CN-121987842-A - Exosome hydrogel and preparation method and application thereof

Abstract

The invention provides an exosome hydrogel, a preparation method and application thereof, wherein the exosome hydrogel comprises a hydrogel matrix, natural active ingredients and exosomes; the hydrogel matrix is prepared from poloxamer, oxidized hyaluronic acid and carboxymethyl chitosan. The poloxamer is subjected to sol-gel conversion under the body temperature condition to form a second network structure, and the two networks mutually penetrate to form a thermosensitive-dynamic covalent double-network structure, so that a double-network hydrogel system with injectability, structural stability and tissue suitability is obtained. The double-network hydrogel matrix can be used as a stable carrier of exosomes and natural active ingredients, realizes continuous and local delivery and synergistic effect of the two active substances at a wound site, and solves the problem of poor retention capacity and activity of exosomes in gelatin methacryloyl hydrogel.

Inventors

• PENG SHA
• CHEN MENGWEI
• MA BAOHUA
• PAN YING
• BAI XIAONAN
• WANG XUEQIN
• WANG CHENLEI

Assignees

• 西北农林科技大学

Dates

Publication Date

20260508

Application Date

20260209

Claims (10)

1. 1. The exosome hydrogel is characterized by comprising a hydrogel matrix, natural active ingredients and exosomes, wherein the natural active ingredients and the exosomes are entrapped in the hydrogel matrix; the hydrogel matrix is prepared from poloxamer, oxidized hyaluronic acid and carboxymethyl chitosan.
2. 2. The exosome hydrogel of claim 1, wherein the exosome is derived from mesenchymal stem cells; and/or the natural active ingredient comprises at least one of quercetin, baicalein, rutin, resveratrol, anthocyanin and curcumin.
3. 3. The exosome hydrogel of claim 1, wherein the mass ratio of poloxamer to oxidized hyaluronic acid is 1 (0.1-1); and/or the mass ratio of the poloxamer to the carboxymethyl chitosan is 1 (0.1-1).
4. 4. A method for preparing an exosome hydrogel according to any one of claims 1 to 3, comprising the steps of: Mixing poloxamer, oxidized hyaluronic acid, carboxymethyl chitosan, natural active ingredients and exosomes in water, and performing a crosslinking reaction to prepare the exosome hydrogel.
5. 5. The method of preparing an exosome hydrogel according to claim 4, wherein the crosslinking reaction is performed at 15-40 ℃.
6. 6. The method for preparing the exosome hydrogel according to claim 4, comprising the following steps: Preparing an aqueous solution 1 containing oxidized hyaluronic acid and poloxamer, preparing an aqueous solution 2 containing quercetin and carboxymethyl chitosan, mixing the aqueous solution 1, the aqueous solution 2 and an exosome, and performing a crosslinking reaction to obtain the exosome hydrogel.
7. 7. The method for producing an injectable hydrogel according to claim 6, wherein the concentration of the oxidized hyaluronic acid in the aqueous solution 1 is 10-30g/mL; And/or the concentration of carboxymethyl chitosan in the aqueous solution 2 is 1-10g/mL.
8. 8. The method for preparing an exosome hydrogel according to claim 4, wherein the method for preparing oxidized hyaluronic acid comprises the step of oxidizing hyaluronic acid with sodium periodate to obtain oxidized hyaluronic acid.
9. 9. Use of an exosome hydrogel according to any one of claims 1-3 in the preparation of a skin lesion repair product.
10. 10. The use according to claim 9, wherein the skin lesion repair product is for repairing full-thickness skin lesions; And/or, the skin lesion repair product is for promoting healing of an infected skin wound.

Description

Exosome hydrogel and preparation method and application thereof Technical Field The invention belongs to the technical field of hydrogels, and particularly relates to an exosome hydrogel and a preparation method and application thereof. Background The skin is used as the largest organ of the organism, and has important functions in maintaining barrier function, regulating body fluid balance, resisting invasion of external pathogens and the like. Clinically, skin injuries caused by burns and scalds, animal bites, postoperative incision infection, endocrine or metabolic abnormalities and other factors are common, and partial wound surfaces are accompanied with tissue defects and even involve the whole skin structure. Wound healing is usually subjected to multiple stages of hemostasis, inflammation, proliferation, remodeling and the like, and the process is easily affected by various factors such as infection, unbalanced inflammatory reaction, insufficient blood supply, increased oxidative stress level, limited epithelial regeneration and the like, so that the problems of delayed healing, reduced repair quality, scar formation and the like are caused. At present, common treatment modes aiming at skin injury comprise debridement, antibacterial or anti-infection treatment, negative pressure sealing drainage, various wound dressings and the like. The method can improve the wound surface environment to a certain extent, but has obvious limitation in complex or tissue defect type wound surface application. For example, the traditional dressing mainly comprises surface coverage, and has limited fitting and filling capabilities on irregular or deep tissue defect wound surfaces, the dressing is easy to change in form under the action of wound exudates, and is difficult to maintain a stable moist microenvironment for a long time, and meanwhile, local administration often has the problems of over-quick initial release and short effective acting time, and is difficult to realize cooperative regulation and control on multiple links such as inflammatory reaction, angiogenesis, tissue regeneration and the like. In recent years, exosomes (Exosomes) derived from mesenchymal stem cells have received widespread attention for their potential role in tissue repair. The mesenchymal stem cell exosome is used as a nanoscale vesicle secreted by cells, is rich in various bioactive components such as protein, miRNA, mRNA and the like, can participate in the processes of regulating inflammatory reaction, promoting angiogenesis, inducing fibroblast and keratinocyte migration proliferation, regulating collagen deposition and the like, and has good application prospect in the field of wound repair. However, the exosomes still face the problems of short residence time, easy degradation or removal, high diffusion speed and the like in the in-vivo application process, so that the effective acting time of the exosomes at wound surface parts is limited, and meanwhile, the sufficient exertion of the exosome functions is further limited due to the lack of stable supporting matrixes and proper microenvironments. Hydrogel dressing is considered as a promising wound treatment carrier because of good biocompatibility, water-bearing property and certain plasticity. The exosomes are loaded in the hydrogel, so that the sustained release and stabilization effect of the exosomes on the local part of the wound surface are hopeful to be realized. However, most of the existing hydrogel systems have single network structures, limited mechanical properties and morphological stability, are mainly suitable for superficial wound surface coverage, have insufficient filling and supporting capabilities for tissue defect type or deep wound surfaces, and in addition, partial hydrogel is easy to generate structural damage under infectious or high exudation environments, and is difficult to realize comprehensive regulation of inflammation control and tissue regeneration. Therefore, development of a hydrogel system which has good biocompatibility, morphological stability and tissue filling capacity and can be used as a carrier of various bioactive substances is still a technical problem to be solved in the field of wound repair. Disclosure of Invention In order to overcome the problems of the prior art, an object of the present invention is to provide an exosome hydrogel. The second object of the present invention is to provide a method for producing the above-mentioned exosome hydrogel. It is a further object of the present invention to provide the use of the exosome hydrogel. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: The first aspect of the invention provides an exosome hydrogel, which comprises a hydrogel matrix, natural active ingredients and exosomes, wherein the natural active ingredients and exosomes are entrapped in the hydrogel matrix; the hydrogel matrix is prepared from poloxamer, oxidized hyaluronic ac