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

本项目探讨了与一系列现代纳米材料相关的毒性、生物相容性以及实际健康和暴露风险。实验将集中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出来，提供一系列定义良好的纳米形貌，用于体外细胞的平行审讯。永生化的小鼠巨噬细胞和人类角质形成细胞将附着在具有纳米级形状和表面化学的理想组合的微贴片上。要测量的生物学终点包括细胞活力、粘附、形态、增殖、氧化剂产生、DNA损伤和促炎细胞因子（如tnf - α）的释放。该项目还将研究新型纳米材料的社会影响，特别关注风险认知和大学纳米材料的安全性。物理、生物和社会科学领域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，这项研究将在纳米尺度上确定尺寸、形状、表面化学和氧化还原活性的组合，从而在一系列材料平台上实现最小的免疫反应和最佳的生物相容性。这种机制的理解可以导致实际的制造和净化指导方针，以确保各种开发和商业纳米材料的内在无毒性。同样的信息可以为纳米材料植入物和设备中生物相容性表面的设计提供指导。该项目的跨学科教育组成部分将培养研究生对新纳米技术的社会、伦理和人类健康影响的更多认识。

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.