Computational Modeling of Scar Formation and Remodeling in Mechanically Loaded Tissues

该奖项的研究目标是开发一种计算模型，可以预测机械载荷如何与其他因素相互作用，以确定多个组织的瘢痕结构。包括皮肤、肌腱、韧带和心脏在内的各种机械负荷组织通过形成富含胶原蛋白的瘢痕对损伤作出反应。正在形成的瘢痕的胶原纤维结构通常是愈合组织继续发挥功能的唯一最重要的决定因素，有证据表明，操纵胶原排列可以改善从心肌梗死后的心脏功能到手术修复肌腱的强度的一切。然而，所有这些疾病的治疗方法，从心肌梗塞的聚合物注射到肌腱损伤的物理治疗程序，都是完全通过试错法设计的，因为没有办法预测拟议的干预措施对愈合组织的长期影响。该奖项下的工作将结合联合收割机基于代理的模型，模拟成纤维细胞的决定在细胞水平与有限元模型，代表力学在组织水平，以了解，纳入和预测的影响，区域异质性，机械负荷的历史，和应变-机械负荷组织中的瘢痕形成依赖于胶原降解。机械负荷组织的愈合和修复影响着一切的社会影响从心脏病发作到工伤再到衰老如果成功的话，这些研究将产生广泛的影响，因为它们能够预测心脏、肌腱、韧带和皮肤中各种治疗干预的长期影响，从而能够通过计算设计更好的治疗策略。该提案下的教育工作旨在通过向学生介绍计算建模的力量以及工程师在整合不断增加的数据供应以理解系统级行为和问题方面的作用，激发多个教育水平的学生学习数学，计算和工程。

The research objective of this award is to develop a computational model that can predict how mechanical loading interacts with other factors to determine scar structure across multiple tissues. A wide range of mechanically loaded tissues including skin, tendon, ligament, and heart respond to injury by forming a collagen-rich scar. The collagen fiber structure of the developing scar is often the single most important determinant of how well the healing tissue continues to function, and evidence suggests that manipulating collagen alignment could improve everything from heart function after myocardial infarction to the strength of surgically repaired tendons. Yet therapies for all of these conditions, from polymer injection into myocardial infarcts to physical therapy routines for tendon injuries, are devised entirely through trial-and-error, because there is no way to predict the long-term effects of proposed interventions on healing tissues. Work under this award will combine agent-based models that simulate fibroblast decisions at the cellular level with finite-element models that represent mechanics at the tissue level to understand, incorporate, and predict the effects of regional heterogeneity, mechanical loading history, and strain-dependent collagen degradation on scar formation in mechanically loaded tissues.Healing and repair of mechanically loaded tissues influences the societal impact of everything from heart attacks to workplace injuries to aging. If successful, these studies could therefore have a broad impact by providing the capability to predict the long-term effects of a wide range of therapeutic interventions in heart, tendon, ligament, and skin, enabling computational design of better treatment strategies. Educational efforts under this proposal aim to excite students at multiple educational levels about studying math, computing, and engineering by introducing them to the power of computational modeling and the role of engineers in integrating the ever-increasing supply of data to understand systems-level behavior and problems.