Functional analysis of limb recovery following autograft treatment of volumetric muscle loss in the quadriceps femoris

• Type of Material: Article
• Authors: Mon Tzu Alice Li, Georgia Institute of Technology; Nick Willett, Emory University; Brent A. Uhrig, Georgia Institute of Technology; Robert Guldberg, Emory University; Gordon L. Warren, Georgia State University
• Language: English
• Date: 2014-06-27
• Publisher: ELSEVIER SCI LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jbiomech.2013.10.057
• Title of Journal or Parent Work: JOURNAL OF BIOMECHANICS
• Volume: 47
• Issue: 9
• Start Page: 2013
• End Page: 2021
• Grant/Funding Information: This work was supported by the U.S. Army Medical Research and Materiel Command (W81XWH-10-2-0006), the National Institute of Health (Grant #1F32AR061236-01), and the NIH Cell and Tissue Engineering training grant (NIH T32 GM008433).
• Keywords: Life Sciences & Biomedicine; SOFT-TISSUE INJURY; BONE REGENERATION; Muscle autograft; SENSORY REINNERVATION; Gait analysis; Preclinical model; OPERATION ENDURING FREEDOM; Biophysics; Muscle functional testing; Science & Technology; RAT MODEL; CATWALK GAIT ANALYSIS; Engineering; LOWER-EXTREMITY TRAUMA; Engineering, Biomedical; Technology; Volumetric muscle loss; EXTRACELLULAR-MATRIX; SKELETAL-MUSCLE; MASS PRESERVATION
• Research Categories: Biophysics, Medical; Engineering, Biomedical; Health Sciences, Medicine and Surgery

Abstract

Severe injuries to the extremities often result in muscle trauma and, in some cases, significant volumetric muscle loss (VML). These injuries continue to be challenging to treat, with few available clinical options, a high rate of complications, and often persistent loss of limb function. To facilitate the testing of regenerative strategies for skeletal muscle, we developed a novel quadriceps VML model in the rat, specifically addressing functional recovery of the limb. Our outcome measures included muscle contractility measurements to assess muscle function and gait analysis for evaluation of overall limb function. We also investigated treatment with muscle autografts, whole or minced, to promote regeneration of the defect area. Our defect model resulted in a loss of muscle function, with injured legs generating less than 55% of muscle strength from the contralateral uninjured control legs, even at 4 weeks post-injury. The autograft treatments did not result in significant recovery of muscle function. Measures of static and dynamic gait were significantly decreased in the untreated, empty defect group, indicating a decrease in limb function. Histological sections of the affected muscles showed extensive fibrosis, suggesting that this scarring of the muscle may be in part the cause of the loss of muscle function in this VML model. Taken together, these data are consistent with clinical findings of reduced muscle function in large VML injuries. This new model with quantitative functional outcome measures offers a platform on which to evaluate treatment strategies designed to regenerate muscle tissue volume and restore limb function.