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PEG-based bioactive hydrogels crosslinked via phosphopantetheinyl transferase

Published online by Cambridge University Press:  01 February 2011

Katarzyna Mosiewicz
Affiliation:
[email protected], Ecole Polytechnique Federal de Lausanne, Laboratory of Stem Cells Bioengineering, Institute of Bioengineering, Lausanne, Switzerland
Kai Johnsson
Affiliation:
[email protected], Ecole Polytechnique Federal de Lausanne, Laboratory of Protein Engineering, Institute of Bioengineering, Lausanne, Switzerland
Matthias P. Lutolf
Affiliation:
[email protected], Ecole Polytechnique Fédérale de Lausanne, Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, Lausanne, Switzerland
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Abstract

State-of-the-art tissue engineering strategies increasingly rely on the performance of bioactive hydrogels formed via cell-friendly crosslinking reactions. Enzymatic reactions possess ideal characteristics for such applications, but they are currently still underexplored in biomaterials design. Here we report the development of hybrid bioactive hydrogels formed via a posttranslational modification reaction using phosphopantetheinyl transferase (PPTase). PPTase was shown to catalyze the covalent crosslinking of CoenzymeA-functionalized poly(ethylene glycol) (PEG) multiarm macromers and recombinantly produced acyl carrier protein (ACP) dimers. Crosslinking kinetics and physicochemical properties of PPTase hydrogels were characterized. Proof-of-principle experiments demonstrate the successful covalent bio-functionalization of gels with a CoA-derivatized cell adhesion peptide. Polymerization of gels in the presence of primary mammalian cells was shown to result in no loss in cell viability compared to a well established, chemically crosslinked gel system.

Type
Research Article
Copyright
Copyright © Materials Research Society 2010

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References

REFERENCES

[1] Lutolf, M. P., Tirelli, N. Cerritelli, S. Cavalli, L. Hubbell, J. A. Bioconjug Chem 12 (2001) 10511056.Google Scholar
[2] DeForest, C. A. Polizzotti, B. D. Anseth, K. S. Nature Materials 8 (2009) 659664.Google Scholar
[3] Hu, B. H. Su, J. Messersmith, P. B. Biomacromolecules 10 (2009) 21942200.Google Scholar
[4] Sperinde, J. J. Griffith, L. G. Macromolecules 30 (1997) 52555264.Google Scholar
[5] Ehrbar, M. Rizzi, S. C. Schoenmakers, R. Hubbell, J. A. Weber, F. E. Lutolf, M. P. Biomacromolecules 8 (2007) 30003007.Google Scholar
[6] Chen, T. H. Embree, H. D. Brown, E. M. Taylor, M. M. Payne, G. F. Biomaterials 24 (2003) 28312841.Google Scholar
[7] Kurisawa, M. Chung, J. E. Yang, Y. Y. Gao, S. J. Uyama, H. Chemical Communications (2005) 43124314.Google Scholar
[8] Hu, B. H. Messersmith, P. B. Journal of the American Chemical Society 125 (2003) 1429814299.Google Scholar
[9] Lambalot, R. H. Gehring, A. M. Flugel, R. S. Zuber, P. LaCelle, M. Marahiel, M. A. Reid, R. Khosla, C. Walsh, C. T. Chemistry & Biology 3 (1996) 923936.Google Scholar
[10] Zhou, Z. Cironi, P. Lin, A. J. Xu, Y. Hrvatin, S. Golan, D. E. Silver, P. A. Walsh, C. T. J. Yin, ACS Chem Biol 2 (2007) 337346.Google Scholar
[11] Wong, L. S. Thirlway, J. Micklefield, J. Journal of the American Chemical Society 130 (2008) 1245612464.Google Scholar
[12] Yin, J. Straight, P. D. McLoughlin, S. M. Zhou, Z. Lin, A. J. Golan, D. E. Kelleher, N. L. Kolter, R., Walsh, C. T. Proceedings of the National Academy of Sciences of the United States of America 102 (2005) 1581515820.Google Scholar
[13] Lutolf, M. P. Hubbell, J. A. Biomacromolecules 4 (2003) 713722.Google Scholar
[14] Mosiewicz, K. A. Johnsson, K. Lutolf, M. P. Journal of the American Chemical Society DOI: 10.1021/ja9098164 (2010).Google Scholar
[15] Keppler, A. Gendreizig, S. Gronemeyer, T. Pick, H. Vogel, H. Johnsson, K. Nature Biotechnology 21 (2003) 8689.Google Scholar