Bioactive orthopaedic implants using nanopatterned 3D materials

Lead Research Organisation: University of Glasgow
Department Name: School of Engineering

Abstract

Today we live longer and longer, and at the same time we have a more active life than ever before. This means that younger and younger patients are now facing partial or total hip replacement. This combined with a longer life expectancy increases the possibility of revision surgery as the life span of prostheses is shorter than the patients? life expectancy. This possesses several problems. Firstly, the success of a hip replacement is lower for younger patients and as a result such surgical procedures are often being delayed by the surgeons. Secondly, revision surgery is significantly less successful and the lifetime of the prostheses is greatly reduced. A major step forward to increase the lifetime of a prosthesis has been for cementless implants. Here the surface of the implant has been roughened thus providing a better locking with the ingrowing bone. Nonetheless, there is still space for significant improvements of current implants.

The bone marrow is a rich source of stem cells which can, provided the correct stimuli, become bone forming cells. When a hip implant in fitted during the surgical procedure it will come in direct contact with the bone marrow. We have discovered a specific nanopattern which promotes the stem cells from the bone marrow to become bone forming cells. This project will take our remarkable discovery from a Petri dish and turn the results into a new generation of orthopaedic implants with improved properties over current ones. To realise this ambitious goal we have devised a clear technology development plan combined with the necessary biological experiments to bring our technology to a large animal stage. Our initial results have been performed on patterned plastic surfaces. However, plastics do not have the required mechanical properties (strength) to be used for prostheses. Such load bearing implants are commonly made in titanium and we will develop methods to pattern such metal implants.

To the best of our knowledge this will be a world s first to develop osseoinductive process (development of immature cells to bone forming cells) on an orthopaedic metal implant surface.

Technical Summary

Current orthopaedic procedures have moved from cemented to cementless implants (held in place by osteointegration). When first implanted there is only 20% contact between the bone and the implant. As osteointegration occurs over a period of several weeks it is essential that the implant fits tightly and that micromotion is minimal post surgery. To increase the bone growth on the implant and increase the life time of the implant, the surface is now coated with hydroxyapetite giving an osteoconductive surface. However, the roughened and coated surfaces do not control the fate of the progenitor cells which will be present after the surgical procedure and importantly during the healing process. Primary cementless total hip arthroplasty results are still worse than cemented shown by national joint registry data (UK and Australian -2% revision at 3 years). However, cementing is technically demanding and therefore not reproducible without a long training curve and will remain intraoperatively more time consuming and therefore an expensive procedure. We know from cadaveric studies that even the best present day cementless prosthesis obtain only a 25% bony on/ingrowth and consequently less than ideal physiological loading. Also, even the best performing smooth taper, cemented stems are associated with abnormal physiological loading (Scottish arthroplasty project shows a ten years fracture rate of 1.7 % for primary THA). We have discovered a unique nanopattern which exactly provides this cue in vitro. A slightly irregular nanopattern of nanosized pits (100 nm diameter and an average of 300 nm centre-to-centre spacing) specifically differentiates skeletal stem cells into bone forming cells with the use of any hormones or growth factors but only driven by the surface topography. In this project we have devised an ambitious plan to translate our in vitro findings into a new generation of orthopaedic implants. To reach this goal, we will develop a number of new patterning methods which will enable us to pattern titanium implants with our unique nanopattern. In a series of ex vivo and in vivo experiments we will move from organotypic cultures to segmental mouse defects. In essence this will bring our technology from the Petri dish to a pre-clinical stage.

This is an ambitions project and to the best of our knowledge this will be a world s first to develop osseoinductive metal implant surface for load bearing implants.

Publications

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Greer AI (2016) Mechanical compatibility of sol-gel annealing with titanium for orthopaedic prostheses. in Journal of materials science. Materials in medicine

 
Description Confidence in Concept
Amount £46,213 (GBP)
Organisation University of Glasgow 
Sector Academic/University
Country United Kingdom
Start 01/2017 
End 02/2018
 
Description EPSRC-DTA PhD studentship
Amount £60,000 (GBP)
Organisation University of Glasgow 
Department School of Engineering Glasgow
Sector Academic/University
Country United Kingdom
Start 10/2010 
End 03/2014
 
Description Centre for Excellence, organs-on-a-chip 
Organisation Oslo University Hospital
Country Norway 
Sector Hospitals 
PI Contribution I am an international PI on the Centre for Excellence hosted by Oslo University. This is a 10 year long project started 2018. My contribution to the project is the development chip technologies for the organoids. This is founded on our long track record on biomaterials development as well as our international recognition on injection moulding.
Collaborator Contribution The partners provide insight to organoid models (liver, pancreas and fat) but have also contributed with hiPS cells to our lab.
Impact 30 years of microfluidics March 2019 DOI: 10.1016/j.mne.2019.01.003
Start Year 2018
 
Description University of Southampton 
Organisation University of Southampton
Department Bone and Joint Research Group
Country United Kingdom 
Sector Academic/University 
PI Contribution Glasgow carries out nanofabrication and supplies University of Southampton with samples for biological experiments
Collaborator Contribution University of Southampton is a directly funded collaborator on this grant. They provide supply of bone marrow derived stem cells. They also carry out in vitro and in vivo experiments in relation to the grant.
Impact Prior to this grant we have published 8 joint papers. This is an interdisciplinary collaboration. Southampton provides expertise in stem cell science and in vivo testing.
 
Description BBC coverage 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact BBC Scotland interviewed the PI at Glasgow University on the development of our nanotechnology and its context to medical applications. The interview was aired in Radio, TV and published on the BBC web pages.

This lead to a significant interest from the public - several members of the public contacts us directly with interest in the technology. The media - several news papers provided additional interviews. Industry - several orthopedic companies took contact with us after the press release.
Year(s) Of Engagement Activity 2012
 
Description Cheltenham Science Festival - Central Exhibit in Discover Zone 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The Stem Cell Mountain featured in 'Doc Brown's Lab' (in keeping with the 2015 Back to the Future Theme) at the famous Cheltenham Science Festival Discover Zone. The team interacted with an estimated 1800 visitors over 6 days. Received feedback such as the following: "Great explanation from volunteers about the stem cell model. My Year 6 pupils could then explain the purpose of the model - great" and "That's how you teach science!"
Year(s) Of Engagement Activity 2015
URL http://www.cheltenhamfestivals.com/science/
 
Description Open Conference "Stem cells for bone regeneration: state-of-the-art research and solutions" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Speaker - Bonebank Conference, Odense, Denmark. "Skeletal stem cells for bone tissue regeneration.".
The audience were peer scientists, clinicians and industrialist to inform, educate and debate developments in translational bone research.
Year(s) Of Engagement Activity 2016
 
Description Scaffolds and cells - making replacement body parts in the lab - Exhibit at the BBSRC Great British Bioscience Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Engaged over 6500 visitors from across the UK as part of the BBSRC run GBBF. EPSRC grant generated the centre piece of our exhibit - the Stem cell mountain - a large interactive pinball machine built in collaboration with Winchester Science Centre to communicate the concept of Stem Cell Potential. In response to the feedback question 'Tell us something from your visit that you found particularly interesting' the answer 'Stem Cells' was one of the most frequently given. Through a conversation at this exhibition a talented international MSc student from Queen Mary's was inspired to commence a PhD project (self-funded) in my group.
Year(s) Of Engagement Activity 2014
 
Description Science Day at University of Southampton 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Science Day ('Stem Cell Mountain' & Bone regenerative medicine display') at University of Southampton - 14/03/15. (Open to the general public - 1000+ visitors)
Year(s) Of Engagement Activity 2008,2011,2013,2015,2016
 
Description Southampton Science and Engineering Festival 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Stem Cell Mountain at the Southampton Science and Engineering Festival (1 day) - regional general public, predominantly families Measure 1: visitors passing stand; 1300 Measure 2: visitors interacting with researchers on the stand; 400
Year(s) Of Engagement Activity 2015
 
Description Speaker at UKRMP Conference UK 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Speaker - Inaugural UK Regenerative Medicine Conference, London. "Size matters - Harnessing biomimetic materials for skeletal tissue engineering."
The audience were peer scientists, clinicians and industrialist to inform, educate and debate developments in translational bone research.
Year(s) Of Engagement Activity 2016
 
Description Stem Cell Mountain Outreach Programme (New Forest Country Show) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Stem Cell Mountain outreach programme at the New Forest Country Show 28/07/15 (general public, farmers, agricultural community. 105,000 people visited over 3 days).
Year(s) Of Engagement Activity 2015
 
Description Stem Cell Mountain at Bestival Music Festival Science Tent 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Stem Cell Mountain at the Bestival Music Festival Science Tent (4 days) - exhibit in shared Science Tent, mixed Festival audience (mainly general public and especially young people 17-25) Measure 1: visitors passing stand; 1400 per day = 5600 Measure 2: visitors interacting with researchers on stand; 500 per day = 2000 Particularly notable was the impact of this activity on the researchers themselves and how they viewed the importance of their own research. For example one researcher reported: "This festival was great to see how amazed people are about the potential of stem cells"
Year(s) Of Engagement Activity 2015
 
Description Stem Cell Mountain at the Glastonbury Music Festival Science Tent 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Stem Cell Mountain exhibit in shared Science Tent, mixed Festival audience (academics, post-docs, science specialists, general public, families and young people) Measure 1: visitors passing stand; 1100 per day = 5500 Measure 2: visitors interacting with researchers on stand; 500 per day = 2500 Engaged classically hard to reached audience. Quote: "I was considering doing a PhD at one point - I didn't think I'd reconsider it here"
Year(s) Of Engagement Activity 2015
 
Description Stem Cell Mountain on Tour - Overview 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The EPSRC funded Stem Cell Mountain Roadshow Exhibit combines the fun of a pin ball machine with a profound metaphor for a key biological concept. The stem cell mountain was designed in collaboration with Winchester Science Centre to bring to life the complex idea of stem cell potential. The exhibit has engaged festival goers at Glastonbury and Bestival, science aficionados at the UK's top Science Festivals, as well as the 100000 visitors per year that visit the Winchester Science Centre where a replica is full time resident (see individual entries for numbers at each event) Qualitative feedback on Stem Cell Mountain from the public: "This model illustrates stem cell science brilliantly, and it's fun too" "The stem cell machine was so brilliant - it really helped to explain how the body works in such an interactive and easy way" "Helpful, informative team of staff on hand" "Interesting to learn why stem cell research is so controversial" "Great explanation from volunteers about the stem cell model. My Year 6 pupils could then explain the purpose of the model - great" "That's how you teach science!" "It's great to see this activity is in the busiest tent in the field" "I'm glad we saw this - it makes a difference" "That's amazing - a really great way to show stem cell analysis" "I was considering doing a PhD at one point - I didn't think I'd reconsider it here" "The stem cell mountain - thank you for having this idea. It's such a clever way to explain the concept" "Such a simple way to represent a very complicated thing" "We need science like this in school. It's so much more interesting" Qualitative feedback from the Stem Cell Mountain team of researchers: "One of the amazing perks that come with researching! Great day, talked to many interesting people from various backgrounds and ages (from 5yr olds to 70 year old ex-specialists in the area). Very good and helpful for both the people that we talk to and for us as researchers" "It made me think my research matters" "It helps you to step back and see the amazing things you get to study in university with fresh eyes" "People were really interested in what are doing in our research" "It is a great opportunity to leave the academic bubble and a useful and interesting attempt to explain science research to a wide audience. The best thing is seeing people's reactions when everything clicks and makes sense to them!" "The stem cell mountain is very impressive. Proud to represent" "This festival was great to see how amazed people are about the potential of stem cells" " A brilliant way to inform the public about the work we do" " A pleasure to meet and collaborate with the range and depth of skills and knowledge in our roving science tent" "I was blown away by the strength, diversity and great nature of the team" "I've really enjoyed manning the stem cell volcano - my first experience of the exhibit. I'd quite like one in my living room!" "It's good to see so many people interested in stem cell research"
Year(s) Of Engagement Activity 2014,2015,2016
 
Description Thomas Hardye School Science Day 
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 A Dorset secondary school open day engaging 300 students with translational stem cell medicine. First experience of public engagement for several colleagues who reported great satisfaction with the experience.
Year(s) Of Engagement Activity 2015
URL http://www.southampton.ac.uk/per/university/roadshow.page
 
Description Winchester Science Festival 
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 Stem Cell Mountain at a three day up and coming science festival. Engaged largely family audience and science festival talk attendees Measure 1: visitors passing stand; 300 per day = 900 Measure 2: visitors interacting with researchers on stand; 150 per day = 450
Year(s) Of Engagement Activity 2015