Molecularly Engineered Self-Assembling Membranes for Cell-Mediated Degradation

last updated: 2014-12-22
ProjectEpitHope :: publications list
TitleMolecularly Engineered Self-Assembling Membranes for Cell-Mediated Degradation
Publication TypePapers in Scientific Journals
Year of Publication2014
AuthorsFerreira D. S., Lin Y. A., Cui H., Hubbell J. A., Reis R. L., and Azevedo H. S.

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.

JournalAdvanced Healthcare Materials
Date Published2014-11-21
URLdegradation;enzyme-responsive materials;hyaluronan;matrix metalloproteinase-1;peptide amphiphiles;self-assembling membranes
KeywordsDegradation, enzyme-responsive materials, Hyaluronan, matrix metalloproteinase-1, peptide amphiphiles, self-assembling membranes
Peer reviewedyes

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