Novel perspective for cold plasma application in the repair of infected severe burn wounds – NOVOPLASM

Burns are the fourth most common type of trauma globally. Each year, between 7 000 and 10 000 burn victims are admitted to hospitals, and 2,000 to 3,000 severe cases are treated in one of the 23 specialised burn care units currently operating in France. Burns are estimated to account for 1 out of 10 injuries encountered by military personnel. Deep burns with extensive total body surface area often remain open for months – creating a favourable condition for the development of local sepsis, and progressively septicaemia. Administration of highly-effective topical and systemic agents is used clinically to prevent and treat burn wound infections. Several species of bacteria, including Staphylococcus aureus (S. aureus) have been associated with resistance to antimicrobial agents. Development of innovative treatment modalities for burn wound infections are urgently needed.
An ideal candidate for alternative therapy to control microbial overgrowth in burn wounds must be effective against multi-drug resistant organisms and biofilm without toxicity to living tissues such as living skin grafts. Ideally, this treatment should also aid cutaneous tissue repair.
NovoPlasm is a multidisciplinary project set to develop an innovative treatment aimed to improve burn wound repair. Within a multidisciplinary setting the Novoplasm consortium members, which consists of physicists, microbiologists, regenerative medicine specialists and medical doctors will use cold plasma technology. At room temperature cold plasma generates reactive oxygen and nitrogen species, which eradicate infection and promote burn wound repair. NovoPlasm is set to promote cutaneous wound healing by reducing microbial burden and biofilm formation. A device will be designed to produce cold plasma by sending speedy electrons through a non-toxic noble gas. The device will be trailed in several biological systems and its therapeutic efficacy will be investigated in preclinical in vitro and in vivo models mimicking burn wound infection. The “multi-jet” device will be designed to treat a large surface area, comprising of several dozens of cm2. As part of the initial project, and as a result of the collaborative efforts between The Pasteur Institute and Armed Forces Biomedical Research Institute a mono-jet plasma device was demonstrated to improve skin graft integration. Furthermore, this plasma device was also shown to prevent bacterial wound infection, which included strains known to be resistant to classically-used antibiotic treatment.
CTIBiotech is a small and medium-sized enterprise (SME) and an important partner in this multidisciplinary project. CTIBiotech will use tissue-engineering approaches and three-dimensional (3D) bioprinting to design human skin equivalents, which will recapitulate wound inflammation and recruitment of phagocytic immune cells. 3D models of wound infection and a humanized murine model of burn wound repair will be used to test the efficacy of cold plasma in reducing wound bioburden and biofilm formation. A preclinical porcine model of burn wound repair will be used to test the feasibility of cold plasma to promote wound healing and reduce infection in experimental wounds designed to recapitulate the gold standard surgical procedures currently used in the clinical setting.
NovoPlasm aims to use a variety of preclinical models, which may help to increase the direct clinical relevance of experimental results. This will help to demonstrate a potentially high therapeutic and commercial value of plasma technology and its use in cutaneous tissue repair.