Award Abstract # 2025505
ISS/Collaborative Research: 3D Bone Marrow Analogs to Determine the Contribution of Mechanical Signals to Aging MSC Function in Microgravity

NSF Org: CMMI
Division of Civil, Mechanical, and Manufacturing Innovation
Recipient: BOISE STATE UNIVERSITY
Initial Amendment Date: August 21, 2020
Latest Amendment Date: June 7, 2023
Award Number: 2025505
Award Instrument: Standard Grant
Program Manager: Shivani Sharma
shisharm@nsf.gov
 (703)292-4204
CMMI
 Division of Civil, Mechanical, and Manufacturing Innovation
ENG
 Directorate for Engineering
Start Date: November 1, 2020
End Date: October 31, 2025 (Estimated)
Total Intended Award Amount: $315,000.00
Total Awarded Amount to Date: $465,051.00
Funds Obligated to Date: FY 2020 = $315,000.00
FY 2021 = $16,000.00

FY 2022 = $78,999.00

FY 2023 = $55,052.00
History of Investigator:
  • Gunes Uzer (Principal Investigator)
    gunesuzer@boisestate.edu
  • Aykut Satici (Co-Principal Investigator)
Recipient Sponsored Research Office: Boise State University
1910 UNIVERSITY DR
BOISE
ID  US  83725-0001
(208)426-1574
Sponsor Congressional District: 02
Primary Place of Performance: Boise State University
Boise
ID  US  83725-1135
Primary Place of Performance
Congressional District:
02
Unique Entity Identifier (UEI): HYWTVM5HNFM3
Parent UEI: HYWTVM5HNFM3
NSF Program(s): GOALI-Grnt Opp Acad Lia wIndus,
Special Initiatives,
Engineering of Biomed Systems,
BMMB-Biomech & Mechanobiology
Primary Program Source: 01002223DB NSF RESEARCH & RELATED ACTIVIT
01002324DB NSF RESEARCH & RELATED ACTIVIT

01002021DB NSF RESEARCH & RELATED ACTIVIT

01002122DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 019Z, 020E, 028E, 116E, 1504, 9150, 9178, 9231, 9251
Program Element Code(s): 150400, 164200, 534500, 747900
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

ABSTRACT

Mechanical signals generated by exercise combat obesity and maintain a healthy musculoskeletal system. Age and reduced physical activity disrupt mechanical signaling and diminish the potency of stem cells within the bone marrow that replenish bone-building cells. Even though poor skeletal health is a major cause of injury and disability among aged individuals, the reason for reduced bone-building responsiveness to exercise in older individuals, compared to younger individuals, remains a knowledge gap. This project will quantify the mechanical forces that cells are subjected to in bone by using novel 3D printed tissue engineering constructs. Combining this technology with the aging conditions caused by microgravity in experiments to be conducted on the International Space Station will reveal the putative connections between aging and physical activity at the cellular level. Ultimately, these efforts may lead to non-pharmacologic, regenerative strategies to improve muscle and bone health in in older adults, in those who must undergo extended bedrest, and astronauts. The multidisciplinary approach taken in this bioengineering project will be an excellent platform to fascinate and engage the next generation of students and young scientists.

A major technical barrier in studying the mechanical environment of mesenchymal stem cells (MSCs) that reside within bone marrow is that there are no model systems currently available that can replicate the mechanical complexity of the bone marrow compartment. To close this gap, this work will develop a 3D printed bone marrow analog system that combines an in vivo environment with the accessibility of an in vitro culture system. This will permit a systematic approach of study. To study cellular mechanical environments within these marrow analogs, the approach will include an experimental setup and a complementary and validated finite element model. These mechanoactive marrow environments will provide a novel tool for mechanobiologists to systematically study the effect of the mechanical environment on cell responses in 3D. Utilization of this novel system in this project will specifically advance mechanobiology knowledge by: (1) quantifying the mechanoresponse of old MSCs in a young bone marrow geometry and vice versa, thereby identifying the contribution of mechanical stress environment to the mechanosignaling capacity of aged MSCs. (2) establishing, for the first time, how the mechanical stress environment contributes to microgravity-simulated aging of MSCs.

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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Birks, Scott and Uzer, Gunes "At the nuclear envelope of bone mechanobiology" Bone , v.151 , 2021 https://doi.org/10.1016/j.bone.2021.116023 Citation Details
Enrriques, Ashton E. and Howard, Sean and Timsina, Raju and Khadka, Nawal K. and Hoover, Amber N. and Ray, Allison E. and Ding, Ling and Onwumelu, Chioma and Nordeng, Stephan and Mainali, Laxman and Uzer, Gunes and Davis, Paul H. "Atomic Force Microscopy Cantilever-Based Nanoindentation: Mechanical Property Measurements at the Nanoscale in Air and Fluid" Journal of Visualized Experiments , 2022 https://doi.org/10.3791/64497 Citation Details
Goelzer, Matthew and Dudakovic, Amel and Olcum, Melis and Sen, Buer and Ozcivici, Engin and Rubin, Janet and van Wijnen, Andre J. and Uzer, Gunes "Lamin A/C Is Dispensable to Mechanical Repression of Adipogenesis" International Journal of Molecular Sciences , v.22 , 2021 https://doi.org/10.3390/ijms22126580 Citation Details
Goelzer, Matthew and Goelzer, Julianna and Ferguson, Matthew L. and Neu, Corey P. and Uzer, Gunes "Nuclear envelope mechanobiology: linking the nuclear structure and function" Nucleus , v.12 , 2021 https://doi.org/10.1080/19491034.2021.1962610 Citation Details
Kennedy, Zeke and Newberg, Joshua and Goelzer, Matthew and Judex, Stefan and Fitzpatrick, Clare K. and Uzer, Gunes "Modeling stem cell nucleus mechanics using confocal microscopy" Biomechanics and Modeling in Mechanobiology , 2021 https://doi.org/10.1007/s10237-021-01513-w Citation Details
Nikitina, Nina and Bursa, Nurbanu and Goelzer, Matthew and Goldfeldt, Madison and Crandall, Chase and Howard, Sean and Rubin, Janet and Zavala, Anamaria and Satici, Aykut and Uzer, Gunes "DataDriven and CellSpecific Determination of NucleiAssociated Actin Structure" Small Structures , 2024 https://doi.org/10.1002/sstr.202300204 Citation Details
Regner, Alexander M and DeLeon, Maximilien and Gibbons, Kalin D and Howard, Sean and Nesbitt, Derek Q and Darghiasi, Seyedeh F and Zavala, Anamaria G and Lujan, Trevor J and Fitzpatrick, Clare K and Farach-Carson, Mary C and Wu, Danielle and Uzer, Gunes "Increased deformations are dispensable for encapsulated cell mechanoresponse in engineered bone analogs mimicking aging bone marrow" Mechanobiology in Medicine , v.3 , 2025 https://doi.org/10.1016/j.mbm.2024.100097 Citation Details
Rubin, Janet and van Wijnen, Andre J. and Uzer, Gunes "Architectural control of mesenchymal stem cell phenotype through nuclear actin" Nucleus , v.13 , 2022 https://doi.org/10.1080/19491034.2022.2029297 Citation Details
Sen, Buer and Xie, Zhihui and Howard, Sean and Styner, Maya and van Wijnen, Andre J. and Uzer, Gunes and Rubin, Janet "Mechanically Induced Nuclear Shuttling of -Catenin Requires Co-transfer of Actin" Stem Cells , v.40 , 2022 https://doi.org/10.1093/stmcls/sxac006 Citation Details
Thompson, Matthew and Woods, Kali and Newberg, Joshua and Oxford, Julia Thom and Uzer, Gunes "Low-intensity vibration restores nuclear YAP levels and acute YAP nuclear shuttling in mesenchymal stem cells subjected to simulated microgravity" npj Microgravity , v.6 , 2020 https://doi.org/10.1038/s41526-020-00125-5 Citation Details

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