Injectable Phenolic-Chitosan Self-Healing Hydrogel with Hierarchical Micelle Architectures and Fast Adhesiveness

Biodegradable self-healing hydrogels are highly desirable materials for therapeutic systems, reusable devices, and intelligent cell/drug carriers. Many research efforts focus on additional functionalities of self-healing hydrogels through physical or chemical strategies/designs. Herein, N-[3-(4-hydroxyphenyl)­propanamido] chitosan and a difunctional Pluronic-F127 crosslinker (DF-PF) were synthesized and reacted to form the phenolic-chitosan self-healing hydrogel (CPF) with a high water content (96.5 wt%). Coherent small-angle X-ray scattering (SAXS) analyses of the hydrogel revealed a fast-forming primary fractal network followed by the gradual formation of a secondary micellar structure (∼12 nm). Such core–shell micellar architectures reinforced the hierarchical structure and endowed the hydrogel with thermoresponsiveness, verified by rheology and SAXS. Owing to the bioinspired phenolic chemistry, the CPF hydrogel was adhesive (binding strength 4–7 kPa) to artificial skin. Together with the rapid (<30 s) gelation kinetics, the hydrogel can be delivered by a dual-syringe as a fast adhesive. Moreover, the fast-gelled nature of the CPF hydrogel allowed spatially homogeneous embedding of mesenchymal stem cells that further developed into multicellular spheroids in 14 days. This new self-healing hydrogel shows multifunctionalities, benefiting from micellar architectures and phenolic modification. The corresponding hierarchical structure investigation provides an insight into the multiscale designs of a next-generation self-healing hydrogel for biomedical applications.