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International Journal of Bioprinting Supramolecular hydrogels as bioinks

an efficient photo-initiator. The resultant photo-initiator such as encapsulation release, cell filtration, and material
demonstrated effective two-photon production capabilities, clearance in vivo. The unique biological properties and
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displaying a low laser threshold and a high accuracy. tunable functions of host–guest supramolecular hydrogels,
Confocal imaging using fluorescence was made possible enabled by diverse and specific host–guest interactions,
without the need for fluorescent probes by exploiting make them smart scaffolds in tissue engineering.
the photo-initiator’s fluorescence characteristics (Figure For instance, CB[6]-conjugated hyaluronic acid and
3C). The 3D synthetic hydrogel scaffold microstructure, polyamine-conjugated HA self-assembled to generate
developed using two-photon polymerization techniques, biocompatible HA hydrogels that provide a controlled
also displayed excellent biocompatibility when cultivated 3D atmosphere for the development of cell-entrapped
with L929 cells. hydrogels and act as synthetic extracellular frameworks. 8,66
Supramolecular gelatin hydrogels containing CB[8]- CB[n]-based supramolecular assembly is a pivotal
based crosslinks were synthesized, as reported by Madl et intervention in biomedical applications and tissue
al. Preassembled CB[8]-FGGC peptide ternary structures engineering. The role of CB[n] chemistry as a potent
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and grafted norbornenes underwent thiol-ene reactions crosslinker in supramolecular hydrogels positions it as
to produce these linkages on demand (Figure 3D). The an excellent candidate for injectable and 3D bioprinting
gels that were produced were injectable, shear-thinning, applications. This chemistry accommodates a wide
and optically clear. These hydrogel-encapsulated human array of biomolecules and therapeutics driven by host–
fibroblast cells displayed excellent vitality and a widely guest interactions. Furthermore, CB[n] offers elevated
distributed shape when cultured. These CB[8]-based mechanical strength, self-healing capabilities, and efficient
gelatin hydrogels have potential uses in drug and cell cell encapsulation, promoting extended cell viability—a
delivery systems, bioprinting, and other fields. key focus in research and development.
Cell encapsulation efficiency is an intriguing 5.2. Cyclodextrin-based supramolecular hydrogels
characteristic, as the responsive dynamic crosslinking of Cyclodextrins (CDs) are starch-derived cyclic
CB[8] supramolecular hydrogels adjusts to cellular forces, oligosaccharides with a torus-like or truncated cone-
thereby enhancing cell viability. Zou et al. developed a like molecular shape having a hydrophobic empty cavity
thermoresponsive micelle-based percolated CB[8] hydrogel and a hydrophilic external face. 71,72 These hydrophilic
network and reported that the NIH-3T3 fibroblasts were groups of the glucopyranose units, projecting toward the
viable even after 30 min post-injection into the patient. outer surface, configure the distinctive features of CDs.
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In another study, the duration of encapsulation for human Each monomer is linked via an α-1,4-glycosidic bond,
fetal lung fibroblasts (MRC-5s) was extended to 7 days in and they are classified depending upon the number of
CB[8]–gelatin supramolecular biopolymers. CB[8]-based linked units, i.e., 6, 7, and 8 for α-CD, β-CD, and γ-CD,
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supramolecular hydrogels are utilized in tissue engineering respectively. 71,72 The height of these monomers remains
and various other biomedical contexts. Specifically, they constant at approximately 0.78 nm. However, their internal
are employed for functions, such as photoluminescence in diameter and cavity volume increase with an increasing
cellular imaging and biosensors and as tunable polymeric number of monomer units. The internal cavity volume is
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nanostructures. 61,64 Apart from CB[8], studies have also directly proportional to the category and K of the guest
looked at the generation of supramolecular hydrogels based molecule, highlighting its high specificity for molecular
eq
on CB[7] and CB[10] host–guest chemistry. 61,65 A hydrogel recognition. The presence of hydroxyl groups at the 2-, 3-,
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has been developed through the combination of nor-seco and 6-positions renders CDs highly adaptable for chemical
CB[10] (NS-CB[10]) and two AdA molecules (AdA- modifications, establishing them as remarkably versatile
four-arm-PEG) to develop a ternary complex. This novel compounds. This structural feature also contributes to
strategy can be used in tissue engineering, cell treatment, their distinction as one of the most easily water-soluble
and medication administration. Notably, the hydrogel hosts. Most importantly, the United States Food and Drug
displayed improved rheological characteristics and self- Administration (FDA) has classified all three CD forms
healing capabilities, with a high storage modulus (4.01 ± as generally recognized as safe (GRAS), and no negative
0.01 kPa) in contrast to an average loss modulus of 0.49 ± side effects have been reported. 72,73 Xia et al. provided
0.13 kPa. The versatile binding affinity of CB[7] has been a comprehensive insight into CD-based hydrogels and
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extensively investigated to develop hydrogels encompassing their chemistry. 74
a diverse array of documented interactions. Notably, a
binding affinity (K ) of 7.2 x 10 M would produce a A multivalently crosslinked guest polymer, forming
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eq

gel structure that emulates the behavior of covalent gels. a 3D-network hydrogel, is commonly regarded as
This distinctive characteristic governs effective processes, a CD-crosslinked polymer hydrogel. This hydrogel
Volume 10 Issue 3 (2024) 10 doi: 10.36922/ijb.3223