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

该项目涉及与一系列现代纳米材料相关的毒性，生物相容性和实际健康和暴露风险。 实验将侧重于哺乳动物细胞与纳米材料和纳米结构表面的相互作用，作为生物相容性和毒性的关键问题。 新的碳涂层微图案芯片将被制造提供一系列明确的纳米形貌的平行审问细胞在体外。 永生化的鼠巨噬细胞和人角质形成细胞将粘附到具有纳米级形状和表面化学的理想组合的微贴片上。待测量的生物学终点包括细胞活力、粘附、形态学、增殖、氧化剂产生、DNA损伤和促炎细胞因子如TNF-α的释放。 该项目还将解决新纳米材料的社会影响，特别关注风险认知和大学纳米材料安全。 物理、生物和社会科学的主要研究人员将与布朗大学的环境、健康和安全专业人员合作，为大学研究实验室制定纳米材料安全指南，并通过网络发布和特殊培训计划传播这些指南。如果成功，这项研究将确定纳米材料的大小、形状、表面化学、和纳米级的氧化还原活性，导致最小的免疫反应和最佳的生物相容性跨越一系列材料平台。 这种机制的理解可以导致实际的制造和纯化准则，以确保在各种开发和商业纳米材料的内在无毒。 同样的信息可以为纳米材料植入物和器械中生物相容性表面的设计提供指导。该项目的跨学科教育部分将培养研究生，提高对新纳米技术的社会，伦理和人类健康影响的认识。

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.