Micropatterned Nanotopography Chips for Probing the Cellular Basis
of Nanomaterial Toxicity and Biocompatibility
A multidisciplinary project at Brown University
Principle Investigators: Robert Hurt, Agnes Kane, Jeffrey Morgan,
Gregory Crawford, Phillip Brown
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-±.
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.
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