Engineering of a bio-functionalized hybrid off-the-shelf heart valve

Engineering of a bio-functionalized hybrid off-the-shelf heart valve
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DOI:
10.1016/j.biomaterials.2013.10.080
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发表时间:
2014-02-01
期刊:
影响因子:
14
通讯作者:
Schenke-Layland, Katja
Schenke-Layland, Katja
中科院分区:
工程技术1区
文献类型:
--
作者:
Hinderer, Svenja;Seifert, Jan;Schenke-Layland, Katja

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目前可用的心脏瓣膜替代物由于小叶增厚、缺乏生长或重塑潜力而在长期性能上受到限制或失败。为了解决这些问题,有必要模拟天然瓣膜细胞外基质(ECM)的多种因素,如结构,机械行为和生化信号。在这里,我们成功地生成了一种适合天然瓣膜叶结构和机械性能的静电纺PEGdma-PLA支架。将瓣膜间质细胞(VICs)和瓣膜内皮细胞(VECs)植入支架上,在生物反应器的生理条件下培养时,该结构表现得像天然小叶。利用原子力显微镜(AFM)从薄片中获得详细的力学信息,这使得杨氏模量的第一个层特异性测量成为可能。有趣的是,与纤维纤维和脑室相比,海绵状纤维硬度要低得多。此外,对人类胎儿心脏瓣膜发育的研究发现,I型胶原和versican是重要的结构蛋白。作为原理证明,这些蛋白质被引入支架,展示了基于自然蓝图的混合阀生物功能的能力。(C) 2013年作者。Elsevier Ltd.出版。版权所有。
Currently available heart valve replacements are limited in long-term performance or fail due to leaflet thickening, lack of growth or remodeling potential. In order to address these issues, it is necessary to mimic multiple factors of the native valvular extracellular matrix (ECM) such as architecture, mechanical behavior and biochemical signals. Here, we successfully generated an electrospun PEGdma-PLA scaffold adapted to the structure and mechanical properties of native valve leaflets. Valvular interstitial cells (VICs) and valvular endothelial cells (VECs) were seeded on the scaffold and when cultured under physiological conditions in a bioreactor, the construct performed like a native leaflet. Atomic force microscopy (AFM) was employed to obtain detailed mechanical information from the leaflets, which enabled the first layer-specific measurement of the Young's modulus. Interestingly, spongiosa stiffness was much lower compared to the fibrosa and ventricularis. Moreover, investigations into human fetal heart valve development identified collagen type I and versican as important structural proteins. As a proof of principle, these proteins were introduced to the scaffold, demonstrating the ability to biofunctionalize the hybrid valve based on natures' blueprint. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.