CAREER: Intradermal Biocompatibility of Nanoparticles as Minimally Invasive Implants for Human Health

这项研究的动机是首席研究员的使命，即开发纳米级生物医学设备，通过皮肤与身体无缝地永久结合，使用类似于美容纹身的微创植入程序。几千年来，人们用最简单的工具将普通的纹身颜料植入人体皮肤，这种颜料是纳米粒子。然而，尽管纹身在美国人口中广泛流行，超过四分之一的人有纹身，但现代纳米技术几乎没有应用于纹身颜料纳米粒子。现在有许多不同的纳米级传感器和设备可用。皮肤作为最外部的器官，为植入它们提供了一个最佳的位置，尤其是当它们可能赋予新的生物医学益处时，比如感知和监测重要健康因素的能力。利用功能性纳米生物传感器取代纹身颜料的机会，以及对普通纹身颜料安全性基本知识的普遍缺乏，促使人们对植入皮肤的纳米颗粒的生物相容性进行更多的研究。这个项目将把纳米技术的工具与一个模型结合起来，以了解如何设计和制造尽可能安全、低过敏性和生物相容性的皮肤纳米植入物。教育和推广工作将把这项研究整合到一个独特的艺术与科学研讨会和其他旨在扩大参与和增强科学与工程多样性的公共推广活动中。这项假设驱动的研究将建立纳米颗粒大小、组成、表面化学、密度和硬度如何影响生物相容性的基础知识。为了表征皮内纳米颗粒的结构-性能-生物相容性关系，研究小组将(i)创建一个纳米颗粒库，其大小、组成、密度和硬度有系统的变化，（ii）将这些纳米颗粒植入小鼠真皮组织，（iii）表征体内关于急性和慢性免疫原性、毒性和生物分布的生物相容性。据推测，更大、更致密的纳米颗粒将最大限度地减少迁移，而更软的纳米颗粒将通过模仿天然组织的机制而减少促炎作用。我们还假设惰性聚合物涂层可以提供一种通过钝化免疫原性表面来改善生物相容性的一般方法。这些假设将通过比较在植入了不同纳米颗粒的无毛小鼠（作为人类皮肤替代品）体内的炎症、基因和光毒性以及生物分布的分析来验证。这些研究将产生重要的见解，以建立确保普通纹身色素和下一代皮内生物医学纳米植入物安全性的一般指导方针。艺术与科学研讨会的成果将包括探索人体艺术与生物医学工程之间的联系。这些结果将使用调查工具进行评估，以了解外联活动如何影响参与者对科学、技术和工程的态度。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This research is motivated by the principal investigator’s mission to develop nanoscale biomedical devices that integrate seamlessly and permanently with the body, via the skin, using minimally invasive implantation procedures akin to cosmetic tattooing. Ordinary tattoo pigments, which have been implanted in human skin for millennia using the simplest of tools, are nanoparticles. However, the modern tools of nanotechnology have scarcely been brought to bear on tattoo pigment nanoparticles, despite the widespread popularity of tattoos among the United States population, over a quarter of which is tattooed. Many different nanoscale sensors and devices are now available. The skin, as the most external organ, offers an optimal site for implanting them, especially when they might confer new biomedical benefits such as the ability to sense and monitor vital health factors. The opportunity to replace tattoo pigments with functional nano-biosensors, as well as the general lack of fundamental knowledge on the safety of ordinary tattoo pigments, motivates the need for more research on the biocompatibility of nanoparticles implanted in the skin. This project will combine the tools of nanotechnology with a model to understand how to design and create skin nano-implants that are as safe, hypo-allergenic, and biocompatible as possible. Education and outreach efforts will integrate this research into a unique art-meets-science workshop and other public outreach activities designed to broaden participation and enhance diversity in science and engineering.This hypothesis-driven investigation will establish fundamental knowledge on how nanoparticle size, composition, surface chemistry, density, and stiffness affect biocompatibility. In order to characterize the structure-property-biocompatibility relationships in intradermal nanoparticles, the research team will (i) create a library of nanoparticles with systematic variations in size, composition, density, and stiffness, (ii) implant these nanoparticles in murine dermal tissue, and (iii) characterize biocompatibility in vivo with respect to acute and chronic immunogenicity, toxicity, and biodistribution. It is hypothesized that larger, denser nanoparticles will minimize migration, while softer nanoparticles will be less pro-inflammatory by mimicking the mechanics of native tissue. It is also hypothesized that inert polymer coatings may provide a general way to improve biocompatibility by passivating immunogenic surfaces. These hypotheses will be tested by comparing assays for inflammation, geno- and phototoxicity, and biodistribution in vivo among hairless mice (as a human skin surrogate) implanted with different nanoparticles in the library. These studies will produce critical insights needed to establish general guidelines that ensure the safety of both ordinary tattoo pigments and the next generation of intradermal biomedical nano-implants. Outcomes of the art-meets-science workshop will include exploring connections between body art and biomedical engineering. These outcomes will be assessed using survey instruments to understand how the outreach activities influence participant attitudes about science, technology, and engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.