Iranian Journal of Veterinary Surgery

Iranian Journal of Veterinary Surgery

Histopathological and Biomechanical Survey on Effect of CoQ10 in Combination with Chitosan Conduit on Deep Digital Flexor Tendon Healing in Rabbits

Document Type : Original Article

Authors
Saba Moghadam
Amir Amniattalab
Department of Pathobiology, Faculty of Veterinary Medicine, Urmia Branch, Islamic Azad University, Urmia, Iran.
10.30500/ivsa.2020.195638.1193
Abstract
Objective- Chitosan is of great interest in regenerative medicine because of its plentiful properties, like biocompatibility, biodegradability and non-toxicity. The objective of the present study was histopathological and biomechanical survey on effect of CoQ10 in combination with chitosan conduit on deep digital flexor tendon (DDFT) healing in rabbits.
Design- Experimental Study
Animals- Eighteen healthy male white New Zealand rabbits
Procedures- The animals were randomized into three groups of 6 animals each. In Controlgroup the DDF tenotomy was performed and the stumps were sutured. In Chitosan group the DDF tenotomy was performed and the stumps were sutured and chitosan conduit was wrapped around the damaged area. In Chit-CoQ10 group the procedure was the same as Chitosan group as well as local administration of 100 µL CoQ10 (100 µg/rabbit) into the Chitosan conduit. The histopathological assessments including inflammation, angiogenesis and collagen fibers arrangement, and biomechanical assessments were performed after 8 weeks.
Results- Histopathological observations showed that the conduit was absorbed and adhesion around the tendon was deceased in Chitosan and Chit-CoQ10 groups. The biomechanical parameters showed significant improvement in Chit-CoQ10 group (p < 0.05). There were no noticeable signs of infection and tissue reaction in the granulation tissue in Chit-CoQ10 group compared to other groups (p < 0.05).
Conclusion and Clinical Relevance- Local administration of CoQ10 in combination with chitosan conduit could accelerate deep digital flexor tendon healing via decrease in adhesion around the tendon with no signs of excessive tissue reaction or infection in rabbits.
Keywords
Tendon healing
Chitosan Conduit
COQ10

Subjects

  1. Hogan MV, Bagayoko N, James R, Starnes T, Katz A, Chhabra AB. Tissue engineering solutions for tendon repair. Journal of the American Academy of Orthopaedic Surgeons, 2011; 19: 134–142.
  2. Majewski M, Schaeren S, Kohlhaas U, Ochsner PE.Postoperative rehabilitation after percutaneous Achilles tendon repair: early functional therapy versus cast immobilization. Disability and Rehabilitation, 2008; 30: 1726–1732.
  3. Sharma P, Maffulli N.Tendon injury and tendinopathy: healing and repair. The Journal of Bone and Joint Surgery, 2005; 87(1): 187-202.
  4. Melamed E, Beutel BG, Robinson D. Enhancement of acute tendon repair using chitosan matrix. American Journal of Orthopedics (Belle Mead, N.J.), 2015; 44(5): 212-216.
  5. Wang D, Mo J, Pan S, Chen H, Zhen H. Prevention of postoperative peritoneal adhesions by Ocarboxymethyl chitosan in a rat cecal abrasion model. Clinical and Investigative Medicine, 2010; 33(4): E254-E260.
  6. Yang Z, Cao H, Gao S, Yang M, Lyu J, Tang K. Effect of tendon stem cells in chitosan/β-glycerophosphate/collagen hydrogel on achilles tendon healing in a rat model. Medical Science Monitor, 2017; 23: 4633-4643
  7. Nivedhitha Sundaram M, Deepthi S, Mony U, Shalumon KT, Chen JP, Jayakumar R. Chitosan hydrogel scaffold reinforced with twisted poly (l lactic acid) aligned microfibrous bundle to mimic tendon extracellular matrix. International Journal of Biological Macromolecules, 2019; 122: 37-44.
  8. Cho MH, Kim KS, Ahn HH, Kim MS, Kim SH, Khang G, Lee B, Lee HB.Chitosan gel as an in situ–forming scaffold for rat bone marrow mesenchymal stem cells in vivo. Tissue Engineering, Part A, 2008; 14(6): 1099-1108.
  9. Khademhosseini A, Vacanti JP, Langer R. Progress in tissue engineering. Scientific American, 2009; 300(5): 64–71.
  10. Houghton PJ, Hylands PJ, Mensah AY, Hensel A, Deters AM. In vitro tests and ethnopharmacological investigations: wound healing as an example. Journal of Ethnopharmacology, 2005; 100(1-2): 100-107.
  11. Agyare C, Boakye YD, Bekoe EO, Hensel A, Dapaah SO, Appiah T. Review: African medicinal plants with wound healing properties. Journal of Ethnopharmacology, 2016; 177: 85-100.
  12. Ramirez-Tortosa MC, Granados S, Ramirez-Tortosa CL, Ochoa JJ, Camacho P, García-Valdés L, Battino M, Quiles JL. Oxidative stress status in liver mitochondria and lymphocyte DNA damage of atherosclerotic rabbits supplemented with water soluble coenzyme Q10. Biofactors, 2008: 32: 263–273.
  13. Mezawa M, Takemoto M, Onishi S, Ishibashi R, Ishikawa T, Yamaga M. Fujimoto M, Okabe E, He P,Kobayashi K. Yokote K. The reduced form of coenzyme Q10 improves glycemic control in patients with type 2 diabetes: An open label pilot study. Biofactors, 2012; 38; 416–421.
  14. Choi BS, Song HS, Kim HR, Park TW, Kim TD, Cho BJ, Kim CJ, Sim SS. Effect of coenzyme Q10 on cutaneous healing in skin-incised mice. Archives of Pharmacal Research, 2009: 32: 907–913.
  15.  Kitamura M, Akamatsu M, Machigashira M, Hara Y, Sakagami R, Hirofuji T, Hamachi T, Maeda K, Yokota M, Kido J, Nagata T, Kurihara H, Takashiba S, Sibutani T, Fukuda M, Noguchi T, Yamazaki K, Yoshie H, Ioroi K, Arai T, Nakagawa T, Ito K, Oda S, Izumi Y, Ogata Y, Yamada S, Shimauchi H, Kunimatsu K, Kawanami M, Fujii T, Furuichi Y, Furuuchi T, Sasano T, Imai E, Omae M, Yamada S, Watanuki M, Murakami S. FGF-2 stimulates periodontal regeneration: Results of a multi-center randomized clinical trial. Journal of Dental Research, 2011; 90: 35–40.
  16. Yoneda T, Tomofuji T, Kawabata Y, Ekuni D, Azuma T, Kataoka K, Kunitomo M, Morita M. Application of coenzyme Q10 for accelerating soft tissue wound healing after tooth extraction in rats. Nutrients, 2014; 6(12): 5756-5769.
  17. Jayasuriya A, Aryeai A and Jayatissa A. ZnO nanoparticles induced effects on nanomechanical behavior and cell viability of chitosan films. Materials Science and Engineering C: Materials for Biological Applications, 2013; 33(7): 3688-3696.
  18. Raisi A, Azizi S, Delirezh N, Heshmatian B and Amini K. Use of Chitosan Conduit for Bridging Small-Gap Peripheral Nerve Defect in Sciatic Nerve Transection Model of Rat. Iranian Journal of Veterinary Surgery, 2010; 5: 89-100.
  19. Yousefi A, Sarrafzadeh-Rezaei F, Asri-Rezaei S, Farshid AA, Behfar M. Fabrication of novel tubular scaffold for tendon repair from chitosan in combination with zinc oxide nanoparticles. Veterinary Research Forum, 2018: 9(2): 105-111.
  20. Raisi A, Azizi S, Delirezh N, Heshmatian B, Amini K. Use of chitosan conduit for bridging small-gap peripheral nerve defect in sciatic nerve transection model of rat. Iranian Journal of Veterinary Surgery, 2010; 5(1,2): 89-100.
  21.  Ao Q, Wang A, Cao W, Zhang L, Kong L, He Q, Gong Y, Zhang X. Manufacture of multimicrotubule chitosan nerve conduits with novel molds and characterization in vitro. Journal of Biomedical Materials Research Part A, 2006; 77(1): 11-18.
  22. Strickland JW.The scientific basis for advances in flexor tendon surgery. Journal of Hand Therapy, 2005; 18(2): 94-110.
  23. Muller SA, Todorov A, Heisterbach PE, Martin I, Majewski M. Tendon healing: an overview of physiology, biology, and pathology of tendon healing and systematic review of state of the art in tendon bioengineering. Knee Surgery, Sports Traumatology, Arthroscopy, 2015; 23(7): 2097-2105.
  24. Behfar M, Sarrafzadeh-Rezaei F, Hobbenaghi R, Dalirezh N, Dalir-Naghadeh B. Effects of uncultured adipose derived stromal vascular fraction on tendon healing in rabbits: A histological and immunohistochemical study. Iranian Journal of Veterinary Surgery, 2009; 4(1,2): 25-36.
  25. Dahlgren LA, van der Meulen MC, Bertram JE, Starrak GS, Nixon AJ. Insulin-like growth factor-I improves cellular and molecular aspects of healing in a collagenase-induced model of flexor tendinitis. Journal of Orthopaedic Research, 2002; 20(5): 910-919.
  26. Paul MD. Barbed sutures in aesthetic plastic surgery: evolution of thought and process. Aesthetic Surgery Journal, 2013; 33(3 Suppl): 17S-31S.
  27. Helary C, Desimone MF. Recent advances in biomaterials for tissue engineering and controlled drug delivery. Current Pharmaceutical Biotechnology, 2015; 16(7): 635-645.
  28. Ippolito E, Natali PG, Postacchini F, Accinni L, De Martino C. Ultrastructural and immunochemical evidence of actin in the tendon cells. Clinical Orthopaedics, 1977; 126: 282-284.
  29. Murray MM, Spector M. Fibroblast distribution in the anteromedial bundle of the human anterior cruciate ligament: the presence of alpha-smooth muscle actin- positive cells. Journal of Orthopaedic Research, 1999; 17: 18-27.
  30. Schurch W, Seemayer TA, Gabbiani G. The myofibroblast: a quarter century after its discovery. American Journal of Surgical Pathology 1998; 22: 141-147.
  31. Serini G, Gabbiani G. Mechanisms of myofibroblast activity and phenotypic modulation. Experimental Cell Research, 1999; 250: 273-283.
  32. Weiler A, Unterhauser FN, Bail HJ, Huning M, Haas NP. Alpha-smooth muscle actin is expressed by fibroblastic cells of the ovine anterior cruciate ligament and its free tendon graft during remodeling. Journal of Orthopaedic Research, 2002; 20: 310-317.
  33. O'Shea K1, Wolfe SW. Two-stage reconstruction with the modified Paneva-Holevich technique. Hand Clinics, 2013; 29(2): 223-233.
  34. Nishimura K, Nakamura RM, diZerega GS. Ibuprofen inhibition of postsurgical adhesion formation: a time and dose response biochemical evaluation in rabbits. Journal of Surgical Research, 1984; 36: 115-124.
  35. Nishimura K, Shimanuki T, diZerega GS. Ibuprofen in the prevention of experimentally induced postoperative adhesions. American Journal of Medicine, 1984; 77: 102-106.
  36. Duci SB, Arifi HM, Ahmeti HR, Manxhuka-Kerliu S, Neziri B, Mekaj AY, Lajqi S, Shahini L. Biomechanical and Macroscopic Evaluations of the Effects of 5-Fluorouracil on Partially Divided Flexor Tendon Injuries in Rabbits. Chinese Medical Journal (Engl,. 2015; 128(12): 1655-1661.
  37. Xia CS, Hong GX, Dou RR, Yang XY. Effects of chitosan on cell proliferation and collagen pro-duction of tendon sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes. Chinese Journal of Traumatololgy, 2005; 8: 369-374.
  38. Wu YF, Mao WF, Zhou YL, Wang XT, Liu PY, Tang JB. Adeno-associated virus-2-mediated TGF-β1 microRNA transfection inhibits adhesion formation after digital flexor tendon injury. Gene Therapy, 2016; 23(2): 167-175.
  39. Bonifasi-Lista C, Lake SP, Small MS, Weiss JA. Viscoelastic properties of the human medial collateral ligament under longitudinal, transverse and shear loading. Journal of Orthopaedic Research. 2005; 23(1): 67-76.

  • Receive Date 24 July 2019
  • Revise Date 02 November 2019
  • Accept Date 07 January 2020
  • First Publish Date 01 April 2020