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

职业：纳米颗粒的皮内生物相容性作为微创植入物促进人类健康

• 批准号: 2235902
• 负责人: Carson Bruns
• 金额: $ 60.52万
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2235902&HistoricalAwards=false
• 关键词: CAREER; Intradermal; Biocompatibility; Nanoparticles; Minimally

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.

这项研究的动机是主要研究人员的使命是开发纳米级生物医学设备，通过皮肤，使用类似于普通纹身颜料的微创植入程序，与身体无缝且永久地结合，数千年来，这种设备已被植入人体皮肤中。使用最简单的工具是纳米颗粒然而，尽管纹身在美国人口中广泛流行，但纳米技术的现代工具几乎没有应用于纹身颜料纳米颗粒。其中四分之一是纹身的，现在有许多不同的纳米级传感器和设备可供使用，皮肤作为最外部的器官，提供了植入它们的最佳位置，特别是当它们可能带来新的生物医学益处时，例如感知和监测生命体的能力。健康因素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普遍缺乏的基础知识，促使需要对植入皮肤的纳米颗粒的生物相容性进行更多研究。将结合纳米技术工具和模型，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活动中。旨在扩大科学和工程领域的参与和增强多样性的公共宣传活动。这种假设驱动的调查将建立有关纳米颗粒尺寸、成分、表面化学、密度和刚度如何影响生物相容性的基础知识，以便表征结构特性。生物相容性关系皮内纳米颗粒，研究小组将（i）创建一个在尺寸、成分、密度和硬度方面具有系统变化的纳米颗粒库，（ii）将这些纳米颗粒植入小鼠真皮组织中，以及（iii）表征体内生物相容性急性和慢性免疫原性、毒性和生物分布被重新认识到，较大、较密的纳米颗粒将最大限度地减少迁移，而较软的纳米颗粒将通过模仿天然的机制而减少促炎作用。还开创性地认为，惰性聚合物涂层可以提供一种通过钝化免疫原性表面来提高生物相容性的通用方法，这些假设将通过比较无毛小鼠（作为人类）体内的炎症、基因毒性和光毒性以及生物分布的测定来检验。这些研究将产生建立一般指南所需的重要见解，以确保普通纹身颜料和下一代皮内生物医学的安全性。艺术与科学研讨会的成果将包括探索人体艺术和生物医学工程之间的联系，这些成果将使用调查工具进行评估，以了解外展活动参与者如何影响对科学、技术和工程的态度。授予 NSF 的法定使命，并通过评估反映使用基金会的智力优点和更广泛的影响审查标准，被认为值得支持。