Nucleoside-Based Supramolecular Hydrogels: From Synthesis and Structural Properties to Biomedical and Tissue Engineering Applications

Abstract

Supramolecular hydrogels are of great interest in tissue scaffolding, diagnostics, and drug delivery due to their biocompatibility and stimuli-responsive properties. In particular, nucleosides are promising candidates as building blocks due to their manifold noncovalent interactions and ease of chemical modification. Significant progress in the field has been made over recent years to allow the use of nucleoside-based supramolecular hydrogels in the biomedical field, namely drug delivery and 3D bioprinting. For example, their long-term stability, printability, functionality, and bioactivity have been greatly improved by employing more than one gelator, incorporating different cations, including silver for antibacterial activity, or using additives such as boric acid or even biomolecules. This now permits their use as bioinks for 3D printing to produce cell-laden scaffolds with specified geometries and pore sizes as well as a homogeneous distribution of living cells and bioactive molecules. We have summarized the latest advances in nucleoside-based supramolecular hydrogels. Additionally, we discuss their synthesis, structural properties, and potential applications in tissue engineering and provide an outlook and future perspective on ongoing developments in the field.

Dynameric G-quadruplex–dextran hydrogels for cell growth applications

“…We previously noted that the gelation process is very fast with the K + , providing stronger hydrogels when compared to other metal ions, Ba 2+ , Mn 2+ , Fe 3+ and Ca 2+ . 8 The structures of hydrogels containing Dex decorated with 100% G (DGH1), 50% G (DGH2) and 30% G (DGH3) were confirmed by circular dichroism (CD), FTIR, and X-ray diffraction (XRD) analyses. The CD spectra of all hydrogels exhibited two major peaks, positive at 235 nm and 300 nm and a characteristic negative contribution at 260 nm, which correlates to the distinctive peaks of the G4-stacked structures (Fig.…”

“…[1][2][3][4] In particular guanosine, a nucleoside and its analogues able to self-assemble into guanosine-quartets (G4) in the presence of various cations or into linear ribbons, have been extensively exploited for the fabrication of supramolecular gels. [4][5][6][7][8] The internal G4 network formed via H-bonding and metal coordination may be cross-linked via dynamic covalent bonds allowing for the encapsulation of large amounts of water molecules. It offers the entire hydrogel self-healable and injectable properties.…”

Optimization of guanosine-based hydrogels with boric acid derivatives for enhanced long-term stability and cell survival

“…In recent years, supramolecular hydrogels have received increasing attention due to their tuneable and reversible character based on small building blocks that link together to form complex networks. Thus, these materials are able to adapt to changing environmental conditions ( Li et al, 2020 ) and can self-heal after experiencing damage ( Godoy-Gallardo et al, 2023 ). Of all the types of supramolecular hydrogels studied that have these properties [e.g., fatty acids ( Nuthanakanti and Srivatsan, 2020 ), sugars ( Goel et al, 2021 ), cholesterol ( Zhang et al, 2021 ), amino acids ( Xie et al, 2020 ), peptides ( Falcone et al, 2020 )] and silk fibroin ( Yao et al, 2022 ; Zou et al, 2022 ), nucleoside-based hydrogels appear most promising for tissue engineering applications.…”

Self-Supporting Hyaluronic Acid-Functionalized G-Quadruplex-Based Perfusable Multicomponent Hydrogels Embedded in Photo-Cross-Linkable Matrices for Bioapplications

“…Frequently, guanosine (G) and its analogues are conjugated with low- and high-molecular-weight molecules to enhance the self-assembly driven hydrogelation, increase the lifetime stability, and assign dynamic multifunctional properties to the developed G-quadruplex supramolecular structures. − In particular, boronic acid is a highly versatile and one of the most commonly used building blocks for multicomponent self-assembly due to its ability to bind molecules containing diol groups, namely cis -1,2-diols, ,,,− such as G. Thereby, it enables the formation of dynamic and reversible cyclic boronate ester bonds-mediated G-quadruplex hydrogels denoting stimuli-responsive behavior, self-healing, injectable, or shape memory properties. ,,,− Recently, Biswas et al engineered a dynamic, stimuli-sensitive polyethylene (PEG)-functionalized G-quadruplex hydrogel for sustained doxorubicin release using 2-formylphenylboronic acid (2-FPBA) and G . Moreover, Tanaka et al reported the preparation of biodegradable and self-healable supramolecular G-quadruplex hydrogels by directly and symmetrically coupling deoxyguanosine monomers to the ends of the PEG chains, in the presence of K + or Na + , holding great promise to be used as drug carriers .…”