Programme Grant Application in Bio Tribology of Articular Cartilage and Substitution Interventions

Lead Research Organisation: University of Leeds
Department Name: Mechanical Engineering

Abstract

Osteoarthritis affects at least 15% of the population. Currently, apart from pharmacological intervention and pain relief the only effective treatment is end stage total joint replacement. Current total joint replacement surgery is highly successful in patients over 65 with relatively low demands, with success rates over 90% at ten years. Osteoarthritis is being diagnosed in increasing numbers of younger and more active patients, who have expectations of an active life style and desire to remain functional and working for extended periods. However, current joint replacement is not as successful in younger patients, with long term wear and osteolysis in the hip and knee, associated with loss of fixation/bone, loosening and higher revision rates. Revision of failed prostheses is currently a large operating burden in the NHS, and these operations are generally more expensive with increased morbidity compared to primary arthroplasty. There is a reluctance to utilise end stage joint replacement in younger and more active patients, and there is a desire to develop tissue sparing substitution treatments and regenerative treatments for early degenerative disease in articulating joints. There is a need to develop research capacity in the functional biotribology of articular cartilage to support research and development of cartilage substitution therapies and regenerative interventions and enable a new generation of pre-clinical studies to be undertaken to accelerate of the translation of new technology to the patient and enhance the safety and efficacy through better short term predictions of long term clinical outcomes.The overall aim of this programme is to develop a new research platform to study the biotribology of full scale, whole natural joints, over extended periods of time, under representative physiological and anatomical conditions (through in vitro experimental and computational models). Once established these novel simulation systems for cartilage biotribology will allow us to work collaboratively with academic and industrial groups to investigate and support development of new surgical interventions for cartilage substitution and regenerative therapies for early intervention in osteoarthritis. Three important natural articulating joint systems of the hip, the knee and the spine will be addressed. The findings from the programme grant will be valuable in helping industry and manufacturers of advanced medical products to develop improved and safer intervention therapies, and for surgeons to make better informed about decisions on use of new therapies. The work will also inform regulatory and standard bodies such as MHRA (UK), FDA (USA) and ISO. This will have tremendous economic benefit to the UK NHS as well as social benefit to the patients.

Publications

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Al-Hajjar M (2013) Wear of novel ceramic-on-ceramic bearings under adverse and clinically relevant hip simulator conditions. in Journal of biomedical materials research. Part B, Applied biomaterials

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Fermor HL (2015) Development and characterisation of a decellularised bovine osteochondral biomaterial for cartilage repair. in Journal of materials science. Materials in medicine

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Hasan J (2014) Current strategies in meniscal regeneration. in Journal of biomedical materials research. Part B, Applied biomaterials

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Hogg P (2015) Development of a terminally sterilised decellularised dermis. in Cell and tissue banking

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Hua X (2015) Geometric parameterisation of pelvic bone and cartilage in contact analysis of the natural hip: an initial study. in Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine

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Li J (2014) Biphasic investigation of contact mechanics in natural human hips during activities. in Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine

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Li J (2014) Experimental validation of a new biphasic model of the contact mechanics of the porcine hip in Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine

 
Description We have developed substantial research capacity and capability, in experimental and computational simulation systems, and fundamental knowledge of the "bio-tribology of articular cartilage and substitution interventions" through full scale anatomical and physiological in vitro models. We have established a world leading position in "natural joint" bio-tribology, which replicates and is equivalent to the position we have previously established in bio-tribology of total artificial joint replacements. This is allowing us to work collaboratively with academic and industrial groups worldwide to support the development of tissue substitution and early interventions osteoarthritis (OA) in the younger and more active population.
Footnote
Articular cartilage is short hand for the natural joint, bone, cartilage and related tissue structures.
Bio- tribology includes studies of biomechanics, kinematics, dynamics and structure-function relationships.
Specific achievements and findings
Novel multidirectional pin on plate tribological simulator for natural bone and cartilage
Long term organ culture of articulating surfaces of natural knee
Long term loading, sliding and organ culture of articulating surfaces of natural knee
A novel six axis biomechanical and biotribological simulation system of natural knee
A new biphasic computational model of biomechanics and biotribology of natural knee
A novel six axis biomechanical and biotribological simulation system of natural hip
A new biphasic computational model of biomechanics and biotribology of natural hip
A new biphasic computational model of biomechanics biotribology of natural functional spinal unit
A six axis simulator for the spine
High resolution imaging and metrology methods to support biotribology and biomechanical simulations
Exploitation Route Commercilised as products by Simulation Solutions

Fee for service contracts for research and product development, design and manufacture through the Univeristy of Leeds, to global industry Industry partners include

DePuy
Tissue Regenix
In vibio
NHSBT
Simulation Solutions All above experiemtnal simulation systems have been developed in collaboration with simulation solutions and are now available as commercial products

Our world leading novel experimental facilties are being used for coalborative academic, clincial and industrial research

Computational models are being used in collaborative research, for collaborative clincial research and as a fee for service for industry research and consutancy
Sectors Healthcare

URL http://imbe.leeds.ac.uk
 
Description Development of natural joint simulators by Simulation Solutions development of acellular scaffolds by NHSBT and Tissue Regenix
First Year Of Impact 2012
Sector Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description international standards committee chair
Geographic Reach Asia 
Policy Influence Type Membership of a guideline committee
Impact international pre clinical testing standards
 
Description Biocomposites
Amount £200,000 (GBP)
Funding ID LMJ 
Organisation Biocomposites 
Sector Private
Country United Kingdom
Start 01/2013 
End 01/2016
 
Description Biomedical research unit
Amount £6,000,000 (GBP)
Funding ID Leeds musculoskeletal biomedical research unit 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2014 
End 03/2017
 
Description CDT 2014-22
Amount £4,000,000 (GBP)
Funding ID CDT TERM 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 06/2014 
End 09/2022
 
Description DTC 208-2017
Amount £7,000,000 (GBP)
Funding ID DTC 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 06/2008 
End 09/2017
 
Description DTP
Amount £2,000,000 (GBP)
Funding ID DTP 
Organisation DePuy Synthes 
Sector Private
Country United States
Start 01/2014 
End 01/2016
 
Description European Research Council advanced award
Amount £2,000,000 (GBP)
Funding ID Proposal 267114 
Organisation European Research Council (ERC) 
Sector Public
Country European Union (EU)
Start 04/2011 
End 04/2016
 
Description Healthcare Technologies Programme Grant
Amount £3,962,447 (GBP)
Funding ID EP/N02480X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2016 
End 09/2021
 
Description IKC
Amount £10,000,000 (GBP)
Funding ID "EP G0324831, EPI0191031, EPJ0176201" 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 04/2009 
End 04/2016
 
Description Medical engineering centre
Amount £4,200,000 (GBP)
Funding ID WELMEC 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2014 
End 09/2015
 
Description NHSBT
Amount £200,000 (GBP)
Funding ID EI 
Organisation NHS Blood and Transplant (NHSBT) 
Sector Public
Country United Kingdom
Start 01/2014 
End 01/2017
 
Description Tissue regenix
Amount £60,000 (GBP)
Funding ID EI 
Organisation Tissue Regenix Ltd 
Sector Private
Country United Kingdom
Start 01/2016 
End 01/2018
 
Description invibio
Amount £400,000 (GBP)
Funding ID LMJ 
Organisation Invibio 
Sector Private
Country United Kingdom
Start 01/2014 
End 12/2016
 
Description senior investigator
Amount £100,000 (GBP)
Funding ID LMBRU 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2014 
End 04/2015
 
Title Hip Joint simulator 
Description In vitro simulator for artificial hip joints 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2013 
Provided To Others? Yes  
Impact Method commercialised by Simulation Solutions 
 
Title Knee joint simulator 
Description artificial knee joint simulator 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2013 
Provided To Others? Yes  
Impact Simulator and simulation method commercialised by simulation solution 
 
Title Natural knee simulator 
Description Simulation system for natural knee 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2013 
Provided To Others? Yes  
Impact Simulator commercially available, Simulation Solutions 
 
Title natural hip simulator 
Description Simulation system for natural hip 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2014 
Provided To Others? Yes  
Impact System commercially availa le from Simulation Solutions 
 
Title spine simulator 
Description Spinal disc simulator 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2012 
Provided To Others? Yes  
Impact Commercialised by Simulation solutions 
 
Title Biomechanical and biotribological simulation model natural hip 
Description Biomechanical and biotribological model of natural hip 
Type Of Material Computer model/algorithm 
Year Produced 2013 
Provided To Others? Yes  
Impact used in follow on research 
 
Title Biomechanical model of functional spinal unit 
Description model of functional spinal unit 
Type Of Material Computer model/algorithm 
Year Produced 2014 
Provided To Others? Yes  
Impact used in follow on research 
 
Title Biotribological model naturala knee 
Description Biotribological model natural knee 
Type Of Material Computer model/algorithm 
Year Produced 2014 
Provided To Others? Yes  
Impact Used in follow on research on regenerative devices 
 
Title wear simulation model artificial hip 
Description wear simulation model artificial hip 
Type Of Material Computer model/algorithm 
Year Produced 2010 
Provided To Others? Yes  
Impact applied in industry contract research 
 
Title wear simulation model artificial knee 
Description wear simulation model artificial knee 
Type Of Material Computer model/algorithm 
Year Produced 2012 
Provided To Others? Yes  
Impact used in industry contract research 
 
Description DePUY International Ltd 
Organisation Depuy International
Country United Kingdom 
Sector Private 
Start Year 2004
 
Description DePuy 
Organisation Depuy International
Country United Kingdom 
Sector Private 
PI Contribution Thirty-three projects.
Collaborator Contribution funds , materilas staff
Impact publications
Start Year 2013
 
Description Depuy International Ltd 
Organisation Depuy International
Country United Kingdom 
Sector Private 
Start Year 2003
 
Description Depuy International Ltd 
Organisation Depuy International
Country United Kingdom 
Sector Private 
Start Year 2004
 
Description NAMSA 
Organisation North American Science Associates Inc
Country United States 
Sector Private 
PI Contribution In vivo testing of dCell bone to detremine osseointegration and biocompatibility
Collaborator Contribution undertaking research work
Impact pubication
Start Year 2015
 
Description National Blood Service 
Organisation NHS Blood and Transplant (NHSBT)
Department National Blood Service
Country United Kingdom 
Sector Public 
Start Year 2003
 
Description Simulation Solutions 
Organisation Simulation Solutions
Country United Kingdom 
Sector Private 
PI Contribution 10 projects in collaboration with Simulation Solutions: High flex knee simulator Natural knee simulator Natural hip simulator Natural spine simulator Natural joint friction simulator knee joint simulator SOP for hip simulator SOP for knee simulator Natural Knee Simulation System Electro mechanical hip simulator method SOP and training
Collaborator Contribution equipment development
Impact publications
Start Year 2014
 
Description Tissue Regenix 
Organisation Tissue Regenix Ltd
Country United Kingdom 
Sector Private 
PI Contribution A total of 12 projects collaborating with Tissue Regenix Acellular ligament graft (Animal) Acellular bone meniscus bone graft (Animal) Acellular OC graft (Animal) Xeno vascular patch Xeno heart valve Decellularised bladder Decellularised meniscus (see also 12b) Acellular porcine flexor tendon graft Development of the dCELL Partial Meniscus In vivo testing of dCell bone to determine osseointegration and biocompatibility In vivo evaluation of decellularised porcine pulmonary roots. Long Term Evaluation of an Acellular Bovine Arterial Graft in an Ovine Arteriovenous Access Model
Start Year 2009
 
Description Tissue Regenix Ltd 
Organisation Tissue Regenix Ltd
Country United Kingdom 
Sector Private 
PI Contribution research
Collaborator Contribution materials Ip
Impact papers
Start Year 2014
 
Title ISO accredited simulation test laboratory 
Description ISO accredited simulation test laboratory for pre clinical testing and trials widely used by customers around globe 
Type Support Tool - For Medical Intervention
Current Stage Of Development Wide-scale adoption
Year Development Stage Completed 2013
Development Status Under active development/distribution
Impact uptake by wide range of companies 
 
Title acellular bone 
Description under development and in in vivo trials 
Type Therapeutic Intervention - Medical Devices
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2014
Development Status Under active development/distribution
Impact under development and in animal trials 
 
Title acellular bone cartilage osteochondral graft 
Description under development 
Type Therapeutic Intervention - Medical Devices
Current Stage Of Development Initial development
Year Development Stage Completed 2014
Development Status Under active development/distribution
Impact under developemnt 
 
Title acellular bone cartilage osteochondral graft 
Description under development NHSBT 
Type Therapeutic Intervention - Medical Devices
Current Stage Of Development Initial development
Year Development Stage Completed 2015
Development Status Under active development/distribution
Impact under development 
 
Title dcell ligament 
Description Under commercial development by tissue Regenix, progressing to CE mark and product launch 
Type Therapeutic Intervention - Medical Devices
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2014
Development Status Under active development/distribution
Clinical Trial? Yes
Impact under commercial development by Tissue Regenix in clinical trial started 2015 proceeding to Ce mark and product launch 2017 
URL https://clinicaltrials.gov/show/NCT02540811
 
Title dcell meniscus 
Description Developed by tissue Regenix In clinical trial started 2015 
Type Therapeutic Intervention - Medical Devices
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2014
Development Status Under active development/distribution
Clinical Trial? Yes
Impact first in man clinical trial started 2015 
URL https://clinicaltrials.gov/show/NCT02270905
 
Title finite element simulation tools to capture patient variation for the analysis of orthopaedic devices across a patient cohort 
Description This project has been led by Dr Ruth Wilcox in partnership with Simpleware Limited. The development of the software add-on has been completed and the final validations with the Leeds data set-set are coming to an end. It is anticipated that a technology demonstrator project will now be undertaken with a company that can demonstrate the utility of the software for evaluating spinal implants. The commercial team is now engaged and discussions with Simpleware around a possible license deal are on-going. It is envisaged that as part of this license deal Simpleware will engage Leeds expertise as part of their offer to companies. In addition Leeds personnel will retain the right to undertake consultancy in their own capacity. 
Type Of Technology Software 
Year Produced 2013 
Impact further research 
 
Title natural hip simulator 
Description natural hip simulator 
Type Of Technology Physical Model/Kit 
Year Produced 2014 
Impact commercial product simulation solutions 
 
Title natural knee simulator 
Description natural knee simulator 
Type Of Technology Physical Model/Kit 
Year Produced 2013 
Impact commercialised by simulation solutions 
 
Company Name Tissue Regenix 
Description Developemnt and manufacture of Regenerative Biological Scaffolds for tissue repair in vascular, cardiovascular and musculoskeletal systems 
Year Established 2007 
Impact aim listed d raised £0m investment value £150m 4 clinical products