BACKGROUND: [corrected] Deep skin burn injuries, especially those on the face, hands, feet, genitalia and perineum represent significant therapeutic challenges. Autologous dermo-epidermal skin grafts (DESG) have become standard of care for treating deep burns. Additionally, human autologous thrombin activated autologous platelet concentrate (APC) has gained acceptance in the setting of wounds. While each of these interventions has been independently shown to accelerate healing, the combination of the two has never been evaluated. We hypothesized that the addition of platelets (source of growth factors and inhibitors necessary for tissue repair) to the DESG (source of progenitor cells and of tissue proteases necessary for spatial and temporal control of growth regulators released from platelets) would create the optimal environment for the reciprocal interaction of cells within the healing tissues. METHODS: We used clinical examination (digital photography), standardised scales for evaluating pain and scarring, in combination with blood perfusion (laser Doppler imaging), as well as molecular and laboratory analyses. RESULTS: We show for the first time that the combination of APC and DESG leads to earlier relief of pain, and decreased use of analgesics, antipruritics and orthotic devices. Most importantly, this treatment is associated with earlier discharges from hospital and significant cost savings. CONCLUSIONS: Our findings indicate that DESG engraftment is facilitated by the local addition of platelets and by systemic thrombocytosis. This local interaction leads to the physiological revascularization at 1-3 months. We observed significant elevation of circulating platelets in early stages of engraftment (1-7 days), which normalized over the subsequent 7 and 90 days.

Institute of Radiodiagnostic and Vice President for Science and Research University Hospital Ostrava Czech Republic

Zobrazit více v PubMed

Prochazka V, Gumulec J, Jaluvka F, Salounova D, Jonszta T, Czerny D, Krajca J, Urbanec R, Klement P, Martinek J, Klement GL. Cell therapy, a new standard in management of chronic critical limb ischemia and foot ulcer. Cell transplantation. 2010;19(11):1413–24. PubMed PMC

Akingboye AA, Giddins S, Gamston P, Tucker A, Navsaria H, Kyriakides C. Application of autologous derived-platelet rich plasma gel in the treatment of chronic wound ulcer: diabetic foot ulcer. The Journal of extra-corporeal technology. 2010;42(1):20–9. PubMed PMC

Kachel E, Callum J, Moussa F, Goldstein J, Fremes S. Treatment of deep sternal wound infections after coronary artery bypass grafting by means of injection of platelet gel: an evolving technology. The Journal of thoracic and cardiovascular surgery. 2010;139(6):e118–20. PubMed

Martinez-Zapata MJ, Marti-Carvajal A, Sola I, Bolibar I, Angel Exposito J, Rodriguez L, Garcia J. Efficacy and safety of the use of autologous plasma rich in platelets for tissue regeneration: a systematic review. Transfusion. 2009;49(1):44–6. PubMed

Morizaki Y, Zhao C, An KN, Amadio PC. The effects of platelet-rich plasma on bone marrow stromal cell transplants for tendon healing in vitro. The Journal of hand surgery. 2010;35(11):1833–41. PubMed PMC

Langer H, May AE, Daub K, Heinzmann U, Lang P, Schumm M, Vestweber D, Massberg S, Schonberger T, Pfisterer I, Hatzopoulos AK, Gawaz M. Adherent platelets recruit and induce differentiation of murine embryonic endothelial progenitor cells to mature endothelial cells in vitro. Circulation research. 2006;98(2):e2–10. PubMed

Stellos K, Seizer P, Bigalke B, Daub K, Geisler T, Gawaz M. Platelet aggregates-induced human CD34+ progenitor cell proliferation and differentiation to macrophages and foam cells is mediated by stromal cell derived factor 1 in vitro. Seminars in thrombosis and hemostasis. 2010;36(2):139–45. PubMed

Pintucci G, Froum S, Pinnell J, Mignatti P, Rafii S, Green D. Trophic effects of platelets on cultured endothelial cells are mediated by platelet-associated fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) Thrombosis and haemostasis. 2002;88(5):834–42. PubMed

Pietramaggiori G, Scherer SS, Cervi D, Klement G, Orgill DP. Tumors stimulate platelet delivery of angiogenic factors in vivo: an unexpected benefit. The American journal of pathology. 2008;173(6):1609–16. PubMed PMC

Lindemann S, Kramer B, Seizer P, Gawaz M. Platelets, inflammation and atherosclerosis. Journal of thrombosis and haemostasis: JTH. 2007;5(Suppl 1):203–11. PubMed

Klement GL, Yip TT, Cassiola F, Kikuchi L, Cervi D, Podust V, Italiano JE, Wheatley E, Abou-Slaybi A, Bender E, Almog N, Kieran MW, Folkman J. Platelets actively sequester angiogenesis regulators. Blood. 2009;113(12):2835–42. PubMed PMC

Italiano JE, Jr, 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 alpha granules and differentially released. Blood. 2008;111(3):1227–33. PubMed PMC

Ma L, Perini R, McKnight W, Dicay M, Klein A, Hollenberg MD, Wallace JL. Proteinase-activated receptors 1 and 4 counter-regulate end-ostatin and VEGF release from human platelets. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(1):216–20. PubMed PMC

Bottcher-Haberzeth S, Biedermann T, Reichmann E. Tissue engineering of skin. Burns : journal of the International Society for Burn Injuries. 2010;36(4):450–60. PubMed

Crkvenjas Z, Tymonova J, Adamkova M, Kadlcik M, Klosova H, Zamecnikova I. Surgical treatment of electrical burns by local flap plastic surgery. Acta chirurgiae plasticae. 2005;47(1):10–12. PubMed

Hermann PC, Huber SL, Herrler T, von Hesler C, Andrassy J, Kevy SV, Jacobson MS, Heeschen C. Concentration of bone marrow total nucleated cells by a point-of-care device provides a high yield and preserves their functional activity. Cell transplantation. 2008;16(10):1059–69. PubMed

Kloppenberg FW, Beerthuizen GI, ten Duis HJ. Perfusion of burn wounds assessed by laser doppler imaging is related to burn depth and healing time. Burns : journal of the International Society for Burn Injuries. 2001;27(4):359–63. PubMed

Draaijers LJ, Tempelman FR, Botman YA, Kreis RW, Middelkoop E, van Zuijlen PP. Colour evaluation in scars: tristimulus colorimeter, narrow-band simple reflectance meter or subjective evaluation? Burns : journal of the International Society for Burn Injuries. 2004;30(2):103–7. PubMed

Kabes AM, Graves JK, Norris J. Further validation of the nonverbal pain scale in intensive care patients. Critical care nurse. 2009;29(1):59–66. PubMed

Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of pruritus. The British journal of dermatology. 2010;162(3):587–93. PubMed PMC

Kovanic PH, Huber MB. The Economics of Information-Mathematical Gnostics for Data Analysis. 2003 http://www.math-gnostics.com.

Mazzucco L, Balbo V, Cattana E, Borzini P. Platelet-rich plasma and platelet gel preparation using Plateltex. Vox sanguinis. 2008;94(3):202–8. PubMed

Mazzucco L, Medici D, Serra M, Panizza R, Rivara G, Orecchia S, Libener R, Cattana E, Levis A, Betta PG, Borzini P. The use of autologous platelet gel to treat difficult-to-heal wounds: a pilot study. Transfusion. 2004;44(7):1013–8. PubMed

Gunaydin S, McCusker K, Sari T, Onur M, Gurpinar A, Sevim H, Atasoy P, Yorgancioglu C, Zorlutuna Y. Clinical impact and biomaterial evaluation of autologous platelet gel in cardiac surgery. Perfusion. 2008;23(3):179–86. PubMed

Coetzee JC, Pomeroy GC, Watts JD, Barrow C. The use of autologous concentrated growth factors to promote syndesmosis fusion in the Agility total ankle replacement. Swiss Foot and Ankle Society. 2005;26(10):840–6. PubMed

Gardner MJ, Demetrakopoulos D, Klepchick PR, Mooar PA. The efficacy of autologous platelet gel in pain control and blood loss in total knee arthroplasty. An analysis of the haemoglobin, narcotic requirement and range of motion. International orthopaedics. 2007;31(3):309–13. PubMed PMC

Khalafi RS, Bradford DW, Wilson MG. Topical application of autologous blood products during surgical closure following a coronary artery bypass graft. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2008;34(2):360–4. PubMed

Akeda K, An HS, Pichika R, Attawia M, Thonar EJ, Lenz ME, Uchida A, Masuda K. Platelet-rich plasma (PRP) stimulates the extracellular matrix metabolism of porcine nucleus pulposus and anulus fibrosus cells cultured in alginate beads. Spine. 2006;31(9):959–66. PubMed

Xu W, Jong Hong S, Jia S, Zhao Y, Galiano RD, Mustoe TA. Application of a partial-thickness human ex vivo skin culture model in cutaneous wound healing study. Laboratory investigation; a journal of technical methods and pathology. 2012;92(4):584–99. PubMed

Xu R, Boudreau A, Bissell MJ. Tissue architecture and function: dynamic reciprocity via extra- and intra-cellular matrices. Cancer metastasis reviews. 2009;28(1–2):167–76. PubMed PMC

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01383187