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

该基金将探索生物可降解聚合物在流体吸附、机械载荷、水解和侵蚀作用下的物理性质、尺寸和形状随时间的变化，这些变化是由聚合物大分子结构的变化驱动的。可生物降解聚合物是一种很有前途的临时生物医学植入材料，可以为受损组织提供机械支持，直到它们愈合。使用可生物降解的聚合物可以为特定患者定制植入物的特定功能。这些材料还允许组织再生，同时避免在其功能寿命结束时需要后续手术移除植入物。可生物降解聚合物的降解是由于水解过程，其中流体扩散到聚合物中，破坏聚合物链并形成单体，最终扩散出聚合物（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，在理解机械载荷和水解过程如何相互交织以及它们对植入物随时间变化的结构完整性和承载能力的影响方面存在知识缺口。该项目将实施一个协同实验和建模策略来解决这一知识差距。该项目还为学生提供技术培训，同时促进保留代表性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，旨在了解聚合物降解中各种刺激之间的相互作用，并共享给公众使用。具体来说，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。将不同形状和尺寸的PLGA试样浸泡在37℃的盐水中，同时承受各种机械载荷。将建立包含聚合物大分子结构和质量变化的非线性时间相关本构模型，以描述机械水解过程中的缠结机制，并预测降解过程中样品几何形状和尺寸的变化。目标是解决1)水解断裂是否纯粹是流体和聚合物分子之间的化学反应，还是由机械载荷引起的断裂导致更短的聚合物链从而加速水解过程；2)不同的机械载荷历史如何改变侵蚀过程，从而逐渐改变种植体的形状和大小。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。

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.