Page 92 - IJB-9-6

International Journal of Bioprinting Review of 3D bioprinted organoids

14 days, confirming the potential application of SLA 3.1. Direct bioprinting vascularization
technology in organoid bioprinting . Direct printing involves using bioink and bioprinting
[70]
Unlike SLA technology, DLP uses an ultraviolet surface technology to print out tubular structures. Coaxial
light source. The light projected from a digital micromirror bioprinting technology is often used in the direct printing of
device illuminates an entire layer of bioink, curing an entire blood vessels. However, without a supporting material, the
layer at a time. Hence, DLP has a much faster printing printed blood vessel structure is prone to deformation or
[83]
speed than SLA . In addition, DLP has a high resolution collapse during the printing process . As a result, the direct
[71]
(less than 20 µm) and cell viability (more than 90%). printing of blood vessels demands high-quality bioink with
DLP technology is widely used in bioprinted organoids better printability, mechanical properties, and angiogenic
[84]
due to its excellent performance. Xie et al. bioprinted potential . Jia et al. developed a hybrid bioink consisting
hydrogel microspheres (MSs) containing BMSC using of GelMA, sodium alginate, and PEGTA, with excellent
DLP technology, which maintained good cell viability after printability, biocompatibility, and mechanical properties that
printing and successfully constructed callus organoids support the survival and proliferation of vascular cells. By
after cartilage induction . However, DLP technology using this cell-loaded hybrid bioink and coaxial bioprinting
[72]
still has room for improvement. Currently, DLP printing technology, they have successfully achieved direct
[85]
technology with different light sources is being investigated bioprinting of perfused vascular structures . Hong et al.
to further reduce the impact on cells and improve cell also applied gelatin to the printing of blood vessel structures.
viability. Additionally, DLP technology has a high demand They synthesized gelatin-PEG-tyramine (GPT) mixed
for bioinks. While meeting traditional requirements, bioinks, in which tyramine has rapid crosslinking properties,
bioinks also need to ensure the photo-polymerization and PEG acts as the spacer material between gelatin and
speed and the fidelity of the printing structure . tyramine to promote rapid gelation. They demonstrated
[73]
one-step bioprinting of perfumable vascular structures
using GPT bioinks and coaxial bioprinting . In addition to
[86]
3. Tissue vascularization strategies mixed bioinks, chemically modified natural bioinks can also
The lack of vascularization is a significant drawback of be used for vascularization direct bioprinting. Barrs et al.
large-scale tissue construction, as the natural diffusion of developed a novel peptide-functionalized alginate hydrogel
oxygen and nutrients can only support tissue growth up to bioink using RGD (integrin-binding state for cell adhesion)
a size of 150 µm. This is also true for organoids, which face and a vascular endothelial growth factor (VEGF)-mimetic
similar challenges. As traditionally-constructed organoids peptide with matrix metalloproteinase cleavable linker
grow beyond a certain size, the exchange of oxygen, (MMPQK) for modification of oxidized alginate. Direct
nutrients, and metabolites can no longer be achieved bioprinting of vascularized tissue units (VTUs), consisting
through natural diffusion, thereby resulting in the loss of the blood vessel and tissue-specific components, was
of cell vitality and the development of necrotic cores . successfully achieved using RGD/MMPQK bioink for
[81]
Przepiorski et al. used a rotating bioreactor to generate vascular components and tissue-specific bioink for tissue-
[87]
hiPSCs-differentiated kidney organoids. They found specific components .
that the core cells of kidney organoids with a diameter 3.2. Indirect bioprinting vascularization
greater than 700 mm were significantly reduced. The Indirect printing involves the use of sacrificial bioinks to
cell viability was not as good as kidney organoids with a print vascular structures. These bioinks can be removed
[82]
smaller diameter . Therefore, it is essential to realize the physically or chemically after printing, leaving a perfusive
vascularization of organoids. Bioprinting technology has and endothelialized hollow lumen. It should be noted
been widely used in vascularization due to its excellent that sacrificial bioinks are usually bioprinted with
performance. Various techniques are now available to extrusion-based bioprinting technology. However, the
achieve the vascularization of bioprinted organoids, lack of resolution in this technology limits the application
including growing the organoids directly onto 3D-printed of sacrificial bioinks in the bioprinting of small-diameter
vascular structures, using growth factors to encourage blood vessels . Additionally, the complexity of indirect
[84]
angiogenesis, and combining endothelial cells with stem printing technology may affect the size and function of
cells or organoids to create organoids with blood vessels the resulting vascular structures. Kolesky et al. adopted
[15]
(Figure 4). Pluronic F127 as the sacrificial bioink and GelMA as the
The printing of blood vessel structures can be divided bioink. Pluronic F127 appears in a solid state, GelMA ink
into direct and indirect printing. Direct bioprinting mainly in a liquid state when the temperature is higher than 22°C,
uses mixed bioinks, while indirect printing uses sacrificial and Pluronic F127 in a liquid state and GelMA ink appear
bioinks. in a solid state when the temperature is lower than 4°C.

Volume 9 Issue 6 (2023) 84 https://doi.org/10.36922/ijb.0112