Wound Healing in Diabetic Foot Ulcer Patients Using Combined Use of Platelet Rich Fibrin and Hyaluronic Acid, Platelet Rich Fibrin and Placebo: An Open Label, Randomized Controlled Trial

Authors

  • Ronald Winardi Kartika FKUI
  • Idrus Alwi Division of Cardiology, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia – Cipto Mangunkusumo Hospital, Jakarta, Indonesia
  • Franciscus D Suyatna Department of Clinical Pharmacology, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
  • Em Yunir Department of Internal Medicine, Faculty of Medicine Universitas Indonesia – Cipto Mangunkusumo Hospital, Jakarta, Indonesia
  • Sarwono Waspadji Department of Internal Medicine, Faculty of Medicine Universitas Indonesia – Cipto Mangunkusumo Hospital, Jakarta, Indonesia
  • Suzana Immanuel Department of Clinical Pathology, Faculty of Medicine Universitas Indonesia – Cipto Mangunkusumo Hospital, Jakarta, Indonesia
  • Saptawati Bardosono Department of Nutrition, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
  • Saleha Sungkar Department of Clinical Parasitology, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
  • Jusuf Rachmat Department of Thorcic Cardiac and Vascular Surgery, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
  • Mirta Hediyati Department of ENT, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
  • Todung Silalahi Department of Internal Medicine, Krida Wacana Christian University, Jakarta, Indonesia

Keywords:

diabetic foot ulcer, platelet-rich fibrin, hyaluronic acid

Abstract

Background: Autologous platelet-rich fibrin (A-PRF) is an adjunctive method for diabetic foot ulcer (DFU) in addition to glycaemic control and debridement. This study aimed to evaluate the role of A-PRF + hyaluronic acid (HA), A-PRF and sodium chloride 0.9% (control) in DFU wound healing. Nowaday, the use of  PRF autologous consider as adjuvant therapy in DFU treatment. Methods: This open-label randomized controlled trial was conducted at Koja District Hospital and Gatot Soebroto Hospital from July 2019 to April 2020. DFU patients with wound duration of three months, Wagner-2, and ulcer size < 40 cm2 were recruited and randomly assigned into A-PRF + AH, A-PRF and control group. On day-0, day-3 and day -7, samples and photographs were taken. Samples were analysed with ELISA and photographs were analysed with ImageJ to calculate granulation index (GI). Statistical analysis was performed using SPSS version 20. Results: Topical therapy with A-PRF + AH was associated with a significant increase in VEGF from day 0 (232.8 pg/mg) vs day 7 (544.5 pg/mg) compared to A-PRF on day 0 (185.7 pg/mg) vs day 7 (272.8 pg/mg), and the controls on day 0 (183.7 pg/mg) vs day 7 (167.4 pg/mg). On evaluation  of VEGF swab, there is increasing significantly in A-PRF+HA group compare others group in day -3 ( p=0.022) and day -7 (p= 0.001).In the A-PRF + AH group, there was a significant decrease in IL-6 from day 0 (106.4 pg/mg) vs day 7 (88.7 pg/mg) compared with PRF on day 0 (91.9 pg/mg) vs day 7 (48,8 pg/mg). IL-6 was increased in the control group from day 0 (125.3 pg/mg) vs day 7 (167.9 pg/mg). On evaluation  of IL-6 swab, there is decreasing significantly in A-PRF+HA group compare others group in day -7 (p= 0.041). Conclusion: The PRF + HA combination increased angiogenesis and reduced inflammation in DFUs and may represent a new DFU therapy.

Author Biography

Ronald Winardi Kartika, FKUI

I am interest in bioinformatika

References

Carvajal Am, Gluud C, Nicola S, Racines DS, Reveiz L, Olivia P. Growth factors for treating diabetic foot ulcers. Cochrane Database Syst Rev. 2015;28(10): 548−55.

Amstrong DG, Cohen K, Courric S, Bharara M, Marston W. Diabetic foot ulcers and vascular insufficiency: our population has changed, but our methods have not. J Diabetes Sci Technol. 2011;5(6): 1591–5.

Jindatanmanusan P, Luanraksa S, Boonsiri T, Nimmanon T, Arnutti P. Wound fluid matrix metalloproteinase-9 as a potential predictive marker for the poor healing outcome in diabetic foot ulcers. Pathol Res Int. 2018;25(4):1−6.

Kany S, Tilman K, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci. 2019;20(23): 6008.

Zubair M, Jamal A. Role of growth factors and cytokines in diabetic foot ulcer healing. Rev Endocr Metab Disord. 2019;20(8):1−11.

Tiaka EK, Papanas N, Mmanolakis N, Georgiadis G, Epidermal growth factor in the treatment of diabetic foot ulcers: an update. Perspectives Vascular Surgery. 2012;24(1):37-44.

Moraes VY, Lenza M, Tamaoki MJ, Faloppa F, Belloti JC. Platelet-rich therapies for musculoskeletal soft tissue injuries. Cochrane Database Syst Rev. 2014;29: 7−19.

Evert P, Onichi K, Jayaram P, Lana JF, Meutner K. Platelet-rich plasma L new performance understandngs and therapeutic consideration in 2020. Int J Mol Sci. 2020;21(20):7794; https://doi.org/10.3390/ijms21207794.

Caruana A, Savina D, Macedo J, Soares S. From platelet-rich plasma to advanced-platelet-rich Fibrin: Biological achievements and clinical advances in modern surgery. Eur J Dent. 2019;13(2):280–6.

Raeissadat S, Rayegani S, Hassanabadi H. Knee osteoarthritis injection choices: platelet- rich plasma (PRP) versus hyaluronic acid (a one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord. 2015;8:18.

Ramos-Torrecillas J, García-Martínez O, De Luna-Bertos E, Oca~Na-Peinado Fm, Ruiz C. Effectiveness of platelet-rich plasma and hyaluronic acid for the treatment and care of pressure ulcers. Biol Res Nurs. 2015;17:1528.

Anikumar TV, Muhamed J, Jose A, et al. Advantage of hyaluronic acid as a component of fibrin sheet for care of acute wound. Biologicals. 2011;39(2):81-8. doi 10.1016/j.biologicals.2011.01.003

Sridharan K, Sivaramakrishnan G. Growth factors for diabetic foot ulcers: mixed treatment comparison analysis of randomized clinical trials. Br J Clin Pharmacol. 2018;84(3):434–44. DOI: 10.1111/bcp.13470

Drela E, Kulwas A, Wieslaw J, Goralczyk B , Boinska J, Drewniak W. VEGF-A and PDGF-BB angiogenic factors and the stage of diabetic foot syndrome advancement. Endocrinol. 2014;65(4):30612.

Amoli M, Ranjbar S, Roohipour N, Sayahpour F, Amiri P, Zahedi P. VEGF gene polymorphism association with diabetic foot ulcer. Diabetes Res Clin Pract. 2011;93:2159.

Tahergorabi Z, Khazae M. Imbalance of angiogenesis in diabetic complications: the mechanisms. Int J Prev Med. 2012;3(12):827–38.

Perez AG, Rodrigues AA, Luzo AC, Lana JF. Fibrin network architectures in pure platelet-rich plasma characterized by fiber radius and correlated with clotting time. J Mater Sci Mater Med. 2014;25(8):1967-77. doi: 10.1007/s10856-014-5235-z.

Pardue E, Ibrahim S, Ramamurthi A. Role of hyaluronan in angiogenesis and its utility to angiogenic tissue engineering. Organogenesis. 2008;4(4): 203–14.

Ilio K, FurukawaKI, Tsuda E, et.al. Hyaluronic acid induces the release of growth factors from platelet-rich plasma Asia-Pacific Journal of Sports Medicine. Arthroscopy, Rehabilitation and Technology. 2016;4: 2732.

Garbin LC, Olver CS. Platelet-rich products and their application to osteoarthritis. J Equine Vet Sci. 2020;86(10):10-18. doi: 10.1016/j.jevs.2019.102820.

Transforming Growth Factor-β1 (TGF-β1)-stimulated Fibroblast to Myofibroblast Differentiation Is Mediated by Hyaluronan (HA)-facilitated Epidermal Growth Factor Receptor (EGFR) and CD44 Co-localization in Lipid Rafts. J. Bio Chemistry. 2013;288(21):14824-38. doi10.1074/jbc.M113.451336

Yazdanpanah L, Nasiri M, Adarvishi S, Literature review on the management of diabetic foot ulcer, World J Diabetes. 2015;6(1):37-53.

doi: 10.4239/wjd.v6.i1.37

Chen WH, Lo WC, Hsu WC. Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy. Biomaterials. 2014;35:9599−607.

Jayakumar R, Prabaharan M, Kumar S, Tamura H, Biomaterials based on chitin and chitosan in wound dressing applications. Biotech Adv. 2012(29):2322-337.

Downloads

Published

2021-10-04

How to Cite

1.
Kartika RW, Alwi I, Suyatna FD, Yunir E, Waspadji S, Immanuel S, Bardosono S, Sungkar S, Rachmat J, Hediyati M, Silalahi T. Wound Healing in Diabetic Foot Ulcer Patients Using Combined Use of Platelet Rich Fibrin and Hyaluronic Acid, Platelet Rich Fibrin and Placebo: An Open Label, Randomized Controlled Trial. Acta Med Indones [Internet]. 2021Oct.4 [cited 2026Oct.21];53(3):268. Available from: https://www.actamedindones.org/index.php/ijim/article/view/1601

Most read articles by the same author(s)

<< < 1 2 3 4 > >>