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International Journal of Bioprinting Bioprinting of β-islet-like constructs

protocols that mimic the pancreas’ mechanism of in vivo investigated angiogenic stimulation to overcome hypoxia
development. Zhu et al. [173] transduced human foreskin in transplanted islets. Lately, some scholars have used a 3D
fibroblasts with nonintegrating episomal reprogramming bioprinter equipped with a coaxial extruder nozzle and
factors, OCT4, SOX2, KLF4, and a short hairpin RNA two distinct cartridges. A coaxial extruder nozzle allows
against p53 into iPSC, and showed that this iPSC could the bioprinting of islets with supporting cells. Several
differentiate into functional β-like pancreatic cells and bioink combinations with various cell types and bioactive
protect mice against chemically induced diabetes. Tateishi molecules can be used in separate chambers. This type of
et al. [174] demonstrated the in vitro generation of functional 3D bioprinting has the potential to fabricate and scale up
β-like cells from iPSCs, which were derived from human the clinically relevant doses of islets with support parts
foreskin fibroblasts. Pagliuca et al. [170] demonstrated that in that include cells and bioactive factors for the survival of
vitro generated β-cells from human iPSCs can ameliorate transplanted islets [155,179] . Liu et al. [155] coaxially printed
hyperglycemia following transplantation into diabetic mice. mouse islets in the core while epithelial progenitor cells and
They described a scalable protocol in which cells express regulatory T cells (Treg) were printed in the shell of strands
appropriate surface markers (NKX6-1/C-peptide) and (Table 3). They printed the bioartificial pancreatic islet using
notable insulin secretory granules. Furthermore, fibroblasts a coaxial bioprinter in alginate-GelMA hydrogel, which has
obtained from skin biopsies from two patients with T1D high viability and insulin-secreting capability in response
were reprogrammed for pluripotency and differentiated to glucose in vitro and after transplantation into C57 mice.
into insulin-producing cells [175] . This information indicates The Βeta-O2 device is a macro encapsulation type that
that preliminary clinical studies on hPSCs-derived β-like supplied immunoisolation and oxygen for transplanted
cell and immunoprotective encapsulation techniques are β-islets [180] . The transplanted islets receive oxygen via daily
warranted (Figure 1B and C) [176] . injection of an oxygenated liquid through a subcutaneous
port. In a case study, one of these devices, which contained
6. Bioprinted pancreas islet human islets, was implanted in the preperitoneal cavity of a
diabetic person and was able to maintain insulin secretion
Despite the long history and numerous publications on islet capacity for approximately 10 months without using
transplantation in the therapy of T1D, the number of clinical immunosuppressive agents [180] . In another study, βAir
trials in this aspect is limited, possibly due to the shortage devices were implanted subcutaneously in four patients
of islet donors and the necessity for the recipients to take with T1D, whose human islets survived, but they have
permanent immunosuppressive drugs. These limitations little insulin secretion ability and a deep skin reaction was
have spawned research into the clinical applications of the observed [181] . Song and Millman [146] developed an approach
encapsulation of β-cells or biofabrication of pancreatic using a PLA scaffold that encapsulated human iPSC-
islets by innovative methods . The bioartificial pancreas derived β-cell spheres in fibrin gel. After transplantation,
[51]
is created by encapsulating islet cells, pancreatic islets, or the cells could secrete insulin for 3 months [146] . Bioprinting
MSC-derived insulin secretory cells in a semi-permeable of pancreatic islets allows for the use of different types
membrane as a physical barrier to protect them against of pancreatic cells to build bioengineered islets, which
the host immune system [177] . Hiscox et al. [178] could can also be encapsulated during the printing process and
create a tissue-engineered prevascularized pancreatic replaced on a vascular bed or vascular tissue structure [182] .
encapsulating device (PPED) using collagen hydrogel. In Although several reports confirm that the transplantation
vitro characterization showed that PPED was functional of islet-like construct into the pancreas works well with
and reacted to glucose impulse fourfold more than islets small animal models, this technology is still in its infancy
without collagen. They implanted it subcutaneously into steps and its clinical implications for human patients need
severe combined immunodeficient (SCID) mice and further studies [183] .
assessed their survival after 7, 14, and 28 days. Using
extrusion-based bioprinting, Akuch et al. [152] created 7. Discussion
scaffold-free tissue fibers that secrete high insulin levels.
They developed these strands using mouse insulinoma (TC3 The extrusion-based bioprinting approach is most
β-cell line) and rat dermal fibroblasts. Marchioli et al. [153] commonly used to fabricate functional pancreatic islet-
transplanted the 3D bioplotted hydrogel-based scaffold like tissue for T1D (Table 3) but this does not mean that
of the β-islet construct into subcutaneous mice. They it is the most appropriate technology to create an artificial
fabricated an artificial pancreas islet using a combination of pancreas. In addition to other emerging tissue engineering
the rat insulinoma-derived β-cell line (INS1E), mouse, and technologies, extrusion bioprinters enable core-shell
human islets in a preplanned 3D scaffold using alginate, printing by a coaxial nozzle and also combined extrusion
alginate-gelatin, alginate-HA, and alginate-Matrigel. They with blue light or UV curing during and after printing .
[84]

Volume 9 Issue 2 (2023) 268 http://doi.org/10.18063/ijb.v9i2.665