Phenolic Extract(s) from Wild Blueberries promote(s) wound healing via vascularization

Abstract

Wounds occur in over 15 million people with approximately $60 billion spent annually on wound care. Deficient vascularization is a significant factor that promotes chronic and non‐healing wounds, ultimately resulting in amputation. Currently, most clinical wound treatments are antibiotics for infection control. Therefore, chronic wounds such as diabetic foot ulcers, ischemic limbs, and pressure ulcers lack treatments for healing. Our lab reported that phenolic extracts (PE) from wild blueberries (WB) promote angiogenesis in HUVEC cells via cell migration, angiogenesis, and VEGF/P13K/AKT pathway. However, the in vivoeffect is still unknown. To investigate the in vivo pathways of PE from WB on vascularized wound healing, we extracted PE from WB by Folin‐Ciocalteu method, and incorporated them into a serum [hyaluronic (HA) gel] and a cream carrier. We grouped fifty‐six Sprague‐Dawley rats into seven groups as follows: Group1 as Control (nothing applied on the skin); Group 2 as the cream base, without the PE; Group 3 as the HA gel base, without PE; Group 4 as the HA gel base with 500 μg/ml of the PE; Group 5 as the cream base with 500 μg/ml of PE; Group 6 as the HA gel base with PE at 1000 μg/ml; and Group7 as the cream base with PE at 1000 μg/ml. We created dorsal surgical wounds on each rat and treated them accordingly for six days. Photographs were taken daily to assess wound closure. Percentage wound closure was determined using ImageJ. Thereafter, the tissues were excised and stained with H&E, visualized and quantified under light microscope for proliferating cells associated with vascular wound closure. We observed 12% increase in wound closure and significant increase in endothelial cells on the wound area with 500 μg/ml of PE in serum (HA gel) treatment when compared to the control without treatment. The results support the potential effect of PE to promote vascularized wound healing. Frozen tissues are currently being analyzed for genes and proteins associated with vascularization. This project is innovative because it provides new insights into the metabolomic pathways of PE treatment in rats used as a wound healing model. Results of this project may be beneficial to patients with chronic wounds promoting vascularization and wound healing, with all natural, inexpensive, no side effect wound healing products, using Phenolic extracted from WB.