Award Abstract # 2135720
BRITE Fellow: Intelligent Nanoscale 3D Biomanufacturing for Human-on-a-Chip

NSF Org: CMMI
Division of Civil, Mechanical, and Manufacturing Innovation
Recipient: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Initial Amendment Date: February 28, 2022
Latest Amendment Date: April 3, 2024
Award Number: 2135720
Award Instrument: Standard Grant
Program Manager: Siddiq Qidwai
sqidwai@nsf.gov
 (703)292-2211
CMMI
 Division of Civil, Mechanical, and Manufacturing Innovation
ENG
 Directorate for Engineering
Start Date: March 1, 2022
End Date: February 28, 2027 (Estimated)
Total Intended Award Amount: $1,000,000.00
Total Awarded Amount to Date: $1,048,000.00
Funds Obligated to Date: FY 2022 = $1,016,000.00
FY 2023 = $16,000.00

FY 2024 = $16,000.00
History of Investigator:
  • Shaochen Chen (Principal Investigator)
    chen168@eng.ucsd.edu
Recipient Sponsored Research Office: University of California-San Diego
9500 GILMAN DR
LA JOLLA
CA  US  92093-0021
(858)534-4896
Sponsor Congressional District: 50
Primary Place of Performance: University of California-San Diego
9500 Gilman Dr., MC 0937
La Jolla
CA  US  92093-0937
Primary Place of Performance
Congressional District:
50
Unique Entity Identifier (UEI): UYTTZT6G9DT1
Parent UEI:
NSF Program(s): BRITE-BoostRschIdeasTransEquit
Primary Program Source: 01002223DB NSF RESEARCH & RELATED ACTIVIT
01002324DB NSF RESEARCH & RELATED ACTIVIT

01002425DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 027E, 084E, 116E, 7237, 7479, 9161, 9178, 9231, 9251
Program Element Code(s): 192Y00
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

ABSTRACT

This Boosting Research Ideas for Transformative and Equitable Advances in Engineering (BRITE) Fellow grant will provide a transformative nanoscale biomanufacturing platform powered by artificial intelligence. At the convergence of advanced additive manufacturing, stem cell biology, biomaterials, and biomechanics, biomanufacturing has the potential for creating three-dimensional biomimetic tissue constructs that can not only redefine the clinical capabilities of regenerative medicine but also transform the toolsets available for various applications such as disease modeling, pre-clinical drug screening, space exploratory and deep ocean studies with human-like tissues, and environmental health and safety studies using engineered human tissues. However, current biomanufacturing technologies have critical bottlenecks: a) they lack the resolution to resolve single cells and are too slow for fabricating a functional three-dimensional human tissues and organs, b) they are often conducted by trial and error, resulting in wasting expensive cells, biomaterials, and time, and c) the lack of systemic interactions with other tissues or organs at the human systemic level. This project aims to address fundamental research issues related to these bottlenecks. On the education side, a comprehensive equity, diversity, and inclusion plan will be developed. Graduate student researchers, undergraduate interns, and K-12 students from diverse backgrounds will have the opportunity to participate in this exciting research project and other outreach programs. As an eminent leader, the principal investigator is poised to make long lasting societal, educational, and commercial impacts on advanced manufacturing and nanoengineering.

The research objectives of the project are to investigate ultrafast, near-field optics for nanoscale control of photo-polymerization in three-dimensional bioprinting, to investigate the machine learning methods for three-dimensional bioprinting, and to study the biomechanics and tissue functions of the bioprinted human-on-a-chip. To achieve these objectives, both theoretical and experimental investigations will be carried out to understand the nanoscale light control for bioprinting. Machine learning methods will be investigated for optimal control of the three-dimensional bioprinting process. The biomechanics issues and tissue functions in the human-on-a-chip will be studied. This will be the first attempt in the field to explore ultrafast near-field optics for bioprinting with nanoscale resolution. This research on machine learning methods is also quite novel, particularly for bioprinting so that traditional trial and error optimization will no longer be needed. Furthermore, the human-on-a-chip integrating major tissues such as heart, liver, lung, kidney in the microfluidic system will be an enabling platform for various applications. By integrating the emerging disruptive technologies in the multidisciplinary domains of biomanufacturing, artificial intelligence, and nanophotonics, this research supports exceptionally innovative, high risk, original, and unconventional research projects that have the potential to create new paradigms in advanced manufacturing.

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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Farah, Elie N and Hu, Robert K and Kern, Colin and Zhang, Qingquan and Lu, Ting-Yu and Ma, Qixuan and Tran, Shaina and Zhang, Bo and Carlin, Daniel and Monell, Alexander and Blair, Andrew P and Wang, Zilu and Eschbach, Jacqueline and Li, Bin and Destici, "Spatially organized cellular communities form the developing human heart" Nature , v.627 , 2024 https://doi.org/10.1038/s41586-024-07171-z Citation Details
Kiratitanaporn, Wisarut and Guan, Jiaao and Berry, David B. and Lao, Alison and Chen, Shaochen "Multimodal Three-Dimensional Printing for Micro-Modulation of Scaffold Stiffness Through Machine Learning" Tissue Engineering Part A , 2023 https://doi.org/10.1089/ten.TEA.2023.0193 Citation Details
Kiratitanaporn, Wisarut and Guan, Jiaao and Tang, Min and Xiang, Yi and Lu, Ting-yu and Balayan, Alis and Lao, Alison and Berry, David B and Chen, Shaochen "3D Printing of a Biomimetic Myotendinous Junction Assisted by Artificial Intelligence" Biomaterials Science , v.12 , 2024 https://doi.org/10.1039/D4BM00892H Citation Details
Levato, Riccardo and Dudaryeva, Oksana and Garciamendez-Mijares, Carlos Ezio and Kirkpatrick, Bruce E. and Rizzo, Riccardo and Schimelman, Jacob and Anseth, Kristi S. and Chen, Shaochen and Zenobi-Wong, Marcy and Zhang, Yu Shrike "Light-based vat-polymerization bioprinting" Nature Reviews Methods Primers , v.3 , 2023 https://doi.org/10.1038/s43586-023-00231-0 Citation Details
Lu, Ting-Yu and Xiang, Yi and Tang, Min and Chen, Shaochen "3D Printing Approaches to Engineer Cardiac Tissue" Current Cardiology Reports , v.25 , 2023 https://doi.org/10.1007/s11886-023-01881-y Citation Details
Miller, Kathleen L. and Sit, Izaac and Xiang, Yi and Wu, Jerry and Pustelnik, Jacob and Tang, Min and Kiratitanaporn, Wisarut and Grassian, Vicki and Chen, Shaochen "Evaluation of CuO nanoparticle toxicity on 3D bioprinted human iPSC-derived cardiac tissues" Bioprinting , v.32 , 2023 https://doi.org/10.1016/j.bprint.2023.e00284 Citation Details
Sun, Yazhi and Wang, Xiaocheng and Tang, Min and Melarkey, Mary K and Lu, Tingyu and Xiang, Yi and Chen, Shaochen "3D Printing of SucculentInspired Microneedle Array for Enhanced Tissue Adhesion and Controllable Drug Release" Advanced Materials Technologies , v.9 , 2024 https://doi.org/10.1002/admt.202400216 Citation Details
Xiang, Yi and Zhong, Zheng and Yao, Emmie J. and Kiratitanaporn, Wisarut and Suy, Malleeka T. and Chen, Shaochen "3D bioprinting of gene delivery scaffolds with controlled release" Bioprinting , v.31 , 2023 https://doi.org/10.1016/j.bprint.2023.e00270 Citation Details
You, Shangting and Xiang, Yi and Hwang, Henry H. and Berry, David B. and Kiratitanaporn, Wisarut and Guan, Jiaao and Yao, Emmie and Tang, Min and Zhong, Zheng and Ma, Xinyue and Wangpraseurt, Daniel and Sun, Yazhi and Lu, Ting-yu and Chen, Shaochen "High cell density and high-resolution 3D bioprinting for fabricating vascularized tissues" Science Advances , v.9 , 2023 https://doi.org/10.1126/sciadv.ade7923 Citation Details
Zhong, Zheng and Chen, Shaochen "Isolation and Expansion of Primary Conjunctival Stem Cells (CjSCs) from Human and Rabbit Tissues" BIO-PROTOCOL , v.12 , 2022 https://doi.org/10.21769/bioprotoc.4569 Citation Details

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