Novel antimicrobial surfaces to combat AMR infections in medical implants and devices

Lead Research Organisation: University of Bristol
Department Name: Oral and Dental Science

Abstract

Despite tremendous improvements in surgical procedures, bacterial infection remains the dominant cause of medical device or implant failure, resulting in significant patient trauma and a huge burden on the NHS. Current solutions to combat such infections are largely based upon incorporation of chemicals (e.g. antibiotics) into the devices, but these approaches have a number of shortcomings. One of the biggest problems is the development of antimicrobial resistance amongst bacteria, which has been described by the government as a 'ticking time bomb' that poses an "apocalyptic" threat to public health. Thus a completely new way of killing antimicrobial-resistant (AMR) bacteria is urgently needed. This project explores a unique physical means to kill AMR bacteria by puncturing their cell walls with tiny spikes. Such structures are inspired by those found in nature on cicada wings and can be incorporated on the surface of implant biomaterials. This project aims to develop a range of innovative surfaces that are able to kill bacteria via nanospikes, including bacteria that are resistant to killing by antibiotics, and to determine exactly how the bacteria are being killed. With further commercial exploitation such novel antimicrobial surfaces have potential to be used for next-generation biomedical devices and implants, with improved performance compared to those devices in current use.

Technical Summary

Medical implants and devices constitute an indispensable and vital component of modern healthcare, resulting in greater survival rates, particularly amongst critically ill patients. However, despite tremendous improvements in surgical procedures, biomaterial-associated bacterial infections remain the dominant cause for prosthetic device or implant failures, resulting in significant patient trauma and a huge healthcare burden on the NHS. Current solutions are largely based upon chemical means (e.g. antibiotics or antimicrobial agents such as silver), which have many shortcomings and limitations. There are also issues associated with the growing problem of antimicrobial resistant (AMR) bacteria. Thus, a completely new way of killing AMR bacteria is urgently needed. In this innovative project we will explore a unique physical means to combat biomaterial-associated bacterial infections, utilising novel surfaces that kill bacteria with nanospikes, that resemble the nanotextured surfaces found on cicada wings in nature and have already been shown to be effective at killing certain bacteria by us. We aim to develop a range of antimicrobial surfaces with nanospikes that exhibit bactericidal properties against a wide variety of infection-associated bacteria. We will also investigate the synergistic effect of enzyme functionalised nanospikes to target peptidoglycan layer within the bacterial cell walls in order to develop novel surfaces with maximum bactericidal properties against AMR bacteria. Taken together, the knowledge generated in this project will be used for the rational design and fabrication of future medical implants and devices to combat AMR infections. This will contribute to the priority areas of national health and the economy, benefiting both patients and the NHS.

Planned Impact

The principal beneficiaries of this research proposal are the general public, especially those who require implanted medical devices. The main impact derives from development of novel antimicrobial biomaterials for use in medical implants or prostheses. Current medical devices have significantly improved modern healthcare, increasing patient survival rates, particularly for those critically ill. However, like other medical interventions, the insertion of medical devices can be associated with serious complications, of which infections remain the most common. This project aims to study novel biomaterials that kill bacteria using unique nanospike structures to rupture bacterial cell walls and are thus resistant to bacterial infection. This approach also has the significant advantage that it utilises a topographical bactericidal mechanism rather than the chemical mechanisms seen with current devices (e.g. antibiotics and silver). Thus this new approach has potential to be effective against antimicrobial resistant (AMR) bacteria. Ultimately development of such antimicrobial biomaterials has potential to improve healthcare practices using medical devices for the benefit of both patient wellbeing and associated socioeconomic costs on a global scale.
Development of novel antimicrobial materials for use in medical devices also has significant potential to attract R&D collaboration/investment from companies who fabricate biomedical implants and prostheses, in particular those transcutaneous implants used in orthopaedics and dentistry where infections remain the major concern. Examples include intraosseous transcutaneous amputation prostheses, external fixation pins, dental implants and abutments. Such devices are also particularly prone to infection by AMR bacteria. The provision of antimicrobial materials that utilise a novel bactericidal mechanism that is equally effective against AMR bacteria therefore has potential to significantly improve current manufacturing practices. Ultimately, exploitation of novel biomaterials for the development of next-generation medical devices with resistance to bacterial infection has potential to transform biomedical/biotechnology industries, and thus contribute to the nation's overall health and wealth creation.

Publications

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Hazell G (2018) Bioinspired bactericidal surfaces with polymer nanocone arrays. in Journal of colloid and interface science

 
Description Featured in UKRI AMR House of Commons Event
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description Biophysical stimulation-enhanced antimicrobial surfaces to combat implant-associated infections
Amount £53,991 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2017 
End 05/2018
 
Description In vitro and in vivo studies of 3D orthopaedic implants with cell-instructive nanotopographies
Amount £699,713 (GBP)
Funding ID MR/S010343/1 
Organisation University of Bristol 
Sector Academic/University
Country United Kingdom
Start 06/2019 
End 05/2022
 
Description In vitro and in vivo study of antimicrobial surfaces 
Organisation University of Cambridge
Department Department of Veterinary Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration is underway through a PhD studentship of Cambridge University with Prof Matthew Allen to test the developed antimicrobial nano-surfaces in a rabbit model.
Collaborator Contribution Prof Allen and his student will perform both in vitro and in vivo testing of our nanostructured surfaces in both 2D substrates and 3D printed implants.
Impact This is a multi-disciplinary collaboration between materials and biological sciences. Joint publications and future grand application are expected.
Start Year 2018
 
Description cell-instructive surfaces 
Organisation Polytechnic University of Catalonia
Country Spain 
Sector Academic/University 
PI Contribution Nanostructured surfaces: generation and characterisation
Collaborator Contribution Functionalisation of nano-surfaces with cell-binding ligands to improve cell attachment while preventing bacterial growth
Impact A joint publication in Scientific Reports. One more in preparation.
Start Year 2017
 
Description Big Bang Bristol 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Big Bang Bristol was a free two-day science, technology, engineering and maths (STEM) extravaganza at the Trinity Arts Centre, Bristol, in July 2017. Visitors will be able to learn about the world-class research taking place in the region, find out about life as a postgraduate and how to become a professor. We have participated and showcased our research on bio-inspired bactericidal nanospike surfaces which attracted a lot of interests in our research.
Year(s) Of Engagement Activity 2017
 
Description From deep-sea sponges to dragonfly wings: Superbug research from unexpected places 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Media coverage of our work on 'fighting bacteria using bio-inspired materials'.
Year(s) Of Engagement Activity 2018
URL https://mrc.ukri.org/news/blog/from-deep-sea-sponges-to-dragonfly-wings-superbug-research-from-unexp...
 
Description Invited talk at IUMRS2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact International conference invited talk
Year(s) Of Engagement Activity 2016
 
Description Invited talk in a workshop by The Sheffield Antimicrobial Resistance Network (SHAMROK). 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited talk in a workshop by The Sheffield Antimicrobial Resistance Network (SHAMROK).
Year(s) Of Engagement Activity 2016
 
Description Invited talk in a workshop organised by the Institute for Molecular Science and Engineering (IMSE) at Imperial College London 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Audience from a number of different department at Imperial, including Materials, Medicine, Mathematics, Life Sciences, Chemical Engineering, Chemistry, and the Imperial NHS Trust attended.
Year(s) Of Engagement Activity 2017
 
Description Invited talk in an international conference of Advanced Materials organised by Newcastle University 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact International audience mostly from Europe attended this conference
Year(s) Of Engagement Activity 2016
 
Description Kill superbugs with nanospears 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Research without boarders
Year(s) Of Engagement Activity 2018
 
Description Nanobio workshop, Leuven, Belgium 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited talk at Nanobio workshop, organised by Vision Dynamics Science & Entrepreneurship. Audiences are mainly from European universities and SMEs. Disseminated our work to wider communities. A collaboration was initiated in this workshop with a UK company (Nanokicking) based in Glasgow.
Year(s) Of Engagement Activity 2017
 
Description Plenary talk at Hunan Bone Summit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary talk to doctors and university
Year(s) Of Engagement Activity 2016