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International Journal of Bioprinting Supramolecular hydrogels as bioinks

crosslinked hydrogels. The concept underlying the dual crosslinking capabilities are stable under long-term
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dynamically sliding physical crosslinking mechanism cell culture conditions, with their mechanical strength
involves introducing interstitial stages of small organic being well-suited for bioprinting applications. Notably,
molecules into hydrogel networks to enhance hydrogen this bioink was assessed for its efficacy in inducing stem
bonds. This straightforward yet effective approach has cell differentiation, utilizing the bone marrow-derived
proven instrumental in achieving stretchable and self- mesenchymal stem cells (MSCs). These findings, as
healing properties in hydrogels. By capitalizing on the reported by Hu et al., underscore the bioprintability and
high nucleophilicity of amino groups in a water medium, versatility of this novel bioink formulation.
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the reaction selectively occurs between carboxyl and
amino groups. This method allows for the design and In another report, a biohybrid gradient supramolecular
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synthesis of hydrogels with exceptional extensibility and scaffold was 3D printed to repair osteochondral defects.
self-healing capabilities. Additionally, the gel exhibited The bioink consisted of cleavable poly(N-acryloyl 2-glycine)
remarkable swelling properties, with swelling ratios of (PACG) and GelMA. To make this biohybrid gradient, the
nearly 10,000% in distilled water and 2250% in phosphate- top layer was modified with PACG-GelMA hydrogel-Mn 2+
buffered saline (PBS). Rat fibroblast cells were used to test combination, whereas the bottom layer was modified with
the biocompatibility of hydrogels, and the results suggest PACG-GelMA hydrogel containing bioactive glass. This
that hydrogels are promising candidates as bioinks for could significantly facilitate simultaneous regeneration of
3D bioprinting. 44 the subchondral bone and cartilage in a rat model. Recently,
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A novel thermogelling block copolymer was employed a binary cell-laden hydrogel composed of guanosine and
to create a cytocompatible supramolecular hydrogel. This guanosine 5’-monophosphate exhibited sufficient stability
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hydrogel undergoes thermogelation within the temperature to ensure scaffold bio-integration during extrusion-based
range from room temperature to body temperature, 3D bioprinting. This development addresses challenges
resulting in the formation of transparent hydrogels. Notably, like material spreading and low shape stability over time. It
these hydrogels exhibit an unconventional bicontinuous exemplifies the potential use of supramolecular hydrogels
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sponge-like gel network with unexpectedly high strength for customized scaffold preparation in tissue engineering.
storage modulus (G’) (Gʹ > 1000 Pa). Derived from a The study demonstrated that a porous scaffold was formed
range of block copolymers featuring thermos-responsive from 3D-printed poly(caprolactone) (PCL) scaffold
poly(2-n-propyl-2-oxazine) (nPrOzi) monomer and integrated with parathyroid hormone (PTH) peptide-
hydrophilic poly(2-methyl-2-oxazoline), the synthesized loaded mesoporous silica NPs (PTH@MSNs) and GelMA/
hydrogel demonstrated suitability for tissue engineering methacrylated silk fibroin (SFMA) composite hydrogel,
applications. Cytocompatibility was confirmed through i.e., a hybrid PTH@MSNs/GelMA/SFMA/PCL (PM@GS/
testing with NIH-3T3 fibroblasts, supported by z-stack PCL) scaffold, which could alleviate critical load-bearing
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analysis, whereby the cells did not sediment in the bioink. bone defects.
In a recent development, Li et al. introduced a bioprintable A layer-wise 3D bioprinting approach was employed
copolymer that emulates the spatial arrangement found in using a dipeptide self-assembled hydrogel. In this method,
sea cucumber papillae and skin macroscale structures. By
strategically incorporating PEG chains with α-CD onto a the bioink was in situ gelled based on the Hofmeister
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polyrotaxane backbone, they achieved adaptable collagen sequence, ensuring high biosafety and biocompatibility.
flexibility, highlighting promising future applications in Supramolecular bioinks were also used in 3D-bioprinted
the 3D bioprinting field. scaffolds for drug release applications. An OglcNAc
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transferase inhibitor (OSMI-4) was incorporated into
A PEG-grafted chitosan-based supramolecular a fast-gelating supramolecular bioink with GelMA and
hydrogel bioink was generated via the relationship acrylated β-CD for spinal cord injury therapy based on
between the host and guest molecules, α-CD and PEG neural stem cells and neuron differentiation.
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side chain, respectively. This hydrogel was printed
using an extrusion-based 3D bioprinter (Regenovo, Based on the previously discussed chemistry and the
China) equipped with a liquid temperature controller. biomaterials used, the collective findings suggest that
Post-printing, the hydrogel was subjected to secondary supramolecular hydrogels are highly suitable as bioinks.
crosslinking with β-galactose-modified chitosan (β-GPS). The hydrogels exhibit cytocompatibility and facilitate
This bioink exhibited a poly-pseudorotaxane (PpRX) effective growth and differentiation of cells. These
structure with shear-thinning properties, attributed to properties render supramolecular hydrogels highly tunable
its dual physical crosslinking mechanism. Consequently, in terms of core strength, stability, biodegradability, and
it was demonstrated that supramolecular hydrogels with versatility in composition for 3D bioprinting applications.

Volume 10 Issue 3 (2024) 7 doi: 10.36922/ijb.3223