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者的使命，开发纳米生物医学设备，无缝和永久地集成与身体，通过皮肤，使用微创植入程序类似于美容纹身。普通的纹身颜料，使用最简单的工具植入人类皮肤数千年，是纳米粒子。然而，纳米技术的现代工具几乎没有被用于纹身颜料纳米颗粒，尽管纹身在美国人口中广泛流行，其中超过四分之一是纹身。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，为植入它们提供了最佳场所，特别是当它们可能带来新的生物医学益处时，例如感知和监测重要健康因素的能力。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的基本知识的普遍缺乏，促使人们需要对植入皮肤的纳米粒子的生物相容性进行更多的研究。这个项目将结合联合收割机的纳米技术的工具与模型，以了解如何设计和创造皮肤纳米植入物是安全的，低过敏性，生物相容性尽可能。教育和推广工作将把这项研究纳入一个独特的艺术满足科学研讨会和其他公共推广活动，旨在扩大参与，提高科学和工程的多样性。这一假设驱动的调查将建立纳米颗粒的大小，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。为了表征皮内纳米颗粒的结构-性质-生物相容性关系，研究小组将（i）创建一个在大小，组成，密度和刚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皮肤组织中，以及（iii）在体内表征急性和慢性免疫原性，毒性和生物分布方面的生物相容性。假设较大、较致密的纳米颗粒将使迁移最小化，而较软的纳米颗粒将通过模仿天然组织的力学而较少促炎。还假设惰性聚合物涂层可以通过钝化免疫原性表面来提供改善生物相容性的一般方法。这些假设将通过比较植入库中不同纳米颗粒的无毛小鼠（作为人类皮肤替代物）中的炎症、基因和光毒性以及体内生物分布的测定来进行测试。这些研究将产生关键的见解，需要建立一般的指导方针，确保普通纹身颜料和下一代皮内生物医学纳米植入物的安全性。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，以了解外展活动如何影响参与者对科学、技术和工程的态度。该奖项反映了NSF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。