阅读说明：本技术 一种医用水凝胶敷料、其制备方法及应用 (Medical hydrogel dressing, and preparation method and application thereof ) 是由 李泽 王培戈 任建安 黄金健 于航 肖志保 于 2020-04-28 设计创作，主要内容包括：本发明具体涉及一种医用水凝胶敷料、其制备方法及应用,所述医用水凝胶敷料包括间充质干细胞、修饰的纤连蛋白、甲基丙烯酸缩水甘油酯黄原胶以及纳米微胶囊水凝胶组成。所述医用水凝胶的制备方法包括：通过改进的双乳法制备包封干细胞生长因子的纳米微胶囊,将纳米微胶囊与甲基丙烯酸缩水甘油酯黄原胶混合涂覆于聚丙烯网片上,并将修饰的纤连蛋白添加在水凝胶表面,通过光照形成结构稳定的水凝胶敷料。该水凝胶本身的成分为天然材料,因此生物相容性极高,可作为细胞生长的支架。搭载了间充质干细胞,通过纳米技术,控制干细胞生长因子缓慢释放,为干细胞生长提供合适的微环境,干细胞通过自身增殖分化并通过旁分泌募集更多干细胞,加速组织愈合,加快病损修复,临床应用前景良好。(The invention particularly relates to a medical hydrogel dressing, a preparation method and application thereof, wherein the medical hydrogel dressing comprises mesenchymal stem cells, modified fibronectin, glycidyl methacrylate xanthan gum and nano microcapsule hydrogel. The preparation method of the medical hydrogel comprises the following steps: the nano microcapsule for encapsulating the stem cell growth factor is prepared by an improved double-emulsion method, the nano microcapsule and glycidyl methacrylate xanthan gum are mixed and coated on a polypropylene mesh, modified fibronectin is added on the surface of hydrogel, and the hydrogel dressing with stable structure is formed by illumination. The hydrogel is made of natural materials, so that the hydrogel has extremely high biocompatibility and can be used as a scaffold for cell growth. The mesenchymal stem cells are carried, the slow release of stem cell growth factors is controlled through a nanotechnology, a proper microenvironment is provided for the growth of the stem cells, the stem cells are proliferated and differentiated by themselves and recruited by paracrine, the tissue healing is accelerated, the lesion repair is accelerated, and the clinical application prospect is good.)

1. The nano microcapsule is characterized in that raw materials of the nano microcapsule comprise growth factors, polylactic acid-glycolic acid copolymer, poloxamer and polyvinyl alcohol.

2. The nano-microcapsule according to claim 1, wherein said growth factor is a type of multifunctional regulatory peptide that affects cell activities by intercellular signaling, selected according to the purpose of use of the microcapsule; preferably, the growth factor is stem cell growth factor, i.e. a mixture of epidermal growth factor, fibroblast growth factor and vascular endothelial growth factor.

3. A process for the preparation of nanocapsules as claimed in claim 1 or 2, wherein said process comprises the following steps: mixing and emulsifying an organic solution of polylactic acid-glycolic acid copolymer and poloxamer with an aqueous solution of polylactic acid-glycolic acid copolymer and stem cell growth factor to obtain an initial emulsion, emulsifying the initial emulsion and a polyvinyl alcohol solution to obtain a double emulsion, removing an organic solvent in the double emulsion to obtain nano particles, and injecting the nano particles and a sodium alginate solution of mineral oil into a water phase to obtain the nano microcapsule.

4. The method for preparing nano-microcapsules of claim 3, wherein the organic solution of the polylactic acid-glycolic acid copolymer and the poloxamer is a solution of the polylactic acid-glycolic acid copolymer and the dichloromethyl ether of the poloxamer;

or mixing the organic solution of the polylactic acid-glycolic acid copolymer and the poloxamer with the aqueous solution of the polylactic acid-glycolic acid copolymer and the stem cell growth factor, and then carrying out ultrasonic emulsification; preferably, the ultrasonic time is 3-4 min;

or emulsifying the initial emulsion and 1.5-2.5% of polyvinyl alcohol solution by a sonic degradation method to obtain double emulsions;

or in the preparation method, the double emulsion is added into the polyvinyl alcohol solution with lower concentration for stirring treatment;

preferably, the polyvinyl alcohol solution with lower concentration is 0.5-0.7% of polyvinyl alcohol solution.

Preferably, the stirring time is 17-23 min;

or the preparation method removes the organic solvent in the double emulsion by rotary evaporation to obtain the nano particles;

preferably, the parameters of the rotary evaporation are as follows: the rotating speed is 12000-14000 rpm; the centrifugation time is 8-12 min.

Preferably, after the nanoparticles are obtained, a washing step is further included.

5. A hydrogel, wherein the raw material for preparing the hydrogel comprises the nano-microcapsules of claim 1 or 2, and further comprises glycidyl methacrylate xanthan gum.

6. The method for preparing the hydrogel according to claim 5, wherein the method comprises mixing glycidyl methacrylate xanthan gum with nano-microcapsules and curing the mixture by light irradiation to obtain the hydrogel.

7. The method for preparing the hydrogel according to claim 6, which comprises the following steps: dissolving glycidyl methacrylate xanthan gum in PBS (phosphate buffer solution) containing a photoinitiator to obtain a glycidyl methacrylate xanthan gum solution, mixing the nano microcapsule and the glycidyl methacrylate xanthan gum solution in a mass ratio of 3-5: 5-7, and performing ultraviolet irradiation to obtain the hydrogel;

preferably, the glycidyl methacrylate xanthan gum solution is prepared by the following specific steps: dissolving glycidyl methacrylate xanthan gum in 0.08-0.12% PBS (phosphate buffer solution) containing a photoinitiator to obtain 8-12% glycidyl methacrylate xanthan gum solution.

Preferably, the photoinitiator is I-2959, i.e., 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropiophenone; in some embodiments, the photoinitiator is present at a concentration of 0.08 to 0.12%.

Preferably, the wavelength of the ultraviolet light is 365nm, and the power per unit area is 6.0W/cm²The irradiation time is 30S;

or the preparation method of the glycidyl methacrylate xanthan gum comprises the following steps: heating a water solution of xanthan gum to 75-85 ℃, then dropwise adding Glycidyl Methacrylate (GMA) into the water solution of xanthan gum, stirring at room temperature, adding an acid solution to adjust the pH value to 4.2-4.8, heating to 75-85 ℃, reacting for 10-14 h to obtain a mixture, placing the mixture in a dialysis membrane for dialysis, and freeze-drying the solution in a dialysis bag after dialysis is completed to obtain the glycidyl methacrylate xanthan gum;

preferably, the water solution of the xanthan gum is 0.5-0.7%;

preferably, the volume ratio of the xanthan gum aqueous solution to the glycidyl methacrylate is 270: 1-2;

preferably, the dialysis membrane has a molecular weight cut-off of 12-14 kDa.

8. Use of the nano-microcapsules of claim 1 or 2 and/or the hydrogel of claim 5 for the preparation of a medical dressing.

9. A medical hydrogel dressing, which is characterized in that the hydrogel of claim 5 and a mesh together form a mesenchymal stem cell carrier;

preferably, the hydrogel is coated on a mesh and forms a gel shape by ultraviolet irradiation to form a culture carrier of the mesenchymal stem cells;

preferably, the mesh is a polypropylene mesh.

10. A method of manufacturing the medical hydrogel dressing of claim 9, the method of manufacturing comprising the steps of:

mixing glycidyl methacrylate xanthan gum and nano microcapsules, coating the mixture on a mesh, adding fibronectin, irradiating to enable substances on the mesh to be colloidal, and placing mesenchymal stem cells on hydrogel for co-culture to obtain the gel-coated nano-particles;

preferably, the fibronectin is acryloyl polyethylene glycol fibronectin;

more preferably, the concentration of the acryloyl polyethylene glycol fibronectin is 0.6-0.7 umol/ml.

Technical Field

The invention belongs to the technical field of medical hydrogel dressings, and particularly relates to a nano microcapsule, a hydrogel applying the nano microcapsule, a medical dressing applying the hydrogel, and preparation methods and applications of the nano microcapsule, the hydrogel and the medical dressing.

Background

The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.

Abdominal sepsis, Abdominal Cavity Syndrome (ACS), abdominal wall defects caused by trauma or surgery are common problems in clinical practice, and there is a consensus that abdominal cavity open therapy for the above patients is currently performed, and the abdominal cavity open therapy means that the skin and the fascia are not directly sutured after the abdominal cavity open surgery, and the abdominal cavity is closed after the organ function is recovered. However, long-term laparotomy is prone to fluid loss and subsequent visceral injury and infection, and patients undergoing open abdominal treatment are at risk of developing entero-air fistulas and "frozen abdomens" and have a low rate of definitive closure of the fascia, and reconstruction of the abdominal wall is the solution to these problems, namely skin grafting when sufficient granulation tissue has formed on the intestinal tract. Temporary Abdominal Closure (TAC) provides protection to the abdominal viscera while the fascia remains open, laying a good foundation for abdominal wall reconstruction.

Conventional temporary abdominal closure means such as covering prosthetic materials have been widely used, for example polypropylene (PP), which has good mechanical properties to increase the strength of the abdominal fascia to prevent retraction of the fascia. It also produces local side effects such as adhesion, erosion and fistula formation, primarily due to the lack of natural tissue to protect internal organs.

Mesenchymal stem cell therapy has been used for damaged tissue regeneration in a variety of diseases. It has the characteristics of easy separation, strong self-renewal capacity, strong proliferation capacity and the like, and is widely applied to the field of regenerative medicine. The mesenchymal stem cells can promote the generation of blood vessels in the healing process of the wound surface and have good curative effect on chronic intractable wounds or wounds which are not healed for a long time. However, the use of stem cell therapy is greatly affected due to poor survival/retention of cells following local stem cell delivery.

Hydrogels are three-dimensional networks of polymeric materials that can absorb or retain large amounts of water or biological fluids. It shows great potential in biomedical applications such as drug delivery, tissue engineering and regenerative medicine. Hydrogels can mimic many of the properties of tissue in vivo and serve as scaffolds for tissue engineering to reconstruct and repair tissue in vivo. The hydrogel is mainly prepared from natural materials, so that the hydrogel has extremely high biocompatibility and can be used as a two-dimensional carrier for cell culture. Furthermore, simple hydrogels only reduce the inflammatory response of cells surrounding the lesion. However, clinical applications of simple hydrogels are greatly limited due to limited local proliferation capacity of the lesion, resulting in general therapeutic effects.

Disclosure of Invention

Aiming at the research background, the invention provides a medical stem cell-loaded xanthan gum hydrogel dressing for abdominal cavity opening, temporary abdominal closing and large-area skin injury. Mesenchymal stem cells are carried on the surface of the medical dressing, and the stem cell growth factors are carried by the nano microcapsule to promote the skin repair of the wound surface and improve the healing quality. In addition, the nano microcapsule is matched with hydrogel formed by the modified xanthan gum, so that hardness conditions and deformation capacity more suitable for growth of fibroblasts are provided.

Based on the technical effects, the invention provides the following technical scheme:

in a first aspect of the present invention, a nano-microcapsule is provided, wherein raw materials of the nano-microcapsule include growth factors, polylactic acid-glycolic acid copolymer, poloxamer and polyvinyl alcohol.

In the nano microcapsule, the polylactic acid-glycolic acid copolymer/poloxamer form microspheres wrapping growth factors. The growth factor is a multifunctional regulatory peptide which influences cell activities through intercellular signal transmission and is adjusted according to the use purpose of the nano microcapsule. When used as a medical dressing, the growth factors that are usually added include epidermal growth factor, vascular endothelial growth factor, fibroblast growth factor, stem cell growth factor, platelet-derived growth factor, and the like.

The invention particularly provides a stem cell growth factor-entrapped nano microcapsule which is used for skin wound surfaces after being co-cultured with mesenchymal stem cells. The nano microcapsule can control and release stem cell growth factors and can promote growth of loaded mesenchymal stem cells.

In a second aspect of the present invention, there is provided a method for preparing the nano-microcapsule of the first aspect, the method comprising the steps of: mixing and emulsifying an organic solution of polylactic acid-glycolic acid copolymer and poloxamer with an aqueous solution of polylactic acid-glycolic acid copolymer and stem cell growth factor to obtain an initial emulsion, emulsifying the initial emulsion and a polyvinyl alcohol solution to obtain a double emulsion, removing an organic solvent in the double emulsion to obtain nano particles, and injecting the nano particles and a sodium alginate solution of mineral oil into a water phase to obtain the nano microcapsule.

The nano microcapsule prepared by the method has excellent drug controlled release capacity, and the release speed of the stem cell growth factor can be regulated by adjusting the diameter of the nano microcapsule. When the product is used for encapsulating growth factors of different types, the body release amount can reach 80%, and the release effect is good. Therefore, the hydrogel prepared by the method can provide a suitable microenvironment for survival and growth of stem cells.

In a third aspect of the present invention, a hydrogel is provided, wherein a raw material for preparing the hydrogel comprises the nano-microcapsules of the first aspect, and further comprises glycidyl methacrylate Xanthan Gum (XG).

In a fourth aspect of the present invention, a preparation method of the hydrogel in the third aspect is provided, wherein the preparation method comprises mixing glycidyl methacrylate xanthan gum with nano microcapsules, and curing by light irradiation to obtain the hydrogel.

Based on the good control effect of the nano microcapsule, the nano microcapsule can realize good drug controlled release effect when being applied to the preparation of medical dressing, or continuously provide nutrient substances for the growth of stem cells to assist wound healing. The invention further provides hydrogel, which provides a curing use form for the nano microcapsule, and in addition, the hydrogel formed by the modified xanthan gum and the microcapsule has good mechanical property when being used as a medical dressing.

In a fifth aspect of the present invention, there is provided a use of the nano-microcapsules of the first aspect and/or the hydrogel of the third aspect in the preparation of a medical dressing.

The invention provides a medical hydrogel dressing, which is a mesenchymal stem cell carrier formed by the hydrogel and the mesh in the third aspect.

In a seventh aspect of the present invention, there is provided a method for manufacturing the medical hydrogel dressing according to the sixth aspect, the method comprising the steps of: mixing glycidyl methacrylate xanthan gum and nano microcapsules, coating the mixture on a mesh, adding fibronectin, irradiating to enable substances on the mesh to be colloidal, and placing mesenchymal stem cells on hydrogel for co-culture to obtain the collagen gel.

The mesenchymal stem cell-loaded hydrogel can solve the problem of limited proliferation capacity of damaged parts through proliferation and differentiation of stem cells. And by paracrine, hundreds of factors including growth factors, cytokines, chemotactic factors, enzymes and the like accelerate the proliferation of tissue cells around the lesion and collect more autologous stem cells, and the mesenchymal stem cell hydrogel is applied to the part of the wound surface to promote the repair of the damaged tissue and improve the healing quality.

The second layer of the hydrogel dressing prepared by the method, namely the polypropylene mesh layer, has good mechanical properties and can effectively prevent peritoneal retraction. The first layer of the hydrogel dressing, namely the stem cell-loaded hydrogel layer, has good flexibility, elasticity and wettability, can greatly reduce abrasion and inflammatory reaction of a polypropylene net on an intestinal tract, has a good effect of protecting an intestinal serous membrane layer, can reduce incidence of soft tissue inflammation, intestinal canal abrasion and intestinal atmospheric fistula, and promotes repair of local damaged tissues by loading mesenchymal stem cells.

In clinical use, the medical hydrogel can reduce rejection probability by separating autologous tissues of a patient, wherein the autologous tissues comprise umbilical cords, bone marrow and fat, and the preferred scheme adopts autologous adipose tissues of the patient for separation culture.

The beneficial effects of one or more of the above technical solutions are as follows:

(1) the medical hydrogel prepared by the method can simulate the extracellular matrix of stem cells, and can be directly sutured in open temporary abdominal closing operation of an abdominal cavity and also can be attached to a larger skin wound surface when in use. The hydrogel raw material is a natural polymer material, and the good biocompatibility of the hydrogel is proved in-vitro cell experiments and animal experiments. And the added photoinitiator and various buffers of the hydrogel dressing have no safety hazard.

(2) The hydrogel dressing prepared by the method has good hardness, the normal form of the hydrogel can be maintained only when the strength is more than 20KPa because the hardness of the hydrogel influences the form of fibroblasts, and the compression test proves that the strength range of the hydrogel is between 0.16 and 0.50MPa, so that the growth condition of the fibroblasts can be better met. In addition, rheological tests show that the interpenetrating double-network hydrogel has better rheological property, namely deformation capacity, than single hydrogel, so that the hydrogel prepared by the method can better fit the wound of a patient with an open abdominal cavity, and further reduces complications.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.

FIG. 1 is a schematic side view of the construction of a medical hydrogel dressing described in example 1;

FIG. 2 is a schematic top view of the structure of the medical hydrogel dressing described in example 1;

in FIGS. 1 to 2, 1 is a stem cell-loaded hydrogel layer, 2 is a polypropylene mesh layer.

FIG. 3 is an electron microscope image of the nano-microcapsules and the hydrogel in example 1;

wherein, fig. 3A is an electron microscope image of the nano microcapsule, and fig. 3B is an electron microscope image of the hydrogel.

FIG. 4 is a graph of the frequency dependent rheological results (strain 1%) for the hydrogel described in example 1;

wherein, FIG. 4A is a hydrogel viscosity profile;

FIG. 4B is a graph of the elastic modulus of a hydrogel.

FIG. 5 is the drug release profile of the nano-microcapsules described in example 1;

wherein, fig. 5A is a release curve chart of the nanocapsule loaded with the vascular endothelial growth factor;

fig. 5B is a release profile of the epidermal growth factor-coated nanocapsule.

FIG. 6 is a graph showing the results of culturing mesenchymal stem cells using hydrogel in example 3;

wherein, fig. 6A is a fluorescence diagram of mesenchymal stem cells after 24h of culture on a hydrogel matrix;

fig. 6B is a fluorescence plot of mesenchymal stem cells after 48h of culture on a hydrogel matrix;

fig. 6C is a histogram of the results of mesenchymal stem cells cultured in 24-well plates and hydrogel matrices (p <0.05, p < 0.01).

FIG. 7 is a graph showing HE staining of granulation tissue 7 days after the abdominal cavity was opened on the wound surface in example 3;

wherein, fig. 7A is a staining result graph of the granulation tissue after 7 days of covering the wound surface with the polypropylene patch;

fig. 7B is a graph of the staining results of granulation tissue after the medical dressing covered the wound surface for 7 days.

Detailed Description

It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.

In order to solve the technical problems, the invention provides a medical hydrogel dressing, a preparation method and an application thereof.

In a first aspect of the present invention, a nano-microcapsule is provided, wherein raw materials of the nano-microcapsule include growth factors, polylactic acid-glycolic acid copolymer, poloxamer and polyvinyl alcohol.

Preferably, the polylactic acid-glycolic acid copolymer and poloxamer are used as carriers of the growth factors.

Preferably, the growth factor is a multifunctional regulatory peptide which influences the cell activity through intercellular signal transmission and is selected according to the use purpose of the microcapsule.

Further preferably, the growth factor is stem cell growth factor, i.e. a mixture of epidermal growth factor, fibroblast growth factor and vascular endothelial growth factor.

In a second aspect of the present invention, there is provided a method for preparing the nano-microcapsule of the first aspect, the method comprising the steps of: mixing and emulsifying an organic solution of polylactic acid-glycolic acid copolymer and poloxamer with an aqueous solution of polylactic acid-glycolic acid copolymer and stem cell growth factor to obtain an initial emulsion, emulsifying the initial emulsion and a polyvinyl alcohol solution to obtain a double emulsion, removing an organic solvent in the double emulsion to obtain nano particles, and injecting the nano particles and a sodium alginate solution of mineral oil into a water phase to obtain the nano microcapsule.

Preferably, the organic solution of the polylactic acid-glycolic acid copolymer and the poloxamer is a solution of the polylactic acid-glycolic acid copolymer and the poloxamer in dichloromethyl ether.

Preferably, the organic solution of the polylactic acid-glycolic acid copolymer and the poloxamer is mixed with the aqueous solution of the polylactic acid-glycolic acid copolymer and the stem cell growth factor and then is emulsified by ultrasound; further preferably, the ultrasonic time is 3-4 min.

Preferably, the initial emulsion and 1.5-2.5% of polyvinyl alcohol solution are emulsified by a sonic degradation method to obtain a double emulsion.

Preferably, the preparation method further comprises the step of adding the double emulsion into the lower-concentration polyvinyl alcohol solution for stirring treatment.

More preferably, the polyvinyl alcohol solution with a lower concentration is 0.5-0.7% of polyvinyl alcohol solution.

Further preferably, the stirring time is 17-23 min.

Preferably, the preparation method removes the organic solvent in the double emulsion by rotary evaporation to obtain the nano particles.

Further preferably, the parameters of the rotary evaporation are as follows: the rotating speed is 12000-14000 rpm; the centrifugation time is 8-12 min.

Further preferably, after the nanoparticles are obtained, a washing step is also included.

Preferably, the aqueous phase is a calcium chloride solution.

In a third aspect of the present invention, a hydrogel is provided, wherein a raw material for preparing the hydrogel comprises the nano-microcapsules of the first aspect, and further comprises glycidyl methacrylate Xanthan Gum (XG).

In a fourth aspect of the present invention, a preparation method of the hydrogel according to the third aspect is provided, wherein the preparation method comprises mixing glycidyl methacrylate Xanthan Gum (XG) with nano-microcapsules, and curing by light to obtain the hydrogel.

Preferably, the preparation method comprises the following specific steps: dissolving glycidyl methacrylate xanthan gum in PBS (phosphate buffer solution) containing a photoinitiator to obtain a glycidyl methacrylate xanthan gum solution, mixing the nano microcapsule and the glycidyl methacrylate xanthan gum solution in a mass ratio of 3-5: 5-7, and performing ultraviolet irradiation to obtain the hydrogel.

Further preferably, the glycidyl methacrylate xanthan gum solution is prepared by the following specific steps: dissolving glycidyl methacrylate xanthan gum in 0.08-0.12% (w/v) PBS solution containing photoinitiator to obtain 8-12% (w/v) glycidyl methacrylate xanthan gum solution.

Further preferably, the photoinitiator is I-2959, i.e. 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropiophenone; in some embodiments, the photoinitiator is present at a concentration of 0.08 to 0.12% (w/v).

More preferably, the wavelength of the ultraviolet light is 365nm, and the unit area power is 6.0W/cm²The irradiation time was 30S.

Preferably, the preparation method of the glycidyl methacrylate xanthan gum comprises the following steps: heating a water solution of xanthan gum to 75-85 ℃, then dropwise adding Glycidyl Methacrylate (GMA) into the water solution, stirring at room temperature, adding an acid solution to adjust the pH value to 4.2-4.8, heating to 75-85 ℃, reacting for 10-14 h to obtain a mixture, placing the mixture in a dialysis membrane for dialysis, and freeze-drying the solution in a dialysis bag after dialysis is completed to obtain the glycidyl methacrylate xanthan gum.

More preferably, the aqueous solution of the xanthan gum is 0.5-0.7% (w/v).

More preferably, the volume ratio of the xanthan gum aqueous solution to Glycidyl Methacrylate (GMA) is 270: 1-2.

Further preferably, the dialysis membrane has a molecular weight cut-off of 12-14 kDa.

In a fifth aspect of the present invention, there is provided a use of the nano-microcapsules of the first aspect and/or the hydrogel of the third aspect in the preparation of a medical dressing.

The invention provides a medical hydrogel dressing, which is a mesenchymal stem cell carrier formed by the hydrogel and the mesh in the third aspect.

Preferably, the hydrogel is coated on the mesh and forms a gel shape by ultraviolet irradiation, so as to form a culture carrier of the mesenchymal stem cells.

Preferably, the mesh is a polypropylene mesh.

In a seventh aspect of the present invention, there is provided a method for manufacturing the medical hydrogel dressing according to the sixth aspect, the method comprising the steps of: mixing glycidyl methacrylate xanthan gum and nano microcapsules, coating the mixture on a mesh, adding fibronectin, irradiating to enable substances on the mesh to be colloidal, and placing mesenchymal stem cells on hydrogel for co-culture to obtain the collagen gel.

Preferably, the fibronectin is acryloyl polyethylene glycol fibronectin.

More preferably, the concentration of the acryloyl polyethylene glycol fibronectin is 0.6-0.7 umol/ml.

In order to make the technical solutions of the present invention more clearly understood by those skilled in the art, the technical solutions of the present invention will be described in detail below with reference to specific embodiments. Vascular endothelial growth factor used in the following examples was purchased from aures biotechnology limited; epidermal growth factor purchased from eboantibody (shanghai) trade ltd; it is not stated that the source reagents are commercially available.