Multiple Stimuli-Responsive Nanozyme-Based Cryogels with Controlled NO Release as Self-Adaptive Wound Dressing for Infected Wound Healing

Wound with drug-resistant bacterial infections has become a serious challenge for the healthcare system, and designing wound dressing to self-adapt to the need of different stage of wound healing remains challenging. Herein, self-adaptive wound dressings with multiple stimuli-responsiveness and antibacterial activity are developed. Specifically, MoS₂ carrying a reactive oxygen species (ROS) responsive nitric oxide (NO) release precursor L-arginine (MSPA) is designed and incorporated into carboxymethyl chitosan/poly(N-isopropylacrylamide) based cryogels (CMCS/PNIPAM) with multiple responsiveness (pH, near infrared (NIR), and temperature) to form self-adaptive antibacterial cryogels that adapt to the therapeutic needs of different stages in infected wound healing. In response to the slightly acidic environment of bacterial infection, the cryogels assist the bacterial capture capacity through acid-triggered protonation behavior, and effectively enhance the photodynamic antibacterial efficiency. Controllable on-demand delivery of ROS, NO, and remote management of infected biofluid are achieved with NIR light as a trigger switch. The multiple stimuli-responsive nanozyme-based cryogels efficiently eliminate MRSA bacterial biofilm through NO assisted photodynamicand photothermal therapy (PDT&PTT). The multiple enzyme-like activities of the cryogels effectively relieved oxidative damage. Notably, these cryogels effectively reduce wound infection, alleviated oxidative stress, and accelerate collagen deposition and angiogenesis in infected wounds, indicating that multiple stimuli-responsive self-adaptive wound dressings provide new ideas for infected wound treatment.