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Method for preparing injectable porous hydrogel microspheres by microfluidic ice crystal method and application of injectable porous hydrogel microspheres

A porous hydrogel and hydrogel technology, which is applied in the fields of pharmaceutical formulation, medical science, prosthesis, etc., can solve the problems of lack of pores in microspheres, the influence of biologically active factors, and changes in the external structure of materials, and achieve good monodispersity , clean energy and high stability

Active Publication Date: 2021-02-26
杭州贤石生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the currently commonly used hydrogel microspheres have the following problems: (1) lack of pores inside the microspheres, resulting in impermeability of nutrients and the inability of internal cells to survive; (3) A chemical cross-linking agent is used in the preparation process, and its degradation products have certain toxicity to the body
[0004] At present, the methods commonly used to prepare porous hydrogels are mainly freeze-drying, particle leaching and air bubble methods. However, these methods have changes in the external structure of the material, pores The size is uncontrollable, only suitable for bulk hydrogels and not suitable for the preparation of micron-sized hydrogel microspheres, etc.

Method used

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  • Method for preparing injectable porous hydrogel microspheres by microfluidic ice crystal method and application of injectable porous hydrogel microspheres
  • Method for preparing injectable porous hydrogel microspheres by microfluidic ice crystal method and application of injectable porous hydrogel microspheres
  • Method for preparing injectable porous hydrogel microspheres by microfluidic ice crystal method and application of injectable porous hydrogel microspheres

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Embodiment 1, preparation and characterization of GelMA (one) preparation of GelMA (see figure 1 )

[0050] Weigh 20g of gelatin, add it to a 2L conical flask and add 200mL PBS, place the conical flask in a water bath at 60°C, stir until the gelatin is completely dissolved, and add dropwise to the conical flask after the gelatin is completely dissolved A total of 16 mL of methacrylic anhydride was added, and the entire dropping process lasted for 1 h. 2 hours after the dropwise addition, 800 mL of PBS preheated to 50° C. was added into the above-mentioned Erlenmeyer flask, and the stirring was continued for 15 minutes. After 15 minutes, the liquid in the Erlenmeyer flask was poured into a dialysis bag with a molecular weight cut-off of 8000-14000, and dialyzed for one day. On the second day, the liquid in the dialysis bag was collected, centrifuged at 37° C. and 7000 rpm, and the supernatant was taken, and the dialysis was continued at 37° C. for three days. Afterwar...

Embodiment 2

[0053] Embodiment 2, the preparation of hydrogel

[0054] Weigh 50 mg (5 wt%) of GelMA prepared in Example 1 and add it into 1 ml of deionized water, heat to 50° C. for 1 hour to dissolve. After fully dissolving, add 5 mg of photoinitiator LAP, and after fully dissolving, store in the dark for future use.

Embodiment 3

[0055] Embodiment 3, the preparation of microfluidic device

[0056] The present invention utilizes a coaxial capillary microfluidic device to prepare water-in-oil (W / O) hydrogel micro-droplets (see schematic diagram of its principle) image 3 ), that is, use the oil phase fluid as the continuous phase to shear the water phase to disperse in the oil phase to form micro-droplets. The principle is that when the continuous phase fluid shears the dispersed phase fluid, when the shear force is greater than the interface between the two phases Under tension, the dispersed phase is sheared into individual dispersed droplets at the interface between the two phases. The invention utilizes self-made glass capillary to design and manufacture a microfluidic device suitable for producing hydrogel microspheres. The production method is simple, and the produced hydrogel microspheres have the characteristics of controllable size, good monodispersity, high repetition rate and the like.

[005...

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Abstract

The invention provides a method for preparing injectable porous hydrogel microspheres by a microfluidic ice crystal method and application of the injectable porous hydrogel microspheres, and the preparation method comprises the following steps: (1) mixing a hydrogel material, a buffer solution and a photoinitiator to obtain a hydrogel solution, and adding dimethyl sulfoxide into the hydrogel solution to obtain an aqueous phase solution; mixing an oily material with a surfactant to obtain an oil phase solution; (2) adding the aqueous phase solution and the oil phase solution into a microfluidicdevice to prepare hydrogel micro-droplets; (3) carrying out low-temperature treatment on the hydrogel micro-droplets to form ice crystals; after the ice crystals are completely formed, maintaining alow-temperature environment, carrying out curing cross-linking under ultraviolet irradiation, and heating to room temperature after cross-linking is completed, so that pores are formed after the ice crystals are melted, and the porous hydrogel microspheres are obtained. The hydrogel microsphere disclosed by the invention has the characteristics of being porous and uniform in pore diameter, can load different types of cells, and has a very great application prospect in the aspects of bone repair, skin defects and the like as an excellent cell carrier.

Description

technical field [0001] The invention belongs to the technical field of preparation of hydrogel materials, and in particular relates to a method for preparing injectable porous hydrogel microspheres by a microfluidic ice crystal method and an application thereof. Background technique [0002] Hydrogel is a three-dimensional network structure containing a large amount of water formed by the cross-linking of hydrophilic polymers. It has the advantages of high hydrophilicity, high viscoelasticity, low friction coefficient, and excellent biocompatibility. Adhesive materials are widely used in biomedical fields such as cell carriers, drug carriers, and tissue engineering. Generally, the construction materials of hydrogels are mainly divided into two types: natural polymers and synthetic polymers. Among them, natural polymer materials refer to polymer materials derived from natural animals and plants, which have excellent biocompatibility and biological activity, mainly including ...

Claims

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Application Information

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IPC IPC(8): C08F299/00C08F2/48C08J3/075C08J9/28C08L55/00A61L27/22A61L27/50A61L27/52A61L27/54A61L27/56
CPCC08F299/00C08F2/48C08J3/075C08J9/28A61L27/52A61L27/56A61L27/50A61L27/54A61L27/222C08J2355/00A61L2400/06A61L2300/602A61L2430/02A61L2430/32A61L2430/24
Inventor 赵静文崔文国俞小华
Owner 杭州贤石生物科技有限公司
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