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Method for preparing degradable microspheres by using 3D printing, and application of degradable microspheres in construction of functional in vitro micro-tissues

A 3D printing and micro-tissue technology, applied in artificial cell constructs, prostheses, tumors/cancer cells, etc., can solve the problems of poor morphological consistency of microspheres, difficult separation of initiators, and difficult to control the particle size of microspheres. Achieve the effect of high uniformity of particle size and shape, good biological properties, and good application value

Inactive Publication Date: 2019-06-18
TSINGHUA UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although the above preparation method is relatively simple and easy, a large number of microspheres can be prepared quickly, however, the particle size of the prepared microspheres is usually difficult to control, and the consistency of the microsphere shape is poor.
Moreover, the organic solvent and reaction initiator used in the preparation process are difficult to remove by separation, which has a great impact on the normal biological activity of adherent cells
The problems of the above preparation methods limit the application of microspheres in tissue engineering

Method used

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  • Method for preparing degradable microspheres by using 3D printing, and application of degradable microspheres in construction of functional in vitro micro-tissues
  • Method for preparing degradable microspheres by using 3D printing, and application of degradable microspheres in construction of functional in vitro micro-tissues

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1 Preparation of biodegradable microspheres for constructing functional in vitro microtissues

[0046] This example takes the natural degradable hydrogel material—sodium alginate hydrogel as an example to prepare degradable microspheres as a raw material, and provides a method for preparing biodegradable microspheres for constructing functional in vitro microtissues ( The preparation process is as figure 1 shown), specifically include the following steps:

[0047] 1. Preparation of sodium alginate hydrogel material

[0048] (1) Preparation of sodium alginate solution:

[0049] ① Taking the preparation of 100ml of 1% sodium alginate solution as an example, weigh 1g of sodium alginate powder and dissolve it in 100ml of 0.9% sterile sodium chloride aqueous solution, and place it in an oven at 70°C for three times. 30 minutes to achieve the purpose of sterilization. Then place it in an oven at 70°C for at least 6 hours to ensure that the sodium alginate is fully...

experiment example 1

[0061] Particle size distribution analysis of experimental example 1 degradable hydrogel microspheres

[0062] The particle size distribution measurement of the degradable hydrogel microspheres prepared in Example 1 and Comparative Example 1, the specific method is as follows:

[0063] After the degradable hydrogel microspheres were fully washed, the particle size distribution of the degradable hydrogel microspheres prepared in Example 1 and Comparative Example 1 was measured using a fully automatic laser particle size distribution analyzer. After measurement, the particle size distribution range of the microspheres prepared in Comparative Example 1 is wider, indicating that the preparation method cannot accurately control the particle size, and compared with Comparative Example 1, the particle size of the hydrogel microspheres prepared in Example 1 The distribution is obviously more concentrated, indicating that the particle size of the degradable hydrogel microspheres prepar...

experiment example 2

[0064] Experimental Example 2 Evaluation of Mechanical Properties of Degradable Hydrogel Microspheres

[0065] The mechanical properties such as mechanical strength and elasticity of the degradable hydrogel microspheres prepared in Example 1 and Comparative Example 1 were tested and evaluated.

[0066] In order to evaluate the mechanical properties of the degradable hydrogel microspheres, the prepared hydrogel microspheres were collected, and the microspheres with similar particle sizes in the hydrogel microspheres prepared in Example 1 and Comparative Example 1 were selected, and the dynamic The tensile elastic modulus of the microspheres was measured by a static fatigue tensile testing machine, and the compressive elastic modulus of the microspheres was measured by the microsphere indentation method. The results show that the elastic modulus of the hydrogel microspheres prepared in Experimental Example 1 is slightly higher than that in Comparative Example 1.

[0067] In ord...

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Abstract

The invention relates to the technical fields of biological manufacturing and tissue engineering, and concretely relates to a method for preparing degradable microspheres by using 3D printing, and anapplication of the degradable microspheres in the construction of functional in vitro micro-tissues. The method for preparing degradable microspheres by using 3D printing comprises the following steps: preparing a biodegradable hydrogel, preparing hydrogel micro-drops by 3D printing, and preparing the hydrogel microspheres by a crosslinking reaction of the hydrogel micro-drops. The hydrogel material with good mechanical properties, formability, biocompatibility and degradability is used as the material for preparing the microspheres, and 3D bio-printing is used to achieve the rapid productionof the hydrogel microspheres with good biocompatibility, degradability and mechanical properties from the hydrogel material; and compared with microspheres prepared by adopting traditional methods, the hydrogel microspheres in the invention have the advantages of accurate and controllable particle size, high particle size uniformity and high form uniformity, are suitable for constructing functional in vitro micro-tissues at different scales, and have good application values in the field of tissue engineering.

Description

technical field [0001] The invention relates to the technical fields of biomanufacturing and tissue engineering, in particular to a method for preparing degradable microspheres based on 3D bioprinting technology and its application in constructing functional in vitro microtissues. Background technique [0002] At present, the production and application of biological microspheres are mainly focused on pharmaceutical use, and they are often used as drug carriers for drug delivery and sustained release in vivo. Different from pharmaceutical microspheres, microspheres used in tissue engineering usually serve as cell scaffolds, providing a carrier for cells to adhere and grow. Therefore, microspheres for tissue engineering should have good biocompatibility and degradability. Microsphere preparation methods in the prior art mainly include emulsification dispersion method, coacervation method and polymerization method. Among them, both the emulsification dispersion method and the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/075C08J3/24B33Y70/00B33Y80/00A61L27/56A61L27/50A61L27/20A61L27/52A61L27/38C12N5/071C12N5/09C08L5/04
Inventor 庞媛何剑宇翁鼎王紫桐周珍珍卢仁浩
Owner TSINGHUA UNIV
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