An injectable in situ hydrogel imitating extracellular matrix and its preparation method and application

Abstract

The invention discloses imitated extracellular matrix injectable in-situ hydrogel and a preparation method and application thereof. The hydrogel is prepared by carrying out a cross-linking reaction between sulfhydrylation gelatin, sulfhydrylation polysaccharides or RGD-containing cell adhesion peptides and polyethylene glycol diacrylate. The composition of the hydrogel is similar to that of the extracellular matrix, so that the hydrogel has high biocompatibility, has the effects of controlled degradation, controlled release and / or cell behavior regulation in performance and can conveniently meet the requirements on different release rates of growth factors or medicines. Meanwhile, the clinical injectable and in-situ forming operation requirements can be met, and the hydrogel has good application prospects in tissue repair and regeneration.

Description

technical field [0001] The invention relates to an injectable in-situ hydrogel imitating extracellular matrix, a preparation method and application thereof. Background technique [0002] For a long time, human beings have been exploring the repair and regeneration of body tissues. In recent years, with the development of biomaterials, tissue engineering and stem cell technology, breakthroughs have been made in the field of tissue repair and regeneration. Current research mainly focuses on two aspects: one is to induce endogenous cells to perform tissue reconstruction in the diseased site by administering drug treatment such as growth factors; the other is to implant cells to play a therapeutic role in the diseased site. In both strategies, the design and development of carrier materials undoubtedly plays an increasingly important role. [0003] First, the degradation of the carrier material should match the tissue growth. Secondly, the carrier used for drug delivery must ...

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Problems solved by technology

[0005] Chinese patent CN101864178A discloses an injectable protein / polypeptide in situ hydrogel for drug sustained release and cell culture, but the hydrogel is made of natural or synthetic protein / polypeptide with cross-linkable phenolic hydroxyl groups Composed of peptides, horseradish peroxidase and hydrogen peroxide, chemically cross-linked hydrogels are rapidly formed under physiological conditions, and the hydrogels prepared by this method do not have controlled degradation, controlled release and / or regulation of cell behavior function, and cross-linking with hydrogen peroxide can cause oxidative toxicity to cells

[0006] Chinese patent CN102718991A discloses a Michael addition reaction between the double bond of polyethylene glycol diacrylate (PEGDA) and the sulfhydryl group on the mercaptolated natural polymer, and simultaneously uses polyethylene glycol and polycaprolactone (PEG- PCL-PEG) triblock copolymer nanoparticles are hydrogels formed as reinforcing agents. Chinese patent CN103665397A discloses a hydrogel and a preparation method thereof, using high molecular weight polyethylene glycol and hyaluronic acid as Raw materials, so that the hydrogel has strong flexibility and certain mechanical strength, both of which use Michael addition reaction to prepare in-situ hydrogel, but the prepared hydrogel does not have controllable degradation and controllable release and / or functions that regulate cellular behavior

Chinese patent CN103467755A discloses a drug sustained-release hydrogel and its preparation method and application. The high-voltage electrostatic droplet method is used to prepare monodisperse drug-containing calcium alginate microspheres, and the drug-loaded calcium alginate microspheres are placed in the hydrogel In the glue network structure, the steps of this method are complicated, and it does not have the functions of controlled degradation, controlled release and / or regulation of cell behavior

[0008] Existing hydrogel carrier materials usually only have a single release rate, which is often limited in practical applications. When the required release rate changes, it is necessary to re-select the appropriate carrier material type and dosage, the type of carrier material and The dosage may change, resulting in the need to spend time, energy and cost on carrier materials when facing active ingredients with different release rate requirements

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