Collaborative Research: Decoding and encoding mechanistic relations between structure and function in crack resistance of articular cartilage and cartilage inspired biomaterials.

关节软骨是一种软组织，它提供光滑的缓冲，并在关节中分配机械负荷。作为一种材料，关节软骨是非常重要的。它只有几毫米厚，通常可以承受10倍于体重的载荷，超过1 -2亿次的载荷循环，并且仍然不会破裂。天然关节软骨的同时强度，抗断裂性（韧性）和寿命在合成材料中仍然是无与伦比的。组织工程、组织修复甚至软机器人应用都迫切需要这种特性。然而，这种特殊韧性背后的分子机制尚不清楚。该项目将了解导致关节软骨韧性的基本原理和机制，并提供标准，就像我们对飞机机翼裂缝所做的那样，用于预测软骨最初未经处理的撕裂进一步断裂的可能性。pi将测试一个假设，即软骨具有如此出色的性能，是因为它由两个相互交织的聚合物网络组成，一个提供机械刚性，一个提供耗散。此外，这种双重网络的组成随组织中的位置而变化。这些想法将通过数值模拟和组织力学性能的实验测量进行比较。利用这种综合方法，pi将阐明关节软骨（AC）断裂韧性的力学结构-功能关系，从而更好地预测软骨力学和失效，并指导新型仿生材料的设计。该项目将为组织衰竭、组织修复疗法和软机器人设计原则提供见解。pi将教育和培训了解物理、工程和生物的新一代科学家，组织旨在向研究生教授沟通技巧的研讨会，并促进STEM劳动力的多样性。关节软骨（AC）是覆盖在骨骼末端的软组织，用于在关节中分配机械负荷。AC细胞相对较少，其网状细胞外基质主要决定其力学响应。与合成材料相比，它的强度、韧性和抗裂性都非常高，但这种特殊韧性背后的分子机制尚不清楚。考虑到AC的非均质性、深度依赖性和多组分结构和组成，现有的连续体描述过于粗粒度，无法完全描述其断裂力学。pi将通过结合刚性渗透理论和微尺度双网络水凝胶模型的新结构功能框架，以及可以为模型开发提供信息和接口的新共聚焦弹性成像实验来研究软骨骨折，从而解决这一挑战。使用这种由多尺度数学建模和最先进的实验组成的综合方法，他们将测试AC韧性产生的假设，因为(i)增强网络状态接近机械相变，允许可调的机械响应，以及（ii）组织是一种多组分非均质复合材料，能够对应力和裂纹钝化产生新的响应。该项目将了解裂缝对软骨和类似软组织的结构和组成的依赖性，以及对加载条件的依赖性，并为组织衰竭和组织修复疗法提供见解。更广泛地说，这个新框架将使这些结构、成分和本构力学性能如何调整以抵抗和钝化仿生和工程材料中的裂缝的新颖和具体的预测成为可能。pi将教育和培训了解物理、工程和生物学的新一代科学家，并促进STEM劳动力的多样性。科恩和博纳萨尔将根据艾伦·阿尔达传播科学中心最近在康奈尔大学举办的科学传播研讨会，为研究生和博士后开发软技能课程单元。Das将通过RIT的McNair项目指导少数族裔和第一代学生。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Non-Technical SummaryArticular cartilage is a soft tissue which provides a smooth cushion and distributes mechanical load in joints. As a material, articular cartilage is remarkable. It is only a few millimeters thick, can routinely bear up to ten times one's body weight over 100-200 million loading cycles, and still avoids fracturing. The simultaneous strength, fracture resistance (toughness), and longevity of native articular cartilage remains unmatched in synthetic materials. Such properties are desperately needed for tissue engineering, tissue repair, and even soft robotics applications. The molecular mechanism underlying this exceptional toughness, however, is not well understood. This project will obtain an understanding of the underlying principles and mechanisms that lead to the toughness of articular cartilage, and provide criteria, as we do for cracks in airplane wings, for predicting the probability that initially untreated tears in cartilage will fracture further. The PIs will test the hypothesis that cartilage has such terrific properties due to the fact that it is comprised of two interweaving polymer networks, one which provides mechanical rigidity and one that provides dissipation. Moreover, this double network changes in composition with location in the tissue. These ideas will be tested using numerical simulation and comparison with experimental measurements of the tissue mechanical properties. Using this integrated approach, the PIs will elucidate mechanical structure-function relations underlying fracture toughness of articular cartilage (AC) which will lead to better predictions of cartilage mechanics and failure, and guide the design of new bioinspired materials. The project will provide insights into tissue failure, tissue repair therapies, and design principles for soft robotics. PIs will educate and train a new generation of scientists who understand physics, engineering, and biology, organize workshops aimed at teaching communication skills to graduate students, and promote diversity in STEM workforce. Technical SummaryArticular Cartilage (AC) is a soft tissue that covers the ends of bones to distribute mechanical load in joints. AC contains relatively few cells and its network-like extracellular matrix primarily determines its mechanical response. Its strength, toughness, and crack resistance are extremely high compared to synthetic materials, but the molecular mechanism underlying this exceptional toughness is not well understood. Given the heterogeneous, depth dependent, and multi-component structure and composition of AC, existing continuum descriptions are too coarse-grained to fully describe its fracture mechanics. The PIs will address this challenge by approaching cartilage fracture with a new structure function framework that combines rigidity percolation theory and microscale double-network hydrogel models, together with new confocal elastography experiments that can inform and interface with the model development. Using this integrated approach consisting of multi-scale mathematical modeling and state-of-the art experiments, they will test the hypothesis that the toughness of AC arises because (i) the reinforcing network state is in proximity to a mechanical phase transition allowing tunable mechanical response, and (ii) the tissue is a multi-component heterogeneous composite enabling novel response to stress and blunting of cracks. The project will obtain an understanding of the dependence of cracks on structure and composition of cartilage and similar soft tissues, as well as on loading conditions, and provide insights into tissue failure, and tissue repair therapies. More broadly, this new framework will enable novel and concrete predictions on how these structure, composition, and constitutive mechanical properties can be tuned to resist, and blunt cracks in biomimetic and engineered materials. PIs will educate and train a new generation of scientists who understand physics, engineering, and biology, and promote diversity in STEM workforce. Cohen and Bonassar will develop soft-skills curriculum units for graduate students and postdocs based on a recent science communication workshop held at Cornell by the Alan Alda Center for Communicating Science. Das will mentor minority and 1st generation students via RIT's McNair Program.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.