Page 274 - IJB-9-2

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

of the pancreas. The efficacy of Matrigel in pancreatic islet for the seeding of β-cells or islets and as vehicles in the
transplantation in animal models has been demonstrated transplantation of constructed pancreatic islet-like tissues
by several groups, although its human clinical applications as well. Song and Millman [146] developed an approach using
have not been studied or at least not confirmed. Haque PLA that encapsulated human iPSC-derived β-cell spheres
et al. [137] reported the maintenance of normoglycemia for in fibrin gel. After transplantation, the cells could secrete
more than two months following the delivery of pancreatic insulin for three months (Table 3). Marchioli et al. [112] used
islet cells and clodronate liposomes in Matrigel, whereas PCL-alginate scaffolds that were functionalized with VEGF
the permanence of diabetic mice could not have lasted for the transplantation of pancreatic islets. Daoud et al. [147]
more than a week if they had received islet cells without have printed PLGA scaffolds that provided support to islets
Matrigel (Table 3). encapsulated in collagen I, fibronectin, and collagen IV
hydrogel (Table 3). The in vitro study confirmed the effect
Biocompatible and synthetic biodegradable polymers of ECM components and PLGA 3D scaffold on insulin
are mainly applied to scaffold-based systems [138] . Synthetic secretion and endocrine-related gene expression compared
polymers have advantages over natural polymers, such as to free-floating islets. [147] . Recently, Gabriela et al. [148] used
a lower risk of infection, a lower risk of immunogenicity, a dual extrusion 3D bioprinter, which was able to develop
and a lower price [139] . Generally, U.S. Food and Drug a hybrid scaffold of hydrogel and PCL functionalized with
Administration (FDA) has approved some synthetic heparin for the regeneration of pseudo-pancreatic islets.
polymers that can be used for biomedical applications, The bioink that they used was a 1:5 ratio of INS1/HUVEC
e.g., PGA, polylactic acid (PLA), poly lactic-co-glycolic cells in GelXA LAMININK-411 hydrogel. According to
acid (PLGA), PCL, and poly ethylene glycol (PEG) [140] . the information website of the company CELLINK, which
Presently, in this category, various branch-type derivatives produces GelXA LAMININK-411, it is a combination of
of PEG, in the form of a hydrogel, alone or combined with GelMA, alginate, xanthan gum, and laminin, which is a
other materials, are used to encapsulate pancreatic islets basic material for the development of pancreatic models.
(Table 3) [141] . The transcriptomic analysis of pseudo-islets showed an
4.1.7. PEG upregulation of β-cell signaling cascades, cell proliferation,
PEG-based derivatives hydrogels are applied as one of and overexpression of ECM proteins and the VEGF
[148]
the most important components in β-islet encapsulation pathway as well (Table 3) .
and even islet transplantation due to their tissue-like 4.2. Scaffold-free strategy
elasticity, biocompatibility, immunoprotective features, The common description for scaffold-free strategy is the
low immunogenic elucidating, and absorbability [142] . development of living tissue using only cells. Athanasiou
Knobeloch et al. [143] reported an injectable PEG hydrogel et al. [149] noted that “scaffoldless tissue engineering refers
for islet encapsulation, promoting islet survival in vitro to any platform that does not require cell seeding or
and in vivo. They made this hydrogel via Michael-type adherence within an exogenous, 3D material.” In other
protocol using a multiarm PEG-vinyl sulfone and a words, the scaffold-free bioinks components are single-
PEG-diSH crosslinker. Islets were encapsulated in the cell suspension, cell sheets, spheroid cell aggregates,
hydrogel and injected into a mouse peritoneal cavity tissue strands or a mixture of two or more of them [150] . In
before gelation was completed. A significant reduction of some protocols, owing to the limitations of scaffolds, cell
the blood glucose levels from 600 to 200 mg/ml was seen “clumps” are referred to as spheroids, which can aid in
2 days after transplanting almost 100-IEQ encapsulated forming complex 3D shapes when put together with mild
islets in the recipient mouse [143] . Although the lack of cell overlap. Scaffolds have commonly been used in the form
adhesive motifs in PEG-based hydrogel has been applied of biocompatible, biodegradable templates for cell seeding
in islet encapsulation, the low interactions of cells with the within. Although complex structures comprising ECM and
scaffold network affect the survival of β-cells for a long viable cells have been successfully made, some problems
time [144] . Researchers have tailored synthetic hydrogels still persist. These include diffusion of nutrients, cell-to-cell
with covalent peptides or proangiogenic factor derivatives communication, vascularization, toxicity, inflammation,
or a combination with natural protein-based hydrogel to immunogenicity, and mechanical incompatibility. One
overcome these deficiencies. Weber et al. [145] demonstrated of the requirements for an ideal scaffold is degradability
that a combination of crosslinked ECM-derived proteins within the recipient, which gives the cells within the
(type I collagen, type IV collagen, fibrinogen, FN, laminin, scaffold a chance to replace the scaffold with their secreted
and vitronectin) with a 3D PEG could induce islets survival own ECM, thereby allowing for continuous maintenance.
and reduction of cell apoptosis after transplantation. This addresses a problem in rapidly degrading scaffolds,
Synthetic polymers have been assumed as a scaffold which leave behind toxic byproducts at a concentration

Volume 9 Issue 2 (2023) 266 http://doi.org/10.18063/ijb.v9i2.665