First Principles Based Computational Framework to Study the Nano and Biomimetic Properties of Hydrogel Polymer Networks for Human Hyaline Cartilage Scaffold-Supported Cell Therapy

本研究将开发一种策略，利用第一性原理理论和计算来确定聚合物水凝胶双网络结构的原子细节，适用于支架支持细胞疗法的发展，以促进软骨再生。加州理工学院材料与加工模拟中心基于第一性原理的分子模拟的最新进展，允许描述具有化学和结构细节的数十万-数百万原子的系统，将使基本框架能够：1)模拟凝胶聚合物网络的关键纳米生物力学特性，包括机械调节；2)提高对调节体内性能的基本机制的理解，以开发新的/增强的材料。这项工作将在原型系统上验证该策略，并为组织工程中的重要应用奠定基础。这项研究对于提高我们对天然软骨的纳米力学特性的理解和增强我们模拟的能力至关重要。软骨具有有限的自我修复能力，涉及软骨组织的肌肉骨骼疾病的传统治疗方法在无法进行局部修复/置换时依赖于外科手术进行全关节置换；事实证明，这些方法长期来看是无效的。肌肉骨骼疾病仍然是美国的主要健康问题之一，给个人/公共卫生保健费用带来巨大的经济负担，导致长期残疾和劳动力生产力下降，并产生进一步的社会经济影响。本研究将招收工程/理工科学生，并将研究成果纳入加州理工学院的“材料原子模拟”课程。

This research will develop a strategy for using first principles theory and computation to determine the atomistic details of polymer hydrogel double network structures applicable in the development of scaffold-supported cell therapies to promote cartilage regeneration. Recent advances in first-principles-based molecular simulations that allow the description of systems with 1,000s-millions of atoms with chemical and structural detail at the Materials and Processing Simulation Center in the California Institute of Technology will enable the essential framework to: 1) simulate the critical nano bio-mechanical properties of gel polymer networks, including mechanoregulation, and 2) develop an increased understanding of fundamental mechanisms that regulate in-vivo performance for the development of new/enhanced materials. This work will validate the strategy on prototypical systems and set the stage for important applications in Tissue Engineering.This research is critical to improve our understanding of, and to enhance our ability to emulate the, nano-mechanical properties of natural cartilage. Cartilage has a limited self-repair capacity and traditional therapies for musculoskeletal conditions involving cartilaginous tissue have relied on surgical procedures for full joint replacements when local repair/replacement is not possible; these methods have proven to be ineffective in the long-term. Musculoskeletal conditions remain as one of the major health concerns in the United States imposing a huge economic load on individual/public health care costs, leading to prolonged disabilities and decreased productivity of our workforce, with further socio-economic impact. Engineering/Science students will be recruited for this research and findings incorporated into a course on "Atomistic Simulation of Materials" at Caltech.