The generation of artificial human tissue by 3D-bioprinting has expanded significantly as a clinically relevant research topic in recent years. However, to produce a complex and viable tissue, in-depth biological understanding and advanced printing techniques are required with a high number of process parameters. Here, we systematically evaluate the process parameters relevant for a hybrid bioprinting process based on fused-deposition modeling (FDM) of thermoplastic material and microextrusion of a cell-laden hydrogel. First, we investigated the effect of the printing temperature of polycaprolactone (PCL), on the junction strength between individual fused filaments and on the viability of immortalized mesenchymal stem cells (iMSC) in the surrounding alginate-gelatin-hydrogel. It was found that a printing temperature of 140 °C and bonds with an angle of 90° between the filaments provided a good compromise between bonding strength of the filaments and the viability of the surrounding cells. Using these process parameters obtained from individual fused filaments, we then printed cubic test structures with a volume of 10 × 10 × 10 mm³ with different designs of infill patterns. The variations in mechanical strength of these cubes were measured for scaffolds made of PCL-only as well as for hydrogel-filled PCL scaffolds printed by alternating hybrid bioprinting of PCL and hydrogel, layer by layer. The bare scaffolds showed a compressive modulus of up to 6 MPa, close to human hard tissue, that decreased to about 4 MPa when PCL was printed together with hydrogel. The scaffold design suited best for hybrid printing was incubated with cell-laden hydrogel and showed no degradation of its mechanical strength for up to 28 days.

近年来，通过 3D 生物打印生成人造人体组织已成为临床相关的研究课题。然而，要生产复杂且可行的组织，需要深入的生物学理解和先进的印刷技术以及大量的工艺参数。在这里，我们基于热塑性材料的熔融沉积建模 (FDM) 和载有细胞的水凝胶的微挤出系统地评估了与混合生物打印工艺相关的工艺参数。首先，我们研究了聚己内酯 (PCL) 的印刷温度对单个融合细丝之间的连接强度以及对周围海藻酸盐-明胶-水凝胶中永生化间充质干细胞 (iMSC) 活力的影响。发现 140°C 的印刷温度和长丝之间以 90° 的角度粘合在长丝的粘合强度和周围细胞的活力之间提供了良好的折衷。使用从单个熔丝获得的这些工艺参数，我们然后打印体积为 10 × 10 × 10 mm 的立方体测试结构³填充图案的不同设计。这些立方体的机械强度变化是针对仅由 PCL 制成的支架以及通过 PCL 和水凝胶的交替混合生物打印逐层打印的水凝胶填充 PCL 支架进行测量的。裸支架显示出高达 6 MPa 的压缩模量，接近人体硬组织，当 PCL 与水凝胶一起打印时，压缩模量降至约 4 MPa。最适合混合打印的支架设计与载有细胞的水凝胶一起孵育，在长达 28 天的时间里，其机械强度没有下降。