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International Journal of Bioprinting Supramolecular hydrogels as bioinks

flexibility, biostability, and the capacity to change their additional triggering can also be provided, such as pH or
structure and characteristics in response to external temperature manipulation, enzymatic reactions, electric
stimuli. 17,18 Hydrogen bonding offers specificity and fields, or other forms of external stimuli. The functional
directionality, enabling the formulation of smart hydrogels qualities of the specific hydrogel, in terms of its mechanical
with pH-responsive properties. 19,20 Conversely, in polar properties, simplicity of assembly, broad tunability, gelation
liquids, hydrogen bonds can readily dissociate. Metal– kinetics, stimuli responsiveness, biocompatibility, and
ligand coordination allows the formulation of robust other aspects, will undoubtedly be determined or modified
hydrogels with superior photoelectric capabilities. by these additional inducers. 22
Host–guest recognition, particularly using CD and
CB[n] macrocycles, provides a powerful platform for 3. Supramolecular hydrogels properties
formulating biocompatible hydrogels with diverse and characteristics
biological applications. Interaction of oppositely charged
polyelectrolytes through electrostatic forces can result in 3.1. Mechanical properties
strong materials, while incorporating a neutral hydrophilic Supramolecular hydrogels exhibit remarkable mechanical
block prevents phase separation and yields supramolecular properties, like toughness, elasticity, and stiffness, because
hydrogels. 21 Combining multiple non-covalent of their 3D non-covalent crosslinked networks, unlike
interactions in one system enhances the biostability, conventional polymer hydrogels (Figure 2). However,
stimuli-responsiveness, and mechanical characteristics their mechanical weakness and susceptibility to fracture
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of the resultant hydrogels. The growing interest in limit their application as structural biomaterials.
supramolecular hydrogels can be observed from the recent Strategies, such as increasing crosslink density, combining
trend in the publications and their specific application in multiple non-covalent interactions, and incorporating
various fields (Figure 1A and B). Different combinations inorganic nanomaterials, have been explored to enhance
of various host molecules and their corresponding guest hydrogel toughness and other mechanical properties.
molecules are presented in Figure 1C. For example, the addition of chemical crosslinkers,
utilization of polyampholytes, and hybridization with
The physiochemical characteristics and macroscopic clay nanosheets have demonstrated improved toughness
behaviors of the resulting hydrogel materials are largely and transparency in supramolecular hydrogels. With
dependent on the thermodynamic and molecular dynamic their non-covalent crosslinked networks, they exhibit
parameters of supramolecular crosslinkages; crosslink mechanical characteristics that are highly tunable and
density is influenced by the equilibrium constant; and the react rapidly to different environmental stimuli, enabling
dynamic character of crosslinkages among the polymer controlled swelling or dissociation. These hydrogels have
chains is influenced by kinetics. By precisely controlling enormous potential for regulated drug delivery and as
the synthesis conditions, such as the temperature, pH, biosensors, particularly for enzyme-responsive systems
concentration, and solvent selection, supramolecular with targeted tumor site delivery in cancer therapy.
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gelation can be achieved to form a stable and functional Self-healing is the remarkable ability to repair damage
supramolecular hydrogel. These hydrogels have potential and restore functionality in aquatic environments when
uses in tissue engineering and regulated drug delivery.
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subjected to an appropriate external stimulus. In contrast
2.3. Supramolecular hybrid hydrogels to hydrogels composed of covalently connected polymers,
Supramolecular hybrid hydrogels incorporate metal these non-covalent supramolecular interactions are
nanostructures (e.g., gold or silver nanoparticles [NPs]) reversible, allowing these materials to repetitively heal at
or inorganic elements (e.g., graphene, clays, carbon the molecular level and fully restore their original material
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nanotubes, quantum dots, etc.) into the crosslinked properties. From a 3D bioprinting perspective, this
networks. Furthermore, they introduce additional property is one of the ideal requirements for 3D bioinks.
functionalities, such as fluorescence, antibacterial activity, The degree of swelling and the retention of water in
chiroptical properties, and electrical conductivity. hydrogels are determined by the crosslinking density
Overall, supramolecular hydrogels offer versatile and hydrophilic properties of the polymer chains. 7,8
platforms for biomedical applications, and their specific Supramolecular hydrogels are formed from the
types, including molecular, polymeric, and hybrid physical entanglement of supramolecular nanofibers
hydrogels, provide distinct advantages and functionalities or supramolecular crosslinking of hydrophilic polymeric
that can be customized for different uses in tissue building blocks, both of which have the ability to retain
engineering, drug delivery, and other biomedical domains. substantial quantities of water in aqueous environment.
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Apart from the common mixing and self-assembling, However, recent advancements have allowed the

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