Biomimetic design, modeling and manufacturing of chitosan/gelatin scaffolds for 3D vascularized liver tissue construct

Despite the significant progress in engineering fairly thin tissues that contain or acquire vascular structures (e.g. skin, cartilage and bladder), it has been markedly difficult to construct metabolically demanding organs with thicker and more complex structures (e.g. heart, lung, kidney, and liver). This research explores a new generation of clinically significant (500cm³) liver tissue constructs made of a new natural polymer composite, imbedded with optimized network of flow channels, and manufactured using innovative structured porogen and lost-wax molding methods to receive a 3D vascularized liver tissue construct. Biomimetic designed liver scaffolds with 3D network of flow channels were optimized based on simulation of fluid flow inside the channel network. Combining structured porogen method, lost-wax molding and freeze-drying technique, both macro (1 cm) and the micro (500μm) scale structures were achieved in chitosan/gelatin liver scaffolds. Liver parenchymal cells were seeded in the 3D scaffolds and cultured for 3 days. Evident cell growth was found both at the bottom and the center of the scaffolds, which indicates the biocompatibility is maintained through the manufacturing process and 3D channels improved cell in-growth.