Elucidating the Biological Role of Autologous Derived Platelet-Rich Plasma Gel in the Treatment of Chronic Diabetic Foot Ulcers.

Abstract

The molecular basis for the use of synthetic growth factors (GFs) in tissue reparation has been poorly investigated. More recently, autologous derived platelet rich growth factor has gained popularity in the field of regenerative/ reparative medicine, mostly because it fits the description of an ideal naturally existing constellation of GFs. However, its efficacy remains controversial. Hence, this study is designed to further elucidate the physiological role of PRP in treating chronic diabetic foot ulcers. Platelet -rich plasma (PRP) and Platelet -poor plasma (PPP) were prepared from blood samples taken from healthy donors and diabetic patients through the use of platelet collecting and concentrating system. The GFs released were measured through immunoassay technique. The effects of the varying concentrations of PRP/PPP in culture media was assessed through tissue culture assay (proliferation, cell migration and angiogenesis assay) on human epithelia keratinocyte, dermal fibroblast and umbilical vein endothelia cell. Furthermore, immuno-histochemistry technique was used to evaluate the differentiation, proliferation, migration and extracellular matrix alterations occurring along wound margins of patients with chronic diabetic ulcers following PRP treatment. A significant difference was observed when the expression of platelet derived growth factor-AA, epidermal growth factor, vascular endothelia growth factor, transforming growth factor and thrombospodin-I released from PRP/PPP were compared between the two groups. There was a significant proliferative, migratory and angiogenic effect of PRP over PPP in the tissue culture assay; however this effect was most prominent with 5% PRP. Overall, hyperproliferative keratin, CD44 and β1-integrin were upregulated in diabetic ulcer keratinocytes as compared with normal foot skin. The clinical study showed that 3 of the 7 diabetic foot ulcer patients treated with PRP achieved complete wound re-epithelisation. We have been able to demonstrate through in vitro studies that PRP has a positive biological effect which mimics normal physiological tissue reparation process.