Developing a combat-relevant translatable large animal model of heterotopic ossification
Richard T. Epperson,
Brad M. Isaacson,
David L. Rothberg,
Raymond E. Olsen,
Brooke Kawaguchi,
John M. Maxwell,
Mary Dickerson,
Paul F. Pasquina,
John Shero,
Dustin L. Williams
Affiliations
Richard T. Epperson
University of Utah, Bone & Biofilm Research Laboratory, Salt Lake City, UT, United States of America; University of Utah, Department of Orthopaedics, Salt Lake City, UT, United States of America; Corresponding author at: Biomedical Polymers Research Building, 20 S 2030 E, Salt Lake City, UT 84112, United States of America.
Brad M. Isaacson
University of Utah, Department of Orthopaedics, Salt Lake City, UT, United States of America; The Geneva Foundation, Tacoma, WA, United States of America; The Center for Rehabilitation Sciences Research, Uniformed Services University, Bethesda, MD, United States of America
David L. Rothberg
University of Utah, Bone & Biofilm Research Laboratory, Salt Lake City, UT, United States of America; University of Utah, Department of Orthopaedics, Salt Lake City, UT, United States of America
Raymond E. Olsen
University of Utah, Department of Orthopaedics, Salt Lake City, UT, United States of America
Brooke Kawaguchi
University of Utah, Bone & Biofilm Research Laboratory, Salt Lake City, UT, United States of America; University of Utah, Department of Orthopaedics, Salt Lake City, UT, United States of America
John M. Maxwell
University of Utah, Bone & Biofilm Research Laboratory, Salt Lake City, UT, United States of America; University of Utah, Department of Orthopaedics, Salt Lake City, UT, United States of America
Mary Dickerson
University of Utah, Office of Comparative Medicine, Salt Lake City, UT, United States of America
Paul F. Pasquina
The Center for Rehabilitation Sciences Research, Uniformed Services University, Bethesda, MD, United States of America; Department of Rehabilitation, Walter Reed National Military Medical Center, Bethesda, MD, United States of America
John Shero
The Center for Rehabilitation Sciences Research, Uniformed Services University, Bethesda, MD, United States of America; Extremity Trauma Center of Excellence, Joint Base San Antonio Fort Sam Houston, San Antonio, TX, United States of America
Dustin L. Williams
University of Utah, Bone & Biofilm Research Laboratory, Salt Lake City, UT, United States of America; University of Utah, Department of Orthopaedics, Salt Lake City, UT, United States of America; The Center for Rehabilitation Sciences Research, Uniformed Services University, Bethesda, MD, United States of America; University of Utah, Department of Pathology, Salt Lake City, UT, United States of America; University of Utah, Department of Bioengineering, Salt Lake City, UT, United States of America
Heterotopic ossification (HO) refers to ectopic bone formation, typically in residual limbs following trauma and injury. A review of injuries from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) indicated that approximately 70% of war wounds involved the musculoskeletal system, largely in part from the use of improvised explosive devices (IED) and rocket-propelled grenades (RPG). HO is reported to occur in approximately 63%–65% of wounded warriors from OIF and OEF. Symptomatic HO may delay rehabilitation regimens since it often requires modifications to prosthetic limb componentry and socket size. There is limited evidence indicating a mechanism for preventing HO. This may be due to inadequate models, which do not produce HO bone structure that is morphologically similar to HO samples obtained from wounded warfighters injured in theatre. We hypothesized that using a high-power blast of air (shockwave) and simulated battlefield trauma (i.e. bone damage, tourniquet, bacteria, negative pressure wound therapy) in a large animal model, HO would form and have similar morphology to ectopic bone observed in clinical samples. Initial radiographic and micro-computed tomography (CT) data demonstrated ectopic bone growth in sheep 24 weeks post-procedure. Advanced histological and backscatter electron (BSE) analyses showed that 5 out of 8 (63%) sheep produced HO with similar morphology to clinical samples. We conclude that not all ectopic bone observed by radiograph or micro-CT in animal models is HO. Advanced histological and BSE analyses may improve confirmation of HO presence and morphology, which we demonstrated can be produced in a large animal model.
