3D printing opportunities in blood vessels
A printing method that allows fine control over rigidity that can better mimic the complex structure of blood vessels has been developed at the University of Colorado. Khai Trung Le reports.
As the rate of cardiovascular disease increases globally, so does the need for credible treatment. Hardened blood vessels are typically associated with cardiovascular disease, highlighting a need for viable artery and tissue replacement that have so far proven challenging. However, a 3D bioprinting technique developed from the University of Colorado Boulder (CU Boulder), USA, that allows localised control on firmness represents a promising step towards printing artificial organs.
Blood vessels have complex geometry that is both highly structured and pliable, requiring similarly malleable rigidity. The paper, Orthogonal programming of heterogeneous micro-mechano-environments and geometries in three-dimensional bio-stereolithography, published in Nature, notes, ‘The move towards well-defined synthetic 3D systems, however, requires precise control of cell migrations in a more physiological 3D environment and is far more challenging with conventional approaches. The 3D spatial heterogeneous micro-mechano-environment may not only impact cell attachment but also lead to preferential cell migrations in response to the different stiffness profiles.’
Hydrogel structures that can soften and stiffen have been successfully created, but are limited to 2D structures. Xiaobo Yin, Associate Professor of Mechanical Engineering at CU Boulder, said, ‘The idea was to add independent mechanical properties to 3D structures that can mimic the body’s natural tissue. This technology allows us to create microstructures that can be customised for disease models.’
The team developed a layer-by-layer printing process with control of stiffness and geometry using free-radical polymerisation (FRP). However, FRP is adversely affected by oxygen inhibition, which causes incomplete curing. Yin said, ‘Oxygen is usually a bad thing in that it causes incomplete curing. We use a layer that allows a fixed rate of oxygen permeation.’
An oxygen inhibition layer between the cured polymer structure and an oxygen-permeable window limits the curing thickness during the construction process. Subsequently, the cured layer thickness modulates to local cross-link density. With greater control over oxygen migration and subsequent light exposure, the method allows researchers control over which areas of an object solidify to be harder or softer, while retaining the same overall geometry.
Several items were printed to assess the variable rigidity, three versions of a structure, a top beam supported by two rods, were printed, each identical in shape, size and materials, but with varying rod rigidity that resulted in some models partially or fully collapsing. Similarly, a statuette of a Chinese warrior was printed with a tough exterior with a soft interior
in the shape of a heart.
The current tabletop-sized printer is compatible with biomaterials of 10 micrometres and up, but the research team hopes to reduce the size even further. ‘This is an encouraging first step in toward our goal of creating structures that function like a healthy cell should […] The challenge is to create an even finer scale for the chemical reactions, but we see tremendous opportunity ahead for this technology and the potential for artificial tissue fabrication,’ Yin said.
Expanded healthcare has been a long-held promise of 3D printing, and recent strides include the first 3D-printed human corneas produced at Newcastle University, UK, and a USA-based company, Organovo, successfully creating small implantable liver ‘organoids’ that can treat chronic liver disease from donor material.
The paper, Orthogonal programming of heterogeneous micro-mechano-environments and geometries in three-dimensional bio-stereolithography, can be read at go.nature.com/2qlGprV