
NSF Org: |
CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems |
Recipient: |
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Initial Amendment Date: | July 2, 2019 |
Latest Amendment Date: | July 2, 2019 |
Award Number: | 1903933 |
Award Instrument: | Standard Grant |
Program Manager: |
Nora Savage
nosavage@nsf.gov (703)292-7949 CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems ENG Directorate for Engineering |
Start Date: | July 1, 2019 |
End Date: | June 30, 2022 (Estimated) |
Total Intended Award Amount: | $200,000.00 |
Total Awarded Amount to Date: | $200,000.00 |
Funds Obligated to Date: |
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History of Investigator: |
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Recipient Sponsored Research Office: |
9500 GILMAN DR LA JOLLA CA US 92093-0021 (858)534-4896 |
Sponsor Congressional District: |
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Primary Place of Performance: |
9500 Gilman Dr., MC 0448 LA JOLLA CA US 92093-0934 |
Primary Place of
Performance Congressional District: |
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Unique Entity Identifier (UEI): |
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Parent UEI: |
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NSF Program(s): |
Nanoscale Interactions Program, ENG NNI Special Studies |
Primary Program Source: |
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Program Reference Code(s): |
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Program Element Code(s): |
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Award Agency Code: | 4900 |
Fund Agency Code: | 4900 |
Assistance Listing Number(s): | 47.041 |
ABSTRACT
While nanotechnology is revolutionizing many industry sectors and having significant impact to our daily lives, investigating the potential negative impacts of nanomaterials becomes ever more important. Most studies that focus on understanding potential health effects are carried out with cells cultured in a petri-dish. While such studies have provided a wealth of information about the importance of nanomaterial's physical, mechanical, and chemical properties in toxicity to cells, they inform less about the interactions of the nanoparticles with human tissues and organs. This project aims to create an engineered 3-dimensional human heart tissue model generated by a novel bioprinting technique, and to use this model to study the impact of nanoparticles on the heart. Success of this this project will eliminate the need for expensive animal model systems in studies of tissue and organ toxicity to nanomaterials. The highly interdisciplinary nature of the project will involve training students across the traditional boundaries, offering exciting topics including bioprinting, tissue engineering, nanotechnology, and biological interactions of nanoparticles. Also, the project will facilitate training broadly across multiple stages of professional and academic development by including graduate students, undergraduate students, and high school students of diverse backgrounds.
Technically, this project will be the first attempt in the field to investigate how nanoparticles interact with 3-dimensional human heart tissues, created by 3-dimensional bioprinting. The first research task aims to establish the bioprinted microscale human heart tissue model and evaluate cell alignment, morphology, gene expression, and cardiac function. The second research task will focus on the synthesis of a suite of monodispersed nanoparticles with varying compositions and surface coatings. Assessment of nano-cardio interactions will be carried out to investigate the effects of these nanoparticles on cell viability, morphology, gene expression, and cardiac force output. From this project, the feasibility of using these engineered human tissue models for nanotoxicity studies will be established. The project is of high-risk. But if successful, the outcomes of the project will lead to high reward since it will provide significant insights into the biocompatibility of nanoparticles to 3-dimensional human tissues. Using human induced pluripotent stem cells derived cardiomyocytes, the project will further reveal individual effects of these nanoparticles. The investigators are well situated and uniquely positioned to tackle these issues. The principal investigator is a pioneer in 3-dimensional bioprinting with an excellent track record for cutting-edge research in biomaterials, bioprinting, and tissue engineering. The co-principal investigator is a leading expert in studying the environmental and health implications of nanomaterials. Such a unique collaboration will lead to transformative results. The highly interdisciplinary nature of the project will enable student training across the traditional boundaries, offering exciting topics including biomanufacturing, nanotechnology and biological interactions of nanoparticles. Also, the project will facilitate training graduate students, undergraduate students, and high school students of diverse backgrounds.
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.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
The objective of this research is to investigate the interactions of nanoparticles and cardiac tissue using a 3D bioprinted human micro-heart model. The research approach includes: 1) establishing a cardiac tissue model using 3D bioprinting for nano-cardio interaction studies, 2) synthesizing a suite of monodispersed nanoparticles of similar size but of different bulk compositions and of different surface coatings, 3) investigating the impacts of nanoparticles on heart tissue viability, maturation, and function.
This work has led to significant outcomes including: 1) successful bioprinting of 3D functional micro-heart tissues using human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs), 2) successful synthesis of a suite of monodispersed nanoparticles and characterization using various techniques such as transmission electron microscopy, X-ray diffraction, and dynamic light scattering, 3) detailed studies of the nanoparticle toxicity against the human micro-heart tissues in terms of heart beating frequency, force output, and the pathways of cardiac toxicity.
During the course of the project, three graduate students have worked in the multi-disciplinary team with significant training in bioprinting, nanoparticle synthesis and characterization, cell culture and tissue function and toxicity studies. Three undergraduate researchers have been involved in this project. The undergraduate students learned how to team up with the graduate students, and learned how to conduct scientific experiments. Eight peer-reviewed journal papers and one book chapter have been published with support from this grant.
Results from this project has been presented in a variety of society meetings, including the Society of Engineering Science Annual Meeting, Select Biosciences Organ-on-a-Chip and 3D-Printing World Congress, American Heart Association Scientific Session, SPIE Photonic West, American Institute of Chemical Engineers meeting, and American Chemical Society meetings. The investigators have also been invited to present the results in several departmental seminars at several universities. Results from this project have also been used as a part of course materials for graduate and undergraduate courses, including Nano 206 - "Nanomanufacturing" (average enrollment 50 students per year), NANO 112 - "Synthesis and Fabrication of Nanoengineering Systems" (average enrollment 80 students per year) at the University of California San Diego.
Last Modified: 10/30/2022
Modified by: Shaochen Chen
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