Developing a combat-relevant translatable large animal model of heterotopic ossification

Area of Science:

• Orthopedics
• Regenerative Medicine
• Trauma Surgery

Background:

• Heterotopic ossification (HO) is ectopic bone formation common in residual limbs after trauma, affecting 63-65% of warfighters from OIF/OEF.
• Symptomatic HO complicates rehabilitation by necessitating prosthetic modifications.
• Current animal models inadequately replicate the morphology of clinical HO samples.

Purpose of the Study:

• To develop a large animal model that produces HO with morphology similar to clinical samples from wounded warfighters.
• To investigate the potential of simulated battlefield trauma to induce HO.

Main Methods:

• A large animal model (sheep) was subjected to a high-power air blast (shockwave) and simulated battlefield trauma (bone damage, tourniquet, bacteria, negative pressure wound therapy).
• Radiography and micro-computed tomography (CT) were used for initial assessment.
• Advanced histological and backscatter electron (BSE) analyses were performed for morphological confirmation.

Main Results:

• Ectopic bone growth was observed in sheep 24 weeks post-procedure.
• Histological and BSE analyses confirmed HO with similar morphology to clinical samples in 5 out of 8 (63%) sheep.
• Not all ectopic bone detected by radiography or micro-CT represents true HO.

Conclusions:

• A large animal model utilizing simulated battlefield trauma can successfully produce HO with clinically relevant morphology.
• Advanced histological and BSE analyses are crucial for accurate HO confirmation and characterization.
• This model provides a foundation for developing effective HO prevention strategies.