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生物聚合物的选择对于使用血管内皮生长因子释放涂层触发血管生成至关重要。

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

机构信息

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.

出版信息

J Mater Sci Mater Med. 2020 Oct 27;31(11):93. 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.

摘要

生物基涂层和释放系统用于促进血管生成的生长因子,旨在克服植入物的血管化和生物整合不足的问题。本研究比较了不同基于生物聚合物的涂层在聚对苯二甲酸乙二醇酯(PET)膜上的均匀性和稳定性、溶胀状态下的涂层厚度、内皮细胞黏附、血管内皮生长因子(VEGF)释放和促血管生成特性。涂层由碳化二亚胺交联的明胶 A 型(GelA)、B 型(GelB)或白蛋白(Alb)和肝素(Hep)组成,或者由自由基交联的明胶甲基丙烯酰基-乙酰基(GM5A5)和肝素甲基丙烯酸盐(HepM5)组成。我们制备了厚度为 8-10 μm 的薄膜,发现所有涂层在洗涤后均均匀。与未涂层的膜相比,所有基于明胶的涂层均增强了原代人内皮细胞的黏附。VEGF 的释放可通过负载浓度进行调节,并且取决于用于涂层的生物聚合物的等电点和亲水性:GelA-Hep 显示出最高的释放量,而 GelB-Hep 和 Alb-Hep 的释放量无明显差异,GM5A5-HepM5 的释放量最低。有趣的是,不仅涂层中释放的 VEGF 量决定了是否诱导了血管生成,而且 VEGF 释放、代谢活性和内皮细胞黏附的组合也起了作用。释放 VEGF 的 GelA-Hep 和 GelB-Hep 涂层在鸡胚绒毛尿囊膜试验中诱导了血管生成,因此这些涂层应考虑进一步进行体内试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ef2/7591429/03ce5cceded1/10856_2020_6424_Fig1_HTML.jpg

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