Usprech Jenna, Chen Wen Li Kelly, Simmons Craig A
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada.
Wiley Interdiscip Rev Syst Biol Med. 2016 Mar-Apr;8(2):169-82. doi: 10.1002/wsbm.1329. Epub 2016 Feb 9.
Tissue-engineered heart valves are promising alternatives to address the limitations of current valve replacements, particularly for growing children. Current heart valve tissue engineering strategies involve the selection of biomaterial scaffolds, cell types, and often in vitro culture conditions aimed at regenerating a valve for implantation and subsequent maturation in vivo. However, identifying optimal combinations of cell sources, biomaterials, and/or bioreactor conditions to produce functional, durable valve tissue remains a challenge. Despite some short-term success in animal models, attempts to recapitulate aspects of the native heart valve environment based on 'best guesses' of a limited number of regulatory factors have not proven effective. Better outcomes for valve tissue regeneration will likely require a systems-level understanding of the relationships between multiple interacting regulatory factors and their effects on cell function and tissue formation. Until recently, conventional culture methods have not allowed for multiple design parameters to be considered at once. Emerging microtechnologies are well suited to systematically probe multiple inputs, in combination, in high throughput and with great precision. When combined with statistical and network systems analyses, these microtechnologies have excellent potential to define multivariate signal-response relationships and reveal key regulatory pathways for robust functional tissue regeneration.
组织工程心脏瓣膜是解决当前瓣膜置换局限性的有前景的替代方案，尤其是对于正在成长的儿童。当前的心脏瓣膜组织工程策略包括生物材料支架、细胞类型的选择，以及通常旨在再生用于植入并随后在体内成熟的瓣膜的体外培养条件。然而，确定细胞来源、生物材料和/或生物反应器条件的最佳组合以产生功能性、耐用的瓣膜组织仍然是一项挑战。尽管在动物模型中取得了一些短期成功，但基于对有限数量调节因子的“最佳猜测”来重现天然心脏瓣膜环境的各个方面的尝试尚未证明是有效的。瓣膜组织再生的更好结果可能需要对多个相互作用的调节因子之间的关系及其对细胞功能和组织形成的影响有系统层面的理解。直到最近，传统的培养方法还无法同时考虑多个设计参数。新兴的微技术非常适合以高通量和高精度系统地组合探测多个输入。当与统计和网络系统分析相结合时，这些微技术具有定义多变量信号响应关系并揭示强大功能组织再生关键调节途径的巨大潜力。
