Skip to main content Skip to main navigation menu Skip to site footer

A new innovation in topical diabetic foot ulcer; hyaluronic acid platelet-rich fibrin (HAPRF) gel - a study in inflammation and angiogenesis

  • Ronald W. Kartika ,
  • Idrus Alwi ,
  • Em Yunir ,
  • Sarwono Waspadji ,
  • Saptawati Bardosono ,
  • Suzzana Immanuel ,
  • Todung Silalahi ,
  • Saleha Sungkar ,
  • Jusuf Rachmat ,
  • Franciscus D. Suyatna ,
  • Mirta Hediyati Reksodiputro ,


Background: Indonesia ranks 6th out of ten countries with the highest number of diabetes patients. An increase followed this condition in the prevalence of diabetic foot ulcers by around 15%. This study demonstrated the ability of combination of Platelet Rich Fibrin (PRF) and Hyaluronic Acid (HA) to reduce inflammation in diabetic foot ulcer (DFU) healing.

Methods: In the baseline, all patients received the same treatment including wound debridement. There were 20 subjects divided into two groups; HAPRF and  PRF. A part of sample was processed into lysate and stored in -80oC. The rest is applied as a topical therapy in DFU base on intervention. We analyzed the inflammation using two methods; swab in DFU and fibrin gel of HAPRF or PRF and ELISA on day-3 and day-7. We also measure the granulation index by digital photograph and analyze use ImageJ at the same time.

Result: There were 20 diabetic patients with DFUs, performed analysis of  IL-6  lysate gel HAPRF decrease  significantly compare with PRF on day 3 (p= 0.038) and day-7 (p = 0.034). Granulation index evaluation, in HAPRF increase on day-3 (p = 0.043), day-7 (p = 0.049), and day-14 (p = 0.041).

Conclusion: A-PRF +HA  administration leads to reduce  IL-6 levels, and accelerated wound healing of DFUs patients. HAPRF  directly aids epithelialization and granulation index.


  1. Cho NH, Shaw JE, Karuranga S. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271?81. doi:10.1016/j.diabres.2018.02.023
  2. Heydari I, Radi V, Razmjou S, Amiri A. International Journal of Diabetes Mellitus Chronic complications of diabetes mellitus in newly diagnosed patients. Int J Diabetes Mellit. 2010;2(1):61?3. doi:10.1016/j.ijdm.2009.08.001
  3. Everett E, Mathioudakis N. Update on management of diabetic foot ulcers. Ann N Y Acad Sci. 2018;11(1):153?65. doi:10.1111/nyas.13569
  4. Caroline C.L.M. Naves. The Diabetic Foot: A Historical Overview and Gaps in Current Treatment. Adv W Care, 2016;5(5):1?7.
  5. Grazul-Bilska AT, Johnson ML, Bilski JJ. Wound healing: The role of growth factors. DrugsToday. 2003;39(10):787?800. doi:10.1358/dot2003.39
  6. Doulton AJM, Armstrong avid G, Kirsner RS. Diagnosis and management of diabetic foot complications. Current Diabetes Update. 2018;2018(2):1?20. doi:10.2337/DB20182-1
  7. Schär MO, Diaz-Romero J, Kohl S, Zumstein MA, Nesic D. Platelet-rich Concentrates Differentially Release Growth Factors and Induce Cell Migration In Vitro. Clin Orthop Relat Res. 2015;473(5):1635?43. doi:10.1007/s11999-015-4192?9
  8. Dhurat R, Sukesh M. Principles and preparation of platelet-rich plasma: A review and author?s perspective. J Cutan Aesthet Surg. 2014;7(4):189?95. doi:10.4103/0974-2077.150734
  9. Dohan D, Choukroun J, Diss A. Platelet Rich Fibrin -A Second Regeneration Platelet Concentrate and Advances in PRF. Indian J Dent Adv. 2016;7(4):53?7 doi:10.5866/2015.7.10251
  10. Vokurka J, Goepfert E, Blahutkova M, Buchalova E, Faldyna M. Concentrations of growth factors in platelet-rich plasma and platelet-rich fibrin in a rabbit model. Vet Med (Praha). 2016;61(10):567?70. doi:10.17221/24/2016-VETMED
  11. Nasirzade J, Kargarpour Z, Hasannia S, Strauss FJ, Gruber R. Platelet-Rich Fibrin Elicits an Anti-Inflammatory Response in Macrophages In Vitro. J Periodontol. 2020;91(2):244?52. doi: 10.1002/JPER.19-0216.
  12. Afat IM, Akdogan ET, Gonul O. Effects of leukocyte- and platelet-rich fibrin alone and combined with hyaluronic acid on pain, edema, and trismus after surgical extraction of impacted mandibular third molars. J Oral Maxillofac Surg. 2018;76(5):926?32. doi: 10.1016/j.joms.2017.12.005.
  13. Russo F, D'Este M, Vadalà G, Cattani C, Papalia R, Alini M, Denaro V. Platelet Rich Plasma and Hyaluronic Acid Blend for the Treatment of Osteoarthritis: Rheological and Biological Evaluation. PLoS One. 2016 Jun 16;11(6):e0157048. doi: 10.1371/journal.pone.0157048.
  14. Wu X, Yang L, Zheng Z, Li Z , Shi J, Li Y, et al. Src promotes cutaneous wound healing by regulating MMP-2 through the ERK pathway. International J of Molecular Med 2016:(37)3:639?48. doi:10.3892/ijmm.2016.2472
  15. Iio K, Furukawa KI, Tsuda E. Hyaluronic acid induces the release of growth factors from platelet-rich plasma. Asia-Pacific J Sport Med Arthrosc Rehabil Technol. 2016;4(3):17?32. doi:10.1016/j.asmart.2016.01.001
  16. Janggan S, Yuda HA, Aris WM, Diana L, Askandar T, Aloe Gel Enhances Angiogenesis in Healing of Diabetic Wound. Indones Biomed J. 2011;3(3):1?12.
  17. Fathi WK. The Effect of Hyaluronic Acid and Platelet - Rich Plasma on Soft Tissue Wound Healing: An Experimental Study on Rabbits. Al-Rafidain Dent J. 2012;12(3):115?25.
  18. Ulcers DF. Role of Interleukin-6 (IL-6) and Indicators of Inflammation in the Pathogenesis of. Aust. J. Basic & Appl. Sci. 2012;6(6):430?5.
  19. Arsianti RW, Parman DW, Lesmana H, Taufiqqurohman M. Effect of Electrical Stimulation in Lower Extremity as Physical Exercise in Type 2 Diabetes Mellitus Patients. Indones Biomed J. 2016;10(1):62?5.
  20. Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol. 2019;26(3):259?65. doi:10.1111/j.1574-695X.1999.tb01397.x
  21. Tuttolomondo A, La Placa S, Di Raimondo D, Bellia C, Caruso A, Lo Sasso B, Guercio Diana G, Ciaccio M, Licata G, et al. Adiponectin, resistin and IL-6 plasma levels in subjects with diabetic foot and possible correlations with clinical variables and cardiovascular co-morbidity. Cardiovasc Diabetol. 2010;9:50-57.
  22. Agrawal M, Agrawal V. Platelet Rich Fibrin and its Applications in Dentistry- A Review Article. Int J Clin Exp Med. 2015;8(5):7922–9.
  23. Ghanaati S, Maawi S, Schaffner Y, Sader R, Choukroun J, Nacopoulos C. Application of liquid platelet-rich fibrin for treating hyaluronic acid-related complications: A case report with 2 years of follow-up, Int J Growth Factors Stem Cells Dent. 2018;1(2):74?77.
  24. Pati Tangsupati, Kwartarini Murdiastut. The Effect of Collagen Activation on Platelet Rich Plasma for Proliferation of Periodontal Ligament Fibroblasts. Indones Biomed J. 2018;10(3):278-83.
  25. Mussano F, Genova T, Munaron L. Cytokine, chemokine, and growth factor profile of platelet-rich plasma. Platelets 2016;27(5):467?71. doi :10.3109. /09537104.2016.1143922
  26. Yang P, Pei Q, Yu T. Compromised wound healing in ischemic type 2 diabetic rats. PLoS One. 2016;11(3):1?19. doi:10.1371. /journal pone.0152068
  27. Landen NZ, Li D. Transition from Inflammation to Proliferation: a critical step during wound healing. Cell Moll Life Sci. 2016;73(1):3861?85
  28. Ghanaati S, Maawi S, Schaffner Y, Sader R, Choukroun J, Nacopoulos C. Application of liquid platelet-rich fibrin for treating hyaluronic acid-related complications: A case report with 2 years of follow-up. Int J Growth Factors Stem Cells Dent. 2018;1(2):74?77.

How to Cite

Kartika, R. W., Alwi, I., Yunir, E., Waspadji, S., Bardosono, S., Immanuel, S., Silalahi, T., Sungkar, S., Rachmat, J., Suyatna, F. D., & Reksodiputro, M. H. (2021). A new innovation in topical diabetic foot ulcer; hyaluronic acid platelet-rich fibrin (HAPRF) gel - a study in inflammation and angiogenesis. Bali Medical Journal, 10(3), 901–908.




Search Panel