CN118384312A

CN118384312A - Anti-adhesion shape memory sponge and application thereof

Info

Publication number: CN118384312A
Application number: CN202311845290.5A
Authority: CN
Inventors: 吕琪; 侯世科; 王秀丹; 史杰; 郭小芹; 孙志广; 杨欣燃; 张语嫣
Original assignee: Tianjin University
Current assignee: Tianjin University
Priority date: 2023-12-29
Filing date: 2023-12-29
Publication date: 2024-07-26

Abstract

The present disclosure relates to biomedical materials, and more particularly, to an anti-adhesion shape memory sponge and application thereof. The substrate material with the shape memory function is a spongy material, is used for filling wounds, achieves the effect of closing the wounds, and can effectively prevent damage or inflammation caused by displacement after implantation. Further, the anti-adhesion film on the surface of the implant provided by the disclosure has a continuously-changing viscosity value from the bonding surface with the substrate material to the exposed surface, and the skeleton component of the bonding surface is the same as the substrate material, so that the bonding strength difference between the anti-adhesion film and the substrate material due to the component difference is avoided. Meanwhile, due to the fact that the viscosity value is continuously changed, when the antibacterial agent is added into the anti-adhesion film, the antibacterial component is more prone to diffusing towards the direction of the substrate material, and in the diffusion process, the viscosity of the anti-adhesion film is reduced along with the reduction of diffusion concentration, so that the slow and stable release of the antibacterial agent is ensured, and the antibacterial action time is prolonged.

Description

Anti-adhesion shape memory sponge and application thereof

Technical Field

The present disclosure relates to biomedical materials, and more particularly, to an anti-adhesion shape memory sponge and application thereof.

Background

Post-traumatic hemorrhage has been one cause of life and health risk for humans. In particular, penetrating and trunk hemorrhages need to be subjected to rapid and effective hemostatic treatments. With the market of hemostatic products such as cyanoacrylate, glutaraldehyde cross-linked albumin, zeolite-based rapid blocks, fibrin-based bandages, and the like, the hemostatic efficiency of surface bleeding is increasing. However, the treatment of incompressible bleeding (e.g., penetrating wounds, organ bleeding) is still based on blood transfusion, blood products and surgical sutures. The current blood products have scarce sources and high preservation requirements; surgical stapling requires a high level of skill in the procedure and high cleanliness in the treatment environment. Thus, the treatment of incompressible bleeding remains an urgent challenge.

In previous studies, the applicant found that the combined use of gelatin and sodium alginate can improve the mechanical properties of the system while maintaining the original hemostatic advantages of gelatin, but that the liquid absorption and mechanical properties need to be further improved when used in incompressible bleeding wounds.

Disclosure of Invention

The present disclosure provides an anti-adhesion implant material with shape memory function to meet the hemostatic requirement of incompressible bleeding wound surface, solve the postoperative risk caused by postoperative adhesion, displacement or bacteria staining of implant simultaneously, make up the deficiency of the existing anti-adhesion implant product, and simultaneously, another object of the present disclosure is to provide a simple and rapid preparation method of the implant material, and to prepare a portable, convenient to use, multifunctional anti-adhesion product by applying the implant material.

In order to achieve the above object, the present disclosure provides the following technical solutions:

In a first aspect, the present disclosure provides an anti-adhesion implant material having a shape memory function, comprising a base material having a shape memory function and an anti-adhesion film on at least one surface of the base material.

In an alternative embodiment, the substrate material is obtained from at least two polymer backbone components by a cross-linking reaction.

In alternative embodiments, the crosslinking is achieved by the incorporation of two or more of the following ions or functional groups: polyvalent cations, amino groups, carboxyl groups, aldehyde groups, imino groups, hydroxyl groups, phenolic hydroxyl groups.

In alternative embodiments, the polymer backbone molecule is selected from alginic acid or an alginate, gelatin, or polydopamine.

In an alternative embodiment, the shape memory anti-adhesion implant material has a imbibition porosity after compression of 100% to 4000%. Preferably, the anti-adhesion implant material with the shape memory function has the imbibition porosity of 100-4000% after compression in water and the imbibition porosity of 100-3000% after compression in blood.

In an alternative embodiment, the anti-adhesive film has a continuously variable tackiness, with the exposed side being the non-tacky side and the bonding side with the base material being the tacky side. Preferably, the bonding surface of the anti-adhesion film and the base material has the same polymer skeleton component as the base material, and the exposed surface has a different polymer skeleton component added additionally.

In an alternative embodiment, the thickness ratio of the base material and the anti-adhesion film is 3 to 50:1.

In an alternative embodiment, the anti-adhesion film contains an antimicrobial agent. Preferably, the antibacterial agent is selected from at least one of silver ions, antibiotics or antibacterial peptides. The anti-adhesion film also contains at least one of a coagulant or a tackifier; preferably, the coagulant is selected from at least one of tranexamic acid, carbon nanofibers, fibrin or thrombin. Preferably, the adhesion promoter comprises transglutaminase.

In a second aspect, the present disclosure provides a method for preparing the anti-adhesion implant material according to the first aspect, which includes preparing a base material through a crosslinking reaction, and then preparing an anti-adhesion film on at least one surface of the base material, to obtain the anti-adhesion implant material.

In an alternative embodiment, the preparation method comprises the steps of crosslinking at least two of polydopamine, gelatin or alginic acid or salt thereof to obtain a base material, coating mixed gel of gelatin and alginic acid or salt thereof on at least one surface of the base material, and spraying a tannic acid and calcium chloride mixed solution on the exposed surface of the mixed gel.

In an alternative embodiment, the preparation method of the base material comprises the steps of mixing 0.1% -10.0% (w/v) gelatin aqueous solution with 1% -10% (w/v) sodium alginate aqueous solution according to a volume ratio of 1:0.5-1:5, adding 0.1g/mL dopamine pre-cooling water solution into a mixed solution of gelatin and sodium alginate according to a volume ratio of 1% (v/v) to 20% (v/v), adding 30 mg/mL-50 mg/mL sodium periodate aqueous solution into the mixed solution according to a volume ratio of 4:1-1:3 with the dopamine pre-cooling aqueous solution, uniformly mixing, and freeze-drying to obtain the base material. More preferably, the base material is subjected to curing crosslinking in glutaraldehyde steam environment. Further preferably, the cured cross-linked substrate material is subjected to a gradient wash with an ethanol solution.

In an alternative embodiment, the mixed gel contains 20.0-50.0% (w/v) gelatin water solution and 1-10% (w/v) alginic acid or its salt water solution in a volume ratio of 1:0.5-1:5.

In an alternative embodiment, after a mixed gel of gelatin and alginic acid or a salt thereof is coated on at least one surface of the base material, the mixed gel is placed in a glutaraldehyde steam environment to be cured and crosslinked, and then a mixed solution of tannic acid and calcium chloride is sprayed on the exposed surface of the mixed gel. Preferably, the mixed solution of tannic acid and calcium chloride contains 1.0% -5% (w/v) of calcium chloride solution and 100mg/ml tannic acid solution in a volume ratio of 1:1-1:5.

In a third aspect, the present disclosure provides the use of the implant material of the first aspect, or the implant material prepared by the preparation method of the second aspect, in the preparation of a hemostatic, antibacterial or anti-adhesion product.

In a fourth aspect, the present disclosure provides an implant dressing comprising the implant material of the first aspect or a dried implant material thereof, or the implant material prepared by the preparation method of the second aspect or a dried implant material thereof.

In a fifth aspect, the present disclosure provides a portable kit comprising the implant material of the first aspect or a dried implant material thereof, or the implant material prepared by the preparation method of the second aspect or a dried implant material thereof.

In a sixth aspect, the present disclosure provides a hemostatic device comprising a pressure applicator and a dried implant material filled in the pressure applicator, the implant material comprising the implant material of the first aspect or prepared by the preparation method of the second aspect.

Preferably, the pressure applicator comprises a syringe.

In a seventh aspect, the present disclosure provides a hemostatic platform or hemostatic system comprising the hemostatic device of the sixth aspect.

In an eighth aspect, the present disclosure provides a method for hemostasis of an incompressible bleeding wound surface, or a method for post-operative hemostasis, anti-adhesion, antibacterial or implant displacement prevention in vivo, comprising applying the implant material of the first aspect or a post-drying implant material thereof, or the implant material prepared by the preparation method of the second aspect or a post-drying implant material thereof, to a post-operative wound site.

The substrate material with the shape memory function is a spongy material, has high liquid absorption capacity, is self-adhesive and is used for filling wounds, and the anti-adhesion film matched with the surface of the substrate material can achieve the effect of closing the wounds. Because the substrate material provided by the disclosure has a shape memory function, after absorbing moisture or plasma, pressure is formed on adjacent tissues, and damage or inflammation caused by displacement after implantation can be effectively prevented while hemostasis is achieved by compression.

Further, the anti-adhesion film on the surface of the implant provided by the disclosure has a continuously-changing viscosity value from the bonding surface with the substrate material to the exposed surface, and the skeleton component of the bonding surface is the same as the substrate material, so that the bonding strength difference between the anti-adhesion film and the substrate material due to the component difference is avoided. Meanwhile, due to the fact that the viscosity value is continuously changed, when the antibacterial agent is added into the anti-adhesion film, the antibacterial component is more prone to diffusing towards the direction of the substrate material, and in the diffusion process, along with the reduction of diffusion concentration, the viscosity of the anti-adhesion film is also reduced, namely the diffusion resistance is reduced, so that the slow and stable release of the antibacterial agent is ensured, and the antibacterial action time is prolonged.

Drawings

In order to more clearly illustrate the embodiments of the present disclosure or the prior art, the drawings that are required in the detailed description or the prior art will be briefly described, it will be apparent that the drawings in the following description are some embodiments of the present disclosure, and other drawings may be obtained according to the drawings without inventive effort for a person of ordinary skill in the art.

FIG. 1 is a physical diagram of a successful sponge material prepared in example 1;

FIG. 2 is a physical diagram of the undesirable sponge material prepared in example 1;

FIG. 3 shows the microstructure and the linking groups of the sponge material prepared in example 1;

FIG. 4 is a graph showing the effect of different crosslinking times on the properties of the sponge material in example 2;

FIG. 5 is a cyclic compression test result of the sponge material in example 2;

FIG. 6 shows the results of an antimicrobial test for sponge material in example 3;

FIG. 7 is a graph showing the TA releasing ability of the anti-blocking layer of the sponge material of example 3;

FIG. 8 illustrates the hemostatic effect of GSDs in an application example;

Figure 9 shows in vitro and in vivo anti-adhesion activity of GSD in application examples.

Detailed Description

For the purposes of making the objects, technical solutions and advantages of the embodiments of the present disclosure more apparent, the technical solutions of the embodiments of the present disclosure will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present disclosure, and it is apparent that the described embodiments are some embodiments of the present disclosure, but not all embodiments.

Definition or terminology of (I)

The following abbreviations are used in connection with the definitions or terms to which the present disclosure relates. 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. The following terms are provided below.

As used herein, the terms "a" and "an" and "the" and similar referents refer to the singular and the plural, unless the context clearly dictates otherwise.

As used herein, the conjunctive term "and/or" between various of the elements is understood to each include a single option and a combined option. For example, when two elements are joined by an "and/or," the first option refers to the applicability of the first element without the second element. The second option refers to the applicability of the second element without the first element. The third option refers to the applicability of the first and second elements together. Any of these options is understood to fall within the meaning and therefore meets the requirements of the term "and/or" as used herein. Concurrent applicability of multiple options is also understood as the term's stated meaning, thus meeting the requirements of the term ' and/or '.

As used herein, the term "shape memory" refers to a material that is capable of recovering its original shape after deformation. In certain embodiments, the materials with shape memory function described in the present disclosure include spongy implant materials, such as implant materials with high elasticity, capable of restoring an original shape, obtained by polymerization, crosslinking, or the like of natural or synthetic polymers. In other embodiments, the shape memory may also be a shape memory alloy, such as, but not limited to, nickel-titanium (e.g., NITINOL) alloys, copper-zinc-aluminum-nickel alloys, copper-aluminum-nickel alloys, and the like.

As used herein, the terms "adhesion" and "blocking" are used interchangeably to refer to the phenomenon whereby tissue films or sites of different tissue sources or different compositions within the body adhere after physical contact, requiring the application of an external force to separate.

As used herein, the term "polymer backbone" refers to a polymeric network in which a plurality of or different polymers are reacted by crosslinking, grafting, etc. to form a carbon chain as a connecting structure, thereby imparting a certain viscosity and mechanical properties to a substrate material or an anti-adhesion film, while a large number of spatial structures are partitioned between the carbon chains, which can be used as a buffer force or to load functional molecules.

As used herein, the term "antimicrobial" refers to a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, archaea, or protozoa. The antimicrobial agent either kills microorganisms or inhibits the growth of microorganisms. In one or more embodiments, the antimicrobial agent includes, but is not limited to, at least one of silver ions, antibiotics, or antimicrobial peptides.

As used herein, the term "accelerator" refers to a substance capable of accelerating the formation of crosslinked complexes resulting from the reaction of backbone components. Such materials are well known to those skilled in the art and may optionally include, but are not limited to, tranexamic acid, carbon nanofibers, fibrin, thrombin, and the like.

(II) detailed technical scheme

It should be noted that, the anti-adhesion implant material disclosed in the present disclosure means that the implanted repair material is anti-adhesion on the exposed surface of the closed wound after implantation, and the base material is an adhesive material capable of being tightly attached to the wound, so as to achieve the functions of postoperative hemostasis, fixation, etc.

In an alternative embodiment, the substrate material is obtained from at least two polymer backbone components by a cross-linking reaction. The crosslinking reaction among the various polymer skeleton components aims at enhancing the viscosity and/or the mechanical strength, simultaneously enabling the substrate material to have higher elasticity, realizing the shape memory function and preventing the situation of implant displacement caused by stress deformation after implantation.

In alternative embodiments, the polymer backbone molecule is selected from alginic acid or an alginate, gelatin, or polydopamine. Among them, the combination of alginic acid (sodium), gelatin and polydopamine is a combination backbone molecule with a preferable shape memory function obtained by the inventors of the present disclosure through an attempt to summarize.

In an alternative embodiment, the thickness ratio of the base material and the anti-adhesion film is from X to X:1.

It should be noted that, the inclusion of the antibacterial agent in the anti-adhesion film means that the implant material provided by the present disclosure is before or early after implantation into the body. After the antibacterial agent in the implant material is in contact with a liquid environment after implantation, the antibacterial agent in the anti-adhesion film can be slowly released, and the antibacterial agent can diffuse into the base material along with the extension of implantation time, so that it is necessary to state that in the service process of the implant material provided by the disclosure, another special product form exists in the body, namely, the anti-adhesion film and the base material simultaneously contain the antibacterial agent. Another special product form, in which the release of the antimicrobial agent in the anti-adhesive film is complete, no longer contains the antimicrobial agent, but the base material still contains residual antimicrobial agent, may also be present. The particular product forms of both of the above-described service processes are well within the purview of those skilled in the art and are, therefore, intended to be within the scope of the present disclosure.

In an alternative embodiment, the preparation method comprises the steps of crosslinking at least two of polydopamine, gelatin or alginic acid or salt thereof to obtain a base material, coating mixed gel of gelatin and alginic acid or salt thereof on at least one surface of the base material, and spraying a tannic acid and calcium chloride mixed solution on the exposed surface of the mixed gel. Wherein, tannic acid and calcium chloride can respectively form a crosslinking reaction with gelatin and alginic acid, so that gelatin and alginic acid or salt thereof which originally have a certain crosslinking degree generate stronger crosslinking reaction to form a film structure with four components crosslinked, the viscosity of the film is obviously reduced, and the substrate surface is endowed with non-viscosity. Meanwhile, since the gelatin and alginic acid mixed gel has a certain cross-linked network, there is a remarkable gradual permeation process after spraying tannic acid and calcium chloride, and since the molecular weight and volume are different, the permeation speed of calcium ions is much faster than tannic acid, so that the cross-linked degree inside the anti-sticking film has a gradual decreasing continuous change along the longitudinal direction from the exposed surface to the surface combined with the substrate material. Accordingly, from the point of view of bonding stress, the bonding surface skeleton components of the anti-adhesion film and the substrate material are consistent, the viscosity difference is small, after crosslinking (such as glutaraldehyde steam crosslinking), the substrate material and the anti-adhesion film are well bonded, and the internal stress is gradually increased along the longitudinal direction from the substrate material to the exposed surface of the anti-adhesion film, and no sudden rise section exists, so that brittle failure is not easy to occur, and the anti-adhesion film can be used in a tissue environment with strong pressure and strong shearing force (such as heart repair).

Wherein the gelatin content of the aqueous gelatin solution is 0.1% to 10% (w/v), alternatively such as 1% to 4% (w/v), for example, including but not limited to 1％(w/v)、1.5％(w/v)、2％(w/v)、2.5％(w/v)、3％(w/v)、3.5％(w/v)、4％(w/v)、4.5％(w/v)、5％(w/v)、5.5％(w/v)、6％(w/v)、6.5％(w/v)、7％(w/v)、7.5％(w/v)、8％(w/v)、8.5％(w/v)、9％(w/v)、9.5％(w/v) or 10% (w/v).

Wherein the sodium alginate content of the aqueous sodium alginate solution is 1% -10% (w/v), alternatively such as 1% -5% (w/v), for example, including but not limited to 1% (w/v), 2% (w/v), 3% (w/v), 4% (w/v), 5% (w/v), 6% (w/v), 7% (w/v), 8% (w/v), 9% (w/v) or 10% (w/v).

Wherein the volume ratio of the gelatin aqueous solution to the sodium alginate aqueous solution is 1:0.5-1:5, optionally 1:0.5-1:2. For example, including but not limited to 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.5, 1:2.0, 1:2.5, 1:3.0, 1:3.5, 1:4.0, 1:4.5, or 1:5.0.

Wherein the aqueous solution of dopamine is added in a volume of 1% (v/v) to 20% (v/v), alternatively 2% (v/v) to 5% (v/v). For example, including but not limited to 1% (v/v), 2% (v/v), 4% (v/v), 6% (v/v), 8% (v/v), 10% (v/v), 12% (v/v), 14% (v/v), 16% (v/v), 18% (v/v), or 20% (v/v).

Wherein the content of sodium periodate in the sodium periodate aqueous solution is 30 mg/mL-50 mg/mL, optionally 35 mg/mL-42 mg/mL. For example, including but not limited to 30mg/mL、31mg/mL、32mg/mL、33mg/mL、34mg/mL、35mg/mL、36mg/mL、37mg/mL、38mg/mL、39mg/mL、40mg/mL、41mg/mL、42mg/mL、43mg/mL、44mg/mL、45mg/mL、46mg/mL、47mg/mL、48mg/mL、49mg/mL or 50mg/mL.

Wherein the volume ratio of the sodium periodate aqueous solution to the dopamine pre-cooling water solution is 4:1-1:3, and optionally 3:1-1:1. For example, including but not limited to 4:1, 3.5:1, 3:1, 2.5:1, 2:1, 1.5:1, 1:1, 1:1.5, 1:2, 1:2.5, or 1:3.

Wherein the content of gelatin in the gelatin aqueous solution is 20.0% -50.0% (w/v), alternatively 25.0% -45.0% (w/v), alternatively 30.0% -40.0% (w/v). For example, including but not limited to 20.0% (w/v), 25.0% (w/v), 30.0% (w/v), 35.0% (w/v), 40.0% (w/v), 45.0% (w/v), or 50.0% (w/v).

Wherein the content of alginic acid or a salt thereof in the aqueous solution of alginic acid or a salt thereof is 1 to 10% (w/v), alternatively 1 to 4% (w/v). For example, including but not limited to 1% (w/v), 2% (w/v), 3% (w/v), 4% (w/v), 5% (w/v), 6% (w/v), 7% (w/v), 8% (w/v), 9% (w/v), or 10% (w/v).

Wherein the volume ratio of the gelatin aqueous solution to the alginic acid or its salt aqueous solution is 1:0.5-1:5, optionally 1:0.5-1:1.5. For example, including but not limited to 1:0.5, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, or 1:5.

Wherein the content of calcium chloride in the calcium chloride solution is 1.0% -5% (w/v), alternatively 1.0% -4% (w/v). For example, including but not limited to 1.0% (w/v), 1.5% (w/v), 2.0% (w/v), 2.5% (w/v), 3.0% (w/v), 3.5% (w/v), 4.0% (w/v), 4.5% (w/v), or 5.0% (w/v).

Wherein the volume ratio of the calcium chloride solution to the tannic acid solution is 1:1-1:5, and optionally 1:2-1:4. For example, including but not limited to 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, or 1:5.

In a fourth aspect, the present disclosure provides an implant dressing comprising the implant material of the first aspect or a dried implant material thereof, or the implant material prepared by the preparation method of the second aspect or a dried implant material thereof. Wherein the "dressing" refers to a wound dressing for application to an existing wound, incision or scar. The present disclosure is directed particularly to a dressing for use in vivo wound repair during surgery, which is required to prevent adhesion between tissues while exhibiting hemostatic effects, and to have certain antibacterial and displacement-preventing functions.

In a fifth aspect, the present disclosure provides a portable kit comprising the implant material of the first aspect or a dried implant material thereof, or the implant material prepared by the preparation method of the second aspect or a dried implant material thereof. The implantation material can be one of the components in the portable tool box, and can be matched with other tools or medical instruments in the tool box to implement surgery or wound surface and wound treatment. The implant material can also be one of the components forming a certain tool or medical instrument in the portable tool kit, and the implant material disclosed by the disclosure can play roles of hemostasis, antibiosis, adhesion prevention and the like in the process of using the tool or medical instrument by medical staff or emergency personnel.

Preferably, the pressure applicator comprises a syringe.

The method of post-operative hemostasis in vivo includes, but is not limited to, applying the implant material provided by the present disclosure to a wound, a wound or a incision that is in or at risk of bleeding, to achieve a therapeutic effect of avoiding bleeding or substantial bleeding prior to wound, wound or incision healing.

The in vivo post-operative anti-adhesion method includes, but is not limited to, applying the implant material provided by the present disclosure between two adjacent tissues, preferably applying a base material to a wound, a wound or a incision of a tissue having a wound, a wound or an incision, to prevent the adhesive film from contacting another adjacent tissue to prevent adhesion between the adjacent tissues. It is easy to understand that when two adjacent tissue contact surfaces each contain a wound, a wound or a knife edge, the implant material provided by the present disclosure can be applied to the wound, the wound or the knife edge of two tissues in the same way, and the anti-adhesion films of the two implant materials are used as contact surfaces, so that the adhesion between the tissues is avoided.

Since the aseptic operating conditions are well established in the prior art, the microorganisms to which the in vivo post-operative antibacterial method is directed are generally microorganisms colonies derived from the fact that when body fluid (e.g., interstitial fluid or blood) flows through the implantation site, microorganisms contained in the body fluid are trapped by the implantation material and proliferate. In certain embodiments of the present disclosure, an antimicrobial agent is added to the anti-adhesion film, which achieves slow and steady release with the special results of the implant material provided by the present disclosure, thereby continuously inhibiting the growth of trapped microorganisms and preventing the formation of colonies.

The method for preventing the implant from being displaced after the in-vivo operation comprises the steps of utilizing the shape memory function of the plant material provided by the disclosure to ensure that when the implant material is deformed or has deformed under the action of mechanical force in tissues or among the tissues in the service process, the implant material is autonomously restored to the service state when being implanted under the action of the shape memory function, or when medical staff detects that the implant is deformed and displaced, or the potential risk of deformation and displacement exists, the shape memory function of the implant material is stimulated through in-vitro or in-vivo condition regulation and control, so that the implant material is promoted to be restored to the state when being implanted.

(II) detailed description of the invention

Some embodiments of the present disclosure are described in detail below with reference to the accompanying drawings. The following embodiments and features of the embodiments may be combined with each other without conflict. The following examples are provided to further illustrate the disclosure, but are not to be construed as limiting the disclosure, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principles of the disclosure are intended to be equivalent substitutes. The technical means used in the examples are conventional means well known to those skilled in the art unless otherwise indicated.

Example 1 preparation of anti-sticking shape memory sponge

1.1 Mixing gelatin water solution and sodium alginate water solution according to a certain proportion, and placing in an ice water bath for precooling. Adding 0.1g/mL of dopamine pre-cooling water solution into the mixed solution of gelatin and sodium alginate according to a certain proportion. Adding the precooled sodium periodate aqueous solution into the mixed solution according to a certain volume ratio with the dopamine precooled aqueous solution, and stirring for 30min in an ice water bath. And (3) placing the stirred mixed solution in an environment of-20 ℃ for low-temperature reaction for 36-48 h. Freeze drying for 48h after reaction, taking out, and placing in glutaraldehyde steam environment for crosslinking for 12-30 h at normal temperature. After crosslinking was completed, gradient washing was performed using an ethanol solution.

1.2 Membranous Structure portion

Mixing gelatin water solution and sodium alginate water solution according to a certain proportion, and placing the mixed sol into a mould.

1.3 Double layer structural bonding

The shape memory sponge part is placed on a sol structure and placed in glutaraldehyde steam for crosslinking for 0.5 to 1 hour. The aqueous solution prepared by the calcium chloride solution and the tannic acid solution with the volume ratio of 100mg/ml is uniformly sprayed on the surface of the sol to form a membranous structure.

Through a plurality of batches of experiments, the specific dosage of each parameter in the preparation steps is adjusted, and whether the gel repairing material which can be compressed and can recover the shape after absorbing water can be obtained is examined. The specific parameters in the above steps, and the shape memory and anti-blocking ability test results in different experimental batches are shown in tables 1 and 2:

table 1 specific parameter comparison table for different experimental batches

Concentration of aqueous gelatin solution (% w/v) in step 1.1	A
		Concentration of sodium alginate aqueous solution (% w/v) in step 1.1	B
Volume ratio of gelatin aqueous solution to sodium alginate aqueous solution in step 1.1	C
		Volume ratio of aqueous dopamine solution to gelatin-sodium alginate mixture	D
Sodium periodate aqueous solution concentration (mg/mL)	E
		Volume ratio of aqueous sodium periodate solution to aqueous dopamine solution	F
Concentration of aqueous gelatin solution (% w/v) in step 1.2	G
		Concentration of sodium alginate aqueous solution (% w/v) in step 1.2	H
Volume ratio of gelatin aqueous solution to sodium alginate aqueous solution in step 1.2	I
		Calcium chloride concentration (% w/v) in step 1.3	J
The volume ratio of the calcium chloride solution to the tannic acid solution in the step 1.3	K

TABLE 2 specific parameter values for different experimental batches

After a lot of attempts, the inventor found that in the preparation method of the sponge material provided in this embodiment, the molding, compressibility and washing ability of the sponge are closely related to the above parameters, wherein the concentration of the gelatin aqueous solution in step 1.1 is 0.1% -10%, preferably 1% -4% (w/v); the concentration of the sodium alginate aqueous solution is 1-10% (w/v), preferably 1-5% (w/v); the volume ratio of the gelatin aqueous solution to the sodium alginate aqueous solution is 1:0.5-1:5, preferably 1:0.5 to 1:2; the volume ratio of the dopamine aqueous solution to the gelatin-sodium alginate mixed solution is 1-20%, preferably 2-5%; the concentration of the sodium periodate aqueous solution is 30-50 (mg/mL), preferably 35-42 (mg/mL); the volume ratio of the sodium periodate aqueous solution to the dopamine aqueous solution is 4:1-1:3, preferably 3:1 to 1:1. the concentration of the gelatin aqueous solution in the step 1.2 is 20% -50% (w/v), preferably 30% -40% (w/v); the concentration of the sodium alginate aqueous solution is 1-10% (w/v), preferably 2-5% (w/v); the volume ratio of the gelatin aqueous solution to the sodium alginate aqueous solution is 1:0.5-1:5, preferably 1:0.5 to 1:1.5; the concentration of calcium chloride in the step 1.3 is 1% -5% (w/v), preferably 1% -4% (w/v); when the volume ratio of the calcium chloride solution to the tannic acid solution in the step 1.3 is 1:1-1:5, the prepared hydrogel sponge material is well molded and has compressibility and water absorption recovery capability, as shown in figure 1. When one or more of the above parameters exceeds the above selected ranges, the sponge material is difficult to form, loses shape memory, and breaks after compression to recover the shape as shown in fig. 2. It should be noted that, due to the excessive number of physical drawings, fig. 1 and fig. 2 are only examples, and not all physical appearances are shown.

Exemplary selection of sponge material obtained in experimental batch 1X-ray photoelectron spectroscopy (XPS) of the sample was recorded with a VGscalabMKIIx-ray photoelectron spectrometer. The morphology of the GSD was observed using a field emission scanning electron microscope (FEIQuanta FEG 250,250). Before observation, a gold layer was sprayed on the surface of the sample. By combining XPS and electron microscope results, the connection modes of the components in the sponge material are determined, and the results are shown in figure 3, so that the main structure of the sponge material obtained in the embodiment is rich in pore structures, and can be kept in a compressed state after simple extrusion. After the liquid has contacted the blood, the liquid enters the void and returns the volume to the pre-compressed state. The hemostatic agent is very favorable for hemostasis, the rapid water absorption capacity can effectively enrich blood cells and platelets, and the swollen refrigerating fluid has compression force on wounds.

For the porous structure, dopamine and sodium periodate are added on a gelatin sodium alginate system in the embodiment. Dopamine is contacted with sodium periodate and oxidized to form aldehyde groups, so that the dopamine becomes a good crosslinking agent. The oxidized dopamine oligomer can undergo a Schiff base and Michael addition reaction with amino groups in gelatin to form a network structure. Molecular entanglement and hydrogen bonding between gelatin and sodium alginate maintains macromolecular interactions within the system. And after glutaraldehyde steam secondary crosslinking, glutaraldehyde and active groups (such as hydroxyl and amino) undergo condensation reaction, so that glutaraldehyde and amino in gelatin can be further crosslinked to improve the overall strength of the material. However, the addition of liquid glutaraldehyde in the reaction system results in self-crosslinking, so that the glutaraldehyde steam crosslinking method is selected to not only make crosslinking more uniform, but also control the crosslinking degree better, thus preparing ideal low-temperature gel.

Further, the progress of these chemical reactions was confirmed by X-ray photoelectron spectroscopy. Due to the presence of polydopamine, there was a significant increase in C2 (C-N) and C3 (o=c-N) in the C1s spectrum of the sponge obtained in experimental batch 1 compared to the sponge obtained in experimental batch 21. Whereas michael addition reactions and schiff base reactions allow gelatin to acquire amino groups for further crosslinking or adhesion to adjacent tissues. After secondary crosslinking with glutaraldehyde vapor, C2 (C-N) of the C1s spectrum decreases, as indicated by d in fig. 4, while C3 (o=c-N) increases. The results show that the amino groups in the gelatin in the presence of glutaraldehyde are depleted and further crosslinked to form o=c-N, improving the stability of the network structure.

For the anti-blocking layer, a smooth membranous structure provides a structural basis for anti-blocking, while the addition of tannic acid increases a layer of antimicrobial properties. As the two layers both take gelatin and sodium alginate as main components, good connection can be formed after glutaraldehyde steam crosslinking.

EXAMPLE 2 examination of crosslinking time

This example examined the effect of glutaraldehyde steam cross-linking time (12 h, 16h, 20h, and 24 h) in step 1.1 on the structure of the resulting sponge material (GSD) on the basis of experimental batch 1 of example 1, four sets of sponge materials of different glutaraldehyde steam cross-linking times were prepared. The resulting sponge material was then subjected to field emission scanning electron microscopy, porosity, swelling ratio and compressive strain measurements, the results of which are shown in fig. 4.

Wherein porosity and swelling ratio were measured by impregnation experiments. In testing porosity, GSD was immersed in ethanol, saturated and removed. The mass m ₁ and m ₂ before and after ethanol soaking were determined. V and ρ are used to represent the volume of the sample and the density of ethanol (0.785 g/cm ³). Each sample was measured in duplicate 3 times. The porosity was then calculated according to the formula (m ₂-m₁)/(ρ×v) ×100%.

In detecting the swelling ratio, GSD (mass is denoted as W _O) is first weighed. Then, the balance is made with deionized water or blood at room temperature and weighted again to give a new mass (noted as W _E), and then the Swelling Ratio (SR) is calculated according to the formula sr= (W _E-W_O)/W_O ×100%.

Upon detection of compressive strain, the GSD (diameter 8mm, initial length 12mm (L ₁)) was compressed and held at that strain for 1min. The compression gauge length is set to L ₂. Thereafter, the sample was free of any load for 3min, and the fixed measurement length was L ₃. Then, the sample is soaked in water for rehydration for 1min, the length of the recovery instrument is measured to be L ₄, the test is circulated for three times, and then each detection index is calculated according to the following formula:

Maximum compressive strain (%) = (L ₁-L₂)/L₁ ×100%;

fixed ratio (%) = (L ₁-L₃)/L₁ ×100%;

recovery (%) = (L ₄-L₃)/L₁ ×100%;

Strain fixation ratio (%) = fixation ratio/maximum compressive strain x 100%.

As can be seen from fig. 4, the interpenetrating macroporous structure is one of the important features of the sponge material provided in this embodiment. As the steam crosslinking time increases, the porosity gradually decreases, as shown by a and b in fig. 4. C in fig. 4 shows that pore collapse occurs when the crosslinking time reaches 24h, due to excessive crosslinking. The pore space of the GSD 16h and GSD 20h groups is more abundant and uniform than GSD 12h, which is most desirable. Further observing the morphology of GSD in free shape, fixed shape and recovered shape state, the pores of GSD are found to disappear with external pressure, recover after contacting with water, and meet the expected design requirement. Indexes such as recovery strain also support good shape recovery performance of GSDs.

The uniform pore structure provides good liquid absorption in addition to supporting good shape recovery properties. During the bleeding phase of the wound, rapid absorption of water from the blood increases the concentration of blood cells; during the recovery phase of the wound, absorbing wound exudates and keeping the wound dry may reduce the incidence of infection. Therefore, the water absorption process of GSD can be observed by means of a water contact angle detector and the dissolution rate of compressed GSD in water and blood environment can be detected. As shown in fig. 4 c, when the water droplets contact the GSD surface, they are immediately absorbed into the void structure, meeting the speed requirements during the hemostatic rescue. Meanwhile, the expansion rate of each group of GSDs is directly proportional to the porosity, the highest porosity of GSDs in water is close to 4000%, and the highest porosity of GSDs in blood is close to 3000%, which is obviously higher than that of GSDs for 24 hours. However, an increase in porosity tends to be accompanied by a decrease in the mechanical properties. GSD shows the best compressive strength (d in fig. 4) within 24 hours at 80% compressive strain.

To test the stability of GSD, the mechanical properties of GSD were tested as follows, using the GSD material test system (GSD 3345) for room temperature compression test and cyclic compression test. GSD was fabricated as a cylinder with a diameter of 8mm and a height of 12 mm. The lyophilized GSDs was first expanded in deionized water and then subjected to a compression test at a strain rate of 100 μm/s for wet GSDs with a maximum compressive strain of 80%. In the cyclic compression test, a drop of water was added around the wet GSDs sample on the platform prior to the test, and then the cyclic compression test was performed using a compressive strain of 80%. The compressive strain was first brought to 80% strain and then released to 0% strain with a constant compressive and strain release rate, repeated 20 times. The results are shown in fig. 5, which shows that 20 cycles at 80% high strain do not cause serious recovery loss for GSD and exhibit good compression elasticity.

EXAMPLE 3 investigation of antibacterial Properties

Infection is an important challenge in the wound healing process, while antibiotics are one of the important functions required in the design of wound care materials. The composition of the GSD provided by the disclosure is different in the double-layer structure, and two different antibacterial modes can be provided respectively, so that the antibacterial requirements of different stages in the wound healing process can be met. In particular, the porous cryogel portion in the substrate can be rapidly sterilized in a short time due to the photo-thermal effect of the catechol structure. Is suitable for severe wound infection and pre-hospital rescue period; the slow release of TA in the upper anti-adhesion membrane structure can achieve a durable antibacterial effect, and is suitable for long-term antibacterial treatment of internal organ injury and postoperative wounds.

To verify two different antibacterial effects, the following experiments were performed in this example:

2.1NIR irradiation auxiliary antibacterial Properties

GSD base material cylinders (noted GSD-up, i.e., lacking an anti-sticking up layer as compared to GSD) with a diameter of 10mm and a height of 5mm, were prepared for photo-crosslinking times of 12h, 16h, 20h, 24h, respectively, then the GSD-up was soaked in 75% alcohol for sterilization, and then equilibrated with sterilized PBS. 10 μl of the bacterial suspension was added to the surface of the swollen GSD in sterile PBS (10 ⁶CFU mL^-1). Thereafter, the samples were exposed to NIR laser irradiation (238 nm,2.0W/cm ²) at intervals of 1 to 3min, respectively. mu.L of bacterial suspension (10 ⁶CFU mL^-1) was suspended in 200. Mu.L of PBS as a negative control, while simultaneously being exposed to NIR laser (806 nm,2.0W/cm ²) 1mL of sterilized PBS was introduced into each well, and any surviving bacteria were resuspended. Then, 1. Mu.L of the above-mentioned resuspension was added to an agar plate, and after culturing at 37℃for 18 hours, the colony forming units on the agar plate were calculated. Antibacterial efficiency is expressed as antibacterial ratio (%) = (control-GSD bacterial count)/control bacterial count) ×100%. The bacteria include escherichia coli and staphylococcus aureus.

2.2 In vitro Release of Tannic Acid (TA)

The columnar GSD (8 mm diameter. Times.10 mm height) with the anti-sticking layer was immersed in 100.0mL of PBS (37 ℃ C., 60 rpm) in a shaking bath. Subsequently, at designated time intervals, 1.0mL of sample was collected and the volume was replenished by adding 1.0mL of fresh PBS. The concentration of TA in PBS was determined by UV absorbance at 278nm using an ultraviolet-visible spectrophotometer (Shimadzu UV 2700). (AGBS 41)

2.3 Antibacterial Activity of GSD-up

GSD-up plates (diameter 10mm, height 2 mm) were soaked in 75% alcohol for sterilization and then equilibrated with sterilized PBS. mu.L of the bacterial suspension was added to the surface in sterilized PBS (10 ⁶CFU mL^-1). As a negative control, 10. Mu.L of bacterial suspension (10 ⁶CFU mL^-1) was suspended in 200. Mu.L of PBS in CFU mL ^-1. After 30min, 1mL of sterilized PBS was introduced per well to re-suspend any surviving bacteria. Then, 3. Mu.L of the above-mentioned resuspension was added to an agar plate, and after culturing at 37℃for 18 hours, the colony forming units on the agar plate were calculated. Antibacterial efficiency is expressed as antibacterial ratio (%) = (control GSD viable bacteria count)/control bacteria count) ×100%.

The results are shown in FIG. 6, wherein the DeltaT-NIR time curve shown in b demonstrates that GSDs have good photo-thermal effects, and that under NIR irradiation (2.0W/cm ²), the GSD fraction increases significantly over 30s and stabilizes after 60 s. Meanwhile, GSDs have good photo-thermal effects. The peripheral temperature is not obviously increased, which is beneficial to the protection of surrounding tissues and reduces the damage to normal tissues. In addition, it is also possible to observe different Δt under different crosslinking time conditions, since as crosslinking time increases, the catechol crosslinking gradually increases resulting in a relatively reduced free catechol, affecting the photothermal effect of the overall GSD. It should be noted that the irradiation intensity of the NIR irradiation in this experiment was set higher to verify the feasibility of the design concept. Related studies have shown that when the irradiation intensity exceeds 50 ℃, both membrane proteins and proteases in the bacteria are denatured, resulting in bacterial death. The light intensity is adjusted according to the principle and the illness state of the patient so as to achieve the ideal application effect. The good photo-thermal effect gives GSDs good antibacterial effect, as shown in figures 6a, c and d, where c is the antibacterial curve of E.coli and d is the antibacterial curve of Staphylococcus aureus. After 60s of NIR irradiation, the antibacterial effect of GSD on coliform bacteria and staphylococcus aureus reaches over 98%, as shown in figure 6 e, a large number of deaths occur on both coliform bacteria and staphylococcus aureus after the GSD-up is contacted, the survival rate is obviously reduced, and the GSD-up has good antibacterial activity. TA is a natural polyphenol component that has been widely studied to demonstrate its good antimicrobial properties. For the anti-blocking layer, the release time of TA may exceed 7 days (as shown in fig. 7), indicating that GSD has a long lasting antimicrobial potential.

Application example 1

Exemplary selection of sponge materials obtained in experimental batch 1 the in vivo hemostatic capacity of GSD was tested using a rat tail-biting model, a rat liver-cutting model, a rat femoral artery injury model, a rat femoral artery and vein injury model, and a rat liver defect bleeding model.

Each experiment was performed according to the rules of animal care for Tianjin medical experiments, with animal protocols by the Yi Shengyuan institutional animal Care and use Committee (Tianjin; YSY-DWLL-2021062). Male Spragali rats (220-250 g) were purchased from Beijing HFK biosciences Inc. (Beijing; SCXK 2023-0005).

1.1 Degradation in vivo and host response

The in vivo degradation behavior of GSD was evaluated using male Dawley rats (SD rats). After anesthesia, square GSD (length=8 mm, height=3 mm) was implanted into the dorsal subcutaneous tissue of the rat. 3 rats were sacrificed at 3 rd, 7 th, 14 th, 28d, respectively. Simultaneously, H & E and Masson trichromatic staining was performed with surgical site tissue.

1.2 Rat tail amputation model

After anesthesia, the tail was cut to 50% length with surgical scissors. After cutting, the tail of the rat was left in air for 5s to ensure normal blood loss. The wound was then covered with gentle pressure using pre-pressed gauze, gelatin sponge and GSD, and data were recorded for bleeding time and body weight loss during hemostasis. Each group had 6 mice.

1.3 Rat liver incision model

Male SD rats were anesthetized and then a 15mm long, 5mm deep wound was made with a scalpel, the wound surface covered with pre-weighted gauze, gelatin sponge and GSD. And the hemostatic time was recorded, and the hemostatic amount was calculated by weighing blood gauze, gelatin sponge or GSD.

1.4 Rat femoral artery injury model

Male SD rats were anesthetized, the epithelial tissue was dissected, and the femoral artery was completely exposed. The artery was severed and bleeding was allowed for 3 seconds to ensure normal blood loss. The wound is then covered with pre-emphasized gauze, gelatin sponge or GSD and the hemostatic time recorded. After hemostasis is completed, the blood gauze, gelatin sponge or GSD is weighed, and the bleeding amount is calculated.

1.5 Rat femoral artery and vein injury model

Male SD rats were anesthetized, and an incision was made in the epithelial tissue to fully expose the femoral artery and vein. The arteries and veins were cut off and bleeding was allowed for 3s to ensure normal blood loss. The wound is then covered with pre-emphasized gauze, gelatin sponge or GSD and the hemostatic time recorded. After hemostasis is completed, the blood gauze, gelatin sponge or GSD is weighed, and the bleeding amount is calculated.

1.6 Rat liver defect bleeding model

Male SD rats were anesthetized and needle biopsied to form a full-thickness hepatic circular wound of approximately 6mm diameter. The bleeding holes were applied with pre-weighted gauze, gelatin hemostatic sponge and GSD, respectively. The hemostatic time was recorded. After hemostasis is completed, the blood gauze, gelatin sponge or GSD is weighed, and the bleeding amount is calculated.

1.7 In vivo anti-adhesion

A rat model of sidewall trauma-cecal abrasion (disc diameter = 10 mm) was selected to confirm the anti-adhesion properties of GSD. All male Sprague SD rats were randomly divided into three groups (n=6): model group without any treatment, commercial hydrogel group and GSD group. After anesthesia, the membrane lesions were induced by abrasion with sterile surgical gauze to establish blind membrane lesions until bleeding but away from the perforation pattern. Then, an incision was made with a scalpel, and peritoneal damage was performed to the opposite abdominal wall. For the GSD group, GSD discs attach to the injured cecal wound surface. Then, the skin of the rat was sutured. Likewise, 0.3mL of a commercially available hydrogel was injected at the wound site. On day 14 after model establishment, all rats were sacrificed and post-operative adhesion was observed. As described in the previous document report 44, a standard adhesion scoring system was used to evaluate the extent of adhesion 44. In addition, H & E and Masson trichromatic staining was performed with surgical site tissue.

1.8 Full-thickness skin defect model

A full-thickness circular skin wound of about 10mm in diameter was formed by needle biopsy. The wound was then coated with gauze and GSD, respectively. All wound tissues were collected on days 5, 10, 15 and analyzed after storage at-80 ℃. Wound surface monitoring, measuring the area of the wound surface by tracking the boundary of the wound surface on a drawing sheet in 3, 7, 10 and 14 days. The calculation formula of the wound shrinkage (%) is as follows:

Wound contraction= (area _{0 Tiantian (Chinese character of 'Tian')} -area _{Day of the day})/(area _{0 Tiantian (Chinese character of 'Tian')}) ×100%.

For biochemical analysis, samples were collected on day 14 and the amount of collagen was estimated using commercial kits (established bioengineering, china) to estimate hydroxyproline content.

1.9 Scratch analysis

L929 cells were seeded at a density of 5X 10 in 6-well plates at 10 ⁵ cells/well, respectively, and cultured until a monolayer of cells was obtained. Then, the cultured medium was removed, and streaking was performed with a 200. Mu.l pipette tip. Non-adherent cells were removed with warm PBS and cells were cultured by adding the leachate. At the designed time point, the medium was removed and the cells were observed under an optical microscope. Each group uses more than 3 images, and Photoshop software is used for analyzing the change of scratch area, and the wound closure condition is calculated as follows:

wound closure (%) = a ₁/A₀ ×100%;

Wherein a ₁ and a ₀ are a residual region and an original scratch region.

Results as shown in fig. 8, in order to sufficiently verify hemostatic properties of GSD, rat tail amputation model, rat liver incision model, rat femoral artery injury model, rat femoral artery and vein injury model, and rat liver defect hemorrhage model were used, five different types of rat models in total, and Gelatin Sponge (GS) (saibital (surgical anti-adhesion liquid) shandong saikos biotechnology company) commonly used in clinical practice was also used as a positive control group to verify whether GSD has significant advantages over the same type of hemostatic material currently available on the market. The bleeding characteristic of the rat tail amputation model is hypotension (compared to femoral artery bleeding), with long bleeding duration, but low bleeding per unit time. In summary, slow and long bleeding characteristics. As shown in fig. 8a, b, c, both the GS group and the GSD group significantly reduced bleeding time and bleeding volume compared to the gauze group. It is worth mentioning that the bleeding amount of the GSD group is reduced by 93.3% and the bleeding time is reduced by 60.2% compared with the gauze group. The hemostatic effect has important significance for improving the success rate of clinical treatment.

D, e, f in fig. 8 are hemostatic effects of the rat liver injury model. The liver has rich blood supply and is an important organ of human body. Bleeding is characterized by a relatively low blood pressure (compared to femoral artery bleeding), but a large amount of bleeding, which cannot be stopped by compression. Therefore, liver injury models are often used to evaluate the hemostatic properties of materials against incompressible bleeding. Compared with gauze group, GS group and GSD group have obvious hemostatic effect. In contrast, the bleeding time and the bleeding amount of the GSD group are obviously lower than those of the GS group, which indicates that the GSD has better hemostatic performance on the wounds and has better clinical application prospect.

The femoral artery is one of the most important arteries of the human body and is also important for the blood circulation of the lower limbs. In the human body structure, the femoral artery is positioned at the junction of the trunk and the lower limbs of the human body, and the common tourniquet is ineffective for hemostasis. It has the characteristics of hypertension, rapid hemorrhage, etc., and is always a major challenge for hemostatic treatment. To verify the hemostatic effect of GSD on such wounds, we completely cut the rat femoral artery, resulting in a severe femoral artery bleeding model. In the experiment, it was observed that after the femoral artery was cut off, blood flow rapidly flowed out with pulsation of blood pressure. In the early stages of the wound, the materials of each group are ineffective in alleviating bleeding, and blood can rapidly penetrate the material and continue to flow out. However, after 90s, the bleeding rate of the GS and GSD groups decreased significantly, the overall bleeding was in a controlled state, while the bleeding of the gauze group was still in an uncontrolled state. This is because compressed GS and GSD expand rapidly upon contact with blood, absorbing blood, while providing longitudinal compressive forces on the damaged vessel, helping to constrict the vessel and reduce blood flow. The first to complete hemostasis was a GSD group with an average hemostasis time of 126.6s, and a GS group of 215.2s, a 41.2% reduction. (g, h, i in FIG. 8) this is due to the increased catechol hydroxyl content in GSDs, which contributes to the activation of the extrinsic pathway, accelerating the overall coagulation process. Further, to simulate an extreme trauma situation, the femoral artery and vein of the rat were simultaneously severed, resulting in an uncontrolled massive hemorrhage situation. As expected, after both vessels are severed at the same time, a large amount of blood flows out of the vessels, at which time the different hemostatic material is rapidly wrapped around the wound. The compressed GSDs expand rapidly, absorbing blood and compressing the wound. After a period of time, as the mass of the tamponade increases, the blood flow gradually decreases and eventually stops altogether. After a period of stabilization, the material was gently removed from the wound, and significant vessel rupture was seen with no secondary bleeding (j in fig. 8). The GSD group bleeding amount was reduced by 54.5% (3274.0 mg) compared to the gauze group bleeding amount 7190.0mg, and the bleeding time was also reduced from 425.2s to 126.6s (k and i in fig. 8).

Because of the difficulty in accessing the bleeding site, narrow and deep penetrating wounds (such as gunshot wounds commonly found on battlefields) are not prevented by most hemostatic materials. This type of wound injury often occurs in tissue, forming a cavity structure with many bleeding points, making hemostasis extremely difficult. In order to simulate this type of wound, a penetrating cylindrical wound with a diameter of 6mm was created on rat liver, the wound surface was pressed with gauze, and the wound interior was filled with GS, GSD for hemostatic treatment. M, n, o in fig. 8 indicates that the hemostatic effect of the internal tamponade is superior to surface compression because of the ability of the internal tamponade to provide better contact material and bleeding points, and the swelling characteristics of GS and GSD provide a more direct compressive force. In addition to physical compression, gelatin contained in GS and GSD activates platelets while providing a powerful hemostatic effect. Activated platelets can further enrich blood cells and platelets, accelerating the formation of blood clots. On this basis, the presence of dopamine activates the extrinsic coagulation pathway and the high number of phenolic hydroxyl groups increases the electrostatic interactions with the erythrocyte membrane. Therefore, GSD has better hemostatic effects than GS.

The in vitro and in vivo anti-adhesion activity of the sponge material obtained in experimental batch 1 was exemplarily selected. As a result, as shown in fig. 9, adhesions are a very high incidence of post-traumatic complications that can lead to pain, ileus, reduced fertility in women, and even death. Therefore, the anti-adhesion property is added in the hemostatic material, so that not only is the wound care optimized, but also the treatment process is simplified, and the efficiency is improved. The sidewall trauma-cecal abrasion rat model is a common model for evaluating the anti-adhesion properties of materials. As shown in fig. 9a, there was a clear adhesion between the cecum and the abdominal wall of the model group rats, which failed to peel, masson showed fibrin deposition at the adhesion site, demonstrating that the adhesion model was successful. To quantify the anti-blocking effect, blocking for each group was scored according to the protocol (Li,H.B.;Wei,X.J.;Yi,X.T.;Tang,S.Z.;He,J.M.;Huang,Y.D.;Cheng,F.,Antibacterial,Hemostasis,Adhesive,Self-Healing Polysaccharides-Based Composite Hydrogel Wound Dressing for the Prevention and Treatment of Postoperative Adhesion.Materials Science&Engineering C-Materials for Biological Applications 2021,123.) reported in the reference. The results demonstrate that both the commercial hydrogel group and the GSD group are effective in reducing the probability and strength of blocking (b in fig. 9). However, since commercial anti-adhesion hydrogel cannot stably appear on the wound surface, adhesion occurs between the cecum and other tissues, and a large amount of material is required to achieve the intended anti-adhesion effect, which increases the economic burden on the patient. The GSD is stable on the surface of the wound due to the adhesion effect of dopamine, and the smooth membrane structure of GSD-up provides a structural basis for the anti-adhesion effect and becomes an effective physical barrier. Related studies have demonstrated that fibroblasts play an important role in the development of adhesions.

While the foregoing is directed to the preferred embodiments of the present disclosure, the present disclosure should not be limited to the embodiments and drawings disclosed. All equivalents and modifications that come within the spirit of the disclosure are desired to be protected by this disclosure.

Claims

1. An anti-adhesion implant material with shape memory function comprises a base material with shape memory function and an anti-adhesion film on at least one surface of the base material.

2. The implant material of claim 1, wherein the base material is obtained from at least two polymer backbone components by a cross-linking reaction.

3. The implant material of claim 2, wherein the crosslinking is achieved by a combination of two or more of the following ions or functional groups: polyvalent cations, amino groups, carboxyl groups, aldehyde groups, imino groups, hydroxyl groups, phenolic hydroxyl groups.

4. The implant material of claim 3, wherein the multivalent cations comprise calcium ions.

5. An implant material according to any one of claims 2 to 4, wherein the polymer scaffold molecule is selected from alginic acid or an alginate, gelatin or polydopamine.

6. The implant material according to any one of claims 1 to 5, wherein the shape memory anti-adhesion implant material has a imbibition porosity after compression of 100% to 4000%.

7. The implant material of claim 6, wherein the shape memory anti-adhesion implant material has a imbibition porosity after compression in water of 100% to 4000% and a imbibition porosity after compression in blood of 100% to 3000%.

8. An implant material according to any one of claims 1 to 7, wherein the anti-adhesion film has a continuously variable adhesion, the exposed surface of which is a non-adhesive surface and the bonding surface with the base material is an adhesive surface.

9. The implant material of claim 8, wherein the bonding surface of the anti-adhesion film and the substrate material has the same polymeric backbone component as the substrate material and the exposed surface has a different polymeric backbone component added in addition.

10. The implant material according to any one of claims 1 to 9, wherein a thickness ratio of the base material and the anti-adhesion film is 3 to 50:1.

11. The implant material according to any one of claims 1 to 10, wherein the anti-adhesion film contains an antibacterial agent;

preferably, the antibacterial agent is selected from at least one of silver ions, antibiotics or antibacterial peptides.

12. The implant material according to any one of claims 1 to 11, wherein the anti-adhesion film contains at least one of a coagulant or a tackifier;

preferably, the coagulant is selected from at least one of tranexamic acid, carbon nanofibers, fibrin or thrombin;

Preferably, the adhesion promoter comprises transglutaminase.

13. The method for preparing an anti-adhesion implant material according to any one of claims 1 to 12, comprising preparing a base material by a crosslinking reaction, and then preparing an anti-adhesion film on at least one surface of the base material to obtain the anti-adhesion implant material.

14. The preparation method according to claim 13, wherein the preparation method comprises crosslinking at least two of polydopamine, gelatin or alginic acid or a salt thereof to obtain a base material, coating a mixed gel of gelatin and alginic acid or a salt thereof on at least one surface of the base material, and spraying a mixed solution of tannic acid and calcium chloride onto an exposed surface of the mixed gel.

15. The preparation method of the base material according to claim 14, wherein the preparation method comprises the steps of mixing 0.1% -10.0% (w/v) gelatin aqueous solution with 1% -10% (w/v) sodium alginate aqueous solution according to a volume ratio of 1:0.5-1:5, adding 0.1g/mL dopamine pre-cooling water solution into a mixed solution of gelatin and sodium alginate according to a volume ratio of 1% (v/v) to 20% (v/v), adding 30 mg/mL-50 mg/mL sodium periodate aqueous solution into the mixed solution according to a volume ratio of 4:1-1:3 with dopamine pre-cooling aqueous solution, uniformly mixing, and freeze-drying to obtain the base material;

Preferably, the substrate material is placed in glutaraldehyde steam environment for curing and crosslinking;

Further preferably, the cured cross-linked substrate material is subjected to a gradient wash with an ethanol solution.

16. The preparation method according to claim 14, wherein the mixed gel contains 20.0 to 50.0% (w/v) gelatin aqueous solution and 1 to 10% (w/v) alginic acid or a salt thereof in a volume ratio of 1:0.5 to 1:5.

17. The preparation method according to claim 14, wherein the mixed gel of gelatin and alginic acid or a salt thereof is coated on at least one surface of the base material, and then the base material is placed in a glutaraldehyde steam environment to be cured and crosslinked, and then a mixed solution of tannic acid and calcium chloride is sprayed on the exposed surface of the mixed gel.

18. The production method according to claim 14 or 17, wherein the mixed solution of tannic acid and calcium chloride contains 1.0 to 5% (w/v) of calcium chloride solution and 100mg/ml of tannic acid solution in a volume ratio of 1:1 to 1:5.

19. Use of the implant material according to any one of claims 1 to 12, or prepared by the preparation method according to any one of claims 13 to 18, for the preparation of hemostatic, antibacterial or anti-adhesion products.

20. An implant dressing comprising the implant material according to any one of claims 1 to 12 or a dried implant material thereof, or an implant material prepared by the preparation method according to any one of claims 13 to 18 or a dried implant material thereof.

21. A portable kit comprising the implant material according to any one of claims 1 to 12 or a dried implant material thereof, or the implant material prepared by the preparation method according to any one of claims 13 to 18 or a dried implant material thereof.

22. A hemostatic device comprising a pressing device and a dried implant material filled in the pressing device, wherein the implant material comprises the implant material according to any one of claims 1 to 12 or prepared by the preparation method according to any one of claims 13 to 18;

preferably, the pressure applicator comprises a syringe.

23. A hemostatic platform or system comprising the hemostatic device of claim 22.