Heart valve cell biomechanics and mechanobiology

心脏瓣膜疾病是加拿大最常见的心脏病病因之一。患病的瓣膜通常通过外科手术由合成材料或动物组织制成的人工瓣膜代替。人工瓣膜的一个主要缺点是，一旦植入体内，它们就不能生长或自我修复。这些限制促使组织工程努力制造能够生长、适应和修复的活体替代瓣膜，就像正常、健康的瓣膜一样。设计功能性心脏瓣膜的关键一步是在组织生长时对其进行机械刺激。这使得组织内的细胞产生更多的组织基质，从而使瓣膜具有更好的机械完整性。然而，关于单个阀细胞对机械力的响应知之甚少。如果能更好地理解施加在细胞上的机械力与由此产生的机械和生物反应之间的关系，就能更好地预测和控制机械刺激对瓣膜组织生长的影响。最终，这将导致设计出具有与健康天然瓣膜相同特性的工程组织。本研究的目标是开发和使用基于计算机的模拟来预测工程阀门组织中单个细胞在机械载荷下的变形或形状变化。该模型将由描述细胞力学性能的特征参数的实验测量来支持。我们还将测量个体细胞对机械刺激的基因表达，并将生物反应与细胞变形联系起来。这项研究将为研究细胞的生物力学调节提供工具，并最终可能用于设计功能性工程组织。虽然我们的研究重点是瓣膜组织，但我们开发的方法将广泛适用于其他组织的工程，如骨，软骨，肌肉和血管。这项研究还将培养学生在生物工程、计算技术和组织工程领域的能力。

Diseases of the heart valves are among the most frequent causes of heart disease in Canada. Diseased valves are often replaced surgically by artificial valves made of synthetic materials or animal tissue. A major drawback of artificial valves is that they do not grow or repair themselves once implanted in the body. These limitations have motivated tissue engineering efforts to make living replacement valves that are able to grow, adapt, and repair, just as normal, healthy valves do.      A key step to engineering functional heart valves is to mechanically stimulate the tissue while it is growing. This causes the cells within the tissue to make more tissue matrix, resulting in a valve with improved mechanical integrity. However, little is known about the response of individual valve cells to mechanical forces. If the relationship between the mechanical forces applied to a cell and the resulting mechanical and biological response were better understood, the effects of mechanical stimulation on valve tissue growth could be better predicted and controlled. Ultimately, this would lead to the design of engineered tissues with the same properties as healthy native valves.      The goal of this research is to develop and use computer-based simulations to predict the deformation or change in shape of individual cells within engineered valve tissue subjected to mechanical loading. The model will be supported by experimental measurements of the characteristic parameters that describe the mechanical properties of the cells. We will also measure gene expression of individual cells in response to mechanical stimulation and correlate the biological response with the deformation of the cell. This research will provide tools to study the biomechanical regulation of cells and ultimately may be used to design functional engineered tissues. While the focus of our research is valve tissue, the approaches we develop will be broadly applicable to the engineering of other tissues such as bone, cartilage, muscle, and blood vessels. This research will also train students in the fields of bioengineering, computational technologies, and tissue engineering.