Structurally dynamic self-healable hydrogel cooperatively inhibits intestinal inflammation and promotes mucosal repair for enhanced ulcerative colitis treatment

Biomaterials. 2023 May 31;299:122184. doi: 10.1016/j.biomaterials.2023.122184. Online ahead of print.ABSTRACTHydrogels are a class of biocompatible materials with versatile functions that have been increasing explored for the localized treatment of ulcerative colitis (UC), but various mechanical stimuli may cause premature hydrogel breakage and detachment, impeding their further clinical translation. Here we report a multifunctional mechanically-resilient self-healing hydrogel for effective UC treatment, which is synthesized through the host-guest interaction between dopamine/β-cyclodextrin-modified hyaluronic acid (HA-CD-DA) and amantadine-modified carboxymethyl chitosan (CMCS-AD). The excessive β-CD cavities allow the incorporation of dexamethasone (DEX), while the porous hydrogel network potentiates the encapsulation of basic fibroblast growth factor (bFGF) and L-alanyl-l-glutamine (ALG). DA moieties in HA components allow firm adhesion of the hydrogel to the ulcerative lesions after in-situ implantation, while the reversible host-guest interaction between CD and AD could enhance the persistence of hydrogel. The hydrogel demonstrated favorable biocompatibility and could continuously release DEX to induce M1-to-M2 repolarization of mucosal macrophages through inhibiting the toll-like receptor 4 (TLR4)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) axis. Furthermore, the co-delivered bFGF and ALG facilitates the regeneration of ulcerative mucosa an...
Source: Biomaterials - Category: Materials Science Authors: Source Type: research