Engineered Peptides-based Hybrid-nested Microneedle Effectively Treat Biofilm-infected Diabetic Wounds

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, we report a hybrid-nested microneedle scaffold (MQW-CMg-MOF) designed for efficient biofilm removal and accelerated healing of diabetic wounds. 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.