NIRT: Micropatterned Nanotopography Chips for Probing the Cellular Basis of Biocompatibility and Toxicity

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This project addresses the toxicity, biocompatibility, and practical health and exposure risks associated with a range of modern nanomaterials. Experiments will focus on the interactions of mammalian cells with nanomaterials and nanostructured surfaces as the key issue in both biocompatibility and toxicity. New carbon-coated micropatterned chips will be fabricated offering a range of well-defined nanotopographies for parallel interrogation by cells in vitro. Immortalized murine macrophage and human keratinocytes will adhere to micropatches possessing desirable combinations of shape and surface chemistry at the nanoscale. The biological endpoints to be measured include cell viability, adhesion, morphology, proliferation, oxidant production, DNA damage, and release of proinflammatory cytokines such as TNF-alpha. The project will also address societal impacts of new nanomaterials with a special focus on risk perception and university nanomaterial safety. Principal investigators in the physical, biological, and social sciences will team with environmental, health, and safety professionals at Brown to formulate nanomaterial safety guidelines for university research laboratories and disseminate those guidelines through web posting and special training programs.If successful, this research will identify the combination of size, shape, surface chemistry, and redox activity at the nanoscale that leads to minimal immune response and optimal biocompatibility across a range of material platforms. Such a mechanistic understanding can lead to practical manufacturing and purification guidelines for ensuring intrinsic non-toxicity in a variety of developmental and commercial nanomaterials. The same information can provide guidelines for the design of biocompatible surfaces in nanomaterial-enabled implants and devices. The cross-disciplinary educational components of this project will train graduate students with an increased awareness of the societal, ethical, and human health implications of new nanotechnologies.