Ehrbar

Group Leader:
Martin Ehrbar
Head of Research

Name of the Institution
Department of Obstetrics
University Hospital Zurich

Street
Schmelzbergstrasse 12

City
8091 Zürich

Phone
+41 (0)44 255 85 13

Fax
+41 (0)44 255 44 30

 

Stéphanie Metzger, PhD student
Yannick Devaud, PhD student
Ulrich Blache, PhD student
Esther Kleiner, technical assistent
Michael Burger, trainee
 
Ehemalige:
Philipp Lienemann, PhD
Anna-Sofia Kiveliö, PhD
Michela Perrini, PhD
Ana Sala Roca, PhD
Ajit Sankar Mallik MD, PhD
Oleg V. Semenov, PhD
Algirdas Ziogas, PhD
Claudia Haller, PhD
Wilfried Bürzle, PhD
 

Main Field of Research, Abstract

Development of fully synthetic modular designed biomaterials. Although naturally occurring biomaterials are well suitable for tissue regeneration approaches, they contain matrix inherent properties that limit their use in engineering applications. In collaboration with the laboratories of Prof. Franz Weber, University Hospital Zürich, Prof. Matthias Lütolf EPFL Lausanne and Prof. Wilfried Weber Bioss Freiburg Germany, we develop a fully synthetic hydrogel platform that can be designed towards specific matrix engineering applications in vitro and in vivo. Building blocks are developed that will allow the combination of features such as mechanical properties, proteolytic susceptibility, integrin binding, and growth factor presentation within the otherwise inert poly (ethylene glycol) PEG hydrogels. Ongoing studies with this materials platform focus on: the study of cell-extracellular matrix interactions, the establishment of in vitro tissue-like constructs, the recruitment and characterization of bone precursor cells, and bone healing in vivo.

Major topics of research

  • Development of adult stem cell implants: Exploration of stem / progenitor cells from human umbilical cord blood, amniotic fluid, and placenta for tissue healing applications other than hematopoietic applications. The objective is to develop cell-based therapeutics for healing of diseased cardiovascular tissue, chronic skin wounds, cartilage or bone. Transplantation of such cells may require their fixation in the treated tissue. We seek the development of implants comprised of adult stem cells in biomaterials that support engraftment and differentiation of adult stem cells.
  • Healing of premature preterm rupture of the fetal membrane (PPROM). PPROM represents a devastating complication in obstetrics for which no treatment exists yet. We seek to develop implant prepared from resorbable biomatrices and human amnion cells that permit to immediately plug the leak in the ruptured membrane and guide wound healing in the following (a concept of sealing and healing). Cell biological and biochemical studies and proteomics are used to identify protein substances that will promote growth of native human amnion tissue in bioengineered healing devices.
  • Development of biomaterial-protein therapeutics for biological revascularization of ischemic tissues or chronic wounds: One implant matrix from our research and development (see below), fibrin matrix formulated with covalently affixed vascular endothelial growth factor, has recently completed safety studies such that it has become approved by the ethical committee of the Kanton of Zurich for clinical studies of treatment of patients with fingertip ulcers. Ongoing studies concern tissue angiogenesis response to implants on the transcriptional level. To this end, we apply Xenogen biophotonic imaging technology and genetically engineered mice in which a luciferase reporter is driven by the promoter of the VEGF receptor 2 to non-invasively monitor the transcriptional response over weeks in the animal.
  • Growth factor-loaded matrix coatings that promote prosthetic graft endothelialization. Synthetic small-diameter blood vessel replacements have a high failure rat, but early endothelialization of the lumenal surface may improve graft patency. In vivo endothelialization of synthetic grafts may be achieved by pretreatment of synthetic graft implants with angiogenic substrates that recruit endothelial cells across the anastomis, from the blood stream, or transmurally.
  • Cell sheet engineering. In collaboration with the laboratory of Prof. Janos Voeros, ETH Zurich, we seek development of three-dimensionally designed composite materials consisting of cell-sheets and polymer hydrogel films for tissue engineering. The basis of the project is a new method of the Voeros laboratory at ETH Zurich that allows for the harvesting of cell sheets by electrochemical means. Such 3D cell/polymer multilayers will be used as a new platform to spatially pattern different cell types for the analysis of complex physiology in vitro and for drug screening applications. Target models are the cellular situation of an adult blood vessel, and instruction of differentiation of stem cells by enddifferentiated cells.

Recent Publications

2015

Milleret V, Buzzi S, Gehrig P, Ziogas A, Grossmann J, Schilcher K, Zinkernagel AS, Zucker A, Ehrbar M, Protein adsorption steers blood contact activation on engineered cobalt chromium alloy oxide layers., Acta Biomaterialia (2015) Epub ahead of print

Perrini M, Mauri A, Ehret AE, Ochsenbein-Kölble N, Zimmermann R, Ehrbar M, Mazza E., Mechanical and microstructural investigation of the cyclic behavior of human amnion, J Biomech Eng, (2015),

Arabella Mauri, Alexander E. Ehret, Michela Perrini, Caroline Maake, Nicole Ochsenbein-Kölble, Martin Ehrbar, Michelle L. Oyend, Edoardo Mazza, Deformation mechanisms of human amnion: Quantitative studies based on second harmonic generation microscopy., J of Biomechanics, (2015), > open in PubMed

2014

Moriyama M, Metzger S, van der Vlies AJ, Uyama H, Ehrbar M, Hasegawa U., Inhibition of Angiogenesis by Antioxidant Micelles., Adv Healthc Mater. , (2014), Epub ahead of print

Milleret V, Ziogas A, Buzzi S, Heuberger R, Zucker A, Ehrbar M., Effect of oxide layer modification of CoCr stent alloys on blood activation and endothelial behavior, J Biomed Mater Res B Appl Biomater. , (2014)

Sacchi V., Mittermayr R., Hartinger J., Martino M., Lorentz K., Wolbank S, Hofmann A, Largo R, Marschall J., Groppa E., Gianni-Barrera R., Ehrbar M., Hubbell JA3, Redl H2, Banfi A7., Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF164., Proc Natl Acad Sci U S A., (2014), 6952-7 > open in PubMed

Hänseler P, Ehrbar M, Kruse A, Fischer E, Schibli R, Ghayor C, Weber FE., Delivery of BMP-2 by two clinically available apatite materials: In vitro and in vivo comparison., J Biomed Mater Res A., (2014), > open in Pubmed

Milleret V, Simona BR, Lienemann PS, Vörös J, Ehrbar M., Electrochemical control of the enzymatic polymerization of PEG hydrogels: formation of spatially controlled biological microenvironments., Adv Healthc Mater., (2014), 508-14 > open in PubMed

Cai WX, Zheng LW, Li CL, Ma L, Ehrbar M, Weber FE, Zwahlen RA., Effect of different rhBMP-2 and TG-VEGF ratios on the formation of heterotopic bone and neovessels., BioMed Research International, (2014), > open in PubMed

Lienemann PS, Devaud YR, Reuten R, Simona BR, Karlsson M, Weber W, Koch M, Lutolf MP, Milleret V, Ehrbar M., Locally controlling mesenchymal stem cell morphogenesis by 3D PDGF-BB gradients towards the establishment of an in vitro perivascular niche., Integr Biol (Camb). (2014). > open in Pubmed

Kivelio A., Ochsenbein-Koelble N., Zimmermann R., Ehrbar M., Engineered cell instructive matrices for fetal membrane healing. Acta Biomater. (2014). > open in PubMed

Metzger S, Lienemann PS, Ghayor C, Weber W, Martin I, Weber FE, Ehrbar M., Modular Poly(ethylene glycol) Matrices for the Controlled 3D-Localized Osteogenic Differentiation of Mesenchymal Stem Cells. Adv Healthc Mater. (2014) > open in Pubmed

Kivelio A., Ehrbar M., Recent Advances in 3 D Tissue Models, Buchartilel in "Engineered Cell Manipulation for Biomedical Application", (2014). > Link

___________________________________________________

2013

Mosiewicz KA, Kolb L, van der Vlies AJ, Martino MM, Lienemann PS, Hubbell JA, Ehrbar M, Lutolf MP, In situ cell manipulation through enzymatic hydrogel photopatterning, Nature Materials, (2013), 1072–1078 > open in PubMed

Kivelio A, Dekoninck P, Perrini M, Brubaker CE, Messersmith PB, Mazza E, Deprest J, Zimmermann R, Ehrbar M, Ochsenbein-Koelble N, Mussel mimetic tissue adhesive for fetal membrane repair: initial in vivo investigation in rabbits, European Journal of Obstetrics & Gynecology and Reproductive Biology, (2013), > open in PubMed

Mauri A, Perrini M, Mateos JM, Maake C, Ochsenbein-Koelble N, Zimmermann R, Ehrbar M, Mazza E., Second harmonic generation microscopy of fetal membranes under deformation: Normal and altered morphology, Placenta, (2013), 1020-6, > open in PubMed

Karlsson M, Rebmann B, Lienemann PS, Sprossmann N, Ehrbar M, Radziwill G, Weber W., Pharmacologically Controlled Protein Switch for ON-OFF Regulation of Growth Factor Activity, Scientific reports, (2013) > open in PubMed

Gübeli RJ, Schöneweis K, Huzly D, Ehrbar M, Charpin-El Hamri G, El-Baba MD, Urban S, Weber W, Pharmacologically triggered hydrogel for scheduling hepatitis B vaccine administration, Scientific reports, (2013) > open in PubMed

Karlsson M, Lienemann PS, Sprossmann N, Heilmann K, Brummer T, Lutolf MP, Ehrbar M, Weber W, A generic strategy for pharmacological caging of growth factors for tissue engineering., Chemical Communications, (2013) > open in PubMed

Cai WX, Zheng LW, Weber FE, Li CL, Ma L, Ehrbar M, Zwahlen RA, Heterotopic bone formation around vessels: pilot study of a new animal model, Bio Research Open Access, (2013) > open in PubMed

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 > open in PubMed

Müller K, Engesser R, Metzger S, Schulz S, Kämpf MM, Busacker M, Steinberg T, Tomakidi P, Ehrbar M, Nagy F, Timmer J, Zubriggen MD, Weber W., A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells., Nucleic Acids Research, (2013), > open in PubMed

Ruiz-Villalba A, Ziogas A, Ehrbar M, Pérez-Pomares JM., Characterization of epicardial-derived cardiac interstitial cells: differentiation and mobilization of heart fibroblast progenitors., PLoS One, (2013), > open in PubMed

Hoffmann DC, Willenborg S, Koch M, Zwolanek D, Mueller S, Becker AK, Metzger S, Ehrbar M, Kurschat P, Hellmich M, Hubbell JA, Eming SA, Proteolytic processing regulates Placental growth factor activities., J Biol Chem., (2013), > open in PubMed

Perrini M, Bürzle W, Haller C, Ochsenbein-Kölble N, Deprest J, Zimmermann R, Mazza E, Ehrbar M., Contractions, a risk for premature rupture of fetal membranes: A new protocol with cyclic biaxial tension, Medical Engineering & Physics, (2013),
> open in PubMed

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2012

Buerzle W, Haller CM, Jabareen M, Egger J, Mallik AS, Ochsenbein-Koelble N, Ehrbar M, Mazza E., Multiaxial mechanical behavior of human fetal membranes and its relationship to microstructure., Biomech Model Mechanobiol., (2012), Epub ahead of print]
> open in PubMed

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
> open in PubMed

Gübeli RJ, Ehrbar M, Fussenegger M, Friedrich C, Weber W., Synthesis and Characterization of PEG-Based Drug-Responsive Biohybrid Hydrogels., Macromol Rapid Commun., (2012), 1280-5
> open in PubMed

Studer D, Lischer S, Jochum W, Ehrbar M, Zenobi-Wong M, Maniura-Weber K., Ribosomal protein l13a as a reference gene for human bone marrow-derived mesenchymal stromal cells during expansion, adipo-, chondro-, and osteogenesis., Tissue Eng Part C Methods., (2012), 761-71 > open in PubMed

Haller CM, Buerzle W, Kivelio A, Perrini M, Brubaker CE, Gubeli RJ, Mallik AS, Weber W, Messersmith PB, Mazza E, Ochsenbein-Koelble N, Zimmermann R, Ehrbar M., Mussel-mimetic tissue adhesive for fetal membrane repair: an ex vivo evaluation., , (2012), Acta Biomater. 2012 Dec;8(12):4365-70 > open in PubMed

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2011

Zeisberger SM, Schulz JC, Mairhofer M, Ponsaerts P, Wouters G, Doerr D, Katsen-Globa A, Ehrbar M, Hescheler J, Hoerstrup SP, Zisch AH, Kolbus A, Zimmermann H., Biological and physicochemical characterization of a serum- and xeno-free chemically defined cryopreservation procedure for adult human progenitor cells., Cell Transplant, (2011), 1241-57 > open in PubMed

Hlushchuk R, Ehrbar M, Reichmuth P, Heinimann N, Styp-Rekowska B, Escher R, Baum O, Lienemann P, Makanya A, Keshet E, Djonov V, Decrease in VEGF expression induces intussusceptive vascular pruning., Arterioscler Thromb Vasc Biol., (2011), 2836-44 > open in PubMed

Sala A, Hänseler P, Ranga A, Lutolf MP, Vörös J, Ehrbar M, Weber FE., Engineering 3D cell instructive microenvironments by rational assembly of artificial extracellular matrices and cell patterning., , (2011), Integr Biol (Camb). 2011 Nov;3(11):1102-11 > open in PubMed

Sala A, Ehrbar M, Trentin D, Schoenmakers RG, Vörös J, Weber FE., Enzyme mediated site-specific surface modification., Langmuir, (2010), 11127-34 > open in PubMed

San Miguel, B., Ghayor, C., Ehrbar, M., Jung, R. E., Zwahlen, R., Hortschansky, P., Schmokel, H., Weber, F., (2009) The chemical NMP as a potent BMP enhancer for bone tissue regeneration Tissue Eng Part A

Ghayor, C., Ehrbar, M., San Miguel, B., Gratz, K. W., Weber, F. E. (2009) cAMP enhances BMP2-signaling through PKA and MKP1-dependent mechanismsBiochem Biophys Res Commun 381, 247-52

Ehrbar, M., Schoenmakers, R., Christen, E.H., Fussenegger, M., and Weber, W. (2008). Drug-sensing hydrogels for the inducible release of biopharmaceuticals. Nature materials.

Ehrbar, M., Zeisberger, S.M., Raeber, G.P., Hubbell, J.A., Schnell, C., and Zisch, A.H. (2008). The role of actively released fibrin-conjugated VEGF for VEGF receptor 2 gene activation and the enhancement of angiogenesis. Biomaterials 29, 1720-1729.

Ehrbar, M., Rizzi, S.C., Schoenmakers, R.G., Miguel, B.S., Hubbell, J.A., Weber, F.E., and Lutolf, M.P. (2007). Biomolecular hydrogels formed and degraded via site-specific enzymatic reactions. Biomacromolecules 8, 3000-3007.

Ehrbar, M., Rizzi, S.C., Hlushchuk, R., Djonov, V., Zisch, A.H., Hubbell, J.A., Weber, F.E., and Lutolf, M.P. (2007). Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering. Biomaterials 28, 3856-3866.

Rizzi, S.C., Ehrbar, M., Halstenberg, S., Raeber, G.P., Schmoekel, H.G., Hagenmuller, H., Muller, R., Weber, F.E., and Hubbell, J.A. (2006). Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part II: biofunctional characteristics. Biomacromolecules 7, 3019-3029.

Weber, C.C., Cai, H., Ehrbar, M., Kubota, H., Martiny-Baron, G., Weber, W., Djonov, V., Weber, E., Mallik, A.S., Fussenegger, M., et al. (2005). Effects of protein and gene transfer of the angiopoietin-1 fibrinogen-like receptor-binding domain on endothelial and vessel organization. The Journal of biological chemistry 280, 22445-22453.

Ehrbar, M., Metters, A., Zammaretti, P., Hubbell, J.A., and Zisch, A.H. (2005). Endothelial cell proliferation and progenitor maturation by fibrin-bound VEGF variants with differential susceptibilities to local cellular activity. J Control Release 101, 93-109.

Ehrbar, M., Djonov, V.G., Schnell, C., Tschanz, S.A., Martiny-Baron, G., Schenk, U., Wood, J., Burri, P.H., Hubbell, J.A., and Zisch, A.H. (2004). Cell-demanded liberation of VEGF121 from fibrin implants induces local and controlled blood vessel growth. Circulation research 94, 1124-1132.


Jabareen M, Mallik AS, Zisch AH*, Mazza E. Mechanical and histological characterization of human fetal membranes. Eur J Obstet Gynecol Reprod Biol, in press *Corresponding author, co-principal investigator

Burkhardt T, Matter C, Lohmann C, Hao C, Luscher T, Zisch AH, Beinder E. Fetal programming of hypertension: Decreased compliance and low IGF-1 levels in umbilical arteries of infants with intrauterine growth restriction. Placenta, Epub ahead of print.

Zisch AH, Zimmermann R. Bioengineering of fetal membrane repair. Swiss Med Wkly 138:596-601 (2008).

Deprest J, Lewi L, Devlieger R, De Catte L, Hoylaerts M, Ochsenbein-Kölble N, Bilic G, Zisch AH, Zimmermann R. Correspondence: Enrichment of collagen plugs with platelets and amniotic fluid cells increases cell proliferation in sealed iatrogenic membrane defects in the foetal rabbit model. Prenatal Diagnosis 28:878-80 (2008)

Davies N, Dobner S, Bezuidenhout D, Schmidt C, Beck M, Zisch AH, Zilla P. The dosage dependence of VEGF stimulation on scaffold vascularization. Biomaterials 29:3531-8 (2008)

Ehrbar M, Zeisberger SM, Raeber G, Hubbell JA, Schnell C, Zisch AH. The role of actively released fibrin-conjugated VEGF for VEGF receptor 2 gene activation and the enhancement of angiogenesis. Biomaterials 11:1720-1729 (2008)

Bilic G, Zeisberger SM, Mallik AS, Zimmermann R, Zisch AH. Comparative characterization of cultured human amnion epithelial and mesenchymal stromal cells for application in cell therapy. Cell Transplantation 17:955-968 (2008).

Parolini, O. et al. Concise Review: Isolation and characterization of stem cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells. Stem Cells 26:300-11 (2008)

Mallik, AS, Fichter MA, Rieder S, Bilic G, Stergioula, S, Henke J, Schneider KTM, Biemer, E, Zimmermann R, Zisch AH*, Papadopulos NA. Fetoscopic closure of punctured fetal membranes with acellular human amnion plugs in a rabbit model Obstet. Gynecol 110:1121-1129 (2007) *corresponding author, principal investigator

Ehrbar M, Rizzi S, Djonov V, Ruslan H, Zisch AH, Hubbell, JA, Weber F, Lutolf MP. Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering Biomaterials 28:.3856-3866 (2007)

Zhou L, Martinez SJ, Haber M, Bouvier D, Doucet G, Fon EA, Zisch AH, Murai KK. EphA4 signaling regulates phspholipase Cy1 activation, cofilin membrane association, and dendritic spine morphology. J Neurosci 9:5127-38 (2007)

Walpoth BH, Zammaretti P, Cikiricioglu M, Khabiri E, Djebaili K, Pache J-C, Tille J-C, Aggoun Y, Morel D, Kalangos A, Hubbell JA, Zisch AH. Enhanced intimal thickening of ePTFE grafts coated with fibrin or fibrin releasing vascular endothelial growth factor in the pig carotid artery interposition model J Thorac Cardiovasc Surg. 133(5):1163-70 (2007)

Helm C-LE, Zisch AH, Swartz M. Engineered blood and lymphatic capillaries in 3-D VEGF-fibrin-collagen matrices with interstitial flow. Biotechnol Bioeng 96 (1):167-76 (2007)

Portmann-Lanz C, Ochsenbein-Köble N, Marquardt K, Lüthi U, Zisch AH, Zimmermann R. Manufacture of a cell-free amnion matrix scaffold that supports amnion cell outgrowth in vitro. Placenta 28:6-13 (2007)

URL

(Institution's Address on Internet and, if available, on Intranet)
www.geburtshilfe.usz.ch