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International Journal of Bioprinting Supramolecular hydrogels as bioinks

azide cycloaddition was employed, utilizing multi-arm PEG, flexibility. In summary, the remarkable versatility,
to crosslink the hyaluronan-based hydrogel. This hydrogel biocompatibility, and widespread acceptance of peptide-
was synthesized de novo using helix-loop-helix peptide based supramolecular hydrogels position them as
conjugation. The fabrication process involved bicyclo[6.1.0] promising bioink candidates for effective 3D bioprinting
nonyne (BCN)-modified HA via carbodiimide chemistry. of tissues. Several comprehensive reviews have previously
Additionally, the modified HA was then crosslinked via been published 15,126,127 that elucidated the diverse
both covalent and supramolecular means with an azide- applications and versatility of peptide and polypeptide-
modified helix-loop-helix polypeptide (JR2EK[N3]), which based supramolecular hydrogels.
folded and dimerized into four-helix bundles. Cell–hydrogel
interactions and biomineralization can be regulated 5.4. DNA-based supramolecular hydrogels
through supramolecular tuning by utilizing a variety of DNA supramolecular hydrogels refer to hydrogels that
complimentary peptides with diverse functions. Notably, are interconnected through DNA hybridization. These
an inexpensive osteogenic growth peptide (OGP) delivery hydrogels have garnered significant interest, owing to
system for sustained release, focusing on long-term bone their exceptional molecular permeability, compatibility
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regeneration, was reported based on the SAP strategy. In with biological systems, degradability, thixotropy, and
addition to demonstrating biocompatibility and promoting ability to self-repair. Consequently, they are highly useful
cell proliferation, the OGP-dimer hydrogel displayed in different fields, including tissue engineering, cell
promise as both a therapeutic option and a bioink for 3D culture, and 3D printing. The inherent design flexibility
bioprinting, particularly in the context of bone regeneration. and stimuli-responsiveness of DNA further broaden
the applications for DNA-based hydrogels, such as the
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Peptide amphiphiles (PAs) are a useful supramolecular development of detection apparatuses and materials with
material with customizable biochemical and nano- shape-memory properties. These hydrogels could be
135
structural characteristics. PAs have been extensively applied hybridized with other materials, such as polyacrylamide,
in tissue engineering, including angiogenesis, neurogenesis, polypeptide, protein, poly(phenylenevinylene), graphene
and bone regeneration. Yan et al. established a thiolated oxide (GO), and carbon nanotube, via ester-amine click
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gelatin 3D-printable bioink augmented with PAs to modify reaction, conjugation, or π–π interactions. Moreover,
its nanostructure and bioactivity, thereby facilitating DNA-based hydrogels can be dual-crosslinked with more
cell incorporation. The bioink was developed through than one DNA molecule. Pure DNA hydrogels were also
a double secondary crosslinking approach, involving formed by branched and linear DNA scaffolds, either via
homo-bi-functional maleimide PEG (MAL-PEG-MAL) self-assembly or pH-triggered crosslinking.
136
and Ca . This method enabled multi-layered bioprinting, DNA supramolecular hydrogels are responsive to
2+
exemplified by the use of a laminin-mimetic IKVAV environmental stimuli (physical and chemical), leading to
(CH [CH ] VVAAEEIKVAV)-based PA system with alterations in the assembly of crosslinking and subsequent
3
2 15
biliary epithelial cells (SV40SM) that displayed remarkable
rheological properties. Additionally, Sather et al. phase transitions. The dynamic response to these triggers
125
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utilized supramolecular polymer aqueous inks, composed enhances the versatility of DNA hydrogels, rendering them
of PAs and chromophore amphiphile (CA), in direct suitable for a range of applications. Various DNA hydrogels
ink writing (DIW) to construct macroscopic ionically have unique responsive behaviors to environmental
crosslinked liquid crystalline hydrogels with modifiable stimuli, such as a pH-sensitive DNA hydrogel with a high
nanoscale arrangement. Intermolecular interactions cytosine content. Similarly, a pH-sensitive hybrid hydrogel
among the self-assembled structures were determined made of DNA and polyacrylamide would exhibit shape-
by the pH and salt concentrations in the system. For memory behavior. Furthermore, when exposed to visible
and UV light, a polyacrylamide–DNA hybrid hydrogel
example, charge density affected the viscosity of the bioink. treated with Azo exhibits reversible volume changes. A
Nonetheless, these hierarchical interactions enhance the carboxymethylcellulose (CMC)–DNA hybrid hydrogel
printability and nanoscale alignment of the hydrogel. 125
with dual crosslinking networks and Azo functionalization
Notably, the formation of π–π stacking and hydrogen exhibits shape-memory characteristics in both visible and
bonds between the precursors of a peptide-based UV light. Temperature variations induce gel–sol conversion
supramolecular hydrogel is dependent on the nature of the in a polyacrylamide–DNA hybrid hydrogel through
precursors. The formation of the stackings and bonds can reversible DNA hybridization. Likewise, a comprehensive
be attained via chemical reactions, such as homologation, DNA hydrogel undergoes phase confirmations in
wittig, catalytic hydrogenation, and coupling reactions. response to temperature changes. Another type of DNA
The stacking and bonds impart key characteristics to gel network would respond to temperature changes by
the hydrogel, such as solubility, hydrophobicity, and releasing doxorubicin (Dox) and gold NPs (AuNPs)

Volume 10 Issue 3 (2024) 18 doi: 10.36922/ijb.3223