Extrusion-based 3D (Bio)Printed Tissue Engineering Scaffolds: Process-Structure-Quality Relationships

Biological additive manufacturing (Bio-AM) has emerged as a promising approach for the fabrication of biological scaffolds with nano- to microscale resolutions and biomimetic architectures beneficial to tissue engineering applications. However, Bio-AM processes tend to introduce flaws in the construct during fabrication. These flaws can be traced to material nonhomogeneity, suboptimal processing parameters, changes in the (bio)printing environment (such as nozzle clogs), and poor construct design, all with significant contributions to the alteration of a scaffold's mechanical properties. In addition, the biological response of endogenous and exogenous cells interacting with the defective scaffolds could become unpredictable. In this review, we first described extrusion-based Bio-AM. We highlighted the salient architectural and mechanotransduction parameters affecting the response of cells interfaced with the scaffolds. The process phenomena leading to defect formation and some of the tools for defect detection are reviewed. The limitations of the existing developments and the directions that the field should grow in order to overcome said limitations are discussed.