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Pre-Seeding of Simple Electrospun Scaffolds with a Combination of Endothelial Cells and Fibroblasts Strongly Promotes Angiogenesis

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Introduction of pro-angiogenic cells into tissue-engineered (TE) constructs (prevascularisation) is a promising approach to overcome delayed neovascularisation of such constructs post-implantation. Accordingly, in this study, we examined the contribution of human dermal microvascular endothelial cells (HDMECs) and human dermal fibroblasts (HDFs) alone and in combination on the formation of new blood vessels in ex-ovo chick chorioallantoic membrane (CAM) assay.

Methods:

Poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) and polycaprolactone (PCL) were first examined in terms of their physical, mechanical, and biological performances. The effect of gelatin coating and co-culture conditions on enhancing endothelial cell viability and growth was then investigated. Finally, the angiogenic potential of HDMECs and HDFs were assessed macroscopically and histologically after seeding on simple electrospun PHBV scaffolds either in isolation or in indirect co-culture using an ex-ovo CAM assay.

Results:

The results demonstrated that PHBV was slightly more favourable than PCL for HDMECs in terms of cell metabolic activity. The gelatin coating of PHBV scaffolds and co-culture of HDMECs with HDFs both showed a positive impact on HDMECs viability and growth. Both cell types induced angiogenesis over 7 days in the CAM assay either in isolation or in co-culture. The introduction of HDMECs to the scaffolds resulted in the production of more blood vessels in the area of implantation than the introduction of HDFs, but the co-culture of HDMECs and HDFs gave the most significant angiogenic activity.

Conclusion:

Our findings showed that the in vitro prevascularisation of TE constructs with HDMECs and HDFs alone or in co-culture promotes angiogenesis in implantable TE constructs.

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Acknowledgement

The authors are grateful to the Turkish Ministry of National Education for the funding of Ph.D. award to Serkan Dikici.

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Correspondence to Sheila MacNeil.

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Ethical approval for the tissue acquisition was granted by the National Research Ethics Service (NRES) Committee Yorkshire and The Humber–Sheffield (REC Ref.: 15/YH/0177, REC opinion date: 03/06/2015).

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Dikici, S., Claeyssens, F. & MacNeil, S. Pre-Seeding of Simple Electrospun Scaffolds with a Combination of Endothelial Cells and Fibroblasts Strongly Promotes Angiogenesis. Tissue Eng Regen Med 17, 445–458 (2020). https://doi.org/10.1007/s13770-020-00263-7

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