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

机械载荷对生物可降解聚合物植入物水解的影响

• 批准号: 2013696
• 负责人: Anastasia Muliana
• 金额: $ 55.1万
• 依托单位: Texas A&M Engineering Experiment Station
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2013696&HistoricalAwards=false
• 关键词: Influence; Mechanical; Loading; Hydrolysis; Biodegradable

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.

该补助金将探索在组合流体吸附，机械负荷，水解和侵蚀下，可生物降解聚合物的物理性质和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。生物可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撑，直到它们愈合。使用可生物降解的聚合物使得能够针对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，同时避免在功能寿命结束时需要后续手术来移除植入物。生物可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涉及在理解机械载荷和水解过程如何相互干扰及其对植入物的时间依赖性结构完整性和承载能力的影响方面的知识差距。该项目将实施一个协同实验和建模策略，以解决这一知识差距。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的各种刺激之间的相互作用，并供公众使用。具体而言，本项目将研究具有不同初始大分子结构（从完全无定形到高度结晶）的聚乳酸乙醇酸（PLGA）聚合物的降解，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样本浸入37 ℃的盐水中，同时承受各种机械载荷。非线性时间依赖性本构模型，将在大分子结构和质量的聚合物的变化，将制定描述在机械水解过程中的缠绕机制，并预测降解过程中的试样的几何形状和尺寸的变化。目的是解决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，或者由机械加载引起的断裂是否导致较短的聚合物链并因此加速水解过程; 2）不同的机械载荷历史如何改变侵蚀过程，该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响进行评估，被认为值得支持审查标准。