Final Report Summary - SPINEFX (SPINEFX: A University–Industry Network for the Training of High-quality Multidisciplinary Researchers to Deliver Enterprising, Cost-effective Surgical Solutions for Spinal Disease and Trauma) Publishable summarySpineFX – Initial Training Network Project Number 23869048 Months: 1st November 2009 – 31st October 2013Co-ordinator – Prof Richard M HallSchool of Mechanical Engineering, University of Leeds, Leeds, UKWebsite – www.spinefx.euSynopsis of the Project Objectives: Overall achievementThe early stage and experienced researchers recruited to SpineFX (www.spinefx.eu) have developed an increased knowledge of the science and technology behind some of society’s foremost medical challenges linked to the spine. The experience gained within SpineFX Consortium will equip these future research leaders with a range of skills needed to deliver pathology-specific interventions and innovative solutions to some of Europe's most urgent healthcare problems: pain and immobility caused by vertebral fracture. All the scientific objectives were accomplished within three broad themes; (i) the basic engineering and biomedical science governing the three main spinal pathologies; (ii) the development of tools for the effective diagnosis of spinal pathology and treatment evaluation; and, (iii) the creation of novel interventions that aid the treatment of fractures, benefit patients' quality of life and improve EU and industry competitiveness. Similarly, all the training objectives were completed in which the Marie Curie Fellows were equipped with high-level skills through the deployment of cutting-edge research supported by network-wide training events, local training and Personal Career Development Plans (PDP). The Early Stage Researchers (ESRs) were based at 4 leading European University-based research institutes, whilst the three experienced researchers (ERs), were located at 3 innovative SMEs (AnyBody Technology A/S, BoneSupport AB, and Ulrich GmbH & Co.KG) which allowed the development of business as well as scientific oriented skills. Eleven ESRs have or will go on to submit a thesis for the degree of PhD. The two short-term ESRs who have not remained in their host group beyond their one year contract have taken up research posts in the USA and Canada. In developing these researchers, we have delivered 7 workshops with both SpineFX and external attendees and a Final Conference at Eurospine 2013. Further, each ESR or ER attended a minimum of one complementary skills course per annum. There was also a mid-term workshop delivered for SpineFX personnel only. In addition, the ESRs and ERs have engaged in exchanges and visits between institutions to utilise equipment and skills not found in their own research centre. A SpineFX identity was developed that designed a distinctive and recognisable logo (see Annex I also includes images from the workshop, final conference and the research activities of the partners).The ERs and ESRs have presented at leading international conferences (54 conference publications – see Annex II) as well as the publication of 9 peer reviewed manuscripts with a further 6 submitted. In addition, 15 of the researchers presented at the final conference, which was a pre-conference day-course entitled ‘SpineFX Final Conference ‘Vertebral Fracture’' at the Annual Eurospine Meeting, which was delivered on 1st October 2013, in Liverpool, UK (see Annex III. Eurospine is Europe’s most prestigious spinal meeting. The website has been updated throughout the project lifetime and is currently up-to-date. We have delivered 7 newsletters outlining activity within SpineFX. Once accepted by the Commission all the 'public' deliverables will be made available on the website to the wider community. Three of the Fellows’ conference presentations were in receipt of awards for their outstanding research: (i) A. BouFrancis - Young Investigator Award, Combined Orthopaedic Research Societies, Venice, October 2013; (ii) H.S. Hosseini - Outstanding Poster Presentation, Day of the Master Program of Biomedical Engineering of the University of Bern - May 2012; and,(iii) G. Marini - Poster Award - Computer methods in Biomechanics and Biomedical Engineering, Berlin, April 2012.Equivalent outputs in terms of exploitation include: 1) Several essential enhancements to the AnyBody Modelling System (Anybody Technology A/S) were completed including development of a new interface for linking with Ansys and Abaqus software packages. This new interface allows multiscale modelling to be undertaken. Additionally an improved spine model has been developed opening up exploitation of the software for the virtual evaluation of medical implants and procedures. 2) A new methodology for testing spinal systems at Ulrich GmbH was developed. New designs of pedicle screws are commonly tested via pull-out testing but this is accomplished with a non-physiological loading direction. The experiments showed that differences in pull-out testing of different screw types did not represent differences found in the more physiological toggle-testing.3) A fully injectable synthetic ceramic bone substitute was enhanced at BONESUPPORT AB. This was designed to offer osteoconductivity and good resorption potential, which will allow for bone in-growth upon implantation. Further research will be undertaken to fully exploit this material's potential.Scientific advances within SpineFX have been numerous and include elements to be exploited elsewhere.• Workpackage 1: An efficient scheme was developed to compare densification of trabecular bone in step-wise compression experiments and finite element analysis. This was enabled through the development of an in-situ step-wise loading chamber which was used to investigate the collapse of trabecular bone samples and vertebral bodies within microCT systems. Following on from this a non-local formulation of a constitutive model for damage and densification of trabecular bone was implemented and validated with experiments.• Workpackage 2: Differences in vertebral morphology from differing pathologies were acquired using microCT. Following on from this the relationship of morphology and bone mineral density to the structural properties were explored with differing behaviours noted between osteoporotic and metastatic bone. A detailed microhardness assessment of myeloma showed no difference to that observed in osteoporosis which suggests that the weakening of the vertebrae is through bone loss alone. • Workpackage 3: A new method for facet joint load measurement was established and was utilised in demonstrating that nucleotomy doubles the load transfer over the facet joints. Results of this vitro study were extended to other motions by means of newly established validated finite element model.• Workpackage 4: A novel bioreactor that can perform simultaneous bi-axial (torsion and compression) loading of intervertebral discs was designed and constructed, guided by simulations of disc mechanics. The degenerative response of the disc to impact loading was described for the first time. Simulations of disc impact and vibration have shown the non-linear dynamic response of the disc, with softening and hardening characteristics dependent on degeneration grade. The molecule EGCG has been shown to have a unique and substantial anti-inflammatory effect on the intervertebral disc. Dose-response studies and pathway analyses have paved the way for clinical translation.• Workpackage 5: A robust and well tested subject-specific morphing workflow was developed, which allowed non-linear scaling of anatomical components within the AnyBody Modeling System (AMS). New interfaces between both ANSYS and Abaqus and the AMS were developed and tested allowing greater potential for co-simulation. Significant developments were made in the AMS spine model with new approaches to modelling the disc, ligaments and facet joints incorporated and verified.• Workpackage 6: The role of the intervertebral disc on vertebral strength was ascertained. An interface between inverse dynamics of the spine and finite element analysis of the vertebral body was realized with the industrial partner AnyBody. Following on from this it was demonstrated that a significant correlation occurs between T2* MRI sequences and the biomechanical properties of degenerated human intervertebral discs which may be exploited clinically.• Workpackage 7: This WP was key to the development of alpha-TCP cements. In parallel, the mechanical response of vertebrae with comminuted fractures to complex loading conditions was simulated. The critical destabilising effect of the fracture planes, and the resulting tensile stresses within the cement, provide a key direction for the development of improved, high-strength cements. The deficiencies of international standards for the development of cements were highlighted.• Workpackage 8: 2-D and 3-D surrogate bone models were benchmarked and identified. A suitable 3D rapid manufacturing techniques for the development of surrogate bone models was finalised, with which models of differing defects could be built. Commercial cements from differing suppliers as well as in-house, experimental materials were assessed within the 2D models, and demonstrated significant differences in behaviour. Model behaviour was pathology specific as well as being dependent on the cement formulation. Discussions on the commercialisation of these models are ongoing.• Workpackage 9: Initial research garnered information on the importance and prevalence of pedicle screw loosening including results of a surgeon survey. Leading on from this work a new application for composite foam vertebrae was generated, which extends the accepted standard (ASTM 1717) to allow for quantification and comparison of fatigue loosening at the interface. Finally, results were reported on the testing of new screw prototypes in cadaveric specimens, composite foam and modeling these systems using the finite element method.Added benefit to Consortium Members has been considerable and include: 1) The FP7 NMP Integrated Project, LifeLongJoints (LLJ), (Grant Agreement Number 310477) worth €13.317 million (EC contribution), which comprises several partners from SpineFX (UNIVLEEDS [coordinator], TUHH, ABT and ETH-Zürich), was successfully negotiated in 2012 and started in April 2013. This programme of research builds on the networking and research undertaken through SpineFX, particularly the integration of different modelling approaches to predict outcomes. The LLJ Coordinator is the same as for SpineFX, i.e. Professor Richard M Hall;2) Co operation between TUHH and BS in which trauma surgeon Dr Jan Kolb and Prof. K. Püschel (University Hospital Hamburg Eppendorf (UKE)) have taken part in the study to examine BONESUPPORT’s resorbable bone cement CERAMENT™;3) Links to the EU-sponsored Virtual Physiological Human Osteoporosis (VPHOP) network through Professor Stephen J. Ferguson, scientist-in-charge at ETH-Zürich;4) Partnerships with two Computer Aided Engineering software companies (ANSYS and Simulia) have been formed by AnyBody Technology A/S and a technical partnership with Materialise whose Mimics software is used for subject-specific modelling (data interface to Mimics has been developed);5) Links between Uppsala University and UNIVLEEDS through a Reintegration Grant entitled ‘SpineGO’ (Grant Agreement Number 268134) - two manuscripts have been submitted for peer review arising from this collaboration;6) A UNIVLEEDS data research management project sponsored by JISC UK which used SPINEFX as a case study. A data management plan was formulated and implemented for the long-term storage of part of the data accrued within the SpineFX project; and,7) Partners are currently working on a further proposal for an ITN within Horizon 2020 to submit in 2014.Quotes from the SpineX fellowsWhat the Fellows said about the SpineFX Initial Training Network:“SpineFX was a great experience from scientific perspective and it was also exciting to be part of such a friendly but professional network. I believe that SpineFX network will stay everlastingly for me”."SpineFX not only provided me with an outstanding opportunity to try new ideas, but it also offered all the benefits of working in a network and to get a broad state of the art knowledge on various topics by meeting experts"."this [SpineFX] provided great opportunities to share and discuss experiences, knowledge and ideas related to our common interests: a life-long implant"."the SpineFX research network helped me to start and pursue the PhD degree at one of the most renowned universities in Europe".“My current position is an excellent continuation from my previous placement within SpineFX and I am very thankful to SpineFX for giving me this unique life-changing opportunity.”"Besides my personal research, I particularly enjoyed all the trainings that SpineFX organized which enabled me get in contact with the other Fellows and enrich my research views. Two years after joining SpineFX, I have no doubt saying that this project gave me the opportunity to mature both professionally and personally in ways I would have never expected".“SpineFX was incredibly beneficial for me in terms of career and personal development. I have had the privilege of being able to establish direct collaborations with six medical institutes, international universities, and four companies. Importantly, I have been able to develop scientific, leadership, and teamwork skills by being given the freedom to supervise six students and work with four surgeons and an experienced researcher in a medical device company on specific scientific projects".“As my objective was mainly to collaborate with Europe’s most outstanding experts, the prestigious Marie Curie SpineFX grant was a precious opportunity for me”.
