Supramolecular assembly of dual crosslinked nanocomposite polysaccharides hydrogel: Integration of injectable, self-healing, and pH-responsive platform for sustained delivery of polyphenols

This study introduces an innovative approach in the field of biomaterials through the development of a multifunctional, printable scaffold designed for the advanced delivery of polyphenols. Addressing challenges of burst-release, poor compounds solubility and bioavailability, we engineered a supramolecular-assembled dual crosslinked hydrogel combining fucoidan (F) and chitosan (CS) encapsulating nanoliposomes. The novel integration of dibenzaldehyde-terminated PEG (DB) within the hydrogel, created a synergistic crosslinking through the formation of the covalent Schiff base bonds and physical interactions which enhanced the hydrogel's overall characteristics. Tailoring F content (DBCS-F), allowed the crosslinking density modulation, yielding a robust gel network structure with enhanced mechanical properties, evidenced by a remarkable compressive stress resistance of 1.73 MPa at 60% strain, coupled with high compressive resilience (79.31% stress recovery after 6 cycles), surpassing single crosslinked hydrogel (DBCS). The rheological analysis further confirmed the hydrogel's improved viscoelasticity, stable network structure, and shear-thinning behavior, affirming its excellent injectability and suitability for 3D printing applications. Most notably, the incorporation of catechin/juglone-loaded nanoliposomes contributed to a pH-responsive sustained release of polyphenols in simulated gastrointestinal conditions. The developed dual crosslinked hydrogel, integrating injectability, self-healing, and pH-responsiveness presents a significant advancement in biomaterials and holds a promising approach for the fabrication of personalized 3D printed scaffolds aimed for sustained and targeted polyphenols release.