Injectable Bioadhesive Hydrogels Scavenging ROS and Restoring Mucosal Barrier for Enhanced Ulcerative Colitis Therapy

Abstract

Despite the progress in the therapy of ulcerative colitis (UC), long-lasting UC remission can hardly be achieved in the majority of UC patients. The key pathological characteristics of UC include an impaired mucosal barrier and local inflammatory infiltration. Thus, a two-pronged approach aiming at repairing damaged mucosal barrier and scavenging inflammatory mediators simultaneously might hold great potential for long-term remission of UC. A rectal formulation can directly offer preferential and effective drug delivery to inflamed colon. However, regular intestinal peristalsis and frequent diarrhea in UC might cause transient drug retention. Therefore, a bioadhesive hydrogel with strong interaction with intestinal mucosa might be preferable for rectal administration to prolong drug retention. Here, we designed a bioadhesive hydrogel formed by the cross-linking of sulfhydryl chondroitin sulfate and polydopamine (CS-PDA). The presence of PDA would ensure the mucosa-adhesive behavior, and the addition of CS in the hydrogel network was expected to achieve the restoration of the intestinal epithelial barrier. To scavenge the key player (excessive reactive oxygen species, ROS) in inflamed colon, sodium ferulic (SF), a potent ROS inhibitor, was incorporated into the CS-PDA hydrogel. After rectal administration, the SF-loaded CS-PDA hydrogel could adhere to the colonic mucosa to allow prolonged drug retention. Subsequently, sustained SF release could be achieved to persistently scavenge ROS in inflammatory areas. Meanwhile, the presence of CS would promote the restoration of the mucosal barrier. Ultimately, scavenging ROS and restoring the mucosal barrier could be simultaneously achieved via this SF-loaded bioadhesive hydrogel scaffold. Our two-pronged approach might provide new insight for effective UC treatment.

Janus hydrogels: merging boundaries in tissue engineering for enhanced biomaterials and regenerative therapies

“…cular or particle migration. [83][84][85][86] Therefore, investigating the surface and interfacial interactions of Janus hydrogels is crucial for a deeper understanding of their properties and applications, particularly in liquid-phase immobilization and multiphase reactions (Fig. 7).…”

Bioadhesive and Injectable Hydrogels and Their Correlation with Mesenchymal Stem Cells Differentiation for Cartilage Repair: A Mini-Review

“…Aldehyde groups [46] Hyaluronic acid-transglutaminase (HA-TG) hydrogel Covalent bonds [47] Self-cross-linked oxidized alginate/gelatin hydrogel Aldehyde groups [48] Doublle cross-linked Hyalourinoc acid hydrogel (Deial Alder clic reaction ad phenyl-boronate ester bond) Catechol groups [49] Tyramine-modified hyaluronic acid (HA-Tyr) hydrogel Adhesion to cartilage due to hyaluronic acid [24] Sulfhydryl chondroitin sulfate and polydopamine (CS-PDA) Catechol groups [50] Gelatine-Methacryloyl(GelMA)-glycol chitosan hydrogel Protein and methacrylate groups [51] Eznymytically cross-linked alginate-dopamine, chondroitin sulfate, and regenerated silk fibroin (AD/CS/RSF) Aldehyde and dopamine groups [52]…”