Sepia Melanin for the Local Deactivation of Matrix Metalloproteinases

Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes that degrade the extracellular matrix and play essential functions in wound healing and tissue remodeling. However, the long-term overexpression of MMPs is associated with a chronic wound environment. Treatments that locally deactivate MMPs have been proposed to improve the outcomes of nonhealing chronic wounds. In this Letter, sepia melanin, a natural biopigment, is explored for the deactivation of MMPs, through chelation of zinc ions. Melanins have chemical functional groups to bind to various metal ions, which we demonstrate can be exploited for the deactivation of MMPs. Melanin’s selectivity for zinc ions, and ability to deactivate MMPs that are associated with chronic wounds (MMP-1, MMP-2, and MMP-9) are examined, and its potential application in wound healing is demonstrated by functional in vitro tissue assays, mimicking the nonhealing wound environment. This is the first demonstration of the use of melanin for MMP deactivation.