Lower back pain (LBP) is the largest cause of morbidity worldwide, yet there remains controversy as to the specific cause leading to poor treatment options and prognosis. Intervertebral disc degeneration (LDD) is reported to account for 50% of LBP in young adults, but the interplay of factors such as genetics, environmental, cellular responses, social and psychological is poorly understood. Unfortunately, the integration of such data into a holistic and rational map of degenerative processes and risk factors has not been achieved, requiring the creation of professional cross-competencies, which current training programmes in biomedicine, biomedical engineering and translational medicine fail to address, individually.

Disc4All aims to tackle this issue through collaborative expertise of clinicians; computational physicists and biologists; geneticists; computer scientists; cell and molecular biologists; microbiologists; bioinformaticians; and industrial partners. It provides interdisciplinary training in data curation and integration; experimental and theoretical/computational modelling; computer algorithm development; tool generation; and model and simulation platforms to transparently integrate primary data for enhanced clinical interpretations through models and simulations. Complementary training is offered in dissemination; project management; responsible research and innovation; ethics; regulation; policy; business strategy; public and patient engagement. Disc4All will train a new generation of internationally mobile professionals with unique skill sets for the development of thriving careers in translational research applied to multifactorial disorders.

Position 1:

Topic: Multiscale modelling of IVD cell activity & potential tissue turnover

Description: The successful candidate will work on the multiscale modelling of the mechanisms of intervertebral disc regulation. Specifically, the work will target the modelling and simulation of bottomup processes of tissue regulation, through which the dynamics of cell activity contributes to disc tissue turnover in specific regions of interest, in response to multifactorial cell stimulations. Different types of intervertebral disc network models will be used and combined to successively incorporate cell culture experimental data, proteomics measurements and eventually gene variant effects. Interplays of biochemical, mechanical and nutritional cell stimulation will be modelled in representative volume elements through agent-based modelling. Eventually, collective cell activity will be linked with heterogeneous cell environments predictable through finite element simulations of disc tissue and organ multiphysics.

Supervision: Jérôme Noailly (UPF)

More information:

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Position 2:

Topic: Bottom-up simulations of spatio-temporal degenerative events in the IVD & biological LDD stratification

Description: The successful candidate will work on the systematization of multiscale modelling of the intervertebral disc regulation for improved LDD stratification. Existing regulatory network and multiphysics models, at the molecular/cell and tissue/organ scales will be locally integrated in relevant regions of interest of the IVD. Such integration will be coupled with different disc model morphologies and molecular signature inputs, from the Twins UK and Northern Finland Birth cohorts. A smart atlas of simulated data will be generated, to eventually enable efficient calculations through metamodeling. Metamodeling will further allow the mining of simulated and real word data altogether, to establish different fingerprints of LDD and the spatio-temporal evolution thereof, characterised by specific hierarchies of risk factors and exploitable clinically.

Supervision: Jérôme Noailly (UPF)

More information:

Do you want to be part of a globally leading research network comprising institutions across Europe? Would you like to learn new skills in medical engineering with a focus on implant design and biotribology? Could you be a future research leader in providing solutions to some of Europe’s most pressing healthcare problems? Do you want to further your career and attain a PhD at one of the UK’s leading research intensive universities? To complete one of these exciting projects you will be based in the Institute of Functional Surfaces and have access to world leading equipment including advanced simulators and other devices for both the tribological / corrosion testing of implants and the characterisation of the surfaces both coated and uncoated.  You will join a recently funded European Training Network (ETN) BioTrib (project ID 956004, call H2020-MSCA-ITN-2020). BioTrib offers high-level doctoral training to a total of 15 Early Stage Researchers (ESRs) of which 3 will be employed at the University of Leeds. The project lead is Prof Richard M Hall at the University of Leeds.  This projects will be supervised by Prof Richard M Hall and Dr Michael Bryant.

Important eligibility rules for this position:

There are no restrictions on the nationality, but applicants must, at the time of recruitment,

(1) have not yet been awarded a doctorate degree and be in the first 4 years (full-time equivalent) of their research careers. This is measured from the date that you obtained the degree which would entitle you to embark on a PhD.

(2) At the time of recruitment, applicants must not have resided or carried out their main activity (work, studies, etc…) in the UK for more than 12 months in the 3 years immediately prior to their recruitment under the BioTrib project. Compulsory national service and/or short stays such as holidays are not taken into account.

Salary:

The Marie Skłodowska-Curie Early Stage Researcher living allowance is fixed at €62,057 per annum including the mobility allowance. This figure is before employer’s and employee’s deductions for national insurance and taxes per year, which will be paid in Sterling using an appropriate conversion rate.

Further details on each of these posts please refer to the applications website for the background, job description and person specification.

http://jobs.leeds.ac.uk/epsme1033

http://jobs.leeds.ac.uk/epsme1034

http://jobs.leeds.ac.uk/epsme1035

To explore the posts further or for any queries you may have, please contact:

Prof Richard M Hall, School of Mechanical Engineering

Email: r.m.hall@leeds.ac.uk

Background and scope of the work

Angiogenesis, the growth of new blood vessels from pre-existing vessels, constitutes a fundamental physiological process during the regeneration of many tissues, including bone. In a DFG-funded collaborative project, we are using a combined experimental/computational approach to investigate how mechanical forces mediate angiogenesis during bone repair. As part of this project, a PhD position is available to investigate the role of mechanical strains on the growth of new blood vessels using mechano-biological computational models.  

Tasks

You will develop computer models of sprouting angiogenesis taking into account the role played by chemical and mechanical signals in vessel patterning. You will work in close collaboration with project partners working in in vitro and in vivo models to inform and validate the computer models.

Your profile

• Master Degree in Mechanical Engineering, Computational Biomechanics, Computational Biology or a related discipline
• Strong programming skills
• Knowledge of finite element analysis
• High motivation, curiosity and commitment to scientific excellence
• Team player skills and enthusiasm to work in a multi-disciplinary, collaborative environment
• Excellent command in written and spoken English
• Independent and responsible attitude, collaborative spirit

What we provide

This position is available for a period of three years with the possibility to be extended if new funding is available. You will work in a friendly team and in a unique research environment. As a PhD student, you will be associated to the Berlin-Brandenburg School of Regenerative Therapies (www.bsrt.de) and benefit from the interaction with international scientists.

Starting date: as soon as possible.

Contact:

If you are interested, please send your CV, motivation letter and two references to: Prof. Sara Checa (sara.checa@charite.de)

We are looking for a PhD student to explore the potential of Neutron scattering for studying soft musculoskeletal tissues and their structural and mechanical changes due to osteoarthritis. The student will be supervised by Prof Hanna Isaksson and Prof Martin Englund and be part of SwedNESS – the Swedish national graduate school for neutron research. 

More information can be found here:
https://lu.varbi.com/en/what:job/jobID:360505/type:job/where:4/apply:1

GENERAL INFORMATION

About this doctorate program

This PhD program has a duration of 3 years. The Doctorate in Health and Technology is an interdisciplinary program, where each PhD student has a supervisor from the technical area (engineering, chemistry etc) and one from the clinical or biological area.

https://www.unibo.it/en/teaching/phd/2020-2021/health-and-technologies

The objective of the interdepartmental Doctoral Programme in Health Sciences and Technologies is to train the next generation of leaders in industrial, clinical, and academic research. Our goal is to develop an organic research programme at the interface between engineering and medicine, which is inspired by the quantitative and integrative approach of physical sciences, and by the latest development in biomedical research, drive the development and clinical translation of disruptive health technologies.

The doctoral training programme will prepare students in conducting research which:

– Extend the comprehension of how human physiology and pathology work in term of physical and chemical mechanisms, and how these mechanisms respond when perturbed by external factors such as therapies, changes in life style, and environmental factors.

– Develop new technologies that by leveraging on this mechanistic understanding pursue a wide spectrum of applications relevant to human health, including prevention, diagnosis, prognosis, treatment, and rehabilitation.

How to apply:

Formal application must be submitted through the UniBo portal:

https://www.unibo.it/en/teaching/phd/information-enrolling-phd-programme/how-to-apply-phd-programme

Each student, depending on their degree, will be able to apply only for a sub-set of projects among those advertised for this PhD program; among them each student will be allowed to select three projects, and name them in order of preference; however, in some cases it might not be possible to satisfy all requests, and some students might be offered a research project different from those they selected.

The full call is available online:

https://www.unibo.it/en/teaching/phd/2020-2021/attachments/cycle-36-call-for-applications/@@download/file/36thCycle_CallForApplications_Def_Web.pdf

Profile of the candidate

We are looking for a highly motivated young researchers with a Master degree (or equivalent) in Mechanical Engineering, Biomedical Engineering, Physics, Material Science, or related disciplines, willing to study and do research at the leading edge of biomechanical engineering, in close contact with a clinical environment.

Individuals expecting to obtain their Master degree before 31 October 2020 can conditionally apply. In order to be admitted to the selection, a student needs a five-year higher education degree, which includes at least one module for each of the following disciplines: mathematics, physics, computer science, biology, physiology, and anatomy.

Candidates must be fluent in English as it will be the language used to interact with supervisors and colleagues during the project, and to interact with partners. Although some understanding of Italian may be useful for daily living, this is not a mandatory requirement. Communication and team-working skills are required in our international team.

Deadline:

Applications must be submitted through the Unibo portal by 21 May 2020, 13:00 Italian time (UTC +1)

Selection procedure: selection takes place in two phases. First the documents submitted by the applicants are examined, with no interaction with the candidates (early June). The eligible applications are shortlisted and the candidates are informed. In the second stage, the shortlisted candidates are interviewed. All interviews are performed remotely, in videoconference (mid-June).

Salary: 19 367 € per year before taxes.

More information: Perspective applicants are encouraged to contact Professor Luca Cristofolini

luca.cristofolini@unibo.it for informal discussion about the research projects.

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PhD PROJECT #1:

Biomechanical evaluation of knee mechanical behaviour and interface stresses with a new concept of alignment for total knee arthroplasty (NEW-KNEE)

Summary

At least one knee replacement out of 5 are dissatisfactory due to continuous pain. This is mainly related to inadequate joint kinematics with the current paradigm for prosthesis alignment, causing painful patellar motions and poor balance of soft tissue. Recently, a different rationale has been proposed based on kinematical alignment (KA). This PhD student will work under the joint supervision of an orthopaedic surgeon focusing on knee replacement, and of two engineers with a background in biomechanical in vitro testing, and numerical modelling respectively. During these three years, the PhD student will develop a numerical to estimate how the knee joint loads are affected by implant positioning, and a series of in vitro tests to measure how this affects the implant-bone interaction.

Objectives of this project

The overall objective of this PhD project is to evaluate in vitro the biomechanical effectiveness of the kinematical alignment (KA) method for total knee arthroplasty (TKA).

The following specific objectives will be tackled:

• How the stresses at bone-prosthesis interface change with the KA alignment respect traditional mechanical alignment (MA)

• How bone stresses propagate in the distal femur and proximal tibia during specific motor tasks

• How the KA alignment interferes with the kinematics of the knee and if there is a threshold of safety in degrees from a mechanical neutral axis

• if KA alignment requires a specific prosthetic design (from the already present on the market) to be successful

This project covers some basic science (improving the understanding of knee biomechanics), it focuses on technological development (implementing a modeling strategy for the human knee) and has clinical relevance (improving the outcome of knee replacement).

The research team

This candidate will have an engineering background. While this will facilitate him/her in grasping the technical part of the project, some time and effort must be dedicated at the beginning to improve his/her understanding of the clinical problem. This project is rooted between three groups:

– The group of Prof. Cristofolini (Department of Industrial Engineering) will provide “training through research” in the area of biomechanics and material characterization. Prof. Marco Viceconti will be the supervisor for all computational aspects.

– The group of Prof Traina will provide training and supervision on the surgical procedures for tendon and ligament repair, on complications, and will supervise the design of the implantation technique.

Prof. Traina and prof. Cristofolini have been intensively collaborating for over 15 years on research projects at the intersection between orthopaedic clinical application and biomechanics research, and specifically on total joint replacement. A strong integration of the two research groups has been achieved by involving the clinical staff in lab activity, and the lab staff in clinical research. This PhD candidate will enjoy this extremely stimulating interdisciplinary environment, and will share his/her research time between clinics (in tight collaboration with Rizzoli Orthopaedic Institute) and biomechanics lab.

The Department of Industrial Engineering includes a large Biomechanics lab that is extremely active in the field of orthopaedic biomechanics. The focus of the biomechanics group directed by prof. Cristofolini within DIN is on the multi-scale biomechanical characterization of skeletal structures and orthopaedic devices, and on the integration of in vitro tests and numerical modeling. Their group, in collaboration with the Electrospinning group, recently developed and characterized innovative regenerative scaffolds. Furthermore, this group is acknowledged internationally for the applications of DIC to biomechanics.

The Dept. of hip and knee primary and revisions prosthetic surgery of Rizzoli Orthopaedic Institute is nationally recognized for the treatment of severe hip and knee conditions primarily through joint replacements. Its activity is mainly focused on surgical treatment of complex cases, analysis and data collection of multiple type of joint replacement surgery through different surgical approach and procedures. Comparison between different procedures and cases are routinely performed in order to continuously improve the patient’s provision of care and to develop innovative implant design and surgical tools The Labs of the Department of Industrial Engineering are equipped with the testing facilities required for this project, including:

– Approved procedures and dedicated space and facilities for safe storage, preparation, testing and disposal of biological tissue specimens (both human and animal)

– Five universal testing machines

– A proprietary multiaxial simulator for biomechanical testing

– State-of-the-art digital image correlation (DIC) system (4-camera system, up to 100 frames per second).

– Access to the In Silico Medicine group computational infrastructure, including high-level workstations, secure storage for clinical data within IOR network, and to a collection of specialised software tools for musculoskeletal dynamics modelling.

Specific skills useful for this PhD project

The following skills will be considered during the selection: good laboratory practice; mechanical testing and experimental stress analysis; handling and testing of biological tissue; orthopaedic biomechanics; mechanical properties of living tissues; Bone biomechanics; Soft tissue mechanics; Prosthetics; in vitro biomechanical testing; experimental stress analysis (digital image correlation); statistics and design of the experiment.

References

1. Howell SM, Kuznik K, Hull ML, Siston RA. Results of an initial experience with custom-fit positioning total knee arthroplasty in a series of 48 patients. Orthopedics. 2008;31:857–863.

2. Abdel MP, Ollivier M, Parratte S, Trousdale RT, Berry DJ, Pagnano MW. Effect of Postoperative Mechanical Axis Alignment on Survival and Functional Outcomes of Modern Total Knee Arthroplasties with Cement: A Concise Follow-up at 20 Years. J Bone Joint Surg Am. 2018 Mar 21;100(6):472-478.

3. Eckhoff DG, Bach JM, Spitzer VM, Reinig KD, Bagur MM, Baldini TH, Flannery NM. Three-dimensional mechanics, kinematics, and morphology of the knee viewed in virtual reality. J Bone Joint Surg Am. 2005;87 Suppl 2:71-80.

4. Castagnini F, Sudanese A, Bordini B, Tassinari E, Stea S, Toni A. Total Knee Replacement in Young Patients: Survival and Causes of Revision in a Registry Population. J Arthroplasty. 2017 Nov;32(11):3368-3372.

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PhD PROJECT #2:

Understanding the causes of junctional failure in lumbar spine fixation through retrospective clinical analysis and in vitro tests

Summary

Fixation of the lumbar spine is associated with a high failure rate, both in young and in elderly patients. This project is expected to improve the general understanding of spinal biomechanics, the effect of different treatment options, including the detrimental effect of some surgical treatments. The main focus will be on the failure of the disc caudal to the fixation (junctional pathology).

This project will start from a retrospective analysis of clinical cases available within the Rizzoli database. The focus will be on the determinants for failure after corrective spinal surgery, including both patient-specific ones (anatomical, radiographical, etc.) and surgical ones (type of correction used).

On the experimental side, we will apply digital image correlation (DIC, a powerful experimental technique to measure deformations during in vitro mechanical tests) to analyze functional spinal units (FSU) and multivertebrae segments. DIC allows investigating both hard and soft tissue at the same time, providing a full-field view of the spine specimen. The focus will be on the biomechanical condition of the intervertebral discs after a range of spine surgery procedures.

Objectives of this project

The purpose of this 3-years project is to improve the understanding about the mechanism leading to failure after fixation of the lumbar region of the spine, with a main focus on the instability associated with failure of the caudal disc (junctional pathology) [1. 2]. While the incidence and consequences of such failures are known, the biomechanical causes are still unclear. In fact, different approaches have been proposed to mitigate this problem, with limited success. One causes of failure for such attempts has been the lack of interdisciplinarity: the surgical technique and instrumentation has been modified, without a strong biomechanical background.

This PhD candidate will integrate his/her clinical background, with dedicated training in biomechanics. He/she will apply in vitro tests to analyze functional spinal units and multi-vertebrae segments. This will provide asystematic quantitative assessment of the determinants of fixation failures. This approach will also enable improving the understanding of the biomechanics of the intervertebral discs and ligaments after different procedures such as facetectomy, instrumentation, etc.

The research team

This candidate will have an engineering background. While this will facilitate him/her in grasping the technical part of the project, some time and effort must be dedicated at the beginning to improve his/her understanding of the clinical problem. This project is rooted between three groups:

– The group of Prof. Cristofolini (Department of Industrial Engineering) will provide “training through research” in the area of biomechanics and material characterization.

– The group of Dr Giovanni Barbanti-Bròdano will provide training and supervision on the surgical procedures for spinal correction, and about the most critical complications.

Dr Barbanti-Bròdano and prof. Cristofolini have been intensively collaborating in the last 5 years on research projects at the intersection between orthopaedic clinical application and biomechanics research, and specifically on spine pathologies. A strong integration of the two research groups has been achieved by involving the clinical staff in lab activity, and the lab staff in clinical research. This PhD candidate will enjoy this extremely stimulating interdisciplinary environment, and will share his/her research time between clinics (in tight collaboration with Rizzoli Orthopaedic Institute) and biomechanics lab.

The Department of Industrial Engineering includes a large Biomechanics lab that is extremely active in the field of orthopaedic biomechanics. The focus of the biomechanics group directed by prof. Cristofolini within

DIN is on the multi-scale biomechanical characterization of skeletal structures and orthopaedic devices, and on the integration of in vitro tests and numerical modeling. Since the beginning (nineties), the focus of this group has been on joint replacement, and in the last decade the group has also been active in the spine area (basic science, osteoporotic fractures, vertebroplasty, fixation). Furthermore, this group is acknowledged internationally for the applications of DIC to biomechanics.

The Complex Structure of Spine Surgery prevalently Oncologic and Degenerative, operating at the Rizzoli Orthopaedic Institute, is a division dedicated to the diagnosis and the treatment of rachis pathologies of oncologic, degenerative and post-traumatic origin. The clinical activity concerns the field of spinal column pathologies: primary and secondary tumors of the mobile rachis and the sacrum, hematopoietic tumors with vertebral localization; degenerative discopathy of the lumbo-sacral rachis, herniated lumbar disc, spondylolisthesis, thoracic-lumbar stenosis, herniated thoracic-rachis disc, pathologies of the cervical rachis; Deformities in adults; Traumatic fractures and insufficiency fractures (osteoporosis). This Complex Structure is the reference center for AOSpine International, a scientific association of vertebral surgeons gathering over 40.000 members worldwide, and favorite destination for all-around specialists for the study and in-depth analysis of the surgical techniquesapplied. The Division participates to the international multicenter Registry for the collection of data on primary tumors of the spinal column (PTRON) and to the international multicenter Registry for the collection of data on metastatic tumors of the spinal column (MTRON), both promoted by the international scientific Association AOSpine Foundation; to the international database for spinal column pathologies “SpineTango”, promoted by the International Association EuroSpine; to the international multicenter study promoted by the Italian Sarcoma Group on the comparison between surgical and radiotherapy treatment of the sacrum chordoma.

The Labs of the Department of Industrial Engineering are equipped with the testing facilities required for this project, including:

– Approved procedures and dedicated space and facilities for safe storage, preparation, testing and disposal of biological tissue specimens (both human and animal)

– Five universal testing machines

– A proprietary multiaxial simulator for biomechanical testing

– Top-of-the-range digital image correlation (DIC) system (4-camera system, up to 100 frames per second). Specific skills useful for this PhD project

The following skills will be considered during the selection: good laboratory practice; mechanical testing and experimental stress analysis; handling and testing of biological tissue; orthopaedic biomechanics; mechanical properties of living tissues; bone biomechanics; soft tissue mechanics; spine biomechanics; in vitro biomechanical testing; experimental stress analysis (digital image correlation); statistics and design of the experiment.

References:

1. Lee, G. A., Betz, R. R., Clements, D. H. & Huss, G. K. Proximal kyphosis after posterior spinal fusion in patients with idiopathic scoliosis. Spine 24, 795–799 (1999).

2. Park et Al. (Spine 29, 17, 2004).

3. Lau, D. et al. Junctional kyphosis and failure after spinal deformity surgery: a systematic review of the literature as a background to classification development. Spine 39, 2093–2102 (2014).

4. Smith, M. W., Annis, P., Lawrence, B. D., Daubs, M. D. & Brodke, D. S. Acute proximal junctional failure in patients with preoperative sagittal imbalance. Spine J. Off. J. North Am. Spine Soc. 15, 2142–2148 (2015).

5. Colangeli S, Barbanti Brodàno G, Gasbarrini A, Bandiera S, Mesfin A, Griffoni C, Boriani S. Polyetheretherketone (PEEK) rods: short-term results in lumbar spine degenerative disease. J Neurosurg Sci. 2015 Jun;59(2):91-6.

6. Yagi, M. et al. Characterization and surgical outcomes of proximal junctional failure in surgically treated patients with adult spinal deformity. Spine 39, E607-614 (2014).

7. Pipola V, Gasbarrini A, Girolami M, Griffoni C, Zaccaro R, Barbanti Bròdano G. Isthmic spondylolisthesis and interspinous process device. Hype, hope, or contraindication? Eur Rev Med Pharmacol Sci. 2019: 2340-44.

8. Barbanti Bròdano G, Lolli F, Martikos K, Gasbarrini A, Bandiera S, Greggi T, Parisini P, Boriani S. Fueling the debate: Are outcomes better after posterior lumbar interbody fusion (PLIF) or after posterolateral fusion (PLF) in adult patients with low-grade adult isthmic spondylolisthesis? Evid Based Spine Care J. 2010 1(1):29-34.

9. Palanca, Ruspi, Cristofolini (2018) “Full-field strain distribution in multivertebra spine segments: An in vitro application of Digital Image Correlation” Medical Engineering & Physics 52: 76-83

10. Palanca, M., Ruspi, M.L., Cristofolini, L., Liebsch, C., Villa, T., Brayda-Bruno, M., Galbusera Fabio, Wilke, H.-J., La Barbera, L., (2020). The strain distribution in the lumbar anterior longitudinal ligament is affected by the loading condition and bony features: an in vitro full-field analysis. PLOS ONE. https://doi.org/10.1371/journal.pone.0227210