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

Abstract

Dynamic G-quadruplex supramolecular hydrogels have aroused great interest in a broad range of bioapplications. However, neither the development of native extracellular matrix (ECM)-derived natural biopolymer-functionalized G-quadruplex hydrogels nor their use to create perfusable self-supporting hydrogels has been explored to date, despite their intrinsic potential as carrier vehicles of therapeutic agents, or even living cells in advanced regenerative therapies, or as platforms to enable the diffusion of nutrients and oxygen to sustain long-term cell survival. Herein, we developed a dynamic co-assembling multicomponent system that integrates guanosine (G), 3-aminophenylboronic acid functionalized hyaluronic acid (HA-PBA), and potassium chloride to bioengineer strong, homogeneous, and transparent HA-functionalized G-quadruplex hydrogels with injectable, thermo-reversible, conductive, and self-healing properties. The supramolecular polymeric hydrogels were developed by hydrogen bonding and π−π stacking interactions between G coupled via dynamic covalent boronate ester bonds to HA-PBA and stabilized by K + ions, as demonstrated by a combination of experiments and molecular dynamics simulations. The intrinsic instability of the self-assembled G-quadruplex structures was used to bioengineer selfsupporting perfusable multicomponent hydrogels with interconnected size and shape-tunable hollow microchannels when embedded in 3D methacrylated gelatin supporting matrices. The microchannel-embedded 3D constructs have shown enhanced cell viability when compared to the bulk hydrogels, holding great promise for being use as artificial vessels for enabling the diffusion of nutrients and oxygen essential for cell survival. The proposed approach opens new avenues on the use of ECM-derived natural biopolymerfunctionalized dynamic G-quadruplex hydrogels to design next-generation smart systems for being used in tissue regeneration, drug screening, or organ-on-a-chip.

A protein-based self-healing hydrogel for prolonged antimicrobial drug delivery with synergistic activity

“…Due to the highly intricate nature of the protein system, the study did not provide a clear understanding of the exact structures of the newly formed fluorophore. 40…”

“…These bonds undergo breakage and reformation in response to applying and removing external force, such as cutting. 38–40 The self-healing property [Fig. S5(b), ESI†] of the hydrogel is shown visually.…”

In-Bath 3D Printing of Anisotropic Shape-Memory Cryogels Functionalized with Bone-Bioactive Nanoparticles

“…Polymeric hydrogels find widespread use in the biomedical field, particularly in tissue engineering, , drug delivery, , and wound healing, , as they showcase important features such as high-water content and similarity to soft tissues. , Despite their functionalities, hydrogels have drawbacks resulting from their 3D nanoporous network, leading to limited cell infiltration and nutrient diffusion, and resulting in suboptimal cell densities within the hydrogel matrix . Additionally, many efforts have been made to develop injectable hydrogels as an alternative to invasive surgical techniques. , This strategy can be implemented as a bulk biomaterial or by using liquid precursors.…”

“… 7 , 8 Despite their functionalities, hydrogels have drawbacks resulting from their 3D nanoporous network, leading to limited cell infiltration and nutrient diffusion, and resulting in suboptimal cell densities within the hydrogel matrix. 9 Additionally, many efforts have been made to develop injectable hydrogels as an alternative to invasive surgical techniques. 10 , 11 This strategy can be implemented as a bulk biomaterial or by using liquid precursors.…”