2021 FDA Science Forum
Metal implants and Immune Response: Development of an Intravital Multiphoton Imaging Method to Assess Immune Responses to Nickel Implants
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Contributing OfficeCenter for Devices and Radiological Health
Abstract
Background
Medical device implants containing metals such as nickel or cobalt are extensively used in long-term joint replacements, stents, and contraceptive devices. However, in a limited subset of individuals, the immune system overreacts to these foreign body implants generating severe responses often requiring surgical removal.
Purpose
The objective of this study is to develop a chronic metal implant model that can be repetitively imaged in-vivo in order to better understand the immune response which will aid FDA's mission to improve the evaluation of the safety and toxicology of future metal implant products which will benefit public health.
Methodology
A novel imaging method was developed where the dynamics of the immune cells around an implant can be chronically monitored and analyzed in a mouse model of metal-induced dermal allergic hypersensitivity. A transgenic mouse ear model is used where green fluorescent protein-labeled dendritic cells/monocytes and labeled T cells can be tracked around an implant using multiphoton imaging. Various sizes of Nickel nanoparticles in a hydrogel tube are being tested in both non-sensitized and pre-sensitized animals in acute and chronic models of metal implant hypersensitivity. Additionally, the endogenous mouse TLR-4 receptor is replaced with its metal-sensitive human counterpart to better predict the immune responses in humans exposed to metal implants.
Results
As observed in wild-type animals, the bright fluorescent dendritic cells formed an even closely spaced array across the epidermis that was largely static with minor process kinetic changes. In contrast in the deeper tissue, a series of veil-like monocyte cells were observed which appear to be rapidly moving macrophages.
Conclusion
The pinna of our transgenic mouse appears to be a promising location to study the dynamics of immune cell responses to metals in-vivo.
