AbstractL2.04 | Application of Avena Sativa Derived Therapeutics β-Glucan and Avenanthramide Accelerate Wound Healing in Mice Via Angiogenic and Anti-inflammatory Mechanisms Hudson C. Kussie2 , William Hahn2 , Filiberto Quintero2 , Dharshan Sivaraj1 , Katharina S. Fischer2 , Andrew Hostler2 , Maia Granoski2 , Dominic Henn4 , Abigail Miller3 , Delaney Schurr3 , Vincent Li3 , William Li3 , Geoffrey C. Gurtner2 , kellen Chen2 1 Stanford University, New York City, NY; 2 Surgery, University of Arizona, Tucson, AZ; 3 The Angiogenesis Foundation, Cambridge, MA; 4 Surgery, University of Texas Southwestern Medical Center, Dallas, TX
Background: Improving wound healing after cutaneous injury decreases complications, prevents chronic wound formation, and improves patient wellbeing. β-Glucan and Avenanthramide (AVE) from oat extracts have previously shown potential to promote wound healing; however, both the mechanism and efficacy of how β-Glucan and AVE affect wound healing remain incompletely understood. In this study, we investigated the dose- and mechanistic effects of subcutaneous injections of β-Glucan and AVE on excisional wound healing in a murine model.
Methods: We utilized 15-week-old C57BL/6 mice in a splinted excisional wounding model to mimic human wound healing. Two dorsal excisional wounds per mouse and three mice per treatment group were used. Each respective group received one of five (0%, 0.1%, 0.5%, 1.0%, 2.0%) differing dosages of AVE dissolved in phosphate buffered saline (PBS) and administered via subcutaneous injection to the wound periphery. In a second set of mice, excisional wounds of each mouse received one of four (0%, 0.1%, 0.5%, 1.0%) differing dosage treatments of β-Glucan dissolved in PBS. Each wound was treated every other day until full wound closure. The wound areas were quantified and expressed as a percentage of the original area. Wound tissue sections were stained for collagen (Masson's Trichrome, Picrosirius Red), for microvessels (CD31), endothelial progenitor cells (EPC) (CD133, CD34), and inflammatory cells (CD45).
Results: 1% β-Glucan and 1% AVE treatment significantly accelerated the rate of wound healing as compared with control mice. Other doses did not significantly improve healing. The mean time for complete wound healing was 10.67 days in the 1% AVE-treated group compared to 12.44 days in the control group (p= 0.032). At day fourteen, 1% AVE also promoted a significant decrease in length and alignment of collagen fibers compared to control (p= 0.033, p= 0.048), and significantly decreased CD45-stained inflammatory cells (p= 0.002). 1% β-Glucan significantly decreased wound size relative to controls at days 8 and 10 (p= 0.009, p= 0.016). At day fourteen, 1% β-Glucan promoted a significant increase in width and length of collagen fibers compared to control (p=0.031, p=0.036). 1% β-Glucan treatment upregulated CD133, CD34, and CD31 expression compared to the control (p=0.001, p=0.036, p=0.040).
Conclusions: 1% β-Glucan and 1% AVE treatment resulted in faster wound closure compared to controls (0%). 1% AVE treatment downregulated inflammatory cell infiltration, which may lead to a more regenerative extracellular matrix (ECM) architecture and accelerate wound healing. 1% β-Glucan treated tissue exhibited more blood vessels than in the control, potentially due to an increase in EPCs, and the resulting ECM with increased collagen fiber size accelerated wound healing. A better understanding of the differing mechanisms driving these naturally derived therapeutics may lead to improved patient wound outcomes.