Preserved bioactivity and tunable release of a SDF1-GPVI bi-specific protein using photo-crosslinked PEGda hydrogels

Marianne K Schesny; Michael Monaghan; Andrea H Bindermann; Désirée Freund; Martina Seifert; Johannes A Eble; Sebastian Vogel; Meinrad P Gawaz; Svenja Hinderer; Katja Schenke-Layland

doi:10.1016/j.biomaterials.2014.04.116

Preserved bioactivity and tunable release of a SDF1-GPVI bi-specific protein using photo-crosslinked PEGda hydrogels

Biomaterials. 2014 Aug;35(25):7180-7. doi: 10.1016/j.biomaterials.2014.04.116. Epub 2014 May 27.

Affiliations

¹ 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.
² Dept. of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), 70569 Stuttgart, Germany.
³ University Women's Hospital, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany.
⁴ Institute for Physiological Chemistry and Pathobiochemistry, University of Münster, 48149 Münster, Germany.
⁵ Institute for Medical Immunology, Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin, 13353 Berlin, Germany.
⁶ Dept. of Internal Medicine III, Eberhard-Karls-Universität Tübingen, 72076 Tübingen, Germany.
⁷ 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.

PMID: 24875761
DOI: 10.1016/j.biomaterials.2014.04.116

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.

Keywords: Bioactivity; Cardiac tissue engineering; Drug release; Hydrogel; Protein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cells, Cultured
Chemokine CXCL12 / metabolism*
Coated Materials, Biocompatible / chemistry
Collagen Type I / chemistry
Drug Delivery Systems / methods
Endothelial Progenitor Cells
Humans
Hydrogels / chemistry*
Hydrogen-Ion Concentration
Mice
Myocardial Infarction / therapy*
Platelet Membrane Glycoproteins / metabolism*
Polyethylene Glycols / chemistry*
Receptors, CXCR4 / chemistry

Substances

Chemokine CXCL12
Coated Materials, Biocompatible
Collagen Type I
Cxcl12 protein, mouse
Hydrogels
Platelet Membrane Glycoproteins
Receptors, CXCR4
platelet membrane glycoprotein VI
poly(ethylene glycol)diacrylate
Polyethylene Glycols