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 space flight. 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:
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 space flight. Specifically, the newly developed ovine model captured the characteristic decrease in osteoblast numbers and increase in osteoclast activity associated with human space flight. 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.
No datasets exist for this study. A final report was archived.
|Mission||Launch/Start Date||Landing/End Date||Duration|