Page 10 - IJB-10-3

International Journal of Bioprinting Supramolecular hydrogels as bioinks

or fluids while retaining their structure, resembling soft methacrylated gelatin (GelMA), enzyme-based, or Schiff’s
biological tissue characteristics. They find applications in base crosslinking. Instead of these, using supramolecular
fields such as food processing, adhesives, and biomedicine, chemistry like host–guest interactions and others can
including drug delivery and tissue engineering. Their high improve the overall properties and structural performance
1
water content and flexibility make them biocompatible of the bioinks to a large extent. These supramolecular
and capable of controlled substance release. Hydrogels chemistry-based hydrogels exhibit multifunctionality,
can also respond to various stimuli like pH, temperature, boasting a diverse array of attributes that contribute to their
and electromagnetic fields. Overall, hydrogels can be versatility and efficacy compared to conventional bioinks.
2
used in a variety of applications because of their special Although several supramolecular hydrogels are reported
physical and chemical characteristics. Supramolecular for tissue engineering applications, this review focuses on
3,4
hydrogels are pliable substances that consist of self- specific examples of supramolecular chemistries exclusive
organized molecules or nanofibers joined by feeble and to 3D bioprinting. Particularly, we emphasize cucurbit[n]
reversible non-covalent interactions, including van der uril (CB[n]) and cyclodextrin (CD)-based host–guest
Waals forces, electrostatic interactions, hydrogen bonding, supramolecular hydrogels, as well as peptide and DNA-
metal–ligand coordination, π–π stacking, and host– based supramolecular structures, for 3D bioprinting and
guest recognition. They are composed of a new type biomedical applications. Additionally, we discuss some of
5,6
of non-covalently crosslinked polymer chains in a 3D the challenges and prospects associated with developing
framework which increases structural adaptability and supramolecular hydrogels and recommend potential
modifies overall performance. Their superior versatility, research avenues for future studies.
7,8
adaptability, dynamic nature, tunability, and high-end
biocompatibility set them apart from conventional 2. Different types of supramolecular
hydrogels in biomedical applications. hydrogels
Supramolecular hydrogels can be divided into three The chemistry and synthesis methods involve designing and
primary types based on the size of their crosslinked selecting suitable building blocks, including crosslinking
networks: macrohydrogels, microhydrogels, and precursors or interacting material components, followed
nanohydrogels. Supramolecular hydrogels having by optimizing the assembly conditions. Supramolecular
7-9
7,8
indefinite crosslinked networks on a macroscale are hydrogels can be categorized into three primary types
called macrohydrogels. These hydrogels, formed through according to the building blocks that were used: (i)
multivalent non-covalent interactions, demonstrate molecular hydrogels, (ii) supramolecular polymeric
significant potential as injectable scaffolds for tissue hydrogels, and (iii) supramolecular hybrid hydrogels.
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regeneration and repair, as well as the regulated
administration of medications, genes, and proteins. 2.1. Molecular hydrogels
Microhydrogels and nanohydrogels have similar Molecular hydrogels encompass the self-assembly
internal structures to macrohydrogels but differ in of low-molecular-weight building blocks, such as
terms of reactivity and size. Microhydrogels have sizes peptide amphiphiles (PAs) or synthetic molecules with
ranging from 1 to 100 µm, similar to human cells, while supramolecular motifs. These components form structures
nanohydrogels, with sizes below 200 nm, can be effectively resembling fibers through non-covalent interactions. The
endocytosed by cells, providing a platform for targeted resulting supramolecular nanofibers undergo non-covalent
delivery of therapeutic agents. Nanohydrogels have crosslinking or entanglement, which creates a 3D network.
potential in bioimaging and drug delivery applications, These hydrogels are characterized by degradation in
and controlling their size becomes crucial for optimizing physiological conditions and a responsiveness to biological
their characteristics, internalization processes, stimuli. 7,8,14,15
cytotoxicity, and medicinal effectiveness. Modifying 2.2. Supramolecular polymeric hydrogels
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the molecular ratio of substances has proven successful Multitopic conventional polymer chains functionalized
in achieving size control of nanohydrogels, enabling the with complementary supramolecular motifs are crosslinked
development of size-regulated supramolecular carriers for to generate supramolecular polymeric hydrogels by
cancer treatment and diagnosis. 10,11 Further research and multivalent non-covalent bonding. The constituents can
advancements in this field are expected to unlock the full be organic molecules, peptides, or polymers that exhibit
potential of nanohydrogels in biomedical applications. 12
direct or indirect non-covalent bonding, including van
Bioinks were reported with predominantly crosslinking der Waals forces, electrostatic interactions, metal–ligand
strategies, such as Ca for alginate-based gels, ultraviolet coordination, hydrogen bonding, and π–π stacking.
5,16
2+
(UV) light-crosslinking for methacrylate-based bioinks like Host–guest supramolecular polymeric hydrogels offer
Volume 10 Issue 3 (2024) 2 doi: 10.36922/ijb.3223