Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information.
Horejs C-M., St-Pierre J-P., Ojala JRM., Steele JAM., da Silva PB., Rynne-Vidal A., Maynard SA., Hansel CS., Rodríguez-Fernández C., Mazo MM., You AYF., Wang AJ., von Erlach T., Tryggvason K., López-Cabrera M., Stevens MM.
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.