Forces Associated with Launch into Space do not Impact Bone FractureHealing

摘要

Segmental bone defects (SBDs) secondary to trauma invariably result in a prolonged recovery with an extended period of limited weight bearing on the affected limb. Soldiers sustaining blast injuries and civilians sustaining high energy trauma typify such a clinical scenario. These patients frequently sustain composite injuries with SBDs in concert with extensive soft tissue damage. For soft tissue injury resolution and skeletal reconstruction a patient may experience limited weight bearing for upwards of 6 months.Many small animal investigations have evaluated interventions for SBDs. While providing foundational information regarding the treatment of bone defects, these models do not simulate limited weight bearing conditions after injury. For example, mice ambulate immediately following anesthetic recovery, and in most cases are normally ambulating within 1–3 days post-surgery. Thus, investigations that combine disuse with bone healing may better test novel bone healing strategies. To remove weight bearing, we have designed a SBD rodent healing study in microgravity (μG) on the International Space Station (ISS) for the Rodent Research-4 (RR-4) Mission, which launched February 19, 2017 on SpaceX CRS-10 (Commercial Resupply Services). In preparation for this mission, we conducted an end-to-end mission simulation consisting of surgicalinfliction of SBD followed by launch simulation and hindlimb unloading (HLU)studies. In brief, a 2 mm defect was created in the femur of 10 week-oldC57BL/6J male mice (n=9–10/group). Three days after surgery, 6groups of mice were treated as follows: 1) Vivarium Control (maintainedcontinuously in standard cages); 2) Launch Negative Control (placed in the samespaceflight-like hardware as the Launch Positive Control group but were notsubjected to launch simulation conditions); 3) Launch Positive Control (placedin spaceflight-like hardware and also subjected to vibration followed bycentrifugation); 4) Launch Positive Experimental (identical to Launch PositiveControl group, but placed in qualified spaceflight hardware); 5) HindlimbUnloaded (HLU, were subjected to HLU immediately after launch simulation teststo simulate unloading in spaceflight); and 6) HLU Control (single housed inidentical HLU cages but not suspended). Mice were euthanized 28 days afterlaunch simulation and bone healing was examined via micro-Computed Tomography(μCT). These studies demonstrated that the mice post-surgery cantolerate launch conditions. Additionally, forces and vibrations associated withlaunch did not impact bone healing (p=0.3). However, HLU resulted in a52.5% reduction in total callus volume compared to HLU Controls(p=0.0003). Taken together, these findings suggest that mice having afemoral SBD surgery tolerated the vibration and hypergravity associated withlaunch, and that launch simulation itself did not impact bone healing, but thatthe prolonged lack of weight bearing associated with HLU did impair bonehealing. Based on these findings, we proceeded with testing the efficacy of FDAapproved and novel SBD therapies using the unique spaceflight environment as anovel unloading model on SpaceX CRS-10.