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Introduction

MultiSim has integrated the ongoing musculoskeletal research within the University of 91̽�� into the grand vision of the grant. This has resulted in the development of models at all scales and integration into a multi-scale platform, with three application workflows:

1. A workflow for the prediction of femoral fractures in osteoporotic patients. We have been able to show that patient-specific predictions of the risk of fracture in post-menopausal woman were more accurate with computer simulations than current clinical standard.
2. The development of computational tools for children musculoskeletal diseases such as the diagnosis of unexplained fractures in the child.
3. The development of a murine platform for the complete study of multiscale modelling and the possibility to validate the tools developed at each scale and their integration from the cell to the organ levels.

A general hypermodelling framework concept was constructed to enable multiscale modelling across space and time by defining inputs and outputs between scales within each application.

In addition, a general IT infrastructure is being developed to provide successful applications as an online service to external users by establishing a workflow of software applications using Taverna.

Download Multiscale Challenge diagram (PDF, 447KB). MultiSim's multiscale challenge: The workflow applications are linked to model scales that they depend on. The scales are: environment, population, body, organ, tissue, cell, molecular.

• The hypermodel links all the scales.
• Application 1, Prediction of osteoporotic fractures links population, body, organ and tissue scales.
• Application 2, Diagnosis of unexplained fractures in the child links body, organ and tissue scales.
• Application 3, murine model, links organ, tissue, cell and molecule scales.

The revised work package diagram (PDF,136 KB) shows how the original MultiSim work packages feed into the application workflows developed.

Application 1 Prediction of Osteoporotic Fractures and Application 3 Murine Model, have subsequently been developed into mature workflows illustrated in the two videos below.

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Application 1 workflow: Prediction of osteoporotic fracture

The video below shows how movement data and image data from image data from MRI and CT scans are be combined to develop musculoskeletal kinematic models and finite element models to predict the risk of fracture.

The Clinical workflow document (PDF, 782KB) provides a summary of the workflow and team that are developing it.

Publications related to Application 1

2023

Altai, Z., Montefiorie, E., Li, X. (2023), "", In: Heifetz, A. (eds) High Performance Computing for Drug Discovery and Biomedicine. Methods in Molecular Biology, Vol 2716. Humana, New York, NY. 

Henson, W. H., Mazzà, C., Dall'Ara, E. (2023), "", PLoS One, 18(3): e0273446.  

2022

Aldieri, A., Terzini, M., Audenino, A. L., Bignardi, C., Paggiosi, M., Eastell, R., Viceconti, M., Bhattacharya, P. (2022), "", Annals of Biomedical Engineering.

Benemerito, I., Montefiori, E., Marzo, A., Mazzà, C. (2022), "", Applied Sciences, 12(24), 12932. 

Montefiori, E., Hayford, C. F., Mazzà, C. (2022), "", Journal of Biomechanics, 136, 111072.

2021

Altai, Z., Montefiori, E., van Veen, B., Paggiosi, M. A., McCloskey, E. V., Viceconti, M., Mazzà, C., Li, X. (2021), “”, PLoS ONE, 16(2): e0245121.

Benemerito, I., Griffiths, W., Allsopp, J., Furnass, W., Bhattacharya, P., Marzo, A., Wood., S., Viceconti, M., Narracott, A. (2021), "", Computer Methods and Programs in Biomedicine, 208, 106200.

Bhattacharya, P., Li, Q., Lacroix, D., Kadirkamanathan, V., Viceconti, M. (2021), "", PLoS One, 16(5): e0251297. 

Conconi, M., Montefiori, E., Sancisi, N., Mazzà, C. (2021), "", Applied Sciences, 11(18), 8348. 

Martelli, S., Giorgi, M., Dall’Ara, E., Perilli, E (2021), “”, Acta Biomaterialia.

Montefiori, E., Hayford, C. F., Mazzà, C. (Preprint), "", Available at Social Science Research Network (SSRN).

Taylor, M., Viceconti, M., Bhattacharya, P., Xinshan, L. (2021), "", Journal of the Mechanical Behavior of Biomedical Materials, 118, 104434.

van Gelder, L., M., A., Angelini, L., Buckley, E., E., Mazzà, C.  (2021), "", Symmetry, 13(9), 1560.

2020

Altai, Z., Viceconti, M., Li, X., Offiah, A. C. (2020), “”, Clinical Radiology, 75 (1), 78.e9-78.e16. 

Benemerito, I., Modenese, L., Montefiori, E., Mazzà, C., Viceconti, M., Lacroix, D., Guo, L. (2020), “”, Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine. .   

Montefiori, E., Kalkman, B. M., Henson, W. H., Paggiosi, M. A., McCloskey, E. V., Mazzà, C. (2020), “”, PLoS ONE.

Ryan, M., Barnett, L., Rochester, J., Wilkinson, J. M., Dall’Ara, E. (2020), “”, Scientific Reports, 10, Article number: 5538.

Ryan, M., Oliviero, S., Costa, M. C., Wilkinson, J. M., Dall’Ara, E. (2020), “”, Materials, 13(20), 4619.

van Veen, B. C., Mazzà, C., Viceconti, M. (2020), “”, IEEE Transactions on Neural Systems & Rehabilitation Engineering, 28 (8).

Wang, N., Niger, C., Li, N., Richards, G. O., Skerry, T. M. (2020), “”, Frontiers in Endocrinology, 11, p 693.

Winsor, C., Li, X., Qasim, M., Henak, C. R., Pickhardt, P. J., Ploeg, H., Viceconti, M. (2020), “”, Bone, 115759.

Yang, W., Lacroix, D., Tan, L. P., Chen, J. (2021), “”, Journal of Materials Research.

2019

Altai, Z., Qasim, M., Li, X., Viceconti, M. (2019), “”, Clinical Biomechanics, 68, pp 137-143.

Montefiori, E., Modenese, L., Di Marco, R., Magni-Manzoni, S., Malattia, C., Petrarca, M., Ronchetti, A., de Horatio, L. T., van Dijkhuizen, P., Wang, A., Wesarg, S., Viceconti, M., Mazzà, C.; MD-PAEDIGREE Consortium (2019), “”, Journal of Biomechanics, 85, pp 27-36.

Montefiori, E., Modenese, L., Di Marco, R., Magi-Manzoni, S., Malattia, C., Petrarca, M., Ronchetti, A., Tanturri de Horatio, L., van Dijkhuizen, P., Wang, A., Wesarg, S., Viceconti, M., Mazzà, C. for the MD-PAEDIGREE Consortium (2019), “”, Annals of Biomedical Engineering, 47 (11), pp 2155-2167.

van Veen, B. C., Montefiori, E., Modenese, L., Mazzà, C., Viceconti, M. (2019), “”, Journal of Biomechanics, 97, 109368.

Viceconti, M., Ascani, D., Mazzà, C. (2019), “”, Journal of Orthopaedic Research.

2018

Bhattacharya, P., Altai, Z., Qasim, M., Viceconti, M. (2018), “”, Biomechanics and Modeling in Mechanobiology, 18 (2), pp 301-318.

Di Marco, R., Scalona, E., Pacilli, A., Cappa, P., Mazzà, C., Rossi, S. (2018), “”, International Biomechanics, 5 (1), pp 1‑8.

Modenese, L., Montefiori, E., Wang, A., Wesarg, S., Viceconti, M., Mazzà, C. (2018), “”, Journal of Biomechanics, 16 (3), pp 216-223.

Shahabpoor, E., Pavic, A. (2018), “”, Journal of Biomechanics.

Shahapoor, E., Pavic, A., Brownjohn, J. M. W., Billings, S. A., Guo, L., Bocian, M. (Published), “”, IEEE Transactions on Neural Systems and Rehabilitation Engineering, 26 (6).

Tagliapietra, L., Modenese, L., Reggiani, M., Ceseracciu, E., Mazzà, C. (2018), “”, Computer Methods in Biomechanics and Biomedical Engineering.

Tamburini, P., Storm, F., Buckley, C., Bisi, M. C., Stagni, R., Mazzà, C (2018), “”, Gait and Posture, 59, pp 248-252.

Viceconti, M., Qasim, M., Bhattacharya, P., Li. X. (2018), “”, Current Osteoporosis Reports.

2017

Dall’Ara, E., Eastell, R., Viceconti, M., Pahr, D., Yang, L. (2016), “”, Journal of the Mechanical Behavior of Biomedical Materials, 63, pp 17-25.

Guo, Y., Storm, F., Zhao, Y., Billings, S. A., Pavic, A., Mazzà, C., Guo, L. (2017), “”, Sensors, 17 (10), pp 2181-2195.

Hannah I., Montefiori E., Modenese L., Prinold, J., Viceconti M., Mazzà C. (2017), “”, Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 231 (5), pp415-422.

Moissenet, F., Modenese, L., Dumas, R. (2017), “”, Journal of Biomechanics, 63, pp 8-20.

Shahabpoor, E., Pavic, A. (2017), “”, Sensors, 17 (9), 2085.

2016

Hannah, I., Sawacha, Z., Guiotto, A., Mazzà, C. (2016), “”, International Biomechanics, 3 (1), pp 50-56.

Lamberto, G., Martelli, S., Cappozzo, A., Mazzà, C. (2016), “”, Journal of Biomechanics, Available online 24 August 2016.

Qasim, M., Farinella, G., Zhang, J., Li, X., Yang, L., Eastell, R., Viceconti, M. (2016), “”, Osteoporosis International, 27 (9), pp 2815-2822.

Storm, F., Buckley, C., Mazzà, C. (2016), “”, Gait and Posture, 50, pp 42-46.

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Application 3 workflow: Murine model

The video below shows how the murine models developed in MultiSim can be used to improve the current preclinical assessment of new interventions through better experiments, better endpoints and validated multiscale models.

The Pre-clinical workflow document (PDF, 445KB) below provides a summary of the workflow and team that are developing it.

Publications related to Application 3

2023

Karali, A., Dall'Ara, E., Zekonyte, J., Kao, A. P., Blunn, G., Tozzi, G. (2023), "", Journal of the Mechanical Behavior of Biomedical Materials, 138, 105636.

Oliviero, S., Millard, E., Chen, Z., Rayson, A., Roberts, B. C., Ismail, H. M. S., Bellantuono, I., Dall'Ara, E. (2023), "", Frontiers in Endocrinology, 13, 1016321.

2022

Dall'Ara, E., Bodely, A. J., Isaksson, H., Tozzi, G. (2022), "", Journal of the Mechanical Behavior of Biomedical Materials, 133, 105297.

Dall'Ara, E., Tozzi, G. (2022), "", Frontiers in Bioengineering and Biotechnology, 10, 1010056. 

Oliviero, S., Cheong, V. S., Roberts, B. C., Diaz, C. A. O., Griffiths, W., Bellantuono, I., Dall'Ara, E. (2022), "", Frontiers in Endocrinology, 13, 915938.

2021

Cheong, V. S., Kadirkamanathan, V., Dall'Ara, E. (2021), "", Frontiers in Bioengineering and Biotechnology, 9, pp 461.

Cheong, V. S., Roberts, B. C., Kadirkamanathan, V., Dall'Ara, E. (2021), "", Acta Biomaterialia, 136, pp 291-305.

Oliviero, S., Owen, R., Reilly, G. C., Bellantuono, I., Dall’Ara, E. (2021), “”, Journal of the Mechanical Behavior of Biomedical Materials, 113 (104190).

Oliviero, S., Roberts, M., Owen, R., Reilly, G. C., Bellantuono, I., Dall’Ara, E. (2021), “”, Biomechanics and Modelling in Mechanobiology.

2020

Ascolani, G., Skerry, T. M., Lacroix, D., Dal’Ara, E., Shuaib, A. (2020), “”, Interface Focus, 11(1): 20190136.

Ascolani, G., Skerry, T. M., Lacroix, D., Dal’Ara, E., Shuaib, A. (2020), “”, BMC Bioinformatics, 21 (114). 

Cheong, V. S., Roberts, B. C., Kadirkamanathan, V., Dall’Ara, E. (2020), “”, Acta Biomaterialia, 116, pp 302-317.

Costa, M. C., Bresani Campello, L. B., Ryan, M., Rochester, J., Viceconti, M., Dall’Ara, D. (2020), “”, Bone Reports, 12, 100257. 

Kusins, J., Knowles, N., Columbus, M., Oliviero, S., Dall’Ara, E., Athwal, G. S., Ferreira, L. M. (2020), “”, Annals of Biomedical Engineering.

Rakowski, A. G., Veličković P., Dall’Ara E., Liò P. (2020), “”, PLoS ONE, 15 (2), e0228962. 

Roberts, B. C., Arrendondo Carrera, H. M., Zanjani-pour, S., Boudiff, M., Wang, N., Gartland, A., Dall’Ara, E. (2020), “”, Scientific Reports, 10, Article number: 8889.

Zanjani-Pour, S., Giorgi, M., Dall’Ara, E. (2020), “”, Frontiers in Bioengineering and Biotechnology, 8: 558815.

2019

Cheong, V. S., Campos Marin, A., Lacroix, D., Dall’Ara, E. (2019), “”, Biomechanics and Modeling in Mechanobiology.

Giorgi, M., Sotirou, V., Franchini, N., Conigliaro, S., Biganardi, C., Nowlan, N. C., Dall’Ara, E., (2019), “”, PLoS One, 14 (1): e0197947.

Oliviero, S., Giorgi, M., Laud, P. J., Dall’Ara, E. (2019), “”, PLoS One, 14 (11): e0225127. 

Roberts, B. C., Giorgi, M., Oliviero, S., Wang, N., Boudiffa, M., Dall’Ara, E. (2019), “”, Bone, 127, pp 260-270.

Shuaib, A., Motan, D., Bhattacharya, P., McNabb, A., Skerry, T. M., Lacroix, D. (2019), “”, Scientific Reports, 9, Article number: 13113.

Zhang, Y., Dall’Ara, E., Viceconti, M., Kadirkamanathan, V. (2019), “”, PLoS One, 14(7): e0219404.

2018

Oliviero, S., Giorgi, M., Dall’Ara, E. (2018), “”, Journal of the Mechanical Behavior of Biomedical Materials, 86, pp 172–184.

2017

Dall’Ara, E., Peña-Fernández, M., Palanca, M., Giorgi, M., Cristofolini, L., Tozzi, G. (2017), “”, Frontiers in Materials: Mechanics of Materials, 4, Article 31.

Oliviero, S., Y., Lu, Y., Viceconti, M., Dall’Ara, E. (2017), “”, Journal of Biomechanics, 65, pp 203-211.

Lu, Y., Boudiffa, M., Dall’Ara, E., Liu, Y., Bellantuono, I., Viceconti, M. (2017), “”, Journal of the Mechanical Behavior of Biomedical Materials, 75, pp 244-251.

2016

Giorgi, M., Verbruggen, S. W., Lacroix, D. (2016), “”, WIREs Systems Biology and Medicine, 8 (6), pp 485-505.

Lu, Y., Boudiffa, M., Dall’Ara, E., Bellantuono, I., Viceconti, M. (2016), “”, Journal of Biomechanics, 49 (10), pp 2095-2099.

Wittkowske, C., Reilly, G. C., Lacroix, D., Perrault, C. M. (2016), “”, Frontiers in Bioengineering and Biotechnology, 4 (87), 22 pages.