Page 43 - IJB-9-5

International Journal of Bioprinting Precise fabrication of engineered vascular networks

Keywords: Swelling compensation; Engineered manufacturing and a sacrifice-based technique . In this
[16]
vasculatures; Additive manufacturing; Sacrificial method, first, a temporary sacrificial template in the shape
materials; Thermoresponsive hydrogels of the designed vasculature is printed. Then, the sacrificial
template is removed to form the engineered vasculature
after encasing in a hydrogel construct. Currently, Pluronic
F-127 (PF-127) and poly (vinyl alcohol) (PVA) occupy
1. Introduction a leading position among sacrificial materials. Jennifer
Mammalian vasculature consists of two connected and A. Lewis’s lab was the pioneer to use PF-127 to produce
highly branched networks that pervade human body and vascularized tissues [17–20] . More recently, to mimic a tumor
[21]
have a significant influence on pathophysiology [1,2] . Tissue microenvironment, Neufeld et al. printed PF-127 as the
engineering is involved in many fields [3–5] . In the past two sacrificial template to create a vascularized glioblastoma
decades, the generation of living model tissues containing model. However, deformation of the template was observed
engineered vasculature has been among the main research after removing the printed PF-127, decreasing the accuracy
topics within the fields of biomanufacturing and tissue of the fabricated vasculature. The swelling of PF-127 may
engineering. Vasculature facilitates the diffusional mass be caused by the hydrophilicity of F-127 at the removal
[22]
transfer of nutrients, oxygen, growth factors, biochemical temperature of 4°C , which makes PF-127 absorb water
signaling factors, carbon dioxide, and metabolic waste from the surrounding environment. PVA is likewise an
from the surroundings to cells and vice versa [6,7] . The attractive sacrificial material for fabricating engineered
success of engineered tissues largely depends on the vasculature due to its biocompatibility and water solubility.
incorporation of stable vasculature that assists the various Nevertheless, the swelling of PVA in the hydrogel and the
biological functions of encapsulated cells. Moreover, the removal process, which are discernible, lead to vasculature
[23]
engineered tissues containing vasculature enable enhanced deformation . Therefore, a specific coating is required
cell infiltration and uniform distribution of nutrients and to alleviate the swelling [24,25] . While the combination of
oxygen, which further augments cellular infiltration rates additive manufacturing and the sacrifice-based technique
and host tissue integration compared to engineered tissues facilitates the fabrication of engineered vasculature, the
without vasculature . Therefore, fabricating engineered deformation caused by swelling of the sacrificial template
[8]
tissues with the incorporation of vasculature becomes has been rarely studied.
critical. The development of a facile method to precisely Despite the flexibility of combining additive
fabricate engineered vasculature is still highly anticipated.
manufacturing and a sacrifice-based technique to
While robust whole-organ vascularization remains a fabricate engineered vasculature, it is also highly
major obstacle , several techniques have been introduced desirable to mitigate the deformation caused by swelling
[9]
to produce hydrogel constructs with vasculature. The of the sacrificial template and develop a facile strategy
most widely used strategies are three-dimensional for precisely preparing engineered vasculature within
(3D) bioprinting , sacrifice-based technique , and hydrogel constructs. Recently, the volume shrinkage of
[10]
[2]
light-assisted processes . Among them, light-assisted thermoresponsive hydrogel has been widely used for
[11]
processes, including digital light projection (DLP) , producing soft robotics and drug delivery carriers [26–30] .
[12]
volumetric printing , and stereolithography , empower In these studies, poly(N-isopropylacrylamide) (PNIPAM)
[13]
[14]
the fabrication of engineered tissues with precise and is one of the most commonly adopted thermoresponsive
complex vasculature. Grigoryan et al. used natural hydrogels. PNIPAM exhibits a lower critical solution
[15]
and synthetic food dyes as photoabsorbers that enable temperature (LCST) at ~32°C, which enables the volume
stereolithographic fabrication of hydrogel constructs shrinkage of PNIPAM in a cell culture environment [31,32] .
containing intricate and functional vascular architectures, Wang et al. used the reversible shrinkage and swelling
[33]
which could be a milestone in fabricating engineered behavior of PNIPAM controlled by near-infrared
vasculature. In their study, a bioinspired alveolar model irradiation to facilitate the penetration of endothelial
with an ensheathing vasculature was successfully produced. cells into the bone scaffold vasculature and promote pre-
Despite impressive progress, light-assisted processes vascularization. The scaffold vasculature enhances host
require specific photoresponsive hydrogels. Moreover, high vessel infiltration deep into the scaffolds. Nonetheless, the
technical light-assisted equipment is essential for precisely dimensions of the scaffold vasculature are uniform owing
fabricating target constructs, which makes light-assisted to the consecutive extrusion and printing of hollow fibers,
processes unscalable for researchers in tissue engineering which makes it difficult to prepare biomimetic vasculature.
and medicine. Another commonly used approach to In our previous study, sacrificial alginate fibers and
fabricate engineered vasculature is combining additive PNIPAM/gelatin methacrylate (GelMA) were combined

Volume 9 Issue 5 (2023) 35 https://doi.org/10.18063/ijb.749