Esther Reina-Romo

Modeling distraction osteogenesis: analysis of the distraction rate.

Distraction osteogenesis is a useful technique aimed at inducing bone formation in widespread clinical applications. One of the most important factors that conditions the success of bone regeneration is the distraction rate. Since the mechanical environment around the osteotomy site is one of the main factors that affects both quantity and quality of the regenerated bone, we have focused on analyzing how the distraction rate influences on the mechanical conditions and tissue regeneration. Therefore, the aim of the present work is to explore the potential of a mathematical algorithm to simulate clinically observed distraction rate related phenomena that occur during distraction osteogenesis. Improvements have been performed on a previous model (Gómez-Benito et al. in J Theor Biol 235:105–119, 2005) in order to take into account the load history. The results obtained concur with experimental findings: a slow distraction rate results in premature bony union, whereas a fast rate results in a fibrous union. Tension forces in the interfragmentary gap tissue have also been estimated and successfully compared with experimental measurements.

Growth mixture model of distraction osteogenesis: effect of pre-traction stresses.

In tensional studies of bone fragments during limb lengthening, it is usually assumed that the stress level in the gap tissue before each distraction step (pre-traction stress) is rather modest. However, during the process of distraction osteogenesis, a large interfragmentary gap is generated and these pre-traction stresses may be important. To date, to the authors’ knowledge, no computational study has been developed to assess the effect of stress accumulation during limb lengthening. In this work, we present a macroscopic growth mixture formulation to investigate the influence of pre-traction stresses on the outcome of this clinical procedure. In particular, the model is applied to the simulation of the regeneration of tibial defects by means of distraction osteogenesis. The evolution of pre-traction forces, post-traction forces and peak forces is evaluated and compared with experimental data. The results show that the inclusion of pre-traction stresses in the model affects the evolution of the regeneration process and the corresponding reaction forces.

Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle) levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields.

Effect of the fixator stiffness on the young regenerate bone after bone transport: Computational approach

Bone transport is a well accepted technique for the treatment of large bony defects. This process is mechanically driven, where mechanical forces play a central role in the development of tissues within the distracted gap. One of the most important mechanical factors that conditions the success of bone regeneration during distraction osteogenesis is the fixator stiffness not only during the distraction phase but also during the consolidation phase. Therefore, the aim of the present work is to evaluate the effect of the stiffness of the fixator device on the interfragmentary movements and the tissue outcome during the consolidation phase. A previous differentiation model (Claes and Heigele, 1999) is extended in order to take into account the different behaviors of the tissues in tension and compression. The numerical results that were computed concur with experimental findings; a stiff fixator promotes bone formation while the excessive motion induced by extremely flexible fixators is adverse for bony bridging. Experimental interfragmentary movement is similar to that computed numerically.

Influence of high-frequency cyclical stimulation on the bone fracture-healing process: mathematical and experimental models

Mechanical stimulation affects the evolution of healthy and fractured bone. However, the effect of applying cyclical mechanical stimuli on bone healing has not yet been fully clarified. The aim of the present study was to determine the influence of a high-frequency and low-magnitude cyclical displacement of the fractured fragments on the bone-healing process. This subject is studied experimentally and computationally for a sheep long bone. On the one hand, the mathematical computational study indicates that mechanical stimulation at high frequencies can stimulate and accelerate the process of chondrogenesis and endochondral ossification and consequently the bony union of the fracture. This is probably achieved by the interstitial fluid flow, which can move nutrients and waste from one place to another in the callus. This movement of fluid modifies the mechanical stimulus on the cells attached to the extracellular matrix. On the other hand, the experimental study was carried out using two sheep groups. In the first group, static fixators were implanted, while, in the second one, identical devices were used, but with an additional vibrator. This vibrator allowed a cyclic displacement with low magnitude and high frequency (LMHF) to be applied to the fractured zone every day; the frequency of stimulation was chosen from mechano-biological model predictions. Analysing the results obtained for the control and stimulated groups, we observed improvements in the bone-healing process in the stimulated group. Therefore, in this study, we show the potential of computer mechano-biological models to guide and define better mechanical conditions for experiments in order to improve bone fracture healing. In fact, both experimental and computational studies indicated improvements in the healing process in the LMHF mechanically stimulated fractures. In both studies, these improvements could be associated with the promotion of endochondral ossification and an increase in the rate of cell proliferation and tissue synthesis.

An Interspecies Computational Study on Limb Lengthening

Distraction osteogenesis is a surgical technique that produces large volumes of new bone by gradually separating two osteotomized bone segments. A previously proposed mechanical-based model that includes the effect of pre-traction stresses (stress level in the gap tissue before each distraction step) during limb lengthening is used here. In the present work, the spatial and temporal patterns of tissue distribution during distraction osteogenesis in different species (sheep, rabbit) and in the human are compared numerically to predict experimental results. Interspecies differential characteristics such as size, distraction protocol, and rate of distraction, among others, are chosen according to experiments. Tissue distributions and reaction forces are then analysed as indicators of the healing pattern. The results obtained are in agreement with experimental findings regarding both tissue distribution and reaction forces. The ability of the model to qualitatively predict the two animal models and the human healing pattern in distraction osteogenesis indicates its potential in understanding the influence of mechanics in this complex process.

Three-Dimensional Simulation of Mandibular Distraction Osteogenesis: Mechanobiological Analysis

Distraction osteogenesis is a surgical process for reconstruction of skeletal deformities, which has been widely investigated from the clinical perspective. However, little has been analyzed about the capability of numerical models to predict the clinical outcome generated by distraction. Therefore, this article presents a finite element analysis of the mechanobiological behavior of a pediatric patient’s mandible with hemifacial microsomia during the distraction process. It focuses on the three-dimensional simulation of a long bone defect in the ramus of the mandible and introduces additional aspects to be considered in the computational simulation as compared to the bidimensional simulation. The evolution of the different tissues within the gap is evaluated and in order to check the effectiveness of the model, the predicted numerical outcome will be compared from a qualitative point of view with radiographies provided by the surgeons. It is shown that the morphology of the mandible changed in a similar manner than that observed clinically. These results reveal that three-dimensional models are useful tools in the predictive assessment of mandibular distraction osteogenesis.

Biomechanical response of a mandible in a patient affected with hemifacial microsomia before and after distraction osteogenesis

Distraction osteogenesis (DO) has gained wide acceptance in the craniofacial surgery due to the huge possibilities it offers. However this orthopaedic field is under continuous development as it still presents uncertainties. In this context, numerical modelling/analysis may help us to design patient specific treatments once they have been experimentally verified. This paper presents a finite element analysis of the biomechanical behavior of a patients mandible with hemifacial microsomia (HFM) before and after distraction. In order to check the effectiveness of the clinical protocol, the predicted biomechanical response will also be compared with that of a symmetrical healthy mandible. Strain and displacement fields, masticatory forces as well as reaction forces at the condyles are evaluated in each mandible analyzed. The results show that the present model is a useful tool to understand the normal function of the mandible and to predict changes due to alterations in the mandible geometry, such as those occurring in hemifacial microsomia.

In Vivo Gait Analysis During Bone Transport

The load bearing characteristics of the intervened limb over time in vivo are important to know in distraction osteogenesis and bone healing for the characterization of the bone maturation process. Gait analyses were performed for a group of sheep in which bone transport was carried out. The ground reaction force was measured by means of a force platform, and the gait parameters (i.e., the peak, the mean vertical ground reaction force and the impulse) were calculated during the stance phase for each limb. The results showed that these gait parameters decreased in the intervened limb and interestingly increased in the other limbs due to the implantation of the fixator. Additionally, during the process, the gait parameters exponentially approached the values for healthy animals. Corresponding radiographies showed an increasing level of ossification in the callus. This study shows, as a preliminary approach to be confirmed with more experiments, that gait analysis could be used as an alternative method to control distraction osteogenesis or bone healing. For example, these analyses could determine the appropriate time to remove the fixator. Furthermore, gait analysis has advantages over other methods because it provides quantitative data and does not require instrumented fixators.

Hyperelastic remodeling in the intrauterine growth restricted (IUGR) carotid artery in the near-term fetus.

A constitutive model for a fiber reinforced hyperelastic material was applied to understand arterial fiber remodeling in a sheep model of Intrauterine Growth Restriction (IUGR). IUGR is associated altered hemodynamics characterized by increased resistance to blood flow in the placenta and elevated fetal arterial pressure and pulsatility. The constitutive model describes the collagen contribution to the mechanics within the arterial wall in both control and IUGR carotid artery through defining the material modulus and the orientation of the microstructure. A sheep model of placental insufficiency induced IUGR (PI-IUGR) was created by exposure of the pregnant ewe to elevated ambient temperatures. Experimental data was collected using pressure-diameter measurements to measure passive compliance in control and PI-IUGR carotid arteries. The constitutive model was optimized to fit the experimental data predicting the material parameters. Specifically, the collagen fiber predicted angle (γ) in the control artery was 49.9° from the circumferential axis while the PI-IUGR was 16.6° with a 23.5% increase in fiber orientation (κ). Quantitative assessment of collagen fiber orientation in secondary harmonic generation images confirmed the shift in orientation between the two groups. Together these suggest vascular remodeling of the ECM fiber orientation plays a major role in arterial stiffening in the PI-IUGR near-term fetal sheep.