Undulating Micro-Geometries for 3D Tissue Scaffolds through Micromachining Approaches

Many native tissues possess three-dimensional (3D) micro-geometries that are essential for their physiological functioning. One vital structure is the dermal papillae, which is a 3D undulating interface between the epidermis and dermis in skin. This structure allows biology to increase the interface area, which improves functions including reinforced mechanical contact, enhanced thermal conductivity, and improved nutrient transmission. While the importance of this structure is broadly understood in community, there is a critical gap in our capability to accurately and reproducibly create these fully-3D micro-topographies. Most current approaches are limited due to 2D fabrication methods, which have not mimicked precisely the natural geometries of dermal papillae. As such, to be able to fabricate these micro-geometries in engineered skin tissues would be a tremendous advance.Here we developed 3D undulated geometries across a range of micro-scales on hydrogel scaffolds for mimicking dermal papillae. We accomplished this by using coupled micro-milling and micro-molding approaches. We first micro-milled master molds with a 3D sine wave matrix so that the structure possesses continuous curvature in all directions; this mimics the undulated geometries. We next developed these into porous hydrogel scaffolds which had the 3D undulating surface from the master molds through micro-molding and lyophilization. We examined the cell-scaffold interfacial response by culturing fibroblasts on the undulating surfaces. We found that the hydrogel scaffolds replicated the precise 3D master molds and the cells grew on the micro-patterned scaffolds over time. Taken together, our micro-milling approach applied to tissue scaffolds paves the way to fabricate more 3D structurally realistic artificial tissues, which will be very beneficial to the areas such as regenerative medicine, tissue engineering, and organ-on-a-chip applications.