Influence of Platelet Concentrates on Wound Healing

Platelet-Rich Plasma Clinical Trial

Official title:

The Influence of Autologous Platelet Concentrates on Human Keratinocyte Proliferation in Vitro and Wound Healing in Vivo

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03667638
• Other study ID #: #1055-2011
• Status: Completed
• Phase: N/A
• Start date: November 2016
• Est. completion date: December 2017

Study information

• Verified date: September 2018
• Source: Hannover Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Chronic soft tissues defects can extend into the fat layer or even deeper and can cause functional disadvantages. Split-thickness skin grafts (STSGs) used to cover these wounds have varying success rates. To improve wound healing in chronic wounds the authors have studied the application of autologous platelet concentrates in a human keratinocyte culture model in vitro and in a combination with surgical procedures in vivo as second line therapy in patients with initially failed wound closure.

Description:

For in vitro testing on keratinocytes a platelet-mediator concentrate (PMC) was processed with a commercially available bed-side system (ATR®, Curasan, Germany). In a clinical study soft tissue defects (n=5) were treated using a combination of surgical debridement and autologous platelet rich plasma (PRP). Time of healing as determined by epithelization as well as Laser Doppler Imaging to visualize blood flow were analyzed. Additionally, changes in "ease of surgical wound closure" were determined. Finally, the quality of life of patients was assessed using a validated questionnaire.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: December 2017
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• exposed tendons, ligaments or bone for >3 weeks

• no healing tendency

Exclusion Criteria:

• sepsis

• intensive care treatment

• continuous smoking

• pregnancy or breast feeding women

• participants of other studies.

Related Conditions & MeSH terms

• Platelet-Rich Plasma
• Wound Healing Delayed
• Wounds and Injuries

Intervention

Combination Product:
• Platelet-Rich Plasma
Adding PRP to wound bed during surgical debridement

Locations

Country	Name	City	State
Germany	Medical School Hannover	Hannover	Niedersachsen

Sponsors (1)

Lead Sponsor	Collaborator
Hannover Medical School

Country where clinical trial is conducted

Germany, 

References & Publications (38)

Achora S, Muliira JK, Thanka AN. Strategies to promote healing of split thickness skin grafts: an integrative review. J Wound Ostomy Continence Nurs. 2014 Jul-Aug;41(4):335-9; quiz E1-2. doi: 10.1097/WON.0000000000000035. Review. — View Citation

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Amable PR, Carias RB, Teixeira MV, da Cruz Pacheco I, Corrêa do Amaral RJ, Granjeiro JM, Borojevic R. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther. 2013 Jun 7;4(3):67. doi: 10.1186/scrt218. — View Citation

Anitua E, Aguirre JJ, Algorta J, Ayerdi E, Cabezas AI, Orive G, Andia I. Effectiveness of autologous preparation rich in growth factors for the treatment of chronic cutaneous ulcers. J Biomed Mater Res B Appl Biomater. 2008 Feb;84(2):415-21. — View Citation

Appel TR, Pötzsch B, Müller J, von Lindern JJ, Bergé SJ, Reich RH. Comparison of three different preparations of platelet concentrates for growth factor enrichment. Clin Oral Implants Res. 2002 Oct;13(5):522-8. — View Citation

Asadi M, Alamdari DH, Rahimi HR, Aliakbarian M, Jangjoo A, Abdollahi A, Bahar MM, Azadmand A, Forghani N, Sadegh MN, Khayamy ME, Seifalian A. Treatment of life-threatening wounds with a combination of allogenic platelet-rich plasma, fibrin glue and collagen matrix, and a literature review. Exp Ther Med. 2014 Aug;8(2):423-429. Epub 2014 May 29. — View Citation

Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008 Sep-Oct;16(5):585-601. doi: 10.1111/j.1524-475X.2008.00410.x. Review. — View Citation

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Berg L, Meyer S, Ipaktchi R, Vogt PM, Müller A, de Zwaan M. [Psychosocial Distress at Different Time Intervals after Burn Injury]. Psychother Psychosom Med Psychol. 2017 Jun;67(6):231-239. doi: 10.1055/s-0042-111006. Epub 2016 Sep 29. German. — View Citation

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Burnouf T, Tseng YH, Kuo YP, Su CY. Solvent/detergent treatment of platelet concentrates enhances the release of growth factors. Transfusion. 2008 Jun;48(6):1090-8. doi: 10.1111/j.1537-2995.2008.01691.x. Epub 2008 Mar 25. — View Citation

Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011 May 19;473(7347):298-307. doi: 10.1038/nature10144. Review. — View Citation

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 Jun;74(3):244-55. — View Citation

Cho JW, Kim SA, Lee KS. Platelet-rich plasma induces increased expression of G1 cell cycle regulators, type I collagen, and matrix metalloproteinase-1 in human skin fibroblasts. Int J Mol Med. 2012 Jan;29(1):32-6. doi: 10.3892/ijmm.2011.803. Epub 2011 Sep 30. — View Citation

Cohn CS, Lockhart E. Autologous platelet-rich plasma: evidence for clinical use. Curr Opin Hematol. 2015 Nov;22(6):527-32. doi: 10.1097/MOH.0000000000000183. Review. — View Citation

Danielsen P, Jørgensen B, Karlsmark T, Jorgensen LN, Agren MS. Effect of topical autologous platelet-rich fibrin versus no intervention on epithelialization of donor sites and meshed split-thickness skin autografts: a randomized clinical trial. Plast Reconstr Surg. 2008 Nov;122(5):1431-40. doi: 10.1097/PRS.0b013e318188202c. — View Citation

Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg. 2004 Nov;114(6):1502-8. — View Citation

Gilliver SC, Ashworth JJ, Ashcroft GS. The hormonal regulation of cutaneous wound healing. Clin Dermatol. 2007 Jan-Feb;25(1):56-62. Review. — View Citation

Gould L, Abadir P, Brem H, Carter M, Conner-Kerr T, Davidson J, DiPietro L, Falanga V, Fife C, Gardner S, Grice E, Harmon J, Hazzard WR, High KP, Houghton P, Jacobson N, Kirsner RS, Kovacs EJ, Margolis D, McFarland Horne F, Reed MJ, Sullivan DH, Thom S, Tomic-Canic M, Walston J, Whitney JA, Williams J, Zieman S, Schmader K. Chronic wound repair and healing in older adults: current status and future research. J Am Geriatr Soc. 2015 Mar;63(3):427-38. doi: 10.1111/jgs.13332. Epub 2015 Mar 6. — View Citation

House SL. Psychological distress and its impact on wound healing: an integrative review. J Wound Ostomy Continence Nurs. 2015 Jan-Feb;42(1):38-41. doi: 10.1097/WON.0000000000000080. Review. — View Citation

Kaltalioglu K, Coskun-Cevher S. A bioactive molecule in a complex wound healing process: platelet-derived growth factor. Int J Dermatol. 2015 Aug;54(8):972-7. doi: 10.1111/ijd.12731. Epub 2014 Oct 14. Review. — View Citation

Kawase T. Platelet-rich plasma and its derivatives as promising bioactive materials for regenerative medicine: basic principles and concepts underlying recent advances. Odontology. 2015 May;103(2):126-35. doi: 10.1007/s10266-015-0209-2. Epub 2015 Jun 4. Review. — View Citation

Khatib M, Jabir S, Fitzgerald O'Connor E, Philp B. A systematic review of the evolution of laser Doppler techniques in burn depth assessment. Plast Surg Int. 2014;2014:621792. doi: 10.1155/2014/621792. Epub 2014 Aug 7. Review. — View Citation

Kim SA, Ryu HW, Lee KS, Cho JW. Application of platelet-rich plasma accelerates the wound healing process in acute and chronic ulcers through rapid migration and upregulation of cyclin A and CDK4 in HaCaT cells. Mol Med Rep. 2013 Feb;7(2):476-80. doi: 10.3892/mmr.2012.1230. Epub 2012 Dec 12. — View Citation

Limbourg A, Korff T, Napp LC, Schaper W, Drexler H, Limbourg FP. Evaluation of postnatal arteriogenesis and angiogenesis in a mouse model of hind-limb ischemia. Nat Protoc. 2009;4(12):1737-46. doi: 10.1038/nprot.2009.185. Epub 2009 Nov 5. — View Citation

Mammoto T, Jiang A, Jiang E, Mammoto A. Platelet rich plasma extract promotes angiogenesis through the angiopoietin1-Tie2 pathway. Microvasc Res. 2013 Sep;89:15-24. doi: 10.1016/j.mvr.2013.04.008. Epub 2013 May 6. — View Citation

Martinez-Zapata MJ, Martí-Carvajal AJ, Solà I, Expósito JA, Bolíbar I, Rodríguez L, Garcia J. Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst Rev. 2012 Oct 17;10:CD006899. doi: 10.1002/14651858.CD006899.pub2. Review. Update in: Cochrane Database Syst Rev. 2016;(5):CD006899. — View Citation

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Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E. Platelets and wound healing. Front Biosci. 2008 May 1;13:3532-48. Review. — View Citation

Okuda K, Kawase T, Momose M, Murata M, Saito Y, Suzuki H, Wolff LF, Yoshie H. Platelet-rich plasma contains high levels of platelet-derived growth factor and transforming growth factor-beta and modulates the proliferation of periodontally related cells in vitro. J Periodontol. 2003 Jun;74(6):849-57. — View Citation

Paul DW, Ghassemi P, Ramella-Roman JC, Prindeze NJ, Moffatt LT, Alkhalil A, Shupp JW. Noninvasive imaging technologies for cutaneous wound assessment: A review. Wound Repair Regen. 2015 Mar-Apr;23(2):149-62. doi: 10.1111/wrr.12262. Review. — View Citation

Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res. 2012;49(1):35-43. doi: 10.1159/000339613. Epub 2012 Jul 11. Review. — View Citation

Robson MC, Maggi SP, Smith PD, Wassermann RJ, Mosiello GC, Hill DP, Cooper DM. Original articles: ease of wound closure as an endpoint of treatment efficacy. Wound Repair Regen. 1999 Mar-Apr;7(2):90-6. — View Citation

Shaw TJ, Martin P. Wound repair at a glance. J Cell Sci. 2009 Sep 15;122(Pt 18):3209-13. doi: 10.1242/jcs.031187. Review. — View Citation

Weibrich G, Kleis WK, Hafner G, Hitzler WE, Wagner W. Comparison of platelet, leukocyte, and growth factor levels in point-of-care platelet-enriched plasma, prepared using a modified Curasan kit, with preparations received from a local blood bank. Clin Oral Implants Res. 2003 Jun;14(3):357-62. — View Citation

Weibrich G, Kleis WK. Curasan PRP kit vs. PCCS PRP system. Collection efficiency and platelet counts of two different methods for the preparation of platelet-rich plasma. Clin Oral Implants Res. 2002 Aug;13(4):437-43. — View Citation

Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003 Jul;83(3):835-70. Review. — View Citation

Xian LJ, Chowdhury SR, Bin Saim A, Idrus RB. Concentration-dependent effect of platelet-rich plasma on keratinocyte and fibroblast wound healing. Cytotherapy. 2015 Mar;17(3):293-300. doi: 10.1016/j.jcyt.2014.10.005. Epub 2014 Nov 21. — View Citation

* Note: There are 38 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Wound Closure	Area of wound closure in % compared to initial size	4 weeks
Secondary	Blood Flow	Blood flow measured in wound margins and wound bed compared to regular skin measured using Laser Doppler Imaging	4 weeks
Secondary	Wound Quality of Life	Quality of patients' life measured using Wound-QoL® Questionnaire before and after Intervention. Seventeen items are included in the Wound-QoL, which could be attributed to three subscales on everyday life, body, and psyche. The paper presents the overall score. A higher value correlates with more wound related burden, meaning a lower value indicates higher qulitiy of life.; More information: https://www.ncbi.nlm.nih.gov/pubmed/24899053	21 days
Secondary	Ease of surgical wound closure	Estimated ease of surgical wound closure. The patients`wound was discussed by at least two surgeons to obtain agreement on a 14- point "Ease of Closure" scale. This was done on day 0 as well as day 21. The scale ranged from a score of 0, meaning the wound was closed or so small as to require no closure technique, to a score of 13, meaning that it was not possible to close the wound with known reconstructive surgical techniques. A higher value therefore correlates with more complex surgery.; More information: https://www.ncbi.nlm.nih.gov/pubmed/10231510	21 days