Biodegradable PLGA/Dextran-CHO/Amikacin scaffold for on-demand antibacterial activity and accelerated wound healing

Bacterial infections continue to pose a significant challenge in the clinical application of implantable biomaterials and devices. While antibiotics remain the primary method for addressing bacterial infections, high-dose antibiotic administration often results in adverse side effects, whereas subinhibitory doses are insufficient to prevent biofilm formation. Here, we report a new biodegradable poly lactic-co-glycolic acid (PLGA) /dextran aldehyde (Dex-CHO)/Amikacin scaffold (PDAs) for on-demand amikacin release alongside sustained EGF delivery to promote wound healing. The PDAs were fabricated by integrating a porous PLGA scaffold with a Dex-CHO/Amikacin gel, cross-linked via Schiff base linkages. The scaffold exhibited excellent cytocompatibility and underwent sustained degradation over a period of 168 days, overcoming the intrinsic bust degradation behavior of PLGA based materials. The bacterial and acidic microenvironment triggered the release of amikacin through the decomposition of pH-sensitive Schiff base bonds between Dex-CHO and Amikacin, conferring high-efficiency (near complete) broad-spectrum antibacterial activity. Additionally, the PDAs served as carriers for EGF, facilitating the healing of bacterial-infected skin defects in rat models. These findings suggest PDAs to be a promising stimuli-responsive antibacterial scaffold for tissue regeneration.