Biomechanics (spine, lower limbs); Mutiphysics (cartilage, intervertebral disc, artery); Biophysics (intervertebral disc nutrition, cytokines); Computational analyses (finite element modelling, numerical optimisations, agent-based modelling); Patient-specific modelling (tissue properties, mesh morphing)
Research in the team of Multiscale and Computational Biomechanics and Mechanobiology (MBIOMM) focuses on the musculoskeletal system, mainly on (i) the interactions between tissue multiphysics and biological processes, and (ii) how these interactions can affect the functional biomechanics of organs. Numerical methods that combine different modelling and simulation techniques are used to describe both the tissues at the organ level, and the tissue-cell interactions at the tissue and cellular levels. The numerical concepts developed are tested against in vivo and in vitro data, which allows model validations, as well as educated interpretations of reported evidences.
On one hand, emphasis is given in the study of the multiscale transfer of mechanical load effects from the system level to the cell level in different cases of simulated treatments or organ/tissue condition. On the other hands, advanced tissue models are used to link observable phenotypes to possible mechanisms of spatiotemporal tissue regulation. Calculations are based on both multiphysics and biophysical concepts to predict different cell environments over time.
Simulation of mutual interactions between strain-induced muscle activation (Left) and intervertebral disc (IVD) pressurization (right) during night rest simulations in a finite element model of the lumbar spine (L1 to L5/S1 IVD)
Most tissue and biophysical models developed so far aimed to study one of the most complex organs of the musculoskeletal system, namely the spine. Thorough knowledge about the functional biomechanics of the lumbar spine has been acquired along the time in relation to computational simulations (J Biomech, 40, 2414-25; Biomech model Mechanobiol, 10, 203-19). In order to capture as best as possible the communications between organ and tissue biomechanics, studies of advanced tissue models have been performed, focussing on the complexiy of the intervertebral disc (Comput Meth Biomech Biomed Engin, 16, 923-8; Front Bioeng Biotechnol, 3, 5) and of the muscle (Front Bioeng Biotechnol, 3, 111) mechanics.
Left: Cell viability predictions given by different mechanotransduction assumptions within a bovine intervertebral model subject to steady-state overloads. Right: Prediction of proteoglycan turnover as a result of the nutrition-dependent cell anabolic activity
In particular, poromechanical intervertebral disc modelling has allowed tissue-level couplings of mechanical deformations with disc cell nutrition issues, adressing the presumably important influence of indirect mechanotransduction in disc maintenance and pathogenesis (MRS Bull, 40, 324-32). This approach showed great promise to interprete organ culture experiments (Poromechanics V, 2193-201) and virtually explore the intricate interactions among tissue condition, organ mechanics, and nutritional cell stress (PLoS Comput Biol, 7, e1002112; J Biomech, 47, 1520-25). Notably, models allowed explicit simulation of the particularities of tissue structures and composition (J Mech Phys Sol, In Press; Osteoarthritis Cartilage, 22, 1053-60), and of organ geometry (Front Bioeng Biotechnol, 3, 5), leading to important insights about the influence of patient specificity on the identified interactions. Care is taken to assess the physical meaning of the tissue model parameters (Front Bioeng Biotechnol, 3, 5) as well as the numerical accuracy of the simulations (J Mech Behav Biomed Mater, 26, 1-10) in order to ensure possible coupling biophysical model simulations at lower scale.
a) Stress distribution in a proximal tibial virtually implanted with cannulated screws or a locking screw plate under external loads. b) Stresses in the devices. c) Stresses induced by the device screws in the adjacent bone and comparison with range of stress values that may induce bone damage.
As for lower scale simulations, modelling approaches from computational systems biology allow descriptions of the stochastic behaviours shaped by collective cell and molecule interactions (Bioinformatics, 2016, In Press). Such approach is currently being explored for both the cardiovascular and the intervertebral disc system. At the organ level, biomechanical models have also been used for implant simulation focussed on either clinical (Int Orth, 2016, In Press; Clin Biomech, 29, 444-50) or implant design (Eur Spine J, 21, S675-87) questions. The educated guesses achieved through theoretical calculations allow improved assessments of treatment or diagnostic strategies, and better selections of the hypotheses to be clinically or experimentally explored. This asset becomes particularly strong in the case of patient-specific modelling where the technical expertise of the MBIOMM team meets that of the other areas of the SIMBIOsys group (Ann Biomed Eng, 2016, In Press).
Dynamic agent-based calculations for the prediction of foam cell (FC) accumulation in arterial intima in atherogenesis, depending on the level of cholestrol (LDL) measured in the blood.
In addition to organ biomechanics, tissue mechanobiology, and cell biophysics, human motion and muscle function are also taken into account at the system level. Motion tracking measurements allow inverse dynamic analyses and static optimizations for the analysis of joint reaction forces and actuator (muscle) activations, respectively. This knowledge is coupled to finite element analyses for integrated explorations of the body, organs and tissues. Strong collaborations are kept with both external laboratories that focus on human motion capture, and clinical centers, so as to apply multiscale modelling to the study of musculoskeletal disorders and treatments based on physical therapy.
Multiscale analysis of the hip joint from body motion (right) to cartilage stress and strain fields (left)