Self-healing chitosan-catechol hydrogel with tailored self-assembled fibrillar or micellar structures for biomedical applications

Mussel-inspired chitosan-catechol hydrogels have garnered attention due to wet adhesion and radical scavenging ability. However, correlation between gel forming conditions and mesoscale self-assembled structures of chitosan derivatives remains to be elucidated. Herein, homogeneous (CC) and fibrillar (CC′) chitosan-catechol hydrogels were selectively fabricated via two different processes, controllable rotary concentration vs. lyophilization-redissolvation. Small-angle X-ray scattering analyses revealed distinct self-assembled structures, nanoclusters (~4.4 nm) for CC hydrogel and nanofibrils (L ~ 13 nm) for CC′ hydrogel. The fibrillar architectures reinforced CC′ with modulus up to ~2.8 kPa, exceeding that of CC by ≥50-fold. Both CC and CC′ can be further reinforced by dynamic long-chain crosslinker, forming chemical network. Micellar crosslinker dampened the strain-hardening of the host network from 98% to 17%, while the linear variant preserved higher energy storage capacity. These self-assembled and crosslinked hydrogels universally possessed injectability, adhesiveness, antioxidation, and self-healing capabilities. Meanwhile, the fibrillar assemblies can guide the alignment and differentiation of neural stem cells. The micellar hydrogel sustains the release of chondrogenic small molecular drug (Y27632) and induces the chondrogenesis of mesenchymal stem cells in the hydrogel. This study establishes a combinatorial chitosan-catechol platform where processing and crosslinking strategies yield various hydrogels with tailored architectures for different biomedical applications.