The choice of biopolymer is crucial to trigger angiogenesis with vascular endothelial growth factor releasing coatings

Christiane Claaßen,Maria-Elli Kotzampasi,Jana Grübel,Kirsten Borchers,Boris V Stanzel,Miriam Dannecker,Günter E M Tovar

doi:10.1007/s10856-020-06424-3

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.

Highlights

Formation of fibrotic encapsulation around implants and tissue engineered grafts remains a fundamental limitation in clinical translation [1, 2]
Controlled release of pro-angiogenic growth factors from hydrogel coatings is expected to stimulate improved bio-integration of implants [10, 14, 15]. For this matter gelatin type B (GelB) coatings releasing basic fibroblast growth factor to induce angiogenesis were investigated in vivo so far [14, 15], and albumin coatings were for example loaded with vascular endothelial growth factor (VEGF) [10]
We developed VEGF releasing coatings based on carbodiimide cross-linked gelatin type A (GelA)-heparin, GelB-heparin, albumin-heparin, and radically cross-linked methacrylmodified gelatin-heparin (GM5A5-HepM5) on polyethylene terephthalate (PET) substrates

Summary

Introduction

Formation of fibrotic encapsulation around implants and tissue engineered grafts remains a fundamental limitation in clinical translation [1, 2]. Controlled release of pro-angiogenic growth factors from hydrogel coatings is expected to stimulate improved bio-integration of implants [10, 14, 15]. For this matter gelatin type B (GelB) coatings releasing basic fibroblast growth factor (bFGF) to induce angiogenesis were investigated in vivo so far [14, 15], and albumin coatings were for example loaded with vascular endothelial growth factor (VEGF) [10]

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