Page 405 - IJB-9-6

International Journal of Bioprinting Biofabrication for islet transplantation

mimic the ECM, heparin-based hydrogels are promising with the ability to enhance islet revascularization and
carriers for islet delivery . A previous study explored engraftment .
[52]
[44]
the application of macromolecular conjugates of heparin Several natural gels including alginate, collagen,
linked with VEGF to promote islet angiogenesis. Moreover, heparin, and silk fibrils have been examined in the field
immobilized heparin on the islet surface has been shown of islet transplantation. However, these gels exhibit limited
to encourage endothelial cell adhesion to the surface of versatility for promoting cell functions. Matrigel offers a
the islets . In contrast, reliance on animal sources for promising solution to establish a physiologically relevant
[45]
obtaining heparin leads to supply and safety concerns, and microenvironment that includes soluble growth factors,
its use is limited owing to clinical issues such as bleeding hormones, and other micro- to macromolecules that play
and thrombocytopenia . To overcome these challenges, critical roles in cellular interactions in vivo. Matrigel also
[44]
researchers have explored alternatives, such as heparin- contains the solubilized basement membrane matrix,
mimicking polymers and hydrogels . Notably, one study which predominantly comprises laminin and collagen
[44]
demonstrated the potential of heparin-mimetic peptide IV and is derived from Engelbreth–Holm–Swarm mouse
nanofiber gels in improving islet function and angiogenesis sarcoma cells, making itself a reconstituted basement
in vitro and in vivo . membrane. The ability of Matrigel to enhance long-term
[46]
Silk, a natural biomaterial, has been extensively insulin secretion has been demonstrated ; however,
[53]
employed in the design of islet encapsulation platforms. the disadvantages associated with its use cannot be
Multiple studies have demonstrated that encapsulation in overlooked. These include the lot-to-lot variability that
silk can potentially replicate the native pancreatic niche frequently occurs during the manufacturing process and
and improve islet function both in vitro and in vivo [47-49] . the complexity and ill-defined nature of its composition,
Additionally, the use of small molecules, cytokines, which makes it difficult to accurately determine which
chemokines, and immunomodulatory agents may signals promote cell function . Additionally, Matrigel
[54]
offer promising strategies for extending cell survival, originating from a tumor source is unsuitable for clinical
maintaining cell function, and minimizing immune use. Given these considerations, it is preferable to develop
responses . Kumar et al. conducted a study aimed at a standardized, non-tumor-derived ECM gel for clinical
[50]
developing 3D silk scaffolds capable of encapsulating use rather than relying on Matrigel.
pancreatic islets to generate bioartificial pancreatic systems
that can sustain insulin release (Figure 2E) . Silk-based 3.3. Synthesized biomaterials
[51]
scaffolds effectively facilitated the formation of islet-like Synthetic biomaterials are attractive platforms for protein
clusters, resulting in improved cell viability, proliferation, and cell delivery in regenerative medicine. Synthetic
and insulin production (Figure 2F). Moreover, the biomaterials offer greater reproducibility and control over
scaffolds were designed to release anti-inflammatory mechanical properties and have a biodegradable and non-
cytokines, which helped reduce inflammatory responses immunogenic structure that can be synthesized on a large
[55]
and promote an immunosuppressive environment scale with consistent mechanical and physical properties .
(Figure 2G). In in vitro study, the scaffolds were observed Unlike natural hydrogels, synthetic polymers are generally
to have immunomodulatory effects through the release of not used as primary materials for islet encapsulation.
anti-inflammatory cytokines and the localized polarization They are predominantly employed in the production of
of macrophages toward the implant site, ultimately favoring scaffolds designed to facilitate tissue formation, as well as
the integration of the graft with host tissues and enhancing in auxiliary roles, such as providing structure and serving
graft function . Research has been conducted to as a culture platform and encapsulation device.
[51]
investigate the use of heparin, sodium salt, and silk fibroin Among the synthetic polymers, polylactic-co-glycolic
solutions to produce cylindrical structures. Mao et al. acid (PLGA) is a highly functional biodegradable polymer
conducted a study and evaluated the therapeutic potential synthesized from two monomers, lactic acid and glycolic
of a macroporous scaffold composed of silk fibroin for islet acid, and offers distinct advantages. PLGA biodegradability
transplantation in diabetic mice . In this study, islets were is of particular importance, as it minimizes the potential
[52]
co-transplanted with either a plain silk fibroin scaffold or a for long-term toxicity and allows for the gradual
heparin-releasing silk fibroin scaffold into the epididymal replacement of the scaffold with new tissue as it degrades.
fat pad of diabetic mice. These results demonstrate that Additionally, versatility is a major advantage of PLGA, as
heparin-releasing silk fibroin scaffolds facilitate islet it can be fabricated into various forms, including fibers,
revascularization and cell proliferation, leading to a more films, and scaffolds, which are well suited for islet delivery
rapid reversal of hyperglycemia. This approach resulted applications [56,57] . Guo et al. fabricated microcarriers in
in the development of a macroporous silk fibroin scaffold the form of PLGA-porous microspheres using a double

Volume 9 Issue 6 (2023) 397 https://doi.org/10.36922/ijb.1024