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The West Lab has worked extensively in the development of surfaces and 3D scaffold materials that provide a high degree of control over cell adhesion and signaling events. These materials support very low levels of protein adsorption, and thus cell-material interactions are restricted to those intentionally engineered into the material design. Hydrogel scaffold materials have also been developed that are degraded in response to cellular proteolytic activity. This allows materials to degrade in response to cell activities such as migration rather than continuous hydrolysis as is seen in common polyesters. We have developed patterning technologies in both 2D and 3D to allow spatial control over cell-material interactions. Image-guided laser scanning lithography has allowed us to recapitulate cellular focal adhesion complexes with nanoscale resolution to control and manipulate cytoskeletal architecture of cells seeded on these patterned surfaces. As shown in Figure 1, we can prepare highly homogeneous cellular arrays using this technology. Two-photon laser scanning lithography allows 3D micropatterning of covalently immobilized peptides and proteins in hydrogels, again with nanoscale resolution, to guide cell migration and network assembly. This technology allows free-form 3D patterning for material fabrication, immobilization of bioactive factors, or manipulation of mechanical properties. As shown in Figure 2, confocal images from tissues can be used to develop patterning instructions in order to recapitulate complex tissue architectures within scaffold biomaterials.