Archives of Plastic Surgery

Korean Society of Plastic and Reconstructive Surgeons (대한성형외과학회)
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The Effects of Polydeoxyribonucleotide on the Survival of Random Pattern Skin Flaps in Rats

  • Chung, Kun Il (Department of Plastic and Reconstructive Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine) ;
  • Kim, Han Koo (Department of Plastic and Reconstructive Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine) ;
  • Kim, Woo Seob (Department of Plastic and Reconstructive Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine) ;
  • Bae, Tae Hui (Department of Plastic and Reconstructive Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine)
  • Received : 2013.01.21
  • Accepted : 2013.03.18
  • Published : 2013.05.15
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Abstract

Background Partial or complete necrosis of a skin flap is a common problem. Polydeoxyribonucleotide (PDRN) can be extracted from trout sperm and used as a tissue repair agent. The aim of this study was to investigate whether PDRN could improve the survival of random pattern skin flaps in rats. Methods Twenty-two male Sprague-Dawley rats were randomly divided into two groups: the PDRN treatment group (n=11) and the control group (n=11). Caudally pedicled random pattern skin flaps were elevated on their dorsal skin and resutured. The treatment group received daily intraperitoneal administration of PDRN (8 mg/kg/day), and the control group received fluid vehicle (NaCl 0.9%, 8 mg/kg/day) from day 0 to day 6. On day 7, the flap survival was evaluated and the harvested tissue surrounding the demarcation line of the necrotic area was stained with H&E, anti-rat vascular endothelial cell growth factor (VEGF) antibody, and PECAM-1/CD31 antibody. Results The average necrotic area of the flap in the PDRN group was significantly smaller when compared with that of the control group. Histologic and immunohistochemical evaluation showed that granulation thickness score and VEGF-positive staining cells were marked higher in the PDRN group than in the control group. PECAM-1/CD31-positive microvascular densities were significantly higher in the PDRN group when compared with the control group. Conclusions This study confirms that PDRN improves the survival of random pattern skin flaps in rats. These results may represent a new therapeutic approach to enhancing flap viability and achieving faster wound repair.

Keywords

References

  1. Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992;267: 10931-4.
  2. Akhavani MA, Sivakumar B, Paleolog EM, et al. Angiogenesis and plastic surgery. J Plast Reconstr Aesthet Surg 2008; 61:1425-37. https://doi.org/10.1016/j.bjps.2008.05.041
  3. Padubidri A, Browne E Jr. Effect of vascular endothelial growth factor (VEGF) on survival of random extension of axial pattern skin flaps in the rat. Ann Plast Surg 1996;37: 604-11. https://doi.org/10.1097/00000637-199612000-00006
  4. Kryger Z, Zhang F, Dogan T, et al. The effects of VEGF on survival of a random flap in the rat: examination of various routes of administration. Br J Plast Surg 2000;53:234-9. https://doi.org/10.1054/bjps.1999.3315
  5. Pierce GF, Tarpley JE, Yanagihara D, et al. Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessation of repair. Am J Pathol 1992;140:1375-88.
  6. Shukla A, Dubey MP, Srivastava R, et al. Differential expression of proteins during healing of cutaneous wounds in experimental normal and chronic models. Biochem Biophys Res Commun 1998;244:434-9. https://doi.org/10.1006/bbrc.1998.8286
  7. Tonello G, Daglio M, Zaccarelli N, et al. Characterization and quantitation of the active polynucleotide fraction (PDRN) from human placenta, a tissue repair stimulating agent. J Pharm Biomed Anal 1996;14:1555-60. https://doi.org/10.1016/0731-7085(96)01788-8
  8. Bianchini P, Tellini N, Morani AM, et al. Pharmacological data on polydeoxyribonucleotide of human placenta. Int J Tissue React 1981;3:151-4.
  9. Galeano M, Bitto A, Altavilla D, et al. Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse. Wound Repair Regen 2008;16: 208-17. https://doi.org/10.1111/j.1524-475X.2008.00361.x
  10. Montesinos MC, Desai A, Chen JF, et al. Adenosine promotes wound healing and mediates angiogenesis in response to tissue injury via occupancy of A(2A) receptors. Am J Pathol 2002;160:2009-18. https://doi.org/10.1016/S0002-9440(10)61151-0
  11. Montesinos MC, Gadangi P, Longaker M, et al. Wound healing is accelerated by agonists of adenosine A2 (G alpha s-linked) receptors. J Exp Med 1997;186:1615-20. https://doi.org/10.1084/jem.186.9.1615
  12. McFarlane RM, Deyoung G, Henry RA. The Design of a Pedicle Flap in the Rat to Study Necrosis and Its Prevention. Plast Reconstr Surg 1965;35:177-82. https://doi.org/10.1097/00006534-196502000-00007
  13. Bitto A, Polito F, Altavilla D, et al. Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model of peripheral artery occlusive disease. J Vasc Surg 2008;48: 1292-300. https://doi.org/10.1016/j.jvs.2008.06.041
  14. Gurunluoglu R, Meirer R, Shafighi M, et al. Gene therapy with adenovirus-mediated VEGF enhances skin flap prefabrication. Microsurgery 2005;25:433-41. https://doi.org/10.1002/micr.20142
  15. Thellung S, Florio T, Maragliano A, et al. Polydeoxyribonucleotides enhance the proliferation of human skin fibroblasts: involvement of A2 purinergic receptor subtypes. Life Sci 1999;64:1661-74. https://doi.org/10.1016/S0024-3205(99)00104-6
  16. Altavilla D, Squadrito F, Polito F, et al. Activation of adenosine A2A receptors restores the altered cell-cycle machinery during impaired wound healing in genetically diabetic mice. Surgery 2011;149:253-61. https://doi.org/10.1016/j.surg.2010.04.024
  17. Guizzardi S, Galli C, Govoni P, et al. Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: a new proposal for bone tissue repair. Life Sci 2003;73:1973-83. https://doi.org/10.1016/S0024-3205(03)00547-2
  18. Bitto A, Galeano M, Squadrito F, et al. Polydeoxyribonucleotide improves angiogenesis and wound healing in experimental thermal injury. Crit Care Med 2008;36:1594-602. https://doi.org/10.1097/CCM.0b013e318170ab5c
  19. Sini P, Denti A, Cattarini G, et al. Effect of polydeoxyribonucleotides on human fibroblasts in primary culture. Cell Biochem Funct 1999;17:107-14. https://doi.org/10.1002/(SICI)1099-0844(199906)17:2<107::AID-CBF815>3.0.CO;2-#
  20. Polito F, Bitto A, Galeano M, et al. Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps. J Vasc Surg 2012;55:479-88. https://doi.org/10.1016/j.jvs.2011.07.083
  21. Lazzarotto M, Tomasello EM, Caporossi A. Clinical evaluation of corneal epithelialization after photorefractive keratectomy in patients treated with polydeoxyribonucleotide (PDRN) eye drops: a randomized, double-blind, placebocontrolled trial. Eur J Ophthalmol 2004;14:284-9. https://doi.org/10.1177/112067210401400402
  22. Rubegni P, De Aloe G, Mazzatenta C, et al. Clinical evaluation of the trophic effect of polydeoxyribonucleotide (PDRN) in patients undergoing skin explants. A Pilot Study. Curr Med Res Opin 2001;17:128-31. https://doi.org/10.1185/0300799039117047
  23. De Aloe G, Rubegni P, Biagioli M, et al. Skin graft donor site and use of polydeoxyribonucleotide as a treatment for skin regeneration: a randomized, controlled, double-blind, clinical trial. Wounds 2004;16:258-63.
  24. Altavilla D, Bitto A, Polito F, et al. Polydeoxyribonucleotide (PDRN): a safe approach to induce therapeutic angiogenesis in peripheral artery occlusive disease and in diabetic foot ulcers. Cardiovasc Hematol Agents Med Chem 2009;7:313-21. https://doi.org/10.2174/187152509789541909

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