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

University Of Colorado At Boulder, Boulder CO

Investigators

Abstract

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. 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.