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Increased Cardiomyocyte Alignment and Intracellular Calcium Transients Using Micropatterned and Drug-Releasing Poly(Glycerol Sebacate) Elastomers
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2018-06-06 00:00:00 , DOI: 10.1021/acsbiomaterials.8b00084
Chenghao Zhu 1 , Andrew E. Rodda 1 , Vinh X. Truong 1 , Yue Shi 1 , Kun Zhou 1 , John M. Haynes 2 , Bing Wang 3 , Wayne D. Cook 1 , John S. Forsythe 1
Affiliation  

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.

中文翻译:

使用微图案化和药物释放型聚癸二酸甘油酯弹性体增加心肌细胞排列和细胞内钙瞬变

心肌组织工程学是用于心肌梗塞恢复的有前途的疗法。心肌组织工程学的成功可能取决于心肌细胞,生存调节信号和可以传递这些信号的灵活生物材料结构的组合。在这项研究中,聚(癸二酸甘油酯)(PGS)在反复的拉伸载荷下表现出稳定的弹性,经过工程改造,可提供以与天然心脏组织相似的方式排列心肌细胞的物理特征。此外,将脑源性神经营养因子(BDNF)的小分子模拟物聚合到PGS中,以实现连续稳定释放。PGS弹性体的微图案化提高了细胞排列,钙瞬态均匀性和细胞连通性。当在PGS上培养时,心肌细胞中钙瞬变的强度增加,PGS释放出小分子BDNF模拟物。这项研究表明,坚固的微图案弹性体膜是将功能性心肌细胞和因子递送至受损或功能障碍的心肌的潜在候选者,并为研究心肌细胞生理学提供了新的体外平台。
更新日期:2018-06-06
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