Carvacrol/cyclodextrin/ceria nanoparticle/hyaluronate hybrid microneedle for promoted diabetic wound healing through the modulation of microenvironment

Delayed healing due to the persistent microenvironment disorder caused by the hyperglycemia and persistent inflammatory reaction is a core pathological characteristic of diabetic wound. Topical microenvironment modulation represents an important avenue to address delayed healing issue. Microneedles are powerful tools for topical microenvironment modulation as they can effectively deliver therapeutic ingredients into the shallow surface layer of the wound based on their depth-limited tissue penetration capability. Herein, a hybrid microneedle composed of carvacrol (CV), cyclodextrin (CD), mesoporous ceria nanoparticles (MCNs) and hyaluronate (HA) is constructed with objective to modulate the microenvironment within the diabetic wound. The hybrid microneedle is constructed via a two-stage process comprising three stepwise embedding procedures in the first stage and four microneedle casting procedures in the second stage. The physical, chemical and antibacterial performances, as well as the in vitro and in vivo therapeutic potentials, of the hybrid microneedle are evaluated. The therapeutic ingredients, mainly CV and MCNs, incorporated in the microneedle can be readily released into the diabetic wound, and effective microenvironment modulation is realized through the designed antibacterial, antioxidant and anti-inflammatory functions. Consequently, the tissue reconstruction processes including cell proliferation and migration, angiogenesis, and collagen deposition are accelerated due to the improved microenvironment.