A kind of injectable hydrogel and preparation method thereof

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...

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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

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