title: Preserved bioactivity and tunable release of a SDF1-GPVI bi-specific protein using photo-crosslinked PEGda hydrogels.
abstract: Chemokine-induced stem cell recruitment is a promising strategy for post myocardial infarction treatment. Injection of stromal cell-derived factor 1 (SDF1) has been shown to attract bone marrow-derived progenitor cells (BMPCs) from the blood that have the potential to differentiate into cardiovascular cells, which support angiogenesis, enabling the improvement of myocardial function. SDF1-GPVI bi-specific protein contains a glycoprotein VI (GPVI)-domain that serves as an anchor for collagen type I (Col I) and III, which are exposed in the wall of injured vasculature. In this study, we generated a cytocompatible hydrogel via photo-crosslinking of poly(ethylene glycol) diacrylate that serves as a reservoir for SDF1-GPVI. Controlled and sustained release of SDF1-GPVI was demonstrated over a period of 7 days. Release features were modifiable depending on the degree of the crosslinking density. Functionality of the GPVI-domain was investigated using a GPVI-binding ELISA to Col I. Activity of the SDF1-domain was tested for its CXCR4 binding potential. Preserved functionality of SDF1-GPVI bi-specific protein after photo-crosslinking and controllable release was successfully demonstrated in vitro supporting the implementation of this drug delivery system as a powerful tool for therapeutic protein delivery in the treatment of cardiovascular ischemic disease.
authors.affiliation: University Women's Hospital, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany; Dept. of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), 70569 Stuttgart, Germany.
authors.forename: Marianne K
authors.initials: MK
authors.lastname: Schesny
authors.affiliation: Dept. of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), 70569 Stuttgart, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Monaghan
authors.affiliation: University Women's Hospital, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany.
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Bindermann
authors.affiliation: Institute for Physiological Chemistry and Pathobiochemistry, University of Münster, 48149 Münster, Germany.
authors.forename: Désirée
authors.initials: D
authors.lastname: Freund
authors.affiliation: Institute for Medical Immunology, Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin, 13353 Berlin, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Seifert
authors.affiliation: Institute for Physiological Chemistry and Pathobiochemistry, University of Münster, 48149 Münster, Germany.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Eble
authors.affiliation: Dept. of Internal Medicine III, Eberhard-Karls-Universität Tübingen, 72076 Tübingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Vogel
authors.affiliation: Dept. of Internal Medicine III, Eberhard-Karls-Universität Tübingen, 72076 Tübingen, Germany.
authors.forename: Meinrad P
authors.initials: MP
authors.lastname: Gawaz
authors.affiliation: Dept. of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), 70569 Stuttgart, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Hinderer
authors.affiliation: University Women's Hospital, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany; Dept. of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), 70569 Stuttgart, Germany; Dept. of Medicine/Cardiology, Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: katja.schenke-layland@igb.fraunhofer.de.
authors.forename: Katja
authors.initials: K
authors.lastname: Schenke-Layland
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D024042:Collagen Type I / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D066026:Endothelial Progenitor Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009203:Myocardial Infarction / Q000628:therapy*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*; D019718:Receptors, CXCR4 / Q000737:chemistry
chemical_list: D054377:Chemokine CXCL12; D020099:Coated Materials, Biocompatible; D024042:Collagen Type I; C515256:Cxcl12 protein, mouse; D020100:Hydrogels; D010980:Platelet Membrane Glycoproteins; D019718:Receptors, CXCR4; C098341:platelet membrane glycoprotein VI; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols
keywords: Bioactivity; Cardiac tissue engineering; Drug release; Hydrogel; Protein