The choice of biopolymer is crucial to trigger angiogenesis with vascular endothelial growth factor releasing coatings
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SPECIAL ISSUE: HYDROGELS IN REGENERATIVE MEDICINE Original Research
The choice of biopolymer is crucial to trigger angiogenesis with vascular endothelial growth factor releasing coatings Christiane Claaßen1 Miriam Dannecker1 Jana Grübel1 Maria-Elli Kotzampasi2 Günter E. M. Tovar Boris V. Stanzel3,4 Kirsten Borchers1,2 ●
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Received: 12 May 2019 / Accepted: 7 September 2020 © The Author(s) 2020
Abstract Bio-based coatings and release systems for pro-angiogenic growth factors are of interest to overcome insufficient vascularization and bio-integration of implants. This study compares different biopolymer-based coatings on polyethylene terephthalate (PET) membranes in terms of coating homogeneity and stability, coating thickness in the swollen state, endothelial cell adhesion, vascular endothelial growth factor (VEGF) release and pro-angiogenic properties. Coatings consisted of carbodiimide cross-linked gelatin type A (GelA), type B (GelB) or albumin (Alb), and heparin (Hep), or they consisted of radically cross-linked gelatin methacryloyl-acetyl (GM5A5) and heparin methacrylate (HepM5). We prepared films with thicknesses of 8–10 μm and found that all coatings were homogeneous after washing. All gelatin-based coatings enhanced the adhesion of primary human endothelial cells compared to the uncoated membrane. The VEGF release was tunable with the loading concentration and dependent on the isoelectric points and hydrophilicities of the biopolymers used for coating: GelA-Hep showed the highest releases, while releases were indistinguishable for GelB-Hep and Alb-Hep, and lowest for GM5A5-HepM5. Interestingly, not only the amount of VEGF released from the coatings determined whether angiogenesis was induced, but a combination of VEGF release, metabolic activity and adhesion of endothelial cells. VEGF releasing GelA-Hep and GelB-Hep coatings induced angiogenesis in a chorioallantoic membrane assay, so that these coatings should be considered for further in vivo testing. Graphical Abstract
Supplementary information The online version of this article (https:// doi.org/10.1007/s10856-020-06424-3) contains supplementary material, which is available to authorized users. * Günter E. M. Tovar [email protected] 1
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Institute of Interfacial Process Engineering and Plasma Technology IGVP, University of Stuttgart, Nobelstr. 12, 70569 Stuttgart, Germany Fraunhofer Institute for Interfacial Engineering and Biotechnology
IGB, Nobelstr. 12, 70569 Stuttgart, Germany 3
Augenklinik Sulzbach, Knappschaftsklinikum Saar, An der Klinik 10, 66280 Sulzbach, Germany
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Fraunhofer Institute for Biomedical Engineering IBMT, Joseph-von-Fraunhofer-Weg 1, 66280 Sulzbach/Saar, Germany
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Journal of Materials Science: Materials in Medicine (2020)31:93
1 Introduction Presently, formation of fibrotic encapsulation around implants and tissue engineered grafts remains a fundamental limitation in clinical translation [1, 2]. Biocompatible hydrogel coatings are suggested
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