The Influence of Mechanical Loading on the Hydrolysis of Biodegradable Polymer Implants

这项资助将探索在聚合物大分子结构变化的驱动下，可生物降解聚合物在流体吸附、机械载荷、水解和侵蚀联合作用下的物理性质以及大小和形状随时间的变化。可生物降解聚合物是一种很有前途的临时生物医学植入物材料，可以为受损组织提供机械支持，直到愈合。使用可生物降解的聚合物可以为特定的患者量身定做植入物的特定功能。这些材料还允许组织再生，同时避免在植入物功能寿命结束时进行后续手术移除植入物。生物可降解聚合物的降解是由于一个水解过程，在这个过程中，流体扩散到聚合物中，打断聚合物链，形成最终扩散出聚合物的单体(侵蚀)。开发有效的可生物降解聚合物植入物的一个关键障碍是了解机械加载和水解过程是如何交织在一起的，以及它们对植入物依赖时间的结构完整性和承载能力的影响方面的知识差距。该项目将实施一项协同实验和建模战略，以解决这一知识差距。该项目还向学生提供技术培训，同时促进留住任职人数不足的学生和退伍军人。此外，将开发基于虚拟现实(VR)和增强现实(AR)的学习模块，旨在了解各种刺激对聚合物降解的相互作用，并供普通公众使用。具体地说，该项目将研究具有不同初始大分子结构的聚乳酸乙醇酸(PLGA)聚合物的降解，从完全无定形到高度结晶，这将提供物理性质和降解行为的变化。不同形状和大小的PLGA样品将在37摄氏度的盐水中浸泡，同时受到各种机械载荷。考虑聚合物大分子结构和质量变化的非线性时变本构模型将被用来描述机械水解过程中的缠绕机制，并预测样品在降解过程中的几何和尺寸变化。其目标是解决1)水解性断裂是否纯粹是流体和聚合物分子之间的化学反应，或者机械加载引起的断裂是否会导致聚合物链变短从而加速水解过程；2)不同的机械加载历史如何改变侵蚀过程，从而逐渐改变植入物的形状和大小。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This grant will explore the time-dependent changes in the physical properties and the size and shape of biodegradable polymers under combined fluid sorption, mechanical loading, hydrolysis, and erosion, which are driven by changes in the polymer macromolecular structures. Biodegradable polymers are promising materials for temporary biomedical implants that can provide mechanical support for damaged tissues until they heal. Using biodegradable polymers enables tailoring the specific functionality of the implants to specific patients. These materials also allow for tissue regeneration while avoiding the need for subsequent surgery to remove the implants at the end of their functional life. The degradation in biodegradable polymers is due to a hydrolytic process in which fluid diffuses into the polymers, breaking the polymer chains and forming monomers that eventually diffuse out of the polymer (erosion). A key obstacle in the development of effective biodegradable polymer implants involves a knowledge gap in understanding how mechanical loading and hydrolytic processes intertwine and their resulting influence on the time-dependent structural integrity and load-carrying ability of the implant. This project will implement a synergetic experimental and modeling strategy to address this knowledge gap. The project also provides students with technical training while promoting the retention of underrepresented students and military veterans. Additionally, virtual reality (VR)- and augmented reality (AR)-based learning modules aimed at understanding the interplay among various stimuli on polymer degradation will be developed and shared for the general public to use. Specifically, this project will investigate degradation in poly-lactic glycolic acid (PLGA) polymers with different initial macromolecular structures, ranging from being fully amorphous to highly crystalline, which will provide variations in the physical properties and degradation behaviors. The PLGA specimens, of different shapes and sizes, will be immersed in saline water at 37oC while being subjected to various mechanical loading. Nonlinear time-dependent constitutive models that incorporate changes in the macromolecular structures and mass of the polymers will be formulated to describe the intertwining mechanisms in the mechano-hydrolytic process and to predict the changes in the geometry and size of the specimens during degradation. The goal is to address 1) whether the hydrolytic scission is purely a chemical reaction between fluid and polymer molecules, or whether the scission induced by mechanical loading leads to shorter polymer chains and therefore accelerates the hydrolytic process; 2) how different histories of mechanical loading alter the erosion process, thereby gradually changing the shape and size of the implant.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.