Infection is the main cause of delayed healing in closed surgical wounds, traumatic and burn wounds, and chronic skin ulcers. Infection control for wounds is a contentious issue, particularly against a background of the antimicrobial resistance (AMR) epidemic.
Furthermore, treatment of wound infections represents a significant economic burden on NHS resources and the quality of life of patients. Dressings and bandages have a major part to play in the modern management of wounds, with silver-containing dressings being the most commonly used for skin wounds. While these treatments have made great strides in reducing microbial bioburden, there may be potential cytotoxic issues regarding high concentrations of silver needed for reducing infection.
Nitric oxide (NO) is a potent antimicrobial agent and has a proven role in wound repair which makes it an excellent candidate for the treatment of wound infections. The aim of this HIP is to improve upon the current silver technologies by embedding NO releasing silver nanoparticles (NP) into state of the art prototype bandages that will exploit NO’s dual wound repair and antimicrobial function. These nanoparticles have been developed with previous EPSRC-funded funding (EP/M027325/1 Engineering Nitric Oxide Delivery Platforms for Wound Healing Applications) and we have shown the NO releasing nanoparticles to be extremely potent at killing bacteria present at very high concentrations. This proposal builds on this work by taking on a “personalised medicine” approach and tailoring release rates and concentrations of NO in different formulations for treating infections in the skin and eye.
We have brought together clinical project partners with specific and complementary skills in skin wound infection and healing, and surface ocular wound infection and healing. Our commercial partners include a world leading US company that specialises in the fabrication, characterisation, and integration of nanomaterials into products and systems and a UK based SME that is at the forefront of reconstructed in vitro skin technologies that is innovating skincare research and development. Through this partnership, we will develop the clinical applicability, and the technical and commercial viability of antimicrobial NO releasing nanoparticles and their incorporation into bandages to accelerate the bench-to-clinic impact of the proposed research.
NO-releasing nanoparticles will be fabricated and optimised to deliver a controlled and sustained release of the therapeutic. We have successfully tethered NO releasing functional groups to silver and gold nanoparticles with control over NO payload. These are first linked to a high molecular weight polymer coatings and then the polymer is conjugated to the particle to ensure high stability. We will optimise the rate of delivery and the amount of site-specific generated NO by controlling the size and shape of the NPs. All NP preparations will be evaluated for their antimicrobial activity against clinically relevant bacterial and fungal strains and their cytocompatibility. These nanoparticles will then be embedded into prototype bandages made from either electrospun polyurethane and alginate or peptide hydrogels depending on their potential application to skin or corneal wounds, respectively. The efficacy of the bandages containing the NO releasing NPs will be tested in in vitro assays and in ex vivo and in vitro 3D models. The development of this technology offers sustainable effective and economic solutions without contributing to the AMR epidemic while simultaneously participating in scientifically excellent, industrially relevant research.