Advance-Platelet Rich Fibrin and Hyaluronic Acid Combination Improves Interleukin-6 and Granulation Index in Diabetic Foot Ulcer Patients

Ronald Winardi Kartika, Idrus Alwi, Franciscus Dhyanagiri Suyatna, Em Yunir, Sarwono Waspadji, Suzanna Immanuel, Todung Silalahi, Saleha Sungkar, Jusuf Rachmat, Saptawati Bardosono, Mirta Hediyati Reksodiputro

Abstract


BACKGROUND: Diabetic foot ulcer (DFU) is the most common and threatening complication of Diabetes Mellitus (DM). Ideal wound dressing for DFU management should relieve symptoms, provide wound protection, and encourage healing. Advanced-Platelet Rich Fibrin (A-PRF) and Hyaluronic Acid (HA) have been proven to improve wound healing process. This study was aimed to demonstrate the ability of combination of A-PRF and HA in reducing inflammation and improving DFU tissue healing.

METHODS: Twenty DFU subjects were involved in this study, and divided into two groups based on the topical fibrin gel treatment: A-PRF + HA group and A-PRF only group. A-PRF was obtained by peripheral blood centrifugation. A-PRF + HA was prepared by homogening A-PRF and AH with a ratio of 1:0.6. Interleukin-6 (IL-6) level, granulation index (GI), numeric pain score (NPS), and inflammation clinical symptoms (ICS) were assessed on day-0, 3, 7 and 14.

RESULTS: Wound swabs’ IL-6 level on day-7 was found to be significantly lower in A-PRF + HA compared to A-PRF alone (p=0.041). The IL-6 level reduction also found to be significant higher either in wound swabs (day 0-7, p=0.015) or fibrin gel (day 0-3, p=0.049; day 0-7, p=0.034). A-PRF + HA treatment significantly increased the GI even since day-3 (p=0.043), with lower NPS (p<0.001), and ICS score.

CONCLUSION: The combination of A-PRF and HA increases the GI in DFU healing by reducing the inflammation state which will induce the angiogenesis process, as well as reducing pain in DFU subjects better than A-PRF alone.

KEYWORDS: inflammation, interleukin-6, wound healing, angiogenesis, proliferation

 


Full Text:

PDF

References


Heydari I, Radi V, Razmjou S, Amiri A. Chronic complications of diabetes mellitus in newly diagnosed patients. Int J Diabetes Mellit. 2010; 2: 61-3, CrossRef.

Alexiadou K, Doupis J. Management of diabetic foot ulcers. Diabetes Ther. 2012; 3: 4, CrossRef.

Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018; 138: 271-81, CrossRef.

Hilton JR, Williams DT, Beuker B, Miller DR, Harding KG. Wound dressings in diabetic foot disease. Clin Infect Dis. 2004; 39(Suppl 2): S100-3, CrossRef.

Everett E, Mathioudakis N. Update on management of diabetic foot ulcers: Diabetic foot ulcers. Ann NY Acad Sci. 2018; 1411: 153-65, CrossRef.

Naves CCLM. The diabetic foot: a historical overview and gaps in current treatment. Adv Wound Care (New Rochelle). 2016; 5: 191-7, CrossRef.

Grazul-Bilska AT, Johnson ML, Bilski JJ, Redmer DA, Reynolds LP, Abdullah A, et al. Wound healing: the role of growth factors. Drugs Today (Barc). 2003; 39: 787-800, CrossRef.

Boulton AJM, Armstrong DG, Kirsner RS, Attinger CE, Lavery LA, Lipsky BA, et al. Diagnosis and Management of Diabetic Foot Complications. Arlington: American Diabetes Association; 2018, NLMID.

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: 1635-43, CrossRef.

Bielecki T, Dohan Ehrenfest DM. Platelet-rich plasma (PRP) and Platelet-Rich Fibrin (PRF): surgical adjuvants, preparations for in situ regenerative medicine and tools for tissue engineering. Curr Pharm Biotechnol. 2012; 13: 1121-30, CrossRef.

Pavan K, Vikram R, Raja B, Jagadish R. Platelet Rich Fibrin: A Second Regeneration Platelet Concentrate and Advances in PRF. Indian J Dent Adv. 2015; 7: 251-4.

Vokurka J, Gopfert E, Blahutkova M, Buchalova E, Faldyna M. Concentrations of growth factors in platelet-rich plasma and platelet-rich fibrin in a rabbit model. Veterinarni Medicina. 2016; 61: 567-70, CrossRef.

Sargowo D, Handaya AY, Widodo M, Lyrawati D, Tjokroprawiro A. Aloe gel enhances angiogenesis in healing of diabetic wound. Indones Biomed J. 2011; 3: 204-15, CrossRef.

Fathi W. 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: 115-25, CrossRef.

Sallam A, El-Sharawy A. Role of interleukin-6 (IL-6) and indicators of inflammation in the pathogenesis of diabetic foot ulcers. Aust J Basic Appl Sci. 2012; 6: 430-5, article.

Snijders GF, van den Ende CHM, van den Bemt BJF, van Riel PLCM, van den Hoogen FHJ, den Broeder AA, et al. Treatment outcomes of a Numeric Rating Scale (NRS)-guided pharmacological pain management strategy in symptomatic knee and hip osteoarthritis in daily clinical practice. Clin Exp Rheumatol. 2012; 30: 164-70, PMID.

Kartika RW, Alwi I, Suyatna FD, Yunir E, Waspadji S, Suzzanna I, et al. The use of image processing in the evaluation of diabetic foot ulcer granulation after treatment with advanced-platelet rich fibrin + hyaluronic acid. Sys Rev Pharm. 2020; 11: 519-26, article.

Geerlings SE, Hoepelman AIM. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Medical Microbiol. 1999; 26: 259-65, CrossRef.

Arsianti RW, Parman DH, Lesmana H, Taufiqqurohman M. Effect of electrical stimulation in lower extremity as physical exercise in type 2 diabetes mellitus patients. Indones Biomed J. 2018; 10: 62-5, CrossRef.

Sridharan K, Sivaramakrishnan G. Growth factors for diabetic foot ulcers: mixed treatment comparison analysis of randomized clinical trials. Br J Clin Pharmacol. 2018; 84: 434-44, CrossRef.

Ghanaati S, Al-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: 74-7, CrossRef.

Tuttolomondo A, La Placa S, Di Raimondo D, Bellia C, Caruso A, Lo Sasso B, 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, CrossRef.

Soewondo P, Ferrario A, Tahapary D. Challenges in diabetes management in Indonesia: a literature review. Global Health. 2013; 9: 63, CrossRef.

Agarwal M, Agarwal V. Platelet rich fibrin and its applications in dentistry-a review article. Int J Clin Exp Med. 2015; 8: 7922-9, PMID.

Mussano F, Genova T, Munaron L, Petrillo S, Erovigni F, Carossa S. Cytokine, chemokine, and growth factor profile of platelet-rich plasma. Platelets. 2016; 27: 467-71, CrossRef.

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: 244-52, CrossRef.

Gill S, Parks W. Metalloproteinases and their inhibitors: Regulators of wound healing. Int J Biochem Cell Biol. 2008; 40: 1334-47, CrossRef.

Tangsupati P, Murdiastuti K. The effect of collagen activation on platelet rich plasma for proliferation of periodontal ligament fibroblasts. Indones Biomed J. 2018; 10: 278-83, CrossRef.

Corey SJ, Kimmel M, Leonard JN, editors. A Systems Biology Approach to Blood. New York, NY: Springer New York; 2014, NLMID.

Iio K, Furukawa KI, Tsuda E, Yamamoto Y, Maeda S, Naraoka T, et al. Hyaluronic acid induces the release of growth factors from platelet-rich plasma. Asia Pac J Sports Med Arthrosc Rehabil Technol. 2016; 4: 27-32, CrossRef.

Afat İM, Akdoğan ET, Gönül 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: 926-32, CrossRef.

Park D, Kim Y, Kim H, Kim K, Lee YS, Choe J, et al. Hyaluronic acid promotes angiogenesis by inducing RHAMM-TGFβ receptor interaction via CD44-PKCδ. Mol Cells. 2012; 33: 563-74, CrossRef.

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. Int J Mol Med. 2016; 37: 639-48, CrossRef.

Yang P, Pei Q, Yu T, Chang Q, Wang D, Gao M, et al. Compromised wound healing in ischemic type 2 diabetic rats. PLos One. 2016; 11: e0152068, CrossRef.




DOI: https://doi.org/10.18585/inabj.v13i2.1501

Indexed by:

                 

                  

               

     

 

The Prodia Education and Research Institute