Understanding the Role of Mechanical Boundary Conditions on Tissue Assembly and Repair in 3D Fibrous Microtissues

了解机械边界条件对 3D 纤维微组织中组织组装和修复的作用

• 批准号: 2311640
• 负责人: Emma Lejeune
• 金额: $ 63.5万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2311640&HistoricalAwards=false
• 关键词: Understanding; Role; Mechanical; Boundary; Conditions

This award will support research that will generate new knowledge about biological tissue assembly and repair. This work will both promote the progress of science and advance national health. Tissue assembly and repair are the fundamental mechanisms that underly wound healing. It is known that mechanical forces control tissue assembly. However, the mechanisms by which forces regulate new tissue formation and its organization remain poorly understood. Essentially, changing the mechanical forces on a tissue can either promote or suppress wound healing. However, the direct relationship between mechanical forces and wound healing outcomes are largely unknown. This award supports the fundamental research to provide knowledge about how mechanical forces will influence tissue assembly and repair in a tightly controlled laboratory setting. Through establishing a combined experimental and computational platform for measuring the interplay between mechanical, chemical, and biological cues, this research will directly advance the design of engineered devices and therapeutics to promote would healing. Thus, results from this research will benefit the U.S. national health, economy, and society as impaired wound healing is a significant medical problem. Finally, this work will include community outreach at the middle school level to educate students about the exciting field of mechanobiology.The objective of this project is to understand how domain boundary conditions (i.e., the boundary restraints that control emergent ECM alignment and tissue geometry) control local tissue repair (i.e., healing through matrix contractility and matrix deposition) via the induced spatially heterogeneous mechanical microenvironment (i.e., self-assembled fiber alignment, tissue strain, and tissue stress). This work tightly integrates in vitro experiments and computational modeling, where the in vitro experiments build on a previously developed three-dimensional in vitro biomimetic gap closure model of tissue assembly and repair. This work will first establish a mechanistic computational model to predict the heterogeneous stresses and strains of microtissue formed around different micropost configurations. Then, it will integrate the mechanistic computational model with timelapse image based experimental data to form a combined mechanistic and data-driven framework to predict the gap closure process. Finally, this framework will be used to define the transition regime between “gap closure” and “gap closure failure” for this in vitro experimental system. In addition to the knowledge gained about biological tissue assembly and repair, this work will establish a generalizable methodology for integrating mechanistic and data driven computational models for mechanobiological systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该奖项将支持研究生物组织组装和维修的新知识的研究。这项工作既可以促进科学的进步，又可以提高国家健康。组织组装和修复是黑社会愈合的基本机制。众所周知，机械力控制组织组装。但是，强制调节新组织形成及其组织的机制仍然很少理解。本质上，改变组织上的机械力可以促进或抑制伤口愈合。但是，机械力与伤口愈合结果之间的直接关系在很大程度上是未知的。该奖项支持基本研究，以提供有关机械力将如何在严格控制的实验室环境中影响组织组装和维修的知识。通过建立一个合并的实验和计算平台，用于测量机械，化学和生物线索之间的相互作用，这项研究将直接推动工程设备和疗法的设计。这项研究的结果将使美国国家健康，经济和社会受到伤害愈合受损是一个重大的医疗问题。最后，这项工作将包括在中学阶段的社区宣传，以教育学生令人兴奋的机制生物学领域。该项目的目的是了解领域边界条件如何（即控制出现的ECM对齐和组织几何形状的边界限制）控制局部组织修复（即，通过矩阵下降和矩阵下降）通过MITRIX降低了Spatiene（I.自组装的纤维比对，组织应变和组织应激）。这项工作紧密地整合了体外实验和计算建模，其中体外实验基于先前开发的三维体外仿生差距闭合组织组装和修复模型。这项工作将首先建立一个机械计算模型，以预测围绕不同的微型构型形成的微动物的异质应力和菌株。然后，它将将机械计算模型与基于时间段图像的实验数据整合在一起，以形成一个组合的机械和数据驱动的框架，以预测间隙封闭过程。最后，该框架将用于定义该体外实验系统“间隙闭合”和“间隙闭合失败”之间的过渡方案。除了获得生物组织组装和维修的知识外，这项工作还将建立一种可概括的方法，用于整合机械系统的机械和数据驱动计算模型。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子和更广泛影响的审查标准来通过评估来获得的支持。