An injectable and antifouling self-fused supramolecular hydrogel for preventing postoperative and recurrent adhesions

Abdominal adhesions is a type of serious complication of abdominal surgery. Existing barrier hydrogels are severely limited in the prevention of adhesions due to their poor controllability and long retention time in vivo. Here, we fabricate a supramolecular hydrogel (PNAGA-PHPMA) by copolymerization of N-acryloyl glycinamide (NAGA), a hydrogen bonding monomer, and highly hydrophilic N-(2-hydroxypropyl) methacrylamide (HPMA). The injectable PNAGA-PHPMA hydrogel cross-linked by reversible hydrogen bonds exhibits tunable rheological properties, preferable self-fused ability governed by H-bonds, excellent antifouling capability, and on-demand retention time in vivo. Squeezed out of a syringe to the abdominal cavity, the fragmented gel piece self-fused into an intact hydrogel, thus demonstrating an efficient inhibitory effect on postoperative abdominal adhesions and recurrent adhesions after adhesiolysis. The molecular mechanism studies reveal that the hydrogel significantly downregulates fibrosis-related cytokines (TGF-beta 1 and Fibrinogen) and pro-inflammatory cytokines (TNF-alpha and IL-6), regulates the fibrinolytic system balance (t-PA and PAI-1), and inhibits the activity of Erk1/2 and p38 kinase in the mitogen-activated protein kinase (MAPK) signaling pathway, thereby showing an excellent anti-fibrotic and anti-inflammatory effect. This injectable and antifouling self-fused supramolecular hydrogel has a profound clinical significance for the prevention of postoperative adhesions and recurrent adhesions.