Engineering Nitric Oxide Delivery Platforms for Wound Healing Applications

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.

Academic: Many research challenges have emerged from the threat of AMR. The current technological framework and capabilities still has many shortcomings that must be addressed to provide sustainable effective and economic solutions. The development of smart dressings to prevent infection without causing AMR while simultaneously encouraging skin tissue regeneration will have an impact on wider academic communities working in antimicrobial surfaces, wound healing, biomaterials and tissue engineering. The University of Liverpool (UoL) has seven institutional research themes, three of which (Materials for the Future, Global Health and Personalised Medicine) has direct impact on the proposed research. Engagement with these themes will bring together multi-disciplinary collaborators on a new area of research which will impact the university's research strategies.

UoL has recently launched an Open Innovation Hub for Antimicrobial Surfaces which is a unique, cross-institutional and industrially supported Centre, focused on the design and engineering of a new generation of intelligent surfaces for advanced biomaterials in medical applications. Membership in this Hub allows the PI's research to be ideally placed for maximum impact not only to those directly working with the Hub, but it will also allow the PI to 'reach out' to the associated SMEs and health institutes. Furthermore the PI is currently the School of Engineering Co-I for the EPSRC institutional bid on 'Bridging the Gaps between Engineering and Physical Science and AMR' grant application. The network of academic researchers involved in this bid spans areas across UoL departments such as engineering, chemistry, microbiology and structural biology. Therefore the PI and PDRA will be ideally placed to interact with this network for gaining maximum impact of the research. Furthermore, the PDRA will join a well-connected, highly active growing research team and will be encouraged to work with collaborators to further their career. This will benefit the UK in terms of advancing its skills research base and training new talent.

Commercially: This project will benefit from the interaction with the SMEs and large enterprises associated with the UoL Open Innovation Antimicrobial Hub. In particular, engagement has already been made with Scapa Healthcare, an SME in advanced wound care therapeutics. Currently, the development of NO releasing surfaces that has a dual therapeutic in outcome of wound repair and antimicrobial effects could feed into developments of their wound dressing products. The development of the core expertise of this project could also lead to other outputs with the potential of impact through commercialisation. The potential to protect any intellectual property from this project will constantly evaluated for commercial exploitation via UoL's Business Gateway department.

Clinical Dermatology: Currently, there is no robust clinical evidence showing that dressings containing antimicrobials (e.g. silver, iodine or honey) are more effective than unmedicated dressings for the prevention or treatment of wounds. 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 dressings alone. The clinical evidence supporting the efficacy of wound healing dressing is sparse and is in need of clinician input into cost and patient implication for the ultimate goal of management of chronic wounds. Engagement with the named clinician at Johns Hopkins Medical School Plastic Surgery Department will have significant impact in on the research outputs by ensuring viable clinically relevant endpoints are maintained.