Abstract

Fucoidan, a marine-derived polysaccharide with versatile biological functions, holds strong potential for biomedical applications but is limited by low viscosity and poor gelling capacity. To address these challenges, we developed a bioengineered fucoidan-based hydrogel (Fuco-PGA B ) by modulating intermolecular interactions with functionalized polyglutamic acid. This molecular design increased hydrogen-bonding density, yielding a hydrogel with robust rheological properties, including pronounced shear-thinning behavior and instantaneous self-healing. These features enable the material to dissipate peristaltic stress while protecting encapsulated bacteria during gastrointestinal transit. The Fuco-PGA B hydrogel enabled efficient oral delivery of both Gram-positive ( Lactiplantibacillus plantarum 90) and Gram-negative ( Escherichia coli Nissle 1917) probiotics. In simulated digestive fluids, probiotic survival increased by more than two orders of magnitude compared to free cells, and in vivo viability was sustained for up to 96 hours. Beyond protection, the hydrogel alleviated oxidative stress in intestinal epithelial cells by maintaining glutathione redox balance, inhibiting lipid peroxidation, enhancing superoxide dismutase activity, and scavenging reactive oxygen species. In a mouse colitis model, probiotic-loaded Fuco-PGA B restored microbial composition by reducing pathogenic species, enriching beneficial taxa, and suppressing inflammation. By integrating the intrinsic properties of fucoidan with a tunable cross-linking strategy, this hydrogel prolongs intestinal retention, enhances probiotic colonization, and improves intervention impact. These findings establish Fuco-PGA B as a promising oral delivery platform for collaborative intervention in inflammatory bowel disease.