Page 76 - IJB-6-4

Applications of 3D bioprinted iPSCs
bioprinting. The use of non-integrative methods creating organ building blocks composed of
and small molecules to activate the pluripotency hundreds of thousands of iPSCs and then rapidly
program in somatic cells represents the safest 3D bioprinting vasculature into those building
approach to produce clinical grade iPSCs cells. blocks . The SWIFT method could create a
[70]
High throughput screening to identify small perfusable cardiac tissue that fuses and beats
molecules for cell reprogramming is ongoing synchronously for more than a week, taking the
in many laboratories, with a goal to establish field of bioprinting vascularized functional tissues
iPSCs free of any exogenously introduced using iPSCs to the next level.
DNA fragments. Incompletely differentiated
cells evoked immune response in transplanted 7 Future perspectives for iPSCs in bioprinting
animals [153] . Therefore, obtaining completely Despite the challenges associated with the use
differentiated cells for therapeutic purpose are of of reprogrammed iPSCs and limitations of
prime importance. Futuristic technology should be bioprinting, the potential of bioprinting iPSC-
focused on establishing safe strategies for genetic
modification of iPSCs, devise efficient methods derived tissue is tremendous in the health-care
for differentiation and purification of iPSCs into field. Resolution of these challenges will have
required cell types in vitro for transplantation. significant implications in the understanding of
After production of iPSCs, there are limitations human diseases and will have major effects on the
in the bioprinting process itself and associated treatment of these diseases. Future perspectives of
challenges in the preparation of optimized bioinks bioprinting iPSCs should focus on:
• Establishing xeno-free and footprint-free
suitable for each cell type. 3D bioprinting has the clinical-grade iPSC reprogramming protocols:
advantage of reconstructing complex structures The use of non-integrative methods and
from computed tomography or magnetic small molecules should be further explored.
resonance imaging images and producing accurate High throughput screening to identify small
structures from predetermined digital designs such molecules for cell reprogramming to establish
as computer-aided design models. The support iPSCs free of any exogenously introduced
DNA fragments would be potential area to
scaffold materials with suitable mechanical focus on.
and biological properties can be designed and • Development of tissue-specific bioinks
printed using advanced 3D printers. Directed for bioprinting: New bioinks with tunable
differentiation of printed iPSCs to different cell mechanical and rheological properties
lineages is required for organ printing. When we that mimic the native tissue ECM is to be
use undifferentiated iPSCs for bioprinting, the developed and a deeper understanding of
cell-bioink interactions must be sought as the
printing parameters should be adjusted to avoid mechanobiology and the molecular pathways
any mechanical damage to the cells, as iPSCs are would have a major effect on the differentiation
highly sensitive cells. Depending on the type of of the bioprinted iPSCs.
the bioprinting method used, the cells are exposed • Improved bioprinting strategies to mitigate
to high shear forces, radiation-induced damage, harmful effects on cells: Since iPSCs are
and electric or thermal stresses during the printing sensitive cells (not as sturdy as cancer cell
lines), the mechanical, thermal, or chemical
process [154,155] . stressors induced by the bioprinting process
Vascularization and innervation of the might result in cell-phenotype changes and
bioprinted tissue are a challenge to achieve. functionality. Strategies to mitigate the
Bioprinted iPSC constructs are unable to form exposure of cells to these process-induced
long-term viable and vascularized tissue. To stressors must be developed.
resolve this problem, researchers at Wyss institute • Integrated bioreactor systems for tissue
maturation: Bioprinting of functional tissues
recently developed a method called sacrificial with iPSC-derived cells would be successful
writing into functional tissue (SWIFT), which is a only if they can be matured and maintained
multistep biomanufacturing process that involves over a long-term in physiologically-relevant

72 International Journal of Bioprinting (2020)–Volume 6, Issue 4