Repairing Volumetric Muscle Loss in the Ovine Peroneus Tertius Following a 3-Month Recovery

Novakova, Stoyna; Rodriguez, Brittany L.; Vega-Soto, Emmanuel E; Nutter, Genevieve P; Armstrong, Rachel; Macpherson, Peter; Larkin, Lisa M.

doi:10.1089/ten.tea.2019.0288

Cited by 22 publications

(17 citation statements)

References 45 publications

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“…To translate these findings towards clinically relevant injuries, researchers implanted allogeneic SMUs into a VML injury in the peroneus tertius muscle of sheep. Sheep implanted with SMUs and engineered neural conduits (ENC; SMU+ENC) maintained increased muscle mass and increased muscle contraction 3 months post injury compared to sheep who did not receive treatment [36]. While the results of this study demonstrated that implantation of SMU+ENC scaffolds improved VML recovery, the extent of force recovery was less than that observed in the prior rat studies, possibly a result of the increased reliance on the diffusion of nutrients into the implanted construct [36].…”

Section: Animal Species Used In Vml Studiesmentioning

confidence: 52%

“…The most common animals employed in VML studies are rodents (mice and rats), although larger mammals such as sheep, canines, and pigs have also been studied due to their clinically relevant size [36,37]. Approximately 88% of studies examining decellularized extracellular matrix (ECM) implant materials on VML injuries utilized mouse or rat models, while only 12% utilized larger animal models such as sheep, dogs, and pigs [37].…”

Section: Animal Species Used In Vml Studiesmentioning

confidence: 99%

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Recent Trends in Injury Models to Study Skeletal Muscle Regeneration and Repair

2020

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Skeletal muscle injuries that occur from traumatic incidents, such as those caused by car accidents or surgical resections, or from injuries sustained on the battlefield, result in the loss of functionality of the injured muscle. To understand skeletal muscle regeneration and to better treat these large scale injuries, termed volumetric muscle loss (VML), in vivo injury models exploring the innate mechanisms of muscle injury and repair are essential for the creation of clinically applicable treatments. While the end result of a muscle injury is often the destruction of muscle tissue, the manner in which these injuries are induced as well as the response from the innate repair mechanisms found in muscle in each animal models can vary. This targeted review describes injury models that assess both skeletal muscle regeneration (i.e., the response of muscle to myotoxin or ischemic injury) and skeletal muscle repair (i.e., VML injury). We aimed to summarize the injury models used in the field of skeletal muscle tissue engineering, paying particular attention to strategies to induce muscle damage and how to standardize injury conditions for future experiments.

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Section: Animal Species Used In Vml Studiesmentioning

confidence: 52%

Section: Animal Species Used In Vml Studiesmentioning

confidence: 99%

Recent Trends in Injury Models to Study Skeletal Muscle Regeneration and Repair

2020

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“…In this study, we sought to address the gap in craniofacial VML knowledge by creating a large animal model of facial VML. In our previous VML studies, we used our engineered skeletal muscle units (SMUs) to treat a 30% VML in both large and small animal models [23,24]. These studies demonstrated significant functional recovery of the SMU-treated groups compared to unrepaired negative controls.…”

Section: Plos Onementioning

confidence: 99%

“…Muscle progenitor cells including satellite cells were isolated as described previously [23,24,[29][30][31][32][33][34]. Briefly, muscle biopsies between 3g and 3.5g were sanitized in 70% ethanol and finely minced with a razor blade.…”

Section: Cell Isolationmentioning

confidence: 99%

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A tissue engineering approach for repairing craniofacial volumetric muscle loss in a sheep following a 2, 4, and 6-month recovery

et al. 2020

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Volumetric muscle loss (VML) is the loss of skeletal muscle that results in significant and persistent impairment of function. The unique characteristics of craniofacial muscle compared trunk and limb skeletal muscle, including differences in gene expression, satellite cell phenotype, and regenerative capacity, suggest that VML injuries may affect craniofacial muscle more severely. However, despite these notable differences, there are currently no animal models of craniofacial VML. In a previous sheep hindlimb VML study, we showed that our lab's tissue engineered skeletal muscle units (SMUs) were able to restore muscle force production to a level that was statistically indistinguishable from the uninjured contralateral muscle. Thus, the goals of this study were to: 1) develop a model of craniofacial VML in a large animal model and 2) to evaluate the efficacy of our SMUs in repairing a 30% VML in the ovine zygomaticus major muscle. Overall, there was no significant difference in functional recovery between the SMU-treated group and the unrepaired control. Despite the use of the same injury and repair model used in our previous study, results showed differences in pathophysiology between craniofacial and hindlimb VML. Specifically, the craniofacial model was affected by concomitant denervation and ischemia injuries that were not exhibited in the hindlimb model. While clinically realistic, the additional ischemia and denervation likely created an injury that was too severe for our SMUs to repair. This study highlights the importance of balancing the use of a clinically realistic model while also maintaining control over variables related to the severity of the injury. These variables include the volume of muscle removed, the location of the VML injury, and the geometry of the injury, as these affect both the muscle's ability to self-regenerate as well as the probability of success of the treatment.

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Gait biomechanics: A clinically relevant outcome measure for preclinical research of musculoskeletal trauma

Motherwell

Hendershot

Goldman

et al. 2021

Journal Orthopaedic Research

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Traumatic injuries to the musculoskeletal system are the most prevalent of those suffered by United States Military Service members and accounts for two‐thirds of initial hospital costs to the Department of Defense. These combat‐related wounds often leave survivors with life‐long disability and represent a significant impediment to the readiness of the fighting force. There are immense opportunities for the field of tissue engineering and regenerative medicine (TE/RM) to address these musculoskeletal injuries through regeneration of damaged tissues as a means to restore limb functionality and improve quality of life for affected individuals. Indeed, investigators have made promising advancements in the treatment for these injuries by utilizing small and large preclinical animal models to validate therapeutic efficacy of next‐generation TE/RM‐based technologies. Importantly, utilization of a comprehensive suite of functional outcome measures, particularly those designed to mimic data collected within the clinical setting, is critical for successful translation and implementation of these therapeutics. To that end, the objective of this review is to emphasize the clinical relevance and application of gait biomechanics as a functional outcome measure for preclinical research studies evaluating the efficacy of TE/RM therapies to treat traumatic musculoskeletal injuries. Specifically, common musculoskeletal injuries sustained by service members—including volumetric muscle loss, post‐traumatic osteoarthritis, and composite tissue injuries—are examined as case examples to highlight the use of gait biomechanics as an outcome measure using small and large preclinical animal models.

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Repairing Volumetric Muscle Loss in the Ovine Peroneus Tertius Following a 3-Month Recovery

Cited by 22 publications

References 45 publications

Recent Trends in Injury Models to Study Skeletal Muscle Regeneration and Repair

Recent Trends in Injury Models to Study Skeletal Muscle Regeneration and Repair

A tissue engineering approach for repairing craniofacial volumetric muscle loss in a sheep following a 2, 4, and 6-month recovery

Gait biomechanics: A clinically relevant outcome measure for preclinical research of musculoskeletal trauma

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