Page 169 - IJB-9-6

International Journal of Bioprinting 3D printing in gastroenterology

disease pathogenesis, drug screening, and microbiome cells tended to induce greater strength and cellular
interaction [82,83] . The related literature is summarized in activity . Madden et al. used bioinks of human intestinal
[89]
Table 4. myofibroblasts (hIMFs) and human intestinal epithelial
While the advantages of printed scaffolds are cells (hIECs) to print layer by layer onto the transwell
unanimously recognized (e.g., highly customized and membrane to form a bilayer structure. Differentiation
controllable, compatible with many types of materials, into polarized and tightly joined epithelial subpopulations
[90]
and producing delicate micro structures) , there are such as chromaffin cells and goblet cells was observed .
[84]
still disadvantages (e.g., expensive equipment, time- However, the researchers used this model to test drugs
consuming, low printing resolution, and requirement of only rather than mechanical properties, peristaltic
bioreactor). The ideal printed scaffolds should have tubular characteristics, and biocompatibilities. Further efforts can
structures with contiguous epithelial linings of different be made to develop implantable sheets and even hollow
functions (e.g., acid and mucus secretion, absorption) intestinal sections. Maina et al. 3D bioprinted a biopatch
and properties of nutrient provision, peristaltic pumping, consisting of hydrogel, rat venous smooth muscle cells,
[91]
and the microbiome. PCL is one of the most commonly and aortic fibroblast cells . They implanted this patch
used printing materials. However, it is not very friendly into a rat enterostomy and found that the sealed intestine
to cell adhesion, although it is reported to have fair maintained integrity with the intraluminal pulsatile flow
biocompatibility, durability, processability, and relatively and exhibited robust histological formation of villi and
slow degradability [79,85] . Further refinement of both inks crypts. To better mimic the histological architecture
and experimental steps is required to meet experimental of villi, Kim et al. fabricated a collagen bioink-based
and clinical requirements. intestinal model in which a single villus was 183 μm wide
and 770 μm tall . The model also contained vascular
[92]
structure, making it perform better in cell growth, mucus
5. What can 3D bioprinting do? secretion, barrier formation, and even absorption function
than the 2D model and 3D model without vasculature.
The above-mentioned printed scaffolds are primarily Kim further improved the bioink by adding decellularized
biomimetic structures without cells. Thus, bioprinting, small intestinal submucosa . They demonstrated that the
[93]
where bioinks containing living cells, is later introduced updated version had a better performance in cell activities
(Table 5). There are generally three kinds of bioprinting than the previously reported version [92,93] . Very few studies
[10]
technologies at the micrometric scale : extrusion- have explored its application in the biliary system. Yan
[87]
based , jetting-based (inkjet and laser-assisted) , et al. printed models with ink containing cholangiocytes
[86]
and vat photopolymerization (stereolithography and and laminin-like amphiphiles that comprise the base
[88]
digital light processing) . It is faster and more efficient membrane. They found that the cells could organize and
than traditional methods as it excludes cell seeding and develop tubular structures with branches . Boyer et al.
[94]
repopulation processes. Most importantly, 3D bioprinting also invented a 3D bioprinted biliary stent infused with
is able to create grafts with spatial relocations of bioinks collagen, human placental MSCs, and cholangiocytes,
with living cells and with microenvironments for cell aiming to improve biliary stent patency and patient care .
[95]
expansion. Therefore, 3D bioprinting is most suitable
for stratified organs with different layers of cells like GI Instead of tubular structures, 3D bioprinting of liver
tract. The treatment of GI diseases requiring surgical organoids has also been attempted in recent years. Yang
interventions usually involves organ reconstruction, defect et al. introduced a printed hepatorganoid that consisted of
repair, and stenosis treatment. The success rate of intestinal HepaRG cells and bioinks of sodium alginate and gelatin .
[96]
allografts is still relatively low due to their immunogenicity. The organoid obtained functions of drug metabolism,
Therefore, implantable organs and materials that do not synthesis of protein, and glycogen storage after proper
lead to immunological rejection, coagulopathy, pathogen culture both in vitro and in vivo. The planted organoid
transmission, and hazardous decomposition byproduct are significantly prolonged the survival of liver failure mice.
needed. Functional tubular organs need a special design to The challenges for 3D bioprinting are finding the optimal
mimic histological layers and physiological functions. 3D formulation of biomaterials with cell components that
bioprinting has been attempted in creating hollow organs meet the requirements of bioprinting, especially for hollow
such as the esophagus, small intestine, and bile duct, but organs. Caution should be taken regarding questions about
not yet in the stomach. personalized ink formulation (i.e., biological composition,
In 2019, Takeoka et al. bioprinted scaffold-free 3D viscosity, mechanical properties, postprocessing gelatin,
tubular structures to repair rat esophageal defects. They and clinical grade), nozzle clotting, cell damage, and
found that a greater proportion of mesenchymal stem prototype sterilization . Hydrogels, whether natural or
[97]

Volume 9 Issue 6 (2023) 161 https://doi.org/10.36922/ijb.0149