Dissolving microneedle-encapsulated drug-loaded nanoparticles and recombinant humanized collagen type III for the treatment of chronic wound via anti-inflammation and enhanced cell proliferation and angiogenesis

Abstract

Nowadays, diabetic chronic wounds impose a heavy burden on patients and the medical system. Persistent inflammation and poor tissue remodeling severely limit the healing of chronic wounds. For these issues, the first recombinant humanized collagen type III (rhCol III) and naproxen (Nap) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticle incorporated hyaluronic acid (HA) microneedle (MN) was fabricated for diabetic chronic wound therapy. As the tailored rhCol III was synthesized based on the Gly483-Pro512 segment, which contained the highly adhesive fragments (GER, GEK) in the human collagen type III sequence, it possessed strong cell adhesion. The mechanical strength of the prepared MN was enough to overcome the tissue barrier of necrosis/hyperkeratosis in a minimally invasive way after being applied in wounds. Subsequently, rhCol III and Nap@PLGA nanoparticles were rapidly released to the wound site within a few minutes. The prepared MN possessed favourable biocompatibility and could effectively facilitate the proliferation and migration of fibroblasts and endothelial cells. Furthermore, the regenerative efficacy of the MN was evaluated in vivo using the diabetic rat full-thickness skin wound model. These results illustrated that the prepared MN could accelerate wound closure by reducing the inflammatory response and enhancing angiogenesis or collagen deposition, indicating their significant application value in wound dressings for chronic wound repair.