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.
Highlights
A perfusable vascular network is necessary to support the mass transport requirements of a metabolically active and highly populated tissue
Following evacuation of the 3D printed model material from the alginate cast, gelatin is subsequently infiltrated into the channels and the alginate is removed by chelation of the cross-linking calcium ions
This template is cast in a collagen or fibrin gel, which can be pre-loaded with cells, and the gelatin liquefied at 378C
Summary
A perfusable vascular network is necessary to support the mass transport requirements of a metabolically active and highly populated tissue. A functioning blood vessel network, which is 3D, hierarchical and perfusable, is a necessary requirement of most functional tissues; the use of channel hierarchy enabling both extensive coverage of the tissue while simultaneously providing the low pressure heads required for efficient diffusion in and out of the bulk. While improving the permeability of tissue engineered constructs, are still limited in the capacity for this exchange in thick samples especially in scaffolds containing biologically relevant cell densities [2]. Tissue engineering, which seeks to fabricate new tissues and organs, requires approaches for the formation of 3D vascular networks in materials suitable for supporting tissue development, of which hydrogels are the most important group
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