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Immunomodulatory Hydrogel Dressings for Timed Drug Release

(K. Spiller and M.Weingarten)

Abstract: Drexel’s biomedical engineers and physicians have developed a novel hydrogel-based dressing that protects the wound while keeping it moist and delivers bioactive compounds that correct the underlying problem in chronic wounds, thus restoring the natural healing process.

Normal wound healing involves three stages: inflammation, proliferation, and remodeling. Diabetic wounds are known for being stalled in the inflammatory state. The new hydrogel-based wound dressing is designed to facilitate the transition of macrophages, the main regulatory cells of inflammation, from pro-inflammatory to pro-healing to pro-remodeling phenotypes, and at appropriate times, to restore the natural healing process. This is achieved by controlled sequential release of two bioactive compounds. The first one, IL4, causes the conversion of the M1 macrophages to M2A macrophages, leading to inhibition of inflammation, suppression of proteolytic activity, promotion of blood vessel maturation, and synthesis of extracellular matrix. After a specified period of time the depot of IL4 is exhausted, and the M2A macrophages revert to a resting phenotype. This reversion causes increased activity of matrix metalloproteases (MMPs) that stimulate the release of the second compound from the hydrogel, IL10. IL10 is prevented from bioactivity until its linkage is cleaved by MMPs, thus allowing the M2A phenotype to thrive long enough to promote cell proliferation and deposition of extracellular matrix components. The macrophage-mediated release of IL10 causes their polarization to the M2C phenotype, which promotes matrix remodeling and finishes the healing process. Thus, this technology exploits new understanding of the chronic wound biology to mediate the release of interleukins that exert control over the sequential actions of macrophages in order to restore the normal process of healing.