Multiscale topographical modulation of cells and bacteria for next generation orthopaedic implants.

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary &Life Sci

Abstract

The UK has an aging population and we need to plan ahead to deal with this. Many of us will outlive the useful lives of parts of our skeleton through e.g. arthritis. Currently, e.g. hip replacements have a good survival rate between 10-15 years but then many patients require revision surgery. This is costly to the NHS and hence taxpayer, time consuming to the surgeon (it is far more complex than primary surgery) and is performed on elderly and frail patients where e.g. use of general anesthetic is a concern.
The surgeons have two major concerns regards current orthopaedic implants. Firstly, the materials used are inert. This means that the body has a low response to the materials. This is an advantage as there is no immune response (inflammation) and a disadvantage as there is no bone response. If selective bioactivity could be produced (i.e. no immune response but increased bone response) then the implant could be locked in place by growing bone and implants for life developed. This lack of bone response means that the implants are not well held and can move about during walking. This is termed micromotion. This leads to failure with time as the extent of micromotion increases. Secondly, they worry about infection control. Even after sterilisation bacteria may be present on the implant materials in low numbers or can be introduced during surgery. If the infection can take hold it has major impact on the implant lifetime and this can result in younger patients having revision surgery and that has much higher failure rates.
We have developed very small, nanoscale patterns that can be used to tune bone growth and prevent bacterial adhesion. We will thus optimise these patterns to achieve bacterial control and bone formation at appropriate points of the implant. A major advantage is that we can process these patterns in titanium, a material commonly used for orthopaedic implants due to its high strength (i.e. it can withstand the weight of the human body as we walk).
Such an approach is a step towards making implants for life and planning ahead for the aging population.

Planned Impact

Beyond academic impact, this research has clear potential benefit for clinicians, current patients and future patients in the UK and rest of the world. There is a real drive to target osteoinduction for orthopaedic implants, and our strong collaboration with clinicians and our old market survey show us that industry and surgeons are worried about osseointegration, but bacterial control is a more pressing concern.

We will continue to develop our understanding of osseointegration, but make bacterial control the major focus of this application. If this can be addressed the benefits will be:

1) Prevention of bacterial adhesion on high-risk, fluid-contacting regions of the implant, as the body would struggle to clear the bacterial cells once adhered.
2) Prevention of migration of bacteria through the metaphyseal / implant bond through increased interdigitation of bone and osteoinduction of cells with the capacity to form bone.
3) Control of slow-emerging infections in the metaphyseal and diaphyseal regions from very low numbers of bacteria present on implants prior to implantation.
4) Slowing of biofilm formation should these slow-emerging infections take hold. This would increase the lifetime of the implant.

Achieving these targets will help to achieve implants for life and at least reduce revision rates. This has clear cost and time implications for the NHS. Reduction of the prevalence of complex and risky revision surgery in elderly patients would have a clear socio-economic impact.

To help us to achieve this, we will work closely with clinicians (facilitated by Meek who will have monthly meetings with the academic team and who will recruit trainees to work alongside the project) and industry (most notably with De Puy who have agreed to regular meetings and data review (subject to confidentiality and IP protection).

Publications

10 25 50
 
Description We investigated how surfaces can be used to support normal bone growth and at the same time reduce bacterial growth. We have identified surfaces that support normal bone marrow cell growth and reduce bacterial growth by 30%. These surfaces have been generated on complex shaped, including 3D printed metals.
Exploitation Route Design of new implants or cell culture assays for understanding bacterial cell death
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description We have shown that bacteria as well as stem cells can be modulated by nanotopography alone. There is no impact yet, but we hope that over the next 5 years impact will be realised.
 
Description Dr M.P. Tsimbouri was awarded a Welcome Trust Institutional Strategic Support Fund (ISSF) to studdy "Metabolite identification and targeting between normal and cancerous cells on titanium surfaces"
Amount £5,000 (GBP)
Organisation University of Glasgow 
Sector Academic/University
Country United Kingdom
Start 06/2019 
End 12/2019
 
Description Engineering growth factor microenvironments - a new therapeutic paradigm for regenerative medicine
Amount £3,661,144 (GBP)
Funding ID EP/P001114/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2016 
End 09/2021
 
Title Antibacterial topography 
Description We have generated titanium topographies that can support human cell growth but that kill bacteria for use in orthopaedic implants or as a cell assay tool. 
Type Of Material Technology assay or reagent 
Year Produced 2015 
Provided To Others? Yes  
Impact NA 
 
Title Analysis of ostoclastogenesis / osteoblastogenesis using human bone marrow derived co-cultures on nanotopographical titania surfaces. 
Description  
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
 
Title Osteogenic and bactericidal surfaces from hydrothermal titania nanowires on titanium substrates 
Description  
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
 
Description Souhtampton Collaboration 
Organisation University of Southampton
Department Bone and Joint Research Group
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a long term collaboration where cells, materials and expertise are shared to drive research
Collaborator Contribution This is a long term collaboration where cells, materials and expertise are shared to drive research
Impact A large number of papers, grants and IP.
 
Description Surgical collaboration 
Organisation NHS Greater Glasgow and Clyde (NHSGGC)
Department Surgery Glasgow and Clyde
Country United Kingdom 
Sector Hospitals 
PI Contribution We are working hard to establish clinical collaborations and to improve orthopaedic/bone related materials to make better implants.
Collaborator Contribution Bone marrow for isolation of stem cells/ expertise and perspective.
Impact We have formed the Glasgow Orthopaedic Research Initiative to bring clinicians and basic scientists together for lab projects and for meetings. We host many clinical trainees in the lab and together have applied for, and secured, funds from CSO, BBSRC, MRC and EPSRC.
Start Year 2009
 
Description Surgical collaboration 
Organisation NHS Greater Glasgow and Clyde (NHSGGC)
Department Surgery Glasgow and Clyde
Country United Kingdom 
Sector Hospitals 
PI Contribution We are working hard to establish clinical collaborations and to improve orthopaedic/bone related materials to make better implants.
Collaborator Contribution Bone marrow for isolation of stem cells/ expertise and perspective.
Impact We have formed the Glasgow Orthopaedic Research Initiative to bring clinicians and basic scientists together for lab projects and for meetings. We host many clinical trainees in the lab and together have applied for, and secured, funds from CSO, BBSRC, MRC and EPSRC.
Start Year 2009
 
Description Surgical collaboration 
Organisation Royal Hospital for Children
Country United Kingdom 
Sector Hospitals 
PI Contribution We are working hard to establish clinical collaborations and to improve orthopaedic/bone related materials to make better implants.
Collaborator Contribution Bone marrow for isolation of stem cells/ expertise and perspective.
Impact We have formed the Glasgow Orthopaedic Research Initiative to bring clinicians and basic scientists together for lab projects and for meetings. We host many clinical trainees in the lab and together have applied for, and secured, funds from CSO, BBSRC, MRC and EPSRC.
Start Year 2009
 
Description Surgical collaboration with Mr Peter Young 
Organisation NHS Greater Glasgow and Clyde (NHSGGC)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Work on orthopaedic biomaterials
Collaborator Contribution Provision of bone marrow for cell isolation
Impact THis has allowed us to establish osteoblast/osteoclast co-culture models
Start Year 2018
 
Description surgical collaboration 
Organisation Glasgow Royal Infirmary
Country United Kingdom 
Sector Hospitals 
PI Contribution We are further interested in assessing the suitability of our identified candidate titanium surfaces in bone cancers. Hence we are collaborating with clinicians to provide us with bone cancer samples.
Collaborator Contribution Clinical expertise and provision of samples.
Impact too early to say
Start Year 2013
 
Description surgical collaboration 
Organisation NHS Greater Glasgow and Clyde (NHSGGC)
Department Bio Repository
Country United Kingdom 
Sector Hospitals 
PI Contribution We are further interested in assessing the suitability of our identified candidate titanium surfaces in bone cancers. Hence we are collaborating with clinicians to provide us with bone cancer samples.
Collaborator Contribution Clinical expertise and provision of samples.
Impact too early to say
Start Year 2013
 
Description Dr Tsimbouri; SULSA's Antimicrobial Resistance Conference, Technology & Innovation Centre, Glasgow, UK- April 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Dr P.M Tsimbouri presented a poster at the SULSA's Antimicrobial Resistance Conference, Technology & Innovation Centre, Glasgow, UK- April 2018
Year(s) Of Engagement Activity 2018
 
Description Ms Laila Damiati Tissue and Cell Engineering Society Conference, 2-4 July 2018, Keele University, Keele, Staffordshire, UK (Turbo talk + Poster). 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Ms Laila Damiati attended the Tissue and Cell Engineering Society Conference, 2-4 July 2018, Keele University, Keele, Staffordshire, UK where she was asked to give a Turbo talk and a Poster presentation.
Year(s) Of Engagement Activity 2018
 
Description 29th Annual Meeting of the European Society for Biomaterials, 9-13 September 2018, Maastricht, the Netherlands 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Ms Laila Damiati attended the 29th Annual Meeting of the European Society for Biomaterials, 9-13 September 2018, Maastricht, the Netherlands and had an Oral presentation.
Year(s) Of Engagement Activity 2018
 
Description BORS 
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 We organised the British Orthopedic Society annual conference in Glasgow. The conference sparked discussion after every talk and new collaborations were initiated between research and clinical groups.
Year(s) Of Engagement Activity 2016
 
Description Biomaterials seminar 
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 Ms Laila Damiati gave a talk at the local Biomaterials seminar session on 15/05/2018
Year(s) Of Engagement Activity 2018
 
Description CCE-GLORI (Glasgow) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation workshop facilitator
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Dr MP Tsimbouri, organised the local CCE-GLORI half day conference twice a year where there were presentations and discussions about collaborative projects between clinicians and scientists.

More clinicians interested in research leading to future funding
Year(s) Of Engagement Activity 2014,2015,2016
 
Description Conference presentation 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact 17 th Annual Meeting of the TCES and the BATB Pre-Conference Training, University
of Manchester, Manchester, UK- 2017 (Poster presented by Laila Damiati).
Year(s) Of Engagement Activity 2017
 
Description Conference presentation 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The Biology of Regenerative Medicine, Wellcome Genome Campus, Hinxton,
Cambridge, UK- 2017 (Poster + 3 minuets talk presentation By Laila Damiati).
Year(s) Of Engagement Activity 2017
 
Description Conference presentation 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact 10 th Annual UK MSC Meeting. Held at the University of York, York, UK- 2016. Attended by Laila Damiati
Year(s) Of Engagement Activity 2016
 
Description Conference talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation by Dr PM Tsimbouri about osteogenic and Bactericidal effects of Ti nanowires.
Year(s) Of Engagement Activity 2016
 
Description DTC 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Dr MP Tsimbouri. Talk sparked questions and discussion

The DTC students were interested in doing a project on the subject covered
Year(s) Of Engagement Activity 2010,2011,2012,2013
 
Description Dr PM Tsimbouri Tissue and Cell Engineering Society Conference, 2-4 July 2018, Keele University, Keele, Staffordshire, UK. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Dr PM Tsimbouri attended the Tissue and Cell Engineering Society Conference, 2-4 July 2018, Keele University, Keele, Staffordshire, UK and had a Poster presentation
Year(s) Of Engagement Activity 2017,2018
 
Description GLORI (Glasgow) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation workshop facilitator
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact GLORI was founded by Prof Dalby and Mr Meek with the aim to bring together Scientists and Clinicians and stimulate collaborations with great success so far.
Dr MP Tsimbouri and Peter Young (Orthopedic registrar) are now taking the responsibility of organising the event this year at a larger scale, with poster and paper presentations.

The event has been successful so far with a number of clinicians engaging in a science project and related funding was awarded to support 3 projects.
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013
 
Description GLORI conference organisation 
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 Planning and Organisation of Dr Monica P Tsimbouri the scientific mentor of the Glasgow Orthopaedic Research Initiative (GLORI). GLORI has been established to encourage collaboration between the basic sciences, applied sciences, engineering and clinic. This has the aim of bringing the latest ideas in basic materials research into use to deliver the next-generation of orthopaedic care. It combines expertise from orthopaedic surgeons, biologists, engineers and chemists not only from Glasgow and Strathclyde Universities but the rest of Scotland too and also with the view to expand to the rest of the UK.
Year(s) Of Engagement Activity 2018
 
Description GLaMOR 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation paper presentation
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact talk sparked questions and discussion afterwards

After the talk,new Orthopedic registrars joined the group for research
Year(s) Of Engagement Activity 2014
 
Description Glasgow Crucible 
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 Dr P. Tsimbouri was selected to attend the Glasgow Crucible, a highly prestigious networking workshop organised by the GU in attempt to promote interdisciplinary collaborations. A potential collaboration arose from this event.
Year(s) Of Engagement Activity 2015
 
Description International Conference presentation 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a poster presentation entitled: "Bifunctional Ti nanotopography with osteogenic potential and anti-microbial actions" by Dr Monica Tsimbouri on 02 July - 07 July 2017 - Hotel Eden Roc, Sant Feliu de Guixols, Catalonia, Spain which trigered a lot of interest and discussion.
Year(s) Of Engagement Activity 2017
URL https://mimeresearch.com/biointerfaces2017/
 
Description Invited talk at BCRT Scotland day May 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact This was an invited talk for Dr Monica P. Tsimbouri by BCRT in Perth May 16th 2017. The presentation was intended for clinical partitioners as well as patients and carers affected by bone cancers. There was a lot of interest and discussions after the talk and Dr Tsimbouri was asked to give a further presenation in the future.
Year(s) Of Engagement Activity 2017
URL https://www.bcrt.org.uk/news/2017/may/our-first-scottish-patient-and-carer-day
 
Description Invited talk at Monklands Hospital, Glasgow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Dr P.M. Tsimbouri was invited by a Clinical colleague to give a talk at the Monklands Hospital. Clinical staff from different backgrounds but especially immunology and microbiology were particularly interested in our work.
Year(s) Of Engagement Activity 2016
 
Description Laila Damiati GLORI 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Ms Laila Damiati presented a poster at the GLORI 2018 meeting
Year(s) Of Engagement Activity 2018
 
Description Local Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Year 1 Project Talk by Laila Damiati, University of Glasgow. March 2017
Year(s) Of Engagement Activity 2017
 
Description Ms Laila Damiati SULSA 2018 conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Ms L. Damiati attended the SULSA's Antimicrobial Resistance Conference, Technology & Innovation Centre, Glasgow, UK- April 2018 and had a poster presentation
Year(s) Of Engagement Activity 2018
 
Description Nanotoxicology Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Invited talk for the Naotoxicology Society
Year(s) Of Engagement Activity 2016
 
Description RSC Biomaterials Chemistry Annual Conference 2019, 9-11 January 2019, Liverpool, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Ms Laila Damiati attaended the RSC Biomaterials Chemistry Annual Conference 2019, 9-11 January 2019, Liverpool, UK and had an Oral presentation.
Year(s) Of Engagement Activity 2019
 
Description Royal Society of Chemistry Biomaterials Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Conference presentation
Year(s) Of Engagement Activity 2017
 
Description School outreach 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Dr Monica P Tsimbouri, organised a talk and workshop on Bone cells, Bones and implants for ages P5-P7 primary school. Stimulated the pupils to thinks about their body and the exiting science behind it. The children had the chance to look down a microscope and later make bone cells and bones.

During and after the workshop there was a lot of discussion. The school requested Dr Tsimbouri to visit he school again next year.
Year(s) Of Engagement Activity 2014
 
Description Scottish Metabolomics Network 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Invited talk
Year(s) Of Engagement Activity 2016
 
Description TCES 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation poster presentation
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact questions and discussion followed presentation

collaborative paper discussion
Year(s) Of Engagement Activity 2014
 
Description YRD2014 Research day (Glasgow) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation poster presentation
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact presentation created interest in the project and a poster prize award to Dr M.P. Tsimbouri

Interest from medical staff to undertake research experience in our lab
Year(s) Of Engagement Activity 2014
 
Description school workshop: Bones and bone cells, 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Dr P.M. Tsimbouri has organised a full day workshop for P5,P6 and P7 school pupils at the Milngavie primary school.
The workshop involves presentation slides and Q/A session with the children about the skeleton, bones and bone cells. This followed by hands on experience looking at fixed cells using bright field microscopes. The children were given colour-in pages and also word searches to take home.
Year(s) Of Engagement Activity 2015,2017
 
Description seminar talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Dr P.M. Tsimbouri presented an update of her work on osteogenic and bactericidal properties of Titanium nanosurfaces at the local Biomaterials seminars series. The talk sparked questions and discussion.
Year(s) Of Engagement Activity 2016