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Matrix metalloproteinases (MMPs) contribute to the breakdown of tissue structures such as the basement membrane, promoting tissue fibrosis. Here we developed an electrospun membrane biofunctionalized with a fragment of the laminin β1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the β1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor β1 and rescues tissue integrity ex vivo and in vivo in a mouse model of peritoneal fibrosis. Importantly, our data demonstrate that the membrane inhibits MMP2 expression. Changes in the expression of epithelial-to-mesenchymal transition (EMT)-related molecules further point towards a contribution of the modulation of EMT. Biomaterial-based presentation of regulatory basement membrane signals directly addresses limitations of current therapeutic approaches by enabling a localized and specific method to counteract MMP2 release applicable to a broad range of therapeutic targets.

Original publication

DOI

10.1038/ncomms15509

Type

Journal article

Journal

Nat Commun

Publication Date

08/06/2017

Volume

8

Keywords

Animals, Biocompatible Materials, Disease Models, Animal, Epithelial Cells, Epithelial-Mesenchymal Transition, Epithelium, Extracellular Matrix, Gene Expression Profiling, HEK293 Cells, Humans, Integrin alpha3beta1, Laminin, Mammary Glands, Human, Matrix Metalloproteinase 2, Membranes, Artificial, Mice, Peritoneal Fibrosis, Peritoneum, Protein Binding, Signal Transduction