The printing quality of biological scaffold is not only affected by the fluidity of bio-ink but also by the printing process parameters, such as the size of the needle, printing height, extrusion speed, and printing speed. Therefore, optimizing the printing process parameters can further improve the molding quality of the biological scaffold. In this study, the printing and deposition process of sodium alginate hydrogel was modeled and analyzed based on the Herschel–Bulkley model by the finite element simulation method. The orthogonal experiment method, control variable method, and response surface method were used to design experiments, and the influences of different printing process parameters on the hydrogel deposition process were investigated. Finally, the optimal combination of printing process parameters was obtained by taking the molding degree and offset of the hydrogel line as optimization objectives. The results show that the strength relationship of the factors affecting the molding degree of the hydrogel line is as follows: printing height > needle diameter > printing speed > extrusion speed, and the strength relationship of the factors affecting the printing offset is as follows: printing height > needle diameter > extrusion speed > printing speed. The optimal combination of printing process parameters is d = 0.34 mm, H = 0.51 mm, v1 = 10 mm/s, and v2 = 7.91 mm/s. Compared with the printing experiment results of the hydrogel line molding degree under the optimal process parameters, the error range is within −11.55%–1.27%, which further demonstrates the reliability of the optimization method of hydrogel extrusion printing process parameters based on numerical simulation and response surface method.
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