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Biocompatible porous frozen gel microspheres and preparation method thereof

A biocompatible and cryogel technology, applied in the field of biocompatible porous cryogel microspheres and its preparation, can solve the difficulty in meeting the needs of three-dimensional cell culture, restrict the construction effect of cell gel complexes, and only It can achieve the effect of simplifying the steps of cell loading, precise size and wide application range in shallow surface layer and other problems

Inactive Publication Date: 2019-07-12
SHANGHAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, such conditional changes usually damage cells, and the components used to initiate polymerization or participate in polymerization may also have strong cytotoxicity, which restricts the construction effect of cell gel complexes.
It is also possible to pre-prepare the gel matrix first, and then carry out subsequent cell loading, but due to the limitation of the macroscopic diffusion size, the cell loading is usually only in the superficial layer, which is difficult to meet the needs of three-dimensional cell culture

Method used

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  • Biocompatible porous frozen gel microspheres and preparation method thereof
  • Biocompatible porous frozen gel microspheres and preparation method thereof
  • Biocompatible porous frozen gel microspheres and preparation method thereof

Examples

Experimental program
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preparation example Construction

[0031] For the preparation method of methacrylic anhydride-modified gelatin, please refer to: Biomacromolecules 2000, 1, 31-38.

[0032] The synthesis of dendritic alkoxy ethers refers to references: Macromolecules, 2008, 41, 3659-3667.

Embodiment 1

[0033] Example 1: Preparation of biocompatible porous cryogel microspheres

[0034] Step 1. Fabrication of cryogel microsphere prepolymer droplets on a microfluidic droplet chip

[0035] use figure 1 For the chip shown in a, 10% GelMA aqueous solution with a mass fraction of 40°C is injected into the liquid inlet of the chip; the initiator ammonium persulfate aqueous solution, TEMED and the aforementioned solution are combined into a structure of one pipeline through two pipelines before being passed into the chip Make a premix. Use a constant temperature environment to keep the chip at a constant temperature of 40 °C. The volatile oil phase HEF7500 (containing 2% EA surfactant produced by RANBiotechnology, US) was introduced as an entrainment flow. Control the flow rate of the water phase GelMA solution to 100 μL / min, the flow rate of the water phase initiator and TEMED mixed solution to 100 μL / min, and the oil phase flow rate to 200 μL / min, through the microfluidic drople...

Embodiment 2

[0038] Example 2: Preparation of porous cryogel microspheres with both biocompatibility and temperature-sensitive environmental responsiveness

[0039] Step 1. Fabrication of cryogel microsphere prepolymer droplets on a microfluidic droplet chip

[0040] use figure 1For the chip shown in b, the aqueous solution of 6% GelMA with a constant temperature of 40°C was injected into the liquid inlet of the chip; the APS aqueous solution, TEMED and the aforementioned solution were premixed by combining two pipes on the chip into one pipe. Use a constant temperature environment to keep the chip at a constant temperature of 40°C. The volatile oil phase HEF7500 (containing 1% RAN Biotechnology, US-produced EA surfactant) was introduced as an entrainment flow. Control the flow rate of the water phase GelMA and dendrimer monomer mixed solution to 30 μL / min, the water phase initiator and TEMED mixed solution flow rate to 30 μL / min, and the oil phase flow rate to 100 μL / min. Gel ball drop...

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Abstract

The invention relates to biocompatible porous frozen gel microspheres and a preparation method thereof. By the aid of a droplet-based microfluidic technology, uniform droplets containing gel prepolymers are formed in a high throughput manner; then frozen gel microspheres are formed through a polymerization reaction under a freezing condition. The microspheres can allow high-density support and growth of cells due to controllable porous structures and rough surface properties. The gel microspheres also have excellent biocompatibility, cytotoxicity caused by re-crosslinking after coating of cells with traditional polymer gel microspheres is avoided, so that the gel microspheres are more convenient and reliable to use as extracellular matrixes. Further, a certain proportion of linear or dendritic alkoxy ether molecules are added to a gel microsphere crosslinked system for preparation of composite gel microspheres, the gel microspheres can be endowed with intelligent temperature response performance, and construction of intelligent bionic matrixes is particularly facilitated. Due to the innovativeness, the material is expected to replace traditional natural extracellular matrixes and widely applied to construction of bionic tissue and organs.

Description

technical field [0001] The present invention relates to a preparation method of polymer functional microspheres with special structure and properties, especially biocompatible porous cryogel microspheres with biocompatibility, high throughput and high uniformity as extracellular matrix and its preparation method. Background technique [0002] Gel is the main form of extracellular matrix and a key component of the cell growth environment, so it is of great significance in cell culture, biological tissue imitation, and artificial organ models. Compared with the two-dimensional cell culture environment of the petri dish, the gel can provide the cells with a three-dimensional environment, which is closer to the natural environment of the cells. Since the metabolic activities and behaviors of cells are closely related to their growth environment, using gel as a carrier to construct cell-related tissue and organ models can more accurately simulate physiological functions and pred...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08F289/00C08F220/30C08J9/00C08J3/24C12N5/00
CPCC08F289/00C08J3/246C08J9/00C08J2333/14C08J2489/00C12N5/00C12N2533/54C08F220/302
Inventor 李文徐碧漪陈艳琼王盈秋张阿方
Owner SHANGHAI UNIV