Biodegradable Supramolecular Materials Based on Cationic Polyaspartamides and Pillar[5]arene for Targeting Gram‐Positive Bacteria and Mitigating Antimicrobial Resistance

Abstract The increasing number of infections caused by pathogenic bacteria has severely affected human society, for instance, numerous deaths are from Gram‐positive methicillin‐resistant Staphylococcus aureus (MRSA) each year. In this work, four biodegradable antibacterial polymer materials based on cationic polyaspartamide derivatives with different lengths of side chains are synthesized through the ring‐opening polymerization of β‐benzyl‐ l ‐aspartate N ‐carboxy anhydride, followed by an aminolysis reaction and subsequent methylation reaction. The cationic quaternary ammonium groups contribute to the insertion of the catiomers into the negatively charged bacterial membranes, which leads to membranolysis, the leakage of bacterial content, and the death of pathogens. Except for wiping out MRSA readily, the biodegradable polymers possessing alterable antibacterial potency can minimize the possibility of microbial resistance and mitigate drug accumulation by virtue of their cleavable backbone. To manipulate the poor biocompatibility of these polycations, carboxylatopillar[5]arene (CP[5]A) is introduced to the polymeric antibacterial catiomers through the supramolecular host–guest approach to obtain novel antibacterial materials with pH‐sensitive characteristics (with CP[5]A departure from cationic quaternary ammonium compounds under acid conditions) and selective targeting of Gram‐positive bacteria. Finally, the facile and robust antibacterial system is successfully applied to in vivo MRSA‐infected wound healing, providing a significant reference for the construction of advanced antibacterial biomaterials.