Construction method of biomimetic vascular network inside large-volume tissue-engineered tissues and organs

Abstract

The invention discloses a method for constructing a bionic vascular network inside a large-volume tissue engineering tissue organ. First, biological information of a certain large-volume tissue of the human body is collected, and input into a computer for high bionic modeling; Using the hydrogel material and a variety of expanded cells from the tissue to perform material-only printing and material-cell hybrid printing, the cavity in the blood vessel is printed with controllable degradable hydrogel; after all hydrogel materials are cured Then, the controllable degradable hydrogel in the blood vessel is removed by means of specific enzymes or chelation reaction or temperature control or illumination, and a vascular network in a large-volume artificial tissue is constructed; the main blood vessels at both ends of the vascular network and the culture medium are transported. The tube is connected to realize the circulation supply and gas exchange of the vascular network of the large-volume artificial tissue. It solves the problem of central feeding of large-volume artificial tissue, so as to realize the long-term survival and biological function of large-volume artificial tissue in vitro.

Description

technical field [0001] The invention belongs to biomedical engineering, and particularly relates to a bionic vascular network in a large-volume artificial tissue based on biological 3D printing and a preparation method thereof. Central feeding issues to achieve long-term survival and biological function of large-volume artificial tissues in vitro. 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, the deep tissue supply obstacle will be caused, making it difficult for the artificial tissue to survive for a long time. In order to solve the problem of deep feeding obstacles, domestic and foreign researchers have carried out a variety of different explorations. For example, cells are seeded on porous scaffolds and immersed in medium for culture, so that nutrients can reach the cells thro...

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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, simple vascular structure, single cells and simple network structure

These two products are limited by the incomplete vascular network 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

The products of some companies may form some pipelines by incorporating endothelial cells during printing, but these pipelines will not form a vascular network with complete functions of blood vessels such as penetration, transportation, and circulation. The functions are very different, it is not a bionic structure, and it is difficult to form a functional vascular network

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