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L\textquoterightinvention concerne les matériaux utilisés pour la réalisation de répliques (ou fantômes) de vaisseaux sanguins patient-spécifiques par une technique de fabrication additive. Ces répliques sont fabriquées en matériaux synthétiques dont les propriétés sont très représentatives de celles déterminées sur des vaisseaux sanguins humains sains ou pathologiques (anévrisme, athérosclérose, dissection...). Grâce à ces matériaux, on peut rapidement fabriquer des fantômes qui présentent les caractéristiques à la fois morphologiques et mécaniques des tissus réels ouvrant leur champ d\textquoterightapplications à différents usages: entrainement préopératoire des chirurgiens, formation des médecins, étude du flux sanguin, validation des algorithmes de traitement d\textquoterightimages...La principale particularité de l\textquoterightinvention réside dans la ma\^ıtrise de la variabilité de propriétés mécaniques des matériaux mis au point, permettant de reproduire le comportement mécanique quel que soit l\textquoterightétat de santé du vaisseau. Ce comportement présente une composante viscoélastique et une composante hyper-élastique.

International audience; This work was carried out within a research project aiming to produce replicas (or phantoms) representing the mechanical behavior of the cardiovascular system as faithfully as possible. Healthy vessels as well as vessels suffering from pathologies should be considered. Various applications of these phantoms can be forecast: repeating surgical procedures before real interventions (including the effect of blood flow), validation of the medical image processing algorithms, assistance in modeling viscoelastic behavior of real tissues ... Specifically, the aim of this work was to validate a method for characterizing the hyper-viscoelastic behavior of silicone tubes by measuring the deformation (Inflation-Extension) using a medical imaging method (ultrasound) while the periodic blood flow is simulated in the tube. This is achieved by inserting the tube in a water circuit where the pressure is controlled to simulate the blood pressure. This circuit is itself immersed in a water bath for transmitting ultrasonic waves. The system was validated by showing that the hyper-viscoelastic behavior measured by this way was consistent with that determined by standard methods such as tensile tests and dynamic mechanical analysis. Diverse silicone formulations, exhibiting behaviors covering the range of those of real arterial tissues, were thus tested. Their behaviors were described on the basis of hyper-viscoelastic model constituted of several Maxwell elements in parallel with a hyperelastic branch (Yeoh model). Eventually, this method can be adapted to determine the hyper-viscoelastic behavior of real blood vessel walls by a non-invasive method based on medical imaging. Hence, it would be helpful to diagnose or predict pathologies affecting the hyper-viscoelastic behavior of the arterial wall.

International audience

The recent advances in 3D-printed silicone (PDMS: polydimethylsiloxane) implants present prospects for personalized implants with highly accurate anatomical conformity. However, a potential adverse effect, such as granuloma formation due to immune reactions, still exists. One potential way to overcome this problem is to control the implant/host interface using immunomodulatory coatings. In this study, a new cytokine cocktail composed of interleukin-10 and prostaglandin-E2 was designed to decrease adverse immune reactions and promote tissue integration by fixing macrophages into M2 pro-healing phenotype for an extended period of time. In vitro, the cytokine cocktail maintained low levels of pro-inflammatory cytokine (TNF-α and IL-6) secretions and induced the secretion of IL-10 and the upregulation of multifunctional scavenging and sorting receptor stabilin-1, expressed by M2 macrophages. This cocktail was then loaded in a gelatine-based hydrogel to develop an immunomodulatory material that could be used as a coating for medical devices. The efficacy of this coating was demonstrated in an in vivo rat model during the reconstruction of a tracheal defect by 3Dprinted silicone implants. The coating was stable on the silicone implants for over 2 weeks, and the controlled release of the cocktail components was achieved for at least 14 days. In vivo, only 33% of the animals with bare silicone implants survived, whereas 100% of the animals survived with the implant equipped with the immunomodulatory hydrogel. The presence of the hydrogel and the cytokine cocktail diminished the thickness of the inflammatory tissue, the intensity of both acute and chronic inflammation, the overall fibroblastic reaction, the presence of oedema and the formation of fibrinoid (assessed by histology) and led to a 100% survival rate. At the systemic level, the presence of immunomodulatory hydrogels significantly decreased pro-inflammatory cytokines such as TNF-α, IFNγ, CXCL1 and MCP-1 levels at day 7 and significantly decreased IL-1α, IL-1β, CXCL1 and MCP-1 levels at day 21. The ability of this new immunomodulatory hydrogel to control the level of inflammation once applied to a 3D-printed silicone implant has been demonstrated. Such thin coatings can be applied to any implants or scaffolds used in tissue engineering to diminish the initial immune response, improve 3 the integration and functionality of these materials and decrease potential complications related to their presence.