Multifunctional ZIF-91-Based GelMA Hydrogel Microneedles Patch with Antibacterial and Anti-Inflammatory Effects for Diabetic Wound Healing

Diabetic wound healing is a global biomedical challenge. Bacterial infection and microenvironmental modulation are major factors in the refractory healing of diabetic wounds. Conventional therapeutic approaches are often hindered by limitations, such as inadequate drug penetration, the rise of antimicrobial resistance, and restricted depth of drug delivery. Nanomedicine is emerging as a prospective drug delivery and anti-infective therapeutic approach in the field of wound management. Herein, all-trans retinoic acid (ATRA) was loaded into a zeolite imidazolate framework-91 salt + (ZIF-91 salt + ). A gelatin methacryloyl (GelMA) hydrogel microneedles (MNs) patch based on this multifunctional ZIFs (denoted as GelMA-ZIF-91 salt + @ATRA MNs patch) was developed, which makes transdermal drug delivery and combinatory treatment for diabetic wound healing feasible. Significantly, ATRA-containing ZIF-91 salt + provides nanocomposites with anti-inflammatory activity through their modulation of macrophage polarization. Crucially, the prepared ZIF-91 salt + showed efficient antibacterial activity against Staphylococcus aureus and Escherichia coli in vitro. Therapeutic effects of the GelMA-ZIF-91 salt + @ATRA MNs patch were verified in a diabetic mouse model with full-thickness cutaneous wounds. A unique MNs patch with antimicrobial, angiogenesis-inducing, and anti-inflammatory properties was designed in accordance with the physiological characteristics of wounds. Collectively, the designed MNs patch based on this multifunctional ZIF-91 salt + provides new insights into diabetic wound therapy.