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J Reconstr Microsurg 2020; 36(01): 041-052
DOI: 10.1055/s-0039-1694740
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Doxorubicin-Immersed Skeletal Muscle Grafts Promote Peripheral Nerve Regeneration Across a 10-mm Defect in the Rat Sciatic Nerve

Hisataka Takeuchi
1   Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Akio Sakamoto
1   Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Ryosuke Ikeguchi
1   Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Soichi Ota
1   Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Hiroki Oda
1   Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Hirofumi Yurie
1   Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Sadaki Mitsuzawa
1   Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Shuichi Matsuda
1   Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
› Author Affiliations Funding None.
Further Information

Publication History

25 February 2019

23 June 2019

Publication Date:
13 August 2019 (online)

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Erratum: Doxorubicin-Immersed Skeletal Muscle Grafts Promote Peripheral Nerve Regeneration Across a 10-mm Defect in the Rat Sciatic NerveJ Reconstr Microsurg 2020; 36(01): e1-e2
DOI: 10.1055/s-0039-3400529

Abstract

Background The treatment of peripheral nerve defects requires bridging materials. Skeletal muscle grafts have been studied as an alternative to nerve autografts because they contain longitudinally aligned basal laminar tubes that are similar to axons. Several pretreatment methods for muscle grafts have promoted axonal regeneration. Here, a new method of doxorubicin pretreatment was used, and the efficacy of the pretreated muscle graft was evaluated in a rat model of a sciatic nerve defect.

Methods A rat model of a 10-mm sciatic nerve defect was analyzed in three settings: muscle grafts with and without doxorubicin pretreatment (M-graft-w-Dox and M-graft-w/o-Dox groups, respectively) and a nerve autograft group (N-graft) (n = 6/group). The M-graft-w-Dox group was immersed in a doxorubicin solution for 10 minutes and rinsed with saline. Analyses of target muscle atrophy, electrophysiology, and histology were performed 8 weeks after grafting.

Results Electrophysiological parameters and target muscle atrophy were significantly superior in the M-graft-w-Dox group compared with the M-graft-w/o-Dox group. Histological assessment revealed the presence of a significantly greater number of regenerated axons in the M-graft-w-Dox group versus the M-graft-w/o-Dox group, while there were no significant differences between the M-graft-w-Dox and N-graft groups. The diameter of myelinated axons of the regenerated nerve in the M-graft-w-Dox group was significantly larger than that in the M-graft-w/o-Dox group, while it was not significantly different compared with the N-graft group.

Conclusion Pretreatment of muscle grafts with doxorubicin promoted significant peripheral nerve regeneration. This method may represent a new option for the treatment of peripheral nerve defects.

Keywords

peripheral nerve - doxorubicin - pretreatment - muscle - graft - nerve regeneration
 

  • References

  • 1 Deumens R, Bozkurt A, Meek MF. , et al. Repairing injured peripheral nerves: bridging the gap. Prog Neurobiol 2010; 92 (03) 245-276
    CrossrefPubMedGoogle Scholar
  • 2 Rochkind S, Shainberg A. Muscle response to complete peripheral nerve injury: changes of acetylcholine receptor and creatine kinase activity over time. J Reconstr Microsurg 2017; 33 (05) 352-357
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Griffin JW, Hogan MV, Chhabra AB, Deal DN. Peripheral nerve repair and reconstruction. J Bone Joint Surg Am 2013; 95 (23) 2144-2151
    CrossrefPubMedGoogle Scholar
  • 4 Lad SP, Nathan JK, Schubert RD, Boakye M. Trends in median, ulnar, radial, and brachioplexus nerve injuries in the United States. Neurosurgery 2010; 66 (05) 953-960
    CrossrefPubMedGoogle Scholar
  • 5 Meek MF, Varejão AS, Geuna S. Use of skeletal muscle tissue in peripheral nerve repair: review of the literature. Tissue Eng 2004; 10 (7-8): 1027-1036
    CrossrefPubMedGoogle Scholar
  • 6 Lee SJ, Zhu W, Nowicki M. , et al. 3D printing nano conductive multi-walled carbon nanotube scaffolds for nerve regeneration. J Neural Eng 2018; 15 (01) 016018
    CrossrefPubMedGoogle Scholar
  • 7 Ding T, Zhu C, Yin JB. , et al. Slow-releasing rapamycin-coated bionic peripheral nerve scaffold promotes the regeneration of rat sciatic nerve after injury. Life Sci 2015; 122: 92-99
    CrossrefPubMedGoogle Scholar
  • 8 Roth F, Fernandes M, Valente SG. , et al. Platelet-rich fibrin conduits as an alternative to nerve autografts for peripheral nerve repair. J Reconstr Microsurg 2017; 33 (08) 549-556
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Sobotka S, Chen J, Nyirenda T, Mu L. Outcomes of muscle reinnervation with direct nerve implantation into the native motor zone of the target muscle. J Reconstr Microsurg 2017; 33 (02) 77-86
    PubMedGoogle Scholar
  • 10 Ide C. Nerve regeneration through the basal lamina of the skeletal muscle. Neurosci Res 1984; 1: 379-391
    CrossrefPubMedGoogle Scholar
  • 11 Glasby MA, Gschmeissner SG, Hitchcock RJ, Huang CL. The dependence of nerve regeneration through muscle grafts in the rat on the availability and orientation of basement membrane. J Neurocytol 1986; 15 (04) 497-510
    CrossrefPubMedGoogle Scholar
  • 12 Glasby MA, Gilmour JA, Gschmeissner SE, Hems TE, Myles LM. The repair of large peripheral nerves using skeletal muscle autografts: a comparison with cable grafts in the sheep femoral nerve. Br J Plast Surg 1990; 43 (02) 169-178
    CrossrefPubMedGoogle Scholar
  • 13 Hall SM, Enver K. Axonal regeneration through heat pretreated muscle autografts. An immunohistochemical and electron microscopic study. J Hand Surg [Br] 1994; 19 (04) 444-451
    CrossrefPubMedGoogle Scholar
  • 14 Mligiliche N, Tabata Y, Endoh K, Ide C. Peripheral nerve regeneration through a long detergent-denatured muscle autografts in rabbits. Neuroreport 2001; 12 (08) 1719-1722
    CrossrefPubMedGoogle Scholar
  • 15 Hems TE, Glasby MA. The limit of graft length in the experimental use of muscle grafts for nerve repair. J Hand Surg [Br] 1993; 18 (02) 165-170
    CrossrefPubMedGoogle Scholar
  • 16 Bertelli JA, Taleb M, Mira JC, Ghizoni MF. The course of aberrant reinnervation following nerve repair with fresh or denatured muscle autografts. J Peripher Nerv Syst 2005; 10 (04) 359-368
    CrossrefPubMedGoogle Scholar
  • 17 Marcoccio I, Vigasio A. Muscle-in-vein nerve guide for secondary reconstruction in digital nerve lesions. J Hand Surg Am 2010; 35 (09) 1418-1426
    CrossrefPubMedGoogle Scholar
  • 18 Tos P, Battiston B, Ciclamini D, Geuna S, Artiaco S. Primary repair of crush nerve injuries by means of biological tubulization with muscle-vein-combined grafts. Microsurgery 2012; 32 (05) 358-363
    CrossrefPubMedGoogle Scholar
  • 19 Pereira JH, Bowden REM, Gattuso JM, Norris RW. Comparison of results of repair of digital nerves by denatured muscle grafts and end-to-end sutures. J Hand Surg [Br] 1991; 16 (05) 519-523
    CrossrefPubMedGoogle Scholar
  • 20 Santo Neto H, Teodori RM, Somazz MC, Marques MJ. Axonal regeneration through muscle autografts submitted to local anaesthetic pretreatment. Br J Plast Surg 1998; 51 (07) 555-560
    CrossrefPubMedGoogle Scholar
  • 21 Meek MF, den Dunnen WF, Schakenraad JM, Robinson PH. Evaluation of several techniques to modify denatured muscle tissue to obtain a scaffold for peripheral nerve regeneration. Biomaterials 1999; 20 (05) 401-408
    CrossrefPubMedGoogle Scholar
  • 22 Segredo MP, Salvadori DM, Rocha NS. , et al. Oxidative stress on cardiotoxicity after treatment with single and multiple doses of doxorubicin. Hum Exp Toxicol 2014; 33 (07) 748-760
    CrossrefPubMedGoogle Scholar
  • 23 Campbell TL, Quadrilatero J. Data on skeletal muscle apoptosis, autophagy, and morphology in mice treated with doxorubicin. Data Brief 2016; 7: 786-793
    Google Scholar
  • 24 Min K, Kwon O-S, Smuder AJ. , et al. Increased mitochondrial emission of reactive oxygen species and calpain activation are required for doxorubicin-induced cardiac and skeletal muscle myopathy. J Physiol 2015; 593 (08) 2017-2036
    CrossrefPubMedGoogle Scholar
  • 25 van Norren K, van Helvoort A, Argilés JM. , et al. Direct effects of doxorubicin on skeletal muscle contribute to fatigue. Br J Cancer 2009; 100 (02) 311-314
    CrossrefPubMedGoogle Scholar
  • 26 Ueno M, Kakinuma Y, Yuhki K. , et al. Doxorubicin induces apoptosis by activation of caspase-3 in cultured cardiomyocytes in vitro and rat cardiac ventricles in vivo. J Pharmacol Sci 2006; 101 (02) 151-158
    CrossrefPubMedGoogle Scholar
  • 27 Lundborg G, Dahlin LB, Danielsen N. , et al. Nerve regeneration in silicone chambers: influence of gap length and of distal stump components. Exp Neurol 1982; 76 (02) 361-375
    CrossrefPubMedGoogle Scholar
  • 28 Kakinoki R, Nishijima N, Ueba Y, Oka M, Yamamuro T. Relationship between axonal regeneration and vascularity in tubulation--an experimental study in rats. Neurosci Res 1995; 23 (01) 35-45
    PubMedGoogle Scholar
  • 29 Ronchi G, Fornasari BE, Crosio A. , et al. Chitosan tubes enriched with fresh skeletal muscle fibers for primary nerve repair. BioMed Res Int 2018; 2018: 9175248
    PubMedGoogle Scholar
  • 30 Whitworth IH, Doré C, Hall S, Green CJ, Terenghi G. Different muscle graft denaturing methods and their use for nerve repair. Br J Plast Surg 1995; 48 (07) 492-499
    CrossrefPubMedGoogle Scholar
  • 31 Mokarram N, Merchant A, Mukhatyar V, Patel G, Bellamkonda RV. Effect of modulating macrophage phenotype on peripheral nerve repair. Biomaterials 2012; 33 (34) 8793-8801
    CrossrefPubMedGoogle Scholar
  • 32 Cattin AL, Burden JJ, Van Emmenis L. , et al. Macrophage-induced blood vessels guide Schwann cell-mediated regeneration of peripheral nerves. Cell 2015; 162 (05) 1127-1139
    CrossrefPubMedGoogle Scholar
  • 33 Jia Y, Yang W, Zhang K. , et al. Nanofiber arrangement regulates peripheral nerve regeneration through differential modulation of macrophage phenotypes. Acta Biomater 2019; 83: 291-301
    CrossrefPubMedGoogle Scholar
  • 34 Kansal S, Tandon R, Verma A. , et al. Coating doxorubicin-loaded nanocapsules with alginate enhances therapeutic efficacy against Leishmania in hamsters by inducing Th1-type immune responses. Br J Pharmacol 2014; 171 (17) 4038-4050
    CrossrefPubMedGoogle Scholar
  • 35 Kansal S, Tandon R, Dwivedi P. , et al. Development of nanocapsules bearing doxorubicin for macrophage targeting through the phosphatidylserine ligand: a system for intervention in visceral leishmaniasis. J Antimicrob Chemother 2012; 67 (11) 2650-2660
    CrossrefPubMedGoogle Scholar
  • 36 Cortes EP, Holland JF, Glidewell O. Amputation and adriamycin in primary osteosarcoma: a 5-year report. Cancer Treat Rep 1978; 62 (02) 271-277
    PubMedGoogle Scholar
  • 37 Mohajeri M, Sahebkar A. Protective effects of curcumin against doxorubicin-induced toxicity and resistance: a review. Crit Rev Oncol Hematol 2018; 122: 30-51
    CrossrefPubMedGoogle Scholar
  • 38 Lebrecht D, Setzer B, Ketelsen UP, Haberstroh J, Walker UA. Time-dependent and tissue-specific accumulation of mtDNA and respiratory chain defects in chronic doxorubicin cardiomyopathy. Circulation 2003; 108 (19) 2423-2429
    CrossrefPubMedGoogle Scholar