The Efficacy of Platelet-rich Plasma Gel and Topical Estradiol Alone or in Combination on Healing of Full-thickness Wounds

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Ozlem H. Nisbet; C. Nisbet; M. Yarim; A. Ozak

Abstract: This randomized study was designed to establish the efficacy of platelet-rich plasma (PRP) gel and topical estradiol alone, or in combination, on healing of full-thickness wounds created on the trunk of rabbits. Fifteen New Zealand white female rabbits and 60 wounds were studied. Four 2.25-cm² full-thickness wounds were created using a template and treatments including a sterile saline solution that were assigned randomly to the wounds. Wounds were bandaged, dressed intermittently, and assessed by wound measurements and a collection of samples at 7, 14, and 21 days to evaluate healing. Variables of interest were hydroxyproline concentration and scored gross and microscopic morphologic characteristics reflective of wound healing. PRP gel + estradiol-treated wounds completely healed faster than wounds given other treatments. Granulation tissue growth to the skin level was faster (P < 0.05) in the PRP gel + estradiol group than the other groups. Only the PRP gel + estradiol group had a significantly lower collagen level than the sterile saline solutions on day 7 (P < 0.05). The PRP gel + estradiol group and estradiol group led to an increase in angiogenesis on day 14 (P < 0.05). Complete epithelization was observed only in the PRP gel + estradiol group compared with the other groups on day 7. PRP gel + estradiol-treatment enhanced healing in full-thickness wounds by reducing the contraction rate with a trend toward accelerating both epithelial migration and the angiogenic response.

Address correspondence to:
Ozlem H. Nisbet, DVM, PhD
Department of Surgery, Faculty of Veterinary Medicine
Ondokuz Mayis University
Kurupelit 55139
Samsun, Turkey

     The primary goal of wound care is to achieve rapid and functional healing with a cosmetic scar.1 Wound healing involves a series of events (ie, clotting, inflammation, organization of granulation tissue, epithelization, and tissue restoration). These events are ensued by stimulation and organization of cellular activities through the interaction of the signals formed by cytokines and growth factors.1–3 Following injury, various growth factors such as platelet-derived growth factor (PDGF), transforming growth factor beta and alpha (TGF-β and TGF-α), platelet-derived endothelial cell growth hormone (PDEGH), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), interleukin l (IL-1), interleukin 2 (IL-2), and platelet-activating factor 4 (PAF-4), are released.1,3–8 These factors play a particular role in restoring tissue (re-epithelization and neovascularization), synthesizing the extracellular matrix, and recruiting mesenchymal cells.3 PRP is a concentrated thrombocyte product that has been used in clinical trials to hasten wound healing.2,5

     Estradiol receptors are known to exist in cells involved in the healing process such as macrophages, fibroblasts, endothelium, and in the cytoplasm and/or nucleus of various cells in the dermis,9 and are reported to indirectly influence the proliferative phase of the wound healing by increasing the production of growth factors.10–12

     To our knowledge, there was no study on the effect of PRP gel and estradiol combination on wound healing in the literature.

     The purpose of the present study was to investigate the clinical, biochemical, and histopathological effects of these substances used either alone or in combination on wounds with substantial loss.

Materials and Methods

     Study population. A total of 15, 6-month-old, New Zealand white female rabbits (2500 ± 300 g body weight), which had been supplied by the Surgical Research Center at Ondokuz Mayis University (Samsun, Turkey) were used in the study.


1. Singer AJ, Clark RAF. Cutaneous wound healing. N Engl J Med. 1999;341(2):738–746.
2. Bhanot S, Alex JC. Current applications of platelet gels in facial plastic surgery. Facial Plast Surg. 2002;18(1):27–33.
3. Crovetti G, Martinelli G, Issi M, et al. Platelet gel for healing cutaneous chronic wounds. Transfus Apher Sci. 2004;30(2):145–151.
4. Sanchez AR, Sheridan PJ, Kupp LI. Is platelet-rich plasma the perfect enhancement factor? A current review. Int J Oral Maxillofac Implants. 2003;18(1):93–103.
5. Woodell-May JE, Ridderman DN, Swift MJ, Higgins J. Producing accurate platelet counts for platelet rich plasma: validation of a hematology analyzer and preparation techniques for counting. J Craniofac Surg. 2005;16(5):757–759.
6. Aghaloo TL, Moy PK, Freymiller EG. Investigation of platelet-rich plasma in rabbit cranial defects: A pilot study. J Oral Maxillofac Surg. 2002;60(10):1176–1181.
7. Fu X, Li X, Cheng B, Chen W, Sheng Z. Engineered growth factors and cutaneous wound healing: success and possible questions in the past 10 years. Wound Repair Regen. 2005;13(2):122–130.
8. Shukla A, Dubey MP, Srivastava R, Srivastava BS. Differential expression of proteins during healing of cutaneous wounds in experimental normal and chronic models. Biochem Biophys Res Commun. 1998;244(2):434–439.
9. Calvin M. Oestrogens and wound healing. Maturitas. 2000;34(3):195–210.
10. May Oh D, Phillips TJ. Sex hormones and wound healing. WOUNDS. 2006;18(1):8–18.
11. Ashcroft GS, Dodsworth J van Boxtel E, et al. Estrogen accelerates cutaneous wound healing associated with an increase in TGF-beta 1 levels. Nat Med. 1997;3(11):1209–1215.
12. Hardman MJ, Ashcroft GS. Hormonal influences on wound healing: a review of current experimental data. WOUNDS. 2005;17(11):313–320.
13. Keast DH, Bowering CK, Evans AW, Mackean GL, Burrows C, D’Souza L. MEASURE: A proposed assessment framework for developing best practice recommendations for wound assessment. Wound Repair Regen. 2004;12(3 Suppl):S1–17.
14. Bergman I, Loxley R. Two improved and simplified methods for the spectrophotometric determination of hydroxyproline. Anal Chem. 1963;35(12):1961–1965.
15. Abramov Y, Golden B, Sullivan M, et al. Histologic characterization of vaginal vs. abdominal surgical wound healing in a rabbit model. Wound Repair Regen. 2007;15(1):80–86.
16. Greenhalgh DG, Sprugel KH, Murray MJ, Ross R. PDGF and FGF stimulate wound healing in the genetically diabetic mouse. Am J Pathol. 1990;136(6):1235–1246.
17. Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg. 2004;62(4):489–496.
18. Pietrzak WS, Eppley BL. Platelet rich plasma: biology and new technology. J Craniofac Surg. 2005;16(6):1043–1054.
19. Sutter WW, Kaneps AJ, Bertone AL. Comparison of hematologic values and transforming growth factor-beta and insulin-like growth factor concentrations in platelet concentrates obtained by use of buffy coat and apheresis methods from equine blood. Am J Vet Res. 2004;65(7):924–930.
20. Man D, Plosker H, Winland-Brown JE. The use of autologous platelet-rich plasma (platelet gel) and autologous platelet-poor plasma (fibrin glue) in cosmetic surgery. Plast Reconstr Surg. 2001;107(1):229–237.
21. Martineau I, Lacoste E, Gagnon G. Effects of calcium and thrombin on growth factor release from platelet concentrates: kinetics and regulation of endothelial cell proliferation. Biomaterials. 2004;25(18):4489–4502.
22. Fennis JP, Stoelinga PJ, Jansen JA. Reconstruction of the mandible with an autogenous irradiated cortical scaffold, autogenous corticocancellous bone-graft and autogenous platelet-rich plasma: an animal experiment. Int J Oral Maxillofac Surg. 2005;34(2):158–166.
23. Petrungaro PS. Using platelet-rich plasma to accelerate soft tissue maturation in esthetic periodontal surgery. Compend Contin Educ Dent. 2001;22(9):729–745.
24. Landesberg R, Roy M, Glickman RS. Quantification of growth factor levels using a simplified method of platelet-rich plasma gel preparation. J Oral Maxillofac Surg. 2000;58(3):297–300.
25. Robiony M, Polini F, Cost F, Politi M. Osteogenesis distraction and platelet-rich plasma for bone restoration of the severely atrophic mandible: preliminary results. J Oral Maxillofac Surg. 2002;60(6):630–635.
26. Morales DE, McGowan KA, Grant DS, et al. Estrogen promotes angiogenic activity in human umbilical vein endothelial cells in vitro and in a murine model. Circulation. 1995;91(3):755–763.
27. Shanker G, Sorci-Thomas M, Adams MR. Estrogen modulates the inducible expression of platelet-derived growth factor mRNA by monocyte/macrophages. Life Sci. 1995;56(7):499–507.
28. Katz MH, Alvarez AF, Kirsner RS, Eaglstein WH, Falanga V. Human wound fluid from acute wounds stimulates fibroblast and endothelial cell growth. J Am Acad Dermatol. 1991;25(6 Pt 1):1054–1058.
29. Battegay EF, Rupp J, Iruela-Arispe L, Sage EH, Pech M. PDGF-BB modulates endothelial proliferation and angiogenesis in vitro via PDGF receptors. J Cell Biol. 1994;125(4):917–945.
30. Calvin M, Dyson M, Rymer J, Young SR. The effect of ovarian hormone deficiency on macrophage infiltration during the inflammatory phase of wound healing in a rat model. WOUNDS. 1998;10(5):158–163.
31. Calvin M. HRT and skin healing-a potential benefit? J Br Menopause Soc. 1998;4(3):9–10.
32. Faler BJ, Macsata RA, Plummer D, Mishra L, Sidawy AN. Transforming growth factor-beta and wound healing. Perspect Vasc Surg Endovasc Ther. 2006;18(1):55–62.
33. Swaim SF, Henderson RA. Wound healing. In: Swaim SF, Henderson RA, eds. Small Animal Wound Management. 2nd ed. Baltimore MD: Williams & Wilkins; 1997:1–12.
34. Henderson JL, Cupp CL, Ross EV, at al. The effects of autologous platelet gel on wound healing. Ear Nose Throat J. 2003;82(8):598–602.
35. Marx RE, Garg AK. The biology of platelets and the mechanism of platelet-rich plasma. In: Marx RE, Garg AK, eds. Dental and Craniofacial Applications of Platelet-Rich Plasma. Chicago, IL: Quintessence; 2005:3–30.
36. Brincat M, Moniz CJ, Studd JW, et al. Long-term effects of menopause and sex hormones on skin thickness. Br J Obstet Gynaecol. 1985;92(3):256–259.
37. Ashcroft GS, Greenwell-Wild T, Horan MA, Wahl SM, Ferguson MW. Topical estrogen accelerates cutaneous wound healing in aged humans associated with an altered inflammatory response. Am J Pathol. 1999;155(4):1137–1146.
38. Carter CA, Jolly DG, Worden CE Sr, Hendren DG, Kane CJ. Platelet-rich plasma gel promotes differentiation and regeneration during equine wound healing. Exp Mol Pathol. 2003;74(3):244–255.
39. Bandyopadhjay B, Fan J, Guan S, et al. A “traffic control” role for TGF-beta 3: orchestrating dermal and epidermal cell motility during wound healing. J Cell Biol. 2006;172(7):1093–1105.

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