Page 403 - IJB-9-6

International Journal of Bioprinting Biofabrication for islet transplantation

need for immunosuppressive measures . The primary the use of oxidized alginate has been explored in the
[29]
objective of an encapsulation device is to establish an development of degradable carriers for insulin delivery and
environment that fosters the normal secretion of insulin islet cell replacement therapy . The key advantage of this
[35]
in response to dynamic fluctuations in blood glucose levels degradable carrier is its ability to prevent the accumulation
while simultaneously safeguarding cell viability through of materials beyond the required insulin dose or islet cell
seclusion from the immune system and facilitating transplantation, thereby addressing the issue of excess
the efficient exchange of nutrients and waste products. material buildup.
However, the thickness of the encapsulation device poses Collagen, the primary protein constituent of
challenges in the exchange of small molecules, which may ECM, is known for its biocompatibility and low
lead to cell death and reduced insulin release. Moreover, the immunogenicity [36,37] . The physical behavior of collagen
inclusion of multiple islets within a single device reduces gels is temperature-dependent, where they become
the available surface area for small-molecule exchange . fluidized at 10–25°C and relatively rigid at 30–37°C .
[30]
[38]
3.2. Natural biomaterials This temperature responsiveness is particularly valuable
Natural biomaterials offer a cell-friendly environment for cell delivery in human body because the solution-
and exceptional biocompatibility, which are the features like pre-gel collagen can be effortlessly transplanted at
incorporated into islet delivery career system. Alginate, a room temperature and subsequently solidified at body
well-known natural biomaterial derived from brown algae temperature. Once implanted, the gel retained its rigid
and naturally occurring polysaccharide, is widely used state, providing mechanical stability and preventing
for islet encapsulation. Upon reaction with multivalent displacement from the implantation site. This property
cations, crosslinking occurs between alginate molecules, renders collagen gels advantageous for use as scaffolds in
resulting in the formation of a robust three-dimensional tissue engineering and cell delivery. Moreover, collagen
(3D) gel network structure. The ionotropic gelation of can serve as a useful tool for cell encapsulation given its
alginate solutions using Ca, Ba, and Fe ions results in water- injectable fiber pore sizes of tens of nanometers, enabling
insoluble alginate, which is known for its biocompatibility the utilization of a collagen fiber membrane that shields
[39]
and mechanical stability. In particular, crosslinked calcium the transplanted tissue from the host immune system .
alginate is suitable for endovascular application . Numerous studies have explored the use of collagen-coated
[31]
Numerous studies have revealed that the long-term culture scaffolds or mixtures of multiple materials, including
viability and survival rate of islet cells improve significantly collagen, to enhance the biocompatibility of transplants and
when the cells are enclosed within alginate capsules. facilitate islet adhesion to surface [40,41] . Conversely, it has
Zhang et al. illustrated that a balanced charged anti- been demonstrated that the combination of collagen with
biofouling alginate/polyethylene imine (PEI) hydrogel- other ECM proteins and growth factors is able to maintain
based encapsulation strategy for islets, which results in glucose homeostasis after islet transplantation, thereby
[42]
insulin independence and immunoisolation, could be enabling successful long-term islet transplantation . Yang
effectively utilized in the treatment of T1D (Figure 2A) . et al. have developed an innovative 3D culture system,
[32]
The encapsulated islets retained their glucose-responsive namely Disque Platform (DP), that effectively replicates the
and insulin-producing properties. Furthermore, the microenvironment and cellular interactions of pluripotent
alginate hydrogel efficiently evaded foreign body reactions stem cell-derived beta cells (SC β cells), thereby improving
in vivo following intraperitoneal implantation into an their viability, differentiation, and functionality (Figure
[43]
immunocompetent streptozotocin-induced diabetic 2C) . DP incorporates critical constituents of the ECM,
mouse model (Figure 2B) . Over time, alginate may such as laminin and type IV collagen. In the 3D condition,
[32]
undergo dissociation as a result of the exchange of divalent the SC β cells exhibited elevated levels of vital transcription
cation crosslinking agents with physiologically abundant factors and junctional structures compared to those
monovalent cations. However, the lack of hydrolases that observed in two-dimensional (2D) monolayer conditions
can break down high-molecular-weight alginate polymers (Figure 2D). This technology has the potential to mitigate
makes complete degradation of alginate unfeasible, thereby the adverse effects of existing small molecules for in vivo
posing a challenge in eliminating alginate from mammals beta cell expansion and provide a renewable supply of islets
through physiological systems . The molecular weight of in vitro for the long-term transplantation of patients with
[33]
[43]
residual alginate polymers commonly surpasses 50 kDa, diabetes .
which exceeds the established renal clearance threshold. Heparin, a well-known natural biomaterial, has
In order to prevent the accumulation of residual polymer, garnered attention in the field of islet transplantation
hydrolytically degradable alginate hydrogels have been owing to its propensity to enhance islet angiogenesis via
formulated via partial oxidation of alginates . Recently, growth factor stabilization. Because of their capacity to
[34]

Volume 9 Issue 6 (2023) 395 https://doi.org/10.36922/ijb.1024