{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:08:44Z","timestamp":1792789724037,"version":"4.5.0"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["K12HD073945"],"award-info":[{"award-number":["K12HD073945"]}]},{"award":["K12HD073945"],"award-info":[{"award-number":["K12HD073945"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University of Tennessee, Knoxville","id":[{"id":"https:\/\/ror.org\/020f3ap87","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/020f3ap87","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Muscles"],"abstract":"<jats:p>Residual muscles after amputation experience mechanical unloading, loss of distal tendon insertion, and reduced excursion, conditions known to cause muscle degeneration. However, the architecture of residual muscles following amputation remains largely unreported. In this pilot, exploratory study, five healthy, skeletally mature, male New Zealand white rabbits underwent unilateral hind-paw ankle disarticulation. The contralateral intact limb served as the within-subject control. Six hindlimb muscles that cross the intact biological ankle were harvested bilaterally at four weeks post-amputation, and muscle mass, length, fiber length, pennation angle, sarcomere length, optimal fiber length (OFL), and physiologic cross-sectional area (PCSA) were measured. All statistical comparisons were based on raw, paired differences in values between sides. Muscle mass and OFL were, on average, lower on the residual side for all muscles; raw differences between sides were significant for mass of LG (p = 0.029) and FDS (p = 0.026) and for OFL of LG (p = 0.026). Based on percent difference between sides, degeneration was most severe in the soleus, which had 63 \u00b1 26% less mass and 51 \u00b1 40% lower optimal fiber length in the residual limb than in the intact contralateral limb. Despite lower mass, average PCSA was generally preserved or increased (though differences were not statistically significant) across all muscles except FDS; this was possibly attributable to disproportionately greater reductions in optimal fiber length than in mass. These results have important potential implications for prosthesis function and, therefore, motivate additional research to identify influential factors and evaluate clinical strategies for preserving residual muscle architecture.<\/jats:p>","DOI":"10.3390\/muscles5030065","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:09:17Z","timestamp":1789553357000},"page":"65","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bilateral Muscle Architecture Differences in a Rabbit Model of Unilateral Hindlimb Transtibial Amputation: A Pilot Study"],"prefix":"10.3390","volume":"5","author":[{"given":"Caleb","family":"Stubbs","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Tickle College of Engineering, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Patrick T.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tickle College of Engineering, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5874-7164","authenticated-orcid":false,"given":"Allison J.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tickle College of Engineering, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Samantha Z.","family":"Bratcher","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tickle College of Engineering, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Alicia A.","family":"Matavosian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tickle College of Engineering, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Cheryl B.","family":"Greenacre","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Bryce J.","family":"Burton","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Stacy M.","family":"Stephenson","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Remigiusz M.","family":"Grzeskowiak","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Alisha P.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-8968","authenticated-orcid":false,"given":"Xiaojuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Office of Innovative Technologies, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-7591","authenticated-orcid":false,"given":"David E.","family":"Anderson","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Dustin L.","family":"Crouch","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tickle College of Engineering, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"036008","DOI":"10.1088\/1741-2552\/aa61bc","article-title":"Musculoskeletal model-based control interface mimics physiologic hand dynamics during path tracing task","volume":"14","author":"Crouch","year":"2017","journal-title":"J. Neural Eng."},{"key":"ref_2","unstructured":"Kyberd, P.J. (2021). Making Hands: A History of Prosthetic Arms, Elsevier."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"041004","DOI":"10.1088\/1741-2552\/ac1176","article-title":"Myoelectric control of robotic lower limb prostheses: A review of electromyography interfaces, control paradigms, challenges and future directions","volume":"18","author":"Fleming","year":"2021","journal-title":"J. Neural. Eng."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/SLA.0000000000003895","article-title":"Reinventing Extremity Amputation in the Era of Functional Limb Restoration","volume":"273","author":"Herr","year":"2021","journal-title":"Ann. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1152\/jappl.1952.5.5.195","article-title":"Biomechanical Consideration in Cineplasty","volume":"5","author":"Blaschke","year":"1952","journal-title":"J. Appl. Physiol."},{"key":"ref_6","first-page":"357","article-title":"Cineplasty as a control input for externally powered prosthetic components","volume":"38","author":"Weir","year":"2001","journal-title":"J. Rehabil. Res. Dev."},{"key":"ref_7","unstructured":"Easton, K., Stubbs, C., Billings, C., Bowers, K., Stephenson, S., Greenacre, C., Anderson, D., and Crouch, D. (2022, January 21\u201325). Muscle-Driven, Implanted Foot-Ankle Prosthesis: Preliminary In Vivo Biomechanics. Proceedings of the North American Congress on Biomechanics 2022, Ottawa, CA, USA."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110599","DOI":"10.1016\/j.jbiomech.2021.110599","article-title":"Understanding lower limb muscle volume adaptations to amputation","volume":"125","author":"Henson","year":"2021","journal-title":"J. Biomech."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/j.apmr.2021.02.008","article-title":"Trunk Muscle Characteristics: Differences Between Sedentary Adults With and Without Unilateral Lower Limb Amputation","volume":"102","author":"Sions","year":"2021","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1007\/s10439-021-02858-0","article-title":"Changes in Tissue Composition and Load Response After Transtibial Amputation Indicate Biomechanical Adaptation","volume":"49","author":"Bramley","year":"2021","journal-title":"Ann. Biomed. Eng."},{"key":"ref_11","first-page":"359","article-title":"Muscle and tendon: Properties, models, scaling, and application to biomechanics and motor control","volume":"17","author":"Zajac","year":"1989","journal-title":"Crit. Rev. Biomed. Eng."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Crouch, D.L., Hall, P.T., Stubbs, C., Billings, C., Pedersen, A.P., Burton, B., Greenacre, C.B., Stephenson, S.M., and Anderson, D.E. (2022). Feasibility of Implanting a Foot-Ankle Endoprosthesis within Skin in a Rabbit Model of Transtibial Amputation. Bioengineering, 9.","DOI":"10.3390\/bioengineering9080348"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/0014-4886(82)90104-2","article-title":"Architectural Alterations of Rat Hind-Limb Skeletal Muscles Immobilized at Different Lengths","volume":"76","author":"Spector","year":"1982","journal-title":"Exp. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S0006-3495(84)84246-0","article-title":"Sarcomere length determination using laser diffraction. Effect of beam and fiber diameter","volume":"45","author":"Lieber","year":"1984","journal-title":"Biophys. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/jmor.1051990108","article-title":"Skeletal muscle architecture of the rabbit hindlimb: Functional implications of muscle design","volume":"199","author":"Lieber","year":"1989","journal-title":"J. Morphol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/S0021-9290(00)00051-8","article-title":"The isometric functional capacity of muscles that cross the elbow","volume":"33","author":"Murray","year":"2000","journal-title":"J. Biomech."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/jmor.1051730206","article-title":"Architecture of the hind limb muscles of cats: Functional significance","volume":"173","author":"Sacks","year":"1982","journal-title":"J. Morphol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1113\/jphysiol.1972.sp009891","article-title":"Physiological and structural changes in the cat\u2019s soleus muscle due to immobilization at different lengths by plaster casts","volume":"224","author":"Tabary","year":"1972","journal-title":"J. Physiol."},{"key":"ref_19","first-page":"424","article-title":"The Effect of Tenotomy on the Structure of Fast and Slow Muscle in the Rabbit","volume":"49","author":"McMinn","year":"1964","journal-title":"Q. J. Exp. Physiol. Cogn. Med. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1682\/JRRD.2010.09.0189","article-title":"Residual limb volume change: Systematic review of measurement and management","volume":"48","author":"Sanders","year":"2011","journal-title":"J. Rehabil. Res. Dev."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Roy, S., Mathew-Steiner, S.S., and Sen, C.K. (2019). Residual limb health and prosthetics. Prosthesis, IntechOpen.","DOI":"10.5772\/intechopen.83819"},{"key":"ref_22","first-page":"1","article-title":"Muscle fibre size and number following immobilisation atrophy","volume":"163","author":"Nicks","year":"1989","journal-title":"J. Anat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1136\/ard.49.5.316","article-title":"Use of intermittent stretch in the prevention of serial sarcomere loss in immobilised muscle","volume":"49","author":"Williams","year":"1990","journal-title":"Ann. Rheum. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1152\/jappl.1995.79.5.1744","article-title":"Effect of skeletal muscle fiber type on the pressor response evoked by static contraction in rabbits","volume":"79","author":"Wilson","year":"1995","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s12668-016-0288-8","article-title":"The Influence of Hindlimb Unloading on Bone and Muscle Tissues in Rat Model","volume":"7","author":"Baltina","year":"2017","journal-title":"BioNanoScience"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gao, Y., Arfat, Y., Wang, H., and Goswami, N. (2018). Muscle Atrophy Induced by Mechanical Unloading: Mechanisms and Potential Countermeasures. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00235"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1093\/gerona\/gly040","article-title":"The Contributions of Fiber Atrophy, Fiber Loss, In Situ Specific Force, and Voluntary Activation to Weakness in Sarcopenia","volume":"73","author":"McPhee","year":"2018","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s00441-018-2955-2","article-title":"Skeletal muscle fibrosis: An overview","volume":"375","author":"Mahdy","year":"2019","journal-title":"Cell Tissue Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/aor.13575","article-title":"Optimizing the decellularization process of an upper limb skeletal muscle; implications for muscle tissue engineering","volume":"44","author":"Naik","year":"2020","journal-title":"Artif. Organs"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e5315","DOI":"10.21769\/BioProtoc.5315","article-title":"Dissection and Whole-Mount Immunofluorescent Staining of Mouse Hind Paw Muscles for Neuromuscular Junction Analysis","volume":"15","author":"Simkin","year":"2025","journal-title":"Bio-Protocol"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Dubuisson, N., Versele, R., Planchon, C., Selvais, C.M., Noel, L., Abou-Samra, M., and Davis-L\u00f3pez de Carrizosa, M.A. (2022). Histological Methods to Assess Skeletal Muscle Degeneration and Regeneration in Duchenne Muscular Dystrophy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232416080"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jbspin.2007.04.019","article-title":"Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy","volume":"75","author":"Marinelli","year":"2008","journal-title":"Jt. Bone Spine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2279","DOI":"10.21769\/BioProtoc.2279","article-title":"Muscle Histology Characterization Using H&E Staining and Muscle Fiber Type Classification Using Immunofluorescence Staining","volume":"7","author":"Wang","year":"2017","journal-title":"Bio-Protocol"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"190","DOI":"10.2106\/JBJS.16.00335","article-title":"Histological Evidence of Muscle Degeneration in Advanced Human Rotator Cuff Disease","volume":"99","author":"Gibbons","year":"2017","journal-title":"J. Bone Jt. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1302\/0301-620X.45B1.60","article-title":"Plastic Treatment of the Muscles and Bone in Amputation Surgery","volume":"45-B","author":"Dederich","year":"1963","journal-title":"J. Bone Jt. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.2106\/00004623-200505000-00016","article-title":"Early quadriceps strength loss after total knee arthroplasty. The contributions of muscle atrophy and failure of voluntary muscle activation","volume":"87","author":"Mizner","year":"2005","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1123\/jab.2013-0334","article-title":"Short Communication: Pennation Angle Variability in Human Muscle","volume":"30","author":"Infantolino","year":"2014","journal-title":"J. Appl. Biomech."}],"container-title":["Muscles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2813-0413\/5\/3\/65\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:22:26Z","timestamp":1789705346000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2813-0413\/5\/3\/65"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["muscles5030065"],"URL":"https:\/\/doi.org\/10.3390\/muscles5030065","relation":{},"ISSN":["2813-0413"],"issn-type":[{"value":"2813-0413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}