Improving the quality of bone tissue regeneration: from bench to bedside via in silico modelling (BRIDGE project)

Tissue engineering is a biomedical engineering field designing and improving man-made living implants to replace diseased or non-functional (parts of) organs. A challenge in tissue engineering is that the complex lab procedures involve a lot of manual work and don’t have clear quality criteria, which is essential for safe clinical applications (1). Consequently, it is very difficult to enlarge these procedures to industrial production levels (2).

Computational models can cope with this complexity and improve the fundamental understanding of the regeneration processes as well as to predict and optimize the patient-specific treatment strategies (3).

The BRIDGE project focusses on bone tissue engineering. State-of-the-art biomimetic processes based on in silico models increase the quantity and quality of the in vivo outcome of the tissue engineering manufacturing process. Moreover, the project aims at understanding and control to the quality of the production process. These factors are important for patient safety ultimately.

In silico models of four key elements (cells, carriers, culture and clinics) are already used in orthopaedics for the planning of complicated surgeries, personalised implant design and the analysis of gait measurements (4).

In one of the studies of the BRIDGE project (5), the critical role of oxygen is examined in bone fracture healing, using a multiscale model that is compared with previous experimental and in silico results. The oxygen model was also applied to a challenging clinical case where it predicted the healing perspectives.

This BRIDGE study demonstrates that in silico models are a powerful tool to further unravel the complex spatiotemporal interplay during the bone repair process, which is a crucial step in the development of safer implants.

(1) Geris L. Model-guided bone tissue engineering: from bench to bedside via in silico modelling (conference abstract). Virtual Physiological Human Conference 2014
(2) Geris L. Biomimetic process design for tissue regeneration: from bench to bedside via in silico modelling. Grant ERC-2011-StG, panel PE8, Biomechanics Research Unit, University of Liège, Liège, Belgium & Prometheus, Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium & Biomechanics Section, KU Leuven, Leuven, Belgium (http://www.kuleuven.be/research/excellence/medical_technologies/geris.html and http://cordis.europa.eu/project/rcn/101422_en.html, accessed on 9 June 2016)
(3) Carlier A, Geris L, Lammens J, Van Oosterwyck H. Bringing computational models of bone regeneration to the clinic. Wiley interdisciplinary reviews. Systems biology and medicine 2015, Vol 7 (4), P 183-194, DOI 10.1002/wsbm.1299
(4) Geris L. Regenerative orthopaedics: in vitro, in vivo … in silico. International Orthopaedics (special issue on regenerative orthopaedics) 2014, Vol 38 (9), P 1771-1778
(5) Carlier A, Geris L, Van Gastel N, Carmeliet G, Van Oosterwyck H. Oxygen as a critical determinant of bone fracture healing-a multiscale model. Journal of Theoretical Biology 2015, Vol 365, P 247-264

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