Zhu Chenghao, Rodda Andrew E, Truong Vinh X, Shi Yue, Zhou Kun, Haynes John M, Wang Bing, Cook Wayne D, Forsythe John S
Department of Materials Science and Engineering, Monash Institute of Medical Engineering, Monash University, Clayton, Victoria 3800, Australia.
Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
ACS Biomater Sci Eng. 2018 Jul 9;4(7):2494-2504. doi: 10.1021/acsbiomaterials.8b00084. Epub 2018 Jun 21.
Myocardial tissue engineering is a promising therapy for myocardial infarction recovery. The success of myocardial tissue engineering is likely to rely on the combination of cardiomyocytes, prosurvival regulatory signals, and a flexible biomaterial structure that can deliver them. In this study, poly(glycerol sebacate) (PGS), which exhibits stable elasticity under repeated tensile loading, was engineered to provide physical features that aligned cardiomyocytes in a similar manner to that seen in native cardiac tissue. In addition, a small molecule mimetic of brain derived neurotrophic factor (BDNF) was polymerized into the PGS to achieve a continuous and steady release. Micropatterning of PGS elastomers increased cell alignment, calcium transient homogeneity, and cell connectivity. The intensity of the calcium transients in cardiomyocytes was enhanced when cultured on PGS which released a small molecule BDNF mimetic. This study demonstrates that robust micropatterned elastomer films are a potential candidate for the delivery of functional cardiomyocytes and factors to the injured or dysfunctional myocardium, as well as providing novel in vitro platforms to study cardiomyocyte physiology.
心肌组织工程是一种用于心肌梗死恢复的有前景的治疗方法。心肌组织工程的成功可能依赖于心肌细胞、促存活调节信号以及能够递送它们的柔性生物材料结构的组合。在本研究中，聚癸二酸甘油酯（PGS）在反复拉伸载荷下表现出稳定的弹性，经设计可提供与天然心脏组织中所见类似的使心肌细胞排列的物理特征。此外，一种脑源性神经营养因子（BDNF）的小分子模拟物被聚合到PGS中以实现持续稳定释放。PGS弹性体的微图案化增加了细胞排列、钙瞬变均匀性和细胞连通性。当在释放小分子BDNF模拟物的PGS上培养时，心肌细胞中钙瞬变的强度增强。本研究表明，坚固的微图案化弹性体薄膜是向受损或功能失调的心肌递送功能性心肌细胞和因子的潜在候选物，同时也为研究心肌细胞生理学提供了新的体外平台。
