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Project Title:  Fracture Healing in Haversian Bone under Conditions of Simulated Microgravity Reduce
Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/24/2011  
End Date: 06/30/2016  
Task Last Updated: 09/26/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Puttlitz, Christian  Ph.D. / Colorado State University 
Address:  1374 Campus Delivery 
Department of Mechanical Engineering and School of Biomedical Engineering 
Fort Collins , CO 80523-1374 
Email: puttlitz@engr.colostate.edu 
Phone: 970-224-9743  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Colorado State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Browning, Raymond  Colorado State University 
Haussler, Kevin  Colorado State University 
McGilvray, Kirk  Colorado State University 
Santoni, Brandon  Foundation for Orthopaedic Research and Education 
Palmer, Ross  Colorado State University 
Easley, Jeremiah  Colorado State University 
Project Information: Grant/Contract No. NNX11AQ81G 
Responsible Center: NASA JSC 
Grant Monitor: Ploeger, Stephanne  
Center Contact:  
stephanne.l.ploeger22@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: NNX11AQ81G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Fracture:Risk of Bone Fracture due to Spaceflight-induced Changes to Bone (IRP Rev F)
Human Research Program Gaps: (1) Fracture01:We do not understand how the space flight environment affects bone fracture healing in-flight (IRP Rev E)
(2) Fracture02:We need to characterize the loads applied to bone for standard in-mission activities (IRP Rev E)
Flight Assignment/Project Notes: NOTE: Extended to 6/30/2016 per NSSC information (Ed., 9/28/15)

NOTE: Extended to 8/23/2015 per HRP and NSSC information (Ed., 10/21/2014)

Task Description: There is a need for information regarding hard and soft tissue healing in microgravity environments, and if impaired healing exists, what countermeasures can be called upon to enhance healing. Research on fracture healing using the rodent hindlimb suspension model shows healing is impaired in simulated microgravity, while clinical research shows that moderate, early mechanical loading caused by weight bearing induces osteogenesis and aids in repair of bone fracture. Further research is needed to determine what loads, if any, should be applied during spaceflight to promote fracture healing.

Most ground-based microgravity models utilize rodent hindlimb suspension to simulate how reduced loading affects isolated physiologic systems. Unfortunately, results derived from these studies are difficult to directly translate to the human condition due to major anatomic and physiologic differences between rodents and humans. Specifically, the differences in rodent and human bone structures become increasingly important when studying orthopaedic issues such as bone maintenance and healing during spaceflight. For example, the basic microstructure of rodent bone, known as “plexiform” bone, lacks the osteons (Haversion systems) that are the main micro-architectural feature of human cortical bone. Furthermore, it is known that the osteogenic and healing potential of rodent bone far exceeds that of adult human tissue.

Due to these limitations in current ground-based microgravity models, there exists a need to develop a ground-based, large animal model of fracture healing in simulated weightlessness that more closely approximates the human condition as has been done in the first year of this study. This animal model should be capable of simulating a wide spectrum of microgravity and able to investigate exercise protocols that may aid in the optimization of the fracture healing cascade. Four specific aims were defined to meet these goals: 1) Develop a ground-based large animal model of bone unloading in order to simulate full weightlessness; 2) interrogate the effects of a simulated microgravity environment on bone fracture healing in a large animal model; 3) develop a computational model of weightbearing in ovine bone under different experimental conditions in order to characterize the loads experienced by the fracture site; and 4) investigate possible countermeasures to the deleterious effects of weightlessness on fracture healing.

Research Impact/Earth Benefits: The data collected during the first year of this study clearly demonstrate that the ovine model of ground-based microgravity effectively simulates the bone loss experienced by astronauts in space and ground-based rodent hindlimb suspension. This model has a major advantage over rodent hindlimb suspension models in that the mature ovine bone structure is nearly identical to that of humans, and future studies utilizing this large animal model (i.e., how hard and soft tissues heal in a microgravity environment, which will be executed in year two of this grant) will be easily translated to the human condition. Furthermore, the study of fracture healing will benefit from the use of a large animal model rather than a rodent model since the healing potential of sheep more closely matches that of humans than rodents.

The ground-based experiments utilizing this large animal (ovine) model directly address the need to know how varying microgravity environments affect fracture healing, as well as determining the applied loads at the fracture healing site through inverse dynamics and finite element simulations. The fracture rehabilitation protocols explored within this study will also aid in determining which mechanical environment leads to enhanced bone healing under microgravity conditions. The data produced during this study will significantly advance the basic mechanobiology of fracture healing by discerning which mechanical signals and environments facilitate enhanced bone healing.

Task Progress & Bibliography Information FY2016 
Task Progress: Specific Aim 3 outlined the development of a finite element of the ovine hindlimb in order to characterize the localized mechanical environment of a healing fracture in simulated microgravity and Earth gravitational environments. A high fidelity finite element (FE) model of the ovine hindlimb extending from the tibia to proximal phalanges was constructed and external fixation componentry was modeled to mimic the experimental methodology of Specific Aim 2. Additionally, a control model was created in which no external fixation componentry was included. Each model underwent a thorough validation process using experimental data from Specific Aims 1 and 2 to ensure model fidelity and robustness of model predictions. In order to simulate the fracture healing process of Specific Aim 2, histological data was utilized to create geometrically-matching fracture calluses on the Microgravity and Control models. Each model was then loaded with ground reaction forces measured during Specific Aim 2 and the local maximum and minimum principal strain as well as hydrostatic pressure predictions for each model were quantified. The findings indicated that the mechanical unloading experienced during simulated microgravity resulted in inhibited fracture healing by inducing fundamental changes in the bone formation processes, specifically by reducing hydrostatic pressure and strain of the healing fracture. These reductions resulted in alterations in the healing process, with animals exposed to a simulated microgravity environment subsequently healing primarily via intramembranous bone formation rather than the typical endochondral ossification process experienced by animals healing in an Earth gravitational environment.

Finally, in Specific Aim 4, two therapeutic countermeasures to the inhibited fracture healing of simulated microgravity unloading were investigated. The methodology of Specific Aim 2 was replicated, and shock wave therapy and low-intensity pulsed ultrasound were administered to animals healing in simulated microgravity and Earth gravitational loading environments. While fracture mechanical competency was not significantly altered following either countermeasure, both treatments significantly elevated osteoblast numbers and bone formation rates in simulated microgravity animals. The outcome of this study suggests that shock wave therapy and low-intensity pulsed ultrasound may be beneficial in situations involving aberrant fracture healing but elicit minimal modifications to the normal healing sequelae.

Bibliography Type: Description: (Last Updated: 03/25/2020) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Gadomski BC, Qin Y-X, Jiao J, McGilvray KC, Easley JT, Palmer RH, Puttlitz CM. "Shock wave therapy and low-intensity pulsed ultrasound accelerate bone formation rates under simulated microgravity conditions." Presented at the 2016 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 8-11, 2016.

2016 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 8-11, 2016. , Feb-2016

Abstracts for Journals and Proceedings Gadomski BC, Lerner ZF, Browning RC, Puttlitz CM. "A finite element investigation of fracture healing under simulated microgravity loading conditions." Summer Biomechanics, Bioengineering and Biotransport Conference, Snowbird, UT, July 17-20, 2015.

Proceedings of the Summer Biomechanics, Bioengineering and Biotransport Conference, Snowbird, UT, July 17-20, 2015. , Jul-2015

Articles in Peer-reviewed Journals Gadomski BC, McGilvray KC, Easley JT, Palmer RH, Jiao J, Li X, Qin Y-X, Puttlitz CM. "An investigation of shock wave therapy and low-intensity pulsed ultrasound on fracture healing under reduced loading conditions in an ovine model." J Orthop Res. 2018 Mar;36(3):921-9. Epub 2017 Aug 11. https://doi.org/10.1002/jor.23666 ; PubMed PMID: 28762588 [Note reported originally in Sept 2016 as in review at Bone with title "Shock wave therapy and low-intensity pulsed ultrasound accelerate bone formation rates under simulated microgravity loading conditions."] , Mar-2018
Articles in Peer-reviewed Journals Gadomski BC, Lerner ZF, Browning RC, Easley JT, Palmer RH, Puttlitz CM. "Computational characterization of fracture healing under reduced gravity loading conditions." J Orthop Res. 2016 Jul;34(7):1206-15. Epub 2016 Jan 8. https://dx.doi.org/10.1002/jor.23143 ; PubMed PMID: 26704186 , Jul-2016
Project Title:  Fracture Healing in Haversian Bone under Conditions of Simulated Microgravity Reduce
Fiscal Year: FY 2015 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/24/2011  
End Date: 06/30/2016  
Task Last Updated: 10/29/2015 
Download report in PDF pdf
Principal Investigator/Affiliation:   Puttlitz, Christian  Ph.D. / Colorado State University 
Address:  1374 Campus Delivery 
Department of Mechanical Engineering and School of Biomedical Engineering 
Fort Collins , CO 80523-1374 
Email: puttlitz@engr.colostate.edu 
Phone: 970-224-9743  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Colorado State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Browning, Raymond  Colorado State University 
Haussler, Kevin  Colorado State University 
McGilvray, Kirk  Colorado State University 
Santoni, Brandon  Foundation for Orthopaedic Research and Education 
Palmer, Ross  Colorado State University 
Easley, Jeremiah  Colorado State University 
Project Information: Grant/Contract No. NNX11AQ81G 
Responsible Center: NASA JSC 
Grant Monitor: Ploeger, Stephanne  
Center Contact:  
stephanne.l.ploeger22@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: NNX11AQ81G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Fracture:Risk of Bone Fracture due to Spaceflight-induced Changes to Bone (IRP Rev F)
Human Research Program Gaps: (1) Fracture01:We do not understand how the space flight environment affects bone fracture healing in-flight (IRP Rev E)
(2) Fracture02:We need to characterize the loads applied to bone for standard in-mission activities (IRP Rev E)
Flight Assignment/Project Notes: NOTE: Extended to 6/30/2016 per NSSC information (Ed., 9/28/15)

NOTE: Extended to 8/23/2015 per HRP and NSSC information (Ed., 10/21/2014)

Task Description: There is a need for information regarding hard and soft tissue healing in microgravity environments, and if impaired healing exists, what countermeasures can be called upon to enhance healing. Research on fracture healing using the rodent hindlimb suspension model shows healing is impaired in simulated microgravity, while clinical research shows that moderate, early mechanical loading caused by weight bearing induces osteogenesis and aids in repair of bone fracture. Further research is needed to determine what loads, if any, should be applied during spaceflight to promote fracture healing.

Most ground-based microgravity models utilize rodent hindlimb suspension to simulate how reduced loading affects isolated physiologic systems. Unfortunately, results derived from these studies are difficult to directly translate to the human condition due to major anatomic and physiologic differences between rodents and humans. Specifically, the differences in rodent and human bone structures become increasingly important when studying orthopaedic issues such as bone maintenance and healing during spaceflight. For example, the basic microstructure of rodent bone, known as “plexiform” bone, lacks the osteons (Haversion systems) that are the main micro-architectural feature of human cortical bone. Furthermore, it is known that the osteogenic and healing potential of rodent bone far exceeds that of adult human tissue.

Due to these limitations in current ground-based microgravity models, there exists a need to develop a ground-based, large animal model of fracture healing in simulated weightlessness that more closely approximates the human condition as has been done in the first year of this study. This animal model should be capable of simulating a wide spectrum of microgravity and able to investigate exercise protocols that may aid in the optimization of the fracture healing cascade. Four specific aims were defined to meet these goals: 1) Develop a ground-based large animal model of bone unloading in order to simulate full weightlessness; 2) interrogate the effects of a simulated microgravity environment on bone fracture healing in a large animal model; 3) develop a computational model of weightbearing in ovine bone under different experimental conditions in order to characterize the loads experienced by the fracture site; and 4) investigate possible countermeasures to the deleterious effects of weightlessness on fracture healing.

Research Impact/Earth Benefits: The data collected during the first year of this study clearly demonstrate that the ovine model of ground-based microgravity effectively simulates the bone loss experienced by astronauts in space and ground-based rodent hindlimb suspension. This model has a major advantage over rodent hindlimb suspension models in that the mature ovine bone structure is nearly identical to that of humans, and future studies utilizing this large animal model (i.e., how hard and soft tissues heal in a microgravity environment, which will be executed in year two of this grant) will be easily translated to the human condition. Furthermore, the study of fracture healing will benefit from the use of a large animal model rather than a rodent model since the healing potential of sheep more closely matches that of humans than rodents.

The ground-based experiments utilizing this large animal (ovine) model directly address the need to know how varying microgravity environments affect fracture healing, as well as determining the applied loads at the fracture healing site through inverse dynamics and finite element simulations. The fracture rehabilitation protocols explored within this study will also aid in determining which mechanical environment leads to enhanced bone healing under microgravity conditions. The data produced during this study will significantly advance the basic mechanobiology of fracture healing by discerning which mechanical signals and environments facilitate enhanced bone healing.

Task Progress & Bibliography Information FY2015 
Task Progress: Simulated microgravity-related alterations in fracture healing were investigated in this study. The employed methodology was based on (1) in vivo experimentation on skeletally mature female ewes to interrogate fracture healing and possible therapeutic countermeasures, and (2) finite element modeling of the ovine hindlimb under simulated microgravity and Earth gravity loading conditions to characterize the micromechanical environment of healing fractures.

In Specific Aim 1, a ground-based, ovine model of skeletal unloading was developed in order to simulate a microgravity loading condition. The external fixation unloading technique utilized in this model was able to induce mechanical unloading of the metatarsus and significant alterations in the relevant radiographical, biomechanical, and histomorphometric parameters characteristic of spaceflight. Specifically, the newly developed ovine model captured the characteristic decrease in osteoblast numbers and increase in osteoclast activity associated with human spaceflight. The unloading methodology developed in Specific Aim 1 was extended to the investigation of fracture healing in a simulated microgravity loading environment in Specific Aim 2. The findings of this study revealed that the mechanical loading environment dramatically affects the fracture healing cascade and resultant mineralized tissue strength, and that animals that healed in a reduced loading environment demonstrated significant reductions in healing rate and callus mechanical competency as compared to animals healing in a 1G Earth gravitational environment.

Specific Aim 3 outlined the development of a finite element of the ovine hindlimb in order to characterize the localized mechanical environment of a healing fracture in simulated microgravity and Earth gravitational environments. External fixation componentry was modeled to mimic the experimental methodology of Specific Aim 2 and correlate model predictions to experimental outcomes. The findings indicate that simulated microgravity unloading decreases hydrostatic stress and principal strain within the callus and fracture gap, resulting in primarily intramembranous bone formation rather than the endochondral bone formation pathway characteristic of Earth-based fracture healing.

Finally, in Specific Aim 4, two therapeutic countermeasures to the inhibited fracture healing of simulated microgravity unloading were investigated. The methodology of Specific Aim 2 was replicated, and shock wave therapy and low-intensity pulsed ultrasound were administered to animals healing in simulated microgravity and Earth gravitational loading environments. While fracture mechanical competency was not significantly altered following either countermeasure, both treatments significantly elevated osteoblast numbers and bone formation rates in simulated microgravity animals. The outcome of this study suggests that shock wave therapy and low-intensity pulsed ultrasound may be beneficial in situations involving aberrant fracture healing but elicit minimal modifications to the normal healing sequelae.

While the results reported in this dissertation work provide an initial foundation to the understanding of fracture healing in reduced gravitational loading environments and possible countermeasures to the negative effects of reduced mechanical loading, additional investigations are warranted. Further investigation of the dose-dependent relationship and long-term healing characteristics of shock wave therapy and low-intensity pulsed will provide valuable information regarding their efficacy as a countermeasure during long-duration spaceflight. These efforts, as well as the investigation of other countermeasures, should be part of future simulated microgravity fracture healing work.

Bibliography Type: Description: (Last Updated: 03/25/2020) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Gadomski BC, McGilvray KC, Easley JT, Palmer RH, Ruehlman D, Roberts M, Puttlitz CM. "Shock wave therapy does not enhance acute fracture strength but may accelerate formation rates under simulated microgravity conditions." 2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015.

2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015. , Jan-2015

Abstracts for Journals and Proceedings Gadomski BC, Lerner ZF, Browning RC, Puttlitz CM. "Finite element modeling of the ovine hindlimb for the investigation of microgravity-related mechaniobiological alterations." 61st Annual Meeting of the Orthopedic Research Society, Las Vegas, Nevada, March 28-31, 2015.

Proceedings of the 61st Annual Meeting of the Orthopedic Research Society, Las Vegas, Nevada, March 28-31, 2015. Poster 1530. , Mar-2015

Articles in Peer-reviewed Journals Gadomski BC, Lerner ZF, Browning RC, Easley JT, Palmer RH, Puttlitz CM. "Computational Characterization of Fracture Healing under Reduced Gravity Loading Conditions." J Orthpaed Res. In Review, as of October 2015. , Oct-2015
Articles in Peer-reviewed Journals Lerner ZF, Gadomski BC, Ipson A, Haussler KK, Puttlitz CM, Browning RC. "Modulating tibiofemoral contact force in the sheep hindlimb via treadmill walking: Predictions from an OpenSim musculoskeltal model." J Orthop Res. 2015 Aug;33(8):1128-33. Epub 2015 May 28. http://dx.doi.org/10.1002/jor.22829 ; PubMed PMID: 25721318 , Aug-2015
Articles in Peer-reviewed Journals Gadomski BC, McGilvray KC, Easley JT, Palmer RH, Santoni BG, Puttlitz CM. "Partial gravity unloading inhibits bone healing responses in a large animal model." J Biomech. 2014 Sep 22;47(12):2836-42. Epub 2014 Aug 7. http://dx.doi.org/10.1016/j.jbiomech.2014.07.031 ; PubMed PMID: 25138631 , Sep-2014
Papers from Meeting Proceedings Gadomski BC, Lerner ZF, Browning RC, Puttlitz CM. "A finite element investigation of fracture healing under simulated microgravity loading conditions." Presented at the Summer Biomechanics, Bioengineering, and Biotransport Conference, Snowbird, Utah, June 17-20, 2015.

Proceedings of the 2015 Summer Biomechanics, Bioengineering, and Biotransport Conference, Snowbird, Utah, June 17-20, 2015. Paper 2015-422. ISBN: 978-0-692-45599-9. , Jun-2015

Project Title:  Fracture Healing in Haversian Bone under Conditions of Simulated Microgravity Reduce
Fiscal Year: FY 2014 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/24/2011  
End Date: 06/30/2016  
Task Last Updated: 06/18/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   Puttlitz, Christian  Ph.D. / Colorado State University 
Address:  1374 Campus Delivery 
Department of Mechanical Engineering and School of Biomedical Engineering 
Fort Collins , CO 80523-1374 
Email: puttlitz@engr.colostate.edu 
Phone: 970-224-9743  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Colorado State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Browning, Raymond  Colorado State University 
Haussler, Kevin  Colorado State University 
McGilvray, Kirk  Colorado State University 
Santoni, Brandon  Foundation for Orthopaedic Research and Education 
Palmer, Ross  Colorado State University 
Easley, Jeremiah  Colorado State University 
Project Information: Grant/Contract No. NNX11AQ81G 
Responsible Center: NASA JSC 
Grant Monitor: Gilbert, Charlene  
Center Contact:  
charlene.e.gilbert@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: NNX11AQ81G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Fracture:Risk of Bone Fracture due to Spaceflight-induced Changes to Bone (IRP Rev F)
Human Research Program Gaps: (1) Fracture01:We do not understand how the space flight environment affects bone fracture healing in-flight (IRP Rev E)
(2) Fracture02:We need to characterize the loads applied to bone for standard in-mission activities (IRP Rev E)
Flight Assignment/Project Notes: NOTE: Extended to 6/30/2016 per NSSC information (Ed., 9/28/15)

NOTE: Extended to 8/23/2015 per HRP and NSSC information (Ed., 10/21/2014)

Task Description: There is a need for information regarding hard and soft tissue healing in microgravity environments, and if impaired healing exists, what countermeasures can be called upon to enhance healing. Research on fracture healing using the rodent hindlimb suspension model shows healing is impaired in simulated microgravity, while clinical research shows that moderate, early mechanical loading caused by weight bearing induces osteogenesis and aids in repair of bone fracture. Further research is needed to determine what loads, if any, should be applied during spaceflight to promote fracture healing.

Most ground-based microgravity models utilize rodent hindlimb suspension to simulate how reduced loading affects isolated physiologic systems. Unfortunately, results derived from these studies are difficult to directly translate to the human condition due to major anatomic and physiologic differences between rodents and humans. Specifically, the differences in rodent and human bone structures become increasingly important when studying orthopaedic issues such as bone maintenance and healing during spaceflight. For example, the basic microstructure of rodent bone, known as “plexiform” bone, lacks the osteons (Haversion systems) that are the main micro-architectural feature of human cortical bone. Furthermore, it is known that the osteogenic and healing potential of rodent bone far exceeds that of adult human tissue.

Due to these limitations in current ground-based microgravity models, there exists a need to develop a ground-based, large animal model of fracture healing in simulated weightlessness that more closely approximates the human condition as has been done in the first year of this study. This animal model should be capable of simulating a wide spectrum of microgravity and able to investigate exercise protocols that may aid in the optimization of the fracture healing cascade. Four specific aims were defined to meet these goals: 1) Develop a ground-based large animal model of bone unloading in order to simulate full weightlessness; 2) interrogate the effects of a simulated microgravity environment on bone fracture healing in a large animal model; 3) develop a computational model of weightbearing in ovine bone under different experimental conditions in order to characterize the loads experienced by the fracture site; and 4) investigate possible countermeasures to the deleterious effects of weightlessness on fracture healing.

Research Impact/Earth Benefits: The data collected during the first year of this study clearly demonstrate that the ovine model of ground-based microgravity effectively simulates the bone loss experienced by astronauts in space and ground-based rodent hindlimb suspension. This model has a major advantage over rodent hindlimb suspension models in that the mature ovine bone structure is nearly identical to that of humans, and future studies utilizing this large animal model (i.e., how hard and soft tissues heal in a microgravity environment which will be executed in year two of this grant) will be easily translated to the human condition. Furthermore, the study of fracture healing will benefit from the use of a large animal model rather than a rodent model since the healing potential of sheep more closely matches that of humans than rodents.

The ground-based experiments utilizing this large animal (ovine) model directly address the need to know how varying microgravity environments affect fracture healing, as well as determining the applied loads at the fracture healing site through inverse dynamics and finite element simulations. The fracture rehabilitation protocols explored within this study will also aid in determining which mechanical environment leads to enhanced bone healing under microgravity conditions. The data produced during this study will significantly advance the basic mechanobiology of fracture healing by discerning which mechanical signals and environments facilitate enhanced bone healing.

Task Progress & Bibliography Information FY2014 
Task Progress: Aim 1 (completed): To date, the work for Specific Aim 1 is 100% complete. The findings of Specific Aim 1 have been presented at the 2012 and 2013 NASA Human Research Program Investigators’ Workshops, the 2013 American Society of Mechanical Engineers Summer Bioengineering Conference, and have been submitted to the Journal of Biomechanics.

Aim 2: To date, the work for Specific Aim 2 is 100% complete. The findings of Specific Aim 2 have been presented at the 2014 NASA Human Research Program Investigators’ Workshop, and have been submitted to the Journal of Biomechanics.

Aim 3: Substantial progress has been made in the development of the musculoskeletal and finite element models of Specific Aim 3. To date, the musculoskeletal model has been validated and muscle forces have been incorporated in the finite element model. Additionally, the finite element model has successfully passed an in vitro and an in vivo validation process. Currently, external fixation and sham finite element models with mid-diaphyseal metatarsal fractures are being finalized. The final phase of Specific Aim 3 is ongoing and consists of utilizing the finite element models to predict the forces, stresses, and strains that are experienced at a simulated diaphyseal fracture site under varying degrees of microgravity. These predictions will be directly correlated with the histological data derived in Specific Aim 2 in order to delineate what specific mechanical signals (e.g., deviatoric stress, hydrostatic stress) are directing the fracture healing cascade under different microgravity environments.

Aim 4: Work on Specific Aim 4 has commenced with the investigation of shock wave therapy as a countermeasure to the inhibited fracture healing of microgravity. The first experimental group is currently undergoing shock wave treatment, and the expected completion date for biomechanical, microCT, and histomorphometric analyses of this portion of Specific Aim 4 is no later than November, 2014. Additionally, the in vivo investigation of low-intensity pulsed ultrasound as a countermeasure to inhibited fracture healing will commence in September, 2014 with an anticipated completion date for all biomechanical, microCT, and histomorphometric analyses no later than May 2015.

Bibliography Type: Description: (Last Updated: 03/25/2020) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Gadomski BC, Lerner ZF, Browing RC, Puttlitz CM. "Development and validation of a finite element model of the ovine hindlimb for the investigation of microgravity loading on skeletal tissue healing." 7th World Congress of Biomechanics, Boston, MA, July 6-11, 2014.

7th World Congress of Biomechanics, Boston, MA, July 6-11, 2014. , Jul-2014

Abstracts for Journals and Proceedings Gadomski BC, McGilvray KC, Easley JT, Palmer RH, Puttlitz CM. "Evaluation of Haversian bone fracture healing in simulated microgravity." 2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014.

2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014. http://www.hou.usra.edu/meetings/hrp2014/pdf/3095.pdf , Feb-2014

Abstracts for Journals and Proceedings Gadomski BC, McGilvray KC, Easley JT, Palmer RH, Puttlitz CM. "An ovine model of simulated microgravity." 2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012.

2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012. , Feb-2012

Articles in Peer-reviewed Journals Gadomski BC, McGilvray KC, Easley JT, Palmer RH, Ehrhart EJ, Haussler KK, Browning RC, Santoni BG, Puttlitz CM. "An in vivo ovine model of bone tissue alterations in simulated microgravity conditions." J Biomech Eng. 2014 Feb;136(2):021020. http://dx.doi.org/10.1115/1.4025854 ; PubMed PMID: 24170133 , Feb-2014
Articles in Peer-reviewed Journals Gadomski BC, McGilvray KC, Easley JT, Palmer RH, Ehrhart EJ, Haussler KK, Browning RC, Santoni BG, Puttlitz CM. "Gravity unloading inhibits bone healing responses in Haversian bone systems." Journal of Biomechanics, In Review, as of June 2014. , Jun-2014
Awards Gadomski B, McGilvray K, Easley J, Palmer R, Puttlitz C. "1st Place Overall Doctoral Student Paper Competition for: BC Gadomski, K C Mcgilvray, JT Easley, RH Palmer, CM Puttlitz. 'Simulating microgravity in a large animal model.' American Society of Mechanical Engineers 2013 Summer Bioengineering Conference, Sunriver, OR, June 26-29, 2013." Jun-2013
Project Title:  Fracture Healing in Haversian Bone under Conditions of Simulated Microgravity Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/24/2011  
End Date: 08/23/2014  
Task Last Updated: 06/23/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Puttlitz, Christian  Ph.D. / Colorado State University 
Address:  1374 Campus Delivery 
Department of Mechanical Engineering and School of Biomedical Engineering 
Fort Collins , CO 80523-1374 
Email: puttlitz@engr.colostate.edu 
Phone: 970-224-9743  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Colorado State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Browning, Raymond  Colorado State University 
Haussler, Kevin  Colorado State University 
McGilvray, Kirk  Colorado State University 
Ryan, Stewart  Colorado State University 
Santoni, Brandon  Foundation for Orthopaedic Research and Education 
Project Information: Grant/Contract No. NNX11AQ81G 
Responsible Center: NASA JSC 
Grant Monitor: Mullenax, Carol  
Center Contact: 281.244.7068 
carol.a.mullenax@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: NNX11AQ81G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Fracture:Risk of Bone Fracture due to Spaceflight-induced Changes to Bone (IRP Rev F)
Human Research Program Gaps: (1) Fracture01:We do not understand how the space flight environment affects bone fracture healing in-flight (IRP Rev E)
(2) Fracture02:We need to characterize the loads applied to bone for standard in-mission activities (IRP Rev E)
Task Description: There is a need for information regarding hard and soft tissue healing in microgravity environments, and if impaired healing exists, what countermeasures can be called upon to enhance healing. Research on fracture healing using the rodent hindlimb suspension model shows healing is impaired in simulated microgravity, while clinical research shows that moderate, early mechanical loading caused by weight bearing induces osteogenesis and aids in repair of bone fracture. Further research is needed to determine what loads, if any, should be applied during spaceflight to promote fracture healing.

Most ground-based microgravity models utilize rodent hindlimb suspension to simulate how reduced loading affects isolated physiologic systems. Unfortunately, results derived from these studies are difficult to directly translate to the human condition due to major anatomic and physiologic differences between rodents and humans. Specifically, the differences in rodent and human bone structures become increasingly important when studying orthopaedic issues such as bone maintenance and healing during spaceflight. For example, the basic microstructure of rodent bone, known as “plexiform” bone, lacks the osteons (Haversion systems) that are the main micro-architectural feature of human cortical bone. Furthermore, it is known that the osteogenic and healing potential of rodent bone far exceeds that of adult human tissue.

Due to these limitations in current ground-based microgravity models, there exists a need to develop a ground-based, large animal model of fracture healing in simulated weightlessness that more closely approximates the human condition as has been done in the first year of this study. This animal model should be capable of simulating a wide spectrum of microgravities and able to investigate exercise protocols that may aid in the optimization of the fracture healing cascade. Four specific aims were defined to meet these goals: 1) Develop a ground-based large animal model of bone unloading in order to simulate full weightlessness; 2) interrogate the effects of a simulated microgravity environment on bone fracture healing in a large animal model; 3) develop a computational model of weightbearing in ovine bone under different experimental conditions in order to characterize the loads experienced by the fracture site; and 4) develop treadmill protocols that enhance bone fracture healing in the presence of simulated microgravity.

Research Impact/Earth Benefits: The data collected during the first year of this study clearly demonstrate that the ovine model of ground-based microgravity effectively simulates the bone loss experienced by astronauts in space and ground-based rodent hindlimb suspension. This model has a major advantage over rodent hindlimb suspension models in that the mature ovine bone structure is nearly identical to that of humans, and future studies utilizing this large animal model (i.e., how hard and soft tissues heal in a microgravity environment which will be executed in year two of this grant) will be easily translated to the human condition. Furthermore, the study of fracture healing will benefit from the use of a large animal model rather than a rodent model since the healing potential of sheep more closely matches that of humans than rodents.

The ground-based experiments utilizing this large animal (ovine) model directly addresses the need to know how varying microgravity environments affect fracture healing, as well as determining the applied loads at the fracture healing site through inverse dynamics and finite element simulations. The fracture rehabilitation protocols explored within this study will also aid in determining which mechanical environment leads to enhanced bone healing under microgravity conditions. The data produced during this study will significantly advance the basic mechanobiology of fracture healing by discerning which mechanical signals and environments facilitate enhanced bone healing.

Task Progress & Bibliography Information FY2013 
Task Progress: Aim 1 (completed): To date, the work for Specific Aim 1 is 100% complete. The findings of Specific Aim 1 have been presented at the 2012 and 2013 NASA Human Research Program Investigators’ Workshops, the 2013 American Society of Mechanical Engineers Summer Bioengineering Conference, and have been submitted for publications to the Journal of Biomechanics.

Aim 2: Solid progress has been made in determining the effects of simulated microgravity on haversian bone healing in Specific Aim 2. Utilizing the previously characterized external fixation device, simulated microgravity was induced for a period of 3 weeks in an animal model resulting in a mean 18% loss in metatarsal bone mineral density. Following the 3-week simulated microgravity exposure period, a 3.0 mm ostectomy was created at the mid-diaphysis of the metatarsal bone and stabilized via an orthopaedic locking plate instrumented with a strain gage. Inhibited in vivo fracture healing occurred in the Microgravity Group as evidenced by an 18% percent increase in orthopaedic plate strain over the 4-week healing period versus a 98% decrease in orthopaedic plate strain in the Earth gravity control group. These findings were further substantiated by biomechanical four-point bending and micro-computed tomography results (µCT) which displayed a statistically significant 88% (p<0.01) decrease in 4-point bending stiffness between the Microgravity and Control Groups as well as an 11-fold (p<0.01) decrease in callus bone volume between the two groups.

Aim 3: Computational models of the sheep hindlimb were created in order to delineate the specific mechanical signals responsible for directing the fracture healing cascade. A musculoskeletal model of the full ovine hindlimb was created from the phalanges to the hip complete with all relevant muscular structures. Physiologic muscle moment arms and attachment sites of the limb were experimentally determined, and proper anthropometric properties of the hindlimb were acquired via dual-energy x-ray absorptiometry (DEXA) scans. In order to validate the musculoskeletal model, a treadmill experiment was performed wherein in vivo hindlimb motion were quantified via three-dimensional stereophotogrammetry, ground-reaction forces of the limb were acquired via a force plate positioned beneath the treadmill belt, and muscle activation was measured via electromyography (EMG) for speeds ranging from 0.25m/s to 1.0 m/s. Muscle activation predictions from the musculoskeletal model were then compared to the experimentally-derived EMG measurements for the various gate speeds in order to verify the model.

A finite element model of the hindlimb was created consisting of the phalanges, metatarsus, hock joint, tibia, and relevant ligamentous structures. Transversely isotropic material properties were assigned to the cortical and cancellous bone constituents while the articular cartilage was modeled with a mooney-rivlin hyperelastic material definition. The finite element model was validated via comparison to experimentally-derived metatarsal surface strain readings as well as three-dimensional stereophotogrammetry motion tracking during simulated hindlimb compression. Metatarsal surface strain and joint rotation predictions of the finite element model were within one standard deviation of the experimental values indicating satisfactory validation of the model.

The remaining three months in Year 2 will be utilized to complete the sample size of the in vivo fracture healing study. Additionally, decalcified and undecalcified histomorphometric analysis will be performed to quantify bone volume, mineralizing surface, mineral apposition rate, bone formation rate, and osteoblast and osteoclast numbers in the fracture callus and within the fracture gap. Computationally, model validation will be completed, and muscle forces predicted by the musculoskeletal model will be incorporated into the finite element model to begin ascertaining which specific mechanical signals are responsible for driving the fracture healing cascade.

Based upon the data generated to date, it is expected that the additional specimens of Specific Aim 2 will conclusively and statistically demonstrate that the mechanical unloading associated with spaceflight significantly inhibits haversian bone healing. The findings of Specific Aim 2 will motivate Specific Aim 4 in which therapeutic interventions capable of increasing the fracture healing cascade during simulated microgravity will be investigated with the direct application to human spaceflight.

Bibliography Type: Description: (Last Updated: 03/25/2020) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Gadomski BC, McGilvray KC, Easley JT, Palmer RH, Puttlitz CM. "Evaluation of a ground-based ovine model of simulated microgravity." 2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013.

2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013. , Feb-2013

Papers from Meeting Proceedings Gadomski B, McGilvray K, Easley J, Palmer R, Puttlitz C. "Simulating microgravity in a large animal model." Presented at the American Society of Mechanical Engineers 2013 Summer Bioengineering Conference, Sunriver, OR, June 26-29, 2013.

American Society of Mechanical Engineers 2013 Summer Bioengineering Conference, Sunriver, OR, June 26-29, 2013. Conference Proceedings. Paper SBC2013-14215. , Jun-2013

Project Title:  Fracture Healing in Haversian Bone under Conditions of Simulated Microgravity Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/24/2011  
End Date: 08/23/2014  
Task Last Updated: 06/26/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   Puttlitz, Christian  Ph.D. / Colorado State University 
Address:  1374 Campus Delivery 
Department of Mechanical Engineering and School of Biomedical Engineering 
Fort Collins , CO 80523-1374 
Email: puttlitz@engr.colostate.edu 
Phone: 970-224-9743  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Colorado State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Browning, Raymond  Colorado State University 
Haussler, Kevin  Colorado State University 
McGilvray, Kirk  Colorado State University 
Ryan, Stewart  Colorado State University 
Santoni, Brandon  Foundation for Orthopaedic Research and Education 
Project Information: Grant/Contract No. NNX11AQ81G 
Responsible Center: NASA JSC 
Grant Monitor: Maher, Jacilyn  
Center Contact:  
jacilyn.maher56@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: NNX11AQ81G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Fracture:Risk of Bone Fracture due to Spaceflight-induced Changes to Bone (IRP Rev F)
Human Research Program Gaps: (1) Fracture01:We do not understand how the space flight environment affects bone fracture healing in-flight (IRP Rev E)
(2) Fracture02:We need to characterize the loads applied to bone for standard in-mission activities (IRP Rev E)
Task Description: There is a need for information regarding hard and soft tissue healing in microgravity environments, and if impaired healing exists, what countermeasures can be called upon to enhance healing. Research on fracture healing using the rodent hindlimb suspension model shows healing is impaired in simulated microgravity, while clinical research shows that moderate, early mechanical loading caused by weight bearing induces osteogenesis and aids in repair of bone fracture. Further research is needed to determine what loads, if any, should be applied during spaceflight to promote fracture healing.

Most ground-based microgravity models utilize rodent hindlimb suspension to simulate how reduced loading affects isolated physiologic systems. Unfortunately, results derived from these studies are difficult to directly translate to the human condition due to major anatomic and physiologic differences between rodents and humans. Specifically, the differences in rodent and human bone structures become increasingly important when studying orthopaedic issues such as bone maintenance and healing during spaceflight. For example, the basic microstructure of rodent bone, known as “plexiform” bone, lacks the osteons (Haversion systems) that are the main micro-architectural feature of human cortical bone. Furthermore, it is known that the osteogenic and healing potential of rodent bone far exceeds that of adult human tissue.

Due to these limitations in current ground-based microgravity models, there exists a need to develop a ground-based, large animal model of fracture healing in simulated weightlessness that more closely approximates the human condition as has been done in the first year of this study. This animal model should be capable of simulating a wide spectrum of microgravities and able to investigate exercise protocols that may aid in the optimization of the fracture healing cascade. Four specific aims were defined to meet these goals: 1) Develop a ground-based large animal model of bone unloading in order to simulate full weightlessness; 2) interrogate the effects of a simulated microgravity environment on bone fracture healing in a large animal model; 3) develop a computational model of weightbearing in ovine bone under different experimental conditions in order to characterize the loads experienced by the fracture site; and 4) develop treadmill protocols that enhance bone fracture healing in the presence of simulated microgravity.

Research Impact/Earth Benefits: The data collected during the first year of this study clearly demonstrate that the ovine model of ground-based microgravity effectively simulates the bone loss experienced by astronauts in space and ground-based rodent hindlimb suspension. This model has a major advantage over rodent hindlimb suspension models in that the mature ovine bone structure is nearly identical to that of humans, and future studies utilizing this large animal model (i.e., how hard and soft tissues heal in a microgravity environment which will be executed in year two of this grant) will be easily translated to the human condition. Furthermore, the study of fracture healing will benefit from the use of a large animal model rather than a rodent model since the healing potential of sheep more closely matches that of humans than rodents. The ground-based experiments utilizing this large animal (ovine) model directly addresses the need to know how varying microgravity environments affect fracture healing, as well as determining the applied loads at the fracture healing site through inverse dynamics and finite element simulations. The fracture rehabilitation protocols explored within this study will also aid in determining which mechanical environment leads to enhanced bone healing under microgravity conditions. The data produced during this study will significantly advance the basic mechanobiology of fracture healing by discerning which mechanical signals and environments facilitate enhanced bone healing.

Task Progress & Bibliography Information FY2012 
Task Progress: Solid progress has been made in establishing the efficacy of the ground-based large animal model of simulated microgravity. In order to simulate microgravity on a large animal model, a transarticular external fixation device was created to reduce the load experienced by the metatarsal bone of the sheep hindlimb. Characterization of the external fixation device was performed by altering the number, material, and diameter of the fixation pins and connecting rods on the device and measuring the resultant decrease in load transferred through the metatarsal bone. The results of the characterization study show that a variety of microgravities may be studied by altering the design of the external fixation device. These data demonstrate that the study of other lunar gravities (Moon, Mars, etc.) is possible with this model. In order to test the in vivo efficacy of the model, two microgravity devices were implanted in an animal model for 8-weeks. Dual energy x-ray absorptiometry results demonstrated losses of 30%-50% in BMD between the treated and contralateral controls in the microgravity groups over 8 weeks, while no differences were observed in the sham group. These changes are further substantiated through micro-computed tomography (µCT) and histomorphometry results which display decreases of 18%-28%, 34%-38%, and 39%-48% in trabecular number, trabecular thickness, and bone volume respectively. Four-point bending tests displayed decreases of 41% in bending modulus between the treated and contralateral metatarsal bones, while diametral compression experiments demonstrated decreases between 25%-30% in diameteral failure load indicating that mechanical as well as radiographic changes occurred due to the simulated microgravity environment. The alterations in BMD with the current ovine microgravity model are similar to changes previously reported by Bloomfield et al. (Bone 2002) of 21% in 28 days and Vico et al. (Bone 1998) of 40% in 6 weeks using hindlimb unloading in skeletally mature male rats.

Computational models of the sheep hindlimb have also been created to assess the loading generated by the musculature and the stresses in the individual bones. A CT scan of a sheep hindlimb was utilized to construct the geometry of a musculoskeletal and finite element model. Appropriate muscles, tendons, and ligaments were attached to the musculoskeletal model, and validation will be performed via ground reaction forces and three-dimensional motion capture data acquired on a custom-built force measuring treadmill. The three-dimensional surfaces from the CT scan were then meshed and imported the finite element solver software. Material properties were assigned, and ligaments were attached. Mesh optimization and model validation will be performed via in vivo strain and kinematic measurements. The muscle and joint reaction forces from the musculoskeletal model will serve as inputs to the finite element model to quantify strain levels experienced in the metatarsal bone at various microgravity levels.

The remaining three months in Year 1 will complete the sample size of the in vivo animal model development, and computational model validation. Based upon the data generated to date, it is expected that these animal specimens will conclusively and statistically demonstrate that the current ovine microgravity model effectively simulates the decline in bone tissue (and associated mechanical properties) that accompanies long-term spaceflights. The architectural and physiological similarities between ovine and human bone will allow future results regarding bone fracture healing in various simulated microgravity environments using this model directly applicable to human spaceflight.

Bibliography Type: Description: (Last Updated: 03/25/2020) 

Show Cumulative Bibliography Listing
 
 None in FY 2012
Project Title:  Fracture Healing in Haversian Bone under Conditions of Simulated Microgravity Reduce
Fiscal Year: FY 2011 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/24/2011  
End Date: 08/23/2014  
Task Last Updated: 10/07/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Puttlitz, Christian  Ph.D. / Colorado State University 
Address:  1374 Campus Delivery 
Department of Mechanical Engineering and School of Biomedical Engineering 
Fort Collins , CO 80523-1374 
Email: puttlitz@engr.colostate.edu 
Phone: 970-224-9743  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Colorado State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Browning, Raymond  Colorado State University 
Haussler, Kevin  Colorado State University 
McGilvray, Kirk  Colorado State University 
Ryan, Stewart  Colorado State University 
Santoni, Brandon  Foundation for Orthopaedic Research and Education 
Project Information: Grant/Contract No. NNX11AQ81G 
Responsible Center: NASA JSC 
Grant Monitor: Baumann, David  
Center Contact:  
david.k.baumann@nasa.gov 
Solicitation / Funding Source: 2010 Crew Health NNJ10ZSA003N 
Grant/Contract No.: NNX11AQ81G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Fracture:Risk of Bone Fracture due to Spaceflight-induced Changes to Bone (IRP Rev F)
Human Research Program Gaps: (1) Fracture01:We do not understand how the space flight environment affects bone fracture healing in-flight (IRP Rev E)
(2) Fracture02:We need to characterize the loads applied to bone for standard in-mission activities (IRP Rev E)
Task Description: Ground-based models of weightlessness and microgravity have provided valuable insights into how dynamic physiological systems adapt or react to reduced loading. Almost all of these models have used rodent hind limb suspension as the means to simulate microgravity on isolated physiological systems. Unfortunately, results derived from these studies are significantly limited when one tries to translate them to the human condition due to significant anatomical and physiological differences between rodents and humans. This is especially relevant with regard to studying orthopaedic issues related to bone maintenance and fracture healing during spaceflight. Therefore, it is clear that a novel animal model of ground-based weightlessness that is directly translatable to the human condition needs to be developed in order for substantial progress to be made in our knowledge of how microgravity affects fracture healing. In light of this, we propose the following four specific aims: (1) develop a ground-based, ovine model of bone unloading in order to simulate full weightlessness, (2) interrogate the effects of a simulated microgravity environment on bone fracture healing using this large animal model, (3) develop a computational model of weightbearing in ovine bone under different experimental conditions in order to characterize the loads experienced by the fracture site, and (4) develop treadmill protocols that enhance bone fracture healing in the presence of simulated microgravity. Successful completion of this project will substantially elevate our understanding of how fracture site loading affects the subsequent healing cascade in the presence of microgravity and will form the foundation for designing future rehabilitation protocols to facilitate bone healing during long-duration spaceflight.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2011 
Task Progress: New project for FY2011.

Bibliography Type: Description: (Last Updated: 03/25/2020) 

Show Cumulative Bibliography Listing
 
 None in FY 2011