Aesthetic Plastic Surgery

, Volume 43, Issue 4, pp 1071–1077 | Cite as

Effect of Polydeoxyribonucleotide on Chondrocutaneous Composite Grafts Survival

  • Jae Won Heo
  • Yong Hun Kim
  • Eon Su Kim
  • Sug Won Kim
  • Jiye KimEmail author
Original Article Basic Science/Experimental



A composite graft is considered the best choice for facial reconstruction because of proper texture, color, and simple surgical techniques. However, due to revascularization by the bridging phenomenon, it has limitations with unpredictable survival rates and can be applied only to small defects. Polydeoxyribonucleotide (PDRN) plays an important role in multiple vascular processes such as angiogenesis via production of a vascular endothelial growth factor and by providing an anti-inflammatory effect by reducing pro-inflammatory cytokines through the adenosine A2 receptor stimulation. Thus, here, we investigated PDRN as a supportive method to improve survival of composite grafts.


Chondrocutaneous composite grafts were applied to both ears of 20 New Zealand White rabbits. The grafts were then rotated and returned to their positions to prevent the original blood flow from the base of the grafts. On postoperative days 1, 3, 6, 9, and 12, PDRN was injected intradermally into the experimental group (20 ears) and normal saline was injected into the control group (20 ears) to exclude bias of pressure effect. After 12 days, graft survival and cutaneous blood flow were examined under laser speckle contrast imaging.


Gross observation indicated that the graft viability in the PDRN group was significantly higher than that in the control group (p < 0.05). Through laser speckle contrast imaging, signal intensity increased from the periphery and progressed centrally with treatment.


Our findings suggest that PDRN may increase blood flow around at the base of the graft, restore the perfusion, and improve the survival of the composite grafts.

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Polydeoxyribonucleotides Tissue transplantation Graft survival 



This work was supported (in part) by the Yonsei University miraeseondo project of 2017 (2017-52-0064).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights

The Animal Care and Experiment Committee of Yonsei Wonju University approved the experimental protocol.

Informed Consent

For this type of study, informed consent is not required.


  1. 1.
    Hong JP (2018) Flap classification and applications. In: Neligan PC (ed) Plastic surgery, 4th edn. Elsevier Saunders, Philadelphia, pp 336–432Google Scholar
  2. 2.
    Scherer SS, Pietramaggiori G, Orgill DP (2018) Skin graft. In: Neligan PC (ed) Plastic surgery, 4th edn. Elsevier Saunders, Philadelphia, pp 214–230Google Scholar
  3. 3.
    Eberlin KR, Busa K, Bae DS, Waters PM, Labow BI, Taghinia AH (2015) Composite grafting for pediatric fingertip injuries. Hand (N Y) 10:28–33CrossRefGoogle Scholar
  4. 4.
    Son D, Kwak M, Yun S, Yeo H, Kim J, Han K (2012) Large auricular chondrocutaneous composite graft for nasal alar and columellar reconstruction. Arch Plast Surg 39:323–328CrossRefGoogle Scholar
  5. 5.
    El-Hennawi DM (2001) Cartilage perichondrium composite graft (CPCG) in pediatric tympanoplasty. Int J Pediatr Otorhinolaryngol 59:1–5CrossRefGoogle Scholar
  6. 6.
    Hartman DF, Goode RL (1987) Pharmacologic enhancement of composite graft survival. Arch Otolaryngol Head Neck Surg 113:720–723CrossRefGoogle Scholar
  7. 7.
    Eo S, Hur G, Cho S, Azari KK (2009) Successful composite graft for fingertip amputations using ice-cooling and lipo-prostaglandin E1. J Plast Reconstr Aesthet Surg 62:764–770CrossRefGoogle Scholar
  8. 8.
    Li EN, Menon NG, Rodriguez ED, Norkunas M, Rosenthal RE, Goldberg NH, Silverman RP (2004) The effect of hyperbaric oxygen therapy on composite graft survival. Ann Plast Surg 53:141–145CrossRefGoogle Scholar
  9. 9.
    Tonello G, Daglio M, Zaccarelli N, Sottofattori E, Mazzei M, Balbi A (1996) Characterization and quantitation of the active polynucleotide fraction (PDRN) from human placenta, a tissue repair stimulating agent. J Pharm Biomed Anal 14:1555–1560CrossRefGoogle Scholar
  10. 10.
    Galeano M, Bitto A, Altavilla D, Minutoli L, Polito F, Calo M, Lo Cascio P, Stagno d’Alcontres F, Squadrito F (2008) Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse. Wound Repair Regen 16:208–217CrossRefGoogle Scholar
  11. 11.
    Montesinos MC, Desai A, Chen JF, Yee H, Schwarzschild MA, Fink JS, Cronstein BN (2002) Adenosine promotes wound healing and mediates angiogenesis in response to tissue injury via occupancy of A(2A) receptors. Am J Pathol 160:2009–2018CrossRefGoogle Scholar
  12. 12.
    Briers JD, Webster S (1996) Laser speckle contrast analysis (LASCA): a nonscanning, full-field technique for monitoring capillary blood flow. J Biomed Opt 1:174–179CrossRefGoogle Scholar
  13. 13.
    Jeon YR, Kang EH, Yang CE, Yun IS, Lee WJ, Lew DH (2014) The effect of platelet-rich plasma on composite graft survival. Plast Reconstr Surg 134:239–246CrossRefGoogle Scholar
  14. 14.
    Choi B, Kang NM, Nelson JS (2004) Laser speckle imaging for monitoring blood flow dynamics in the in vivo rodent dorsal skin fold model. Microvasc Res 68:143–146CrossRefGoogle Scholar
  15. 15.
    Lee KS, Lim Y, Choi J, Kim NG, Kim JS (2013) Composite graft including bone tissue: a case report of successful reattachment of multiple fingertip oblique amputation. J Plast Reconstr Aesthet Surg 66:e43–46CrossRefGoogle Scholar
  16. 16.
    Mc LC (1954) Composite ear grafts and their blood supply. Br J Plast Surg 7:274–278CrossRefGoogle Scholar
  17. 17.
    Squadrito F, Bitto A, Irrera N, Pizzino G, Pallio G, Minutoli L, Altavilla D (2017) Pharmacological activity and clinical use of PDRN. Front Pharmacol 8:224CrossRefGoogle Scholar
  18. 18.
    Thellung S, Florio T, Maragliano A, Cattarini G, Schettini G (1999) Polydeoxyribonucleotides enhance the proliferation of human skin fibroblasts: involvement of A2 purinergic receptor subtypes. Life Sci 64:1661–1674CrossRefGoogle Scholar
  19. 19.
    Lee JH, Han JW, Byun JH, Lee WM, Kim MH, Wu WH (2018) Comparison of wound healing effects between Oncorhynchus keta-derived polydeoxyribonucleotide (PDRN) and Oncorhynchus mykiss-derived PDRN. Arch Craniofac Surg 19:20–34CrossRefGoogle Scholar
  20. 20.
    Bitto A, Polito F, Irrera N, D’Ascola A, Avenoso A, Nastasi G, Campo GM, Micali A, Bagnato G, Minutoli L, Marini H, Rinaldi M, Squadrito F, Altavilla D (2011) Polydeoxyribonucleotide reduces cytokine production and the severity of collagen-induced arthritis by stimulation of adenosine A(2A) receptor. Arthritis Rheum 63:3364–3371CrossRefGoogle Scholar
  21. 21.
    Bitto A, Oteri G, Pisano M, Polito F, Irrera N, Minutoli L, Squadrito F, Altavilla D (2013) Adenosine receptor stimulation by polynucleotides (PDRN) reduces inflammation in experimental periodontitis. J Clin Periodontol 40:26–32CrossRefGoogle Scholar
  22. 22.
    Hwang KH, Kim JH, Park EY, Cha SK (2018) An effective range of polydeoxyribonucleotides is critical for wound healing quality. Mol Med Rep 18:5166–5172Google Scholar
  23. 23.
    Guizzardi S, Galli C, Govoni P, Boratto R, Cattarini G, Martini D, Belletti S, Scandroglio R (2003) Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: a new proposal for bone tissue repair. Life Sci 73:1973–1983CrossRefGoogle Scholar
  24. 24.
    Kim S, Kim J, Choi J, Jeong W, Kwon S (2017) Polydeoxyribonucleotide improves peripheral tissue oxygenation and accelerates angiogenesis in diabetic foot ulcers. Arch Plast Surg 44:482–489CrossRefGoogle Scholar
  25. 25.
    Kim JY, Pak CS, Park JH, Jeong JH, Heo CY (2014) Effects of polydeoxyribonucleotide in the treatment of pressure ulcers. J Korean Med Sci 29(Suppl 3):S222–227CrossRefGoogle Scholar
  26. 26.
    De Aloe G, Rubegni P, Biagioli M, Taddeucci P, Fimiani M (2004) Skin graft donor site and use of polydeoxyribonucleotide as a treatment for skin regeneration: a randomized, controlled, double-blind, clinical trial. Wounds 16:258–263Google Scholar
  27. 27.
    Jeong W, Yang CE, Roh TS, Kim JH, Lee JH, Lee WJ (2017) Scar prevention and enhanced wound healing induced by polydeoxyribonucleotide in a rat incisional wound-healing model. Int J Mol Sci 18:1698CrossRefGoogle Scholar
  28. 28.
    Chung KI, Kim HK, Kim WS, Bae TH (2013) The effects of polydeoxyribonucleotide on the survival of random pattern skin flaps in rats. Arch Plast Surg 40:181–186CrossRefGoogle Scholar
  29. 29.
    Polito F, Bitto A, Galeano M, Irrera N, Marini H, Calo M, Squadrito F, Altavilla D (2012) Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps. J Vasc Surg 55:479–488CrossRefGoogle Scholar
  30. 30.
    Bitto A, Polito F, Altavilla D, Minutoli L, Migliorato A, Squadrito F (2008) Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model of peripheral artery occlusive disease. J Vasc Surg 48:1292–1300CrossRefGoogle Scholar
  31. 31.
    Bitto A, Galeano M, Squadrito F, Minutoli L, Polito F, Dye JF, Clayton EA, Calo M, Venuti FS, Vaccaro M, Altavilla D (2008) Polydeoxyribonucleotide improves angiogenesis and wound healing in experimental thermal injury. Crit Care Med 36:1594–1602CrossRefGoogle Scholar
  32. 32.
    Lazzarotto M, Tomasello EM, Caporossi A (2004) Clinical evaluation of corneal epithelialization after photorefractive keratectomy in a patients treated with polydeoxyribonucleotide (PDRN) eye drops: a randomized, double-blind, placebo-controlled trial. Eur J Ophthalmol 14:284–289CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery 2019

Authors and Affiliations

  1. 1.Department of Plastic and Reconstructive SurgeryWonju Severance Christian Hospital, Wonju College of Medicine, Yonsei UniversityWonju-siRepublic of Korea

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