Document Type: Research(Original) Article

Authors

1 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

2 Laparoscopy Research Center, Shiraz University of medical Sciences, Shiraz, Iran

3 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

4 Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

5 International Branch, Shiraz University of Medical Sciences, Shiraz, Iran

6 Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Platelet-rich plasma (PRP) is an attractive preparation in regenerative medicine due to its potential role on the healing process in different experimental models. This study was designed to investigate the wound healing activity of a new formulation of PRP. Different gel-based formulations of PRP were prepared. Open excision wounds were made on the back of male Sprague-Dawley rats, and PRP gel was administered topically once daily until the wounds healed completely (12 days). The results revealed that the tested PRP formulation significantly accelerated the wound healing process by increasing the wound contracting, tissue granulization, vascularization, and collagen regeneration. Interestingly, we found that there were no significant differences between PRP formulation and its gel base in all above mentioned parameters. Although this investigation showed that PRP formulation had significant wound healing effects, but the PRP gel base also had significant wound healing properties. This might indicate the wound healing properties of the PRP gel ingredients in the current investigation.

Keywords

  1. Stojadinovic A, Carlson JW, Schultz GS, Davis TA, Elster EA. Topical advances in wound care. Gynecologic oncology 2008;111;S70-S80.
  2. White JG, Platelet morphology. Vol. 45. 1971: Academic Press, New York.
  3. Alsousou J, Thompson M, Hulley P, Noble A, Willett K. The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery A REVIEW OF THE LITERATURE. Journal of Bone & Joint Surgery, British Volume 2009;91;987-996.
  4. Italiano JE, Richardson JL, Patel-Hett S, Battinelli E, Zaslavsky A, Short S, Ryeom S, Folkman J, Klement GL. Angiogenesis is regulated by a novel mechanism: pro-and antiangiogenic proteins are organized into separate platelet α granules and differentially released. Blood 2008;111;1227-1233.
  5. Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound healing. The Yale journal of biology and medicine 2010;83.
  6. Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma from basic science to clinical applications. The American journal of sports medicine 2009;37;2259-2272.
  7. Pierce GF, Mustoe TA, Lingelbach J, Masakowski VR, Griffin GL, Senior RM, Deuel TF. Platelet-derived growth factor and transforming growth factor-beta enhance tissue repair activities by unique mechanisms. The Journal of cell biology 1989;109;429-440.
  8. Burnouf T, Goubran HA, Chen T-M, Ou K-L, El-Ekiaby M, Radosevic M. Blood-derived biomaterials and platelet growth factors in regenerative medicine. Blood Rev 2013;27;77-89.
  9. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 2009;37;1528-1542.
  10. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiological reviews 2003;83;835-870.
  11. Everts PAM, Knape JTA, Weibrich G, Schonberger J, Hoffmann J, Overdevest EP, Box HAM, van Zundert A. Platelet-rich plasma and platelet gel: a review. Journal of ExtraCorporeal Technology 2006;38.
  12. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plastic and reconstructive surgery 2004;114;1502-1508.
  13. Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 1998;85;638-646.
  14. Andia I, Sanchez M, Maffulli N. Basic science: molecular and biological aspects of platelet-rich plasma therapies. Operative Techniques in Orthopaedics 2012;22;3-9.
  15. Everts PAM, Devilee RJJ, Brown Mahoney C, Eeftinck-Schattenkerk M, Box HAM, Knape JTA, Van Zundert A. Platelet gel and fibrin sealant reduce allogeneic blood transfusions in total knee arthroplasty. Acta Anaesthesiologica Scandinavica 2006;50;593-599.
  16. Eppley BL, Pietrzak WS, Blanton M. Platelet-rich plasma: a review of biology and applications in plastic surgery. Plastic and reconstructive surgery 2006;118;147e-159e.
  17. Moreira Teixeira LS, Leijten JCH, Wennink JWH, Chatterjea AG, Feijen J, van Blitterswijk CA, Dijkstra PJ, Karperien M. The effect of platelet lysate supplementation of a dextran-based hydrogel on cartilage formation. Biomaterials 2012;33;3651-3661.
  18. Ma L, Elliott SN, Cirino G, Buret A, Ignarro LJ, Wallace JL. Platelets modulate gastric ulcer healing: role of endostatin and vascular endothelial growth factor release. Proceedings of the National Academy of Sciences 2001;98;6470-6475.
  19. Fresno L, Fondevila D, Bambo O, Chacaltana A, Garcia F, Andaluz A. Effects of platelet-rich plasma on intestinal wound healing in pigs. The Veterinary Journal 2010;185;322-327.
  20. Almdahl SM, Veel T, Halvorsen P, Vold MB, Mølstad P. Randomized prospective trial of saphenous vein harvest site infection after wound closure with and without topical application of autologous platelet-rich plasma. European Journal of Cardio-Thoracic Surgery 2011;39;44-48.
  21. Barry BW, Meyer MC. The rheological properties of carbopol gels I. Continuous shear and creep properties of carbopol gels. International Journal of Pharmaceutics 1979;2;1-25.
  22. Kamerzell TJ, Esfandiary R, Joshi SB, Middaugh CR, Volkin DB. Protein–excipient interactions: Mechanisms and biophysical characterization applied to protein formulation development. Advanced drug delivery reviews 2011;63;1118-1159.
  23. Tsai PK, Volkin DB, Dabora JM, Thompson KC, Bruner MW, Gress JO, Matuszewska B, Keogan M, Bondi JV, Middaugh CR. Formulation design of acidic fibroblast growth factor. Pharmaceutical research 1993;10;649-659.
  24. Samani SM, Jamshidzade A, Raoufi SMS, Mardani Z. Topical gel formulation and stability assessment of platelet lysate based on turbidimetric method. Trends in Pharmaceutical Sciences 2015;1;75-82.
  25. Horwitz W, Senzel A, Reynolds H, Park DL, others. Official methods of analysis of the Association of Official Analytical Chemists. Official methods of analysis of the Association of Official Analytical Chemists 1975.
  26. Ahanger AA, Leo MD, Gopal A, Kant V, Tandan SK, Kumar D. Pro-healing effects of bilirubin in open excision wound model in rats. International wound journal 2014.
  27. Woessner JF, Jr. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys 1961;93;440-7.
  28. Moezi L, Heidari R, Amirghofran Z, Nekooeian AA, Monabati A, Dehpour AR. Enhanced anti-ulcer effect of pioglitazone on gastric ulcers in cirrhotic rats: The role of nitric oxide and IL-1b. Pharmacol Rep 2013;65;134-143.
  29. Carter MJ, Fylling CP, Parnell LKS. Use of platelet rich plasma gel on wound healing: a systematic review and meta-analysis. Eplasty 2011;11.
  30. Arnell P, Ekre O, Oscarsson N, Rosen A, Eriksson M, Svanberg T, Samuelsson O, Hyperbaric oxygen therapy in the treatment of diabetic foot ulcers and late radiation tissue injuries of the pelvis2012: HTArapport.
  31. Anitua E, Sanchez M, Orive G, Andia I. The potential impact of the preparation rich in growth factors (PRGF) in different medical fields. Biomaterials 2007;28;4551-60.
  32. Margadant C, Sonnenberg A. Integrin–TGF-β crosstalk in fibrosis, cancer and wound healing. EMBO reports 2010;11;97-105.
  33. Anitua E, Sanchez M, Orive G, Andia I. Delivering growth factors for therapeutics. Trends Pharmacol Sci 2008;29;37-41.
  34. Frechette JP, Martineau I, Gagnon G. Platelet-rich plasmas: growth factor content and roles in wound healing. Journal of Dental Research 2005;84;434-439.
  35. Stacey MC, Mata SD, Trengove NJ, Mather CA. Randomised double-blind placebo controlled trial of topical autologous platelet lysate in venous ulcer healing. Eur J Vasc Endovasc Surg 2000;20;296-301.