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Multi-casting approach for vascular networks in cellularized hydrogels

Published version
Peer-reviewed

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Authors

Justin, AW 
Brooks, RA 
Markaki, AE 

Abstract

Vascularization is essential for living tissue and remains a major challenge in the field of tissue engineering. A lack of a perfusable channel network within a large and densely populated tissue engineered construct leads to necrotic core formation, preventing fabrication of functional tissues and organs. We report a new method for producing a hierarchical, three-dimensional (3D) and perfusable vasculature in a large, cellularized fibrin hydrogel. Bifurcating channels, varying in size from 1 mm to 200-250 µm, are formed using a novel process in which we convert a 3D printed thermoplastic material into a gelatin network template, by way of an intermediate alginate hydrogel. This enables a CAD-based model design, which is highly customizable, reproducible, and which can yield highly complex architectures, to be made into a removable material, which can be used in cellular environments. Our approach yields constructs with a uniform and high density of cells in the bulk, made from bioactive collagen and fibrin hydrogels. Using standard cell staining and immuno-histochemistry techniques, we showed good cell seeding and the presence of tight junctions between channel endothelial cells, and high cell viability and cell spreading in the bulk hydrogel.

Description

Keywords

vascularization, three-dimensional printing, vascular networks, hydrogel

Journal Title

Journal of the Royal Society Interface

Conference Name

Journal ISSN

1742-5689
1742-5662

Volume Title

13

Publisher

Royal Society Publishing
Sponsorship
Engineering and Physical Sciences Research Council (EP/L504920/1)
European Research Council (240446)
This research was supported by the European Research Council (ERC, grant no. 240446), and an Engineering for Clinical Practice Grant from the Department of Engineering, University of Cambridge. A.W.J. acknowledges the support of the Engineering and Physical Sciences Research Council (EPSRC) through a PhD studentship (EP/L504920/1). R.A.B. gratefully acknowledges financial support from the National Institute for Health Research.