Micro- and nano-patterning of titanium surfaces for optimal osseointegration of orthopaedic implants

Lead Research Organisation: University of Glasgow
Department Name: School of Life Sciences

Abstract

Currently, orthopaedic surgeons are limited to the type of materials they can use in load bearing joint replacements (e.g. knee and hip) due to the need to support the weight and function of the body. Commonly used are titanium (Ti) and its alloys. Such procedures, however, have a limited lifespan due to a combination of lack of direct bone contact with the metal exacerbated by soft tissue formation; this allows micromotion and ultimately failure. Surgeons face a mounting pressure due to firstly an aging population (in the developed world in 1950, there were 9.3 people under 20 for every person over 65, by 2025 this ratio is forecast to be 0.59 people under 20 for every person older than 65) and associated problems of rheumatoid arthritis and secondly a more sports active younger populations and problems associated with osteoarthritis. Due to the present lifespan of these procedures (The 10 year failure rate for revision hip surgery was 26% in a Norwegian study of 4762 operations) patients will have to wait longer with pain before surgeons will consider operations. The metals are hard to work with due their material properties and so success to date with surface treatments to encourage direct bone growth and hence develop implants for life have been limited.We have recently demonstrated that specific nanoscale cues in the topography of a material surface can mean the difference between stem cell differentiation to bone and stem cell differentiation to fibrous tissue. Furthermore, we believe that this is merely an introduction to the range of effects obtainable through nanoscale design. That such small alterations in the material surface can have such large effects on stem cells makes it clear that nanoscale design could have significant impact in the rational design of orthopaedic biomaterials. Crucial issues for the development of 'intelligent' orthopaedic biomaterials such as bioactive load-bearing stems are: (1) ability to pattern into suitable materials (e.g. Ti) this has not previously been achieved other than using non-specific and random roughening, (2) achieving both mechanical interdigitation (microfeatures) and direct bone bonding (nanocues and microcues) and (3) generating prototype designs using this technology, which will permit the scale-up and development by industry thereby significantly impacting and benefiting patient health.

Publications

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Brydone AS (2011) Grooved surface topography alters matrix-metalloproteinase production by human fibroblasts. in Biomedical materials (Bristol, England)

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Chong DS (2014) Luminal surface engineering, 'micro and nanopatterning': potential for self endothelialising vascular grafts? in European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery

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Chong DS (2015) Nanotopography and plasma treatment: redesigning the surface for vascular graft endothelialisation. in European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery

 
Description We have for many years investigated nanopatterns to control bone cell development - but this has always been in plastics. In order to make the patterns interesting to orthopaedic surgeons the patterns need to be in titanium. Hence, this project focussed on patterning titanium with osteogenic nanopatterns.
Exploitation Route Design of new implants.
Sectors Healthcare,Manufacturing, including Industrial Biotechology

 
Description We have moved this work forwards to also focus on anti-bacterial coatings using nanotopography. We have also, as part of an MRC award, taken our patterning in titanium throught to in vivo testing that has been successful. This will help us to collaborate with orthopaedic manufacturers. The work has also helped us to engage industry as part of our recently awarded Centre for Doctoral Training looking at 3D tissue models for drug discovery and where there is interest in cell friendly anti-microbials.
Sector Healthcare,Manufacturing, including Industrial Biotechology
Impact Types Societal,Economic

 
Description Glasgow Orthopaedic Research Initiative
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Description training of practioners and researchers
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
 
Description training of practioners and researchers
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
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 05/2019 
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 Public
Country United Kingdom
Start 09/2016 
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 
 
Description Collaboration with Anacail (Spin off) 
Organisation Anacail Ltd
Country United Kingdom 
Sector Private 
PI Contribution We have stabilized a collaboration with Anacail to sterilize protein coating preserving the bioactivity. This will allow the commercialization of future implants in sterilize conditions.
Collaborator Contribution The have been performing the sterilization of the samples and given ideas.
Impact We have been able to find a range of doses to preserve the bioactivity of the big protein coatings and sterilize the samples at the same time. In the future we are going to be working towards finding the right amount of doses to preserve the bioactivity of smaller molecules (such as growth factors).
Start Year 2017
 
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 'Implantology' for Meet the Expert event at Glasgow Science Centre 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I designed and delivered activities with a group of colleagues, and we discussed elements of cell biology and the science behind biomedical implants with many different age-groups and with varying experience of science.

After this event, I undertook additional public engagement training at the Glasgow Science Centre, and people commented that the event sparked their interest in this field.
Year(s) Of Engagement Activity 2012
 
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 Bright Club (stand-up comedy to convey research) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I performed stand-up comedy about my research to an audience of 120 on the night of the event, and the performance has been viewed another 477 times on YouTube, including overseas. The performance sparked interest and discussion about regenerative medicine.

I have been contacted by members of the public and other researchers who saw my performance at the event or via YouTube and became interested in my research, and the University Entrepreneur-in-Residence, who asked me to perform at another event.
Year(s) Of Engagement Activity 2011
 
Description Cell block science 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Presented at prisoner outreach day at HMP Shotts
Year(s) Of Engagement Activity 2019
 
Description Conference attendance-RSC Biomaterials Chemistry Annual Conference 
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 delivered an oral presentation at the RSC Biomaterials Chemistry Annual Conference, Liverpool, UK.
"Role of nanotopography and bioactive coated 2D/ 3D titanium lattices on mesenchymal stem cells and Pseudomonas aeruginosa behaviour"

There was discussion and chance of networking post presentation.
Year(s) Of Engagement Activity 2019
 
Description Conference attendance: TERMIS EU 2019 
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 delivered an oral presentation at the TERMIS EU 2019, Rhodes, Greece.
"Engineered bioactive coatings for 2D/3D titanium implants to enhance osteogenesis and reduce biofilm formation"

The conference was very interesting and conversation with other scientists led to new ideas.
Year(s) Of Engagement Activity 2019
 
Description Conference organisation CCE-GLORI 2019 
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 The local CCE-GLORI workshop is organised by Dr Monica P. Tsimbouri every year. It is a workshop where postgraduate students present their work to their peers and supervisors and discussion then follows the talks.
This is highly beneficial to students and promotes collaboration.
Year(s) Of Engagement Activity 2019
 
Description Conference organisation-GLORI2020 
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 Dr Monica P. Tsimbouri organises GLORI bi-annually. This conference encourages 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, plastic surgeons, biologists, engineers and chemists.
The conference is free for attendance and involves oral and poster presentations from professionals, scientists, clinicians and postgraduate students. It is always well attended.
It is sponsored by industry who are also involved in the conference.
Year(s) Of Engagement Activity 2020
 
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 Debate on stem cell ethics 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Presentations and panel stimulated discussion with attendees.

There were articles written after the event by Oxbridge Biotech Roundtable and the Humanist Society, and I was contacted some time afterwards by a member of the public who was interested in stem cell therapy.
Year(s) Of Engagement Activity 2013
URL http://www.oxbridgebiotech.com/review/featured/obr-glasgow-the-ethical-issues-surrounding-stem-cell-...
 
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 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 GLORI-2018 
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 National orthopedic conference in Glasgow where about 60 audience attended.
Year(s) Of Engagement Activity 2018
 
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 Media interest BBC (nanokicking) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Talk sparked public interest

Many interested enquirers.
Year(s) Of Engagement Activity 2012
 
Description Media interest BBC (orthopaedic materials) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Sparked public interest

Enquieries from the public
Year(s) Of Engagement Activity 2013
 
Description Media interest BBC (stem cell growth) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Talk sparked public interest

Enquieries from the public
Year(s) Of Engagement Activity 2011
 
Description Mentoring school pupils on laboratory placements 
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 The pupils gained lab experience and performed some research, and this sparked their interest in scientific careers and Biology, and led to scientific discussion. The pupils presented the results of their study at a national meeting with other Nuffield Foundation bursary pupils and invited guests.

The Nuffield Foundation has continued to send pupils to our laboratory on lab placements.
Year(s) Of Engagement Activity 2012
 
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 Poster presentation 
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 Layla Damiati presented a poster at GLORI2018
Year(s) Of Engagement Activity 2018
 
Description Poster presentation-Euro Biofilm 2019 
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 presented poster at the Euro Biofilm 2019, Glasgow, UK.
"Pseudomonas aeruginosa quorum-sensing signal molecules interfere with human mesenchymal stem cells on bioactive coated 2D/3D titanium implants"
Year(s) Of Engagement Activity 2019
 
Description Poster presentation: 30th annual conference of the European society of biomaterials 
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 presentated a poster at the
30th annual conference of the European society of biomaterials, Dresden, Germany.
"Bioengineered nontopographical coating to drive osteointegration and reduce implant infection"

A lot of interest was expressed.
Year(s) Of Engagement Activity 2019
 
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 SSN invited talk 
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 to present the use of nanotopography on Titanium orthopedic implants and the use of Nanokicking Bioreactor for bone regeneration and also as a tool for the descovery of metabolic targets in bone cancer for pharma.
Year(s) Of Engagement Activity 2016
 
Description School visit (Lenzie Academy) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Talk led to questions and discussion about careers in Biology

After the talk, the school asked for another talk the following year as they thought it had been successful.
Year(s) Of Engagement Activity 2010
 
Description School visit (Lenzie Academy) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Talk led to questions and discussion about careers in Biology

After my talk, the school asked me to be involved in another event (as a judge for their science fair)
Year(s) Of Engagement Activity 2011
 
Description School visit (careers talk in Bishopbriggs Academy) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Talk stimulated questions and discussion with pupils.

I was invited by the Society of Biology to give this careers talk and was asked to participate in future events. The school noted that the event was a success in stimulating thinking and discussion about careers in Biology.
Year(s) Of Engagement Activity 2012
 
Description School visit (judging research poster competition for school Science Fair - Lenzie Academy) 
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 Pupils were interested in research and scientific discussion.

The school asked me to participate in further activities.
Year(s) Of Engagement Activity 2012
 
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 2010 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation paper presentation
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Dr Monica P Tsimbouri. exiting discussion after talk

Interested parties continued discussion
Year(s) Of Engagement Activity 2010
 
Description TCES 2012 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation paper presentation
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Dr P Tsimbouri. talk sparked questions and discussion afterwards

Engagement with company Reps and received very good discount on equipment.
Year(s) Of Engagement Activity 2012
 
Description TERMIS EU 2011 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation paper presentation
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Dr Monica P Tsimbouri. Talk sparked questions and discussion afterwards

There was further discussion during a later session about my talk
Year(s) Of Engagement Activity 2011
 
Description Talk at GLORI2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Dr Monica P Tsimbouri delivered a talk on behalf of Prof Dalby at GLORI2018
Year(s) Of Engagement Activity 2018
 
Description UKSB 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation paper presentation
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Dr M. P. Tsimbouri. Interesting discussion following presentation

Discussion lead to problem solving for a fellow scientist
Year(s) Of Engagement Activity 2010
 
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