Extracellular Matrix‐Inspired Antibacterial Fibrous Hydrogels Containing Polyhexamethylene Biguanide and Gd3+

Abstract Traditional bulk hydrogels containing antibiotics or metal ions often fall short in effectively treating wound infections due to mechanical limitations, bacterial resistance, and potential cytotoxicity. To address these challenges, an extracellular matrix (ECM)‐inspired antibacterial fibrous hydrogel featuring an anisotropic topological structure is developed that closely mimics the natural ECM environment. A novel antibacterial agent, PHMB‐VAN‐Gd (PVG), is synthesized by reacting polyhexamethylene biguanide (PHMB) with O‐Vanillin (VAN) to form the Schiff base ligand PHMB‐VAN (PV), followed by coordination with gadolinium ions (Gd 3 ⁺). Employing silk fibroin (SF) as the matrix, the PVG complex is incorporated into fibrous hydrogels through electrospinning, generating structures that replicate the fibrous architecture of the ECM. The resulting SF‐PVG fibrous hydrogels exhibited robust antibacterial activity, effectively inhibiting bacterial growth and biofilm formation. Furthermore, the aligned fiber orientation and substantial mechanical strength of these hydrogels facilitated cellular functions, promoting cell attachment and proliferation. This study underscores the significant potential of SF‐PVG hydrogels for wound infection treatment.