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Controllable gradient stent loaded with drugs, active factors and cells, 3D printing method of controllable gradient stent and special multi-nozzle 3D printer

A 3D printer and active factor technology, applied in the field of 3D printing of biological tissues and organs, can solve the problems of inability to achieve precise structure, no cells, poor controllability of the scaffold structure, etc., to achieve a simple and flexible printing process, and solve the problem of low adhesion rate. Effect

Active Publication Date: 2021-04-02
SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Although the first type has a more precise structural design, the scaffold itself does not contain cells. After implanting the defect site, the cells need to be guided to grow into the scaffold, which may easily lead to uneven growth of cells in the scaffold and "hollowing" phenomenon, or The constructed scaffold has large pores and it is difficult to obtain micropores below 100 μm, so that it cannot provide a three-dimensional support environment conducive to cell growth, so it is not easy for cells to adhere during culture
[0005] Although the second type introduces exogenous cells, the formed scaffold still has the problem of poor structural controllability and the inability to achieve precise structures.
[0006] The third type of current 3D printing technology printing method is relatively simple, commonly used single-nozzle printing method, which can only print brackets constructed with a single material
When the local structure of the two kinds of scaffolds is required to be combined, the problem that the double-layer gradient interface is not firm and easy to fall off is likely to occur
Therefore, it is impossible to realize the construction of complex tissues and organs
[0007] Therefore, in view of the above-mentioned related technologies, the inventor believes that there is a defect in the current technology that it is impossible to provide a controllable gradient scaffold with high precision and bionic complex tissues and organs

Method used

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  • Controllable gradient stent loaded with drugs, active factors and cells, 3D printing method of controllable gradient stent and special multi-nozzle 3D printer
  • Controllable gradient stent loaded with drugs, active factors and cells, 3D printing method of controllable gradient stent and special multi-nozzle 3D printer
  • Controllable gradient stent loaded with drugs, active factors and cells, 3D printing method of controllable gradient stent and special multi-nozzle 3D printer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Embodiment 1 Osteochondral integrated scaffold

[0065] The osteochondral integrated scaffold of Example 1 includes a subchondral bone layer scaffold, a cartilage layer scaffold, and a hydrogel layer containing anti-inflammatory drugs in sequence from bottom to top, and the three-layer structure is firmly connected.

[0066] Among them, the subchondral bone layer scaffold is printed by printing ink-1 containing polycaprolactone and β-tricalcium phosphate, the molecular weight of the polycaprolactone used is 10000-100000, and the content of β-tricalcium phosphate is 5 %~40%;

[0067] The cartilage layer scaffold is printed alternately by two kinds of ink materials, namely printing ink 2 containing polycaprolactone and small molecular organic compound Kartogenin (KNG), containing double-bond hyaluronic acid, human mesenchymal stem cells hBMSCs, UV photoinitiator, water printing ink three 3; wherein, the molecular weight of the polycaprolactone used in printing ink two 2 ...

Embodiment 2

[0079] Embodiment 2 large size bone tissue support

[0080] Large-scale bone tissue scaffolds were alternately printed in one step by two materials in a multi-jet 3D bioprinter.

[0081] Wherein, the first material is printing ink 1 composed of polycaprolactone and β-tricalcium phosphate, the molecular weight of the polycaprolactone used is 10,000-100,000, and the content of β-tricalcium phosphate is 5%-40%;

[0082]The second material is a printing ink mixed with double bond grafted gelatin, double bond grafted sodium alginate, ultraviolet photoinitiator, water, human bone marrow mesenchymal stem cells and human umbilical vein endothelial cells; the double bond used The mass fraction of grafted gelatin is 5% to 20%, the mass fraction of double bond modified sodium alginate is 1% to 10%, the ultraviolet photoinitiator is 0.05% to 0.1%, and the rest is water; The densities of stromal stem cells and human umbilical vein endothelial cells were both controlled at 1×10 6 ~3×10 6...

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Abstract

The invention relates to the technical field of biological tissue and organ 3D printing, in particular to a controllable gradient stent loaded with drugs, active factors and cells, a 3D printing method of the controllable gradient stent and a multi-nozzle 3D printer. The controllable gradient stent is formed through one-step alternate printing; the integrated gradient stent at least comprises twomaterials, namely a first material and a second material, wherein the first material is loaded with one or more of the drugs, the active factors or the cells; the second material is loaded with one ormore of the drugs, the active factors or the cells; and the first material and the second material are alternately printed to construct the integrated gradient stent. The integrated gradient stent constructed by the invention and loaded with the drugs, the active factors or the cells does not have the problems that a double-layer gradient interface is not firm and easy to fall off. The integratedgradient stent of the three-dimensional cells is constructed in a multi-nozzle alternate printing manner, and a foundation is provided for construction of complex tissues and organs of organisms.

Description

technical field [0001] This application relates to the technical field of 3D printing of biological tissues and organs, in particular to a controllable gradient scaffold loaded with drugs, active factors and cells, its 3D printing method and a multi-nozzle 3D printer. Background technique [0002] For a long time, researchers have tried to construct complex tissues and organs in the body through tissue engineering methods, so as to solve the problem of repairing damaged tissues in clinical practice and many problems such as infection, rejection, and donor shortage faced by organ transplantation. However, the functional microenvironment of different tissues and organs is quite different. Therefore, it is of great significance to choose the appropriate technology to successfully construct tissues and organs with differential functionalization in vitro, realize the gradient scaffold that can load cells and can simultaneously regulate the microenvironment to promote repair and re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B29C64/135B29C64/171B29C64/205B29C64/227B29C64/314B33Y10/00B33Y30/00B33Y40/00B33Y40/10
CPCB29C64/135B29C64/171B29C64/205B29C64/227B29C64/314B33Y10/00B33Y30/00B33Y40/00B33Y40/10
Inventor 阮长顺彭刘琪陈志刚王品品吴明明
Owner SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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