Nanofabrication and magnetic active cell patterning for vascular engineering – NMVASC

This project intitled «Nanofabrication and magnetic active cell patterning for vascular engineering», acronyme NMVASC, is submitted to the ASTAR/ANR Joint Call for Proposals in Nanotechnology area.

This projet will associate 4 partners from France (2) and Singapore (2).
- Partner 1: Inserm U698, Cardiovascular Bioengineering Group - France
- Partner 2: CNRS UMR 7057, Biological Physics Group - France
- Partner 3: National University of Singapore, Bioengineering, Regenerative Nanomedicine Lab - Singapore
- Partner 4: Institute of Materials Research and Engineering (IMRE), Nanoimprinting Group – Singapore

Development of a functional small-diameter vascular graft for the treatment of vascular disease remains a challenge for coronary arterial bypass surgeries and lower limb peripheral arterial disease. Recent evidence indicates that endothelialization of bypass grafts by establishment of a confluent and stable endothelial cell layer in the lumen of vascular grafts is critical for long-term patency of small-diameter vascular grafts. In vivo, cells are surrounded by topographical and biochemical cues in their microenvironment with native extracellular matrix comprising nanoscaled features in the form of nanofibers, nanopores, and nano-ridges. Therefore, we hypothesize that by creating well-defined nano-textured patterns on a vascular graft surface, we could create a nano-environment suitable for endothelial cell adhesion and migration that would lead to improved graft patency.

In this context, we intend to develop novel nano- and microfabrication technique to enhance endothelial cell-substrate interactions on materials that have been previously developped by Partner 1. These materials, based on natural polysaccharides and synthetic polyvinyl alcohol, have proven to be effective as vascular grafts in a rat model. However, incomplete endothelialization of the lumen surface was obtained. Addition of nanotopographical cues on these biomaterials will be investigated by partners 3 and 4 for creating an optimal microenvironment for endothelial cells, using nanofabrication technologies, such as solvent casting and nanoimprinting lithography.
Since physical signals sensed by cells, such as the mechanical properties of the matrix (local rigidity, adhesiveness, architecture, etc.) are increasingly emerging as determinants of cell survival, proliferation, migration and differentiation, we intend to examine the influence of the physical and mechanical properties of nano- and micro-patterned substrates on cell adhesion. Endothelial cell responses, such as cell proliferation and migration as well as cytoskeleton organization, to these nanostructured materials will be evaluated by partners 1 and 3.
The development of micro-organized magnetic substrates by partner 2 will allow us to control the geometry of cell assembly in either two or three dimensions, on both non-patterned and patterned substrates. We will create these mechanical constraints by inducing cells to internalize magnetic nanoparticles and then submitting them to a magnetic field gradient.
Finally, we will prepare tubular scaffolds from the nanopatterned materials, we will apply controlled and modulable local magnetic constraints permitting structured cell assembly in order to culture cells into tubular grafts and we will investigate these tubular scaffolds as vascular replacement in a rat model (all partners).