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磁共振成像评估心肌梗死后大鼠模型中心脏弹性组织支架生物材料的重塑。

Magnetic resonance imaging evaluation of remodeling by cardiac elastomeric tissue scaffold biomaterials in a rat model of myocardial infarction.

机构信息

Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.

出版信息

Tissue Eng Part A. 2010 Nov;16(11):3395-402. doi: 10.1089/ten.TEA.2010.0213. Epub 2010 Jul 20.

Abstract

Grafting of elastomeric biomaterial scaffolds may offer a radical strategy for the prevention of heart failure after myocardial infarction by increasing efficacy of stem cell delivery as well as acting as mechanical restraint devices to constrain scar expansion. Biomaterials can be partially optimized in vitro, but their in vivo performance is most critical and should ideally be monitored serially and noninvasively. We used magnetic resonance imaging (MRI) to assess three scaffold materials with a range of structural moduli equal to or greater than myocardial tissue: poly(glycerol sebacate) (PGS), poly(ethyleneterephathalate)/dimer fatty acid (PED), and TiO(2)-reinforced PED (PED-TiO(2)). Patches, 1  cm in diameter, were grafted onto the hearts of infarcted rats, with biomaterial-free infarcted rat hearts used as controls. MRI was able to determine scaffold size and location on the heart and identified unexpectedly rapid in vivo degradation of the PGS compared with previous in vitro testing. PED patches did not withstand in vivo attachment, but the more rigid PED-TiO(2) material was detrimental to heart function, increasing chamber and scar sizes and reducing ejection fractions compared with controls. In contrast, the mechanically compatible PGS scaffold successfully reduced hypertrophy, giving it potential for limiting excessive postinfarct remodeling. PGS was unable to support systolic function, but it would be suitable for strategies to deliver cardiac stem/progenitor cells, to limit remodeling during the period of functional cellular integration, and to degrade after cell assimilation by the heart. This work has also shown for the first time the value of using MRI as a noninvasive tool for evaluating and optimizing therapeutic biomaterials in vivo.

摘要

弹性生物材料支架的移植为预防心肌梗死后心力衰竭提供了一种新策略,其不仅可以提高干细胞的递送效率,还可以作为机械约束装置来限制瘢痕扩张。生物材料可以在体外进行部分优化,但它们的体内性能至关重要,理想情况下应进行连续的、非侵入性监测。我们使用磁共振成像(MRI)来评估三种结构模量等于或大于心肌组织的支架材料:聚(甘油-癸二酸酯)(PGS)、聚(对苯二甲酸乙二醇酯)/二聚脂肪酸(PED)和 TiO2 增强 PED(PED-TiO2)。将 1cm 直径的补片移植到梗死大鼠的心脏上,将无生物材料的梗死大鼠心脏作为对照。MRI 能够确定心脏上支架的大小和位置,并意外地发现 PGS 在体内的降解速度比之前的体外测试要快。PED 补片无法在体内附着,但更硬的 PED-TiO2 材料对心脏功能有害,与对照组相比,它增加了心室和瘢痕的大小,降低了射血分数。相比之下,机械相容的 PGS 支架成功地减少了心肌肥厚,使其有可能限制梗死后的过度重塑。PGS 无法支持收缩功能,但它适合用于输送心脏干细胞/祖细胞的策略,以限制功能细胞整合期间的重塑,并在被心脏吸收后降解。这项工作还首次表明,使用 MRI 作为评估和优化体内治疗性生物材料的非侵入性工具具有价值。

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