KR102395413B1 - Method for reconstructing hydrogel - Google Patents

Abstract

The present application provides a step of stretching a polymer hydrogel comprising ionic and covalent bonds, a solvent exchange step of immersing the stretched polymer hydrogel in a solvent, and forming an additional ionic cross-linkage between the polymer hydrogels. It relates to a method for restructuring a hydrogel, including.

Description

Hydrogel restructuring method {METHOD FOR RECONSTRUCTING HYDROGEL}

The present application relates to a method for restructuring a hydrogel.

A hydrogel refers to a material in which hydrophilic polymers are cross-linked, and 90% or more of the components are made of water. These hydrogels have a porous structure due to high water content and cross-linking of polymers, and can have relatively soft physical properties compared to general polymer materials, and thus can be used in various industrial fields.

However, these hydrogels have disadvantages such as difficulty in stable loading of drugs due to high water content and porous structure, and early dissolution in places where a load above a certain level is applied due to low tensile strength.

In order to overcome this problem, a technique for stretching the hydrogel in one direction, a technique for adding a cross-linkage to the polymer of the hydrogel, a technique for mixing two or more polymers with different physical properties, etc. have been proposed, but the unidirectional stretching technique is the inside of the hydrogel There was no significant change in the arrangement and density of

In addition, a technique for drying a hydrogel stretched in one direction has been proposed and a method for producing a hydrogel with improved mechanical properties is known, but the hydrogel dried after stretching by the method becomes stiff and extensibility deteriorates, There is a disadvantage that the degree of reinforcement is weak.

Korean Patent Application Laid-Open No. 10-2017-0018691, which is the background technology of the present application, relates to a method for producing a hydrogel with improved mechanical strength and a hydrogel with improved mechanical strength produced thereby. The above publication discloses a method of improving the mechanical strength of a hydrogel by forming a cross-linkage between linear polymers constituting an ionic bond inside the hydrogel by using a step of elongating the hydrogel and a cation, but the publication The patent does not recognize the step of exchanging the solvent to improve the mechanical strength of the hydrogel.

The present application is intended to solve the problems of the prior art described above, and an object of the present application is to provide a method for restructuring a hydrogel and a hydrogel with improved physical properties accordingly.

In addition, an object of the present invention is to provide a biomaterial comprising the hydrogel.

However, the technical problems to be achieved by the embodiments of the present application are not limited to the technical problems described above, and other technical problems may exist.

As a technical means for achieving the above technical problem, the first aspect of the present application is a step of stretching a polymer hydrogel comprising an ionic bond and a covalent bond, a solvent exchange step of immersing the stretched polymer hydrogel in a solvent, and It provides a method of restructuring a hydrogel, comprising the step of forming an additional ionic cross-linkage between the polymer hydrogels.

According to one embodiment of the present application, by the solvent exchange step, the moisture inside the polymer hydrogel may be removed, but is not limited thereto.

According to one embodiment of the present application, the solvent is selected from the group consisting of isopropyl alcohol (IPA, isopropyl alcohol), methanol, ethanol, chloroform (CHCl ₃ ), acetone (CH ₃ COCH ₃ ), and combinations thereof may include, but is not limited to.

According to one embodiment of the present application, the step of forming the ionic cross-linking may be performed by immersing the polymer hydrogel in a solution, but is not limited thereto.

According to one embodiment of the present application, the solution is Al, Ba, Ca, Au, Pt, Ti, Ag, Ni, Zr, Ta, Zn, Nb, Cr, Co, Mn, Fe, Mg, Si, W, Cu , and may include a cation selected from the group consisting of combinations thereof, but is not limited thereto.

According to one embodiment of the present application, by the solvent exchange step and the ion crosslinking step, the polymer hydrogel may have anisotropic properties, but is not limited thereto.

According to one embodiment of the present application, the elongation ratio relative to the initial length of the elongated polymer hydrogel may be greater than 1 and less than or equal to 8, but is not limited thereto.

According to one embodiment of the present application, the rate of change in physical properties of the hydrogel may be different depending on the distance between the surface of the hydrogel and the center of the hydrogel, but is not limited thereto.

According to one embodiment of the present application, the polymer hydrogel is Alginate (Alginic acid), AM (acrylamide), MBAA (N,N'-methylenebisacrylamide), TMEDA (N,N,N',N'-tetramethylethylenediamine), APS (ammonium persulfate), CaSO ₄ , PEO(poly(ethylene oxide)), PPO(poly(propylene oxide)), PEG(polyethylene glycol), PLA(poly(L-lactic acid)), PLGA(poly(L-glycolic) acid)), PNIPAM (poly(Nisopropylacrylamide)), poly(phosphorylcholine), poly(organophosphazene), Glycerol-2-phosphage, and combinations thereof may include, but is not limited to.

In addition, the second aspect of the present application provides a hydrogel with improved physical properties by restructuring by the method according to the first aspect.

According to one embodiment of the present application, the core (core) and the surface (edge side) of the hydrogel may have different physical properties, but is not limited thereto.

According to one embodiment of the present application, the hydrogel may have a gradient of physical properties in a direction perpendicular to the direction in which it is stretched, but is not limited thereto.

According to one embodiment of the present application, the weight of the hydrogel with improved physical properties may be 80% to 90% of the weight of the hydrogel before the physical properties are improved, but is not limited thereto.

In addition, a third aspect of the present application relates to a biological material comprising the hydrogel according to the second aspect.

According to one embodiment of the present application, the biological material may include, but is not limited to, one selected from the group consisting of cartilage, artificial tissue, stem cell medium, and combinations thereof.

The above-described problem solving means are merely exemplary, and should not be construed as limiting the present application. In addition to the exemplary embodiments described above, additional embodiments may exist in the drawings and detailed description.

In the prior art for enhancing the physical properties of the hydrogel, there were unidirectional stretching and crosslinking techniques. However, there was a disadvantage that the degree of strengthening of physical properties was not high because it was difficult to increase the arrangement and density of the hydrogel only by conventional unidirectional stretching.

Accordingly, a conventional technique for increasing the arrangement and density of the hydrogel by drying after unidirectional stretching has been proposed, but the hydrogel restructured according to the prior art has a disadvantage in that extensibility deteriorates because it becomes stiff.

According to the above-described means for solving the problems of the present application, the restructuring method of the hydrogel according to the present application includes the step of exchanging the solvent after stretching, so that the arrangement and density of the polymer network inside the hydrogel can be increased. The physical properties can be improved.

In addition, the restructuring method of the hydrogel according to the present application can control the degree of improvement of the physical properties of the hydrogel according to the use.

However, the effects obtainable herein are not limited to the above-described effects, and other effects may exist.

1 is a flowchart of a method for restructuring a hydrogel according to an embodiment of the present application.
2 is a schematic diagram of a method for restructuring a hydrogel according to an embodiment of the present application.
3 is a schematic diagram of a method for restructuring a hydrogel according to an embodiment of the present application.
4 is a photo of the restructuring step of the hydrogel according to an embodiment of the present application.
5 is a step-by-step photograph of the hydrogel according to an embodiment of the present application.
6 is a photograph of the tensile step of the hydrogel according to a comparative example of the present application.
7 shows the degree of polarization of the hydrogel according to an Example and Comparative Example of the present application.
8 is a graph showing the weight of the hydrogel according to an embodiment of the present application.
9 is an SEM image of a hydrogel according to an example and a comparative example of the present application.
10 is a DSC (Differential Scanning Calorimetry) curve of the hydrogel according to an embodiment of the present application.
11 is a graph of the mechanical properties of the hydrogel according to an embodiment of the present application.
12 is a graph of the mechanical properties of a hydrogel according to an embodiment and a comparative example of the present application.
13 is a graph of the mechanical properties of a hydrogel according to an embodiment and a comparative example of the present application.
Figure 14 (a) is a graph for the swelling properties of the hydrogel according to an Example and Comparative Example of the present application, (b) is a graph for mechanical properties after swelling.

Hereinafter, embodiments of the present application will be described in detail with reference to the accompanying drawings so that those of ordinary skill in the art to which the present application pertains can easily carry out.

However, the present application may be implemented in several different forms and is not limited to the embodiments described herein. And in order to clearly explain the present application in the drawings, parts irrelevant to the description are omitted, and similar reference numerals are attached to similar parts throughout the specification.

Throughout this specification, when a part is "connected" to another part, this includes not only the case of being "directly connected", but also the case of being "electrically connected" with another element interposed therebetween. do.

Throughout this specification, when a member is positioned “on”, “on”, “on”, “on”, “under”, “under”, or “under” another member, this means that a member is positioned on the other member. It includes not only the case where they are in contact, but also the case where another member exists between two members.

Throughout this specification, when a part "includes" a certain component, it means that other components may be further included, rather than excluding other components, unless otherwise stated.

As used herein, the terms "about," "substantially," and the like are used in a sense at or close to the numerical value when the manufacturing and material tolerances inherent in the stated meaning are presented, and to aid in the understanding of the present application. It is used to prevent an unconscionable infringer from using the mentioned disclosure in an unreasonable way. Also, throughout this specification, "step to" or "step to" does not mean "step for".

Throughout this specification, the term "combination of these" included in the expression of the Markush form means one or more mixtures or combinations selected from the group consisting of the components described in the expression of the Markush form, and the components It is meant to include one or more selected from the group consisting of.

Throughout this specification, reference to “A and/or B” means “A or B, or A and B”.

Hereinafter, the method for restructuring the hydrogel of the present application will be described in detail with reference to embodiments and examples and drawings. However, the present application is not limited to these embodiments and examples and drawings.

As a technical means for achieving the above technical problem, the first aspect of the present application is a step of stretching a polymer hydrogel comprising an ionic bond and a covalent bond, a solvent exchange step of immersing the stretched polymer hydrogel in a solvent, and It provides a method of restructuring a hydrogel, comprising the step of forming an additional ionic cross-linkage between the polymer hydrogels.

1 is a flowchart of a method for restructuring a hydrogel according to an embodiment of the present application, FIG. 2 is a schematic diagram of a method for restructuring a hydrogel according to an embodiment of the present application, and FIG. 3 is according to an embodiment of the present application It is a schematic diagram of a method for restructuring a hydrogel.

Specifically, (a) of FIG. 2 is a hydrogel in a state in which a polymer including an ionic bond and a polymer including a covalent bond are mixed, (b) is the elongation of the hydrogel, and (c) is the hydrogel The gel is immersed in the solvent, and (d) is an additional ionic cross-linkage between the polymer hydrogels. In addition, Figure 3 relates to the dehydration degree and shape of the polymer hydrogel in the solvent exchange step.

The hydrogel according to the present application is also referred to as a hydrogel, and water-soluble polymers are physically bonded such as hydrogen bonding, van der Waals forces, hydrophobic interactions, polymer crystals, and/or chemically bonded such as covalent bonding, It refers to a material that can have fluidity or elasticity by including moisture therein. In general, hydrogels have a three-dimensional network structure and are not soluble in water, can have various chemical compositions and mechanical properties depending on the physical properties of water-soluble polymers, and are easy to process.

However, the hydrogel has a disadvantage in that it is lost in a short period of time through an early dissolution process in the portion where the load is concentrated due to its low tensile strength, and it is difficult to stably mount other materials therein due to its high moisture content and porosity.

Provided herein is a method for preparing a hydrogel with improved mechanical properties through a restructuring method such as further performing tensile, solvent exchange, and ionic cross-linking.

First, a polymer hydrogel including ionic and covalent bonds is stretched (S100).

According to one embodiment of the present application, the polymer hydrogel is Alginate (Alginic acid), AM (acrylamide), MBAA (N,N'-methylenebisacrylamide), TMEDA (N,N,N',N'-tetramethylethylenediamine), APS (ammonium persulfate), CaSO ₄ , PEO(poly(ethylene oxide)), PPO(poly(propylene oxide)), PEG(polyethylene glycol), PLA(poly(L-lactic acid)), PLGA(poly(L-glycolic) acid)), PNIPAM (poly(Nisopropylacrylamide)), poly(phosphorylcholine), poly(organophosphazene), Glycerol-2-phosphage, and combinations thereof may include, but is not limited to.

For example, the polymer hydrogel may include an ionic bond by Alginate and a covalent bond by AM, and the AM may be poly acrylamide (PAM) during the formation of the polymer hydrogel. Specifically, the Alginate may be cross-linked through CaSO ₄ , the MBAA may aid in cross-linking of the PAM covalent network, and TMEDA and APS are each an accelerator of cross-linking by the PAM and It can be used as an initiator.

In this regard, the CaSO ₄ , MBAA, TMEDA and APS are materials for cross-linking the polymer hydrogel, and other materials may be used instead.

According to one embodiment of the present application, the polymer hydrogel may include, but is not limited to, an ionic polymer and a covalent polymer.

The ion-binding polymer according to the present application refers to a polymer material capable of cross-linking cations and ions as a material constituting the hydrogel, and the covalent bonding polymer according to the present application is a material constituting the hydrogel and covalent between the covalent bonding polymers It refers to a material capable of forming a bonded cross-linking point.

For example, when the polymer hydrogel includes a covalently bonded polymer acrylamide and MBAA, the acrylamide and the acrylamide and the MBAA may be bonded to each other by ultraviolet rays.

In order to apply the restructuring method of the hydrogel according to the present application, it has extensibility that is not cut even in the stretching process, includes a hydrophilic polymer network so that dehydration can occur in the solvent exchange process, and is contracted by dehydration in the ionic bonding process. Hydrophilic ionically binding polymers and/or hydrophilic covalently binding polymers can be used, in which the structure is restored and additional ionic crosslinking can occur at the same time.

Referring to (a) of Figure 2, the polymer hydrogel may have a covalent cross-linked point and an ionic cross-linked point even before performing an ionic cross-linking step to be described later. Specifically, the polymer hydrogel may include a first cation by the ion-binding polymer.

According to one embodiment of the present application, the elongation ratio relative to the initial length of the elongated polymer hydrogel may be greater than 1 and less than or equal to 8, but is not limited thereto. For example, the elongation relative to the initial length of the elongated polymer hydrogel is greater than about 1 to about 8 or less, about 2 to about 8 or less, about 3 to about 8 or less, about 4 to about 8 or less, about 5 greater than about 8 or less, greater than about 6 to about 8 or less, greater than about 7 to about 8 or less, greater than about 1 to about 2 or less, greater than about 1 to about 3 or less, greater than about 1 to about 4 or less, greater than about 1 to about 5 or less, greater than about 1 to about 6 or less, greater than about 1 to about 7 or less, greater than about 2 to about 7 or less, greater than about 3 to about 6 or less, or greater than about 4 to about 5 or less it is not

Referring to Figure 2 (b), when the polymer hydrogel is stretched, the ion-bonding polymers partially damage the cross-linking, but the cross-linking point of the covalently-bonded polymer is maintained to prevent tensile failure of the polymer hydrogel. can

Then, a solvent exchange step of immersing the elongated polymer hydrogel in a solvent is performed (S200).

According to one embodiment of the present application, by the solvent exchange step, the moisture inside the polymer hydrogel may be removed, but is not limited thereto.

As described above, since the polymer hydrogel is basically a water-soluble material, it may contain moisture therein, and the internal moisture may adversely affect the physical properties of the polymer hydrogel, so physical properties caused by dehydration or the internal moisture It is necessary to prevent deterioration.

The solvent exchange step, by removing the moisture inside the polymer hydrogel and adding the solvent instead of the moisture, it is possible to increase the arrangement and density of the polymer network of the stretched polymer hydrogel.

According to one embodiment of the present application, the solvent is selected from the group consisting of isopropyl alcohol (IPA, isopropyl alcohol), methanol, ethanol, chloroform (CHCl ₃ ), acetone (CH ₃ COCH ₃ ), and combinations thereof may include, but is not limited to.

Specifically, the ion-binding polymer and the covalently-binding polymer included in the polymer hydrogel have hydrophilicity, but have low affinity with the solvent. Therefore, when the elongated polymer hydrogel is immersed in the solvent, the moisture inside the polymer hydrogel moves in the direction of the solvent that does not contain water, whereas the solvent has a low affinity with the polymer hydrogel. It does not penetrate into the polymer hydrogel by the figure. Therefore, while the outflow of moisture inside the polymer hydrogel is free from the surface of the polymer hydrogel, the solvent impregnated with the polymer hydrogel cannot be introduced into the polymer hydrogel. In this regard, the rate of dehydration may be different depending on the surface of the polymer hydrogel.

According to one embodiment of the present application, the rate of change in physical properties of the hydrogel may be different depending on the distance between the surface of the hydrogel and the center of the hydrogel, but is not limited thereto.

2(c) and 3, when the polymer hydrogel is immersed in the solvent, the smaller the distance between the surface of the polymer hydrogel and the center of the polymer hydrogel, the faster it is dehydrated, and an X-shaped form may have (upper part of FIG. 3 ).

However, when the moisture inside the polymer hydrogel is naturally dried, dehydration proceeds evenly on all surfaces of the polymer hydrogel, but since the dehydration rate is slower than the solvent exchange step, the naturally dried polymer hydrogel is It may have a reduced shape of the non-naturally dried polymer hydrogel (lower part of FIG. 3 ).

The dehydrated polymer hydrogel may have a shape similar to that of the polymer hydrogel before dehydration by introducing moisture in the ionic cross-linking step to be described later.

According to one embodiment of the present application, the weight of the hydrogel that has undergone the solvent exchange step and has not been subjected to the ionic crosslinking step may be 10% to 20% of the weight of the hydrogel before the physical properties are improved, but, It is not limited. For example, the weight of the hydrogel that has undergone the solvent exchange step and has not been subjected to the ionic crosslinking step is about 10% to about 20%, about 11% to about 20% of the weight of the hydrogel before the physical properties are improved. %, about 12% to about 20%, about 13% to about 20%, about 14% to about 20%, about 15% to about 20%, about 16% to about 20%, about 17% to about 20%, about 18% to about 20%, about 19% to about 20%, about 10% to about 11%, about 10% to about 12%, about 10% to about 13%, about 10% to about 14%, about 10 % to about 15%, about 10% to about 16%, about 10% to about 17%, about 10% to about 18%, about 10% to about 19%, about 11% to about 19%, about 12% to about 18%, about 13% to about 17%, about 14% to about 16%, or about 14% to about 15%, but is not limited thereto.

Water corresponding to about 80% to about 90% of the weight of the hydrogel by the solvent exchange step was removed by the solvent exchange step, but the reduced weight of the hydrogel can be recovered in the ionic cross-link formation process to be described later can

Then, an additional ionic cross-linkage is formed between the polymer hydrogels (S300).

According to one embodiment of the present application, the step of forming the ionic cross-linking may be performed by immersing the polymer hydrogel in a solution, but is not limited thereto.

According to one embodiment of the present application, the solution is Al, Ba, Ca, Au, Pt, Ti, Ag, Ni, Zr, Ta, Zn, Nb, Cr, Co, Mn, Fe, Mg, Si, W, Cu , and may include a cation selected from the group consisting of combinations thereof, but is not limited thereto.

According to one embodiment of the present application, the cation (second cation) of the solution may have a higher binding affinity than the cation (first cation) present in the hydrogel, but is not limited thereto. .

The binding affinity relates to the performance of the ion exchange resin, and relates to the conditions under which the cation or anion of the ion exchange resin is exchanged with the cation or anion in the solution. However, when the valency of the first cation and the second cation are different, the difference between the form in which the second cation binds to the ion-binding polymer and the form in which the first cation binds to the ion-binding polymer may occur, so that the first cation and the second cation cannot be determined simply by binding affinity.

For example, when the first cation is Ca ²⁺ , the second cation is selected from the group consisting of Al ³⁺ , Ba ²⁺ , Fe ³⁺ , Pb ²⁺ , Sr ²⁺ , and combinations thereof. It may include, but is not limited to.

According to one embodiment of the present application, the cation in the solution may ionically bond with the first cation inside the polymer hydrogel, or may be substituted with the first cation to ionically cross-link the ion-binding polymer and, but is limited thereto it is not

When the hydrogel, which has undergone the solvent exchange step, is immersed in the solution, the cations in the solution are substituted with the cations inside the ion-binding polymer and the ion-binding polymer or the cations inside the hydrogel to improve the mechanical properties of the hydrogel. can be

According to one embodiment of the present application, the polymer hydrogel immersed in the solution may expand by moisture, but is not limited thereto.

Specifically, the water inside the polymer hydrogel by the solvent exchange step is dehydrated to the outside of the polymer hydrogel, the polymer hydrogel may shrink in volume. The volume-contracted polymer hydrogel is immersed in the solution and undergoes an ionic bonding step, while moisture in the solution may penetrate into the polymer hydrogel at the same time. Together with the moisture inside the solution, the cations inside the solution may be transferred to the inside of the polymer hydrogel, but the present invention is not limited thereto.

In addition, in the case of the solvent penetrating into the polymer hydrogel in the solvent exchange step, it may be diluted and discharged by moisture flowing into the polymer hydrogel in the ionic crosslinking step.

Referring to (d) of Figure 2, the cation (second cation) in the solution can cross-link the ion-binding polymers together with the first cation in the polymer hydrogel.

The restructured polymer hydrogel is subjected to the solvent exchange step and the ion crosslinking step in a state in which it is stretched in one direction. At this time, the polymer hydrogel stretched by an external force can be restored to its original form when the external force is removed. Therefore, in the restructuring method according to the present application, in order to maintain the polymer hydrogel in an elongated state, the polymer hydrogel is stretched, the stretched polymer hydrogel is immersed in the solvent, and the polymer hydrogel is immersed in the solution. including the process of making

According to one embodiment of the present application, by the solvent exchange step and the ion crosslinking step, the polymer hydrogel may have anisotropic properties, but is not limited thereto.

In general, when the physical properties of a specific object are different in at least one direction, the specific object may be said to be anisotropic. Since the ion-binding polymer and the covalent bonding polymers inside the polymer hydrogel are fixed by the solvent exchange step and the ionic bonding step in a state with an aligned structure in the elongated direction, the restructured The polymer hydrogel may have different physical properties in the stretched direction and in a direction perpendicular to the stretched direction.

However, when the solvent exchange step and the ionic bonding step are applied after the hydrogel is stretched in a plurality of directions, the polymers inside the hydrogel may have an elongated state in various directions and thus may have isotropy.

In addition, the second aspect of the present application provides a hydrogel with improved physical properties by restructuring by the method according to the first aspect.

With respect to the hydrogel according to the second aspect of the present application, detailed descriptions of parts overlapping with the first aspect of the present application are omitted, but even if the description is omitted, the contents described in the first aspect of the present application are in the second aspect of the present application the same can be applied

According to one embodiment of the present application, the core (core) and the surface (edge side) of the hydrogel may have different physical properties, but is not limited thereto.

Specifically, since the water on the surface of the hydrogel flows out faster than the water on the core in the solvent exchange step, the surface of the hydrogel and the core of the hydrogel may have a difference in the porous structure. A density difference may occur due to the difference in the porous structure, and physical properties such as a melting point may be different due to the density difference.

According to one embodiment of the present application, the hydrogel may have a gradient of physical properties in a direction perpendicular to the direction in which it is stretched, but is not limited thereto.

The difference in physical properties of the core and the surface of the hydrogel may be determined by porosity, internal crystal size, etc., but is not limited thereto.

Specifically, the hydrogel naturally dried without going through the solvent exchange step does not have a porous structure because moisture is evenly dehydrated in all areas inside the hydrogel, and there is no internal crystal size gradient. can

However, the hydrogel that has undergone the solvent exchange step may have a porous structure, and the porosity is higher in the core of the hydrogel than the surface of the hydrogel. In addition, in the hydrogel that has undergone the solvent exchange step, a phase separation may occur in the solvent exchange process, resulting in a gradient of crystal size inside.

Accordingly, the hydrogel with improved physical properties according to the present application can maintain the shape of the hydrogel by necking propagation rather than being destroyed by cracks even when necking occurs.

The physical properties of the hydrogel may be measured by differential scanning calorimetry (DSC), differential thermal analysis (DTA), or the like. DSC according to the present application is a measurement method that detects a temperature difference between two materials that occurs when heating a reference material and a measurement material as a difference in energy input, and DTA is a measurement method that occurs when a reference material and a measurement material are heated. A method for measuring the temperature difference.

As will be described later, when the hydrogel is analyzed by the DSC analysis method, the graph of the core of the hydrogel and the surface of the hydrogel was measured differently. This means that the physical properties of the surface and the core of the hydrogel are different.

According to one embodiment of the present application, the weight of the hydrogel with improved physical properties may be 80% to 90% of the weight of the hydrogel before the physical properties are improved, but is not limited thereto. For example, the weight of the hydrogel with improved physical properties is about 80% to about 90%, about 81% to about 90%, about 82% to about 90%, about 83 of the weight of the hydrogel before the physical properties are improved. % to about 90%, about 84% to about 90%, about 85% to about 90%, about 86% to about 90%, about 87% to about 90%, about 88% to about 90%, about 89% to about 90%, about 80% to about 81%, about 80% to about 82%, about 80% to about 83%, about 80% to about 84%, about 80% to about 85%, about 80% to about 86 %, about 80% to about 87%, about 80% to about 88%, about 80% to about 89%, about 81% to about 89%, about 82% to about 88%, about 83% to about 87%, about 84% to about 86%, or about 85%, but is not limited thereto.

Comparing the weight of the hydrogel having undergone the solvent exchange step and not subjected to the ionic crosslinking step and the hydrogel having improved physical properties by performing up to the ionic crosslinking step, the hydrogel before the physical properties are improved It can be seen that there is a difference of about 45% to about 55% of the weight. This is because, in the ionic crosslinking step, the moisture inside the solution passes through the solvent exchange step and flows into the hydrogel that has not been subjected to the ionic crosslinking step.

In general, the hydrogel may contain moisture, but the volume may expand by the moisture, but the hydrogel according to the present application maintains the binding of the polymer network stably by additional ionic cross-linking even when immersed in the solution. The degree of penetration of moisture inside the polymer network may be low, and thus the degree of volume expansion (swellability) may be low.

According to one embodiment of the present application, the hydrogel may have an optical anisotropy (optical anisotropy), but is not limited thereto.

Optical anisotropy according to the present application means that optical properties such as speed and wavelength of light in a material can be changed according to the direction of vibration of light. The hydrogel may be disposed between materials having polarization and used instead of liquid crystal.

Polarization according to the present application means a property that can vibrate in a specific direction. In general, light vibrates in all directions perpendicular to the traveling direction, but when light is passed through a material having polarization, only light vibrating in one direction can pass.

For example, when light is irradiated to a polarizing plate in a horizontal direction, only light vibrating in the horizontal direction and in a horizontal direction may pass through the polarizing plate. The light vibrating in the horizontal direction and the horizontal direction can only pass through the horizontal polarizing plate, but cannot pass through the vertical polarizing plate.

However, when the hydrogel is disposed between the polarizing plate in the horizontal direction and the polarizing plate in the vertical direction, the vibration direction is changed while the light passing through the polarizing plate in the horizontal direction passes through the hydrogel, so that the polarizing plate in the vertical direction is can pass

Through the optical anisotropy, the anisotropy of the hydrogel can be confirmed.

In addition, a third aspect of the present application relates to a biological material comprising the hydrogel according to the second aspect.

With respect to the biological material according to the third aspect of the present application, detailed descriptions of parts overlapping with the first and second aspects of the present application are omitted, but even if the description is omitted, the first and/or second aspects of the present application The contents described in can be equally applied to the third aspect of the present application

According to one embodiment of the present application, the biological material may include, but is not limited to, one selected from the group consisting of cartilage, artificial tissue, stem cell medium, and combinations thereof.

The present invention will be described in more detail through the following examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present application.

[Example 1]

Alginate, acrylamide (AM), MBAA, TMEDA, APS, CaSO ₄ were mixed, molded on a glass plate to be flattened, irradiated with UV light, and stored for one day to prepare a fully cross-linked hydrogel (Alg /PAM).

Then, the Alg/PAM was stretched in one direction, and the stretched length was fixed using tongs. Then, the elongated hydrogel was immersed in IPA (isopropyl alcohol) for about 3 hours to perform a solvent exchange step.

Then, the hydrogel was immersed in AlCl ₃ solution for 2 hours to form a restructured hydrogel Al-Alg/PAM (RsEC; remodeling and subsequent solvent exchange followed by ionic crosslinking)

Figure 4 is a photograph of the restructuring step of the hydrogel according to the embodiment.

[Comparative Example 1]

In Example 1, the restructured hydrogel Al-Alg/PAM was formed by immersion in AlCl ₃ solution without performing a solvent exchange step (RsC; remodeling and subsequent ionic crosslinking)

[Comparative Example 2]

Alg/PAM of Example 1 was used as it was.

[Comparative Example 3]

Same as Example 1, except that natural drying was performed without performing a solvent exchange step (RsDC; remodeling and subsequent natural drying followed by ionic crosslinking)

[Experimental Example 1]

5 and 6 are photographs of the tensile steps of the hydrogels according to the Examples and Comparative Examples.

5 and 6, when necking occurs after tensioning in the hydrogel according to the comparative example, cracks occur due to the necking, but in the hydrogel according to the embodiment, even if necking occurs after tensioning, the necking occurs. It can be confirmed that this only propagates and does not develop into cracks.

Specifically, in the hydrogel of the above example, the arrangement of the polymer network and the crosslinking density are improved by the solvent exchange step, and since there is a gradient of physical properties between the center and the surface, the tensile stress is transferred to a region other than the necking region. While disseminated

Since the hydrogel of the comparative example does not include the solvent exchange step, the tensile stress may be concentrated in the necking region and cracks may occur.

[Experimental Example 2]

7 shows the degree of polarization of the hydrogel according to the Examples and Comparative Examples. Specifically, (a) of FIG. 7 is a polarized optical spectroscopy image of RsEC, (b) is a polarization microscope image of RsC, (c) is a polarization microscope image of Alg/PAM, (d) is It is a graph showing the brightness of RsEC, RsC, and Alg/PAM.

Referring to FIG. 7 , the Alg/PAM hydrogel (Comparative Example 2) has optical isotropic, whereas the RsEC hydrogel (Example) or the RsC hydrogel (Comparative Example 1) exhibits optical anisotropy. Because it has, it can be confirmed the polarization of the RsEC hydrogel according to the above embodiment.

[Experimental Example 3]

8 is a graph showing the weight of the hydrogel according to the embodiment. Specifically, (a) of Figure 8 shows the weight of the hydrogel in the solvent exchange step, (b) shows the change in weight when immersed in AlCl ₃ solution.

Referring to FIG. 8 , the Alg/PAM hydrogel is rapidly dehydrated by IPA, so that the weight can be reduced by up to 80%. Alg/PAM hydrogel dehydrated by IPA absorbs moisture contained in AlCl ₃ solution, but ionic cross-linking occurs by Al and swelling is suppressed, so the original weight may be reduced by 20%.

[Experimental Example 4]

9 is an SEM image of a hydrogel according to the Example and Comparative Example, FIG. 10 is a DSC (Differential Scanning Calorimetry) curve of the hydrogel according to the Example, and FIG. 11 is a mechanical diagram of the hydrogel according to the Example It is a graph for physical properties, and FIGS. 12 and 13 are graphs for mechanical properties of hydrogels according to the Examples and Comparative Examples. Specifically, (a) of FIG. 9 is an SEM image of RsEC, (b) is an SEM image of RsDC, and the temperature shown in FIG. 10 is the melting point of the surface (edge side) and the core (core), respectively.

Referring to FIGS. 9 and 10 , it can be seen that RsEC is a porous material whose porosity increases toward the center, and its melting point increases as it approaches the center.

Specifically, the high crystallinity of the surface of RsEC suppresses the generation and propagation of cracks during tensile RsEC, and since RsEC has a higher surface crystallinity than RsDC, RsEC can have superior tensile strength compared to RsDC.

In addition, referring to FIGS. 11 and 12 , the RsEC has an elastic modulus, tensile strength, and toughness that increase according to the degree of elongation compared to the initial length (length of Alg/PAM). can check that At this time, it can be confirmed that RsEC, which is stretched twice compared to the initial length, has a higher level of elastic modulus, tensile strength, and toughness than RsC or Alg/PAM hydrogel.

Moreover, referring to FIG. 13 , it can be confirmed that RsEC has a faster dehydration rate, a higher strain, and higher toughness and tensile strength than RsDC, compared to RsDC.

[Experimental Example 5]

Figure 14 (a) is a graph for the swelling properties of the hydrogels according to the Examples and Comparative Examples, (b) is a graph for the mechanical properties after swelling.

Referring to FIG. 14 , it can be confirmed that the RSEC does not exceed 85% by weight of moisture even when swollen by moisture, and has excellent tensile strength.

The foregoing description of the present application is for illustration, and those of ordinary skill in the art to which the present application pertains will understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present application. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. For example, each component described as a single type may be implemented in a dispersed form, and likewise components described as distributed may be implemented in a combined form.

The scope of the present application is indicated by the following claims rather than the above detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be construed as being included in the scope of the present application.

Claims (15)

elongating the polymer hydrogel including ionic and covalent bonds;
A solvent exchange step of immersing the elongated polymer hydrogel in a solvent, and
forming additional ionic cross-links between the polymer hydrogels;
including,
According to the distance between the surface of the hydrogel and the center of the hydrogel, the rate of change of the physical properties of the hydrogel is different,
A method for restructuring a hydrogel.
The method of claim 1,
By the solvent exchange step, the moisture inside the polymer hydrogel is removed, the restructuring method of the hydrogel.
The method of claim 1,
The solvent is selected from the group consisting of isopropyl alcohol (IPA, isopropyl alcohol), methanol, ethanol, chloroform (CHCl ₃ ), acetone (CH ₃ COCH ₃ ), and combinations thereof. Hydrogel restructuring method.
The method of claim 1,
The step of forming the ionic cross-linkage will be performed by immersing the polymer hydrogel in a solution, the restructuring method of the hydrogel.
5. The method of claim 4,
The solution is composed of Al, Ba, Ca, Au, Pt, Ti, Ag, Ni, Zr, Ta, Zn, Nb, Cr, Co, Mn, Fe, Mg, Si, W, Cu, and combinations thereof. A method for restructuring a hydrogel, comprising a cation selected from the group.
The method of claim 1,
By the solvent exchange step and the ion crosslinking step, the polymer hydrogel is anisotropic (anisotropic), the restructuring method of the hydrogel.
The method of claim 1,
The elongation ratio relative to the initial length of the elongated polymer hydrogel is more than 1 and less than 8, the restructuring method of the hydrogel.
delete The method of claim 1,
The polymer hydrogel is Alginate (Alginic acid), AM (acrylamide), MBAA (N,N'-methylenebisacrylamide), TMEDA (N,N,N',N'-tetramethylethylenediamine), APS (ammonium persulfate), CaSO ₄ , PEO(poly(ethylene oxide)), PPO(poly(propylene oxide)), PEG(polyethylene glycol), PLA(poly(L-lactic acid)), PLGA(poly(L-glycolic acid)), PNIPAM(poly( Nisopropylacrylamide)), poly(phosphorylcholine), poly(organophosphazene), Glycerol-2-phosphage, and a method of restructuring a hydrogel comprising one selected from the group consisting of combinations thereof.
[Claim 10] The hydrogel having improved physical properties by being restructured by the method according to any one of claims 1 to 7 and 9.
11. The method of claim 10,
The core (core) and the surface (edge side) of the hydrogel will have different physical properties, the hydrogel.
12. The method of claim 11,
The hydrogel is one in which a gradient of physical properties is formed in a direction perpendicular to the direction in which it is stretched.
11. The method of claim 10,
The weight of the hydrogel with improved physical properties is 80% to 85% of the weight of the hydrogel before the physical properties are improved, the hydrogel.
A biological material comprising the hydrogel according to claim 10.
15. The method of claim 14,
The biomaterial comprises a material selected from the group consisting of cartilage, artificial tissue, stem cell medium, and combinations thereof.

Images