NSF/FDA SIR: Three-Dimensional In Vitro Modeling of Interactions Between Orthopedic Wear Particles, Biofilm, and Macrophages

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Non-technical Abstract:This award under the NSF/FDA Scholar-in-Residence program is for a collaborative project to study how wear particles from medical devices interact with bacteria in the body, and how this may lead to loosening of medical implants. The use of total joint implants has been expanding to younger and more active patient populations. Though effective in restoring joint motion and enabling patient independence, the surface of joint implants can wear over time, producing microscopic wear debris. This project studies how these particles interact with bacteria in the body, and furthermore how both wear particles and bacteria affect the function of inflammatory cells. It is a follow-on to previous projects under the same program to design and test advanced models of tissue for studying interactions between immune cells and microscopic wear debris generated by medical implants. The project team has extensive experience fabricating 3D environments mimicking physiological conditions necessary that can be used to understand the cellular mechanisms of inflammation. The work presents an opportunity for collaborative research between academic and government research labs benefitting public health and safety.Technical Abstract: The goal of this one year Scholar-in-Residence program is to understand how wear particles, biofilm, and immune cells act in concert to contribute to aseptic loosening of total joint arthroplasty devices. Importantly, it applies advanced, biomaterial-based 3D tissue models that mimic the physiological environment. Specifically, the intellectual merit of this project focuses on using such models to simulate the in vivo scenario of direct contact between biofilm attached-wear particles and macrophages contributing to altered inflammatory response and osteolysis. The project benefits from the expertise of the Stegemann lab (U. Michigan) in fabricating physiologically-relevant in vitro tissue constructs, in collaboration with the technology and experience at the OSEL labs at FDA in physicochemical testing and evaluation of the interaction between wear particles, biofilm, and macrophages. The first objective of the project is to evaluate the propensity of wear particles from implant materials for bacterial adhesion and biofilm formation based on their physicochemical characteristics. Wear debris from representative materials (Polyethylene, PEEK, PMMA, Co-Cr, CP-Ti) are comprehensively characterized and their physicochemical properties are correlated with the ability to support biofilms produced by Staphylococcus aureus, a bacterium commonly associated with orthopedic infections. The second objective is to quantitate the inflammatory and osteolytic response of wear particles in the context of their interactions with biofilm, using 3D in vitro tissue models with or without bone allograft fragments. Wear particles (+/- biofilm) and macrophages are incorporated into 3D engineered tissue models and the biological responses of the materials are assessed. This project has broader impact on the regulatory priorities of the FDA by developing preclinical models of materials used in FDA-regulated products, which can be used to detect, identify, and quantify biological interactions. There is a need for a better understanding of the interplay between wear particles and biofilm, and their combined effects on the potential development of serious chronic inflammation caused by medical devices. Advanced biomaterials-based tools enable FDA to better evaluate the suitability of newly-emerging materials used in medical devices, decreasing the regulatory burden, and accelerating their path to the market.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.