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.
(Relevance): By 2050, the number of individuals over the age of 65 is expected to increase by 71% to nearly 2 billion individuals worldwide, with over 75% of these individuals having at least one chronic condition. As a result there is an increasing demand for implantable medical devices intended to treat these disorders. The overarching goals of the proposed work are to define the effects of aging upon the host immune response to implantable materials, to explore the mechanisms by which changes in the host immune response are mediated, and to develop methods that manipulate the host immune response to improve outcomes in aged individuals.
| LoPresti, Samuel T; Brown, Bryan N (2018) Effect of Source Animal Age upon Macrophage Response to Extracellular Matrix Biomaterials. J Immunol Regen Med 1:57-66 |
| Stahl, Elizabeth C; Haschak, Martin J; Popovic, Branimir et al. (2018) Macrophages in the Aging Liver and Age-Related Liver Disease. Front Immunol 9:2795 |
| Brown, Bryan N; Haschak, Martin J; Lopresti, Samuel T et al. (2017) Effects of age-related shifts in cellular function and local microenvironment upon the innate immune response to implants. Semin Immunol 29:24-32 |
