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enhances drug solubility through conjugation or formation which is beneficial for cell transplantation. 83,84 Sun et al.
85
of solid dispersions. In addition, PEG can be combined developed a porous hydrogel based on PNIPAAm as an
with other chemical groups to design drug delivery systems integrated platform for spheroid bioinks preparation.
sensitive to pH, reducing environments, or enzymatic The non-adhesive porous structure of the hydrogel
activity, enabling targeted drug release at specific sites. In facilitates the efficient fabrication of adipose-derived
organoid culture, the biocompatibility of hydrogels is crucial stem cell spheroids with excellent bio-preservation and
for the proper differentiation of stem cells. PEGylated drugs chondrogenic differentiation. 85
often exhibit reduced acute toxicity, and the “stealth” effect
can minimize immune system recognition of the drugs, 3.2.3. Polyisocyanate peptides (PIC)-based hydrogels
decreasing adverse reactions. Klotz et al. developed PIC hydrogels are polymeric materials formed by PICs.
80
81
a PEG hydrogel platform that mimics the biological PICs are polymers with rigid main chains that self-assemble
functions of the basement membrane while maintaining into hydrogels in solution. These molecular chains typically
the simplicity, customizability, and reproducibility of feature specific amino acid sequences or other functional
synthetic materials. This platform successfully engineered groups that mimic the mechanical and chemical properties
large blood vessels and capillaries within liver organoids. 81 of the natural ECM. Liu et al. developed PIC hydrogels
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3.2.2. Poly(N-isopropylacrylamide) (PNIPAAm) as simplified models of the ECM to investigate the impact
hydrogel of different parameters on cellular behavior. The study
primarily altered the stiffness and stress sensitivity of the
PNIPAAm is a temperature-responsive polymer known hydrogels, affecting the contacts between cells and polymers
for its pronounced hydrophilic-hydrophobic transition and the efficiency of stress transfer by regulating the polymer
at a specific temperature. This property has garnered chain length and the density of peptide adhesive sites. 87
significant attention in smart materials. Its chemical
structure consists of long-chain polymers formed by the The classification of hydrogels is presented in Table 2.
free radical polymerization of N-isopropyl acrylamide 4. Clinical applications of organoid
monomers. The distinctive isopropyl side chain gives it a
low critical solution temperature (LCST) of approximately hydrogels
32°C. Below this temperature, PNIPAAm hydrogels swell 4.1. Circulatory system
and exhibit hydrophilic properties, while above the LCST,
they undergo a phase transition to a hydrophobic state, 4.1.1. Heart
expelling water. Physical cross-linking can occur near The human heart is one of the most structurally complex
82
body temperature, enhancing the mechanical strength organs, originating from the mesoderm into a cardiac
of the hydrogel and allowing for rapid in situ gelation, crescent. It is composed of cardiomyocytes, accounting for

Table 2. Application of different types of hydrogels in organoid culture
Types of hydrogels Components Essence Advantage References
Natural hydrogel Decellularized Complex network structure Low immunogenicity 58
components extracellular matrix secreted by cells
Alginate Natural polymer derived Excellent non-immunogenicity, gelation 65
from seaweed properties
Chitosan The chemical structure Excellent biocompatibility, biodegradability, 68
closely resembles mucoadhesive properties, antibacterial
glycosaminoglycans activity, and rapid mechanical recovery under
compressive loads
Hyaluronic acid Glycosaminoglycan Excellent biocompatibility, biodegradability, 70
non-toxicity, and non-immunogenicity
Collagen A key component of the Excellent biocompatibility, economical 74
extracellular matrix
Silk Protein fiber Unique properties 77
Artificially derived Polyethylene glycol-based Versatile polymer high solubility, high targeting, low acute 78
hydrogel hydrogel toxicity
Poly (N-isopropyl A temperature-responsive A pronounced hydrophilic-hydrophobic 80
acrylamide) hydrogel polymer material transition at a specific temperature
Hydrogels based on Polymeric materials formed Emulate certain mechanical and chemical 83,84
polyisocyanate peptides by polyisocyanides properties of the natural extracellular matrix

Volume 1 Issue 2 (2025) 8 doi: 10.36922/or.8262