136
behavior of the printed vascular constructs still need to be optimized. Another drawback of the scaffold-free approach is the difficulty of producing large-scale vascular
tissues [42].
The biomaterials used in the 3D printing process have a critical impact on the
quality of the fabricated vascular tissue. Generally speaking, an ideal bioprinting
material would provide structural integrity with adequate mechanical strength after
printing, promote engraftment with host tissue while avoiding immunogenicity, and
facilitate cell proliferation, aggregation, and differentiation. The physical characteristics of the bioink, such as viscosity, mechanical strength, pore size, etc., must be
considered when deciding which type of 3D printing technology to employ, given
the limitations of the various technologies as previously described. Additionally, the
pore size of the bioink must also be considered, given its impact on extracellular
matrix deposition, which in turn determines cellular adhesion and organization.
Cellular organization within the printed hydrogel has a tremendous influence on
cell-cell signaling and plays a key role in the nutritional transfer critical for cellular
metabolism. In fact, post-print cell viability is shown to be correlated to pore size by
Domingos et al. [9]. Lastly, cytocompatibility of the bioink, with the host tissue and
the immunogenicity of the printed material, must also be considered when evaluating the long-term success of the printed tissues. Studies investigating the 3D printing of vascular tissue have demonstrated high cell viability, but the degradation rate
of the 3D printed vascular scaffolds, when engrafted in vivo, indicates that immunogenicity of these constructs must be further evaluated.
Self-assembly of cell aggregates (spheroids) in the scaffold-free printing
approach has shown great promise and is an important milestone in scaffold-free 3D
bioprinting. Currently, different approaches to speed up the cellular assembly in
spheroid formation are under investigation. Additionally, maturogenic factors,
which are biochemical molecules, are shown to improve the cohesive properties of
spheroids by Hadju et al. [20]. The use of magnetized bioinks to print physiologically robust spheroids with enhanced cell-cell communication has also been demonstrated [10, 43]. Lastly, the lockyball technique has been demonstrated to improve
the regenerative capacity of scaffold-free vascular tissue constructs, by using a
microscaffold with hooks, to reduce mechanical stress on printed spheroids [8].
Regarding the application to fabrication of vascular tissue, 3D printing methodology has the potential for use in the large-scale production of microvascular networks. The highly controllable deposition of bioink during printing allows for the
production of a wide range of sizes and types of vascular networks. However, there
is still much research needed in order to print biomimetic vascular tissue constructs
that are optimized for use in clinical applications.
An emerging application of 3D printing technology in vascular engineering is
the creation of patient-specific TEVGs. It caters to the patient’s native vascular anatomy and potentially allows for more optimized hemodynamics after surgery. This
would reduce unnecessary power loss and cardiac workload and thereby delay the
onset of heart failure, especially in young patients with congenital heart disease.
Advances in imaging techniques and the virtual surgical planning strategy, described
by Siallagan et al., have also allowed for the construction and precise implantation
E. Yeung et al.
behavior of the printed vascular constructs still need to be optimized. Another drawback of the scaffold-free approach is the difficulty of producing large-scale vascular
tissues [42].
The biomaterials used in the 3D printing process have a critical impact on the
quality of the fabricated vascular tissue. Generally speaking, an ideal bioprinting
material would provide structural integrity with adequate mechanical strength after
printing, promote engraftment with host tissue while avoiding immunogenicity, and
facilitate cell proliferation, aggregation, and differentiation. The physical characteristics of the bioink, such as viscosity, mechanical strength, pore size, etc., must be
considered when deciding which type of 3D printing technology to employ, given
the limitations of the various technologies as previously described. Additionally, the
pore size of the bioink must also be considered, given its impact on extracellular
matrix deposition, which in turn determines cellular adhesion and organization.
Cellular organization within the printed hydrogel has a tremendous influence on
cell-cell signaling and plays a key role in the nutritional transfer critical for cellular
metabolism. In fact, post-print cell viability is shown to be correlated to pore size by
Domingos et al. [9]. Lastly, cytocompatibility of the bioink, with the host tissue and
the immunogenicity of the printed material, must also be considered when evaluating the long-term success of the printed tissues. Studies investigating the 3D printing of vascular tissue have demonstrated high cell viability, but the degradation rate
of the 3D printed vascular scaffolds, when engrafted in vivo, indicates that immunogenicity of these constructs must be further evaluated.
Self-assembly of cell aggregates (spheroids) in the scaffold-free printing
approach has shown great promise and is an important milestone in scaffold-free 3D
bioprinting. Currently, different approaches to speed up the cellular assembly in
spheroid formation are under investigation. Additionally, maturogenic factors,
which are biochemical molecules, are shown to improve the cohesive properties of
spheroids by Hadju et al. [20]. The use of magnetized bioinks to print physiologically robust spheroids with enhanced cell-cell communication has also been demonstrated [10, 43]. Lastly, the lockyball technique has been demonstrated to improve
the regenerative capacity of scaffold-free vascular tissue constructs, by using a
microscaffold with hooks, to reduce mechanical stress on printed spheroids [8].
Regarding the application to fabrication of vascular tissue, 3D printing methodology has the potential for use in the large-scale production of microvascular networks. The highly controllable deposition of bioink during printing allows for the
production of a wide range of sizes and types of vascular networks. However, there
is still much research needed in order to print biomimetic vascular tissue constructs
that are optimized for use in clinical applications.
An emerging application of 3D printing technology in vascular engineering is
the creation of patient-specific TEVGs. It caters to the patient’s native vascular anatomy and potentially allows for more optimized hemodynamics after surgery. This
would reduce unnecessary power loss and cardiac workload and thereby delay the
onset of heart failure, especially in young patients with congenital heart disease.
Advances in imaging techniques and the virtual surgical planning strategy, described
by Siallagan et al., have also allowed for the construction and precise implantation
E. Yeung et al.