γ-polyglutamic acid-encapsulated metformin-loaded Ga-Car-MOF and hydrocaffeic acid-modified chitosan double-layer...

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 Ga³⁺ 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.