
NSF Org: |
CMMI Division of Civil, Mechanical, and Manufacturing Innovation |
Recipient: |
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Initial Amendment Date: | November 30, 2015 |
Latest Amendment Date: | January 13, 2016 |
Award Number: | 1600118 |
Award Instrument: | Standard Grant |
Program Manager: |
Steve Schmid
CMMI Division of Civil, Mechanical, and Manufacturing Innovation ENG Directorate for Engineering |
Start Date: | August 17, 2015 |
End Date: | December 31, 2018 (Estimated) |
Total Intended Award Amount: | $300,947.00 |
Total Awarded Amount to Date: | $310,947.00 |
Funds Obligated to Date: |
FY 2016 = $10,000.00 |
History of Investigator: |
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Recipient Sponsored Research Office: |
201 OLD MAIN UNIVERSITY PARK PA US 16802-1503 (814)865-1372 |
Sponsor Congressional District: |
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Primary Place of Performance: |
101 Hammond Building University Park PA US 16802-1400 |
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): | Manufacturing Machines & Equip |
Primary Program Source: |
01001617DB NSF RESEARCH & RELATED ACTIVIT |
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
The goal of this project is to establish a new frontier in bioprinting science and technology. This will be accomplished by studying the bioprinting of bone tissue directly into a defect site on an animal model. The research in this study will have a direct impact on the first-time bioprinting of living cells and nucleic acid loaded in polymers in surgery settings for bone tissue fabrication, which will benefit society by working toward the establishment of an alternative solution for skull defects. Skull defects are devastating and affect millions of people each year; about 7%, or 227,500, of the children born each year in the United States are affected by birth defects in the skull. Bioprinting in surgery settings will eventually be applied to other organs and will considerably improve quality of life for the affected people. Broader-impact activities will include training, education, and participation of underrepresented populations in summer camps and workshops, as well as the integration of next-generation bioprinting science into both graduate and undergraduate education.
The research objectives of this project are three-fold: 1) to understand bioprinting behavior of a composite bioink, 2) to determine the effects of bioprinting and the bioink parameters on the release profile and the transfection efficiency of plasmid, and 3) to understand bioprintability of porous tissue constructs in defects and establish the relationship between the manufacturing conditions of tissue constructs and bone tissue formation. Accomplishing these objectives will allow the exploration of advanced bioprinting technologies in operating rooms. In this project, the following tasks will be performed. First, a novel composite bioink (reinforced with collagen, stem cells, a thermo-sensitive gel, and plasmid) will be processed and characterized to research its bioprinting behavior. Then, bioprinting of plasmid will be studied to understand the role of bioprinting and the bioink parameters on sequential release and transfection efficiency of plasmid. Next, in situ multi-arm bioprinting will be studied to investigate manufacturability of multiple tissue constructs in critical-size cranial defects in rat models. Finally, the regenerated bone tissue, bioprinted under various manufacturing conditions, will be characterized and quantified using tissue histology and micro-computed tomography.
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.
With this project, three-dimensional (3D) bioprinting of cells, proteins and genes in surgical settings has been demonstrated for cranial tissue repair, which enabled the successful regeneration of bone tissue. A new bioink formulation has been introduced and the rheological, biological and mechanical properties of that bioink were tuned to facilitate its extrusion into critical-size rat calvarial defects in aseptic conditions. It has been demonstrated that the addition of osteogenic particles, including plasmid deoxyribonucleic acid (DNA), micro ribonucleic acid (miRNA), bone morphogenetic protein-2 (BMP-2), or hydroxyapatite nano-particles, at increasing concentrations enhanced bone tissue regeneration in six weeks post implantation. Moreover, 3D Laser scanning has been integrated into bioprinting process planning in order to generate toolpath for in situ bioprinting into calvarial defects. In addition, bioprinting of composite tissues, including cranium and bi-layered skin tissue, has been demonstrated in a stratified arrangement on rats in surgical settings for the first time in the literature.
During the project, three PhD students and three REU students have been trained on various aspects of 3D bioprinting such as synthesis and preparation of bioink materials, extrusion- and droplet-based bioprinting process development, 3D cell culture, animal handling and maintenance, and tissue characterization techniques. One of the PhD students already graduated and the other two have passed their comprehensive exams and are in the last year of their PhD studies. The PI has delivered more than 40 invited talks or seminars and the key results have been shared with the public and tissue engineering and bioprinting communities. In addition, one of the PhD students in the PI's laboratory has delivered more than 10 oral and poster presentations at local, national and international conferences.
Last Modified: 03/08/2019
Modified by: Ibrahim T Ozbolat
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