Volumetric muscle loss leads to permanent disability following extremity trauma

Corona, Benjamin T.; Rivera, Jessica C.; Owens, Johnny G.; Wenke, Joseph C.; Rathbone, Christopher R.

doi:10.1682/jrrd.2014.07.0165

Cited by 198 publications

(150 citation statements)

References 20 publications

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“…Skeletal muscle has a robust capacity to recover from injury in which there is not a significant loss of the underlying ECM blueprint. However, when there is traumatic muscle injury and more than 20% of the muscle mass is lost (VML), the regenerative process will not resolve and there will be a functional deficit (Corona and others 2015; Garg and others 2014a; Grasman and others 2015; Grogan and others 2011). Though VML itself has been investigated, the response to VML in the aged population has yet to be explored.…”

Section: Discussionmentioning

confidence: 99%

“…Towards that end we are particularly interested in understanding the response of muscle to volumetric muscle loss injury (Corona and others 2015; Grogan and others 2011). In response to strains, contusions, and crush injuries, in which the myocytes and satellite cell pool are damaged but the underlying muscle structure is largely preserved, muscle has a strong capacity for regeneration (Hill and others 2003; Mauro 1961; Stratos and others 2013).…”

Section: Introductionmentioning

confidence: 99%

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Recovery from volumetric muscle loss injury: A comparison between young and aged rats

Kim

Kasukonis

Brown

et al. 2016

Experimental Gerontology

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Termed volumetric muscle loss (VML), the bulk loss of skeletal muscle tissue either through trauma or surgery overwhelms the capacity for repair, leading to the formation of non-contractile scar tissue. The myogenic potential, along with other factors that influence wound repair are known to decline with age. In order to develop effective treatment strategies for VML injuries that are effective across a broad range of patient populations, it is necessary to understand how the response to VML injury is affected by aging. Towards this end, this study was conducted to compare the response of young and aged animal groups to a lower extremity VML injury. Young (3 months, n=12) and aged (18 months, n=8) male Fischer 344 rats underwent surgical VML injury of the tibialis anterior muscle. Three months after VML injury it was found that young TA muscle was on average 16% heavier than aged muscle when no VML injury was performed and 25% heavier when comparing VML treated young and aged animals (p<0.0001, p<0.0001). Peak contractile force for both the young and aged groups was found to decrease significantly following VML injury, producing 65% and 59% of the contralateral limbs’ peak force, respectively (p<0.0001). However, there were no differences found for peak contractile force based on age, suggesting that VML affects muscle’s ability to repair, regardless of age. In this study, we used the ratio of collagen I to MyoD expression as a metric for fibrosis vs. myogenesis. Decreasing fiber cross-sectional area with advancing age (p<0.005) coupled with the ratio of collagen I to MyoD expression, which increased with age, supports the thought that regeneration is impaired in the aged population in favor of fibrosis (p=0.0241). This impairment is also exacerbated by the contribution of VML injury, where a 77-fold increase in the ratio of collagen I to MyoD was observed in the aged group (p<0.0002). The aged animal model described in this study provides a tool for investigators exploring not only the development of VML injury strategies but also the effect of aging on muscle regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recovery from volumetric muscle loss injury: A comparison between young and aged rats

Kim

Kasukonis

Brown

et al. 2016

Experimental Gerontology

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“…Additionally, the relative incidence of type III open fractures was high in extremity injuries, which also involve loss of surrounding soft tissue (e.g. VML injury) [Owens et al, 2007;Belmont et al, 2013;Corona et al, 2015]. Because of limitations in specifically tracking VML injury in clinical registries, it is currently not precisely known how many VML injuries occurred and what size VML in a specific muscle unit promoted significant loss of function.…”

Section: Clinical Observations Of Vml Injurymentioning

confidence: 99%

Pathophysiology of Volumetric Muscle Loss Injury

Corona

Wenke

Ward

2016

Cells Tissues Organs

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134

108

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Volumetric muscle loss (VML) injuries are prevalent in civilian and military trauma patients and are known to impart chronic functional deficits. The frank loss of muscle tissue that defines VML injuries is beyond the robust reparative and regenerative capacities of mammalian skeletal muscle. Given the nature of VML injuries, there is a clear need to develop therapies that promote de novo regeneration of skeletal muscle fibers, which can integrate with the remaining musculature and restore muscle strength. However, the pathophysiology of VML injuries is not completely defined, and, therefore, there may be other opportunities to improve functional outcomes other than de novo regeneration. Herein, clinical and preclinical studies of VML were reviewed to ascertain salient manifestations of VML injury that can impair limb function and muscle strength. The limited clinical data available highlighted proliferative fibrosis secondary to VML injury as a viable target to improve limb range of motion. Selected preclinical studies that used standardized neuromuscular functional assessments broadly identified that the muscle mass remaining after VML injury is performing suboptimally, and, therefore, percent VML strength deficits are significantly worse than can be explained by the initial frank loss of contractile machinery. Potential mechanisms of suboptimal strength of the remaining muscle mass suggested within the literature include intramuscular nerve damage, muscle architectural perturbations, and diminished transmission of force. Collectively, both clinical and preclinical data indicate a complex pathophysiology after VML that presents multiple therapeutic targets. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel

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“…Orthopedic extremity trauma is a major problem in both military and civilian populations, resulting in long‐term functional disability and substantial medical cost . Volumetric muscle loss (VML) injury is the traumatic loss or surgical removal of skeletal muscle that is often accompanied by severe neuromusculoskeletal injuries.…”

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confidence: 99%