CAREER: Training Diverse Scientists to Design Bionanomaterials for Imaging and Labeling of Therapeutic Stem cells

Non-technical abstract:

This CAREER award made by the Biomaterials Program in the Division of Materials Research to Oregon State University focuses on nanomaterials research to advance national health. New nanomaterials combine cell-labeling and imaging capabilities to visually track stem-cell-based regenerative medicine therapies longitudinally in real-time via optical coherence tomography (OCT) imaging.

The materials from this project will allow researchers to study the migration and survival after transplantation in vivo, capabilities that currently do not exist. Highly reflective nanomaterials improve the resolution of OCT imaging to visualize single cells. The modified coatings on nanoparticle surfaces adhere to therapeutic stem cells, protect nanomaterials from degradation in biological environments, and make them stealthy to evade the immune system.

The project develops safe and stable nanomaterials and advances the field by improving understanding of how the properties of the coated nanomaterials influence their stability, cellular uptake, and retention without compromising cell health and function. It also advances the potential of preclinical research by providing new tools for studying the safety and efficacy of therapeutic stem cells.

The project will benefit society by addressing convergent challenges in human health and nanomedicine and by providing broadly applicable new materials for (1) diagnostic imaging, (2) drug delivery, and (3) preclinical research tools to advance cell-based therapies for retinal diseases, cancer, and neurodegeneration. The investigator integrates this research with a comprehensive education program to inspire and train the next generation of diverse scientists in bionanomaterials research for nanomedicine.

The educational platform comprises an Ignite in STEM research program; enrichment curriculum focused on professional skills; and a course-based research experience that provides K12 and undergraduate students from underserved communities with authentic experiences, transferable skills as chemists, and opportunities to reveal the hidden curriculum needed to build strong scientific and professional identities for retention in STEM.

Technical abstract:

Current methods for evaluating cell-based therapies, i.e., gaining insights into cell migration, integration, and survival after transplantation rely on histological analysis of tissues post-mortem. This approach is costly and requires that many animals be sacrificed. The ability to track these cells longitudinally in vivo is hampered by the inability to identify transplanted cells with current imaging methods.

This NSF CAREER award is focused on studying how hybrid membrane-coated nanomaterials (HMNPs) may be optimized as optical coherence tomography (OCT) contrast agents and nanolabels for cell-based therapies, uniquely advancing the capabilities of preclinical studies focused on cell transplantation. Creating membranes to coat nanomaterials that give them “stealth” abilities to evade the immune system represents a frontline nanotechnology challenge in imaging, diagnostic, and drug delivery.

The design rules for these coatings in imaging cell-based therapies remain unknown. While prior work shows that membrane-based nanoparticles improve biocompatibility and drug delivery, the ability to use HMNPs to label and visualize transplanted cells using OCT, as this project aims to do, has not yet been realized. The first aim of the project focuses on the synthesis and characterization of HMNPs with high scattering efficiency and reflectance for OCT imaging and membrane architectures with ligands on the HMNPs that attach extracellularly or intracellularly to cells.

The second focuses on understanding how the size, shape, and surface chemistry of HMNPs influence their ability to engage and facilitate their cellular uptake and retention. The third focuses on understanding how the structural features of HMNPs and symbiotic cell-labeling influence their reflectance properties and OCT contrast. Together these aims advance fundamental knowledge of HMNPs as preclinical tools to improve the study of cell-based therapies.

This project integrates research and professional development skills to increase the number of diverse scientists in STEM by (a) creating a strong outreach program to engage and connect high school STEM students with nanomaterials research, (b) implementing a programmatic enrichment arc in the chemistry majors to hardwire success in chemistry with transferable asset-based skills, and (c) creating a Course-based Undergraduate Research Experience (CURE) focused on interfacing nanomaterials with biological systems.

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.