A kind of injectable hydrogel and preparation method thereof

A technology for injecting water and gel, which is applied in the field of biomedical materials and tissue engineering, can solve the problems of uncontrollable degradation rate, destruction of three-dimensional matrix cross-linked network, and reduced clearance rate, etc., and achieves the effect of controllable degradation rate

Active Publication Date: 2022-07-08
湖南美柏生物医药有限公司
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, during the dissolution process, the three-dimensional matrix cross-linked network of ECM proteins will be destroyed, and there are various active enzyme components that can degrade ECM protein components in the implanted body, such as matrix metalloproteinases and cathepsins, etc. Therefore, injection The pure extracellular matrix implanted in the body will be degraded rapidly in a short period of time, and its degradation rate is uncontrollable, so its function as a bioscaffold in vivo will be limited
[0005] To overcome these limitations, new methods have been developed to fabricate internal vascular structures using solid free-form synthetic materials such as polymers. Polyethylene glycol (PEG) is a well-biosoluble polymeric compound widely used in In the fields of medicine, food and industry, PEG has good hydrophilicity. In the field of medicine, PEGylation of proteins can increase the water solubility of antibodies or recombinant proteins, and at the same time reduce the clearance rate of these protein drugs in the blood, and the synthesis is linear. In addition, multi-arm branched chain structures can also be synthesized, and different functional groups can be modified on the multi-arm branched chain structure to make PEG form various self-crosslinking hydrogels. The gel lacks good biological induction and cannot effectively induce tissue regeneration in the body
[0006] A series of collagen scaffold-based tissue engineering products are currently being developed, that is, collagen-based biomaterials form dispersions of fibers, films, sheets, sponges, and fibrils, and these forms of biomaterials can potentially be used as scaffolds for tissue engineering, Used to repair or enhance body tissues, but in many practical tissue engineering applications, the structure and proteolysis susceptibility of reconstituted protein hydrogels in bioscaffold systems still have many shortcomings compared with native tissues, besides In addition, the method of improving the physical properties of collagen gels based on covalent cross-linking in the prior art is relatively complicated, requiring thiolation of natural proteins first, and UV irradiation or additional initiators and photoinitiators to induce

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of injectable hydrogel and preparation method thereof
  • A kind of injectable hydrogel and preparation method thereof
  • A kind of injectable hydrogel and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] A preparation method of an injectable hydrogel, comprising the following steps:

[0034] (1) Take the adipose tissue and freeze and thaw it for 3 times, then soak it in 0.4mol / L NaCl hypertonic liquid for 4 hours, and then soak it in 0.9mol / L NaCl for 4 hours to break the fat cells; then use 0.24wt% NaCl The trypsin solution was digested at 35°C for 3 hours, rinsed with deionized water for 3 hours, treated with isopropanol for 12 hours to remove fat, and then treated with 0.9 wt% sodium dodecyl sulfate for 2 hours. 0.9% polyethylene glycol octyl phenyl ether was treated for 48 hours to perform decellularization treatment to obtain an acellular matrix, and the decellularized matrix was lyophilized for 36 hours at minus 80°C and 0.038 mbar for use;

[0035] (2) using 0.5 mg / mL pepsin to enzymolyze the lyophilized acellular matrix in an acidic environment for 12 hours, and then inactivating the pepsin to obtain a 6 mg / mL extracellular matrix protein solution for future use...

Embodiment 2

[0038] like figure 1 As shown, a preparation method of an injectable hydrogel comprises the following steps:

[0039] (1) Take the adipose tissue repeatedly freeze and thaw 4 times, then put it into 0.5mol / L NaCl hypertonic liquid for 4 hours, and then soak it in 1mol / L NaCl for 4 hours to break the fat cells; then use 0.25t% pancreas The protease solution was digested at 37°C for 6 hours, rinsed with deionized water for 4h, treated with isopropanol for 18h after washing to remove fat, then treated with 1wt% sodium dodecyl sulfate for 18h, and then treated with 1% The polyethylene glycol octyl phenyl ether was treated for 48h to carry out decellularization treatment to obtain an acellular matrix, which was lyophilized at minus 80°C and 0.04mbar for 36h for use;

[0040] (2) using 3 mg / mL pepsin to hydrolyze the lyophilized acellular matrix in an acidic environment for 18 hours, and then inactivating the pepsin to obtain a 20 mg / mL extracellular matrix protein solution for lat...

Embodiment 3

[0043] A preparation method of an injectable hydrogel, comprising the following steps:

[0044] (1) Take the adipose tissue repeatedly freeze and thaw 6 times, then put it in 0.6mol / L NaCl hypertonic liquid for more than 4 hours, and then soak it in 1.1mol / L NaCl for 5 hours to break the fat cells; then use 0.26wt% The trypsin solution was digested at 38 °C for 10 hours, rinsed with deionized water for 4 hours, treated with isopropanol for 24 hours to remove fat, and then treated with 1.1 wt% sodium dodecyl sulfate for 24 hours. Treat with 1.1% polyethylene glycol octyl phenyl ether for 50 hours to perform decellularization treatment to obtain an acellular matrix, which is lyophilized at minus 80°C and 0.042 mbar for 38 hours for later use;

[0045] (2) using 5 mg / mL pepsin to enzymolyze the lyophilized acellular matrix for 24 hours in an acidic environment, and then inactivating the pepsin to obtain a 40 mg / mL extracellular matrix protein solution for future use;

[0046] (3...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses an injectable hydrogel and a preparation method thereof. The preparation method comprises the following steps: sequentially carrying out cell fragmentation, proteolysis for the first time, cleaning, degreasing treatment and decellularization treatment of biological tissue to obtain a decellularized matrix; The acellular matrix was freeze-dried for use; the lyophilized acellular matrix was subjected to proteolysis for the second time to obtain a water-soluble extracellular matrix protein solution of 6-40 mg / mL; the extracellular matrix protein solution was mixed with 10-100 mg / mL ml multi-arm modified polyethylene glycol containing succinimide group, and / or sulfhydryl group, and / or maleimide group, and / or amino group is cross-linked to obtain injectable water gel. Injectable hydrogels are made by the methods described above. The preparation method provided by the invention is simple, and the prepared hydrogel not only has the biological inducibility of collagen, but also has the property of controllable degradation rate of polymer materials.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials and tissue engineering, and in particular relates to an injectable hydrogel used as an in vivo biological scaffold and a preparation method thereof. Background technique [0002] Tissue engineering is an emerging discipline that combines cell biology and material science to construct tissues or organs in vitro or in vivo. Classical tissue engineering approaches require the use of living cells and basic scaffolds of cell culture to mimic and replace the natural structure of the tissue while providing temporary functional support for the cells. [0003] It is well known that there is a complex extracellular matrix (ECM) between most mammalian cells, which is a macromolecule that is synthesized by animal cells and secreted into the extracellular space and distributed on the cell surface or between cells. The composition can be divided into three categories: ① glycosaminoglycans and prot...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(China)
IPC IPC(8): A61L27/18A61L27/22A61L27/50A61L27/52A61L27/58C08J3/075C08J3/24
CPCA61L27/227A61L27/18A61L27/50A61L27/58A61L27/52C08J3/075C08J3/246A61L2400/06C08J2389/00C08J2371/02C08L89/00C08L71/02
Inventor 易小玉
Owner 湖南美柏生物医药有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap