134
5.2.4.2 Application
Microvascular Network Creation (Table 5.1)
Norotte et al. described a novel technique in fabricating small-diameter multilayer
tubular vascular grafts (diameter ~900 um) using HUVSMCs, human skin fibroblasts (HSFs), and porcine aortic smooth muscle cells (PASMCs) [41]. The team
employed scaffold-free 3D printing technology to produce a cylindrical agarose
support mold. Spheroids prepared from the co-culture of mixed cells were printed
into the mold to allow fusion and maturation of the tissue. The team was also able
to print a double-layer vascular tubular structure using the same technique. However,
it was noted that tissues printed using these techniques matured faster and had suboptimal porous geometries.
Vascular Graft Creation (Table 5.2)
Kelm et al. first attempted a two-step scaffold-free fabrication process to create
vascular tissue [25]. The first step of this process involved microtissue fabrication
using human myofibroblasts (HMFs), pig articular chondrocytes (PACs), and
human articular chondrocytes (HACs). The second step involved the amalgamation
of mouse myoblasts and HUVECs, in a cylindrical agarose cast, to produce a microtissue tubular structure (diameter ~3 mm). The microtissue was then implanted in
the chorioallantoic membrane (CAM) of a chicken embryo for evaluation of vascularization potential in vivo. The printed tissues demonstrated successful angiogenic
potential in vivo.
Tan et al. printed a larger vascular construct model (~5 mm diameter) using a
scaffold-free approach and evaluated the cell-cell interaction between living cells in
the construct [48]. The team used a robotic microdroplet system, to construct a
hydrogel mold into which spheroids created from co-culture of human aortic smooth
muscle cells (hSMCs) and human umbilical vein endothelial cells (HUVECs) were
printed. They found that collagen type 1, which was extensively secreted from the
printed cells, was essential to spheroid adhesion and maturation of the vascular
construct.
Xu et al. investigated the fabrication of different shapes of tubular structures
[53]. The group created zigzag 2–3 mm caliber tubular structures using a scaffoldfree bioink containing mouse fibroblasts. The fabrication process, which involved
inkjet 3D printing technology with alternating speeds of the print head, made use of
the overhang of each sequential layer of bioink (a distance about 20 um) to create a
slightly curved shape in the printed tube. The printed constructs had high cell viability of over 80%. This study demonstrated the capacity of 3D printing to fabricate
vascular constructs with complex geometries that better mimic native human
vasculature.
Taking the fabrication of scaffold-free vascular constructs a step further,
Kucukgul et al. proposed a method for patient-specific scaffold-free 3D printing of
E. Yeung et al.
5.2.4.2 Application
Microvascular Network Creation (Table 5.1)
Norotte et al. described a novel technique in fabricating small-diameter multilayer
tubular vascular grafts (diameter ~900 um) using HUVSMCs, human skin fibroblasts (HSFs), and porcine aortic smooth muscle cells (PASMCs) [41]. The team
employed scaffold-free 3D printing technology to produce a cylindrical agarose
support mold. Spheroids prepared from the co-culture of mixed cells were printed
into the mold to allow fusion and maturation of the tissue. The team was also able
to print a double-layer vascular tubular structure using the same technique. However,
it was noted that tissues printed using these techniques matured faster and had suboptimal porous geometries.
Vascular Graft Creation (Table 5.2)
Kelm et al. first attempted a two-step scaffold-free fabrication process to create
vascular tissue [25]. The first step of this process involved microtissue fabrication
using human myofibroblasts (HMFs), pig articular chondrocytes (PACs), and
human articular chondrocytes (HACs). The second step involved the amalgamation
of mouse myoblasts and HUVECs, in a cylindrical agarose cast, to produce a microtissue tubular structure (diameter ~3 mm). The microtissue was then implanted in
the chorioallantoic membrane (CAM) of a chicken embryo for evaluation of vascularization potential in vivo. The printed tissues demonstrated successful angiogenic
potential in vivo.
Tan et al. printed a larger vascular construct model (~5 mm diameter) using a
scaffold-free approach and evaluated the cell-cell interaction between living cells in
the construct [48]. The team used a robotic microdroplet system, to construct a
hydrogel mold into which spheroids created from co-culture of human aortic smooth
muscle cells (hSMCs) and human umbilical vein endothelial cells (HUVECs) were
printed. They found that collagen type 1, which was extensively secreted from the
printed cells, was essential to spheroid adhesion and maturation of the vascular
construct.
Xu et al. investigated the fabrication of different shapes of tubular structures
[53]. The group created zigzag 2–3 mm caliber tubular structures using a scaffoldfree bioink containing mouse fibroblasts. The fabrication process, which involved
inkjet 3D printing technology with alternating speeds of the print head, made use of
the overhang of each sequential layer of bioink (a distance about 20 um) to create a
slightly curved shape in the printed tube. The printed constructs had high cell viability of over 80%. This study demonstrated the capacity of 3D printing to fabricate
vascular constructs with complex geometries that better mimic native human
vasculature.
Taking the fabrication of scaffold-free vascular constructs a step further,
Kucukgul et al. proposed a method for patient-specific scaffold-free 3D printing of
E. Yeung et al.