Assessing the Impacts of Aging upon the Macropahge Response to Implantable Materials

摘要： 可植入材料的最终成败总是取决于局部宿主组织的反应 每个解剖部位的材料和相关的重塑过程。免疫的相互作用 植入材料的系统历来被认为是一种负面事件 有组织降解、植入物包裹和/或失败。最近，先天免疫系统的作用， 尤其是巨噬细胞对可植入材料的反应重新受到关注。它 现在已经证明，巨噬细胞依赖于塑料和上下文相关的极化曲线 (例如，M1促炎与M2抗炎)，也能够影响改善的组织整合 和植入后的表现。这种对建设性、规范性和 巨噬细胞的基本作用代表了宿主-植入物相互作用的经典范例的背离。 事实上，基于生物材料的组织重建方法现在似乎是可取的 适应和促进免疫系统的参与，以促进积极的结果。然而， 推动这类活动的能力取决于对东道主的深入、上下文相关的理解 对生物材料的反应。 这项拟议的工作旨在定义在老化背景下宿主对生物材料的反应。尽管 老年患者越来越多地使用植入式医疗设备，衰老对宿主反应的影响 从未被调查过。免疫衰老，巨噬细胞功能和极化的失调， 老年人急性免疫反应的延迟分解都已得到证实。这将会 提示老年人对生物材料的宿主反应应该与老年人显著不同。 更年轻的个体。然而，研究老化对宿主对生物材料的反应的研究 这种反应对老年个体的长期整合和功能的影响从来没有 已经完成了。因此，显然有必要阐明衰老对寄主反应的影响 开发可植入材料，满足日益老龄化的人口的需求。 拟议工作的总体目标是确定衰老对宿主反应的影响 可植入材料，探索衰老改变宿主反应的机制，并开发 控制宿主反应以改善老年人重塑结果的方法。

Abstract: The ultimate success or failure of implantable materials is invariably a function of the local host tissue response to the materials and the associated remodeling process at each anatomical site. The interaction of the immune system with implantable materials has historically been considered to be a negative occurrence associated with tissue degradation, implant encapsulation, and/or failure. Recently, the role of the innate immune system, particularly that of macrophages, in the response to implantable materials has received renewed attention. It has now been shown that macrophages, depending upon plastic and context-dependent polarization profiles (e.g. M1 pro-inflammatory vs. M2 anti-inflammatory), are also capable of affecting improved tissue integration and performance following implantation. This emerging understanding of the constructive, regulatory, and essential role of macrophages represents a departure from classical paradigms of host-implant interactions. Indeed, it now appears desirable that biomaterial-based approaches to tissue reconstruction should both accommodate and promote involvement of the immune system to facilitate positive outcomes. However, the ability to promote such activity is predicated upon an in-depth, context-dependent understanding of the host response to biomaterials. The proposed work seeks to define the host response to biomaterials in the context of aging. Despite the increasing usage of implantable medical devices in aged patients, the impacts of aging upon the host response have never been investigated. Immunosenescence, dysregulation of macrophage function and polarization, and delayed resolution of acute immune responses in aged individuals have all been demonstrated. This would suggest that the host response to biomaterials in aged individuals should differ significantly from that in younger individuals. However, studies examining the effects of aging upon the host response to biomaterials and the implications of this response for long-term integration and function in aging individuals have never been performed. Thus, there is a clear need to elucidate the impacts of aging upon the host response in order to develop implantable materials which address the needs of an increasingly aged population. The overarching goals of the proposed work are to define the effects of aging upon the host response to implantable materials, to explore the mechanisms by which aging alters the host response, and to develop methods that manipulate the host response to improve remodeling outcomes in aged individuals.