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Title

Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information

AuthorsHorejs, Christine-Maria; Rynne-Vidal, Ángela; López-Cabrera, Manuel; Stevens, Molly M.
Issue Date8-Jun-2017
PublisherNature Publishing Group
CitationNature Communications 8 (2017)
AbstractMatrix 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.
URIhttp://hdl.handle.net/10261/166372
Identifiersdoi: 10.1038/ncomms15509
issn: 2041-1723
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