γ-polyglutamic acid-encapsulated metformin-loaded Ga-Car-MOF and hydrocaffeic acid-modified chitosan double-layer microneedle patch for accelerated bacterial-infected wound healing.

Bacteria deep in the wound can cause prolonged inflammation and dysfunctional angiogenesis, impeding healing and potentially leading to chronic conditions, disability, or even death. To address this, we developed a double-layer metal-organic framework (MOF) microneedle (MN) patch system (GCM-MN-CSH), designed to accelerate the healing of infected wounds through programmed therapy. The GCM-MN-CSH system consists of a hydrocaffeic acid-modified chitosan (CSH) hydrogel patch and a metformin (Met)-loaded Ga-Car-MOF (GCM)-based γ-polyglutamic acid matrix MN array (GCM-MN). The GCM nanoparticles were incorporated in the MN tips. The deep, localized penetration of GCM-MN, combined with the multifunctional activity of GCM, enables effective delivery of GCM nanoparticles into the dermis. These nanoparticles acid-response release Ga ions and benzylpenicillin carboxylate, which possess antimicrobial activity, as well as Met, which promotes tissue regeneration. The adhesive CSH patch not only helps create a controlled, moist environment at the wound site but also provides antimicrobial properties on the surface. Together, the components of the GCM-MN-CSH system work synergistically to control infection, reduce inflammation, stimulate tissue proliferation, support tissue remodeling, and ultimately enable programmed wound healing. This advanced system offers a promising therapeutic platform for the management of infected wounds.