Heterogeneous tumor model as well as preparation method and application thereof

A tumor and model technology, applied in biochemical equipment and methods, tumor/cancer cells, animal cells, etc., can solve the problems of lack of interaction, physiological morphology, functional differences and inhomogeneity of gene expression, etc., and achieve good application prospects , Improving the effect of printing and forming, the effect of promoting proliferation and differentiation and angiogenesis

Pending Publication Date: 2022-08-09
TSINGHUA BERKELEY SHENZHEN INST
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The two-dimensional cell culture model lacks sufficient intercellular, intracellular and cell-matrix interactions in vivo, and its physiological morphology, gene expression, functionality, etc. are significantly different from those in the in vivo environment
Although tumor microspheres have a certain tumor structure, which is divided into cell necrosis area, cell quiescence area and cell proliferation area, they cannot be cultured for a long time and the size formation is not uniform; although cell culture in three-dimensional hydrogel creates a three-dimensional matrix for cell survival environment, but cannot regulate the spatial distribution of cells, and it is difficult to reproduce the complex microenvironment of tumors
The cell culture model on microfluidics is between the two-dimensional model and the three-dimensional model, which is convenient for observing the interaction between cells, but it cannot simulate the real structure of solid tumors

Method used

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  • Heterogeneous tumor model as well as preparation method and application thereof
  • Heterogeneous tumor model as well as preparation method and application thereof
  • Heterogeneous tumor model as well as preparation method and application thereof

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Embodiment 1

[0038] The present embodiment provides a breast cancer heterogeneous tumor model, and the specific preparation steps are as follows:

[0039] (1) Structural design of heterogeneous tumor models in vitro

[0040] According to the spatial structure characteristics of the heterogeneous microenvironment of human solid tumors, solidworks software was used to design the three-dimensional three-dimensional map of the tumor clone area and tumor stromal area close to the natural tumor tissue microenvironment; the tumor clone area was 2.5mm and 3.5mm in diameter and 0.6 in height. mm of two small cylinders, the tumor stromal area is surrounded by the tumor clonal area, forming a large cylinder with a diameter of 10 mm and a height of 0.6 mm.

[0041] (2) Preparation of hydrogel materials

[0042]Methacrylated gelatin (GelMA) and gelatin and photoinitiator phenyl-2,4,6-trimethylbenzoyllithium phosphite (LAP) were dissolved in phosphate buffered saline (PBS) and mixed well , forming a h...

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Abstract

The invention belongs to the technical field of tumor model manufacturing, and discloses a heterogeneous tumor model and a preparation method and application thereof. The heterogeneous tumor model comprises a tumor cloning region and a tumor interstitial region around the tumor cloning region; the tumor cloning area is formed by three-dimensional biological printing of tumor cloning biological ink, and the tumor interstitial area is formed by three-dimensional biological printing of tumor interstitial biological ink; the tumor cloning bio-ink and the tumor interstitial bio-ink both contain a hydrogel material; the hydrogel material comprises a photo-crosslinking gel and a thermal response gel. The heterogeneous tumor model can maintain highly heterogeneous and fine microenvironment characteristics of in-vivo tumors, and can realize physiological and pathological functions of the tumors in an in-vitro culture process, in particular to formation of a bionic tumor microvascular network. Therefore, the heterogeneous tumor model has good application prospects in the fields of cancer occurrence and development and drug resistance mechanism research, tumor drug sensitivity detection, new anti-cancer drug screening and the like.

Description

technical field [0001] The invention belongs to the technical field of tumor model manufacturing, and in particular relates to a heterogeneous tumor model and a preparation method and application thereof. Background technique [0002] Malignant tumor (also known as cancer) is a disease with high lethality, and its morbidity and mortality have been on the rise in recent years, seriously threatening people's life, health and quality of life. An "accomplice" that develops and hinders drug treatment occurs. In addition to heterogeneous tumor cells, the tumor microenvironment also includes stromal cells such as macrophages, fibroblasts, adipocytes, and endothelial cells. The extracellular matrix is ​​a complex network structure composed of some biological macromolecules, which provides structural support for surrounding cells and tissues, and also interacts with tumor cells and interstitial cells to generate mechanical and mechanical signals, thereby regulating the biological pr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/09C12N5/071C12Q1/02
CPCC12N5/0693C12N5/0631C12N5/0656C12N5/069C12N5/0697G01N33/5011C12N2533/56C12N2533/54C12N2513/00C12N2537/10C12N2503/02G01N2500/10
Inventor 孙伟弥胜利袁天莹郭钟伟
Owner TSINGHUA BERKELEY SHENZHEN INST
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