| NSF Org: |
CMMI Division of Civil, Mechanical, and Manufacturing Innovation |
| Recipient: |
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| Initial Amendment Date: | July 20, 2016 |
| Latest Amendment Date: | April 28, 2017 |
| Award Number: | 1634997 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Steve Schmid
CMMI Division of Civil, Mechanical, and Manufacturing Innovation ENG Directorate for Engineering |
| Start Date: | August 1, 2016 |
| End Date: | July 31, 2018 (Estimated) |
| Total Intended Award Amount: | $99,845.00 |
| Total Awarded Amount to Date: | $115,845.00 |
| Funds Obligated to Date: |
FY 2017 = $16,000.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
900 S CROUSE AVE SYRACUSE NY US 13244 (315)443-2807 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
318 Bowne hall Syracuse NY US 13244-1200 |
| 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: |
01001718DB 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
Bioprinting has emerged as a promising approach to generate functional tissues and organs, as well as tissue analogs for regenerative medicine, pharmacology, toxicology, and disease modeling. Bioprinting technologies generally involve the encapsulation of living cells within biocompatible bioinks (such as hydrogels). However, with current technologies, capillary-sized networks cannot be printed within bioprinted constructs. These capillary-sized networks are critical for maintaining viability of tissue constructs and, therefore, are at the center of establishing the widespread application of current technologies. Ultrafast pulsed lasers are uniquely capable of machining capillary-sized networks within bioprinted constructs, however the impact of ultrafast laser machining on biological constructs is not known. This award supports fundamental research on effects of ultrafast laser micromachining on cellular damage. Research results will be useful for the development of a novel hybrid process combining laser micromachining and stereolithography bioprinting to produce bioprinted constructs that contains capillary-sized networks.
The research objective is to establish the relationship between ultrafast laser variables and cellular damage within cell-laden gelatin-based hydrogel biomaterials. To achieve this research objective, hydrogel constructs will be prepared by encapsulating mesenchymal progenitor cells within gelatin methacrylate hydrogel via ultraviolet crosslinking. Femtosecond laser multiphoton absorption process will be used to micromachine channels (about 10 microns in diameter) within the cell-laden hydrogel constructs. These constructs will have different cell densities (10,000 - 10,000,000 cells/mL), hydrogel concentration (7-18% w/v), and photoinitiator concentration (0.05-0.5% w/v). Experiments will be conducted under different ultrafast laser parameters: laser fluency from 0 to 25 J/cm^2, pulse energy from 0 to 100 nJ, and scanning speed from 0.1 to 10 mm/s. Cellular damage within hydrogel constructs will be evaluated by the following parameters: radial zones of cellular viability measured by confocal imaging of calcein AM-ethidium homodimer biomarkers, DNA damage measured using Comet assay, and function (ability to proliferate and produce extracellular matrix) measured using confocal imaging of EdU and Movat's fluorescent biomarkers.
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.
Bioprinting has emerged as a promising approach to generate tissue analogs for regenerative medicine, pharmacology, toxicology, and disease modeling applications. Bioprinting involves the encapsulated of living cells within biocompatible hydrogel-based bioinks. However, with current technologies, capillary-sized networks cannot be printed within bioprinted constructs. In this work, a femtosecond laser machining platform was set up, and machining of capillary sized densified lines and ablated lines in gelatin methacrylate (GelMA) hydrogel was demonstrated. Empirical relationship between machined size and laser parameters (power, scanning speed, depth of machining) was obtained. High viability of encapsulated cells near laser-machined line patterns was obtained. A fluorescence dye was perfused through capillary-sized channels proving that laser machined channels were not blocked by debris. The laser setup was also used to discover a new method to align cells in localized user-defined orientations using femtosecond laser enabled hydrogel densification. Densified line patterns were used to preferential align variety of cells such as mouse fibroblasts and osteocytes, and human endothelial cells and human induced pluripotent stem cells derived mesenchymal stem cells. Cellular alignment as a function of cell-culture time, line spacing, and modification-depth was characterized. Although a variety of methods have been used to control cellular alignment in 2D, recapitulating the organized 3D cellular alignment found within native tissues remains a challenge. The method discovered in this work can be potentially used for the creation of organized engineered tissues.
Last Modified: 08/08/2018
Modified by: Pranav Soman
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