Discovering How Stress Induced Histomorphogenesis Effects the Long-term Leaching from an Implanted Medical Device using Phase Field Models

这个项目将使用计算机模拟来更好地理解医疗植入物对周围组织的影响。许多人受益于植入的医疗设备，以恢复身体功能造成的伤害，疾病，癌症，或衰老。塑料和其他聚合物通常用于髋关节植入物、膝关节植入物以及这些设备周围的涂层。如果其中潜在的有害化学物质渗入人体，可能会造成伤害。现有的计算机模拟可以用来预测设备在短期内释放的物质量。然而，这些模型不能准确地捕捉长期暴露，因为它们没有考虑在愈合过程中发生的组织变化。该奖项支持基础研究，以提供生成计算机模拟所需的知识，以解释植入装置附近的组织变化。结果包括更好地了解这些变化如何影响组织渗透性，并可能有助于评估医疗设备带来的风险。此外，本研究将进一步加深我们对生物组织转运特性的理解，支持三个高优先级的调控科学项目，并为本科生提供资助的研究机会。相场建模是一种强大的技术，可以用来模拟相变随空间和时间变化的非均质材料。单个元素的特征由字段参数确定，这些参数使单个元素能够随时间发展，从而使单个模型能够有效地捕获复杂的依赖时间的行为。本研究选择它是因为它能够模拟组织从常规植入前表型到与异物囊相关的纤维和无血管组织的转化。由于元件特性是由场控制的，而不是与特定元件永久相关，因此不同组织表型之间的边界位置可以随着愈合的进展而移动，并且单相场模型可以在整个愈合过程中捕获系统的组织形态学变化和生物运输特性。这项工作将是相场建模的首次应用，以表征植入医疗设备周围复杂的异质组织结构的演变。此外，它也将是第一个量化通过异质组织植入物释放可浸出化学物质的模型。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 project will use computer simulations to better understand the effects of a medical implant on the surrounding tissue. Many people benefit from implanted medical devices to restore body function caused by injury, disease, cancer, or aging. Plastics and other polymers are commonly used in hip implants, knee implants, and coatings around these devices. This could cause harm if potentially hazardous chemicals within them leach into the body. Existing computer simulations can be used to predict the amount of material released from a device for short-term exposure. However, these models cannot accurately capture long-term exposure because they do not consider changes in the tissue that occur during the healing process. This award supports fundamental research to provide knowledge needed to generate computer simulations that account for tissue changes near an implanted device. Outcomes include developing a better understanding of how these changes impact tissue permeability and may contribute to the assessment of the risk posed by medical devices. In addition, this research will further enhance our understanding of transport properties in biological tissue, support three high priority regulatory science projects, and provide undergraduates with funded research opportunities.Phase field modeling is a powerful technique that can be used to model heterogeneous materials that change phase over space and time. The characteristics of an individual element are identified by field parameters that enable individual elements to evolve over time, giving a single model the ability to effectively capture complex time-dependent behavior. It was selected for this study because of its ability to model the transformation of tissue from regular preimplantation phenotypes to fibrous and avascular tissue associated with the foreign body capsule. Because the element characteristics are controlled by the field and not permanently associated with specific elements, the boundary location between different tissue phenotypes can move as healing progresses and a single-phase field model can capture both the histomorphological changes and the biotransport properties of the system through the entire duration of the healing process. This work will be the first application of phase field modeling to characterize the evolution of the complex heterogeneous tissue structure surrounding an implanted medical device. Furthermore, it will also be the first model that quantifies the release of leachable chemicals by an implant through heterogeneous tissues.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.