Biomolecule presenting matrices
In nature, the distribution and activity of growth factors is often modulated by extracellular matrix (ECM) components (Figure 1).

In order to adapt these evolved principles for tissue engineering approaches, we are  developing novel ECM-mimicking strategies for delivery and presentation of biomolecules (e.g. growth factors and cytokines) from synthetic as well as natural biomimetic matrices (Figure 2). We have engineered fibrin and PEG hydrogels for slow, continuous, and cell-mediated delivery of vascular endothelial growth factor (VEGF). In a proof-of-concept study in a murine model, this material-based VEGF-delivery strategy has shown robust induction of angiogenesis (formation of new vessels) in absence of commonly observed adverse VEGF treatment effects (vessel leakage).

Currently, we are developing versatile growth factor immobilization and delivery strategies for in vitro as well as in vivo applications that allow generation of 3D patterned micro- environments (Figure 3), hydrogel based purification, and inducible release of growth factors (Figure 4).


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M. Ehrbar, S.M. Zeisberger, G.P. Raeber, J.A. Hubbell, C. Schnell, A.H. Zisch, The role of actively released fibrin-conjugated VEGF for VEGF receptor 2 gene activation and the enhancement of angiogenesis, Biomaterials., (2008), 1720-1729

M. Ehrbar, V.G. Djonov, C. Schnell, S.A. Tschanz, G. Martiny-Baron, U. Schenk, J. Wood, P.H. Burri, J.A. Hubbell, A.H. Zisch, Cell-demanded liberation of VEGF121 from fibrin implants induces local and controlled blood vessel growth, Circ Res, (2004), 1124-32

Lienemann P.S., Lutolf M.P., Ehrbar M., Biomimetic hydrogels for controlled biomolecule delivery to augment bone regeneration., Adv Drug Deliv Rev., (2012), 1078-89

Lienemann PS, Karlsson M, Sala A, Wischhusen HM, Weber FE, Zimmermann R, Weber W, Lutolf MP, Ehrbar M., A versatile approach to engineering biomolecule-presenting cellular microenvironments., Adv Healthc Mater., (2013), 292-6

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Figure 4