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viscosity bioink, to allow for cell migration within the vascular construct [3]. This
study used GelMA (gelatin methacrylate) and alginate bioinks laden with HUVECs.
GelMA is a collagen in the photopolymerizable methacrylate (MA) family, which
is cross-linked after printing using UV radiation. HUVEC growth and alignment in
the vascular channel was successfully demonstrated. The group reported synchronous beating of cardiomyocytes, after secondary seeding of cardiomyocytes into the
constructs, thereby demonstrating the potential for use of the construct as a platform
for further tissue engineering applications.
Jia et al. demonstrated the ability to print various shapes and sizes (inner diameter 400–1000 um) of perfusable vascular network structures [24]. The group used
a coaxial nozzle system to print bioink composed of gelatin methacryloyl (GelMA),
poly(ethylene glycol)-tetra-acrylate (PEGTA), and sodium alginate. PEGTA is a
branched, tetravalent chemical structure derivative of poly(ethylene glycol) (PEG).
In this study, the PETGA increased the physical strength of the construct by increasing cross-links with GelMA. The encapsulation of HUVECs and human mesenchymal stem cells (hMSCs) into the bioink was used to evaluate the cytocompatibility
of this printing methodology. Surface modification with ethylenediaminetetraacetic
acid (EDTA) solution was done after bioprinting, to enhance cell migration and
proliferation. The group reported optimal cell density as well as highly organized
cell migration patterns. This study was significant in that it demonstrated the capacity to print well-organized vascular networks that could be adequately perfused.
Zhang et al. evaluated the cardiac tissue remodeling by seeding cardiomyocytes into
the organized vascular scaffold [54]. The group used HUVEC-encapsulated bioink
to print vascular tissue scaffolds, which were then seeded with neonatal rat cardiomyocytes, to create an endothelialized microvascular structure. Bioink composed of
GelMA, alginate, and endothelial cells was used to construct the microfibrous scaffold. Cardiomyocytes were then seeded into the interstitial spaces, in the multiple
layers of the highly organized vascular network. The mechanical properties of these
constructs were affected by the distance between layers of the scaffold. The degree
of HUVEC dispersion within the scaffold resembled the pattern of native blood vessels. Synchronous beating of cardiomyocytes in the endothelialized microenvironment was noted within 3 days, after seeding. Perfusion of the construct under a
bioreactor improved the viability of cardiomyocytes. The team also explored the
endothelialized myocardial model in response to doxorubicin, a common oncological drug. The HUVECs and cardiomyocytes showed a dose-dependent response to
the drug, demonstrating the potential utility of the printed vascular construct for
pharmacologic testing.
Indirect extrusion 3D bioprinting techniques have allowed researchers to create
complicated networks of materials in predetermined geometries, by manipulating
the design of the sacrificial materials. Microvasculature networks with small caliber
diameters have been developed and investigated by several research groups. Wu
et al. used aqueous Pluronic F127, a copolymer with two hydrophilic poly(ethylene
oxide) (PEO) parts and one hydrophobic poly(propylene oxide) (PPO), in a PEOPPO- PEO arrangement, acting as the sacrificial material in a hydrogel matrix to
construct various sized vascular channels [51]. They examined the mechanical
5 3D Printing Technology for Vascularization
viscosity bioink, to allow for cell migration within the vascular construct [3]. This
study used GelMA (gelatin methacrylate) and alginate bioinks laden with HUVECs.
GelMA is a collagen in the photopolymerizable methacrylate (MA) family, which
is cross-linked after printing using UV radiation. HUVEC growth and alignment in
the vascular channel was successfully demonstrated. The group reported synchronous beating of cardiomyocytes, after secondary seeding of cardiomyocytes into the
constructs, thereby demonstrating the potential for use of the construct as a platform
for further tissue engineering applications.
Jia et al. demonstrated the ability to print various shapes and sizes (inner diameter 400–1000 um) of perfusable vascular network structures [24]. The group used
a coaxial nozzle system to print bioink composed of gelatin methacryloyl (GelMA),
poly(ethylene glycol)-tetra-acrylate (PEGTA), and sodium alginate. PEGTA is a
branched, tetravalent chemical structure derivative of poly(ethylene glycol) (PEG).
In this study, the PETGA increased the physical strength of the construct by increasing cross-links with GelMA. The encapsulation of HUVECs and human mesenchymal stem cells (hMSCs) into the bioink was used to evaluate the cytocompatibility
of this printing methodology. Surface modification with ethylenediaminetetraacetic
acid (EDTA) solution was done after bioprinting, to enhance cell migration and
proliferation. The group reported optimal cell density as well as highly organized
cell migration patterns. This study was significant in that it demonstrated the capacity to print well-organized vascular networks that could be adequately perfused.
Zhang et al. evaluated the cardiac tissue remodeling by seeding cardiomyocytes into
the organized vascular scaffold [54]. The group used HUVEC-encapsulated bioink
to print vascular tissue scaffolds, which were then seeded with neonatal rat cardiomyocytes, to create an endothelialized microvascular structure. Bioink composed of
GelMA, alginate, and endothelial cells was used to construct the microfibrous scaffold. Cardiomyocytes were then seeded into the interstitial spaces, in the multiple
layers of the highly organized vascular network. The mechanical properties of these
constructs were affected by the distance between layers of the scaffold. The degree
of HUVEC dispersion within the scaffold resembled the pattern of native blood vessels. Synchronous beating of cardiomyocytes in the endothelialized microenvironment was noted within 3 days, after seeding. Perfusion of the construct under a
bioreactor improved the viability of cardiomyocytes. The team also explored the
endothelialized myocardial model in response to doxorubicin, a common oncological drug. The HUVECs and cardiomyocytes showed a dose-dependent response to
the drug, demonstrating the potential utility of the printed vascular construct for
pharmacologic testing.
Indirect extrusion 3D bioprinting techniques have allowed researchers to create
complicated networks of materials in predetermined geometries, by manipulating
the design of the sacrificial materials. Microvasculature networks with small caliber
diameters have been developed and investigated by several research groups. Wu
et al. used aqueous Pluronic F127, a copolymer with two hydrophilic poly(ethylene
oxide) (PEO) parts and one hydrophobic poly(propylene oxide) (PPO), in a PEOPPO- PEO arrangement, acting as the sacrificial material in a hydrogel matrix to
construct various sized vascular channels [51]. They examined the mechanical
5 3D Printing Technology for Vascularization