生物三维打印细胞负载水凝胶类组织的精准优化

生物三维打印技术与水凝胶的完美结合,可为制造复杂结构功能的组织器官提供一种极具吸引力的解决方案。定制打印细胞负载水凝胶类组织的内部结构,可以更好地仿生真实组织器官的三维微环境,对打印后细胞生长、组织形成和功能再生至关重要。但水凝胶理化特性多变,精准打印与设计结构匹配的多孔结构仍然极具挑战。提出基于光学相干层析成像技术(OCT)的生物三维打印细胞负载水凝胶类组织的精准优化方法,通过自制的三维扫频OCT系统无损在线成像打印组织块和定量评价结构参数,迭代降低设计与打印间的结构差异,提高细胞负载水凝胶打印的精准性和稳定性。实验结果表明,基于OCT无损定量表征结果反馈优化打印参数设置,指导打印过程,使得细胞负载水凝胶类组织的结构形态参数与设计值的偏差从40%左右控制到7%以内,包括内部孔隙尺寸、支撑尺寸、孔隙率、表面积、体积五项关键参数;细胞培养两周后的存活率从80%左右显著提高到90%以上。研究表明OCT技术为批量定制细胞负载水凝胶类组织、生物三维打印组织和器官等提供了具有潜力的精准化工具。

Precise Optimization of 3D Bio-Printing Cell-Laden Hydrogel Construct

The combination of 3D bio-printing technology and hydrogel provides an attractive solution for manufacturing tissues and organs with complex structures and functions. The internal constructs can be custom-printed to imitate the 3D microenvironment of tissues and organs, which is critical for cell growth, tissue formation and regeneration after printed. However, precise matching between the printed and the design is still challenging due to variable physical and chemical properties of hydrogel. In this paper, an optimized method based on optical coherence tomography (OCT) for 3D bio-printing cell-laden hydrogel construct was proposed. The tissue was imaged by 3D non-destructive homemade OCT system, and quantitatively characterized, then the mismatch of structural parameters between the design and the printed was reduced using the experimentally obtained equations, and the accuracy and stability of 3D bio-printing were improved. The results demonstrated that the deviation of the key structural parameters between the printed and the design was controlled to less than 7%, which was much lower than the deviation about 40% reached by conventional 3D bio-printing. The controlled parameters included pore size, strut size, porosity, surface area and pore volume. And the cell viability of two weeks incubation was increased from about 80% to over 90%. It was concluded that online quantitative evaluation and feedback iterative analysis system based on OCT provided a potential tool for mass customization of cell-laden hydrogel tissues, 3D bio-printing tissues and organs.