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

这项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学细节，适用于支架支持的细胞疗法的开发，以促进软骨再生。加州理工大学材料与加工模拟中心基于第一性原理的分子模拟技术的最新进展，可以描述具有1,000-数百万个原子的系统，并提供详细的化学和结构信息，这将使基本框架能够实现：1)模拟凝胶聚合物网络的关键纳米生物机械性能，包括机械调节，以及2)加深对调节体内性能的基本机制的理解，以开发新型/增强型材料。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性能的理解和增强我们的模拟能力至关重要。软骨的自我修复能力有限，涉及软骨组织的肌肉骨骼疾病的传统治疗方法依赖于外科手术，在局部修复/替换不可能的情况下进行完全关节置换；这些方法已被证明长期无效。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了巨大的经济负担，导致长期残疾和劳动力生产率下降，并产生进一步的社会经济影响。工程/科学专业的学生将被招募参加这项研究，研究结果将被纳入加州理工大学的一门关于材料的原子模拟的课程。

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.