Simultaneous Delivery of Multiple Antimicrobial Agents by Biphasic Scaffolds for Effective Treatment of Wound Biofilms

Biofilms pose a major challenge to control wound‐associated infections. Due to biofilm impenetrability, traditional antimicrobial agents are often ineffective in combating biofilms. Herein, a biphasic scaffold is reported as an antimicrobial delivery system by integrating nanofiber mats with dissolvable microneedle arrays for the effective treatment of bacterial biofilms. Different combinations of antimicrobial agents, including AgNO3, Ga(NO3)3, and vancomycin, are incorporated into nanofiber mats by coaxial electrospinning, which enables sustained delivery of these drugs. The antimicrobial agents‐incorporated dissolvable microneedle arrays allow direct penetration of drugs into biofilms. By optimizing the administration strategies, drug combinations, and microneedle densities, biphasic scaffolds are able to eradicate both methicillin‐resistant Staphylococcus aureus (MRSA) and MRSA/Pseudomonas aeruginosa blend biofilms in an ex vivo human skin wound infection model without necessitating surgical debridement. Taken together, the combinatorial system comprises of nanofiber mats and microneedle arrays can provide an efficacious delivery of multiple antimicrobial agents for the treatment of bacterial biofilms in wounds. A new combinatorial delivery system is developed by integrating dissolvable microneedle arrays with electrospun nanofiber mats. This system can efficaciously deliver AgNO3, Ga(NO3)3 or vancomycin individually or collectively to treat Staphylococcus aureus biofilms in an ex vivo human skin wound infection model.