An Injectable, Self-Healing Hydrogel Based on G-Quadruplexes/Phenylboronic Acid Composites with Antibacterial Activity

Abstract

Injectable and self-healing hydrogels hold tremendous promise for biomedical applications; however, synchronously integrating robust mechanical adaptability, excellent cytocompatibility, and intrinsic antibacterial capabilities within a single matrix remains a significant challenge. In this study, we engineered an injectable, self-healing hydrogel based on dynamic cross-linking using guanosine-derived G-quadruplex supramolecular self-assembly and 3-aminophenylboronic acid (3-APBA)-mediated dynamic boronate ester. Systematic evaluation of various phenylboronic acid derivatives, GMP concentrations, K+ sources, and 3-APBA levels on gelation behavior yielded an optimized formulation. Scanning electron microscopy revealed that the optimized hydrogel exhibits a continuous, interconnected porous network structure after lyophilization. Thioflavin T fluorescence enhancement assays and circular dichroism spectroscopy further verify the formation of G-quadruplex-related ordered assemblies within the system. Rheological assessments demonstrate elasticity-dominated gel behavior, pronounced shear-thinning characteristics, and reversible structural breakdown and recovery under high and low strain cycles, indicating excellent injectability and self-healing properties. In vitro cytocompatibility evaluations show that the hydrogel possesses favorable cellular compatibility. Further antimicrobial studies reveal excellent in vitro antibacterial activity against Staphylococcus aureus and Escherichia coli. In summary, the injectable, self-healing G-quadruplex hydrogel constructed in this study integrates a porous architecture, dynamic reversibility, and robust biological functionality, highlighting its promising potential in antibacterial applications.