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

7/1/2009
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Author(s):

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

A study on post-menopausal women showed that topical estradiol treatment has provided a significant increase in hydroxyproline and collagen content of the skin.³⁶ Another study on elderly men and women investigated the effect of topical estrogen on wound healing; the amount of collagen in the estrogen-treated group showed a constant increase in both genders compared to the placebo group.^28,37 Full-thickness wounds (with substantial loss) were created in the back of ovariectomized young female rats and local intradermal estradiol was injected; re-epithelization and collagen deposition was increased and wound healing was facilitated in the treatment group. Cellular mechanisms suggested to be responsible for these changes are increased secretion of latent TGF-β1 by dermal fibroblasts that were stimulated by estrogen.¹¹ In the present study, fibrosis was moderate in all groups on day 7, but became intense on days 14 and 21. Absence of a notable difference between the groups may be due to the use of young and intact females that possess high levels of estrogen. Collagen and hydroxyproline levels increased steadily in all groups over time, especially on day 14. Although statistically insignificant, the increase was greater in the PRP gel + estradiol-treated group compared to the other groups.

PRP contains EGF, which induces replication, migration, and stimulation of the basal skin cells and mucous membrane, which form the components of the basement membrane.³⁵ These increases are consistent with other studies.^17,38 Carter et al³⁸ found that treatment of lower equine limb wounds with PRP induced accelerated epithelial differentiation and produced tissue with organized, interlocking collagen bundles. Marx¹⁷ determined that patients had earlier and faster epithelization with less pain in PRP-treated split-thickness skin graft donor sites. Estrogen was shown to accelerate the wound-healing process with faster epithelization and suppressing the inflammatory response with a concurrent increase in matrix deposition.¹¹ In the present study, slight epithelization was present only in the PRP gel + estradiol-treated group on day 7 of the study, whereas, no epithelization was observed in the other groups. No significant differences were observed between the treatment groups and the sterile saline solution group regarding epithelization on day 14, but the epithelization rate was higher in PRP gel-treated and PRP gel + estradiol-treated groups than in the other groups. Epithelization started in the early period due to a shortened latent period, even though it was an open wound. Bandyopadhyay et al³⁹ report that human serum selectively promotes epidermal cell migration and halts dermal cell migration. In contrast, human plasma promotes dermal but not epidermal cell migration. In this study, the PRP gel and estradiol combination seemed to have a tendency to accelerate epidermal cell migration. The estradiol may help to promote epidermal cell migration.

Conclusion

Clinical evaluation showed that wound healing was faster and hydroxyproline content was the highest in the group that was treated with PRP gel and estradiol combination compared to the sterile saline solution group. Histopathological evaluation showed that angiogenesis and epithelization started in the first week and advanced rapidly. This may indicate that the combined use of estradiol and PRP gel accelerates the inflammatory reaction and initiates the healing process earlier.

Two limitations of this study were the small sample size and use of female rabbits led to statistical outcomes that might not have been sensitive enough to detect the differences caused by the treatments in all cases. This might have affected the results, and therefore, the conclusions of this study.

References:

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.