A dual cross-linked pillar[5]arene/porphyrin-based supramolecular polysaccharide hydrogel for promoted wound healing by combating multidrug-resistant bacteria and biofilm eradication.

Inappropriate use of antibiotics has emerged a large number of "multidrug-resistant bacteria" during the past decades, leading to a formidable challenge to global health. Photodynamic therapy exhibits effective antibacterial effects by the generation of abundant reactive oxygen species (ROS). However, the planar conjugated structure of most photosensitizers results in their close π-π stacking and the low ROS yield. Herein, we reported a dual cross-linked Pillar[5]arene/porphyrin-based supramolecular hydrogel for combating multidrug resistant bacteria and biofilm eradication. The supramolecular hydrogel consists of hyaluronic acid, naphthalene-functionalized positive charged porphyrin, and aldehyde-functionalized Pillar[5] arene via dual cross-linking by Schiff base bonding and host-guest interaction. Notably, the steric hindrance of Pillar[5]arene/porphyrin host-guest complexes effectively inhibits the π-π stacking of porphyrins and thereby enhances ROS generation. In vitro and in vivo antibacterial and biofilm disruption studies confirmed the outstanding antibacterial, biofilm eradication, and multidrug-resistant bacteria infected wound healing of the supramolecular hydrogel. The dynamic chemical bonding and host-guest interaction dual cross-linked hydrogel provides a promising strategy for addressing drug-resistant bacterial infections and promoting wound healing.