Project | EpitHope :: publications list |
Title | Molecularly Engineered Self-Assembling Membranes for Cell-Mediated Degradation |
Publication Type | Papers in Scientific Journals |
Year of Publication | 2014 |
Authors | Ferreira D. S., Lin Y. A., Cui H., Hubbell J. A., Reis R. L., and Azevedo H. S. |
Abstract | The use of peptide engineering to develop self-assembling membranes that are responsive to cellular enzyme activities is reported. The membranes are obtained by combining hyaluronan (HA) and a rationally designed peptide amphiphile (PA) containing a proteolytic domain (GPQGIWGQ octapeptide) sensitive to matrix metalloproteinase-1 (MMP-1). Insertion of an octapeptide in a typical PA structure does not disturb its self-assembly into fibrillar nanostructures neither the ability to form membranes with HA. In vitro enzymatic degradation with hyaluronidase and MMP-1 shows that membranes containing the MMP-1 substrate exhibit enhanced enzymatic degradation, compared with control membranes (absence of MMP-1 cleavable peptide or containing a MMP-1 insensitive sequence), being completely degraded after 7 days. Cell viability and proliferation is minimally affected by the enzymatically cleavable functionality of the membrane, but the presence of MMP-1 cleavable sequence does stimulate the secretion of MMP-1 by fibroblasts and interfere with matrix deposition, particularly the deposition of collagen. By showing cell-responsiveness to biochemical signals presented on self-assembling membranes, this study highlights the ability of modulating certain cellular activities through matrix engineering. This concept can be further explored to understand the cellular remodeling process and as a strategy to develop artificial matrices with more biomimetic degradation for tissue engineering applications. |
Journal | Advanced Healthcare Materials |
Date Published | 2014-11-21 |
DOI | 10.1002/adhm.201400586 |
URL | degradation;enzyme-responsive materials;hyaluronan;matrix metalloproteinase-1;peptide amphiphiles;self-assembling membranes |
Keywords | Degradation, enzyme-responsive materials, Hyaluronan, matrix metalloproteinase-1, peptide amphiphiles, self-assembling membranes |
Rights | restrictedAccess |
Peer reviewed | yes |
Status | published |