126
in these channels. This printed construct was used to further evaluate the efficacy of
biofabricating vascular networks.
Multi-scale vascular network fabrication was further demonstrated by Lee et al.
using a combination of materials including rat collagen type 1, HUVECs, and gelatin [32]. This multi-scale vascular network consisted of a single vascular channel
with smaller-sized, branching vascular sprouts. HUVEC viability was improved
when the bioink was formulated with higher cell concentrations and when the
HUVECs were placed in a flow culture after printing, which involved perfusing the
printed vascular tissue with medium. There was no significant difference in the
permeability of the unlined and the cell-lined vascular constructs. A larger vascular
network with a capillary system was constructed by Lee et al. using a similar principle [33]. The group created two vascular channels with numerous smaller, branching, interconnected channels. Fibrin, HUVEC, and normal human lung fibroblast
(NHIF) were incubated in the spaces between the channels. Two weeks after printing, this study demonstrated the formation of a mature capillary network with
HUVEC integration into the microvasculature, thus illustrating the potential for
using 3D printing techniques to construct sophisticated vascular networks on a
capillary- sized scale.
Vascular Graft Creation (Table 5.2)
Tubular structure fabrication using 3D inkjet printing was first introduced by Kesari
et al. in the Boland laboratory [26]. The group used a modified HP697c inkjet
printer to fabricate cylindrical structures, 2 mm in diameter, using alginate and rat
smooth muscle cells (SMCs). The SMCs were added in a layer-by-layer manner
with manual cell suspension, where the SMCs were pipetted into the hydrogel construct during the process of alginate deposition. Printed cell viability and alignment
were demonstrated using this methodology. Furthermore, the printed vascular constructs demonstrated vasoreactive ability when tested using vasoconstriction agonist endothelin-1 (ET-1) solution. This study is a noted milestone in the 3D inkjet
printing of vascular tissue.
Larger vascular constructs for use in regenerative medicine and organ transplantation have also been investigated. Challenges in printing large-scale constructs
include ensuring adequate physical support of the large structures, as well as ensuring the long-term viability of the printed cells due to the increased distance over
which nutrients and metabolites must be transferred within these larger constructs.
Campos et al. fabricated large vascular constructs (diameter ~5 mm), which were
immersed in a solution of high-density hydrophobic fluorocarbon, to enhance the
physical properties of the vascular constructs [11]. Cell growth and the rate of extracellular matrix secretion were both increased in the fluorocarbon solution submersed constructs. Moreover, the contact angle of the droplet in these constructs
was shown to be significantly higher, indicating that a higher printing precision and
resolution were obtained using this technique. Blaeser et al. used this same
submersion method to fabricate a cell-laden arterial bifurcated vasculature of 5 mm
E. Yeung et al.
in these channels. This printed construct was used to further evaluate the efficacy of
biofabricating vascular networks.
Multi-scale vascular network fabrication was further demonstrated by Lee et al.
using a combination of materials including rat collagen type 1, HUVECs, and gelatin [32]. This multi-scale vascular network consisted of a single vascular channel
with smaller-sized, branching vascular sprouts. HUVEC viability was improved
when the bioink was formulated with higher cell concentrations and when the
HUVECs were placed in a flow culture after printing, which involved perfusing the
printed vascular tissue with medium. There was no significant difference in the
permeability of the unlined and the cell-lined vascular constructs. A larger vascular
network with a capillary system was constructed by Lee et al. using a similar principle [33]. The group created two vascular channels with numerous smaller, branching, interconnected channels. Fibrin, HUVEC, and normal human lung fibroblast
(NHIF) were incubated in the spaces between the channels. Two weeks after printing, this study demonstrated the formation of a mature capillary network with
HUVEC integration into the microvasculature, thus illustrating the potential for
using 3D printing techniques to construct sophisticated vascular networks on a
capillary- sized scale.
Vascular Graft Creation (Table 5.2)
Tubular structure fabrication using 3D inkjet printing was first introduced by Kesari
et al. in the Boland laboratory [26]. The group used a modified HP697c inkjet
printer to fabricate cylindrical structures, 2 mm in diameter, using alginate and rat
smooth muscle cells (SMCs). The SMCs were added in a layer-by-layer manner
with manual cell suspension, where the SMCs were pipetted into the hydrogel construct during the process of alginate deposition. Printed cell viability and alignment
were demonstrated using this methodology. Furthermore, the printed vascular constructs demonstrated vasoreactive ability when tested using vasoconstriction agonist endothelin-1 (ET-1) solution. This study is a noted milestone in the 3D inkjet
printing of vascular tissue.
Larger vascular constructs for use in regenerative medicine and organ transplantation have also been investigated. Challenges in printing large-scale constructs
include ensuring adequate physical support of the large structures, as well as ensuring the long-term viability of the printed cells due to the increased distance over
which nutrients and metabolites must be transferred within these larger constructs.
Campos et al. fabricated large vascular constructs (diameter ~5 mm), which were
immersed in a solution of high-density hydrophobic fluorocarbon, to enhance the
physical properties of the vascular constructs [11]. Cell growth and the rate of extracellular matrix secretion were both increased in the fluorocarbon solution submersed constructs. Moreover, the contact angle of the droplet in these constructs
was shown to be significantly higher, indicating that a higher printing precision and
resolution were obtained using this technique. Blaeser et al. used this same
submersion method to fabricate a cell-laden arterial bifurcated vasculature of 5 mm
E. Yeung et al.