Process optimization for coaxial extrusion-based bioprinting: A comprehensive analysis of material behavior, structural precision, and cell viability

Coaxial extrusion-based bioprinting (CEBB), as a widely applied multimaterial bioprinting technology, demonstrates significant potential in the field of biomanufacturing. However, the fabrication of high-precision hierarchically structured concentric core-shell fibers, while ensuring high cell viability, poses a challenge. Herefore, systematic analysis of the CEBB is mandatory for process optimization concerning production efficiency and printing quality. This paper systematically describes the entire process of CEBB through analytical method, computational fluid dynamics (CFD) and experimental evaluation. Taking pre-crosslinked alginate-collagen bioink as an example, we used gelatin as a sacrificial material to fabricate a double-layered hollow structural scaffold encapsulating human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs). From the rheological behavior of bioink within the coaxial nozzle to the deposition of core-shell strands onto the substrate, we employed mathematical modeling and simulation for analysis, and verified the results against actual prints. A series of characterization tests were conducted to evaluate the impact of material composition and structure on the permeability, mechanical properties, and cell proliferation of the hollow bioscaffold. For potential cell damage during extrusion, we evaluated shear stress and exposure time, both direct influencing factors,which relate to feed volumetric flow rate. Based on the aforementioned research findings, we optimized the printing operation parameters and established encapsulated cell viability, print fidelity and precision, core-shell structural dimensions, and core-shell structural integrity and uniformity as evaluation criteria for CEBB processes. The workflow of systematic analysis and evaluation of CEBB process in this study is applicable to diverse bioinks and coaxial nozzle sizes, effectively reducing time and material costs in the bioengineering industry.