Neurological
heterotopic ossification (NHO) is characterized by abnormal bone growth in soft tissue and joints in response to injury to the central nervous system. The ectopic bone frequently causes
pain, restricts mobility, and decreases the quality of life for those affected. NHO commonly develops in severe
traumatic brain injury (TBI) patients, particularly in the presence of concomitant musculoskeletal
injuries (i.e.
polytrauma). There are currently no animal models that accurately mimic these combinations of
injuries, which has limited our understanding of NHO pathobiology, as well as the development of
biomarkers and treatments, in TBI patients. In order to address this shortcoming, here we present a novel rat model that combines TBI,
femoral fracture, and muscle
crush injury. Young adult male Sprague Dawley rats were randomly assigned into three different injury groups: triple
sham-injury, peripheral injury only (i.e.,
sham-TBI + fracture + muscle injury) or triple injury (i.e., TBI + fracture + muscle injury). Evidence of ectopic bone in the injured hind-limb, as confirmed by micro-computed tomography (μCT), was found at 6-weeks post-injury in 70% of triple injury rats, 20% of peripheral injury rats, and 0% of the
sham-injured controls. Furthermore, the triple injury rats had higher ectopic bone severity scores than the
sham-injured group. This novel model will provide a platform for future studies to identify underlying mechanisms,
biomarkers, and develop evidence based pharmacological treatments to combat this debilitating long-term complication of TBI and
polytrauma.