A precisely patterned selectively adhesive tissue patch and a method for preparing the same

Abstract

The present invention relates to a precisely patterned selective adhesive tissue patch and a preparation method thereof, wherein the selective adhesive tissue patch is a composite structure, which is composed of an adhesive layer hydrogel and a non-adhesive layer substrate; the adhesive layer is a hydrogel containing an adhesive group with a hollow pattern; the non-adhesive layer substrate is a substrate that does not contain an adhesive group; the preparation method is: in a flat-bottomed container, a non-adhesive layer substrate, a B mold, and a pouring adhesive layer hydrogel precursor solution are sequentially laid, and ultraviolet light is irradiated to form an adhesive layer hydrogel to obtain a precisely patterned selective adhesive tissue patch; the number of B molds is more than one, and it is vertically arranged on the non-adhesive layer substrate to prevent ultraviolet light from irradiating a local area of ​​the substrate. The selective adhesive tissue patch of the present invention can accurately control the adhesion area, realize selective adhesion to the tissue, and does not adhere to other tissues or affect tissue regeneration; the preparation method of the present invention has a simple process and a wide range of applications.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical materials and relates to a precisely patterned selectively adhesive tissue patch and a preparation method thereof. Background Art

[0002] When the soft tissue of the human body is injured, defective or diseased, surgery is often required to repair the diseased area or remove the diseased tissue. For example, when a tumor appears in the lungs, the defect needs to be sutured after surgical resection; when there is a defect in the abdominal wall, a hernia patch needs to be sutured at the defect for repair, etc. However, the suture line can easily cause the surrounding tissue to pull on the suture, causing repair failure or tissue damage. The use of tissue patches with adhesion effects can solve the above problems. The patch adheres to the tissue through covalent bonds, hydrogen bonds or intermolecular forces, without the need for sutures, which greatly reduces stress concentration.

[0003] Patent CN202110474325.3 prepares a self-adhesive hydrogel, which is an adhesive material as a whole, but cannot achieve local adhesion; Patent CN202111140549.7 prepares a single-sided adhesive tissue patch, which is single-sided overall adhesion, but cannot achieve single-sided local adhesion; Patent CN201810636701.2 prepares a tissue patch with a microneedle surface. Although the surface shape is specially designed, the problem of partial adhesion is not solved; CN202110552908.3 prepares a double-layer tissue patch with one side as a whole adhesion, but does not solve the problem of partial adhesion.

[0004] Therefore, all parts of existing tissue patches that overlap with tissues are made of adhesive materials. The regeneration environment of soft tissues in the body is complex, which will lead to other troubles despite the problem of stress concentration. For example, when applied to full-thickness abdominal wall defects, the self-adhesive tissue patch will adhere to the abdominal wall while also adhering to the intestines exposed at the defect, forming tissue adhesions. Compared with other materials used for soft tissue repair, adhesive groups are not conducive to cell growth and affect the speed of tissue regeneration at the defect.

[0005] Therefore, it is of great significance to study a precisely patterned selectively adhesive tissue patch and its preparation method to solve the problem that the existing technology cannot selectively adhere to tissues, easily adheres to other tissues, and affects tissue regeneration. Summary of the invention

[0006] The purpose of the present invention is to solve the problems existing in the prior art and to provide a precisely patterned selectively adhesive tissue patch and a preparation method thereof.

[0007] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0008] A precisely patterned selectively adhesive tissue patch has a composite layer structure, consisting of an adhesive layer hydrogel and a non-adhesive layer substrate; the adhesive layer hydrogel is a hydrogel containing adhesive groups, and the adhesive layer hydrogel has a hollow pattern; the non-adhesive layer substrate is a substrate that does not contain adhesive groups.

[0009] As the preferred technical solution:

[0010] In the above-mentioned precisely patterned selectively adhesive tissue patch, the thickness of the non-adhesive layer substrate is 100 to 4000 microns, and the thickness ratio of the non-adhesive layer substrate to the adhesive layer hydrogel is 1 to 200:1.

[0011] As described above, in a precisely patterned selective adhesive tissue patch, the adhesive layer hydrogel is obtained by irradiating a photo-crosslinkable adhesive layer hydrogel precursor solution with ultraviolet light, and the photo-crosslinkable adhesive layer hydrogel precursor solution includes a photo-crosslinkable polymer precursor, a biocompatible natural macromolecule, an adhesive substance, a crosslinking agent, a photoinitiator and water.

[0012] A precisely patterned selective adhesion tissue patch as described above, wherein the non-adhesive layer substrate is a hydrogel, a fiber assembly or a cast film; the hydrogel raw materials include but are not limited to one or any combination of natural biological materials and synthetic materials; the hydrogel forming process includes but is not limited to one or more combinations of frozen crystallization, chemical crosslinking, thermal crosslinking, self-assembly, and charge attraction; the fiber assembly forming process includes but is not limited to one or more combinations of weaving, knitting, braiding, meltblowing, electrospinning, spunbonding, composite method or 3D printing.

[0013] In the above-mentioned precisely patterned selectively adhesive tissue patch, the non-adhesive layer substrate is a fiber assembly containing a polyphenol polymer on the surface; the photo-crosslinkable polymer precursor is a polymer that can be activated by free radicals I and II, free radicals I are generated by the polyphenol polymer under the irradiation of ultraviolet light, free radicals II are generated by the photoinitiator under the irradiation of ultraviolet light, and the crosslinking agent is used to connect the activated photo-crosslinkable polymer precursor;

[0014] Under ultraviolet light irradiation, there are two kinds of free radicals in the system, which are recorded as free radical I and free radical II. Free radical I is provided by polyphenol polymers (after ultraviolet light is irradiated on polyphenol polymers, the aromatic ring in the polyphenol is cracked, and the phenol is oxidized to produce α, β-unsaturated aldehydes, carbon-centered free radicals, which then react with molecular oxygen to produce peroxides. These unstable intermediates can undergo single-molecule ring closure to produce bicycloalkoxy free radicals). Free radical I is concentrated around the fiber, that is, the concentration of free radical I near the fiber is higher than the concentration of free radical I at other positions. Free radical II is provided by photoinitiator, and free radical II is uniformly dispersed in the system, that is, the concentration of free radical II near the fiber is close to the concentration of free radical II at other positions, which ultimately leads to a higher free radical concentration around the fiber than at other positions. Therefore, the photocrosslinkable polymer precursor is concentrated around the fiber for crosslinking reaction, so that the degree of physical entanglement between the photocrosslinkable polymer precursor and the fiber is high, thereby improving the interface strength between the fiber and the hydrogel (mainly composed of photocrosslinkable polymer precursor and water). In addition, there are van der Waals forces (van der Waals forces are common between molecules, and are essentially the mutual attraction between charges) and hydrogen bonds (formed by polyphenol polymers and hydroxyl groups, amino groups, alkyl groups, carboxyl groups, ester groups, etc. in the hydrogel) between the hydrogel and the fiber, which can also improve the interface strength between the fiber and the hydrogel.

[0015] The preparation process of the fiber assembly containing polyphenol polymer on the surface of the precisely patterned selectively adherent tissue patch as described above is as follows: immersing the fiber assembly in a polyphenol solution and shaking at 25 to 40° C. for 3 to 48 hours.

[0016] According to the method for preparing an interface-stable fiber / hydrogel composite scaffold as described above, the thickness of the fiber assembly is 200 to 4000 microns; the polyphenol solution is an aqueous solution of a polyphenol material, the polyphenol material is one or more of dopamine and its derivatives, tannic acid, catechol and its derivatives, and the content of the polyphenol material in each 1 mL of the polyphenol solution is 0.1 to 500 mg; the bath ratio of the fiber assembly to the polyphenol material is 1:10 to 100.

[0017] A precisely patterned selectively adhesive tissue patch as described in any of the above items, wherein in the photo-crosslinkable adhesive layer hydrogel precursor solution, the photo-crosslinkable polymer precursor is one or more of acrylamide and its derivatives, acrylic acid and its derivatives, gelatin derivatives, collagen derivatives, alginate derivatives, cellulose derivatives, dextran derivatives, hyaluronic acid derivatives, polyethylene glycol diacrylate and its derivatives, and the content is 1 to 40wt%;

[0018] The biocompatible natural macromolecule is one or more of gelatin and its derivatives, collagen and its derivatives, alginate and its derivatives, cellulose and its derivatives, dextran and its derivatives, hyaluronic acid and its derivatives, and the content is 0.5 to 30 wt%;

[0019] The adhesive substance is acrylic acid-N-succinimide ester and its derivatives, and the content is 0.5-5wt%;

[0020] The crosslinking agent is one or more of N,N-methylenebisacrylamide, methacrylated gelatin, dimethyl diimide, N,N'-bisacrylamide, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide, and the content is 0.1-2wt%;

[0021] The photoinitiator is one or more of benzoin, benzoin dimethyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin butyl ether, diphenyl acetone, α,α-dimethoxy-α-phenylacetophenone, α,α-diethoxyacetophenone, α-hydroxyalkyl phenone, α-aminoalkyl phenone, aromatic acyl phosphine oxide, bisbenzoylphenyl phosphine oxide, benzophenone, 2,4-dihydroxybenzophenone, Michler's ketone, thiopropoxythioxanthone and isopropylthioxanthone, and the content is 0.1-2wt%.

[0022] For the precisely patterned selectively adhesive tissue patch as described above, the wavelength of the ultraviolet light is 250 to 400 nm and the irradiation time is 20 to 90 minutes.

[0023] The present invention also provides a method for preparing a precisely patterned selective adhesive tissue patch as described in any of the above items, wherein a non-adhesive layer substrate, a B mold, and a photo-crosslinkable adhesive layer hydrogel precursor solution are sequentially laid in a flat-bottomed container, and then ultraviolet light is irradiated to form an adhesive layer hydrogel to obtain a precisely patterned selective adhesive tissue patch;

[0024] The number of B-molds is more than one, and they are vertically arranged on the non-adhesive layer substrate to cover the local area of ​​the non-adhesive layer substrate to prevent ultraviolet light exposure; the overall shape and size of all areas on the surface of the non-adhesive layer substrate covered by the B-molds are the same as the hollow area of ​​the adhesive layer hydrogel; the height of the B-mold is not less than the thickness of the adhesive layer hydrogel; along the vertical direction, the shape and size of each cross section of the B-mold are the same.

[0025] As the preferred technical solution:

[0026] In the method described above, the B mold is a column with closed ends made of a material that is not transparent to ultraviolet light.

[0027] According to the method described above, after pouring the photo-crosslinkable adhesion layer hydrogel precursor solution, mold A is also laid. Mold A is a cylinder made of ultraviolet light transparent material, which is vertically arranged on the non-adhesive layer substrate with the bottom of the cylinder on top; along the vertical direction, the shape and size of each cross section of mold A are the same; the shape and size of the cross section of mold A are the same as the non-hollow area of ​​the adhesion layer hydrogel.

[0028] The principle of the present invention is:

[0029] In the self-adhesive tissue patch of the present invention, the non-adhesive layer substrate and the adhesive layer hydrogel are interconnected by intermolecular forces and physical entanglement. The principle of patterning is as follows: the shapes of mold A and mold B are designed to be interlocked. When mold B is placed on the substrate, a photo-crosslinkable adhesive layer hydrogel precursor solution is cast. The area covered by mold B cannot contact the precursor solution. After covering mold A, the photo-crosslinkable adhesive layer hydrogel precursor solution is evenly distributed in other positions except the area covered by mold B. Since mold A is light-transmitting, the hydrogel in the area covered by mold A is solidified after ultraviolet light cross-linking. Since there is no photo-crosslinkable adhesive layer hydrogel precursor solution in the area covered by mold B, no adhesive layer hydrogel is formed, thereby achieving patterning. And since mold B is not light-transmitting, even if the photo-crosslinkable adhesive layer hydrogel precursor solution diffuses to the area covered by mold B, photo-crosslinking cannot be achieved, and adhesive layer hydrogel cannot be formed. Figures 1 to 7 As shown, the shapes of the A mold 1 and the B mold 2 can be designed into any shapes as long as the two can be completely fitted together.

[0030] When the patch is attached to the tissue, the adhesive layer hydrogel can be firmly bonded to the tissue that needs to be adhered, and the exposed non-adhesive layer substrate formed by patterning can contact the tissue that does not want to be adhered, achieving the effect of anti-adhesion and more stable repair. The non-adhesive layer substrate allows the tissue to regenerate faster on its surface. Furthermore, the non-adhesive layer substrate can be additionally functionalized to achieve multifunctional repair.

[0031] Beneficial Effects

[0032] (1) A precisely patterned selectively adhesive tissue patch of the present invention can precisely control the adhesion area to achieve selective adhesion to tissues without adhering to other tissues or affecting tissue regeneration;

[0033] (2) The present invention provides a method for preparing a precisely patterned selectively adhesive tissue patch, which has a simple process and a wide range of applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 A mold of the present invention;

[0035] Figure 2 for Figure 1 The B model that matches the A model;

[0036] Figure 3 For use Figure 1 A model and Figure 2 When the B-mold is used, a front view of a process for preparing a precisely patterned selectively adherent tissue patch of the present invention;

[0037] Figure 4 An A mold and a B mold of the present invention;

[0038] Figure 5 For use Figure 4 When the combined mold is used, a front view of a process for preparing a precisely patterned selectively adherent tissue patch of the present invention;

[0039] Figure 6 An A mold and a B mold of the present invention;

[0040] Figure 7 For use Figure 6 When the combined mold is used, a front view of a process for preparing a precisely patterned selectively adherent tissue patch of the present invention;

[0041] Among them, 1-A mold, 2-B mold, 3-non-adhesive layer substrate. DETAILED DESCRIPTION

[0042] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall within the scope limited by the appended claims of the application equally.

[0043] The test method for the peel strength per unit area between the non-adhesive layer substrate and the adhesive layer hydrogel in the following embodiments and comparative examples is as follows:

[0044] A local area of ​​the selective adhesion tissue patch was selected, where the adhesion layer hydrogel had no hollow areas, and the local area was rectangular with a length of 150 mm and a width of 25 mm. The non-adhesive layer substrate and the adhesion layer hydrogel were peeled off along the length of the rectangle with a peeling length of 75 mm. The peeled part was then clamped with a clamp, and the sample was stretched at a speed of 250 mm / min. The peeling strength was calculated using the force load in N / m.

[0045] Example 1

[0046] A method for preparing a fiber assembly, the specific process is as follows:

[0047] The weaving raw material is polyethylene terephthalate yarn, the yarn linear density is 100 denier, the woven fabric is prepared with a 1 / 1 plain weave structure, the warp density and weft density are 200 threads / cm, and the product thickness is 0.6 mm.

[0048] Example 2

[0049] A method for preparing a fiber assembly, the specific process is as follows:

[0050] The knitting raw material is polypropylene yarn with a yarn density of 50 denier. The knitted mesh is prepared with a closed warp flat structure. The padding yarn number is GB: 1-0 / 1-2 / / , the transverse density is 10wpc, the longitudinal density is 15cpc, and the product thickness is 0.5 mm.

[0051] Example 3

[0052] A method for preparing a fiber assembly, the specific process is as follows:

[0053] The electrospinning raw material was polycaprolactone (Aladdin, P299384) particles, which were dissolved in chloroform at a concentration of 0.12 g / ml. A 19G needle was used, the injection speed was 1.2 ml / h, the spinning was carried out at a voltage of 20 kV, the receiving distance was 15 cm, the drum speed was 30 rpm, and the product thickness was 0.2 mm.

[0054] Example 4

[0055] A method for selectively adhering tissue patches with precise patterning, comprising the following steps:

[0056] (1) Preparation of raw materials;

[0057] The non-adhesive layer substrate is a fiber assembly containing a polyphenol polymer on the surface, and the preparation process thereof is as follows: the fiber assembly of Example 1 is immersed in an aqueous solution of a polyphenol material at a bath ratio of 1:10 and shaken at 25° C. for 48 hours; the polyphenol material is dopamine (Merrill, M62581), and the content of the polyphenol material in each 1 mL of the aqueous solution of the polyphenol material is 5 mg;

[0058] The photo-crosslinkable adhesive layer hydrogel precursor solution is composed of a photo-crosslinkable polymer precursor, a biocompatible natural macromolecule, an adhesive substance, a crosslinking agent, a photoinitiator and water;

[0059] The photo-crosslinkable polymer precursor was acrylamide (Aladdin, A108470) with a content of 20 wt %;

[0060] The biocompatible natural macromolecule was gelatin (McLean, G821281), with a content of 10 wt %;

[0061] The adhesive substance is acrylic acid-N-succinimidyl ester (Aladdin, N159034), with a content of 2wt%;

[0062] The cross-linking agent was N,N-methylenebisacrylamide (Rohn's reagent, R013208), with a content of 0.5 wt%;

[0063] The photoinitiator is benzoin (sigma, B8681), with a content of 0.5wt%;

[0064] (2) in a flat-bottomed container, sequentially laying a non-adhesive layer substrate, laying a B mold, pouring a photo-crosslinkable adhesive layer hydrogel precursor solution, laying an A mold, and irradiating with ultraviolet light with a wavelength of 250 nm until an adhesive layer hydrogel is formed to obtain a precisely patterned selective adhesive tissue patch; the thickness ratio of the non-adhesive layer substrate to the adhesive layer hydrogel is 1:1;

[0065] The B mold is a column with closed ends made of a material that is not transparent to ultraviolet light. The number of B molds is more than one, and it is vertically arranged on the non-adhesive layer substrate to cover a local area of ​​the non-adhesive layer substrate to prevent ultraviolet light exposure; the overall shape and size of all areas on the surface of the non-adhesive layer substrate covered by the B mold are the same as the hollow area of ​​the adhesive layer hydrogel; the height of the B mold is not less than the thickness of the adhesive layer hydrogel; along the vertical direction, the shape and size of each cross section of the B mold are the same;

[0066] The A mold is a cylinder made of ultraviolet light transparent material, which is vertically arranged on the non-adhesive layer substrate with the bottom of the cylinder on top; along the vertical direction, the shapes and sizes of the cross sections of the A mold are the same; the shape and size of the cross section of the A mold are the same as the non-hollow area of ​​the adhesive layer hydrogel.

[0067] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 450N / m.

[0068] Example 5

[0069] A method for selectively adhering tissue patches with precise patterning, comprising the following steps:

[0070] (1) Preparation of raw materials;

[0071] The non-adhesive layer substrate is a fiber assembly containing a polyphenol polymer on the surface, and the preparation process thereof is as follows: the fiber assembly of Example 1 is immersed in an aqueous solution of a polyphenol material at a bath ratio of 1:20 and shaken at 27° C. for 44 hours; the polyphenol material is a dopamine derivative (sigma, H8502), and the content of the polyphenol material in each 1 mL of the aqueous solution of the polyphenol material is 15 mg;

[0072] The photo-crosslinkable adhesive layer hydrogel precursor solution is composed of a photo-crosslinkable polymer precursor, a biocompatible natural macromolecule, an adhesive substance, a crosslinking agent, a photoinitiator and water;

[0073] The photo-crosslinkable polymer precursor is an acrylamide derivative (sigma, 109606) with a content of 20 wt %;

[0074] The biocompatible natural macromolecule was a gelatin derivative (Aladdin, M398240) with a content of 8 wt %;

[0075] The adhesive substance is acrylic acid-N-succinimidyl ester (Aladdin, N159034), with a content of 3wt%;

[0076] The cross-linking agent was methacrylated gelatin (source leaf, S29881), with a content of 0.8 wt%;

[0077] The photoinitiator was benzoin dimethyl ether (Jiuding Chemical, BE337), with a content of 1 wt%;

[0078] (2) in a flat-bottomed container, sequentially laying a non-adhesive layer substrate, laying a B mold, pouring a photo-crosslinkable adhesive layer hydrogel precursor solution, laying an A mold, and irradiating with ultraviolet light with a wavelength of 260 nm until an adhesive layer hydrogel is formed to obtain a precisely patterned selective adhesive tissue patch; the thickness ratio of the non-adhesive layer substrate to the adhesive layer hydrogel is 10:1;

[0079] The B mold is a column with closed ends made of a material that is not transparent to ultraviolet light. The number of B molds is more than one, and it is vertically arranged on the non-adhesive layer substrate to cover a local area of ​​the non-adhesive layer substrate to prevent ultraviolet light exposure; the overall shape and size of all areas on the surface of the non-adhesive layer substrate covered by the B mold are the same as the hollow area of ​​the adhesive layer hydrogel; the height of the B mold is not less than the thickness of the adhesive layer hydrogel; along the vertical direction, the shape and size of each cross section of the B mold are the same;

[0080] The A mold is a cylinder made of ultraviolet light transparent material, which is vertically arranged on the non-adhesive layer substrate with the bottom of the cylinder on top; along the vertical direction, the shapes and sizes of the cross sections of the A mold are the same; the shape and size of the cross section of the A mold are the same as the non-hollow area of ​​the adhesive layer hydrogel.

[0081] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 480N / m.

[0082] Example 6

[0083] A method for selectively adhering tissue patches with precise patterning, comprising the following steps:

[0084] (1) Preparation of raw materials;

[0085] The non-adhesive layer substrate is a fiber assembly containing a polyphenol polymer on the surface, and the preparation process thereof is as follows: the fiber assembly of Example 1 is immersed in an aqueous solution of a polyphenol material at a bath ratio of 1:30 and shaken at 29° C. for 36 hours; the polyphenol material is dopamine (Merrill, M62581), and the content of the polyphenol material in each 1 mL of the aqueous solution of the polyphenol material is 100 mg;

[0086] The photo-crosslinkable adhesive layer hydrogel precursor solution is composed of a photo-crosslinkable polymer precursor, a biocompatible natural macromolecule, an adhesive substance, a crosslinking agent, a photoinitiator and water;

[0087] The photo-crosslinkable polymer precursor is acrylic acid (Aladdin, A103526), ​​with a content of 30 wt %;

[0088] The biocompatible natural macromolecule was alginic acid (Aladdin, A110570), with a content of 3 wt %;

[0089] The adhesive substance is acrylic acid-N-succinimidyl ester (Aladdin, N159034), with a content of 3wt%;

[0090] The cross-linking agent was dimethyl diimide ester (Henan Weitixi Chemical Technology Co., Ltd., ALFA-), with a content of 1 wt%;

[0091] The photoinitiator was benzoin ethyl ether (McLean, B824728), with a content of 1 wt%;

[0092] (2) in a flat-bottomed container, sequentially laying a non-adhesive layer substrate, laying a B mold, pouring a photo-crosslinkable adhesive layer hydrogel precursor solution, laying an A mold, and irradiating with ultraviolet light with a wavelength of 270 nm until an adhesive layer hydrogel is formed to obtain a precisely patterned selective adhesive tissue patch; the thickness ratio of the non-adhesive layer substrate to the adhesive layer hydrogel is 20:1;

[0093] The B mold is a column with closed ends made of a material that is not transparent to ultraviolet light. The number of B molds is more than one, and it is vertically arranged on the non-adhesive layer substrate to cover a local area of ​​the non-adhesive layer substrate to prevent ultraviolet light exposure; the overall shape and size of all areas on the surface of the non-adhesive layer substrate covered by the B mold are the same as the hollow area of ​​the adhesive layer hydrogel; the height of the B mold is not less than the thickness of the adhesive layer hydrogel; along the vertical direction, the shape and size of each cross section of the B mold are the same;

[0094] The A mold is a cylinder made of ultraviolet light transparent material, which is vertically arranged on the non-adhesive layer substrate with the bottom of the cylinder on top; along the vertical direction, the shapes and sizes of the cross sections of the A mold are the same; the shape and size of the cross section of the A mold are the same as the non-hollow area of ​​the adhesive layer hydrogel.

[0095] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 490N / m.

[0096] Example 7

[0097] A method for selectively adhering tissue patches with precise patterning, comprising the following steps:

[0098] (1) Preparation of raw materials;

[0099] The non-adhesive layer substrate is a fiber assembly containing a polyphenol polymer on the surface, and the preparation process thereof is as follows: the fiber assembly of Example 2 is immersed in an aqueous solution of a polyphenol material at a bath ratio of 1:40 and shaken at 31° C. for 30 hours; the polyphenol material is tannic acid (Rohn's reagent, R071388), and the content of the polyphenol material in each 1 mL of the aqueous solution of the polyphenol material is 130 mg;

[0100] The photo-crosslinkable adhesive layer hydrogel precursor solution is composed of a photo-crosslinkable polymer precursor, a biocompatible natural macromolecule, an adhesive substance, a crosslinking agent, a photoinitiator and water;

[0101] The photo-crosslinkable polymer precursor is an acrylic acid derivative (sigma, 155721) with a content of 30 wt %;

[0102] The biocompatible natural macromolecule was an alginate derivative (Aladdin, M303578) with a content of 2 wt %;

[0103] The adhesive substance is acrylic acid-N-succinimidyl ester (Aladdin, N159034), with a content of 3.5wt%;

[0104] The cross-linking agent is N,N'-bisacrylcystamine (Jiuding Chemical, B-AX257), with a content of 1wt%;

[0105] The photoinitiator was benzoin isopropyl ether (Ron's reagent, R052702), with a content of 1 wt%;

[0106] (2) in a flat-bottomed container, sequentially laying a non-adhesive layer substrate, laying a B mold, pouring a photo-crosslinkable adhesive layer hydrogel precursor solution, laying an A mold, and irradiating with ultraviolet light with a wavelength of 300 nm until an adhesive layer hydrogel is formed to obtain a precisely patterned selective adhesive tissue patch; the thickness ratio of the non-adhesive layer substrate to the adhesive layer hydrogel is 40:1;

[0107] The B mold is a column with closed ends made of a material that is not transparent to ultraviolet light. The number of B molds is more than one, and it is vertically arranged on the non-adhesive layer substrate to cover a local area of ​​the non-adhesive layer substrate to prevent ultraviolet light exposure; the overall shape and size of all areas on the surface of the non-adhesive layer substrate covered by the B mold are the same as the hollow area of ​​the adhesive layer hydrogel; the height of the B mold is not less than the thickness of the adhesive layer hydrogel; along the vertical direction, the shape and size of each cross section of the B mold are the same;

[0108] The A mold is a cylinder made of ultraviolet light transparent material, which is vertically arranged on the non-adhesive layer substrate with the bottom of the cylinder on top; along the vertical direction, the shapes and sizes of the cross sections of the A mold are the same; the shape and size of the cross section of the A mold are the same as the non-hollow area of ​​the adhesive layer hydrogel.

[0109] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 500N / m.

[0110] Example 8

[0111] A method for selectively adhering tissue patches with precise patterning, comprising the following steps:

[0112] (1) Preparation of raw materials;

[0113] The non-adhesive layer substrate is a fiber assembly containing a polyphenol polymer on the surface, and the preparation process thereof is as follows: the fiber assembly of Example 2 is immersed in an aqueous solution of a polyphenol material at a bath ratio of 1:50 and shaken at 33° C. for 20 hours; the polyphenol material is catechol (sigma, PHL82372), and the content of the polyphenol material in each 1 mL of the aqueous solution of the polyphenol material is 200 mg;

[0114] The photo-crosslinkable adhesive layer hydrogel precursor solution is composed of a photo-crosslinkable polymer precursor, a biocompatible natural macromolecule, an adhesive substance, a crosslinking agent, a photoinitiator and water;

[0115] The photocrosslinkable polymer precursor was an alginate derivative (Shenzhen Huanuo Biotechnology Co., Ltd., HN-ALM-RGD) with a content of 2 wt %;

[0116] The biocompatible natural macromolecule was cellulose (Aladdin, C104844) with a content of 2 wt %;

[0117] The adhesive substance is a derivative of acrylic acid-N-succinimidyl ester (Xi'an Kaixin Biotechnology Co., Ltd., 1325208), with a content of 2.5 wt%;

[0118] The cross-linking agent is N,N'-dicyclohexylcarbodiimide (Jiuding Chemical, N001R), with a content of 1.5wt%;

[0119] The photoinitiator is benzoin butyl ether (Huaxia Chemical, 11755), with a content of 1.5wt%;

[0120] (2) in a flat-bottomed container, sequentially laying a non-adhesive layer substrate, laying a B mold, pouring a photo-crosslinkable adhesive layer hydrogel precursor solution, laying an A mold, and irradiating with ultraviolet light with a wavelength of 330 nm until an adhesive layer hydrogel is formed to obtain a precisely patterned selective adhesive tissue patch; the thickness ratio of the non-adhesive layer substrate to the adhesive layer hydrogel is 80:1;

[0121] The B mold is a column with closed ends made of a material that is not transparent to ultraviolet light. The number of B molds is more than one, and it is vertically arranged on the non-adhesive layer substrate to cover a local area of ​​the non-adhesive layer substrate to prevent ultraviolet light exposure; the overall shape and size of all areas on the surface of the non-adhesive layer substrate covered by the B mold are the same as the hollow area of ​​the adhesive layer hydrogel; the height of the B mold is not less than the thickness of the adhesive layer hydrogel; along the vertical direction, the shape and size of each cross section of the B mold are the same;

[0122] The A mold is a cylinder made of ultraviolet light transparent material, which is vertically arranged on the non-adhesive layer substrate with the bottom of the cylinder on top; along the vertical direction, the shapes and sizes of the cross sections of the A mold are the same; the shape and size of the cross section of the A mold are the same as the non-hollow area of ​​the adhesive layer hydrogel.

[0123] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 510 N / m.

[0124] Example 9

[0125] A method for selectively adhering tissue patches with precise patterning, comprising the following steps:

[0126] (1) Preparation of raw materials;

[0127] The non-adhesive layer substrate is a fiber assembly containing a polyphenol polymer on the surface, and the preparation process thereof is as follows: the fiber assembly of Example 3 is immersed in an aqueous solution of a polyphenol material at a bath ratio of 1:70 and shaken at 36° C. for 10 hours; the polyphenol material is tannic acid (Ron's reagent, R071388), and the content of the polyphenol material in each 1 mL of the aqueous solution of the polyphenol material is 50 mg;

[0128] The photo-crosslinkable adhesive layer hydrogel precursor solution is composed of a photo-crosslinkable polymer precursor, a biocompatible natural macromolecule, an adhesive substance, a crosslinking agent, a photoinitiator and water;

[0129] The photo-crosslinkable polymer precursor is a gelatin derivative (sigma, 900629) with a content of 10 wt %;

[0130] The biocompatible natural macromolecule was a cellulose derivative (Aladdin, C104844) with a content of 2 wt %;

[0131] The adhesive substance is a derivative of acrylic acid-N-succinimidyl ester (Xi'an Kaixin Biotechnology Co., Ltd., 1325208), with a content of 3 wt %;

[0132] The cross-linking agent is N,N'-diisopropylcarbodiimide (Jiuding Chemical, N005A), with a content of 2 wt%;

[0133] The photoinitiator is diphenylacetophenone (Jiuding Chemical, PI570), with a content of 2 wt%;

[0134] (2) in a flat-bottomed container, sequentially laying a non-adhesive layer substrate, laying a B mold, pouring a photo-crosslinkable adhesive layer hydrogel precursor solution, laying an A mold, and irradiating with ultraviolet light with a wavelength of 360 nm until an adhesive layer hydrogel is formed to obtain a precisely patterned selective adhesive tissue patch; the thickness ratio of the non-adhesive layer substrate to the adhesive layer hydrogel is 160:1;

[0135] The B mold is a column with closed ends made of a material that is not transparent to ultraviolet light. The number of B molds is more than one, and it is vertically arranged on the non-adhesive layer substrate to cover a local area of ​​the non-adhesive layer substrate to prevent ultraviolet light exposure; the overall shape and size of all areas on the surface of the non-adhesive layer substrate covered by the B mold are the same as the hollow area of ​​the adhesive layer hydrogel; the height of the B mold is not less than the thickness of the adhesive layer hydrogel; along the vertical direction, the shape and size of each cross section of the B mold are the same;

[0136] The A mold is a cylinder made of ultraviolet light transparent material, which is vertically arranged on the non-adhesive layer substrate with the bottom of the cylinder on top; along the vertical direction, the shapes and sizes of the cross sections of the A mold are the same; the shape and size of the cross section of the A mold are the same as the non-hollow area of ​​the adhesive layer hydrogel.

[0137] The final precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 530N / m.

[0138] Example 10

[0139] A method for selectively adhering tissue patches with precise patterning, comprising the following steps:

[0140] (1) Preparation of raw materials;

[0141] The non-adhesive layer substrate is a fiber assembly containing a polyphenol polymer on the surface, and the preparation process thereof is as follows: the fiber assembly of Example 3 is immersed in an aqueous solution of a polyphenol material at a bath ratio of 1:100 and shaken at 40° C. for 3 hours; the polyphenol material is a catechol derivative (sigma, M13203), and the content of the polyphenol material in each 1 mL of the aqueous solution of the polyphenol material is 70 mg;

[0142] The photo-crosslinkable adhesive layer hydrogel precursor solution is composed of a photo-crosslinkable polymer precursor, a biocompatible natural macromolecule, an adhesive substance, a crosslinking agent, a photoinitiator and water;

[0143] The photocrosslinkable polymer precursor was a collagen derivative (Xi’an Qiyue Biotechnology Co., Ltd., ColMA Kit) with a content of 3 wt %;

[0144] The biocompatible natural macromolecule was dextran (Aladdin, D400777) with a content of 4 wt %;

[0145] The adhesive substance is a derivative of acrylic acid-N-succinimidyl ester (Xi'an Kaixin Biotechnology Co., Ltd., 1325208), with a content of 3 wt %;

[0146] The cross-linking agent is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (Aladdin, E106172), with a content of 2 wt%;

[0147] The photoinitiator is α,α-dimethoxy-α-phenylacetophenone (source leaf, S45044), with a content of 2wt%;

[0148] (2) in a flat-bottomed container, sequentially laying a non-adhesive layer substrate, laying a B mold, pouring a photo-crosslinkable adhesive layer hydrogel precursor solution, laying an A mold, and irradiating with ultraviolet light with a wavelength of 400 nm until an adhesive layer hydrogel is formed to obtain a precisely patterned selective adhesive tissue patch; the thickness ratio of the non-adhesive layer substrate to the adhesive layer hydrogel is 200:1;

[0149] The B mold is a column with closed ends made of a material that is not transparent to ultraviolet light. The number of B molds is more than one, and it is vertically arranged on the non-adhesive layer substrate to cover a local area of ​​the non-adhesive layer substrate to prevent ultraviolet light exposure; the overall shape and size of all areas on the surface of the non-adhesive layer substrate covered by the B mold are the same as the hollow area of ​​the adhesive layer hydrogel; the height of the B mold is not less than the thickness of the adhesive layer hydrogel; along the vertical direction, the shape and size of each cross section of the B mold are the same;

[0150] The A mold is a cylinder made of ultraviolet light transparent material, which is vertically arranged on the non-adhesive layer substrate with the bottom of the cylinder on top; along the vertical direction, the shapes and sizes of the cross sections of the A mold are the same; the shape and size of the cross section of the A mold are the same as the non-hollow area of ​​the adhesive layer hydrogel.

[0151] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 550N / m.

[0152] Embodiment 11

[0153] A method for selectively adhering a tissue patch with precise patterning is basically the same as Example 4, except that the non-adhesive layer substrate is a hydrogel with a thickness of 600 microns.

[0154] The preparation process of the hydrogel is as follows: sodium alginate (Aladdin, S100128) is dissolved in water to form a solution with a concentration of 0.02 g / ml, the solution is poured into a mold, frozen overnight and freeze-dried; the freeze-dried product is taken out and placed in a calcium chloride (Aladdin, C118704) aqueous solution with a concentration of 0.05 g / ml for 2 hours according to a bath ratio of 1:100 to obtain a sodium alginate hydrogel.

[0155] The final precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel is a hydrogel containing adhesion groups, and the adhesion layer hydrogel has a hollow pattern; the non-adhesion layer substrate is a substrate that does not contain adhesion groups; the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 450N / m.

[0156] Example 12

[0157] A method for selectively adhering a tissue patch with precise patterning is basically the same as that of Example 4, except that the non-adhesive layer substrate is the fiber assembly prepared in Example 1.

[0158] The final precisely patterned selective adhesion tissue patch has a composite layer structure, which is composed of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel is a hydrogel containing adhesion groups, and the adhesion layer hydrogel has a hollow pattern; the non-adhesion layer substrate is a substrate that does not contain adhesion groups; the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 400N / m.

[0159] Compared with Example 1, the peel strength per unit area of ​​Example 12 is much smaller than that of Example 1. This is because the surface of the fiber assembly does not contain polyphenols, and there is a lack of covalent bonding between the fiber assembly and the adhesive hydrogel.

[0160] Example 13

[0161] A method for selectively adhering a tissue patch with precise patterning is basically the same as Example 4, except that the non-adhesive layer substrate is a cast film with a thickness of 600 microns.

[0162] The preparation process of the casting film is as follows: polycaprolactone (Aladdin, P299384) is dissolved in chloroform (Sinopharm Reagent, 10006818CK) to form a solution with a concentration of 0.12 g / ml, the solution is poured on a plate, air-dried to evaporate the solvent, and a casting film is obtained.

[0163] The final precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel is a hydrogel containing adhesion groups, and the adhesion layer hydrogel has a hollow pattern; the non-adhesion layer substrate is a substrate that does not contain adhesion groups; the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 380N / m.

[0164] Embodiment 14

[0165] A method for selectively adhering tissue patches with precise patterning is basically the same as Example 4, except that the photoinitiator is α,α-diethoxyacetophenone (Sigma, 227102), the crosslinker is N-hydroxysuccinimide (Aladdin, H109330), and the biocompatible natural macromolecule is a dextran derivative (Sigma, 86524).

[0166] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 490N / m.

[0167] Embodiment 15

[0168] A method for selectively adhering tissue patches with precise patterning is basically the same as Example 4, except that the photoinitiator is α-hydroxyalkyl phenone (Sigma, 405655), the crosslinker is a mixture of N,N-methylenebisacrylamide (Sigma, 1108970050) and methacrylated gelatin (Source Leaf, S29881) in a mass ratio of 1:1, and the biocompatible natural macromolecule is hyaluronic acid (McLean, H909938).

[0169] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 495 N / m.

[0170] Example 16

[0171] A method for selectively adhering tissue patches with precise patterning is basically the same as Example 4, except that the photoinitiator is α-aminoalkylphenone (Sigma, 405639) and the biocompatible natural macromolecule is a hyaluronic acid derivative (Aladdin A293527).

[0172] The final precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 505N / m.

[0173] Embodiment 17

[0174] A method for selectively adhering tissue patches with precise patterning is basically the same as Example 4, except that the photocrosslinkable polymer precursor is a cellulose derivative (Xi'an Qiyue Biotechnology Co., Ltd., CMC-g-AE), the photoinitiator is an aromatic acylphosphine oxide (Sigma, 415952), and the biocompatible natural macromolecule is collagen (Sigma, C9791).

[0175] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 500N / m.

[0176] Embodiment 18

[0177] A method for selectively adhering tissue patches with precise patterning is basically the same as Example 4, except that the photoinitiator is bisbenzoylphenylphosphine oxide (Sigma, 511447) and the biocompatible natural macromolecule is a collagen derivative (Sigma, C4361).

[0178] The final precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 505N / m.

[0179] Embodiment 19

[0180] A method for selectively adhering a tissue patch with precise patterning is substantially the same as in Example 4, except that the photoinitiator is benzophenone (Sigma, B9300).

[0181] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 501N / m.

[0182] Embodiment 20

[0183] A method for selectively adhering tissue patches with precise patterning, substantially the same as in Example 4, except that the photocrosslinkable polymer precursor is a dextran derivative and the photoinitiator is 2,4-dihydroxybenzophenone (Aladdin, D110121);

[0184] The preparation steps of the dextran derivatives are as follows:

[0185] (1) Dissolve dextran in 90 ml of dimethyl sulfoxide (sigma, D2650) to form solution I with a glucose concentration of 0.11 g / ml;

[0186] (2) adding glycidyl methacrylate (sigma, 151238) and 4-(N,N-dimethylamino)pyridine (sigma, 107700) to solution I to form solution II; wherein the concentration of glycidyl methacrylate in solution II is 0.016 g / ml, and the concentration of 4-(N,N-dimethylamino)pyridine in solution II is 0.02 g / ml;

[0187] (3) stirring solution II at 30° C. for 30 hours to obtain a reaction solution;

[0188] (4) The reaction solution of step (3) was added dropwise to 400 ml of anhydrous ethanol (Sigma, 1070172511), allowed to stand and filtered to obtain a white precipitate;

[0189] (5) The white precipitate was dissolved in distilled water, the pH was adjusted to 7, dialyzed in deionized water at 4° C. for 4 days, and freeze-dried to obtain a dextran derivative.

[0190] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 510 N / m.

[0191] Embodiment 21

[0192] A method for selectively adhering tissue patches with precise patterning is basically the same as Example 4, except that the photoinitiator is Michler's ketone (Source Leaf, S19213).

[0193] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 500N / m.

[0194] Embodiment 22

[0195] A method for selectively adhering tissue patches with precise patterning is basically the same as Example 4, except that the photocrosslinkable polymer precursor is a hyaluronic acid derivative (Shanghai Zhenzhun Biotechnology Co., Ltd., ZCR-HA-301) and the photoinitiator is thiopropoxythioxanthone (B&K Technology, 513069).

[0196] The ultimately produced precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 480N / m.

[0197] Embodiment 23

[0198] A method for selectively adhering tissue patches with precise patterning is basically the same as Example 4, except that the photocrosslinkable polymer precursor is polyethylene glycol diacrylate (Source Leaf, S28835) and the photoinitiator is isopropylthioxanthone (Sigma, 34222).

[0199] The final precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 485N / m.

[0200] Embodiment 24

[0201] A method for selectively adhering tissue patches with precise patterning is basically the same as Example 4, except that the photocrosslinkable polymer precursor is a polyethylene glycol diacrylate derivative (Sigma, 463183), and the photoinitiator is a mixture of Michler's ketone (Source Leaf, S19213) and isopropylthioxanthone (Sigma, 34222) in a mass ratio of 1:1.

[0202] The final precisely patterned selective adhesion tissue patch has a composite layer structure, consisting of an adhesion layer hydrogel and a non-adhesion layer substrate; the adhesion layer hydrogel has a hollow pattern, and the peel strength per unit area between the non-adhesion layer substrate and the adhesion layer hydrogel is 485N / m.

Claims

1. A precisely patterned selectively adhesive tissue patch, characterized in that: It has a composite layer structure, consisting of an adhesive layer hydrogel and a non-adhesive layer substrate; the adhesive layer hydrogel is a hydrogel containing adhesive groups, and the adhesive layer hydrogel has a hollow pattern; the non-adhesive layer substrate is a substrate without adhesive groups; The adhesive layer hydrogel is obtained by irradiating a photo-crosslinkable adhesive layer hydrogel precursor solution with ultraviolet light, wherein the photo-crosslinkable adhesive layer hydrogel precursor solution comprises a photo-crosslinkable polymer precursor, a biocompatible natural macromolecule, an adhesive substance, a crosslinking agent, a photoinitiator and water; In the photo-crosslinkable adhesion layer hydrogel precursor solution, the photo-crosslinkable polymer precursor is one or more of acrylamide and its derivatives, acrylic acid and its derivatives, gelatin derivatives, collagen derivatives, alginate derivatives, cellulose derivatives, dextran derivatives, hyaluronic acid derivatives, polyethylene glycol diacrylate and its derivatives, and the content is 1 to 40 wt%; The biocompatible natural macromolecule is one or more of gelatin and its derivatives, collagen and its derivatives, alginate and its derivatives, cellulose and its derivatives, dextran and its derivatives, hyaluronic acid and its derivatives, and the content is 0.5 to 30 wt%; The adhesive substance is acrylic acid-N-succinimide ester and its derivatives, and the content is 0.5-5wt%; The crosslinking agent is one or more of N,N-methylenebisacrylamide, methacrylated gelatin, dimethyl diimide, N,N'-bisacrylamide, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide, and the content is 0.1-2wt%; The photoinitiator is one or more of benzoin, benzoin dimethyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin butyl ether, diphenyl acetone, α,α-dimethoxy-α-phenylacetophenone, α,α-diethoxyacetophenone, α-hydroxyalkyl phenone, α-aminoalkyl phenone, aromatic acyl phosphine oxide, bisbenzoylphenyl phosphine oxide, benzophenone, 2,4-dihydroxybenzophenone, Michler's ketone, thiopropoxythioxanthone and isopropylthioxanthone, and the content is 0.1-2wt%.

2. A precisely patterned selectively adhesive tissue patch according to claim 1, characterized in that: The thickness of the non-adhesive layer substrate is 100 to 4000 microns, and the thickness ratio of the non-adhesive layer substrate to the adhesive layer hydrogel is 1 to 200:

1.

3. A precisely patterned selectively adhesive tissue patch according to claim 2, characterized in that: The non-adhesive layer substrate is a hydrogel, a fiber assembly or a cast film.

4. A precisely patterned selectively adhesive tissue patch according to claim 3, characterized in that: The non-adhesive layer substrate is a fiber aggregate with a polyphenol polymer on the surface, the polyphenol polymer is polymerized from polyphenol materials, and the polyphenol material is one or more of dopamine, dopamine derivatives, tannic acid, catechol and catechol derivatives; the photocrosslinkable polymer precursor is a polymer that can be activated by free radicals I and II, free radicals I are generated by the polyphenol polymer under the irradiation of ultraviolet light, free radicals II are generated by the photoinitiator under the irradiation of ultraviolet light, and the crosslinking agent is used to connect the activated photocrosslinkable polymer precursor.

5. A precisely patterned selectively adhesive tissue patch according to claim 1, characterized in that: The wavelength of the ultraviolet light is 250 to 400 nm, and the irradiation time is 20 to 90 minutes.

6. A method for preparing a precisely patterned selectively adhesive tissue patch as claimed in any one of claims 1 to 5, characterized in that: In a flat-bottom container, a non-adhesive layer substrate, a B mold, and a photo-crosslinkable adhesive layer hydrogel precursor solution are sequentially laid, and then ultraviolet light is irradiated to form an adhesive layer hydrogel to obtain a precisely patterned selectively adhesive tissue patch; The number of B-molds is more than one, and they are vertically arranged on the non-adhesive layer substrate to cover a local area of ​​the non-adhesive layer substrate to prevent ultraviolet light exposure; the overall shape and size of all areas on the surface of the non-adhesive layer substrate covered by the B-molds are the same as the hollow area of ​​the adhesive layer hydrogel; the height of the B-mold is not less than the thickness of the adhesive layer hydrogel; Along the vertical direction, the shapes and sizes of the cross sections of the B mold are the same.

7. The method according to claim 6, characterized in that The B-mold is a column with closed ends made of a material that is not transparent to ultraviolet light.

8. The method according to claim 6, characterized in that After pouring the photo-crosslinkable adhesion layer hydrogel precursor solution, mold A is also laid. Mold A is a cylinder made of ultraviolet light transparent material, which is vertically arranged on the non-adhesive layer substrate with the bottom of the cylinder on top; along the vertical direction, the shapes and sizes of the cross sections of mold A are the same; the shape and size of the cross section of mold A are the same as the non-hollow area of ​​the adhesion layer hydrogel.

Images