Mechanically enhanced gelatin chilled hydrogel as well as preparation method and application thereof

A technology of freezing water and hydrogel, which is applied in medical science, absorbent pads, non-active ingredients of polymer compounds, etc., can solve the problems of short degradation cycle, limited promotion, monomer residue, etc., and achieve good biocompatibility and prolong life. The effect of the degradation cycle

Active Publication Date: 2021-05-07
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage is that factors such as poor mechanical properties and too short degradation cycle greatly limit the further promotion of these natural polymer gels in the field of tissue engineering.
Using small molecular monomers (such as acrylamide, etc.) to participate in cross-linking or doping with nanoparticles (such as hydroxyapatite (HA) and bioglass (BG), etc.) is a common way to improve the mechanical strength of cryogels. However, there will be problems such as monomer residues and limited increase: For example, Song et al. used BG to be incorporated into GelMA jelly to increase the calculated value of Young's modulus from about 80kpa to about 170kpa (Song K, Seunghun L, Sivashanmugam A, et al. al.Bioglass-Incorporated Methacrylated Gelatin Cryogel for Regeneration of Bone Defects[J].Polymers,2018,10(8):914.); Gu et al. used HA nanowires to enhance GelMA gelatin, and its Young's modulus ranged from about Increase from 35Kpa to 55Kpa (20% strain) (Gu L, Zhang J, Li L, et al. Hydroxyapatitenanowire composited gelatin cryogel with improved mechanical properties and cell migration for bone regeneration[J].Biomedical Materials,2019.)
In addition, due to the osteogenic effect or vascularity of HA and BG particles, this kind of composite jelly is only suitable for bone repair or dressing, which is not conducive to broadening the practical application range of jelly

Method used

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  • Mechanically enhanced gelatin chilled hydrogel as well as preparation method and application thereof
  • Mechanically enhanced gelatin chilled hydrogel as well as preparation method and application thereof
  • Mechanically enhanced gelatin chilled hydrogel as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Embodiment 1: Preparation of low solid content jelly (concurrently load-bearing test)

[0041] (1) Preparation of GelMA and SF-GMA

[0042] Dissolve 1g of gelatin in 10ml of 1×PBS buffer at 50°C, stir for 30 minutes until the gelatin is completely dissolved, use a micro-injection pump to continuously inject 0.6ml of methacrylic anhydride within 30 minutes, and then continue to react for 3 hours. The product was transferred to an 8-12kDA dialysis bag, and dialyzed at 40°C, the water was changed twice a day for 7 days, and the dialyzed product was freeze-dried to obtain white spongy methacrylylated gelatin (GelMA). Store at low temperature.

[0043] Add 1g of silk fibroin to 7ml of saturated lithium bromide solution at 60°C and stir for 40 minutes to dissolve it to obtain a silk fibroin solution, inject 0.3ml of glycidyl methacrylate into the silk fibroin solution, and stir for 3 hours to react , the stirring rate is 100-250rpm, the product is transferred to a 8-12kDA d...

Embodiment 2

[0050] Embodiment 2: preparation of higher solid content jelly

[0051] (1) Preparation of GelMA, SF-GMA and APS solutions

[0052] Prepare GelMA, SF-GMA solution, etc. according to the method of Example 1, weigh 0.45g APS and add it into 15ml ultrapure water, stir until APS is completely dissolved, and place the APS solution in a refrigerator at 4°C for use.

[0053] (2) Preparation of higher solid content (15%) GelMA / SF-GMA composite frozen hydrogel

[0054] Dissolve 1.2g of GelMA in 2.182ml of deionized water, then add 6.818ml of concentrated SF-GMA solution with a mass fraction of 8.8%, let stand at 40°C for 5min and stir well, then add 60μl of TEMED and mix well, and finally add 3ml of APS solution and stirred for 10s to mix the material, then divided into molds and stored at -30°C for cross-linking treatment (inducing free radical cross-linking), the time of cross-linking treatment is 24h, induction Frozen hydrogels form.

[0055] (3) Post-treatment of jelly

[0056]...

Embodiment 3

[0057] Example 3: Preparation of jelly with different solid content (and SEM morphology characterization)

[0058] (1) Preparation of GelMA, SF-GMA and APS solutions:

[0059] Prepare GelMA and SF-GMA solutions according to the method of Example 1, weigh 0.45g APS and add it to 15ml ultrapure water, dissolve it and place it in a refrigerator at 4°C for use.

[0060] (2) Preparation of GelMA / SF-GMA composite jelly with different solid contents:

[0061] In a series of vials, add the components of the hydrogel precursor solution in sequence according to the parameters in Table 1 and mix thoroughly. Finally, add the ammonium persulfate solution and stir for 10 seconds to mix the precursor solution, and then immediately transfer it to the mold and stored at -20°C for 12 hours to induce frozen hydrogel formation.

[0062] Table 1: Component ratios of frozen hydrogels with different solid contents

[0063]

[0064](3) Post-processing and characterization of frozen hydrogels

...

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Abstract

The invention discloses mechanically enhanced gelatin frozen hydrogel as well as a preparation method and application thereof. The method comprises the following steps: compounding methylacryloylated gelatin and a glycidyl acrylate modified silk fibroin solution, adding an ammonium persulfate/tetramethylethylenediamine initiator solution to realize free radical crosslinking at low temperature, and inducing an SF-GMA molecular chain to form a hydrophobic crystal (beta-sheet structure) by post-treatment of a methanol solution to obtain the frozen hydrogel. The frozen hydrogel has a through macroporous structure of about 200 [mu]m under a swelling equilibrium condition, the compression modulus of the frozen hydrogel can be enhanced from 0.057 Mpa to 0.523 Mpa, the degradation period of the frozen hydrogel in an environment containing type II collagenase is prolonged from 7 days to 28 days, the degradation residue is 60%, and the frozen hydrogel has good biocompatibility. The method provided by the invention is simple in preparation process, effectively enhances the performance of the jelly, and has a good application prospect in the fields of drug delivery, tissue repair and the like.

Description

technical field [0001] The invention relates to the technical field of manufacturing composite hydrogel materials, in particular to a mechanically reinforced gelatin frozen hydrogel and its preparation method and application. Background technique [0002] Macroporous hydrogels have the characteristics of high specific surface area and internal through-hole structure, and have the ability of rapid exchange of support substances and cell migration, so they have broad prospects in biomedical fields such as drug sustained release, cell carriers, and tissue engineering scaffolds. Because the macroporous gels prepared by the current porogen method often have deficiencies such as porogen residues and prone to closed pores, frozen hydrogels (hereinafter referred to as jelly) prepared by cryogelation have become more and more popular in recent years. focus on. [0003] If the hydrogel is prepared by cross-linking below the freezing point of the system, it is called jelly. Its formin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/075C08H1/00A61K9/06A61K47/42A61L15/32A61L15/42A61L15/64A61L27/22A61L27/52A61L27/58C08L89/00
CPCC08J3/075A61K47/42A61K9/06A61L15/32A61L15/325A61L15/42A61L15/64A61L27/222A61L27/227A61L27/52A61L27/58A61L2430/02A61L2430/06C08J2389/00C08J2489/00C08L89/00
Inventor 方立明潘西满陈文祥钟华苏健裕
Owner SOUTH CHINA UNIV OF TECH
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