Synergistic antibacterial and antifouling wound dressings: Integration of photothermal-activated no release and zwitterionic surface modification

Global bacterial infections are a serious public health problem, posing significant challenges to global health and healthcare systems. The constant threat posed by bacterial infections, particularly those stemming from biofilms, remains a critical challenge in the realm of wound management and treatment. Biofilms are structured communities of bacteria encased within a protective matrix, not only resist conventional antibiotics but also withstand host defenses, complicating the healing process(Nabawy et al., 2021). In the pressing global struggle against bacterial infections and antibiotic resistance, emerging, innovative approaches have become an urgent issue(Jeong et al., 2023). The development of wound dressings that can address the dual needs of eradicating bacteria and preventing biofilm formation is essential for advancing the treatment of infected wounds.

One pioneering method that has attracted much attention involves the use of nitric oxide (NO) for its unique antimicrobial properties, which has shown significant potential in combating bacteria and eradicating resilient biofilm infections(Fasiku et al., 2022, Li et al., 2020, Sundaram et al., 2016). As an antimicrobial agent, NO could directly modify membrane proteins and induce DNA strand breaks via induced nitrosylation and oxidative stress, resulting in broad-spectrum antimicrobial activity while averting the use of antibiotics and avoiding bacterial resistance(Pelgrift and Friedman, 2013, Tamir et al., 1996). Moreover, as a small and diffusible molecule, NO exhibits a unique capacity to penetrate these biofilm structures, disrupting them and weakening their defense mechanisms. Therefore, there is an increasing interest in the precise control of the therapeutic amounts of NO release against bacterial resistance. For the precise control of NO release, near infrared (NIR) is a convenient non-invasive trigger and generate localized heat(Duan et al., 2023). The NO donors through the NIR laser irradiation can lead to the accurate control of site, timing and dosage of NO from matrix material, such as nanoparticles, hydrogels, wound dressings(Duan et al., 2023, Zhu et al., 2022, Zou et al., 2023). Therefore, NO combined with hyperthermia can inhibit the growth of bacteria, enhance blood flow, and promote wound repair, which exhibit promising potential in view of wound healing(Wang et al., 2019, Wang et al., 2023, Zhu et al., 2023).

However, bacteria colonize a wound, they can multiply rapidly and form biofilms, which are structured communities of bacteria that are highly resistant to antibiotics and host immune defenses(Hassani et al., 2024, Liu et al., 2023, Zhu et al., 2023). The induced proteins can mediate biofouling by cells or bacteria and adhered on the wound dressing to cause secondary injuries and severely delay the healing process. Therefore, eradicating bacterial biofilm infection is essential for wound dressings(Guo et al., 2022, Miranda-Calderon et al., 2023). To address bacterial resistance in wound care, healthcare professionals and researchers focus on strategies such as appropriate wound cleaning and debridement, using targeted and appropriate antibiotics when necessary, minimizing antibiotic use when possible, promoting good infection control practices, and developing new antimicrobial agents or alternative therapies(Lv et al., 2023, Wu et al., 2021).

Recently, zwitterionic materials such as polyphosphorylcholine, polysulfobetaine and polycarboxybetaine, sulfobetaine (SBMA), carboxybetaine or phosphobetaine have been shown to exhibit ultra-high resistance to non-specific protein adsorption and long-term resistance to bacterial biofilm formation(Asadikorayem et al., 2020, He and Liu, 2024, Zhang et al., 2022). Among zwitterionic materials, polymers and copolymers of SBMA are widely studied because the monomer can be readily synthesized and purified at relatively low cost. They form a tight hydration layer at the surface of functionalized materials, which is the key for their non-fouling property. In a nutshell, antifouling functional groups promoting the formation of a hydration layer should be in contact with the wound(Venault et al., 2020).

In the field of antifouling wound dressing, combating bacteria and biofilm infections remains a significant challenge. In this work, to prevent attachment and reduce bacterial biofilm formation on the wound dressing, we designed sulfobetaine (SBMA) decorated PCL/NO donors electrospinning membranes to treat the wound healing. Firstly, NO donors were loaded to mesoporous polydopamine (MPDA) and complex with PCL in solution to electrospin nanofiber. Irradiated by 808 nm, NO donors were triggered by photo-thermal effects and rapidly release NO gas, which can effectively kill bacteria and disperse biofilms. Secondly, to functionalized the membrane surface, polyethyleneimine 10,000 (PEI) was added into PCL and electrospin membranes, which can introduce SBMA groups via Michael addition reaction. The wound dressings with zwitterionic surface that can effectively prevent protein adsorption and biofilm formation. The rapid bacteria-killing ability and avoiding bacterial infection were assayed in vitro and in vivo. This therapeutic strategy merges nanofibrous structures, photothermal properties, and NO delivery to provide a comprehensive platform to bacterial battles and biofilm eradication.

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