Engineering Nitric Oxide Delivery Platforms for Wound Healing Applications

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There are a few public health issues of greater importance globally than antimicrobial resistance (AMR). AMR does not recognise borders; thereby necessitating the fight to be a coordinated multidisciplinary effort. In this 'post-antibiotic era' the urgency for new technologies that do not rely on traditional antibiotics to combat infection is in essential. Currently there is no robust clinical evidence showing that dressings containing antimicrobials are more effective than unmedicated dressings for the prevention or treatment of chronic wounds. Systemic reviews of advanced dressings constantly show the lack of high-quality studies with clinically relevant endpoints. Indeed, wound dressings account for about £120 million of prescribing costs in primary care in England each year, with more than £25 million being spent on silver based antimicrobial dressings alone. The clinical evidence supporting the efficacy of these dressings is sparse and is in need of clinician input into cost and patient implication for the ultimate goal of management and healing of chronic wounds. The goal of this project is to strategically develop the technology to fabricate advanced wound dressings by trying to fight infection (without contributing to AMR) and simultaneously encouraging skin tissue regeneration. Successful treatment of a chronic wounds depends on identifying and treating factors that impede the healing process. It has recently been recognised that bacteria that are found in chronic wounds reside in communities called biofilms which contribute to infection and delayed healing. Therefore, standard wound management becomes more complex and new solutions need to be biofilm-targeted. Nitric Oxide (NO) is an effective therapeutic for chronic wound healing as it has been proven as a potent anti-biofilm agent and it plays a key role in active wound regeneration. The mode of action of NO is different to conventional antibiotics and as such will not contribute to AMR. The aim of this project is to develop a platform to release NO from model dressings by tethering compounds containing caged NO reservoirs which are able to release NO in a controlled and sustained manner in order to exploit its dual role. This is achieved in 4 steps. Firstly, the design and development of functionalised model dressing surfaces by environmentally friendly manufacturing processes is performed. Secondly, these functionalised surfaces will be modified to have a nitrogen group on the exterior of the surface. This nitrogen group will allow for attachment of the caged NO reservoirs. Thirdly, the caged NO reservoirs will be optimised in terms of dose and release. Finally, these surfaces will be tested for efficacy of killing bacteria while remaining non-toxic to human cells. This innovative NO delivery platform proposed addresses the demand for effective wound healing technologies that has the properties to expand the clinical applicability of this exceptional molecule in wound care. By developing this technology there is a real opportunity to be part of the solution targeting this epidemic while simultaneously participating in scientifically excellent, industrially relevant research.