Avenanthramide and -Glucan Therapeutics Accelerate Wound Healing Via Distinct and Nonoverlapping Mechanisms

ADVANCES IN WOUND CARE(2024)

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Abstract
Objective: Given the significant economic, health care, and personal burden of acute and chronic wounds, we investigated the dose dependent wound healing mechanisms of two Avena sativa derived compounds: avenanthramide (AVN) and beta-Glucan. Approach: We utilized a splinted excisional wound model that mimics human-like wound healing and performed subcutaneous AVN and beta-Glucan injections in 15-week-old C57BL/6 mice. Histologic and immunohistochemical analysis was performed on the explanted scar tissue to assess changes in collagen architecture and cellular responses. Results: AVN and beta-Glucan treatment provided therapeutic benefits at a 1% dose by weight in a phosphate-buffered saline vehicle, including accelerated healing time, beneficial cellular recruitment, and improved tissue architecture of healed scars. One percent AVN treatment promoted an extracellular matrix (ECM) architecture similar to unwounded skin, with shorter, more randomly aligned collagen fibers and reduced inflammatory cell presence in the healed tissue. One percent beta-Glucan treatment promoted a tissue architecture characterized by long, thick bundles of collagen with increased blood vessel density. Innovation: AVN and beta-Glucan have previously shown promise in promoting wound healing, although the therapeutic efficacies and mechanisms of these bioactive compounds remain incompletely understood. Furthermore, the healed ECM architecture of these wounds has not been characterized. Conclusions: AVN and beta-Glucan accelerated wound closure compared to controls through distinct mechanisms. AVN-treated scars displayed a more regenerative tissue architecture with reduced inflammatory cell recruitment, while beta-Glucan demonstrated increased angiogenesis with more highly aligned tissue architecture more indicative of fibrosis. A deeper understanding of the mechanisms driving healing in these two naturally derived therapeutics will be important for translation to human use.
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Key words
excisional wound healing,tissue architecture,inflammation,angiogenesis,avenanthramide,beta-Glucan
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