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Microchannels for controlling cellular mechanotransduction

Periodic Reporting for period 1 - CHANNELMAT (Microchannels for controlling cellular mechanotransduction)

Période du rapport: 2017-10-01 au 2019-03-31

The macroscopic and microscopic geometry of a biomaterial are key elements in providing space for cell growth. In addition, the mechanical properties of a biomaterial have great impact on cellular proliferation, migration and differentiation, as well as on cell adhesion. Controlling the geometry of a biomaterial by mimicking natural 3D cellular environments plus tailoring its mechanical features lead to a platform for studying cellular mechanotransduction. Our materials represent a 3D environment based on soft hydrogels that contain interconnected micron-sized channels. In addition, both stiffness and biological functionalization of the hydrogels are tunable during or after the synthesis of the scaffolds. For instance, the matrix stiffness is well-defined by the type of hydrogel (e.g. pNIPAM or pAAM) and by cross linker concentration, so that we could reach bulk moduli of 1 kPa, 10 kPa and 30 kPa. In addition, high-throughput fabrication is possible. We can also modify the surface of the hydrogels with different adhesion ligands such as collagen.
The microchannels in our hydrogels can provide spatially controlled cell-surface contact areas of up to 80%, thus the properties of the hydrogel are expected to have great impact on cell interaction and behavior. Very decisive are in this context the mechanical properties of the biomaterial, to mimic the mechanical properties of natural cellular environments and thus to control cellular mechanotransduction pathways (i.e. the ability of a cell to react on the mechanical properties of their surroundings). To test mechanotransduction, the proliferation and differentiation of mesenchymal stem cells (MSC) were studied on microchannel-containing PAAm hydrogels. The differentiation of the MSCs into three anchorage-dependent cell types, such as neurons, myoblasts, and osteoblasts were studied using lineage-specific markers. The neurogenic and myogenic differentiation of the MSCs on the materials with ~1 kPa and ~10 kPa, respectively, shows the strong influence of microchannel-containing PAAm’s stiffness on differentiation. However, MSCs hardly migrated into the micro channels so that the materials need to be equipped with larger proves to allow MSC growth.
A second application field of the microchannel-containing hydrogels is the capture of human pathogenic Acanthamoeba castellanii from the supernatant of a solution, where it turned out that the microchannel-containing hydrogels are very promising. Therefore we are currently focusing on this application, as we expect a high potential for applying our materials to prevent Acanthemoeba infections and thus to avoid acanthamoaba keratitis diseases among contact lens users in the future.