000171782 001__ 171782
000171782 005__ 20180317093220.0
000171782 0247_ $$2doi$$a10.1016/j.biomaterials.2010.10.016
000171782 02470 $$2ISI$$a000287073000006
000171782 037__ $$aARTICLE
000171782 245__ $$aSPARC-derived protease substrates to enhance the plasmin sensitivity of molecularly engineered PEG hydrogels
000171782 269__ $$a2011
000171782 260__ $$c2011
000171782 336__ $$aJournal Articles
000171782 520__ $$aBioactive hydrogels formed from the Michael-type addition reactions of end-functionalized poly (ethylene glycol) macromers with thiol-containing protease-sensitive peptide crosslinkers have previously been described as matrices for cell-induced enzymatic remodeling. In this study, we sought to develop materials formulations with different degradation profiles by evaluating peptides derived from secreted protein acidic and rich in cysteine (SPARC) as potential substrates for plasmin, matrix metalloproteinase (MMP)-1, and MMP-2. Michaelis-Menten analysis showed that different peptides could provide a range of k(cat) values for each enzyme. In most cases, hydrogels formed with crosslinker peptides that had higher k(cat) values degraded faster when exposed to the appropriate enzyme(s), and fibroblasts showed increased cell proliferation and cell spreading when cultured in the faster degrading hydrogels. Further, greater cell invasion was observed from aortic ring segments embedded in the faster degrading hydrogels. The addition of the SPARC-derived peptides to the repertoire of protease-sensitive crosslinkers increases the potential application of these materials by providing enhanced susceptibility to plasmin. Further, the graded increases in k(cat) and the differential responses for plasmin, MMP-1, and MMP-2 can be used to engineer hydrogels with degradation properties tuned to the enzymes produced by particular cell types, allowing for broader in vivo application. (C) 2010 Elsevier Ltd. All rights reserved.
000171782 6531_ $$aBiodegradation
000171782 6531_ $$aBiomimetic material
000171782 6531_ $$aCell spreading
000171782 6531_ $$aHydrogel
000171782 6531_ $$aMatrix metalloproteinase
000171782 6531_ $$aPeptide
000171782 6531_ $$aMatrix Metalloproteinases
000171782 6531_ $$aSequence Specificities
000171782 6531_ $$aExtracellular Matrices
000171782 6531_ $$aGlycol) Hydrogels
000171782 6531_ $$aCell-Adhesive
000171782 6531_ $$aCathepsin K
000171782 6531_ $$aDegradation
000171782 6531_ $$aActivation
000171782 6531_ $$aExpression
000171782 6531_ $$aPeptides
000171782 700__ $$aPatterson, J.
000171782 700__ $$aHubbell, J. A.
000171782 773__ $$j32$$q1301-1310$$tBiomaterials
000171782 909CO $$ooai:infoscience.tind.io:171782$$particle$$pSV
000171782 909C0 $$0252372$$pSV$$xU10445
000171782 917Z8 $$x141360
000171782 937__ $$aEPFL-ARTICLE-171782
000171782 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000171782 980__ $$aARTICLE