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International Journal of Bioprinting Biofabrication for islet transplantation

and positive insulin staining confirmed the sustained non-endocrine cells, such as islet endothelial cells (iECs),
functionality of the device over an extended period in vitro (Figure 7B). Furthermore, controlled-size islet
(Figure 6E). This study effectively demonstrated the spheroids exhibit higher drug sensitivity than intact
potency of the device through its ability to reinstate islets . Patel et al. developed a microphysiological system
[81]
normoglycemia in diabetic mice for a duration of 3 months that enables continuous dynamic culture of pancreatic
post-encapsulation of proliferative cells . Mridha et al. organoids in a 3D hydrogel, highlighting the importance of
[78]
developed a method for providing allogeneic beta cell a dynamic in vitro microenvironment for primary organoid
[82]
therapies without the need for antirejection drugs . To function preservation . To compare traditional culture
[79]
achieve this, they propose the utilization of a bioengineered methods with the newly developed microphysiological
hybrid device that consists of microencapsulated beta cells system, rodent- and human-derived islets were embedded
enclosed within 3D polycaprolactone (PCL) scaffolds in alginate, and in vitro and in silico assessments were
created through the melt electrospin writing technique. The performed. Their results indicated that dynamic culture of
researchers successfully demonstrated the construction of hydrogel-embedded islets within the microphysiological
[82]
an implantable, consistent, and retrievable hybrid device system had a superior impact on islet viability . Bauer
that facilitates vascularization and enhances the viability et al. elucidated the advancement of a microfluidic two-
of encapsulated islets and subcutaneously implanted organ-chip architecture for investigating the pancreatic
the device in an allotransplantation environment while islet–liver interplay in the context of drug discovery
circumventing the requirement for immunosuppression . and the identification of novel therapeutic interventions
[79]
(Figure 7C) . The model capitalized on genetically
[83]
4.2. Microfabrication of cell-laden devices encoded human pancreatic islet microtissues and liver
Extensive research and development efforts have been spheroids subjected to glucose- and insulin-free cell culture
dedicated to the advanced microfabrication of microfluidic medium. These findings suggest that insulin secretion by
and lab-on-a-chip devices owing to their numerous islet microtissues activates glucose uptake by liver spheroids,
advantages, including rapid analysis, biocompatibility, whereas the liver in isolation exhibits reduced efficiency in
affordability, and automation. Although these devices glucose consumption (Figure 7D) . However, sample size
[83]
were initially constructed from costly materials such as limitations constitute a primary drawback of the majority of
silicon wafer and glass, recent investigations have focused microfluidic systems, rendering them unsuitable for quality
on the utilization of emerging soft polymeric materials control of islets after isolation, as they require a considerable
(e.g., PDMS) that confer benefits such as automation number of islets. One of the primary impediments to
and high-throughput screening in the realm of tools and microfluidic systems is their inherent limitations in terms
laboratory equipment. of sample size. Because of this limitation, it is challenging to
acquire a sufficient number of islets for islet transplantation
Compared with traditional systems, microfluidic [84]
systems offer superior control over the spatial and within a microfluidic system .
temporal distribution of chemical and physical stimuli 4.3. Bioprinting technology
at the cellular level, thereby enabling the development of 3D bioprinting is one of the most promising technologies
diverse microsystems tailored to various tissue engineering for the simultaneous induction of vascularization and
applications. The emergence of organ-on-a-chip platforms, prevention of inflammation [85,86] . It is also a state-of-the-
which synergize cell biology, engineering, and biomaterial art technology for constructing complex tissue-engineered
advancements with microfluidics, has introduced structures. Using multiple dispensing system, various
innovative systems capable of mimicking the physiological cells and materials can be placed precisely at the desired
or pathophysiological milieu of specific organs. These locations simultaneously. Among the various types of 3D
devices represent a pioneering model for pharmaceutical bioprinting technologies, extrusion-based bioprinting
agent screening and the investigation of specific diseases. techniques are most commonly used for the development
Numerous microfluidic devices have been developed in the of 3D-printed pancreatic tissue [71, 87–89] . Generally, an
field of diabetes to simulate native islet microenvironments extrusion-based bioprinting technique driven by a
and explore pancreatic beta cell kinetics . Jun et al. created pneumatic or mechanical system continuously forces the
[80]
functional islet spheroids using a microfluidic chip that bioink through a nozzle to form predefined filaments. A
mimicked interstitial flow, reduced shear cell damage, bioink is a solution of a biomaterial or a mixture of several
and addressed islet size heterogeneity through precise 3D biomaterials in the form of a hydrogel. One of the common
engineering of microsized islet spheroids (Figure 7A) . characteristics of bioinks is that the hydrogels are viscous
[81]
The authors observed that flow not only enhanced the enough to remain stable until crosslinking to create pre-
health of islets, but also promoted the maintenance of designed constructs after printing .
[90]

Volume 9 Issue 6 (2023) 404 https://doi.org/10.36922/ijb.1024