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cells require suitable interconnected voids for effective Due to its numerous reactive functional groups, HA can
communication. Alginate scaffolds can be prepared using be readily functionalized, allowing for various structural
gas foaming, microfluidic foaming, electrostatic spinning, modifications and novel crosslinking strategies to broaden
leaching techniques, and freeze-drying, creating a suitable its range of applications. Wu et al. utilized HA hydrogels
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microenvironment for organoid culture. While alginate as a 3D culture model to promote the self-assembly and
hydrogels have broad potential in cartilage regeneration, neural differentiation of human iPSC (hiPSC)-derived
they have a few limitations, including limited mechanical neural progenitor cells. Soft methacrylated HA hydrogels
properties, instability in degradation, and durability significantly enhanced neural differentiation of neural
during application. Various methods have been developed progenitor cells, providing an effective platform for research
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to address these issues. For example, Fang et al. utilized into central nervous system disorders. 75
microfluidic droplet technology to achieve high-throughput
generation of organoids within alginate microbeads. The 3.1.5. Collagen
tumor masses within these alginate microbeads exhibit Collagen is the most abundant protein in the animal kingdom
both tubular and solid-like structures, demonstrating high and a key component of the ECM. It can be easily and cost-
similarity in cellular phenotype and lineage of the original effectively isolated from tissues, such as skin, tendons, and
tumors. In addition, in a study where alginate hydrogels pericardium, and is widely used as a biomaterial. Collagen
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were used as an alternative to traditional Matrigel, it exhibits excellent biocompatibility, providing an ideal
was found that alginate supported neurogenesis and environment for cell adhesion and proliferation, making it an
gliogenesis in spinal cord organoids with similar efficiency. excellent material for tissue regeneration. Randriamanantsoa
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Furthermore, alginate reduced the expression of non-spinal et al. successfully developed a complex tubular 3D
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cord markers, such as FOXA2, indicating its potential to architecture resembling pancreatic tissue by embedding
regulate neural fate formation. single mouse pancreatic ductal adenocarcinomas within a
3.1.3. Chitosan collagen matrix, thereby capturing the growth process and
morphological evolution of the tumors. Although collagen
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The chemical structure of chitosan closely resembles that of is primarily responsible for the tensile properties of natural
GAGs, which are key components of the ECM essential for connective tissues, collagen hydrogels generally exhibit low
cell-cell adhesion. It exhibits excellent biocompatibility, mechanical performance without covalent crosslinking,
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biodegradability, mucoadhesive properties, and which can be challenging for regenerating stiffer and stronger
antibacterial activity while demonstrating rapid mechanical natural tissues, such as bone. 78
recovery under compressive loads. This makes it an
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excellent support and growth environment for cells, with 3.1.6. Silk
wide applications in tissue regeneration and drug delivery. Silk fibroin (SF) is a protein fiber secreted by arthropods
However, chitosan still has certain limitations. Despite and other organisms. Its unique properties allow it to be
its toughness and flexibility, it lacks adequate mechanical utilized in various biomaterial forms, including films,
strength and requires suitable crosslinking agents during sponges, scaffolds, tubes, electrospun fibers, and hydrogels,
a complex preparation process. Upadhyay et al. cross- making it widely applicable in the biomedical field. Gupta
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linked amine-enhanced hydrogels without chitosan et al. used SF to support the growth and differentiation
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using glutaraldehyde, which increased the rigidity and of primary cells and iPSC-derived kidney tissues. The silk
mechanical resistance of the chitosan hydrogel, providing scaffolds supported the differentiation of key epithelial cell
a favorable environment for cell adhesion and proliferation types and facilitated structural formation. Moreover, the
of 3D-cultured MSCs and chondrocytes. 71
epithelial cells in the SF scaffolds expressed appropriate
3.1.4. Hyaluronic acid (HA) molecular markers, indicating that the epithelial-
mesenchymal transition process successfully produced
HA is a GAG present in the human body, particularly epithelial cells resembling nephron units. This demonstrates
in the ECM of bodily fluids and tissues. It is essential the potential of SF as a scaffold material for iPSC-derived
for maintaining tissue hydration and plays a key role kidney tissues. 79
in cell proliferation, differentiation, and inflammatory
responses. It demonstrates significant biological activity, 3.2. Components of synthetic hydrogels
leading to the development of biomedical products based 3.2.1. Polyethylene glycol (PEG)-based hydrogel
on its biocompatibility, biodegradability, non-toxicity,
and non-immunogenicity properties. However, HA PEG is a versatile polymer with extensive pharmaceutical
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hydrogels generally face challenges, such as inadequate applications. Composed of repeating ethylene glycol units,
mechanical strength and susceptibility to degradation by PEG is widely used in various drug delivery systems due
hyaluronidase. 73 to its diverse chemical structures and molecular weights. It

Volume 1 Issue 2 (2025) 7 doi: 10.36922/or.8262