Page 19 - IJB-10-3

International Journal of Bioprinting Supramolecular hydrogels as bioinks

possesses significant shear-thinning and self-healing morphology, making it appropriate for the development
characteristics. Polymers, such as poly(ethylene oxide) of injectable drug formulations. NIH-3T3 fibroblasts
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(PEO), PEG, poly(propylene oxide) (PPO), or co- were used to assess biocompatibility, and when exposed
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polymers with blocks of PEO and/or PPO, alone as PEO- to an elevated dosage of 50 mg/mL for a period of 48 h,
PPO-PEO (Pluronics), 72,76 or in combination with various the TH50 composition did not exhibit any toxicity. In
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blocks, such as poly[(R)-3-hydroxybutyrate] or PCL, are contrast, Dai and colleagues described a novel injectable
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generally suitable guest molecules. 71,79 The aforementioned and reversible supramolecular gel that exhibited host–guest
characteristics can also be attained using more functional inclusion complexation between the binary medicine-
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and responsive substances, such as cholesterol, Ad, Azo, loaded micelle and the α-CD. The micelle was composed
ferrocene, and arylazopyrazole (AAP). 71,80 of self-assembled eight-arm PEG-betulinic acid (BA)/
hydroxycamptothecin (HCPT) in water. In the hydrogel,
Further, if the CD-based interactions provide a highly
compact polymer network of hydrogels, such forms the outer-exposed PEG chains in the micelle were threaded
into α-CD cavities, positioned along its sides.
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are referred to as supramolecular nanogels. Nanogels
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typically contain branched and star-shaped structures or The UV-initiated copolymerization of a gel and
micellar assemblies, constituting miniaturized hydrogels a supramolecular crosslinker can also be utilized for
with expected charge distributions. Simple polymer supramolecular hydrogel production, whereby the CD host
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networks are converted to nanogels either by linking can accommodate a guest polymer. In a study by Zhou et al.
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or threading CDs to the polymer chains or through (Figure 4A), octa-CD polyhedral oligomeric silsesquioxane
inter-hydrogen bonding among CDs. Due to their ease (OCDPOSS) reacted with acrylamide-modified Ad (Ad-
of preparation and biocompatibility, nanogels exhibit AAm) to form a star-shaped supramolecular crosslinker,
improved encapsulation efficiency, thus emerging as which then copolymerized with acrylamide to form the
promising drug delivery depots. supramolecular hydrogel. The multivalent interlinking
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demonstrated super-stretchability, rapid self-healing, and
Cyclodextrins (CDs) can also be employed to develop
low molecular weight (LMW) hydrogels. This involves injectability of the hydrogels. Moreover, these hydrogels
are expected to be biocompatible and can be employed
the amalgamation of CDs or CD derivatives as a daisy as hydrophobic drug delivery systems. However, these
chain structure (host–guest interaction). CD-modified supramolecular hydrogels are not mechanically strong.
peptide hydrogels and self-assembled surfactant hydrogels Miller et al. utilized supramolecular guest–host assembly
with CD lead to supramolecular configuration. In tissue for making a mechanically robust hydrogel with fibrillar
engineering, these gels supported better spreading of topography. They combined methacrylate-modified HA
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cells. For example, NIH-3T3 fibroblast cells were spread electro-spun hydrogel nanofiber segments, incorporating
more efficiently in RGD-modified non-covalently linked β-CD (host) and Ad (guest) supramolecular chemistry
β-CD hydrogel. 81,82 Recently, an AAP-altered pentapeptide (Figure 4B). The gel exhibited a six-fold increase in
gelator Nap-GFFYS-based magneto-photo-responsive mechanical strength compared to its parent materials,
LMW supramolecular hydrogel was developed employing alongside excellent self-healing and shear-thinning
a modular co-assembly technique. β-CDs are multivalently qualities. Moreover, the fibrous gel could support the
crosslinked with the Nap-GFFYS-AAP gelator, involving hMSCs with > 85% cell viability for at least 7 days. Recent
the host–guest chemistry of CDs and the self-assembly studies demonstrated promising potential for utilizing
of peptides. Moreover, β-CD vesicles were embedded CDs in specific molecular recognition activities with
with superparamagnetic cobalt ferrite NPs to impart the nanomaterials to construct hydrogels with enhanced
magnetism. This embedment affects the stiffness of the molecular recognition capabilities. In a recent study,
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hydrogel, while the magnetism affects the storage modulus. the surface of 2D MoS was conjugated with β-CD via a
Additionally, the hydrogel’s stiffness may be reversibly one-pot nucleophilic exchange between monotosylated
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altered by employing UV or visible light irradiation to β-CD and the sulfur atoms of MoS . The resultant material
deactivate the AAP moiety and the hydrophobic cavity of was crosslinked with Ad-modified gelatin, employing
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the β-CD interface, respectively. supramolecular guest–host assembly. This self-healable
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Wang et al. have developed a biocompatible cum and flexible gel displayed a tenfold higher storage modulus
injectable polyrotaxane hydrogel mainly for drug delivery than gelatin. In addition to this, the inherent properties of
applications. A four-arm PEG (4-PEG) was non-covalently MoS , like biodegradability, biocompatibility, antibacterial
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crosslinked with α-CD by supramolecular host–guest activity, high loading capacity, and photothermal property,
chemistry. The gel was characterized by potential suggest that the new supramolecular polymer gels could
thixotropic shear-thinning behavior with macro-porous serve as a potential solution for tissue engineering. 86

Volume 10 Issue 3 (2024) 11 doi: 10.36922/ijb.3223