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International Journal of Bioprinting Supramolecular hydrogels as bioinks

(e.g., elastic modulus: 4–62 kPa), resulting in the as a minimally invasive tool for tissue defect filling or
development, growth, and customary release of HepaRG corneal cell introduction for self-regeneration. 119
spheroids. Since no crosslinkers have been used, it is Researchers made efforts to improve the mechanical
expected that there will be a decrease in cell damage properties, cell adhesion, and proliferation, thereby
attributed to chemical reactions. In addition, the providing a native ECM-like environment for
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N-terminal is essential if the two peptides are short and 3D-bioprinted scaffolds using bioinks containing peptides
contain Lys-Cys residues at the C-terminal. Such highly (Figure 5C). An in situ gelled dipeptide, Fmoc-YK bioink,
thixotropic gels were found to be effective for 3D cell based on the Hofmeister sequence in the presence of sulfate
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proliferation. A coupling reaction could also be adopted ions, was developed to achieve adjustable mechanical
to fabricate peptide-based supramolecular hydrogels as in strength and controllable degradation properties. Fmoc-
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normal hydrogel synthesis. Through a thiourea-catechol YK contributed to hydrophobic and π–π interactions,
(TU-Cat) coupling reaction, a catechol-modified peptide while lysine provided electrostatic interactions and
(Cat-RGD) can bioactivate a mechanically inert hydrogel. hydrogen bonding. The DMEM-toughened scaffold was
The engineered peptide (Cat-RGD) with host thiourea- prepared using a layer-wise 3D printing method without
linked (TU) monoacrylated β-CDs monomers were used any crosslinking agent, ensuring cell culture stability,
to create robust hydrogels, leading to enhanced cell and biocompatibility, and biosafety for organoid culture.
tissue adhesion.
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In a study by Chu et al., it was reported that a 20%
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Additionally, the amalgamation of magnetic NPs proangiogenic self-assembling peptide nanofiber hydrogel
(MNPs) into a gel matrix expanded its applications in (SLg)-based 3D-printed framework (in combination with UV-
the biomedical field. Embedded MNPs enabled remote crosslinking GelMA) established the best collagenous fibrous
modulation of the hydrogel’s physical properties via an structure for fast revascularization and dermal regeneration
exterior magnetic field, leading to long-lasting changes (Figure 5D). The hydrogel’s nanofibrous structure, formed
in mechanical properties and adjustments in the 3D through hydrophilic and hydrophobic interactions between
structure, potentially inducing anisotropy. Mañas-Torres alternating amino acids, resembled the native ECM. The loose
et al. developed biocompatible and biodegradable Fmoc- porous structure of the nanofibrous hydrogel 3D scaffolds was
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FF and Fmoc-RGD short peptide hydrogels (7:3 ratio) conducive to cell migration, infiltration, and growth, especially
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incorporated with MNPs. This hybrid hydrogel, serving those of endothelial origin. In another approach, Zhou et
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as a 3D scaffold, demonstrated improved self-healing al. developed a lysine peptide–dendrimer-reinforced bioink
properties, mechanical stability, good biocompatibility, (HC-PDN) containing the peptide–dendrimer-branched PEG
and injectability. It was confirmed that the use of MNPs with end-grafted norbornene (PDN) and cysteine-modified
with the supramolecular peptide hydrogel improved its HA (HC). The addition of ethylene end-groups extensively
physical properties. 118 promoted the attaching of abundant moieties, leading to
enhanced thiol-ene-promoted crosslinking in HC-PDN.
With similar objectives, Farsheed et al. established This subsequently increased the rheological and mechanical
the printability of a multidomain peptide (MDPs)- characteristics of HC-PDN and significantly reduced the
based supramolecular nanofibrous hydrogel at low accumulation of reactive oxygen species (ROS) compared
concentrations. The precursors, N’-acetylated cationic to methacrylated HA (HAMA). As a result, a diverse and
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MDP (K2[SL]6E2) and C’-amidated anionic MDP biomimetic hepatic tissue was created by co-culturing HepG2-
(E2[SL]6E2), formed dynamic nanofibers through C3As, LX-2s, and EA.hy.926s cells in 3D-bioprinted scaffolds
supramolecular forced assembly (Figure 5B). The of HC-PDN, demonstrating the vital roles of the native liver. 120
temperature-independent extrusion-based 3D-bioprinted Chiesa et al. attempted to predict biomaterial
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MDP structures displayed variations in cellular activity printability with respect to extrudability and long-term
that were charge-dependent in vitro, such as fast mechanical stability of the scaffold using finite element (FE)
proliferation and high viability. Overall, the work has simulation. An SAP hydrogel containing β-sheet-forming
generated an enhanced version of self-assembled peptide F9 peptide (FEFKFEFKK; F: Phe; E: Glu; K: Lys) underwent
(SAP)-based 3D bioprinting bioink. Dankers et al. piston-driven extrusion 3D bioprinting, showcasing
reported a UPy moieties-based supramolecular hydrogel versatility in printing complex structures, such as the human
for corneal stromal construct development. The hybrid ear. Furthermore, a specific peptide folding-mediated
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hydrogels revealed striking similarities, positioning the interaction-based 3D printable hydrogel was developed
fully synthetic hydrogel as a promising candidate for by Aronsson et al. using a tunable covalent biorthogonal
mimicking the stromal ECM and demonstrating potential crosslinking strategy. In this case, strain-promoted alkyne-
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Volume 10 Issue 3 (2024) 17 doi: 10.36922/ijb.3223