Anita Shukla1
Brown University1
The wound repair and regeneration process is greatly complicated by the presence of infections. Chronic wounds in particular are highly prone to infection. As a prominent example, nearly 60% of individuals with diabetic foot ulcers develop infections. Preventing and treating wound infections is a critical challenge in promoting successful tissue repair. The existence of biofilms and antimicrobial-resistant microorganisms within wound environments further complicates the effective treatment of these infections. In this talk, I will describe recent approaches we have taken to treat wound infections using hydrogel biomaterials and nanoparticle therapeutic formulations. I will discuss the development of a bacteria-responsive hydrogel drug delivery platform that can provide on-demand treatment of wound infections, while facilitating tissue repair. These hydrogels respond to the presence of beta-lactamases, which are bacteria-produced enzymes that are a common cause of antibiotic resistance. Upon exposure to beta-lactamases, the hydrogel backbone undergoes degradation, leading to the release of encapsulated antibacterial liposomes. Our findings using a <i>Pseudomonas aeruginosa</i>-infected murine skin abrasion wound model indicate complete clearance of infection within one day of treatment. Importantly, there were no instances of infection recurrence during the four-day wound monitoring period. Furthermore, timely eradication of the infection helped promote wound healing, as evidenced by histological analysis revealing rapid regeneration of the epidermis. Notably, the hydrogel itself exhibited no signs of toxicity. I will also describe our work on the development of bacteria-responsive gelatin nanoparticles that have demonstrated promising antibiofilm efficacy against prevalent wound infection-causing bacteria, including <i>Vibrio vulnificus </i>and <i>P. aeruginosa</i>. Overall, the technologies described in this talk are biocompatible and effective at eliminating wound infections, thus holding immense potential for promoting effective wound healing.