Construction of Biomimetic Tissues with Anisotropic Structures via Stepwise Algorithm-Assisted Bioprinting.

Tissue-specific natural anisotropic microstructures play an important role in the normal functioning of tissues, yet they remain difficult to construct by current printing techniques. Herein, a stepwise algorithm-assisted bioprinting technology for the construction of biomimetic tissues with a customizable anisotropic microstructure by combining the Adaptive Mesh Generation algorithm and the Greedy Search algorithm is developed. Based on the mechanical topology optimization design mechanism, the Adaptive Mesh Generation algorithm can generate controllable anisotropic mesh patterns with the minimum free energy in plane models according to tissue-specific requirements. Subsequently, the Greedy Search algorithm can program the generated pattern data into optimized printing paths, effectively avoiding structural deformations caused by the multiple stacking of materials and reducing the printing time. The developed bioprinting technique is suitable for various types of bioinks including polymers, hydrogels, and organic/inorganic complexes. After combining with a calcium phosphorus bioink, the compound algorithm-assisted bioprinting technique successfully customizes femurs with biomimetic chemical compositions, anisotropic microstructures, and biological properties, demonstrating its effectiveness. Additionally, algorithm-assisted bioprinting is generally suitable for most commercial extrusion bioprinters that function in the geometric code (G-code) drive mode. Therefore, the algorithm-assisted extrusion bioprinting technology offers an intelligent manufacturing strategy for the customization of anisotropic microstructures in biomimetic tissues.