Tissue engineering bionic liver lobe structure based on 3D printing of living cells and preparation method thereof

Abstract

The invention discloses a tissue engineering bionic liver lobe structure based on 3D printing of living cells and a preparation method thereof. Firstly, biological information of human body liver lobes is collected, and inputted into a computer for high biomimetic modeling; then, material separated printing and material-cell mixed printing output are performed with a hydrogel material and cells for constructing liver, bile duct epithelium, blood vessel endothelium, smooth muscle and fibroblast and the like required for the human liver lobes by a biological 3D printer, wherein a hollow part inblood vessels and bile ducts is printed by a casting agent; after all the hydrogel materials are solidified, the casting agent in the blood vessels and bile ducts are removed by means of enzymes or chelating reactions or temperature control or illumination and the like, and a vascular system and a bile duct system in the artificial bile duct-containing liver lobes are constructed. The circulationfeeding of the vascular system of the bionic liver lobes and gas exchange are achieved by connection of main blood vessels at two ends of the vascular system and a delivery pipe of a culture solution.The long-term survival and biological function of the bionic liver lobes in vitro and in vivo are achieved.

Description

technical field [0001] The invention belongs to biomedical engineering, and particularly relates to a tissue engineering bionic liver lobe structure based on living cell 3D printing and a preparation method, that is, to prepare an artificial vascularized bile duct that can survive for a long time and has biological functions by adopting the method of biological 3D printing liver lobe. Background technique [0002] Existing artificial tissues are usually prepared by in vitro three-dimensional culture of cells, and only small-volume artificial tissues can be prepared. When the thickness of the artificial tissue exceeds 2 mm, it will cause deep tissue supply barriers, making it difficult for the artificial tissue to survive for a long time. In order to solve the problem of deep support barriers, researchers at home and abroad have carried out various explorations. For example, cells are seeded on porous scaffolds and soaked in medium for culture, so that nutrients can reach t...

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Problems solved by technology

For example, cells are seeded on a porous scaffold and soaked in the medium for culture, so that nutrients can reach the cells through the pores, but this method has certain limitations: as the cells grow, the pores in the scaffold will be filled by cells. The flow of nutrients is blocked, and the large-volume artificial tissue formed by this method is difficult to form the functional integration of cells in normal tissues due to the barrier of the scaffold material; in addition, some researchers use hydrogel materials that can induce blood vessel ingrowth However, this method still has the problem of deep support obstacles. When the blood vessels have not grown into the deep part, the deep cells will It has died due to lack of nutrients, and it is difficult to achieve long-term survival of real large-scale artificial tissues

The second product has the problems of short survival time, poor mechanical strength and simple vascular structure (single cell and simple network structure)

These two products are limited by the incomplete vascular system and in vitro support system, and both have the problem of limited size of the printed artificial liver tissue. After the size is limited, there is no way to simulate some functions of large-volume liver tissue, such as the lack of bile ducts. This structure lacks the function of bile transport

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