Non-technical: This award under the NSF/FDA Scholar-in-Residence program by the Biomaterials program in the Division of Materials Research to University of Michigan Ann Arbor is to design and test a 3D hydrogel model for studying interactions between immune cells and microscopic particles produced by the wear and tear of medical implants in the body. The use of implants has been expanding to younger and more active patient populations. Though effective in restoring joint motion and enabling patient independence, joint implants have a finite lifespan because of their surfaces breakdown, and body's inflammatory response to microscopic particles produced by the wear and tear of these implants. This project will develop advanced methods to study how inflammatory cells interact with wear particles, with the goal of informing the development of more robust and thorough standards for predicting and categorizing the biological response to new implant materials. The project team has extensive experience in fabricating 3D environments mimicking physiological conditions necessary that can be used to understand the cellular mechanisms of inflammation. The proposed studies present an opportunity for collaborative research among academic, government and industrial research labs benefitting public health and safety.

Technical Abstract

The goal of this one-year Scholar-in-Residence award is to design and test 3D tissue engineered models in evaluating macrophage response and inflammation to polymeric wear debris characteristic of implant devices. Use of such implants (Class II special controls) can result in long-term complications including chronic inflammation and osteolysis. Polymeric wear debris generated by normal use has been identified as a primary factor determining device lifetime, and therefore new wear-resistant polymers have been introduced to increase the longevity of these implants. Rigorous standards and testing are necessary to preserve patient safety, and this project will create 3D biomimetic tissue models to capture physiological responses in vitro. This 3D model is expected to recapitulate the inflammatory response in the context of the full range of stimuli in the extracellular microenvironment. Therefore the intellectual merit of the project is based on providing an advanced tissue model for testing the role of material properties on wear particle bioactivity, bridging the current gap that exists between simple 2D in vitro models and animal models or clinical trials. The specific aims include: 1) develop a 3D engineered tissue model with maximum sensitivity and selectivity to characterize cell response to polymeric wear debris; and 2) apply engineered model to study the relationship between physiochemical properties of wear debris generated from selected polymers with macrophage response. Specifically, wear debris from polyether ether ketone and polycarbonate urethane will be compared against ultra-high molecular weight polyethylene for markers of macrophage activation and inflammatory response, as determined by particle concentration, size, shape, surface texture, surface charge, and polarity. The broader impact of this project is its contribution in developing the fundamental understanding of how material properties determine biological responses. In addition, this study is expected to meet the growing needs at FDA for better model systems in evaluating biomaterials. Such a system addresses patient safety and efficacy issues regarding implant success and potentially reduces costs of new device development by providing a less burdensome and more rapid method for material testing, compared to in vivo models or retrieved explants.

National Science Foundation (NSF)
Division of Materials Research (DMR)
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Germano Iannacchione
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Regents of the University of Michigan - Ann Arbor
Ann Arbor
United States
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