Biomimetic scaffolds with three-dimensional undulated microtopographies

Abstract Many human and animal tissues naturally possess three-dimensional (3D) micro-scale geometries enabling certain physiological functions. Absence of these microgeometries in engineered tissues may undermine the effectiveness of corresponding tissue repair and regeneration. This paper introduces a novel approach to create tissue scaffolds with biomimetic 3D undulated microtopographies. The mechanical micromilling technology is used for precise and reproducible fabrication of poly(methyl methacrylate) (PMMA) master molds with 3D undulated microtopographies. Poly(dimethylsiloxane) (PDMS) production molds are then created using the master molds through elastomer molding. Next, gelatin-chondroitin-6-sulfate-hyaluronic acid (Gel-C6S-HA) is filled into the PDMS molds in its gel form, lyophilized to obtain solid porous scaffolds, and covalently cross-linked to control biodegradability. The utility of the final porous scaffolds with undulated microtopographies mimicking dermal papillae of skin is demonstrated in vitro by culturing neonatal human fibroblasts (NHFs) on the scaffold surfaces for up to 7 days. The assessment of the mold and scaffold geometries demonstrates high accuracy and reproducibility of the PMMA mold fabrication, as well as well-controlled undulated microtopographies and porous microstructures of the final scaffolds. The analysis of cell responses to the undulated microtopographies shows the biocompatibility and effectiveness of the final scaffolds, as well as unique cellular response to these biomimetic topographies at the macroscopic level.