Evaluation of topical erythropoietin application on the healing outcome of gingival graft recipient site; a randomized controlled clinical trial

Siamak Yaghobee, Nina Rouzmeh, Mina Taheri, Hoori Aslroosta, Sanaz Mahmoodi, Masoomeh Mohammadnejad Hardoroodi, Pardis Soleimanzadeh Azar, Afshin Khorsand, Siamak Yaghobee, Nina Rouzmeh, Mina Taheri, Hoori Aslroosta, Sanaz Mahmoodi, Masoomeh Mohammadnejad Hardoroodi, Pardis Soleimanzadeh Azar, Afshin Khorsand

Abstract

Background: Free gingival graft (FGG) is a highly predictable method to increase the width of keratinized gingiva. Various materials have been reported to accelerate the wound healing process. Considering the positive effect of EPO on dermal wound healing this study aimed to investigate the effects of EPO on the rate of healing and degree of inflammation in free gingival grafts.

Methods: Seventeen patients with bilateral lack of keratinized gingiva in mandible were selected for this clinical trial. The surgical intervention was performed after phase I periodontal therapy. Recipient site was prepared apical to the mucogingival line, and FGG was harvested from the palate. Before graft placement, the test side and control side were treated with 1 ml of EPO 4000 IU/ml and distilled water, respectively, for 2 min. On days 7, 14, 21, 28, 60, and 90 after surgery, the grafted sites were examined by blinded observers to compare the healing and inflammation of the areas.

Results: All the 17 patients completed the surgeries and follow-up examinations. Direct examination revealed significantly better healing in EPO group only on the 28th day. Assessment of the photographs showed a significant value in favor of the test group at some other time points as well. The EPO group demonstrated less inflammation, which was statistically significant in many time points. The graft area was 80.88 ± 30.21 mm2 and 71.35 ± 15.62 mm2 in the EPO and control groups, respectively. The difference was not significant, though.

Conclusions: Topical application of erythropoietin can accelerate the healing of gingival grafts and reduce the inflammation during healing period. The final graft outcome, nevertheless, does not seem to be influenced by EPO. Trial registration This was a split-mouth randomized controlled clinical trial (IRCT201201278830N1). The first registration date: 2016-10-22.

Keywords: Erythropoietin; Gingiva; Inflammation; Wound healing.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Consort flow diagram
Fig. 2
Fig. 2
a Baseline FGG treatment EPO group, b baseline FGG treatment control group, c 7 days postop EPO group, d 7 days postop control group, e 14 days postop EPO group, f 14 days postop control group, g 21 days postop EPO group, h 21 days postop control group, i 28 days postop EPO group, j 28 days postop control group, k 60 days postop EPO group, l 60 days postop control group, m 90 days postop EPO group, n 90 days postop control group

References

    1. Cairo F. Periodontal plastic surgery of gingival recessions at single and multiple teeth. Periodontol 2000. 2017;75(1):296–316. doi: 10.1111/prd.12186.
    1. Brackett RC, Gargiulo AW. Free gingival grafts in humans. J Periodontol. 1970;41(10):581–6. doi: 10.1902/jop.1970.41.10.581.
    1. Camargo PM, Melnick PR, Kenney EB. The use of free gingival grafts for aesthetic purposes. Periodontol. 2001;27(1):72–96. doi: 10.1034/j.1600-0757.2001.027001072.x.
    1. Mormann W, Schaer F, Firestone AR. The relationship between success of free gingival grafts and transplant thickness. Revascularization and shrinkage--a one year clinical study. J Periodontol. 1981;52(2):74–80. doi: 10.1902/jop.1981.52.2.74.
    1. Oliver RC, Loe H, Karring T. Microscopic evaluation of the healing and revascularization of free gingival grafts. J Periodontal Res. 1968;3(2):84–95. doi: 10.1111/j.1600-0765.1968.tb01908.x.
    1. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453(7193):314–21. doi: 10.1038/nature07039.
    1. Gümüş P, Buduneli E. Graft stabilization with cyanoacrylate decreases shrinkage of free gingival grafts. Aust Dent J. 2014;59(1):57–64. doi: 10.1111/adj.12149.
    1. Kathariya R, Jain H, Jadhav T. To pack or not to pack: the current status of periodontal dressings. J Appl Biomater Funct Mater. 2015;13(2):e73-86. doi: 10.5301/jabfm.5000215.
    1. Pilloni A, Rimondini L, De Luca M, Bernard GW. Effect of hyaluronan on calcification-nodule formation from human periodontal ligament cell culture. J Appl Biomater Biomech. 2003;1(1):84–90.
    1. Briguglio F, Briguglio E, Briguglio R, Cafiero C, Isola G. Treatment of infrabony periodontal defects using a resorbable biopolymer of hyaluronic acid: a randomized clinical trial. Quintessence Int. 2013;44(3):231–40. doi: 10.3290/j.qi.a29054.
    1. Currò M, Matarese G, Isola G, Caccamo D, Ventura VP, Cornelius C, Lentini M, Cordasco G, Ientile R. Differential expression of transglutaminase genes in patients with chronic periodontitis. Oral Dis. 2014;20(6):616–23. doi: 10.1111/odi.12180.
    1. Taşdemir Z, Alkan BA, Albayrak H. Effects of ozone therapy on the early healing period of deepithelialized gingival grafts: a randomized placebo-controlled clinical trial. J Periodontol. 2016;87(6):663–671. doi: 10.1902/jop.2016.150217.
    1. Yildiz MS, Gunpinar S. Free gingival graft adjunct with low-level laser therapy: a randomized placebo-controlled parallel group study. Clin Oral Investig. 2019;23(4):1845–1854. doi: 10.1007/s00784-018-2608-6.
    1. Akram Z, Vohra F, Javed F. Low-level laser therapy as an adjunct to connective tissue graft procedure in the treatment of gingival recession defects: A systematic review and meta-analysis. J Esthet Restor Dent. 2018;30(4):299–306. doi: 10.1111/jerd.12377.
    1. Jelkmann W. Molecular biology of erythropoietin. Intern Med. 2004;43(8):649–59. doi: 10.2169/internalmedicine.43.649.
    1. Savino R, Ciliberto G. A paradigm shift for erythropoietin: no longer a specialized growth factor, but rather an all-purpose tissue-protective agent. Cell Death Differ. 2004;11(Suppl 1):S2-4. doi: 10.1038/sj.cdd.4401469.
    1. Sorg H, Krueger C, Schulz T, Menger MD, Schmitz F, Vollmar B. Effects of erythropoietin in skin wound healing are dose related. Faseb j. 2009;23(9):3049–58. doi: 10.1096/fj.08-109991.
    1. Melashchenko OV, Meniailo ME, Malashchenko VV, Gazatova ND, Goncharov AG, Seledtsova GV, Seledtsov VI. Erythropoietin Directly Affects Human Macrophage Functionality. Curr Pharm Biotechnol. 2018;19(11):902–909. doi: 10.2174/1389201019666181031164520.
    1. Isogai R, Takahashi M, Aisu K, Horiuti Y, Aragane Y, Kawada A, Tezuka T. The receptor for erythropoietin is present on cutaneous mast cells. Arch Dermatol Res. 2006;297(9):389–94. doi: 10.1007/s00403-005-0615-3.
    1. Selzer E, Wacheck V, Kodym R, Schlagbauer-Wadl H, Schlegel W, Pehamberger H, Jansen B. Erythropoietin receptor expression in human melanoma cells. Melanoma Res. 2000;10(5):421–6. doi: 10.1097/00008390-200010000-00003.
    1. Bodo E, Kromminga A, Funk W, Laugsch M, Duske U, Jelkmann W, Paus R. Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin. Faseb J. 2007;21(12):3346–54. doi: 10.1096/fj.07-8628com.
    1. Buemi M, Galeano M, Sturiale A, Ientile R, Crisafulli C, Parisi A, Catania M, Calapai G, Impala P, Aloisi C, Squadrito F, Altavilla D, Bitto A, Tuccari G, Frisina N. Recombinant human erythropoietin stimulates angiogenesis and healing of ischemic skin wounds. Shock. 2004;22(2):169–73. doi: 10.1097/.
    1. Haroon ZA, Amin K, Jiang X, Arcasoy MO. A novel role for erythropoietin during fibrin-induced wound-healing response. Am J Pathol. 2003;163(3):993–1000. doi: 10.1016/s0002-9440(10)63459-1.
    1. Hamed S, Ullmann Y, Masoud M, Hellou E, Khamaysi Z, Teot L. Topical erythropoietin promotes wound repair in diabetic rats. J Invest Dermatol. 2010;130(1):287–94. doi: 10.1038/jid.2009.219.
    1. Hamed S, Ullmann Y, Egozi D, Daod E, Hellou E, Ashkar M, Gilhar A, Teot L. Fibronectin potentiates topical erythropoietin-induced wound repair in diabetic mice. J Invest Dermatol. 2011;131(6):1365–74. doi: 10.1038/jid.2011.15.
    1. Buemi M, Vaccaro M, Sturiale A, Galeano MR, Sansotta C, Cavallari V, Floccari F, D’Amico D, Torre V, Calapai G, Frisina N, Guarneri F, Vermiglio G. Recombinant human erythropoietin influences revascularization and healing in a rat model of random ischaemic flaps. Acta Derm Venereol. 2002;82(6):411–7. doi: 10.1080/000155502762064520.
    1. Galeano M, Altavilla D, Cucinotta D, Russo GT, Calo M, Bitto A, Marini H, Marini R, Adamo EB, Seminara P, Minutoli L, Torre V, Squadrito F. Recombinant human erythropoietin stimulates angiogenesis and wound healing in the genetically diabetic mouse. Diabetes. 2004;53(9):2509–17. doi: 10.2337/diabetes.53.9.2509.
    1. Mohyeldin A, Lu H, Dalgard C, Lai SY, Cohen N, Acs G, Verma A. Erythropoietin signaling promotes invasiveness of human head and neck squamous cell carcinoma. Neoplasia. 2005;7(5):537–43. doi: 10.1593/neo.04685.
    1. Yaghobee S, Rouzmeh N, Aslroosta H, Mahmoodi S, Khorsand A, Kharrazifard MJ. Effect of Topical Erythropoietin (EPO) on palatal wound healing subsequent to Free Gingival Grafting (FGG) Braz Oral Res. 2018;32:e55. doi: 10.1590/1807-3107bor-2018.vol32.0055.
    1. Hosseinjani H, Hadjibabaie M, Gholami K, Javadi M, Radfar M, Jahangard-Rafsanjani Z, Hosseinjani E, Shabani N, Vaezi M, Ghavamzadeh A. The efficacy of erythropoietin mouthwash in prevention of oral mucositis in patients undergoing autologous hematopoietic SCT: a double-blind, randomized, placebo-controlled trial. Hematol Oncol. 2017;35(1):106–112. doi: 10.1002/hon.2250.
    1. Bjorn H. Free transplantation of gingiva propria. Sveriges Tandlak T. 1963;22:684.
    1. Galeano M, Altavilla D, Bitto A, Minutoli L, Calo M, Lo Cascio P, Polito F, Giugliano G, Squadrito G, Mioni C, Giuliani D, Venuti FS, Squadrito F. Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds. Crit Care Med. 2006;34(4):1139–46. doi: 10.1097/.
    1. Bader A, Lorenz K, Richter A, Scheffler K, Kern L, Ebert S, Giri S, Behrens M, Dornseifer U, Macchiarini P, Machens HG. Interactive role of trauma cytokines and erythropoietin and their therapeutic potential for acute and chronic wounds. Rejuvenation Res. 2011;14(1):57–66. doi: 10.1089/rej.2010.1050.
    1. Tsao CJ, Kao RH, Cheng TY, Huang CC, Chang SL, Lee FN. The effect of recombinant human erythropoietin on hemostatic status in chronic uremic patients. Int J Hematol. 1992;55(2):197–203.
    1. Cases A, Escolar G, Reverter JC, Ordinas A, Lopez-Pedret J, Revert L, Castillo R. Recombinant human erythropoietin treatment improves platelet function in uremic patients. Kidney Int. 1992;42(3):668–72. doi: 10.1038/ki.1992.333.
    1. Malyszko J, Suchowierska E, Malyszko JS, Mysliwiec M. A comprehensive study on hemostasis in CAPD patients treated with erythropoietin. Perit Dial Int. 2002;22(5):582–92. doi: 10.1177/089686080202200509.
    1. Singh AB, Singh M, Palekar S, Levy S, Nunn C, Mann RA. The effects of recombinant human erythropoietin on the cell mediated immune response of renal failure patients. J Med. 1992;23(5):289–302.
    1. Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol. 2007;127(3):514–25. doi: 10.1038/sj.jid.5700701.
    1. Fayazzadeh E, Ahmadi SH, Rabbani S, Boroumand MA, Salavati A, Anvari MS. A comparative study of recombinant human basic fibroblast growth factor (bFGF) and erythropoietin (EPO) in prevention of skin flap ischemic necrosis in rats. Arch Iran Med. 2012;15(9):553–6.

Source: PubMed

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