Rodríguez-Fernández, C. (Clara)
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- Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information(Nature Research, 2017) Horejs, C.M. (Christine-Maria); Erlach, V.T. (Von Thomas); Maynard, S.A. (Stephanie A.); Stevens, M.M. (Molly M.); Rynne-Vidal, A. (Angela); Wang, A.J. (Alex J.); Hansel, C.S. (Catherine S.); You, A.Y.F. (Amanda Y.F.); Ojala, J.R.M. (Juha R. M.); Tryggvason, K. (Karl); López-Cabrera, M. (Manuel); Mazo, M. (Manuel); Barros-da-Silva, P. (Patricia); St-Pierre, J.P. (Jean-Philippe); Rodríguez-Fernández, C. (Clara); Steele, J.A.M. (Joseph A.M.)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 b1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the b1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor b1 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.