Bilayer hydrogel microneedles with mild photothermal effect promote infectious skin regeneration

Abstract

The misuse of antibiotics and the development of bacterial resistance remain “bottlenecks” in the treatment of infected wounds. Photothermal therapy (PTT) is a new type of non-invasive treatment technology; as the temperature increases, the survival rate of bacteria decreases. When the photothermal temperature rises approximately or over 50 °C, it may cause irreversible damage to normal tissues, which is detrimental to collagen deposition and blood vessel formation, and even affects the healing effect. So we used a strategy combining mild photothermal therapy (MPTT) (approximately 45 °C) and drug release to improve the microenvironment of wound infection and promote repair of skin defects. Therefore, we innovatively designed a bilayer hydrogel microneedle (FG MN) with the chitosan/aldoxylated polyethylene glycol/sodium alginate/Cu²⁺ (CPSC) hydrogel baseplate, meanwhile, the drug 5-fluorouracil (5-FU) and photothermal gold nanorods (GNRs) were introduced into the needle tips. The upper hydrogel substrate induced tissue regeneration and the lower needle tips dissolved quickly to facilitate drug delivery. After 5 minutes of laser irradiation using 808 nm near-infrared (NIR), the temperature of FG MNs increased, which triggered the release of 5-FU. In vitro, they achieved 99% antimicrobial efficiency and biofilm inhibition, as well as significant pro-angiogenic ability. Meanwhile, they showed accelerated wound healing, promotion of granulation tissue neogenesis and collagen deposition in animal models of infected wounds in vivo. Thus, this study presents an advanced delivery system with light-triggered antimicrobial activity, which provides new inspiration for the treatment of infected wounds in a reparative manner.