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International Journal of Bioprinting Supramolecular hydrogels as bioinks

applications. Their diverse crosslinking possibilities, for up to a week, successfully inhibiting tumor expansion in
particularly with biologically relevant biomacromolecules, an animal model of therapeutic-resistant hepatocarcinoma.
further broaden their applications. Supramolecular This work presented the injectable MPEG-PCL-PEI/α-
hydrogels enhance drug delivery precision, ensuring CD supramolecular hydrogels as a versatile platform for
targeted release and optimizing therapeutic efficacy on-demand gene delivery and personalized medicine
for improved medical treatments. Supramolecular applications. In a mice model, a Dox/GC-PF127 hydrogel
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hydrogel formation typically utilizes precursors such significantly increased Dox buildup in tumor tissue while
as dexamethasone sodium phosphate, ketoprofen minimizing accumulation in normal tissues, leading to
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hydrogelator (peptide), α-CD, 145,146 cationic MPEG-b- effective tumor growth inhibition. This research highlights
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PCL-b-PEI (MPEG-PCL-PEI), and monofunctional the potential of the injectable Dox/GC-PF127 hydrogel as
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cationic UPy amine. 147 a promising system for localized tumor chemotherapy.
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A gel composition containing Ca and dexamethasone A local RNAi delivery method was developed with an
2+
sodium phosphate (Dex) could transition between liquid amine-PEG supramolecular gel that regulates the release
and gel states, contingent upon the concentrations of Ca of microRNAs and anti-miRs in their respective therapies.
2+
and Dex, for tunable thixotropic properties. Additionally, Effective ways for controlled RNAi therapy were achieved
the gel could regulate the rate of drug release by altering the by the modification of cholesterol, which regulates the
concentration of Ca . These hydrogels are self-assembled release of microRNA. Additionally, the introduction of
2+
through intermolecular aromatic–aromatic interactions, positively charged additive molecules into the gel controls
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facilitated by the ionic interactions between Ca and the the release mechanism. Supramolecular hydrogels
2+
phosphate groups of Dex. Higher concentrations of Ca are vastly used in numerous drug delivery applications
2+
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ions lead to increased crosslinking density, resulting in a because of their versatility and tunability. Recently, an
macroscopic sol–gel transition. The covalent translation injectable hydrogel depot technology was developed for
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of ketoprofen (drug) into self-assembling prodrugs the treatment of type 2 diabetes. This hydrogel-based
enabled the formation of supramolecular drug-loaded therapy sustained glucagon-like peptide (GLP)-1 receptor
hydrogels. The interface of α-CD and MPEG-PCL-PEI, agonists (RA) delivery over 42 days with a single injection,
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a copolymer that can bond with anionic pDNA for gene promising a once-every-four-months therapy for type 2
transfer, was employed to produce a similar hydrogel. diabetes management. 149
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To create Dox-loaded micelles, a glycol chitosan-Pluronic Supramolecular hydrogels have advanced as versatile
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F127 copolymer (GC-PF127) was utilized. The micelles vehicles for therapeutic delivery, allowing the regulated
exhibited pH-sensitive surface charges and were capable release of medicines, genes, and proteins into pathological
of forming an injectable hydrogel when α-CD was added. tissues. The high water content and mechanical
7
The hydrogel demonstrated the prolonged release of characteristics similar to tissue, coupled with their ability
Dox-loaded micelles and was supported with remarkable for in situ gel formation and responsiveness to bio-
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injectability, shear responsiveness, and rapid recovery. related stimuli, render these hydrogels highly relevant for
The gel was well-tolerated when injected into the eyes of therapeutic applications. 150,151 Moreover, these hydrogels
rats, effectively reducing inflammation compared to the have demonstrated potential for pH-controlled drug
traditional Dex solution. Hence, Dex supramolecular delivery in cancer therapy, as well as efficient gene delivery
hydrogel may be a good alternative for treating non- and protein encapsulation. 152,153 Supramolecular hydrogels
infectious uveitis, with a low risk of adverse effects such offer promising strategies to enhance therapeutic efficacy,
as lens opacity and problems with blood vessels in the reduce side effects, and improve targeted delivery in several
eye. A ketoprofen hydrogelator reportedly increased biomedical applications.
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cyclooxygenase 2 (COX-2) selectivity over COX-1, reduced
inflammatory cytokine concentration, and induced cell 6.2. Supramolecular hydrogels for wound
death in fibroblast-like synoviocytes. These hydrogels, healing applications
when injected into a joint cavity, demonstrated sustained Insufficient vascularization and an extended inflammatory
release and retention of the therapeutic agent, making them response lead to a poor and delayed healing process,
a promising candidate for localized treatment strategies warranting the need for fast and better wound management.
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for conditions like rheumatoid arthritis. The MPEG- Hydrogels can mediate or assist the healing process by
PCL-PEI copolymers exhibit improved gene transfection acting as a reservoir for anti-inflammatory, anti-bacterial,
efficiency and lower cytotoxicity compared to a standard and vascular regenerative substances, apart from providing
gene transfection agent. The hydrogel system demonstrates mechanical support at the wound site. In general, the in situ
controlled release of the therapeutic Bcl-2 conversion gene injectability and shear-thinning properties of hydrogels

Volume 10 Issue 3 (2024) 26 doi: 10.36922/ijb.3223