KR101564745B1 - Preparation methods of porous foam composed chitosan-gelatin-algin using ultrasonication and radiation - Google Patents

Abstract

The present invention relates to a process for preparing a water-soluble chitosan-algin-gelatin porous foam using ultrasound and radiation, and a process for preparing a water-soluble chitosan-algin-gelatin porous foam according to the present invention comprises dissolving an acid necessary for dissolving chitosan And it is possible to omit the pH control step for preventing precipitation by the ionic bonding between the conventional cationic chitosan and the anionic alginic acid by using ultrasonic waves and it is also possible to use a chemical crosslinking agent which is harmful to the human body and is a problem of residual toxicity The radiation and freeze-drying step can be carried out to improve the mechanical properties such as porosity and water absorption, and at the same time to produce a foam having a uniform internal structure.

Description

Preparation of porous foamed chitosan-gelatin-based ultrasound and radiation using ultrasound and radiation -

The present invention relates to a process for preparing a water-soluble chitosan-algin-gelatin porous foam using ultrasound and radiation.

Polymer porous supports are widely used as scaffolds for wound healing, burn healing, drug delivery, and damaged tissue regeneration. In particular, the support for regeneration of injured tissue is required to have a structure and stability suitable for culturing a sufficient amount of extracted and isolated cells from a small amount of tissue, and has biocompatibility and biodegradability that do not show side effects after transplantation. Therefore, the biodegradable scaffold for effectively regenerating and growing cells must have a porous structure capable of adhering to the surface of the scaffold and forming a three-dimensional structure, and it is easy to move moisture and cell growth factors It should be suitable for cell attachment and growth. In addition, the porous supporter must have good compatibility with surrounding tissues after transplantation into the body, have no side effects such as inflammation reaction, and have biocompatibility because they do not remain as foreign substances after self-biodegradation after tissue regeneration. Therefore, a porous support having excellent biocompatibility, biodegradability, and mechanical properties is essential for tissue regeneration and restoration.

Currently, polymeric materials used in the production of porous support for tissue regeneration include natural polymeric materials such as chitosan, gelatin, algin and collagen, and natural polymers such as polyamino acids, polyanhydrides, poly-epsilon -caprolactones, polyorthoesters, polyglycols Acid, polylactic acid, and copolymers thereof. Particularly, the natural polymer materials used in the production of the porous support have high biocompatibility and are decomposed into metabolites in the body when they are transplanted into the body and are not released into the body or toxic to the body. Therefore, they are widely used as a medical polymer material as well as a porous support material .

Chitosan is a substance which can be obtained abundantly from the natural world and can be widely supplied as a commodity. Chitosan is a kind of aminopolysaccharide that exists in nature. It is a natural substance obtained by deacetylation of chitin contained in the cell wall of microorganism such as crab, shrimp shell, squid bone, mold, mushroom and bacteria. And has biocompatibility. It has biochemical properties such as cell binding and biotissue culture, antibacterial and hemostatic action, cholesterol lowering action, intestinal metabolism, anticancer action by immunity enhancement, liver function improvement and hypoglycemic action, It is known to have physiological functions such as detoxification of heavy metals.

Algin is an anionic natural polymer extracted from brown algae and is known to be used as a medical material such as dressings for wound dressing.

Gelatin is a hydrolyzate of collagen, which is a biological component, and is a natural protein. Unlike collagen, it is known to inhibit antigenicity, increase biodegradability and biocompatibility, and has recently been reported to have a high hemostatic effect.

On the other hand, various methods for producing a porous support of a polymer scaffold have been attempted. Examples of the method for producing the porous support include a method of mixing a monocrystalline salt of a certain size into a polymer aqueous solution and drying the mixture, then dissolving and extracting the salt, a method of making a polymeric fiber into a nonwoven fabric in the form of a mesh, And then freezing it with liquid nitrogen and lyophilizing it.

Compared to the porous support prepared by using the synthetic polymer, the porous support using the natural polymer is advantageous in terms of biocompatibility, but the polymeric support easily dissolves due to its weak mechanical properties and moisture or body fluids. Therefore, it is general that a support using most natural polymer materials improves the mechanical properties of the support through a chemical treatment such as a cross-linking agent.

However, a porous support using a crosslinking agent may exhibit cytotoxicity due to a small amount of crosslinking agent remaining therein, and may exhibit toxicity to surrounding organs due to crosslinking agents after transplantation. Therefore, research is needed to minimize the use of crosslinking agents or to increase the mechanical properties of supports without using crosslinking agents.

Patent Document 1 is directed to a method for producing a chitosan-gelatin-algin sponge using ultrasonic waves, wherein a strong ultrasonic wave is irradiated to form a gel by ionic bonding between cationic chitosan and anionic alginic acid to prevent the formation of precipitates, But the water absorption rate is lower than that of the chitosan-gelatin-algin sponge prepared by irradiation, and the physical properties of the sponge are not excellent.

Thus, the present inventors have found that the use of water-soluble chitosan in the preparation of water-soluble chitosan-algin-gelatin porous foam does not use an acid necessary for dissolving chitosan, A pH adjusting step for preventing the formation of precipitates by the use of a chemical crosslinking agent which is harmful to the human body and which is a problem of residual toxicity is carried out and ultrasonic waves, And a method for producing a foam having a uniform internal structure. The present invention has been completed based on this finding.

Korean Patent No. 10-0569227

It is an object of the present invention to provide a process for producing a water-soluble chitosan-algin-gelatin porous foam.

It is an object of the present invention to provide a water-soluble chitosan-algin-gelatin porous foam produced by the above-described method.

In order to achieve the above object,

The present invention relates to a method for preparing a chitosan-containing solution, comprising the steps of: (1) irradiating ultrasonic waves by mixing a water-soluble chitosan solution and an algin solution;

Adding a gelatin solution to the mixed solution of step 1 and performing radiation crosslinking (step 2); And

And lyophilizing the crosslinked mixed solution of step 2 (step 3). The present invention also provides a method for producing a water-soluble chitosan-algin-gelatin porous foam.

The present invention also provides a water-soluble chitosan-algin-gelatin porous foam produced by the above-described method.

The method for preparing a water-soluble chitosan-algin-gelatin porous foam according to the present invention does not use an acid necessary for dissolving chitosan by using water-soluble chitosan, and by using ionic bonding of chitosan and anionic adult, Can be omitted, and a radiation and freeze-drying step can be carried out without using a chemical crosslinking agent which is harmful to the human body and is a problem of residual toxicity, so that mechanical properties such as porosity and moisture absorption rate And at the same time, a foam having a uniform internal structure can be produced.

1 is a graph showing the air permeability of the foam prepared in Examples 1 to 6 and Comparative Examples 1 and 2. FIG.
FIG. 2 is a graph showing moisture absorption rates of the foam prepared in Comparative Examples 2 and 4 according to immersion time of distilled water. FIG.
Fig. 3 is a photograph of foam form of Comparative Example 2 and Example 2 before lyophilization.
4 (a) is a foam of Comparative Example 3, (b) is a foam of Example 2, (c) is a foam of Comparative Example 3 after being immersed in distilled water for 6 hours, Lt; / RTI > is a photograph of the foam form of Example 2 after being immersed for a time.
5 is an inside photograph of the foam of Example 2 irradiated with ultrasound and radiation.

Hereinafter, the present invention will be described in detail.

The present invention relates to a method for preparing a chitosan-containing solution, comprising the steps of: (1) irradiating ultrasonic waves by mixing a water-soluble chitosan solution and an algin solution;

Adding a gelatin solution to the mixed solution of step 1 and performing radiation crosslinking (step 2); And

And lyophilizing the crosslinked mixed solution of step 2 (step 3). The present invention also provides a method for producing a water-soluble chitosan-algin-gelatin porous foam.

Hereinafter, the manufacturing method will be described step by step.

First, in the manufacturing method according to the present invention, step 1 is a step of mixing a water-soluble chitosan solution and an algin solution and irradiating ultrasonic waves.

Specifically, step 1 is a step of irradiating ultrasound to prevent precipitation of ionic bonds during mixing of chitosan and algin and to uniformly mix them. In order to prevent the formation of conventional precipitates, the step of adjusting pH by using an acidic solvent having high toxicity has been performed. However, the step of adjusting the pH by irradiating ultrasonic waves in step 1 may be omitted.

The ultrasonic intensity in step 1 is preferably 10-1000 W, more preferably 500-1000 W, but is not limited thereto, so long as the water-soluble chitosan and algin are uniformly mixed.

The ultrasonic irradiation time in step 1 is preferably from 10 minutes to 3 hours, more preferably from 30 minutes to 2 hours. However, if the water-soluble chitosan and algin can be mixed uniformly, I never do that. When the ultrasonic dispersion time is less than 10 minutes, precipitates are formed and the porous foam is insufficiently formed to be uniformly formed, and when the time exceeds 3 hours, decomposition occurs on the surface or inside of the porous foam.

The water-soluble chitosan solution of step 1 is preferably used at a concentration of 1 - 10 wt%, more preferably at a concentration of 2 - 6 wt%. When the concentration of the water-soluble chitosan is less than 1 wt%, the radiation crosslinking rate and the mechanical strength of the porous foam are lowered. When the concentration exceeds 10 wt%, stirring becomes difficult.

The solution of step 1 is preferably used at a concentration of 1 to 10% by weight, more preferably at a concentration of 2 to 6% by weight. When the concentration of the alginic acid solution is less than 1 wt%, the radiation crosslinking ratio and the mechanical strength of the porous foam are lowered. When the concentration is more than 10 wt%, the water absorption rate of the porous foam is lowered .

Furthermore, the concentration ratio of the water-soluble chitosan and the alginic acid in step 1 is preferably 1: 10: 1 - 5, more preferably 3: 2. In the case of mixing out of the range of the concentration ratios, there is a high possibility that precipitates due to some ionic bonds of chitosan and algin are generated, so that the intensity or time of the ultrasonic waves to be irradiated must be increased and the mechanical properties and radiation crosslinking rate A problem arises.

Next, in the manufacturing method according to the present invention, step 2 is a step of adding a gelatin solution to the mixed solution of step 1 and performing radiation crosslinking.

Specifically, the step 2 is a step of irradiating a crosslinking reaction of the mixed solution of chitosan and algin with the gelatin solution of step 1 above. A cross-linking reaction is performed using a chemical cross-linking agent and an organic solvent having high toxicity, and a step of removing residual chemical cross-linking agent and organic solvent is performed. However, by irradiating the radiation in the step 2, The manufacturing method of the foam can be simplified.

The radiation intensity in step 2 is preferably 5 to 50 kGy, more preferably 10 to 30 kGy. When the irradiation dose is less than 5 kGy, there is a problem that the degree of crosslinking is lowered. When it is used in excess of 50 kGy, there is a problem that radiation and gelatin may cause radiation decomposition and unnecessary radiation is abused. The radiation may be gamma rays, electron beams, ion beams, ultraviolet rays, X-rays, or the like.

In addition, it is preferable to irradiate the radiation dose of step 2 in the range of 1 - 20 kGy per hour, more preferably 5 - 10 kGy, but the mixed solution of the water soluble chitosan and the alginic acid in step 1 and the gelatin solution are uniformly It is not limited to the time for radiation crosslinking.

The gelatin solution in step 2 is preferably used in a concentration of 1 - 10 wt%, more preferably in a concentration of 2 - 6 wt%. When the concentration of the gelatin is less than 1 wt%, the radiation crosslinking ratio and the mechanical strength of the porous foam are lowered. When the concentration is more than 10 wt%, the water absorption of the porous foam is lowered.

The gelatin solution of step 2 is preferably mixed with the water-soluble chitosan solution of step 1 at a concentration ratio of 1: 10: 1 - 5, more preferably a concentration ratio of 3: 2, It is most preferable to mix them at the same concentration. In the case of mixing outside the range of the concentration ratio, the strength and time of the ultrasonic wave or radiation to be irradiated for uniformly cross-linking the water-soluble chitosan and the mixed solution of the alginic acid and the gelatin solution must be increased, and the radiation crosslinking rate and the mechanical properties Is lowered.

Next, in the production method according to the present invention, step 3 is a step of lyophilizing the cross-linked mixed solution of step 2 above.

Specifically, step 3 is a step of maintaining the shape and size of pores formed in the cross-linked mixed solution in step 2.

The lyophilization of step 3 is preferably performed at -50 to -180 ° C for 12 to 120 hours, more preferably at -50 to -80 ° C for 72 to 120 hours. If it is out of the above range, it is difficult to maintain the shape and size of pores formed in the cross-linked mixed solution in step 2.

As described above, the method for preparing a water-soluble chitosan-algin-gelatin porous foam according to the present invention is characterized in that pH adjustment step for preventing precipitation by ionic bonding of chitosan and anionic alginic acid using ultrasound A radiation and freeze-drying step is carried out without using a chemical crosslinking agent which can be omitted, which is harmful to human body and which is a problem of residual toxicity, so that mechanical properties such as porosity and moisture absorption rate are improved, Can be prepared.

The present invention also provides a water-soluble chitosan-algin-gelatin porous foam produced by the above-described method.

The water-soluble chitosan-alginate-gelatin porous foam prepared using the ultrasonic wave and the radiation according to the present invention exhibits remarkably improved porosity and water absorption rate than the foam prepared by using ultrasonic waves or radiation alone (see Examples 1 to 3 ) Tissue-engineered cell scaffold.

Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples.

It should be noted, however, that the following examples and experimental examples are illustrative of the present invention, and the present invention is not limited by the following examples and experimental examples.

< Example  Process for the preparation of water soluble chitosan-alginate gelatin porous foam using radiation and ultrasound.

Water-soluble chitosan solution (6 wt%, 2 mL) and algin solution (4 wt%, 2 mL) were mixed and ultrasonicated at 1000 W was irradiated for 30 min (step 1); Gelatin solution (4% by weight, 2 mL) was added to the mixed solution of step 1 and cross-linking was performed by irradiating with 10 kGy intensity (step 2); And a cross-linked mixed solution of the step 2 were cooled at -20 ° C for 12 hours and lyophilized at -70 ° C for 120 hours (step 3) to prepare a water-soluble chitosan-algin-gelatin porous foam .

< Example  Method for preparing soluble chitosan-alginate gelatin porous foam using radiation and ultrasound.

Water-soluble chitosan solution (6 wt%, 2 mL) and algin solution (4 wt%, 2 mL) were mixed and ultrasonicated at 1000 W was irradiated for 30 min (step 1); Gelatin solution (4% by weight, 2 mL) was added to the mixed solution of step 1 and cross-linking was performed by irradiating with 20 kGy intensity (step 2); And a cross-linked mixed solution of the step 2 were cooled at -20 ° C for 12 hours and lyophilized at -70 ° C for 120 hours (step 3) to prepare a water-soluble chitosan-algin-gelatin porous foam .

< Example  Method for preparing water-soluble chitosan-alginate gelatin porous foam using radiation and ultrasound.

Water-soluble chitosan solution (6 wt%, 2 mL) and algin solution (4 wt%, 2 mL) were mixed and sonicated at 1000 W for 60 min (step 1); Gelatin solution (4% by weight, 2 mL) was added to the mixed solution of step 1 and cross-linking was performed by irradiating with 10 kGy intensity (step 2); And a cross-linked mixed solution of the step 2 were cooled at -20 ° C for 12 hours and lyophilized at -70 ° C for 120 hours (step 3) to prepare a water-soluble chitosan-algin-gelatin porous foam .

< Example  Method for preparing water-soluble chitosan-algin-gelatin porous foam using radiation and ultrasound.

Water-soluble chitosan solution (6 wt%, 2 mL) and algin solution (4 wt%, 2 mL) were mixed and sonicated at 1000 W for 60 min (step 1); Gelatin solution (4% by weight, 2 mL) was added to the mixed solution of step 1 and cross-linking was performed by irradiating with 20 kGy intensity (step 2); And a cross-linked mixed solution of the step 2 were cooled at -20 ° C for 12 hours and lyophilized at -70 ° C for 120 hours (step 3) to prepare a water-soluble chitosan-algin-gelatin porous foam .

< Example  Method for preparing water-soluble chitosan-algin-gelatin porous foam using radiation and ultrasound.

Water-soluble chitosan solution (6 wt%, 2 mL) and algin solution (4 wt%, 2 mL) were mixed and sonicated at 1000 W for 120 min (step 1); Gelatin solution (4% by weight, 2 mL) was added to the mixed solution of step 1 and cross-linking was performed by irradiating with 10 kGy intensity (step 2); And a cross-linked mixed solution of the step 2 were cooled at -20 ° C for 12 hours and lyophilized at -70 ° C for 120 hours (step 3) to prepare a water-soluble chitosan-algin-gelatin porous foam .

< Example  Method for preparing water-soluble chitosan-algin-gelatin porous foam using radiation and ultrasound.

Water-soluble chitosan solution (6 wt%, 2 mL) and algin solution (4 wt%, 2 mL) were mixed and sonicated at 1000 W for 120 min (step 1); Gelatin solution (4% by weight, 2 mL) was added to the mixed solution of step 1 and cross-linking was performed by irradiating with 20 kGy intensity (step 2); And a cross-linked mixed solution of the step 2 were cooled at -20 ° C for 12 hours and lyophilized at -70 ° C for 120 hours (step 3) to prepare a water-soluble chitosan-algin-gelatin porous foam .

< Comparative Example  Method for preparing water soluble chitosan-alginate gelatin porous foam using radiation.

Add water-soluble chitosan solution (6 wt%, 2 mL) and algin solution (4 wt%, 2 mL) and gelatin solution (4 wt%, 2 mL) And crosslinking was carried out. The crosslinked mixed solution was cooled at -20 캜 for 12 hours and lyophilized at -70 캜 for 120 hours to prepare a water-soluble chitosan-algin-gelatin porous foam.

< Comparative Example  Method for preparing water-soluble chitosan-algin-gelatin porous foam using radiation.

Add water-soluble chitosan solution (6 wt%, 2 mL) and algin solution (4 wt%, 2 mL) and gelatin solution (4 wt%, 2 mL) And crosslinking was carried out. The crosslinked mixed solution was cooled at -20 캜 for 12 hours and lyophilized at -70 캜 for 120 hours to prepare a water-soluble chitosan-algin-gelatin porous foam.

< Comparative Example  Method for preparing soluble chitosan-alginate gelatin porous foam using ultrasound.

Add water-soluble chitosan solution (6 wt%, 2 mL) and algin solution (4 wt%, 2 mL) and gelatin solution (4 wt%, 2 mL) Was crosslinked for 120 minutes. The crosslinked mixed solution was cooled at -20 캜 for 12 hours and lyophilized at -70 캜 for 120 hours (step 3) to prepare a water-soluble chitosan-algin-gelatin porous foam.

< Experimental Example  1> Evaluation of Porosity of Water-Soluble Chitosan-Algin-Gelatin Porous Foam

In order to evaluate the uniformity and porosity of the pores formed in the water-soluble chitosan-alginate-gelatin porous foam produced by the production method according to the present invention, the foam prepared in Examples 1 to 6 and Comparative Examples 1 and 2 was subjected to air permeability (Gurley type densometer, Toyoseiki, Japan). The results are shown in Fig.

1 is a graph showing the air permeability of the foam prepared in Examples 1 to 6 and Comparative Examples 1 and 2. FIG.

As shown in Fig. 1, the foams of Examples 1 to 6 according to the present invention irradiated with ultrasound and radiation, compared to the foams of Comparative Example 1 and Comparative Example 2 irradiated only with radiation without irradiation of ultrasonic waves, exhibited improved porosity .

Compared with the foams of Comparative Example 1, Examples 1, 3 and 5, which were manufactured using the radiation intensity of 10 kGy, Comparative Example 2, Examples 2, 4 and 6 prepared by using the radiation intensity of 20 kGy (Sec / 100 mL), the cross-linking between the polymer of chitosan, alginate and gelatin increases and the porosity increases as the radiation dose increases.

Further, comparing the foams of Comparative Example 1, Examples 1, 3 and 5 or the foams of Comparative Example 2, Examples 2, 4 and 6, porosity is improved as the irradiation time of the ultrasonic waves is increased.

Therefore, it can be seen that the method of producing foam according to the present invention using ultrasound and radiation is an efficient method of producing a foam having improved porosity as compared with the case of using ultrasonic waves or radiation alone.

< Experimental Example  2> Evaluation of Water Absorption Rate of Water-Soluble Chitosan-Algin-Gelatin Porous Foam

In order to evaluate the water absorption rate (%) of the water-soluble chitosan-algin-gelatin porous foam produced by the production method according to the present invention, the dried weight of the foam prepared in Comparative Examples 2 to 3 and Example 4, The foam was immersed in distilled water to measure the weight of the absorbed foam, and the water absorption rate (%) with time was calculated by the following formula (1).

[Equation 1]

FIG. 2 is a graph showing moisture absorption rates of the foam prepared in Comparative Examples 2 and 4 according to immersion time of distilled water. FIG.

As shown in FIG. 2, the foam of Comparative Example 3 prepared by irradiating only ultrasonic waves was decomposed in 10 minutes after immersion in distilled water, and the water absorption rate could not be measured. The foam of Comparative Example 2 prepared by irradiating only the radiation and the foam of Example 4 prepared by irradiating ultrasound and radiation according to the present invention were compared with each other at the initial stage of immersion time of 10 minutes. The foam of Example 4 showed a water absorption difference of about 1,700% compared to the foam of Comparative Example 2. In addition, the foam of Example 4 according to the present invention reached a maximum water absorption rate after 40 minutes of immersion time, and showed a difference in water absorption rate of about 5000% from the foam of Comparative Example 2. In the foam of Comparative Example 2, The maximum moisture uptake rate was shown when 1 hour of immersion time had passed.

Accordingly, it can be seen that the method of producing a foam using ultrasonic waves and radiation according to the present invention exhibits a remarkably superior water absorption effect than the conventional method of producing a foam using only ultrasonic waves or the method of producing a foam using only radiation. Thus, the process according to the present invention may be useful as a process for preparing a water-soluble chitosan-algin-gelatin porous foam having a significantly improved water uptake.

< Experimental Example  3> Evaluation of uniformity of water-soluble chitosan-alginate gelatin porous foam

In order to examine the effect of the manufacturing method according to the present invention on the uniformity of the water-soluble chitosan-algin-gelatin porous foam, the following experiment was conducted.

In order to evaluate the uniformity of the foam with and without irradiation of the ultrasonic waves, the foam of Example 2 in which ultrasonic waves were irradiated and the foam of Comparative Example 2 in which ultrasonic waves were not irradiated were prepared before the step of performing freeze- The photograph is shown in Fig.

In order to evaluate the uniformity of the foam with or without irradiation, the foam of Comparative Example 3 and the foam of Example 2 irradiated with the radiation and the foam of Comparative Example 3 and Example 2 were immersed in distilled water For 6 hours, and then photographs of the foam were shown in FIG.

Further, the inside of the foam of Example 2 irradiated with ultrasonic waves and radiation was photographed with an electron microscope (Model: JSM-6390; manufacturer: JEOL, Japan) and is shown in Fig.

Fig. 3 is a photograph of foam form of Comparative Example 2 and Example 2 before lyophilization.

4 (a) is a foam of Comparative Example 3, (b) is a foam of Example 2, (c) is a foam of Comparative Example 3 after being immersed in distilled water for 6 hours, Lt; / RTI &gt; is a photograph of the foam form of Example 2 after being immersed for a time.

5 is an inside photograph of the foam of Example 2 irradiated with ultrasound and radiation.

As shown in FIGS. 3 to 5, it can be seen that by irradiation with ultrasonic waves and radiation, the form of the foam becomes more uniform.

Accordingly, the process for preparing the water-soluble chitosan-algin-gelatin porous foam according to the present invention can be useful as a method for producing porous foam which is uniform.

Claims (11)

A step of mixing ultrasound with water-soluble chitosan solution and algin solution at an intensity of 500 - 1000 W for 30 minutes to 3 hours (step 1);
Adding a gelatin solution to the mixed solution of step 1 and performing radiation crosslinking (step 2); And
And lyophilizing the cross-linked mixed solution of step 2 (step 3).
The method according to claim 1,
Wherein the water-soluble chitosan solution of step 1 is used at a concentration of 1 - 10 wt%.
The method according to claim 1,
Wherein the alginic acid solution is used in a concentration of 1 to 5% by weight.
delete delete The method according to claim 1,
Wherein the gelatin solution of step 2 is used in a concentration of 1 to 5% by weight.
The method according to claim 1,
Wherein the radiation of step 2 is irradiated at a rate of 1 - 100 kGy.
The method according to claim 1,
Wherein the radiation of step 2 is irradiated at a rate of 1 to 20 kGy per hour.
The method according to claim 1,
Wherein the freeze-drying of step 3 is carried out at -20 to -180 ° C.
The method according to claim 1,
Wherein the mixing ratio of the water-soluble chitosan solution, the alginate solution and the gelatin solution is 3: 2: 2 by weight.
A water-soluble chitosan-algin-gelatin porous foam produced by the method of claim 1.

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