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The effectiveness of topical hyaluronic acid on decreasing Interleukin-6 and acceleration of wound healing (Push Score) in Wagner II-III diabetic foot ulcer in Dr. Soetomo Hospital Surabaya


Background: A diabetic foot ulcer is a complication that often occurs in patients with diabetes mellitus. The healing process of a chronic wound is more complicated and requires more complex treatment. There is an increase in IL-1, IL6, and TNF-α pro-inflammatory cytokines in a chronic wound. Hyaluronic acid (HA) is a component that has been used for a long time and is known to help the wound healing process. This study was at a time to determine the effectiveness of hyaluronic acid on the reduction of interleukin-6 in accelerating the healing of Wagner II-III diabetic foot ulcers.

Methods: This study is an experimental, randomized study of pre and post-test design on diabetic foot ulcer patients with the Wagner II-III classification who were controlled at the thoracic, cardiac, and vascular surgery polyclinic at Dr. Soetomo Hospital Surabaya. Data were analyzed using SPSS version 20 for Windows.

Result: About 39 samples are willing to participate in the study, divided into 20 samples in the treatment group and 19 in the control group. The mean concentrations of IL-6 in the treatment group before and after the intervention were 280.70±155.50 ng/ml and 126.60±145.60 ng/ml. There was a significant decrease in IL-6 levels (p<0.05) before and after the intervention. The mean concentrations of IL-6 in the control group pre and post were 315.20±127.40 ng/ml and 136.30±134.60 (p<0.05). The decrease in the control and treatment groups was no statistically significant difference (p>0.05). There was no significant difference in the PUSH Score (p>0.05) in the two groups before intervention/treatment. The decrease of wound area in the control and treatment groups were -4.80 ((-0.40)-(-24.50)) and -4.8 ((-0.70)-(-30.90)) (p>0.05).

Conclusion: Topical hyaluronic acid and wound care using 0.9% NaCl reduced interleukin-6 levels, PUSH scores, and wound area in Wagner II-III diabetic foot ulcers.


  1. Mulyani WRW, Sanjiwani MID, Sandra, Prabawa IPY, Lestari AAW, Wihandani DM, et al. Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes. 2020;13:559-568.
  2. Kemenkes RI. Hari Diabetes Sedunia Tahun 2018. Pusat Data dan Informasi Kementerian Kesehatan Republik Indonesia. 2019;1–8.
  3. Saputra MKA, Semadi IN, Widiana IGR. Wound treatment with hyaluronic acid and silver sulfadiazine promote better epithelialization compared to polyurethane and normal saline in diabetic foot ulcer. Indones J Biomed Sci. 2019;13(2):67–71.
  4. Rathur HM, Boulton AJM. The diabetic foot. Clin Dermatol. 2007;25(1):109–20.
  5. Gatot D, Lindarto D, Mardia AI. Incidence of deep vein thrombosis in patients with diabetic foot ulcers. Bali Medical Journal. 2019;8(2):551-554.
  6. Noor S, Zubair M, Ahmad J. Diabetic foot ulcer- A review on pathophysiology, classification and microbial etiology. Diabetes Metab Syndr Clin Res Rev. 2015;9(3):192–199.
  7. Masuelli L, Tumino G, Turriziani M, Modesti A, Bei R. Topical Use of Sucralfate in Epithelial Wound Healing: Clinical Evidence and Molecular Mechanisms of Action. Recent Pat Inflamm Allergy Drug Discov. 2009;4(1):25–36.
  8. Preethi SP, Dhanasekaran V. Comparative study of efficacy and cost effectiveness of topical sucralfate and conventional dressings in diabetic ulcers. Int J Surg Sci. 2019;3(4):435–438.
  9. Barrois B, Carles M, Rumeau M, Tell L, Toussaint J-F, Bonnefoy M, et al. Efficacy and Tolerability of Hyaluronan (ialuset) in the Treatment of Pressure Ulcers. Drugs R D. 2007;8(5):267–273.
  10. Sudarsa IW, Semadi IN, Riasa NP. Hyaluronic Acid Caused of Wider Epithelialization Compare to Normal Saline in Severe Diabetic Ulcer. Bali Medical Journal. 2012;1(1):32-35.
  11. Chen CP, Hung W, Lin SH. Effectiveness of hyaluronic acid for treating diabetic foot: a systematic review and meta-analysis. Dermatol Ther. 2014;27(6):331-336.
  12. George-Saintilus E, Tommasulo B, Cal CE, Hussain R, Mathew N, Dlugacz Y, et al. Pressure ulcer PUSH score and traditional nursing assessment in nursing home residents: do they correlate? J Am Med Dir Assoc. 2009;10(2):141-144.
  13. Zubair M, Malik A, Ahmad J. Plasma adiponectin, IL-6, hsCRP, and TNF-α levels in subject with diabetic foot and their correlation with clinical variables in a North Indian tertiary care hospital. Indian J Endocrinol Metab. 2012;16(5):769-776.
  14. Bekeschus S, Schmidt A, Napp M, Kramer A, Kerner W, von Woedtke T, et al. Distinct cytokine and chemokine patterns in chronic diabetic ulcers and acute wounds. Exp Dermatol. 2017;26(2):145–147.
  15. Kartika RW, Alwi I, Suyatna FD, Yunir E, Waspadji S, Immanuel S, et al. The role of VEGF, PDGF and IL-6 on diabetic foot ulcer after Platelet Rich Fibrin + hyaluronic therapy. Heliyon. 2021;7(9):e07934.
  16. Ramos-Torrecillas J, García-Martínez O, De Luna-Bertos E, Ocaña-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(2):152–158.
  17. Hon J, Lagden K, McLaren AM, O’Sullivan D, Orr L, Houghton PE, et al. A prospective, multicenter study to validate use of the pressure ulcer scale for healing (PUSH©) in patients with diabetic, venous, and pressure ulcers. Ostomy Wound Manag. 2010;56(2):26–36.
  18. Lee Y, Yun TK, Han S. Effect of Hyaluronic Acid Dressing on Diabetic Ulcer Healing -A Pilot Study. J Korean Wound Management Soc. 2014;10(2):67-74.
  19. Hwang Y, Park YJ, Shim D-W, Lee M, Park KH, Suh JW, et al. Hyaluronic Acid Dressing in the Treatment of Diabetic Foot Ulcer. Foot Ankle Orthop. 2016;1(1):2473011416S0007.

How to Cite

Gulo, C. I. H., Puruhito, & Novida, H. (2022). The effectiveness of topical hyaluronic acid on decreasing Interleukin-6 and acceleration of wound healing (Push Score) in Wagner II-III diabetic foot ulcer in Dr. Soetomo Hospital Surabaya. Bali Medical Journal, 11(3), 1049–1053.




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