Combination of Hyaluronic Acid with Advance-Platelet Rich Fibrin to Reduce Chronic Inflammation: a study in IL-6 and Granulation Index

BACKGROUND: Type-2 Diabetes mellitus patients have risk of diabetic foot ulcers (DFUs) ranging from 15% to 25% with morbidity of 5% in the first 12 months, and the mortality rate at 5 years is around 42%. AIM: This research was conducted to study the novelty of a combining Hyaluronic Acid (HA) with Advanced Platelet Rich Fibrin (A-PRF) to reduce inflammation in DFUs healing through raising granulation index. METHODS: The study used a randomized control trial design, done from July 2019-March 2020 at Gatot Soebroto Army Hospital and Koja District Hospital, Jakarta. Subjects were DFU wound area < 40 cm². At the start of the study all subjects received the same treatment, debridement and standard wound care. Twenty subjects were recruited according to the rule of thumb and were randomly divided into two groups namely topical A-PRF + HA (n = 10) and NaCl 0.9% (control) groups (n = 10). A part of the sample was processed into lysate and stored in -80^oC. The rest is applied as a topical therapy in DFU base on intervention (A-PRF+HA or NaCl as a control). We analyzed the inflammation use swab sampling in DFU and analyze use ELISA on day- 3 and day-7. We also measured the wound area by a digital photograph and analyzed using ImageJ at the same time. RESULT: From this research, it was obtained 20 DFU subjects with Wagner 2 classification. We also performed analysis of IL-6 from swab topical DFU. A-PRF+HA group was significantly lower than NaCl (control) from swab DFU on day -3 (p = 0,,049) and day-7 (p = 0.041). In A-PRF+HA group affected on increase epithelialization process/ decrease wound area on day-3 (p = 0.016), day-7 (p = 0.048), and day-14 (p= 0.03 CONSLUSION: With the homogeneous gel formation of A-PRF + HA, it will accelerate the formation of granulation tissue compared to conventional NaCl therapy through reduce inflammation by decrease IL-6 levels. In addition, the combination A-PRF + HA has the effect of accelerating the formation of epithelialization shown by decreasing wound area in intervention group.