WO2023158240A1

WO2023158240A1 - Method for manufacturing skin phantom for measuring skin elasticity in vitro, and method for evaluating skin elasticity

Info

Publication number: WO2023158240A1
Application number: PCT/KR2023/002277
Authority: WO
Inventors: 노윤화; 김호영; 조성윤; 김현지; 최재환; 강승현; 박명삼
Original assignee: 코스맥스 주식회사; 서울대학교산학협력단
Priority date: 2022-02-16
Filing date: 2023-02-16
Publication date: 2023-08-24
Also published as: KR20230123553A; KR102672730B1

Abstract

The present invention relates to a method for manufacturing a skin phantom for measuring skin elasticity in vitro, and to a method for evaluating elasticity. A method for manufacturing a skin phantom, according to one embodiment of the present invention, comprises the steps of: preparing a dermis by forming a hydrogel from a dermal raw material containing a derived protein; preparing an epidermis from an epidermal raw material that is an elastic body; combining the epidermis and the dermis; and injecting a fluid into the dermis.

Description

Manufacturing method of skin phantom for in vitro skin elasticity measurement and skin elasticity evaluation method

The present invention relates to a method for manufacturing a skin phantom and a method for evaluating skin elasticity, and more particularly, to a method for manufacturing a skin phantom capable of measuring skin elasticity in vitro and a method for evaluating skin elasticity.

Phantom is an object created to analyze and study the effects of external stimuli or the environment on the human body. Since it is difficult to conduct various studies and analyzes on the actual human body due to ethical issues, research is being conducted with phantoms that have similar physical and biological characteristics to human tissue for the purpose of the experiment.

The phantom simulates various parts of the human body according to the contents of the experiment. For example, in an experiment to treat skin diseases, a phantom that simulates the elasticity of the human skin is manufactured and used.

However, conventionally, there is no phantom that properly simulates elasticity such as skin elasticity outside the body, making it difficult to conduct an experiment in a situation similar to the elasticity of actual human skin.

Such prior art is technical information possessed by the inventor for derivation of the present invention or acquired during the derivation process of the present invention, and cannot necessarily be referred to as known art disclosed to the general public prior to filing the present invention.

The present invention is an invention to solve the above problems, and provides a method for manufacturing a skin phantom having elasticity similar to that of an actual human skin and a method for evaluating skin elasticity.

However, these problems are exemplary, and the problem to be solved by the present invention is not limited thereto.

A method for manufacturing a skin phantom according to an embodiment of the present invention includes preparing the dermis by forming a hydrogel from a dermal raw material containing an induced protein, preparing the epidermis from an elastic epidermal raw material, bonding the dermis and injecting a fluid into the dermis.

In the method for manufacturing a skin phantom according to an embodiment of the present invention, the preparing of the dermal skin comprises preparing a hydrogel using gelatin as the induction protein, and cross-linking the hydrogel. and freeze-drying the hydrogel.

In the method for manufacturing a skin phantom according to an embodiment of the present invention, the step of preparing the hydrogel is to fill the chamber with distilled water and gelatin to satisfy 5 wt% of gelatin, dissolve the gelatin, and then mold the dermal skin. It can be dried by injecting a gelatin solution.

In the method for manufacturing a skin phantom according to an embodiment of the present invention, the step of crosslinking the hydrogel may include filling a chamber with a 1 wt% glutaraldehyde (GTA) solution and immersing the hydrogel in the GTA solution. there is.

In the method for manufacturing a skin phantom according to an embodiment of the present invention, the step of crosslinking the hydrogel is immersing the hydrogel together with the dermal mold in the GTA solution, and then 6 to 12 hours after immersing the dermal mold. After removal, the hydrogel may be immersed in the GTA solution again.

In the method for manufacturing a skin phantom according to an embodiment of the present invention, in the step of freeze-drying the hydrogel, the hydrogel is put into a freezing device to freeze, and then put into a desiccator connected to a cold trap. it can be dried.

In the method for manufacturing a skin phantom according to an embodiment of the present invention, in the freeze-drying of the hydrogel, the ice may be sublimated and removed by maintaining the refrigerating device at a pressure equal to or less than the triple point of water.

In the method for manufacturing a skin phantom according to an embodiment of the present invention, the step of planarizing the surface of the dermal skin may be further included.

In the manufacturing method of the skin phantom according to an embodiment of the present invention, in the manufacturing of the epidermis, a polymer containing silicone and a silicone diluent may be used as the elastic body.

In the manufacturing method of the skin phantom according to an embodiment of the present invention, in the manufacturing of the epidermis, the polymer may be rotated with a spin coater to have a predetermined thickness before the polymer is cured.

A method for evaluating the elasticity of a skin phantom according to an embodiment of the present invention includes the steps of measuring a force received by the skin phantom over time by holding a probe pressed on the skin phantom by a predetermined depth for a predetermined time, Calculating a time constant in response to the force applied to the skin phantom by fitting the force received by the phantom over time with Equation 1, which is an exponential decay function, and the force received over time by the skin phantom in Equation 2 Calculating the modulus of elasticity by substituting into

… … Equation 1, F is the force applied to the skin phantom, a and b are constants, t is time, τ ₁ and τ ₂ are time constants,

… … Equation 2, F _s is the force received by the skin phantom in a normal state, E is Young's modulus (MPa), R is the radius of the probe P (mm), d is the depth of the probe P (mm), υ is Poisson's ratio.

Other aspects, features, and advantages other than those described above will become clear from the detailed description, claims, and drawings for carrying out the invention below.

A method for manufacturing a skin phantom and a method for evaluating skin elasticity according to an embodiment of the present invention manufactures a skin phantom having elasticity similar to that of real skin outside the body using a material not derived from the human body, and evaluates the elasticity of the skin based thereon. can

1 and 2 show a method of manufacturing a skin phantom according to an embodiment of the present invention.

Figure 3 shows the steps of preparing the epidermis according to an embodiment of the present invention.

4 shows a state in which a gelatin solution is injected into a dermal mold according to an embodiment of the present invention.

5 shows a freeze-drying process according to an embodiment of the present invention.

6a to 6f show a stress relaxation test according to an embodiment of the present invention.

7 shows a stress relaxation test according to the diameter of a probe according to an embodiment of the present invention.

8 shows a stress relaxation test according to the depth of the probe according to an embodiment of the present invention.

Since the present invention can apply various transformations and have various embodiments, specific embodiments will be illustrated in the drawings and described in detail in the description of the invention. However, this is not intended to limit the present invention to specific embodiments, and should be understood to include all conversions, equivalents, or substitutes included in the spirit and scope of the present invention. In describing the present invention, even if shown in different embodiments, the same identification numbers are used for the same components.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, and when describing with reference to the drawings, the same or corresponding components are assigned the same reference numerals, and overlapping descriptions thereof will be omitted. .

In the following embodiments, terms such as first and second are used for the purpose of distinguishing one component from another component without limiting meaning.

In the following examples, expressions in the singular number include plural expressions unless the context clearly dictates otherwise.

In the following embodiments, terms such as include or have mean that features or components described in the specification exist, and do not preclude the possibility that one or more other features or components may be added.

In the drawings, the size of components may be exaggerated or reduced for convenience of explanation. For example, since the size and thickness of each component shown in the drawings are arbitrarily shown for convenience of description, the present invention is not necessarily limited to the illustrated bar.

In the following embodiments, the x-axis, y-axis, and z-axis are not limited to the three axes of the Cartesian coordinate system, and may be interpreted in a broad sense including these. For example, the x-axis, y-axis, and z-axis may be orthogonal to each other, but may refer to different directions that are not orthogonal to each other.

When an embodiment is otherwise implementable, a specific process sequence may be performed differently from the described sequence. For example, two processes described in succession may be performed substantially simultaneously, or may be performed in an order reverse to the order described.

Terms used in this application are only used to describe specific embodiments, and are not intended to limit the present invention. In this application, the terms "include" or "have" are intended to designate that there is a feature, number, step, operation, component, part, or combination thereof described in the specification, but one or more other features It should be understood that the presence or addition of numbers, steps, operations, components, parts, or combinations thereof is not precluded.

1 and 2 show a method for manufacturing a skin phantom 10 according to an embodiment of the present invention, FIG. 3 shows steps for manufacturing an epidermis 200 according to an embodiment of the present invention, and FIG. 4 shows a state in which the gelatin solution is injected into the dermal skin mold 300 according to an embodiment of the present invention, and FIG. 5 shows a freeze-drying process according to an embodiment of the present invention.

The skin phantom 10 according to an embodiment of the present invention may be an object that simulates the elasticity of human skin. For example, the skin phantom 10 can simulate the elasticity of the dermis and epidermis of the skin, and can be used for various experiments instead of the actual human body. In one embodiment, the skin phantom 10 may not include materials derived from a human body such as cells.

1 to 5, the method for manufacturing a skin phantom according to an embodiment of the present invention includes the steps of forming a hydrogel 110 from a dermal raw material containing an induced protein to prepare the dermal skin 100, an elastic body It may include preparing the epidermis 200 from a phosphorus epidermal raw material, combining the epidermis 200 and the dermis 100, and injecting a fluid into the dermis 100.

In one embodiment, the steps of preparing the dermal skin 100 include preparing a hydrogel 110 using gelatin as an inducing protein, cross-linking the hydrogel 110, and hydrogel 110 Freeze-drying may be included.

First, the dermal skin 100 is prepared by forming the hydrogel 110 from the dermal raw material containing the induced protein. In one embodiment, the dermal raw material may include gelatin among induced proteins. Gelatin is a material obtained by decomposing collagen, a fibrous protein commonly found in animal, particularly mammalian tissue, into small chains, and is suitable for skin-simulating materials. For example, the hydrogel 110 may be prepared using a predetermined gelatin powder and distilled water.

More specifically, the step of manufacturing the hydrogel 110 may be filled with distilled water and gelatin in a chamber, dissolving the gelatin, and injecting the gelatin solution into the dermal skin mold 300 to dry it.

In one embodiment, the mass ratio of gelatin in the gelatin solution may be 4% to 16%. As described below in this numerical range, the stress relaxation test result is an exponential decay function.

When expressed as , the modulus of elasticity

, G ₁ and G ₂ , G ₀ satisfies a value of 5 kPa to 15 kPa.

For example, distilled water and gelatin are filled in a chamber having a capacity of 60 ml to satisfy 5 wt% of gelatin, the chamber is placed in a beaker, etc., and then distilled water is put between the chamber and the beaker to heat the bath. Here, a hot plate may be used for bathing. Operating conditions of the hot plate are not particularly limited, and may be, for example, 130° C., 120 rpm, and 1 hour. The chamber is removed when the gelatine is completely dissolved to form a gelatine solution.

In the next chamber, the gelatin solution is injected into the dermal skin mold 300 . For example, as shown in FIG. 4 , the dermal skin mold 300 may include a base 310 , a well 320 and a cover 330 . The base 310 is a member that accommodates and supports other members of the dermal skin mold 300, and may have a rectangular parallelepiped shape with an empty inside. A plurality of wells 320 may be disposed inside the base 310 . The well 320 may have a well shape with an empty inside to accommodate the gelatin solution therein. The shape, size, and arrangement of the well 320 are not particularly limited and may be appropriately selected depending on the hydrogel 110 to be manufactured. The cover 330 may be disposed above the base 310 to completely cover the plurality of wells 320 .

In one embodiment, all members constituting the dermal skin mold 300 are made of a transparent material, and the inside can be observed with the naked eye even from the outside.

The hydrogel 110 may be obtained by injecting the gelatin solution into the well 320 of the dermal skin mold 300 using a pipette or the like, and then covering the cover 330 and solidifying it. For example, the hydrogel 110 can be obtained by putting the dermal skin mold 300 in a refrigerator or the like to harden the gelatin solution (Fig. 2(a)).

In the next step of crosslinking the hydrogel 110, an immersion liquid may be filled in a chamber and the hydrogel 110 may be immersed in the immersion liquid. For example, a glutaraldehyde (GTA) solution as an immersion solution of 1 wt % may be filled in a chamber, and the hydrogel 110 may be immersed in the GTA solution. Accordingly, the GTA solution may diffuse into pores formed inside the hydrogel 110 .

The carbonyl group of the GTA solution is chemically combined with the amine of the gelatin chain constituting the hydrogel 110, thereby forming a stronger and longer crosslinked chain. Accordingly, the strength of the hydrogel 110 made of gelatin or the like can be increased, and in particular, as will be described later, the shape can be maintained even when fluid is injected into the skin phantom 10 .

Through this, it is possible to prevent pores of the dermal skin 100 from being damaged in the process of injecting the fluid into the skin phantom 10 after the subsequent freeze-drying process.

In one embodiment, the step of crosslinking the hydrogel 110 is to immerse the hydrogel 110 together with the dermal mold 300 in the GTA solution, remove the dermal mold 300 after 6 to 12 hours, and then remove the hydrogel 110. The gel 110 may again be immersed in the GTA solution.

When the hydrogel 110 is separated from the dermal skin mold 300 in a state in which the hydrogel 110 is not completely crosslinked, the hydrogel 110 may be damaged during the separation process. In order to prevent this, in the present invention, the hydrogel 110 may be immersed in the GTA solution for a predetermined time (eg, 6 to 12 hours) to complete crosslinking, and then the separation process may be performed.

Through this, the hydrogel 110 can be inserted into the well 320 of the dermal skin mold 300 to diffuse the GTA solution into the internal pores while maintaining its shape. In addition, after removing the dermal skin mold 300, the hydrogel 110 is immersed in the GTA solution again, so that the GTA solution is sufficiently supplied to the inner circumferential surface of the well 320 and the pores of the outer circumferential surface of the hydrogel 110 in contact with the bottom surface. It can diffuse (Fig. 2 (b)).

Next, the hydrogel 110 is freeze-dried. In one embodiment, the hydrogel 110 is put into a freezing device to freeze the hydrogel 110. The temperature of the refrigeration unit may be -20 °C and the freezing time may be 6 hours. In one embodiment, after the hydrogel 110 is primarily frozen, the hydrogel 110 may be taken out of the freezing device, the frost formed on the surface thereof removed, and then frozen again for a predetermined period of time. Here, the secondary freezing time is shorter than the primary freezing time, and may be, for example, 15 minutes to 30 minutes (Fig. 2(c)).

More specifically, frost made of water is inevitably generated on the surface of the hydrogel 110 during the first freezing process. If the drying process proceeds as it is in this state, unnecessary time may be required to dry the frost. To prevent this, the ice is removed after the first freezing process, and a second freezing process is performed in case some of the ice contained inside is melted during the defrosting process.

During the freezing process, the GTA solution and water, which have been diffused in the pores of the hydrogel 110, freeze and increase the size of the pores, so that elasticity similar to that of human skin can be simulated. More specifically, when the hydrogel 110 is frozen, ice crystals are formed in the internal pores, thereby changing nanoscale pores into microscale pores. Through this, it is possible to well simulate pores of real human skin having a microscale.

In one embodiment, in the step of freezing the hydrogel 110, the pressure of the refrigeration device may be maintained below the triple point of water to sublimate and remove the ice included in the hydrogel 110. That is, microscale ice crystals are formed inside the hydrogel 110 during the freezing process, and by sublimating and removing them, a sponge structure having an empty space can be formed. As will be described later, the skin phantom 10 may be completed by injecting a fluid into an empty space.

Then, the frozen hydrogel 110 is dried. For example, as shown in FIG. 5, the hydrogel 110 taken out of the refrigeration device is put into a desiccator 400. A drying agent such as silica gel, calcium oxide, calcium sulfate or calcium chloride is included inside the desiccator 400, and the hydrogel 110 may be placed near the drying agent ((d) of FIG. 2).

In one embodiment, one side of the desiccator 400 is connected to the cold trap 500 to keep the inside at a low temperature, and one side of the cold trap 500 is connected to the vacuum pump 600 to keep the desiccator 400 ) can be maintained in a vacuum. Through this, the hydrogel 110 can be dried in a low-temperature vacuum state.

In one embodiment, a step of planarizing the surface of the dermal skin 100 may be further included. For example, the plurality of dermal skins 100 obtained after the freeze-drying step may be in a state of being seated on the dermal skin mold 300. In this state, the upper surface of the plurality of dermal skins 100 can be flattened using a blade for flattening to make the thickness uniform.

In the step of manufacturing the skin 200, a polymer including silicone and a silicone diluent may be used as an elastic body. The step of preparing the epidermis 200 does not necessarily proceed after the step of preparing the dermal skin 100, and may be performed before or concurrently with the step of preparing the dermal skin 100.

In one embodiment, a polymer may be prepared by mixing a silicone thinner (for example, 10w% of silicone diluent) with addition-type silicone (addition cure silicone) as silicone. Here, the additive-type silicone may be commercially available smooth-sil 960. Through this, it is possible to manufacture the epidermis 200 having a modulus of elasticity similar to or equal to that of the epidermis of the human body. That is, the modulus of elasticity of the epidermis of the human body is generally 1 MPa, and the modulus of elasticity of the epidermis 200 prepared in this way may also have a value of 1 MPa or close thereto (Fig. 2(e)).

The next polymer is made to have a predetermined thickness. For example, the polymer may be rotated using a spin coater before the polymer is cured, so that the polymer has a thickness of 0.1 mm, which is the epidermal thickness of actual skin (Fig. 2(f)). Accordingly, the epidermis 200 is shaped.

Next, the dermis 100 and the epidermis 200 are combined. For example, as shown in FIG. 2, the epidermal skin 200 may be disposed on the upper surface of the dermal skin 100 (FIG. 2(g)). More specifically, the spin-coated epidermis 200 is before it is completely cured, and when the epidermis 200 in this state is placed on the dermal skin 100 where the drying process is completed, the silicone is cured and naturally the epidermis 200 ) is combined with the dermal skin (100).

The fluid may then be injected into the dermal skin (100). For example, the freeze-dried dermal skin 100 may be immersed in water or an aqueous glycerin solution for 30 minutes or more to ensure that the fluid is sufficiently injected into the pores. Alternatively, the fluid may be injected into the dermal skin 100 through an eyedropper or the like (Fig. 2(h)).

More specifically, actual skin has micro-scale pores, and the pores are filled with extracellular fluid (ECF). In order to simulate this, in the present invention, the viscoelasticity of the skin can be well simulated by injecting a fluid into the dermal skin (100).

When the step of injecting the fluid is completed, the fluid is sufficiently diffused in the pores of the dermal skin 100, and finally the skin phantom 10 is completed.

The component ratio of the skin phantom 10 manufactured in an embodiment may be dermal skin 100:epidermal skin 200:fluid = 1:1:2.5 based on mass. That is, it may be polymer:gelatin:fluid = 1:1:2.5 based on mass. In one embodiment, the mass ratio of the dermis and the fluid may be 1:1 to 1:10.

In one embodiment, the height of the dermal skin 100 of the skin phantom 10 may be 2 mm, and the height of the epidermal skin 200 may be 0.10 mm.

Through such a configuration, the method for manufacturing a skin phantom according to an embodiment of the present invention can manufacture a skin phantom 10 that does not contain materials derived from the human body and can simulate the elasticity of real skin outside the body. .

실시예Example

6A to 6F show a stress relaxation test, FIG. 7 shows a stress relaxation test according to the diameter of the probe P, and FIG. 8 shows a stress relaxation test according to the depth of the probe P.

First, the inventors of the present invention devised an experiment for measuring skin elasticity. A test to measure skin elasticity was conducted through a stress relaxation test. More specifically, as shown in FIG. 6A, after pressing the sample (S), which is pigskin, with the probe (P) quickly to a predetermined depth (H), the force applied to the sample (S) while maintaining the corresponding depth Changes were measured over time (see Figs. 6b and 6c). The probe P is wired/wireless connected to a measuring device (not shown), and the magnitude of the measured force can be checked in real time.

As shown in FIG. 6D, the experimental results show that the magnitude of the force applied to the sample S by the probe P is the greatest until the predetermined depth H is reached, and then the force applied to the sample S over time It was found that the size of was decreased exponentially.

That is, through the stress relaxation test on the skin, it was found that the force applied to the skin decreases exponentially with time when a certain depth is reached, and it was confirmed that this can be expressed as an exponential decay function. Therefore, it was confirmed that the elasticity of human skin can be simulated by manufacturing the skin phantom 10 so that the stress relaxation test result for the skin phantom 10 can be expressed as an exponential decay function.

Meanwhile, the present inventors have found that it is difficult to properly represent the stress relaxation test result for the skin phantom 10 when the stress relaxation test result for the skin phantom 10 is expressed as an exponential decay function using one time constant.

Accordingly, the stress relaxation test for the skin phantom 10 was modeled as shown in FIG. 6E, and it was expressed as an exponential decay function according to the equation below.

That is, in the stress relaxation test of the skin phantom 10 in the present invention, a model using two time constants was utilized by combining two exponential decay functions. As a result, as shown in FIG. 6f, it was found that the model using two time constants simulated the actual measurement data (black dots in FIG. 6f) much better than the model using one time constant. In the above equation, among the time constants, τ ₁ is smaller than τ ₂ . Also, when τ ₁ is smaller than τ ₂ , the coefficient b of the term corresponding to τ ₁ is related to the collagen content, and the coefficient c of the term corresponding to τ ₂ is related to the elastin content.

Next, an indentation simulation was performed using a modeling program (ABAQUS) based on the elasticity of the epidermis, dermis, and subcutaneous fat. Specifically, the thickness and elastic modulus of the epidermis, dermis, and subcutaneous fat were set to 100㎛, 2mm, 2mm, and 1MPa, 35kPa, and 2kPa, respectively, and an anisotropic elasticity model was applied to the epidermis, and an isotropic viscoelastic model was applied to the dermis and subcutaneous fat. has been applied.

In addition, a stress relaxation test was conducted on the simulated skin model by varying the diameter and depth of the probe (P). More specifically, as shown in FIG. 7, the stress relaxation test could be expressed as an exponential decay function as described above, and the initial value and the steady state value of the force received by the skin model were different depending on the diameter of the probe P, It was found that the time constants had almost the same values (when the probe diameters were 5 mm, 1 mm, and 0.2 mm, the time constants were 0.3384 s, 0.3343 s, and 0.3610 s, respectively).

In addition, as shown in FIG. 8, although the initial value and the steady state value of the force received by the skin model were different depending on the depth of the probe P, it was found that the time constant had almost the same value (the depth of the probe was 1000 In the case of μm, 250 μm, and 50 μm, the time constants are 0.3653 s, 0.3717 s, and 0.3610 s, respectively).

That is, in the stress relaxation test, it was found that the value of the time constant of the skin model was constant in the stress relaxation test even if the specific conditions of the experiment were changed, such as the diameter of the probe P or the depth of the probe P. Through this, it was confirmed that the time constant is an important factor in implementing elasticity of the epidermal phantom 10, and that it is important to manufacture the epidermal phantom 10 to have a time constant similar to that of actual skin.

Next, a stress relaxation test was performed on the skin phantom 10 manufactured according to the above-described manufacturing method. That is, the force applied to the skin phantom 10 over time was measured by pressing the probe P on the epidermal phantom 10 to a certain depth and holding it for a predetermined time. And a computing device including a processor, which is an exponential decay function based on the magnitude of the force measured by the probe P.

The time constants τ ₁ and τ ₂ were calculated by fitting with . Specifically, the fitting result is

, and among the two time constants, τ ₁ was calculated to be 0.12 s.

In addition, the elastic modulus of the skin phantom 10 was calculated by substituting the measurement result into the Hertz contact mechanics equation using a computing device (here, force F is a steady state value).

where F _s is the steady state value, E is Young's modulus (MPa), R is the radius of the probe P (mm), d is the depth of the probe P (mm), and υ is Poisson's ratio (0.495) .

As a final result, the modulus of elasticity of the skin phantom 10 was 53.4 kPa, which was similar to the modulus of elasticity of actual human skin, 49.9 kPa. In addition, it was found that the time constant of the skin phantom 10, 0.12 s, was included in the range of 0.088 to 0.877, which is the range of the time constant of the actual skin (Reference: SJM Yazdi, K.-S. Cho, and N. Kang. "Characterization of the viscoelastic model of in vivo human posterior thigh skin using ramp-relaxation indentation test." Korea-Australia Rheology Journal 30.4 293-307 (2018)).

Through such a configuration, the elasticity evaluation method of the skin phantom according to an embodiment of the present invention fits the stress relaxation test of the skin phantom 10 with an exponential decay function and then simulates the elasticity of the actual skin (especially the time constant). ) can be set. Through this, the skin phantom 10 may be manufactured to have a value similar to the elasticity of actual skin. In addition, the elasticity evaluation method of the skin phantom 10 according to an embodiment of the present invention can be applied to evaluate the elasticity of skin derived from an actual human body or animal.

As such, the present invention has been described with reference to the embodiments shown in the drawings, but this is only an example. Those skilled in the art can fully understand that various modifications and equivalent other embodiments are possible from the embodiments. Therefore, the true technical protection scope of the present invention should be determined based on the appended claims.

Specific technical details described in the embodiments are examples, and do not limit the technical scope of the embodiments. In order to briefly and clearly describe the description of the invention, descriptions of conventional general techniques and configurations may be omitted. In addition, the connection of lines or connection members between the components shown in the drawing is an example of functional connection and / or physical or circuit connection, which can be replaced in an actual device or additional various functional connections, physical connections, or circuit connections. In addition, if there is no specific reference such as "essential" or "important", it may not necessarily be a component necessary for the application of the present invention.

“Above” or similar designations described in the description and claims of the invention may refer to both singular and plural, unless otherwise specifically limited. In addition, when a range is described in an embodiment, it includes an invention in which individual values belonging to the range are applied (unless there is no description to the contrary), and each individual value constituting the range is described in the description of the invention. same. In addition, if there is no clear description or description of the order of steps constituting the method according to the embodiment, the steps may be performed in an appropriate order. Embodiments are not necessarily limited according to the order of description of the steps. The use of all examples or exemplary terms (eg, etc.) in the embodiments is simply to describe the embodiments in detail, and unless limited by the claims, the examples or exemplary terms limit the scope of the embodiments. It is not. In addition, those skilled in the art will appreciate that various modifications, combinations and changes may be made according to design conditions and factors within the scope of the appended claims or equivalents thereof.

The present invention can be used in industries related to skin phantoms.

Claims

preparing a dermis by forming a hydrogel from a dermal raw material containing an induced protein;

Preparing an epidermis from an elastic skin raw material;

combining the epidermis and the dermis; and

Injecting a fluid into the dermal skin; including, skin phantom manufacturing method.
According to claim 1,

The step of preparing the dermis is

preparing a hydrogel using gelatin as the induction protein;

Cross-linking the hydrogel; and

Freeze-drying the hydrogel; containing, skin phantom manufacturing method.
According to claim 2,

The step of preparing the hydrogel is to fill the chamber with distilled water and gelatin to satisfy 5 wt% of gelatin, dissolve the gelatin, and then inject the gelatin solution into the dermal mold to solidify.
According to claim 2,

In the step of crosslinking the hydrogel, a chamber is filled with a 1 wt% glutaraldehyde (GTA) solution, and the hydrogel is immersed in the GTA solution.
According to claim 4,

In the step of crosslinking the hydrogel, the dermal mold is removed after 6 to 12 hours after the hydrogel is immersed in the GTA solution together with the dermal mold, and then the hydrogel is immersed in the GTA solution again. manufacturing method.
According to claim 2,

In the step of freeze-drying the hydrogel, the hydrogel is put into a refrigeration device to freeze, and then put into a desiccator connected to a cold trap to dry it.
According to claim 6,

In the freeze-drying of the hydrogel, the freezing device is maintained at a pressure below the triple point of water to sublimate and remove the ice.
According to claim 2,

Further comprising the step of planarizing the surface of the dermis, skin phantom manufacturing method.
According to claim 1,

The step of manufacturing the epidermis uses a polymer containing silicone and a silicone diluent as the elastic body, skin phantom manufacturing method.
According to claim 9,

In the manufacturing of the epidermis, the polymer is rotated with a spin coater before the polymer is cured to have a predetermined thickness.
measuring a force received by the skin phantom over time by holding the probe pressed on the skin phantom by a predetermined depth for a predetermined time;

Calculating a time constant in response to the force applied to the skin phantom by fitting the force received by the skin phantom over time with Equation 1, which is an exponential decay function; and

Calculating the elastic modulus by substituting the force received by the skin phantom over time into Equation 2; Skin elasticity evaluation method comprising a.

… … Equation 1, F is the force applied to the skin phantom, a and b are constants, t is time, and τ 1 and τ 2 are time constants

… … Equation 2, F s is the force received by the skin phantom in a normal state, E is Young's modulus (MPa), R is the radius of the probe P (mm), d is the depth of the probe P (mm), υ is Poisson's ratio.