A Novel Hybrid Membrane VAD as First Step Toward Hemocompatible Blood Propulsion.

Heart failure is a raising cause of mortality. Heart transplantation and ventricular assist device (VAD) support represent the only available lifelines for end stage disease. In the context of donor organ shortage, the future role of VAD as destination therapy is emerging. Yet, major drawbacks are connected to the long-term implantation of current devices. Poor VAD hemocompatibility exposes the patient to life-threatening events, including haemorrhagic syndromes and thrombosis. Here, we introduce a new concept of artificial support, the Hybrid Membrane VAD, as a first-of-its-kind pump prototype enabling physiological blood propulsion through the cyclic actuation of a hyperelastic membrane, enabling the protection from the thrombogenic interaction between blood and the implant materials. The centre of the luminal membrane surface displays a rationally-developed surface topography interfering with flow to support a living endothelium. The precast cell layer survives to a range of dynamically changing pump actuating conditions i.e., actuation frequency from 1 to 4 Hz, stroke volume from 12 to 30 mL, and support duration up to 313 min, which are tested both in vitro and in vivo, ensuring the full retention of tissue integrity and connectivity under challenging conditions. In summary, the presented results constitute a proof of principle for the Hybrid Membrane VAD concept and represent the basis for its future development towards clinical validation.

In Vitro Endothelialization of Surface-Integrated Nanofiber Networks for Stretchable Blood Interfaces.

Despite major technological advances within the field of cardiovascular engineering, the risk of thromboembolic events on artificial surfaces in contact with blood remains a major challenge and limits the functionality of ventricular assist devices (VADs) during mid- or long-term therapy. Here, a biomimetic blood-material interface is created via a nanofiber-based approach that promotes the endothelialization capability of elastic silicone surfaces for next-generation VADs under elevated hemodynamic loads. A blend fiber membrane made of elastic polyurethane and low-thrombogenic poly(vinylidene fluoride- co-hexafluoropropylene) was partially embedded into the surface of silicone films. These blend membranes resist fundamental irreversible deformation of the internal structure and are stably attached to the surface, while also exhibiting enhanced antithrombotic properties when compared to bare silicone. The composite material supports the formation of a stable monolayer of endothelial cells within a pulsatile flow bioreactor, resembling the physiological in vivo situation in a VAD. The nanofiber surface modification concept thus presents a promising approach for the future design of advanced elastic composite materials that are particularly interesting for applications in contact with blood.

Adaptive reorientation of endothelial collectives in response to strain.

Mature epithelial monolayers share the ability to coherently respond to external mechanical stimuli. Tissue remodeling requires cell shape changes and coordinated movements. Human endothelia provide an exquisite example of such emerging collective activities. As part of their function in maintaining body homeostasis under variable hemodynamic loadings, endothelial ensembles must dynamically adapt to wall shear stress and cyclic deformation. While the alignment of several types of cells, including fibroblasts, osteoblasts and epithelial tissues, in response to various flow conditions or wall shear stress levels has been described in detail, less is known about collective endothelial remodeling under pure wall deformation. Here, using a custom-developed bioreactor, we exposed mature human endothelia to two distinct physiological levels of cyclic loading, generating overlapping gradients of strain. Endothelial cells remodeled depending on the level of imposed strain yielding local variations of cell density. In particular, a collective cell orientation orthogonal to the main direction of strain was observed at low levels of wall deformation, while cells reoriented parallel to the main direction of strain at high levels of wall deformation. The tissue adaptation depended on the establishment of mature adherens junctions, which were reinforced by the polarized recruitment of the adaptor protein vinculin. The pivotal role of cell-to-cell junctions was confirmed by the biochemical inhibition of vascular endothelial cadherin homotypic contacts, which impaired the collective remodeling. Together, our data establish wall deformation as an independent determinant of endothelial architecture with direct implications in vascular physiopathology.

Inverse poroelasticity as a fundamental mechanism in biomechanics and mechanobiology.

Understanding the mechanisms of deformation of biological materials is important for improved diagnosis and therapy, fundamental investigations in mechanobiology, and applications in tissue engineering. Here we demonstrate the essential role of interstitial fluid mobility in determining the mechanical properties of soft tissues. Opposite to the behavior expected for a poroelastic material, the tissue volume of different collagenous membranes is observed to strongly decrease with tensile loading. Inverse poroelasticity governs monotonic and cyclic responses of soft biomembranes, and induces chemo-mechanical coupling, such that tensile forces are modulated by the chemical potential of the interstitial fluid. Correspondingly, the osmotic pressure varies with mechanical loads, thus providing an effective mechanism for mechanotransduction. Water mobility determines the tissue's ability to adapt to deformation through compaction and dilation of the collagen fiber network. In the near field of defects this mechanism activates the reversible formation of reinforcing collagen structures which effectively avoid propagation of cracks.How soft tissues respond to mechanical load is essential to their biological function. Here, the authors discover that - contrary to predictions of poroelasticity - fluid mobility in collagenous tissues induces drastic volume decrease with tensile loading and pronounced chemo-mechanical coupling.