Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes.: Part 1:: Development and physicochernical characteristics

被引:166
作者
Rizzi, SC
Hubbell, JA [1 ]
机构
[1] Swiss Fed Inst Technol, Inst Biol Engn & Biotechnol, CH-1015 Lausanne, Switzerland
[2] Ecole Polytech Fed Lausanne, Dept Mat, Lausanne, Switzerland
[3] Ecole Polytech Fed Lausanne, Integrated Biosci Inst, Lausanne, Switzerland
[4] Univ Zurich, Zurich, Switzerland
关键词
D O I
10.1021/bm049614c
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Toward the development of synthetic bioactive materials to support tissue repair, we present here the design, production, and characterization of genetically engineered protein polymers carrying specific key features of the natural extracellular matrix, as well as cross-linking with functionalized poly(ethylene glycol) (PEG) to form hybrid hydrogel networks. The repeating units of target recombinant protein polymers contain a cell-binding site for ligation of cell-surface integrin receptors and substrates for plasmin and matrix metalloproteinases (MMPs), proteases implicated in wound healing and tissue regeneration. Hydrogels were formed under physiological conditions via Michael-type conjugate addition of vinyl sulfone groups of end-functionalized PEG with thiols of cysteine residues, representing designed chemical cross-linking sites within recombinant proteins. Cross-linking kinetics was shown to increase with the pH of precursor solutions. The elastic moduli (G ') and swelling ratios (Q(m)) of the resulting hydrogels could be varied as a function of the stoichiometry of the reacting groups and precursor concentration. Optima of G ' and Q(m), maximum and minimum, respectively, were obtained at stoichiometry ratios r slightly in excess of 1 (r = cysteine/vinyl sulfone). The pool of technologies utilized here represents a promising approach for the development of artificial matrixes tailored for specific medical applications.
引用
收藏
页码:1226 / 1238
页数:13
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