Preparation method of photocuring hydrogel microspheres capable of promoting angiogenesis

Abstract

The invention discloses a preparation method of photocuring hydrogel microspheres capable of promoting angiogenesis, and belongs to the technical field of biological material preparation. The hydrogel microsphere is a high-specificity angiogenesis promoting material, has the effects of promoting cell adhesion, increasing vascular permeability, denaturation of an extracellular matrix, migration and proliferation of vascular endothelial cells, angiogenesis and the like, and can be prepared in batches. The hydrogel microspheres are prepared by the following steps: by taking a natural-source high polymer material gelatin as a substrate material, modifying the gelatin through methacrylic anhydride, grafting a vascular endothelial growth factor (VEGF) onto a molecular skeleton of methacrylic acid acylated gelatin by adopting a covalent linkage method on the basis, and then forming the microspheres in batches under the action of an electric field. The controllable light-cured hydrogel microspheres prepared by the method have good biocompatibility, can be degraded in vivo, have the effect of promoting vascularization, can actively induce cell adhesion, and have good application prospects in regenerative medicine and clinical treatment.

Description

technical field

[0001] The invention relates to the technical field of biomaterial preparation, in particular to a method for preparing controllable light-curable hydrogel microspheres that can promote angiogenesis.

[0002] technical background

[0003] Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (vascular permeability factor, VPF), is a highly specific factor that promotes the growth of vascular endothelial cells. Matrix degeneration, vascular endothelial cell migration, proliferation and angiogenesis. VEGF and its receptors are expressed in human placental trophoblast cells and vascular endothelial cells, indicating that VEGF is involved in normal pregnancy, the regulation of placental angiogenesis and the physiological invasion of trophoblast cells. However, currently existing peptide hydrogels cannot effectively control their degradation rate.

[0004] At present, in the field of biomedical materials, most of them are specific ...

Examples

Embodiment 1

[0030] A method for preparing photocurable hydrogel microspheres that can promote angiogenesis, specifically comprising the following steps:

[0031] (1) Add sodium carbonate to the obtained deionized water, dilute and adjust the pH to 7.4, add gelatin to the sodium carbonate solution at a ratio of 100g / L, stir and dissolve at 50°C, then add methacrylic anhydride, methyl The volume mass ratio of acrylic anhydride to gelatin is 2:1. After the reaction is completed, dialyze with deionized water at room temperature for 5 days, change the water every 12 hours, and the molecular weight cut-off of the dialysis bag is 8KDa-14Kda. Acrylic acylated gelatin.

[0032] (2) Dissolve methacrylic acylated gelatin in deionized water at a ratio of 100g / L, then add succinic anhydride, the volume-to-mass ratio of succinic anhydride to methacrylic acylated gelatin is 1:1.6. Stir and react for 24 hours; after the reaction is completed, dialyze with deionized water at room temperature for 5 days, ...

Embodiment 2

[0052] A method for preparing photocurable hydrogel microspheres that can promote angiogenesis, specifically comprising the following steps:

[0053] (1) Add sodium carbonate to the obtained deionized water, dilute and adjust the pH to 8, add gelatin to the sodium carbonate solution at a ratio of 50g / L, stir and dissolve at 35°C, then add methacrylic anhydride, methyl The volume mass ratio of acrylic anhydride to gelatin is 1:1. After the reaction is completed, dialyze with deionized water at room temperature for 5 days, change the water every 12 hours, and the molecular weight cut-off of the dialysis bag is 8KDa-14Kda. Acrylic acylated gelatin.

[0054] (2) Dissolve methacrylic acid acylated gelatin in deionized water at a ratio of 50g / L, then add succinic anhydride, the volume-mass ratio of succinic anhydride to methacrylic acid acylated gelatin is 1:1, at 25°C Stir and react for 24 hours; after the reaction is completed, dialyze with deionized water at room temperature for...

Embodiment 3

[0061] A method for preparing photocurable hydrogel microspheres that can promote angiogenesis, specifically comprising the following steps:

[0062] (1) Add sodium carbonate to the obtained deionized water, dilute and adjust the pH to 10, add gelatin to the sodium carbonate solution at a ratio of 200g / L, stir and dissolve at 60°C, then add methacrylic anhydride, methyl The volume mass ratio of acrylic anhydride to gelatin is 3:1. After the reaction is completed, use deionized water to dialyze at room temperature for 5 days, and change the water every 12 hours. The molecular weight cut-off of the dialysis bag is 8KDa-14Kda. Acrylic acylated gelatin.

[0063] (2) Dissolve methacrylic acid acylated gelatin in deionized water at a ratio of 200g / L, then add succinic anhydride, the volume mass ratio of succinic anhydride to methacrylic acid acylated gelatin is 1:3, at 55℃ Stir and react for 24 hours; after the reaction is completed, dialyze with deionized water at room temperature...

technical field

[0001] The invention relates to the technical field of biomaterial preparation, in particular to a method for preparing controllable light-curable hydrogel microspheres that can promote angiogenesis.

[0002] technical background

[0003] Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (vascular permeability factor, VPF), is a highly specific factor that promotes the growth of vascular endothelial cells. Matrix degeneration, vascular endothelial cell migration, proliferation and angiogenesis. VEGF and its receptors are expressed in human placental trophoblast cells and vascular endothelial cells, indicating that VEGF is involved in normal pregnancy, the regulation of placental angiogenesis and the physiological invasion of trophoblast cells. However, currently existing peptide hydrogels cannot effectively control their degradation rate.

[0004] At present, in the field of biomedical materials, most of them are specific ...

Examples

Embodiment 1

[0030] A method for preparing photocurable hydrogel microspheres that can promote angiogenesis, specifically comprising the following steps:

[0031] (1) Add sodium carbonate to the obtained deionized water, dilute and adjust the pH to 7.4, add gelatin to the sodium carbonate solution at a ratio of 100g / L, stir and dissolve at 50°C, then add methacrylic anhydride, methyl The volume mass ratio of acrylic anhydride to gelatin is 2:1. After the reaction is completed, dialyze with deionized water at room temperature for 5 days, change the water every 12 hours, and the molecular weight cut-off of the dialysis bag is 8KDa-14Kda. Acrylic acylated gelatin.

[0032] (2) Dissolve methacrylic acylated gelatin in deionized water at a ratio of 100g / L, then add succinic anhydride, the volume-to-mass ratio of succinic anhydride to methacrylic acylated gelatin is 1:1.6. Stir and react for 24 hours; after the reaction is completed, dialyze with deionized water at room temperature for 5 days, ...

Embodiment 2

[0052] A method for preparing photocurable hydrogel microspheres that can promote angiogenesis, specifically comprising the following steps:

[0053] (1) Add sodium carbonate to the obtained deionized water, dilute and adjust the pH to 8, add gelatin to the sodium carbonate solution at a ratio of 50g / L, stir and dissolve at 35°C, then add methacrylic anhydride, methyl The volume mass ratio of acrylic anhydride to gelatin is 1:1. After the reaction is completed, dialyze with deionized water at room temperature for 5 days, change the water every 12 hours, and the molecular weight cut-off of the dialysis bag is 8KDa-14Kda. Acrylic acylated gelatin.

[0054] (2) Dissolve methacrylic acid acylated gelatin in deionized water at a ratio of 50g / L, then add succinic anhydride, the volume-mass ratio of succinic anhydride to methacrylic acid acylated gelatin is 1:1, at 25°C Stir and react for 24 hours; after the reaction is completed, dialyze with deionized water at room temperature for...

Embodiment 3

[0061] A method for preparing photocurable hydrogel microspheres that can promote angiogenesis, specifically comprising the following steps:

[0062] (1) Add sodium carbonate to the obtained deionized water, dilute and adjust the pH to 10, add gelatin to the sodium carbonate solution at a ratio of 200g / L, stir and dissolve at 60°C, then add methacrylic anhydride, methyl The volume mass ratio of acrylic anhydride to gelatin is 3:1. After the reaction is completed, use deionized water to dialyze at room temperature for 5 days, and change the water every 12 hours. The molecular weight cut-off of the dialysis bag is 8KDa-14Kda. Acrylic acylated gelatin.

[0063] (2) Dissolve methacrylic acid acylated gelatin in deionized water at a ratio of 200g / L, then add succinic anhydride, the volume mass ratio of succinic anhydride to methacrylic acid acylated gelatin is 1:3, at 55℃ Stir and react for 24 hours; after the reaction is completed, dialyze with deionized water at room temperature...

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