Three-dimensional biomimetic tissue scaffolds, as well as methods of manufacture of these scaffolds. The method is fully customizable to create a biomimetic tissue scaffold with shapes, densities, and geometries similar or identical to the tissue it imitates. For example, physiologically realistic collagen/PEG villi created using the method are designed to have a high-aspect ratio and curvature similar to villi found in the human small intestine. Accordingly, the biomimetic tissue scaffolds serve as an improved in vitro model for a wide variety of physiological research, as well as pharmacological testing and drug, compound, and/or metabolite uptake by cells growing on the scaffold, among many other uses.