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，该模型可以预测机械载荷如何与其他因素相互作用，从而确定跨多个组织的疤痕结构。各种机械负荷组织，包括皮肤、肌腱、韧带和心脏，对损伤的反应是形成富含胶原蛋白的疤痕。正在形成的疤痕的胶原纤维结构通常是决定愈合组织如何继续发挥作用的最重要的因素，有证据表明，操纵胶原纤维排列可以改善一切，从心肌梗死后的心脏功能到手术修复的肌腱的强度。然而，所有这些疾病的治疗方法，从心肌梗死的聚合物注射到肌腱损伤的常规物理治疗，都是通过反复试验设计出来的，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基于代理的模型，在细胞水平上模拟成纤维细胞的决定，以及在组织水平上代表力学的有限元模型，以理解、整合和预测区域异质性、机械负荷历史和应变依赖性胶原降解对机械负荷组织中疤痕形成的影响。机械组织的愈合和修复影响着从心脏病发作到工作场所伤害到衰老等各种社会影响。如果成功，这些研究可以通过提供预测心脏、肌腱、韧带和皮肤的广泛治疗干预的长期效果的能力，从而产生广泛的影响，使更好的治疗策略的计算设计成为可能。本提案下的教育努力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，来激发不同教育水平的学生学习数学、计算和工程的兴趣。

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.