Abstract
Diabetic wounds exhibit impaired angiogenesis, drug-resistant bacterial infections, and oxidative damage to the microenvironment, presenting ongoing clinical challenges. In this research, we designed a core-shell structured multifunctional microneedle (MN) array patch (CS-SDFP/HA-Ag@MOF-PAL) to expedite the healing of infected diabetic wounds. The core consists of 10,000 MV hyaluronic acid (HA) and sucrose, integrated with Ag@MOF loaded with Palmatine (Ag@MOF-PAL). The shell, composed of chitosan (CS), encapsulates SDFP (CS-SDFP). Upon application to an infected diabetic wound, the shell swells, releasing the HA core, which dissolves to release Ag@MOF-PAL. The Ag@MOF targets and eradicates bacteria and eliminates biofilms of bacteria in the wound area, such as Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, while PAL mitigates chronic inflammation in wound macrophages via the NF-κB and MAPK signaling pathways. As the wound microenvironment normalizes, the SDFP released from the swollen CS recruits adipose-derived stem cells (ADSCs) and promotes angiogenesis to facilitate wound repair. Our experiments demonstrate that CS-SDFP/HA-Ag@MOF-PAL accelerates wound healing in a diabetic rat model with Pseudomonas aeruginosa-infected wounds. The property of this core-shell structured multifunctional MN patch presents considerable potential for the development of therapeutic strategies aimed at the healing of infected diabetic wounds.