Engineering solutions to back pain: an interdisciplinary approach

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

Abstract

At some point during our lifetimes, eight out of ten of us will experience low back pain. For some, a course of painkillers and a period of recovery will be enough to alleviate the symptoms, but this is not always the case and many people continue to suffer long term pain and discomfort. In joints such as the hip and knee, replacement surgery has become commonplace and is highly successful in reducing pain and restoring movement. In the spine however, corresponding treatments are still in their infancy and have yet to prove their long term effectiveness.It may seem farfetched to imagine that in less than two decades spinal treatments could develop to a level where back pain will be effectively treated using keyhole surgery and other minimally invasive techniques. However it is not beyond the realms of possibility if progress in the basic sciences along with developments in imaging and computer modelling continue. Perhaps most importantly, the understanding accrued in these many disciplines must be effectively harnessed and integrated. The aim of this research is to enable such a step change in spinal treatments to occur. Through the Exploration Funding, computer models of the spine will be developed in collaboration with experts from the basic sciences as well as clinicians and industrialists. These models will be used to investigate new implant materials and treatment techniques for back pain.The spine constantly undergoes complex biological, biochemical and mechanical processes which must be taken into account if new treatments are to be effective. Experimental tests will be used to assess these factors in isolation and the results combined into the computer models. There is much variation in the properties of the spinal structures both from one patient to another, and even along the length of an individual's back. These variations will also be simulated in the computer models to see how effective a treatment will be for a range of different patients. The computer models will enable new spinal treatments to be developed and optimised to bring maximum benefit to the patient before they are introduced into hospitals.By the end of the five year period of the Exploration Funding, a new and reliable method of testing spinal interventions will have been developed and research initiated to create a range of novel optimised treatments for back pain. In ten years time, this could lead to a new range of treatment options and, by 2020, effective minimally invasive treatment for back pain could become a reality.

Publications

10 25 50
 
Description The aim of this Challenging Engineering grant was to develop computer models of the spine to investigate new implant materials and treatment techniques for back pain. In parallel, two promising new treatments were identified (vertebroplasty and nucleus augmentation) and pilot studies undertaken to develop both the procedures themselves and the testing platforms necessary to optimise them before their introduction into patients.

One of the reasons for the failure of previous spinal treatments is that there is much variation in the properties of the spinal structures from one patient to another, but pre-clinical testing is often undertaken under standardised conditions or on small numbers of specimens. As part of this grant, over 70 vertebrae were imaged using micro computed tomography (microCT - a 3D high resolution x-ray method) providing a major new database of information about the variation in vertebrae from one person to another. The vertebrae were then characterised in terms of their bone properties at different levels, from the level of the cells to the shape of the overall bone in both biological and mechanical terms. This information is being used to determine how the microscopic changes that occur in diseases such as osteoporosis can be related to clinical measurements, and will help clinicians identify which vertebrae are at risk of fracture. A new methodology was developed and validated for generating computational models, using finite element methods, from the image database of the vertebrae, allowing spinal treatments to be evaluated across a patient population rather than just on a single 'average' model. New methodologies were also developed to enable minimally invasive treatments for fractured vertebrae to be investigated in the laboratory and using computational models. This work focussed on 'vertebroplasty', a technique in which cement is injected into a fractured vertebra to stabilise the fracture and reduce pain. A novel method was developed that enabled specimens of cement-augmented bone to be microCT imaged under load, so that their behaviour could be more fully investigated, which led to a more robust methodology for simulating this technique in computational models. A workshop was also held (as part of Creativity@home funding) with the research team and leading clinicians to identify the scientific barriers to the more widespread introduction of vertebroplasty clinically. This work is now being taken forwards through a European Research Council (ERC) grant.

A workshop was also held with leading clinicians and academics to identify the major challenges to successful treatment of disc degeneration, one of the leading causes of back pain. Following the workshop, research was focussed on a treatment to augment the nucleus of the disc, the central gel-like structure which becomes fibrous and loses height in disc degeneration. A new range of self-assembling peptides were characterised and optimised for use in nucleus augmentation. A patent has been submitted and this work is being taken forward through follow-on funding from the EPSRC. New methodologies for imaging and modelling the intervertebral discs were also developed. These include use of clinical magnetic resonance imaging (MRI) to identify the different components of the disc in both unloaded and loaded states, providing information on the mechanical behaviour of the tissue that is necessary for the design of new treatments. This work is being taken forward through follow-on funding from the ERC.

In summary, through this funding new methodologies were developed to better understand and model the spine and spinal therapies. The modelling methods developed enable patient variation to be taken into account at an early stage of testing and are now being used to evaluate and optimise a range of treatments. Two new minimally invasive spinal interventions were also investigated and their development into clinical solutions is now being taken forward through follow-on funding.
Exploitation Route A patent has been submitted for the peptides developed as part of this grant, and their development into a treatment is being taken forward through follow-on funding from the EPSRC (£1M, PI Wilcox, 'ULTRASPINE' grant ref EP/K020757/1 ) in collaboration with the University of Oxford.

The database of microCT images of vertebrae has been used in collaboration with an industrial partner (Simpleware ltd, Exeter UK) to develop new code for generating finite element models that can represent patient variance. This work was developed though Proof of Concept funding provided by the Innovation and Knowledge Centre in Regenerative Therapies and Medical Devices at the University of Leeds, and will be developed further through European Research Council funding (EUR 1.5M, PI Wilcox, 'Back to Back' reference 306615).

The computational methodologies developed in this grant have been adapted for the analysis of other orthopaedic applications. This includes a major grant from the British Orthopaedic Association in collaboration with a leading orthopaedic surgeon to investigate treatments for periprosthetic fracture (£400k, PI Tsiridis, 'Latta Fellowship'). In addition, the work has fed into two major grants (EPSRC Programme grant in Cartilage Biotribology (£4.5M, PI Fisher, ref EP/G012172/1) and the Wellcome/EPSRC Centre of Excellence in Medical Engineering (£11M, PI Fisher, 'WELMEC' ref 088908/Z/09Z) where the computational techniques developed are being used to evaluate a number of clinical interventions.
Sectors Healthcare

 
Description The major outcomes from this work were new methodologies for testing spinal interventions (experimental and computational) and the development of a novel peptide gel for nucleus augmentation, based on the design requirements derived from the mechanical testing, and informed by close liaison with clinicians (including targeted workshops that were held through the grant). A patent has been submitted for the peptides developed as part of this grant (now awarded in US, pending in EU), a commercialisation plan has been developed and industrial partners are currently being sought to develop this into a clinical product. This work is being further developed for other applications and taken forwards through PhD projects and further grant funding for an in vivo study. Using the data acquired in this study, a collaboration with an industrial partner (Simpleware ltd, Exeter UK) was initiated to develop new code for generating finite element models that can represent patient variance. This has been successfully completed and validated. The methods are currently being adapted for other joints, including through a Healthcare Impact Partnership grant with an orthopaedic manufacturer.
First Year Of Impact 2012
Sector Digital/Communication/Information Technologies (including Software),Healthcare
Impact Types Economic

 
Description Hosted visit of Lord Prior, Undersecretary of State for Health on fact-finding mission to Leeds University and Depuy Synthes
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description Member of Arthritis Research Biomechanics and Bioengineering Centre Cardiff Scientific Advisory Board
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Participation in a advisory committee
 
Description Membership of Royal Academy of Engineering Panel for Biomedical Engineering
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact The panel has published a number of reports and briefing papers. Details are here: http://www.raeng.org.uk/policy/engineering-policy/panel-for-biomedical-engineering/publications
URL http://www.raeng.org.uk/policy/engineering-policy/panel-for-biomedical-engineering
 
Description Versus Arthritis Research Advisory Group - Ruth Wilcox
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description EPSRC Programme Grant
Amount £4,536,888 (GBP)
Funding ID EP/G012172/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 05/2009 
End 06/2015
 
Description ERC Starting grant
Amount € 1,500,000 (EUR)
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start 12/2012 
End 11/2017
 
Description Healthcare Impact Partnership
Amount £1,025,492 (GBP)
Funding ID EP/N02480X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 06/2016 
End 05/2021
 
Description Healthcare Technologies Programme Grant
Amount £3,962,447 (GBP)
Funding ID EP/N02480X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 10/2016 
End 09/2021
 
Description ULTRASPINE: Ultrasound-Enabled Minimally Invasive Disc Replacement
Amount £991,843 (GBP)
Funding ID EP/K020757/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2013 
End 03/2018
 
Description Versus Arthritis Proof of Concept Grant 22031
Amount £100,000 (GBP)
Funding ID 22031 
Organisation Versus Arthritis 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2018 
End 10/2020
 
Title Data Associated with paper titled: Peptide:glycosaminoglycan hybrid hydrogels as an injectable intervention for spinal disc degeneration. 
Description Data Associated with paper titled: Peptide:glycosaminoglycan hybrid hydrogels as an injectable intervention for spinal disc degeneration. Data includes FTIR, TEM, optical micrographs, and processed numeric data used in the figures. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact Database has been made openly available. It has been used internally by other researchers in the group and university. External access has not yet been cited. 
URL https://doi.org/10.5518/47
 
Title Mengoni and Wilcox Ovine FSU data 
Description 8 cervical functional spinal units from 5 ovine spines: CT scan images, mechanical compression (load, displacement, pressure and image information) and FE models 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact Database released with paper to enable other researchers to access and compare data. Greater impact likely in future once data has been used. 
URL http://archive.researchdata.leeds.ac.uk/id/eprint/22
 
Title Ovine annulus fibrosus interlamellar material model calibration data set 
Description Experimental data: microscopy images and geometrical data of unloaded and radially loaded samples of ovine lumbar annulus fibrosus tissue; Computational data: input file and raw results of load/extension FE models built from the experimental data; Results data: values of calibrated interlamellar behaviour 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact Data released to enable other researchers to apply or reuse for additional purposes. Great impact likely once data has been used and published. 
URL http://archive.researchdata.leeds.ac.uk/id/eprint/2
 
Title microCT vertebra database 
Description Database of over 50 high resolution scans of vertebrae made using microCT 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact follow-on funding obtained to use database to develop new modelling methods for spine to represent patient variation (EPSRC IKC proof of concept) and ERC Starting grant 
 
Description Simpleware Ltd 
Organisation Simpleware Ltd
Country United Kingdom 
Sector Private 
PI Contribution Co-development of new software
Collaborator Contribution Project partner of major grants providing expertise, access to new software features
Impact Successful collaboration led to joint Proof of Concept study to develop new software funded through EPSRC IKC
 
Title NOVEL PEPTIDE COMPLEXES 
Description The invention relates to novel self-assembling peptide complexes comprising a charged peptide and a polysaccharide, methods of producing them and uses therefor. The novel self-assembling peptide complexes of the present invention have particular utility in the restoration of biomechanical or biochemical function of a variety of biological tissues, for example and without limitation, in degenerated spinal discs, osteoarthritic joints, damaged cartilage, meniscus, ligaments, tendons, dental, ophthalmic and cardiovascular and blood vessel tissues. The invention provides inter alia methods of repairing and or restoring biomechanical or biochemical function of biological tissues and scaffolds for the support of cell growth. 
IP Reference US2016058871 
Protection Patent granted
Year Protection Granted 2016
Licensed No
Impact Follow on funding obtained for first in vivo study
 
Title Novel peptide complexes 
Description The invention relates to novel self-assembling peptide complexes comprising a charged peptide and a polysaccharide, methods of producing them and uses therefor. The novel self-assembling peptide complexes of the present invention have particular utility in the restoration of biomechanical or biochemical function of a variety of biological tissues, for example and without limitation, in degenerated spinal discs, osteoarthritic joints, damaged cartilage, meniscus, ligaments, tendons, dental, ophthalmic and cardiovascular and blood vessel tissues. The invention provides inter alia methods of repairing and or restoring biomechanical or biochemical function of biological tissues and scaffolds for the support of cell growth. 
IP Reference WO2014167310 
Protection Patent application published
Year Protection Granted 2014
Licensed No
Impact Follow-on funding obtained. Commercialisation workshop held as a demonstrator for JRI Ltd and used to map routes for future commercialisation/impact. Further applications being explored through PhD projects.
 
Description Creativity at home 
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 Creativity@home funding used to train PDRAs in facilitation followed by an event to bring together leading clinicians from UK on topic of vertebroplasty to help inform our future research strategy.

Outcomes from meeting include raised awareness of our research in clinical community, several potential future collaborators identified, and clinical opinion that has helped shape our future research activity in this area.
Year(s) Of Engagement Activity 2013
 
Description Local engagement activities 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Schools
Results and Impact Stands always very popular with large numbers of delegates attending and requests to hold follow-on activities with schools and exhibit at future events.

Extremely positive feedback from attendees, teachers and parents, leading to increasing requests to provide exhibits for other events
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013,2014
 
Description Royal Academy of Engineering Panel for Biomedical Engineering 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Event promoted collaboration and career development for early-career medical engineers with advice from expert mentors and funders.

Feedback from delegates very positive with 100% rating the networking opportunities and quality of the speakers and mentors as good or excellent.
Year(s) Of Engagement Activity 2014
URL http://www.raeng.org.uk/publications/reports/young-researchers-futures-meeting-orthopaedic
 
Description Science for a Successful Nation 
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 Presented stand depicting our research highlights to illustrate the importance of sustained funding as part of the EPSRC Science for a Successful Nation event
Year(s) Of Engagement Activity 2015
URL https://www.epsrc.ac.uk/newsevents/news/sciencesuccessfulnation/