A multifunctional chemotactic-antibacterial ChMA–AgNPs hydrogel for the treatment of carbapenem-resistant Pseudomonas aeruginosa-infected wounds

Abstract

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) wound infections are very pathogenic and highly resistant to some other drugs. Passive antimicrobial dressings are conventional, but lack effectiveness, which is a problem in the management of wounds. The objective of this research study is to elucidate the chemotactic effects of L-lysine on the clinically relevant CRPA and construct a multifunctional hydrogel dressing that integrates the task of active chemotaxis and antimicrobial effects. Initially, in vitro chemotaxis assays, such as agar assays, were used to confirm the potent and specific chemotactic activity of L-lysine against CRPA. The bacteria exhibited a tendril-like movement that corresponds to positively charged mediators. Then, a ChMA–AgNPs composite hydrogel was prepared based on a methacrylamide chitosan (ChMA) with L-lysine and silver nanoparticles (AgNPs) loaded on it. Physicochemical characterization indicated that the AgNPs were firmly encased in the material without being leached substantially, thereby minimizing tissue toxicity by silver ions. The concentration gradient of L-lysine directed bacteria towards the hydrogel, facilitating the targeted elimination of CRPA. The tests carried out in vivo using a full-thickness skin defect model in mice infected with CRPA showed that the ChMA–AgNPs hydrogel had a significant effect on the purulent exudation of wound sites. It also enhanced the rate of re-epithelialization, improved orderly collagen fiber deposition and neovascularization and successfully suppressed the expression of inflammatory mediators, including TNF-α and IL-6, thereby healing the wounds adeptly on postoperative day 14. Overall, the ChMA–AgNPs chemotactic antibacterial hydrogel designed in the present study demonstrates encouraging prospects of clinical use because it offers a novel therapeutic approach for managing CRPA-infected wounds via the synergistic effect of active chemotaxis-assisted bactericidal action and wound healing.