学和免疫染色证实了补片与包括成纤维细胞、平滑肌细胞、心外膜细胞和未成熟心肌细胞在内的天然心脏细胞的整合。总之,具有特定生物力学特性的去细胞生物材料可促进梗死心肌的内源性能力,减轻梗死后的重构并改善心脏功能。