Examples of multiscale and multiphysics numerical modeling of biological tissues.

Predictive theoretical-numerical modeling of the behavior and evolution of biological tissue is a difficult task since many of the required knowledge tools (experimental, theoretical and numerical) are still not well understood. We present here some methodologies and results specific to multiscale and multiphysics numerical modeling of biological tissues applied to the predictive behavior of cortical veins depending on their local constituents' microstructure and for bone remodeling and reconstruction as a function of the local mechanobiology. Although further work is required to improve the accuracy of the developed models, the proposed approaches highlight their potential usefulness for understanding the mechanical-biological couplings, short and long term predictions of biological evolutions as well as possible further transfer to medical applications.

Additive manufacturing of a monolithic optical force sensor based on polarization modulation.

One of the specific interests of optical sensors is their compatibility with harsh environments. The polarization modulated force sensor we propose offers this advantage, in addition to low cost and ease of manufacturing thanks to its acrylate 3D printed monolithic design. All the polarization control is indeed achieved using the geometry of a single component making unnecessary future alignments. The complex geometry of the transducer is obtained thanks to the 3D printing process. This process and the resulting material optical properties are described. The sensor concept and the fabrication method are experimentally investigated. A monolithic force sensor in the required range of 20 N is exhibited for application in the field of MR-compatible robotics. The potentiality of 3D printing for optical application in the design of the force sensor is illustrated.

Assessing the three-dimensional collagen network in soft tissues using contrast agents and high resolution micro-CT: Application to porcine iliac veins.

The assessment of the three-dimensional architecture of collagen fibers inside vessel walls constitutes one of the bases for building structural models for the description of the mechanical behavior of these tissues. Multiphoton microscopy allows for such observations, but is limited to volumes of around a thousand of microns. In the present work, we propose to observe the collagenous network of vascular tissues using micro-CT. To get a contrast, three staining solutions (phosphotungstic acid, phosphomolybdic acid and iodine potassium iodide) were tested. Two of these stains were showed to lead to similar results and to a satisfactory contrast within the tissue. A detailed observation of a small porcine iliac vein sample allowed assessing the collagen fibers orientations within the medial and adventitial layers of the vein. The vasa vasorum network, which is present inside the adventitia of the vein, was also observed. Finally, the demonstrated micro-CT staining technique for the three-dimensional observation of thin soft tissues samples, like vein walls, contributes to the assessment of their structure at different scales while keeping a global overview of the tissue.

Evolution of the three-dimensional collagen structure in vascular walls during deformation: an in situ mechanical testing under multiphoton microscopy observation.

The collagen fibers' three-dimensional architecture has a strong influence on the mechanical behavior of biological tissues. To accurately model this behavior, it is necessary to get some knowledge about the structure of the collagen network. In the present paper, we focus on the in situ characterization of the collagenous structure, which is present in porcine jugular vein walls. An observation of the vessel wall is first proposed in an unloaded configuration. The vein is then put into a mechanical tensile testing device. As the vein is stretched, three-dimensional images of its collagenous structure are acquired using multiphoton microscopy. Orientation analyses are provided for the multiple images recorded during the mechanical test. From these analyses, the reorientation of the two families of collagen fibers existing in the vein wall is quantified. We noticed that the reorientation of the fibers stops as the tissue stiffness starts decreasing, corresponding to the onset of damage. Besides, no relevant evolutions of the out of plane collagen orientations were observed. Due to the applied loading, our analysis also allowed for linking the stress relaxation within the tissue to its internal collagenous structure. Finally, this analysis constitutes the first mechanical test performed under a multiphoton microscope with a continuous three-dimensional observation of the tissue structure all along the test. It allows for a quantitative evaluation of microstructural parameters combined with a measure of the global mechanical behavior. Such data are useful for the development of structural mechanical models for living tissues.

A new multiscale model for the mechanical behavior of vein walls.

The purpose of the present work is to propose a new multiscale model for the prediction of the mechanical behavior of vein walls. This model is based on one of our previous works which considered scale transitions applied to undulated collagen fibers. In the present work, the scale below was added to take the anisotropy of collagen fibrils into account. One scale above was also added, modeling the global reorientation of collagen fibers inside the vessel wall. The model was verified on experimental data from the literature, leading to a satisfactory agreement. The proposed multiscale approach also allows the extraction of local stresses and strains at each scale. This approach is presented here in the case of vein walls, but can easily be extended to other tissues which contain similar constituents.

Investigation of the human bridging veins structure using optical microscopy.

In this paper, we investigated the brain-sinus junction and especially the bridging veins linking these two organs. Two types of optical microscopy were used: conventional optical microscopy and digital microscopy. We used thin histological sections prepared from a human brain, and stained with Masson's trichrome, hemalun and orcein. Finally we observed the path of the bridging vein inside the brain-skull interface. At smaller scales, wavy collagen fiber bundles were found and characterized inside the vein walls. Taking into account the orientations of the different sections with reference to frontal planes, we found that the bridging vein has a very complex geometry, which increases the difficulty to determine fiber orientations in its walls. Nevertheless, we found that collagen fiber bundles are mainly circumferentially oriented in the superior sagittal sinus walls. In this paper, we were able to characterize precisely the path of the bridging vein from the brain to the sinus, with different magnifications.