Engineered Peptides‐Based Hybrid‐Nested Microneedle Effectively Treat Biofilm‐Infected Diabetic Wounds

Abstract Diabetic wounds with biofilm present a significant challenge in wound care, often leading to chronic inflammation, recurrent infections, impaired healing, and in severe cases, amputations. Addressing this critical challenge requires a multifaceted treatment strategy. Herein, a hybrid‐nested microneedle scaffold (MQW‐CMg‐MOF) designed for efficient biofilm removal is reported and healing of diabetic wounds is accelerated. This scaffold integrates as a multifaceted system: the bottom layer features a nested microneedle patch embedded with vancomycin, the antimicrobial peptide W379, and the angiogenic QK peptide, while the top layer consists of chitosan cryogels incorporated with magnesium metal–organic frameworks. The nested microneedle patches are engineered to penetrate and mechanically disrupt biofilms and enable a programmed release of embedded agents, effectively addressing infection and promoting angiogenesis. Simultaneously, the cryogels serve as a substrate for scavenging reactive oxygen species and supporting cell ingrowth. The microneedle patches show substantial biofilm removal in vitro and in a preclinical diabetic swine biofilm‐infected wound model compared to the control. Most importantly, the combined hybrid‐nested microneedle arrays and cryogels effectively combat biofilm infection and promote wound healing in type 2 diabetic (db/db) mice. Overall, this multifunctional hybrid system shows promise in facilitating biofilm removal and enhancing the healing of diabetic wounds.