Tissue-adhesive, antibacterial, and macrophage-reprogramming hydrogel for sealing colorectal anastomotic leakage and promoting healing

Intestinal anastomosis is indispensable for treating inflammatory bowel disease and colorectal cancer, yet anastomotic leakage (AL) remains a frequent, life-threatening complication that markedly prolongs hospitalization. Conventional suturing affords limited protection against leakage and infection. Here, we report an injectable, multifunctional hydrogel (PGOT) composed of γ-poly(glutamic acid) conjugated with L-cysteine and dopamine (γ-PGA-Cys-DA), oxidized konjac glucomannan (OKGM), and tannic acid (TA). Dynamic thiol-aldehyde cross-linking affords rapid gelation (∼12 s) and repeatable self-healing, while catechol and polyphenol moieties confer strong wet-tissue adhesion and mechanical resilience that tolerates intestinal peristalsis and luminal pressure. <i>In vitro</i> and <i>in vivo</i> studies show that PGOT exhibits broad-spectrum antibacterial activity, robust pro-angiogenic properties, and effectively reprograms macrophages toward an M2 reparative phenotype. Application of PGOT to a rat colorectal anastomosis significantly reduces the incidence of AL and accelerates regenerative healing. These findings demonstrate that PGOT provides immediate mechanical sealing combined with bioactive regulation of the wound microenvironment, offering a promising strategy to improve postoperative outcomes after intestinal anastomosis.