Biomimetic natural polysaccharide-peptide hydrogels via hierarchical co-assembly: A dynamic nanofibrous shield for active intervention of postoperative adhesions.

Abstract

Postoperative adhesions are common and serious complications following abdominal and gynecological surgery, leading to chronic pain, infertility, and intestinal obstruction, yet safe and effective clinical options remain limited. Inspired by the ordered architecture of the extracellular matrix (ECM), we engineered an injectable biomimetic hydrogel composed of naturally derived building blocks through the hierarchical co-assembly of hyaluronic acid (HA) and the antimicrobial peptide Temporin-SHF (SHF). Driven primarily by hydrophobic interactions and further stabilized by hydrogen bonding and π-π stacking, this crosslinker-free process yields a robust, ordered nanofibrous network with favorable biocompatibility. Functionally, the hydrogel integrates antibacterial activity against the tested bacterial strains, rapid hemostatic performance, and a physical barrier reinforced by the ordered nanofibrous architecture. Notably, it operates through a dual mechanism: serving as a "Dynamic Nanofibrous Shield," in which the highly hydrated HA-rich interface, together with the ordered nanofibrous topography, contributes to reduced protein adsorption and cell adhesion, while actively modulating the wound microenvironment by inhibiting fibroblast activation and suppressing pro-inflammatory cytokine expression. In rat models of abdominal and intrauterine adhesions, the hydrogel significantly reduced adhesion severity through coordinated antibacterial, anti-inflammatory, hemostatic, and antifibrotic effects. This study establishes a bioinspired strategy that integrates dynamic structural shielding with active biological regulation, offering a promising approach for preventing complex postoperative adhesions.