Engineering Fellowships for Growth: Building advanced materials to treat vision loss

Lead Research Organisation: University of Liverpool
Department Name: Institute of Ageing and Chronic Disease

Abstract

Innovations in biomaterials science and engineering have the potential to make a significant contribution to the development of treatments for ophthalmic diseases and thus to reduce the burden of vision loss on the global community. Underpinning these developments is the design and production of advanced materials with key features that drive the biological response required to overcome the destructive nature of the disease. To achieve these outcomes there is an urgent need for engineers, scientists and clinicians to combine their knowledge and expertise to address the eye healthcare problems of the 21st century especially with an ageing population. Four key areas will be developed within this Fellowship:
1) The design and development of novel materials for contact lenses using environmentally friendly manufacturing processes; overcoming problems associated with silicone-based hydrogels and permitting modification to incorporate bioactive molecules for wound healing and antimicrobial agent delivery combating corneal infection,
2) The design of advanced gels to replace damaged corneas; overcoming current problems associated with biological materials such as collagen or amniotic membrane with the potential for greater control, reduced immunogenicity and thus more rapid product translation to the clinic,
3) The development of functionalised surfaces for conjunctival cell transplantation using novel atmospheric pin plasmas for spatially resolved surface modification without requiring high vacuum manufacturing,
4) The development of controlled substrates for cell expansion using surfaces designed to model the extracellular environment promoting expansion under well-defined GMP conditions to allow a more rapid translation of these cells in therapeutic applications.
This fellowship will allow me to use my expertise to develop advanced materials for ophthalmic applications and to co-ordinate the efforts of a number of academics into a major hub of activity and allow me to provide the expertise in the design of novel substrates to take forward advanced cell therapies for eye disease being developed by several groups both within the UK and internationally. Bringing together expertise in advanced materials with these groups will produce world leading research output with the potential for industrial exploitation and clinical translation capable of making a substantial impact on the UK economy and healthcare. This fellowship will allow me to exploit my leadership role within the University to build on the existing cross-faculty collaborations already established and through my mentoring roles to develop the next generation of academics to fulfil future leadership positions and ensure continuation of the strength of ophthalmic bioengineering at the University. It fits with the University's strategic priorities, and will enhance 'Materials for the Future' which is one of our 7 Institutional research themes. My existing collaborations with industry will provide a basis for further exploitation of new technologies into the commercial sector and my strong collaboration with clinicians at St Paul's Eye Unit, Royal Liverpool University Hospital, will allow me to reach out to the clinical ophthalmic community. I will exploit my existing international reputation to strengthen the position of Liverpool and the UK as a focus for leading world class research with impact in ophthalmic biomaterials and engineering.
For an individual the loss of sight is estimated to have a financial impact of £20k pa. For the UK economy the annual cost is around £6.5 billion in terms of direct healthcare costs and indirect costs such as unpaid carers and loss of employment. Emotionally the loss of vision can be devastating to the individual. This established career fellowship will provide the platform from which to build a centre of excellence in ophthalmic bioengineering with the capability to make a substantial contribution to addressing these problems.

Planned Impact

Academic: The fellowship will have a large impact on the core team to be developed from this project. I shall gain the opportunity to bring together the expertise from across the University to make a significant progress in the development of advanced materials for overcoming vision loss. The replacement lecturer and the PDRAs will benefit from the cross-disciplinary expertise available and being able to build their research expertise. This will have a major impact on their careers and should lead to future leadership roles. The progress made by the core team and the wider input from cross-disciplinary groups in the University will have a significant impact on the ophthalmic biomaterials community in the UK and internationally in terms of advancing the knowledge and understanding.
Commercially: There is potential for this project to have an impact on the two SMEs with direct input into this project. The development of the gels into contact lens would be a new product stream for SpheriTech Ltd and could feed into developments of their wound dressing products. The development of collaboration between SpheriTech and UltraVision could help to establish a route to exploitation and sales. The cell culture substrates developed with Biomer Technology Ltd could provide a new extension of their current product base. The development of the expertise of the core team over the life time of the project could lead to other outputs with the potential of impact through commercialisation. We will make use of contact with the KTNs to explore these potential outcomes. The potential to protect any intellectual property from this project will be kept under review for future commercial exploitation via the University's Business Gateway department.
Clinical Ophthalmology: Right from the start of the project we will engage with clinical colleagues and this will have a significant impact in terms of increasing their understanding on how materials and surfaces can influence the cellular response and thus how to use this to address their clinical problems. Their input will benefit the whole project and through this approach there is potential to have an impact on future research and on patient care in the longer term. Visual impairment in the UK is a major societal challenge in the face of an already over-burdened healthcare system and is also a serious financial drain on the economy. The financial impact for the individual is estimated to be £20,000 per patient registered blind per year. According to the RNIB the annual cost of sight loss to the UK economy is at least £6.5 billion made up of direct health care costs, such as eye clinics, prescriptions and operations of £2.14 billion and £4.34 billion in indirect costs, such as unpaid carer costs and reduced employment rates. This proposal has the potential to reduce these burdens and increase both the quality of life for patients and lead to significant cost savings across health care providers in the long term.
NC3Rs: A significant impact could be generated from the use of the tissue equivalent gels as an in vitro model of the cornea. All academics working on potential new drug/consumer product need to evaluate them using rigorous toxicity/safety testing before approval. The cornea demonstrates particular sensitivity to numerous irritants but unfortunately, corneal tissue complexity makes ocular drug development and substance validation particularly challenging. Recent European directives (2010/63/EU) prohibit laboratory animal use for cosmetic and toxicity testing, so development of an alternative is therefore crucial, particularly for future ophthalmic drug development. Currently, no reliable and validated human in vitro corneal substitute exists, creating a unique opportunity relevant to the biotechnology, cosmetics and pharmaceutical industries, for a biomimetic human cornea to become the new standardised and reliable in vitro testing platform.

Publications

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Cauldbeck H (2016) Controlling drug release from non-aqueous environments: Moderating delivery from ocular silicone oil drug reservoirs to combat proliferative vitreoretinopathy. in Journal of controlled release : official journal of the Controlled Release Society

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Cauldbeck H (2018) Modulated release from implantable ocular silicone oil tamponade drug reservoirs in Journal of Polymer Science Part A: Polymer Chemistry

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Gallagher AG (2016) A Novel Peptide Hydrogel for an Antimicrobial Bandage Contact Lens. in Advanced healthcare materials

 
Description We have been developing novel gels for corneal replacement and contact lenses and thus far we have demonstrated that we can control the properties of the gels to improve the interaction of corneal epithelial and endothelial cells with the surface of the gel. This work is continuing to find the best composition.

We have also demonstrated that we can control the properties to produce gels similar to commercially available contact lenses. Taking these we have demonstrated that we can modify the surface of the gels to make them antimicrobial

We have developed the gels for corneal tissue engineering applications. Specifically in relation to corneal endothelial cell transplantation. We have optimised the properties of the gels for attachment, growth and functionality of these cells. We are developing the surgical technique for implantation of these gel/cell constructs.

We have developed a methodology to synthesise these gels into porous 3D constructs and have demosntrated that they can support ocular stromal fibroblasts as a potential corneal stromal construct.

We have developed the peptide hydrogel as a corneal epithelial cell bandage demonstrating that human corneal epithelial cells grown on the gel for 7 days can tranfer onto a wounded cornea and subsequently repopulate the entire corneal surface.

We have also been developing surfaces for expansion of cells in culture for future transplantation therapies. We have demonstrated that conjunctival epithelial and goblet cells can be expanded in culture on these surfaces with the objective of future use in conjunctival cell therapies.
Exploitation Route We are continuing to work very well with our industrial collaborators to do this
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description I have continued to present my research at public events to increase awareness of this research and how it can bring benefit to society. I have also continued to have discussions with my industial partners of how to progress the output of this research towards clinical and commercial practice
First Year Of Impact 2015
Sector Education,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal

 
Description Antimicrobial Bandages for the Treatment of Wound Infections
Amount £854,545 (GBP)
Funding ID EP/P023223/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2017 
End 03/2020
 
Description Antimicrobial bandage contact lenses
Amount £767,633 (GBP)
Funding ID MR/R006334/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 11/2017 
End 10/2020
 
Description Creation of bio-synthetic corneal endothelial grafts for transplantation using novel peptide gels
Amount £113,322 (GBP)
Funding ID 5051/ 52 
Organisation Fight for Sight 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2017 
End 10/2019
 
Description IAA printing hydrogels
Amount £8,138 (GBP)
Organisation University of Liverpool 
Sector Academic/University
Country United Kingdom
Start 03/2016 
End 12/2016
 
Description IPE for treatment of retinal diseases
Amount £64,509 (GBP)
Organisation James Kent 
Sector Private
Country United Kingdom
Start 10/2017 
End 09/2020
 
Description KE Voucher - Endothelial cell transplantation
Amount £9,118 (GBP)
Organisation University of Liverpool 
Sector Academic/University
Country United Kingdom
Start 11/2016 
End 07/2017
 
Description Preclinical Evaluation of a New Chemical Cross-Linker for the Treatment of Keratoconus
Amount £50,000 (GBP)
Organisation University of Liverpool 
Sector Academic/University
Country United Kingdom
Start 03/2019 
End 12/2019
 
Description Preclinical Evaluation of a New Chemical Cross-Linker for the Treatment of Keratoconus
Amount £1,000,000 (GBP)
Funding ID EP/R511729 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2019 
End 03/2020
 
Description Rapid, point of care diagnostic device for corneal infection
Amount £12,257 (GBP)
Organisation United Kingdom Research and Innovation 
Department Global Challenges Research Fund
Sector Public
Country United Kingdom
Start 11/2018 
End 03/2019
 
Description Thin, rollable and transparent gel matrix for corneal endothelial cell transplantation
Amount £45,988 (GBP)
Organisation UK Regenerative Medicine Platform 
Sector Academic/University
Country United Kingdom
Start 01/2015 
End 06/2015
 
Description Transplanting cells to the retina
Amount £450,000 (GBP)
Funding ID LIN2504 
Organisation Royal Liverpool And Broadgreen University Hospitals Nhs Trust Charitable Funds 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2017 
End 07/2019
 
Description Cell and Gene Therapy Catapult 
Organisation Cell Therapy Catapult
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Development of the surgical procedure required to implant the corneal endothelial cell/gel construct
Collaborator Contribution Advice on clinical translation
Impact this collaboration is multidiscplinary. There are no outputs yet
Start Year 2016
 
Description Cross-linking of the Sclera 
Organisation Santen Pharmaceutical Co., Ltd
Country Japan 
Sector Private 
PI Contribution Provision of our novel cross-linking technology
Collaborator Contribution Evaluation of our technology in in vitro and in vivo experiments on the stiffening of the sclera
Impact No outputs yet, multidisciplinary collaboration including pharmaceutical company, bioengineering and clinical ophthalmology
Start Year 2007
 
Description Rapid diagnosis of corneal infection 
Organisation University of Edinburgh
Department Queen's Medical Research Institute Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Evaluation of antimicrobial peptides with environmentally sensitive fluorescent probes that can detect Gram +ve and Gram -ve bacterial species attached to our novel peptide bandage contact lenses and their development as a rapid diagnostic tool for corneal infection
Collaborator Contribution Contribution of the anitmicrobial peptides and know how
Impact Research data resulting from a new collaboration, submission of research grants to continue collaboration, introduction to our Indian partners
Start Year 2017
 
Description bandage contact lenses 
Organisation SpheriTech Ltd
Country United Kingdom 
Sector Private 
PI Contribution Development of novel hydrogel contact lenses
Collaborator Contribution Advise and materials
Impact three paper 6 conference presentations 3 postgraduate projects (PhD, MRes)
Start Year 2013
 
Description Cross-faculty Ophthalmic Bioengineering Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact This activity brought together experts in a range of areas related to Ophthalmic Bioengineering including clinicians, scientists and engineers. The objective was to highlight the expertise that was available and build collaborations across the University. It led to many in depth discussions and new partnerships being formed.
Year(s) Of Engagement Activity 2015
 
Description Filming with ITN for EPSRC 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I was involved in presenting a part on film on 'Engineering our World' and it was designed to highlight leaders in engineering and diversity
Year(s) Of Engagement Activity 2015
URL https://itnproductions.wistia.com/medias/lvm9o018pt
 
Description Improving the world though engineering - Engineering Day, Wirral Arts Festival (sponsored by IMechE) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Public lecture designed to highlight the breadth of engineering and how it influences our lives. It involved a lecture and a panel discussion to answer questions
Year(s) Of Engagement Activity 2019
 
Description Invited presentation at RAMS2019 (recent appointments in materials science) - Liverpool 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact RAMS2019 aims to connect and support early career academics and senior post-doctoral researchers in industry or academia working in Materials Science. The event involved being a plenary speaker as well as joining in the panel discussion to mentor and inspire early career academics and researchers.
Year(s) Of Engagement Activity 2019
 
Description Invited presentation at the Asia Pacific Association in Ophthalmology conference in Hong Kong 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited lecture in a session on Application of Nanotechnology in Eye Disease highlighting new opportunities to the predominantly clinical audience
Year(s) Of Engagement Activity 2018
 
Description Invited presentation at the Biomaterials Discovery annual workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Lecture on Developing poly-e-lysine hydrogels for ophthalmic applications at the Biomaterials Discovery Programme grant conference demonstrating how the materials properties can be tailored for a specific application.
Year(s) Of Engagement Activity 2018
 
Description Invited presentation at the President's session of the Royal College of Ophthalmology on Biomaterials and their Optimisation for Use in the Treatment of Vision Loss 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Prestigious presentation at a major clinical conference
Year(s) Of Engagement Activity 2017
 
Description Invited seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Research seminar to Biomedical Engineers at the University of Glasgow. Introducing the Ophthalmic Bioengieering research topic. Developing new collaborations
Year(s) Of Engagement Activity 2020
 
Description Invited seminar at the Hong Kong Polytechnic University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited seminar aimed to encourage new research collaborations
Year(s) Of Engagement Activity 2018
 
Description Lecture for Fight for Sight speaker network 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Lecture of Biomaterials and their role in the treatment of vision loss at EYECARE2018 conference and exhibition for optometrists and ophthalmologists representing Fight for Sight and to spread the word about their research and its impact
Year(s) Of Engagement Activity 2018
 
Description Materials to shape our vision; How advanced materials are fighting the loss of sight 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact I presented to around 20 members of the general public in a pub. There was a lot of interest in the materials I showed them and this generated a lot of discussion. On the back of this i have been invited to take part in two more similar events
Year(s) Of Engagement Activity 2019
 
Description Public lecture to the Thirteen Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact This was a presentation to an audience of around 70 retired professionals who organise a wide ranging programme of interesting presentations. I introuduced the importance of engineering and materials in overcoming vision loss. It generated a lot of interesting questions. I received very positive feedback, particularly around being able to present a complex subject in a very accessible way to the intellegent generalist.
Year(s) Of Engagement Activity 2020
 
Description RISE connect - Please do not let me be misunderstood: Making sense of science 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Talkeoke style debate designed to help help participants make connections with with politicians and policy makers and communicate their science
Year(s) Of Engagement Activity 2018
 
Description Royal Society MP pairing Scheme 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact This scheme is designed to help provide links between academics scientists and engineers and politicians and civil servants. We spend 4 days, 2 at Westminster and 2 with our 'pair'. I was paired with a Civil Servant from the Home Office Centre for Applied Science and Technology. I was able to attend a Science and Technology Select Committee Session. We had a day of presentation and discussions with the Government office for Science. From this I found out more about how to interact with the government policy makers and how my expertise could be relevant to them
Year(s) Of Engagement Activity 2015
 
Description SciBar presentation - Kirby, Liverpool 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Presentation in a Pub in Liverpool to highlight sciences to the public
Year(s) Of Engagement Activity 2019
 
Description SciBar presentation Liverpool City Centre 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Presentation in a Pub in Liverpool to highlight sciences to the public
Year(s) Of Engagement Activity 2019
 
Description Women in Engineering 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact This was an event organised by the IET to encourage young women into engineering careers by presenting the steps I had taken to build my career
Year(s) Of Engagement Activity 2019