Page 272 - IJB-9-2

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

degrades and is replaced by the cells’ own ECM. Because of a tissue-like stable environment in which cells can easily
their high water content and special molecular properties, proliferate and differentiate. Although this plexus can
hydrogels have flexibility and adaptability to conditions provide mechanical signals, biochemical inductions and
and can be used in various situations, from industrial to a net for cell connection, hydrogel scaffolds are used to
biological systems. Hydrogels have been broadly used construct a wide range of tissues in bioengineering and
for biomedical applications, such as biosensors, contact regenerative medicine.
lenses, drug delivery, and tissue engineering [93–95] . In 4.1.1. Alginate hydrogels
tissue engineering, hydrogels are often used as networks Alginate is a natural anionic polysaccharide acquired from
to support cells and biological factors to reconstruct brown seaweed. The negative charge of alginic acid is due
artificial tissue and carriers for the delivery of bioactive to the carboxylic groups of β-D-mannuronic acid and α-L-
molecules . One application is to encapsulate secretory glucuronic acid, which are linked by a 1,4-glycosidic bond.
[96]
cells and stabilize them to deliver bioactive molecules to Alginate is a biocompatible polymer widely used in tissue
the target tissues. The encapsulation of pancreatic islets engineering due to its properties, such as cost-effectiveness
using several hydrogels is the current strategy to make and gentle gelling properties in the presence of metal
up a semi-privileged environment to prevent rejection by ions [108] . The encapsulation of pancreatic islets using
separating the transplanted cells from the host immune alginate-based hydrogels has been widely studied [109,110] .
system simultaneously; it will be a permeable membrane Hals et al. [111] reported that alginate microencapsulation
without the need for toxic immunosuppression. The semi- of human islets compared to non-encapsulated does not
permeable layer allows the passing based on diffusions give rise sensitivity to acute hypoxia. One study found that
for small molecules, such as glucose, oxygen, nutrients, the use of alginate and polycaprolactone (PCL) scaffolds in
and insulin, but blocks the entrance of agents with large the presence of vascular endothelial growth factor (VEGF)
molecular structures, such as antibodies and cytotoxic increased angiogenesis and maintained islet function
immune cells. Hydrogels have been used as bioinks in and viability [112] . Bloch et al. [113] developed an artificial
3D bioprinting approaches because of their printability pancreatic islet that used a thermophilic strain of the
and the fact that they act as scaffold and ECM substitutes unicellular alga chlorella as an oxygen generator for the
after crosslinking. The niche or 3D environment in which pancreatic islets encapsulated in alginate. Furthermore, rat
cells live determines their morphology and maturation islets were printed in alginate/methylcellulose bioink into
characteristics after printing. It is expected that by using macroporous 3D constructs that could survive for up to
tailored bioinks, the native habitat of a given cell type 7 days in vitro (Table 3) [114] .
might be simulated effectively .
[97]
Hydrogels have been introduced as an attractive 4.1.2. Chitosan hydrogels
medium in regenerative medicine because of their ability to These polymers are derived from chitin shells of shrimps
encapsulate cells and bioactive molecules . A hydrogel is by deacetylating in alkali solutions. Structurally, chitosan
[98]
a 3D biocompatible polymeric network that can swell in an comprises N-acetyl-D-glucosamine and D-glucosamine.
aqueous solution. The hydrophilic polymers that make up Thus, it has primary and secondary hydroxyl groups as
the backbone of a hydrogel can either be naturally derived well as amine groups in the deacetylated unit. Because
polysaccharides, proteins, GAGs (e.g., alginate, chitosan, of the biocompatibility and biodegradability of chitosan,
collagen, gelatin, fibrin, and HA) or synthetic polymeric it is considered in the field of tissue engineering and
materials (e.g., PEG, poly[ethylene oxide], poly[vinyl drug delivery [115] . A study conducted on xenogeneic islet
alcohol], and poly[propylene fumarate]) . The high transplantation confirmed the protective effects of chitosan
[99]
volume of water along the network is due to the existence on pancreatic islets [116,117] . The combination of chitosan
of hydrophilic groups, such as hydroxyl (–OH), amine with the collagen matrix increases the crosslink density
(–NH ), carboxylic acid (–COOH), amide (–CONH ), and mechanical strength and can enhance the viability of
2
2
and sulfonate (–SO H) groups . Hydrogels can simulate circulating angiogenic cells [118] .
[96]
3
natural extracellular matrices and living tissues due to 4.1.3. HA hydrogels
their high water content, porosity, softness, and flexibility. HA is a nonsulfated high molecular weight GAG [119] . HA
Polymer chains are connected in hydrogels using several is synthesized by integral membrane synthases, which
physical and chemical methods to crosslink between interfere in water transport and tissue hydration [120] .
polymer strands [100,101] . They can polymerize in response Structurally, HA is a linear, anionic mucopolysaccharide
to environmental stimuli, including temperature [102] , light constructed of repeating disaccharides of D-glucuronic
intensity [103,104] , pH [105,106] , and chemical or biochemical acid and N-acetyl-D-glucosamine arranged alternately [119] .
agents, such as ions and enzymes [107] . Hydrogels can create HA has been considerably used in the tissue engineering

Volume 9 Issue 2 (2023) 264 http://doi.org/10.18063/ijb.v9i2.665