Multifunctional Fucoidan-loaded Zn-MOF-Encapsulated Microneedles for MRSA-Infected Wound Healing

Infected wound healing remains a serious challenge in clinical practice due to I) infection by diverse pathogens with drug resistance; II) long-term inflammation of lesions, which inhibits tissue regeneration; and III) infection by pathogens that can survive intracellularly to evade antibiotic treatment. Microneedle patches as wound dressings with antibacterial activity and regeneration capacity are desirable for wound healing. Herein, we used a Zn-MOF (ZIF) loaded with low molecular weight fucoidan (Fu) and further coated with hyaluronic acid (HA) as a biomedical agent to fabricate a microneedle patch (HAZ@Fu MN) that can realize transdermal drug delivery, intracellular and extracellular antibacterial activity and combination therapy for MRSA-infected wounds. Multifunctional HAZ@Fu NPs are mixed with photocrosslinked gelatin methacryloyl (GelMA) and then loaded into the tips of the MN patch. Enabling the HAZ@Fu NPs to reach the deep layer of the dermis, further targeting surviving MRSA at the subcellular level, which is facilitated by the HA coating. The released Zn2+ and Fu can damage the bacterial capsule, and also conducive to tissue regeneration. It has been demonstrated that HAZ@Fu MN, benefiting from these features, can dramatically inhibit MRSA and accelerate epithelial regeneration, inflammation resolution and neovascularization. The therapeutic effects of HAZ@Fu MN were demonstrated with MRSA-infected full-thickness cutaneous wounds in a mouse model. These results indicate that the combination of HAZ@Fu and degradable MN is of great value for promoting infected wound healing.