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Collagen-based 3D printing bioink, its preparation method and application

A 3D printing and collagen technology, applied in the field of bioengineering, can solve the problems of ineffective promotion of cell growth and differentiation, slow cross-linking speed, and low cytocompatibility, and achieve excellent cytocompatibility, mild reaction conditions, and extensive The effect of applying the foreground

Active Publication Date: 2021-10-22
WUQI BIOMEDICAL TECH (JIANGSU) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] There are many problems in the existing 3D printing bio-ink, including: slow cross-linking speed, after the printed scaffold reaches a certain number of layers, it needs to be further cross-linked and solidified with a cross-linking agent; it has certain cytotoxicity, and the introduced photoinitiator is toxic. The cross-linking agent glutaraldehyde, etc. make it difficult for the printed scaffold to be further applied in biomedicine; the cytocompatibility is not high, and it cannot effectively promote cell growth and differentiation, etc.
For example, the bio-ink preparation method in CN108310463A needs to solidify and characterize the gel support with toxic cross-linking agents such as glutaraldehyde, which cannot meet the needs of realizing ink and cell blending printing; the bio-ink preparation method in CN110171131A needs to add toxic photoinitiators to trigger Stent curing
The bio-ink preparation method in CN109575683A has a curing time as long as 15min-30min, which is difficult to realize fast multi-layer printing
In addition, more and more synthetic polymers and other natural polymers have been used to synthesize 3D printing bioinks, but their further applications are prevented due to their ineffective degradation or low cytocompatibility.

Method used

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  • Collagen-based 3D printing bioink, its preparation method and application
  • Collagen-based 3D printing bioink, its preparation method and application
  • Collagen-based 3D printing bioink, its preparation method and application

Examples

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preparation example Construction

[0032] In some embodiments, the preparation method of the aldylated hydroxyl-containing polymer comprises: at room temperature, in a protective atmosphere, the hydroxyl-containing polymer, p-aldehyde benzoic acid and 4-dimethylaminopyridine Dissolve in an anhydrous organic solvent, then add N,N'-dicyclohexylcarbodiimide, and react at 20-37°C for 15-20 hours. Wherein, the molecular equivalent ratio of the hydroxyl-containing polymer, p-aldehyde benzoic acid, 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide can be 1:3~4:0.3~ 0.4: 5-6. The anhydrous organic solvent may use tetrahydrofuran or the like, but is not limited thereto. The protective atmosphere may be selected from a nitrogen atmosphere, an inert atmosphere or a mixed atmosphere thereof, and is not limited thereto.

[0033] Another aspect of the embodiments of the present invention provides a method for preparing a collagen-based 3D printing bio-ink, comprising: mixing and reacting a collagen solution and a p...

Embodiment 1

[0056] Embodiment 1: A collagen-based 3D printing bio-ink provided in this embodiment includes a matrix and a solvent, wherein the mass concentration of the matrix is ​​20 mg / ml.

[0057] Further, the composition of the matrix is ​​collagen, tannic acid, and formylated hydroxyl-containing polymers, which are composed of collagen: tannic acid: formylated hydroxyl-containing polymers = 1:0.01-0.02 :1.

[0058] Further, the solvent is an acetic acid solution with a mass fraction of 0.1%. Wherein, the aldylated hydroxyl-containing macromolecule is formed after the hydroxyl-containing macromolecule undergoes an aldylation treatment. The hydroxyl-containing macromolecule uses hyaluronic acid.

[0059] Further, tannic acid is a natural plant-derived polyphenol containing 5 galloyl groups, also known as tannic acid, which can also be replaced by other plant polyphenols, such as epigallocatechin, one of gallic acid one or more combinations.

[0060] The bioink can be prepared by th...

Embodiment 2

[0070] Example 2: The collagen-based 3D printing bioink provided in this example, its preparation method and application method are basically the same as in Example 1, the difference is that the mass concentration of the matrix in the ink is 30mg / ml, and the concentration of the solvent is 0.5wt % acetic acid solution. The hydroxyl-containing macromolecule adopts dextran. Plant polyphenols use gallic acid. In the matrix, the mass ratio is collagen:gallic acid:formylated hydroxyl-containing polymer=1:0.05:4. In the process of preparing the aldylated hydroxyl-containing polymer, the molecular weight ratio between the hydroxyl-containing polymer, p-formylbenzoic acid, 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide The ratio is 1:3:0.4:6.

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Abstract

The invention discloses a collagen-based 3D printing bio-ink, its preparation method and application. The bio-ink of the present invention is mainly composed of biocompatible polymers and trace amounts of plant-derived polyphenols, etc., is safe and non-toxic, has high biocompatibility, and has a simple preparation process and low cost, and can be used in alkaline Fast curing by triple cross-linking reaction in gelatin coagulation bath. The collagen scaffold prepared by 3D printing using the biological ink of the present invention has high strength and stability, and can be widely used as a bioengineering scaffold.

Description

technical field [0001] The invention relates to a biomedical material, in particular to a collagen-based 3D printing bio-ink, its preparation method and application, and belongs to the technical field of bioengineering. Background technique [0002] 3D biological (cell) printing is an additive manufacturing technology developed in recent years for the manufacture of tissues or organs in vivo and in vitro. This new tissue engineering technology can precisely position cells, growth factors and other components on the biological scaffold. various parts. The development of 3D bioprinting technology is of great significance for solving clinical medical problems such as organ defects and for the development of personalized medicine and regenerative medicine. For 3D bioprinting technology, one of its core elements is the manufacture of bioink. An ideal bio-ink usually needs to meet the following requirements: (1) rapid prototyping (curing) ability; (2) mild reaction conditions su...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61L27/24A61L27/00A61L27/20A61L27/18A61L27/50B33Y70/10B33Y80/00
CPCA61L27/00A61L27/18A61L27/20A61L27/24A61L27/50B33Y70/00B33Y80/00C08L5/08C08L5/02C08L5/16C08L3/02C08L71/02
Inventor 陈艳艳杨文戴建武
Owner WUQI BIOMEDICAL TECH (JIANGSU) CO LTD