3D biology-printed hydrogel ink and preparation method thereof

A bioprinting and hydrogel technology, which is applied in drug delivery, pharmaceutical formulation, medical science, etc., can solve the problems of difficult balance between printing materials and cell activity, and achieve the effects of not being easily deactivated, ensuring a living environment, and promoting adhesion

Inactive Publication Date: 2019-11-01
苏州苏新瑞可医疗科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to provide a hydrogel ink for 3D bioprinting and its preparation method,

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] 5wt% sodium alginate, 6wt% porcine spinal cord acellular matrix hydrogel, 10wt% sheep dermis soft tissue-derived extracellular matrix nanofiber micropowder, 1wt% VEGF, 0.1wt% acetic acid, mixed with water, Stir until it is completely dissolved, adjust the pH to 7, add 1.5wt% extracellular vesicle suspension (concentration: 0.5mg / ml, mouse epithelial cell extracellular vesicle suspension), and mix well to obtain 3D printing bio-ink .

[0023] According to 5x10 5 cells / mL mouse fibroblasts were mixed with the resulting bioink to obtain cell bioink.

[0024] Cell bio-ink 3D printing conditions: 3D printer nozzle moving speed is 250mm / min, cell bio-ink extrusion speed is 260mm / min, and the obtained cell-loaded hydrogel has a compressive modulus of 130kPa. After printing, mouse fibroblasts The survival rate reached 91%, and after 7 days of culture, the cell survival rate reached 96%.

Embodiment 2

[0026] 7wt% sodium alginate, 8wt% porcine small intestinal submucosa acellular matrix hydrogel, 12wt% sheep dermis soft tissue-derived extracellular matrix nanofiber micropowder, 2wt% VEGF, 0.2wt% phosphoric acid, and water Mix and stir until completely dissolved, adjust the pH to 6.8, 2.5wt% extracellular vesicle suspension (0.7mg / ml concentration, extracellular vesicle suspension of porcine small intestinal mucosal epithelial cells), mix evenly to obtain 3D printing bioink.

[0027] According to 1x10 6 cells / mL Human vascular endothelial cells were mixed with the obtained bioink to obtain cell bioink. Cell bio-ink 3D printing conditions: 3D printer nozzle moving speed is 450mm / min, cell bio-ink extrusion speed is 470mm / min.

[0028] The compressive modulus of the obtained cell-loaded hydrogel was 120kPa. After printing, the survival rate of human vascular endothelial cells reached 85%, and after 7 days of culture, the cell survival rate reached 93%.

Embodiment 3

[0030] With 8wt% gelatin, 3wt% human spinal cord decellularized matrix hydrogel, 10wt% bovine dermis soft tissue derived extracellular matrix nanofiber micropowder, 3wt% RGD (sequence is composed of arginine, glycine and aspartic acid Acid composition), 0.1wt% acetic acid, mixed with water, stirred until completely dissolved, adjusted to pH 7, added 4wt% extracellular vesicle suspension (concentration is 0.45mg / ml, extracellular vesicles of Zebu skin cells suspension), mixed evenly to obtain 3D printing bio-ink.

[0031] According to 2x10 7 cells / mL mouse fibroblasts were mixed with the resulting bioink to obtain cell bioink.

[0032] Cell bio-ink 3D printing conditions: 3D printer nozzle moving speed is 250mm / min, cell bio-ink extrusion speed is 260mm / min, and the obtained cell-loaded hydrogel has a compressive modulus of 130kPa. After printing, mouse fibroblasts The survival rate reached 94%, and after 7 days of culture, the cell survival rate reached 98%.

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Abstract

The invention discloses 3D biology-printed hydrogel ink and a preparation method thereof. The 3D biology-printed hydrogel ink is prepared from the following components in percentage by weight: 1-10% of a solidifiable polymer, 1-10% of acellular matrix hydrogel, 1-10% of an extracellular vesicle suspension, 5-15% of a biomacromolecule material, 1-5% of a bioactive molecule, 0.1-0.5% of a solvent accelerating agent and the balance of water, and the total mass is 100%. According to the solidifiable polymer, water-soluble natural polysaccharide and natural high-polymer materials are adopted, and compatibility of the solidifiable polymer with cells is solved. In order to further improve the solidifiable polymer to provide establishment of a 3D model, the biomacromolecule material is added in biological ink, the solidifiable polymer can be assisted to further improve the ink viscosity, so that the mechanical strength of a final 3D model is better; and secondly, the biomacromolecule materialcan further provide substances required by part cells growing, and activity of the cells is guaranteed.

Description

technical field [0001] The invention belongs to the technical field of 3D printing and biomaterials, and in particular relates to a 3D bioprinting hydrogel ink and a preparation method thereof. Background technique [0002] Biological 3D printing technology has the characteristics of high precision, high efficiency, and personalized manufacturing. It has attracted enough attention in the field of biomedicine and has a very broad application prospect. The core technology of bio-3D printing is the three-dimensional controlled assembly process of cells. According to the digital model of organ anatomy, by controlling the 3D assembly of individual cells and cell clusters, it can be integrated into the human body's metabolic system for repairing and replacing lesions. Fabrication of artificial organs of tissues and organs. At present, bio-3D printing has made some progress in the reconstruction of structural tissues including teeth, bones, and cartilage. [0003] Bio-ink, bio-pr...

Claims

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Application Information

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IPC IPC(8): A61L27/36A61L27/38A61L27/52A61L27/54A61L27/22
CPCA61L27/227A61L27/3604A61L27/3633A61L27/3804A61L27/52A61L27/54A61L2300/414A61L2400/12
Inventor 刘刚黄靖栋刘军
Owner 苏州苏新瑞可医疗科技有限公司
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