A composite rotator cuff patch and methods of making and using the same

Abstract

The present application relates to a kind of composite rotator cuff patch and its preparation method and application, belong to the field of biomaterials technology.The structure layer and biological layer are all biological medical materials, do not need to introduce crosslinking agent, and by the structure layer and biological layer alternate composite design, avoid the problem that traditional synthetic material is not degradable or short degradation period, with controllable degradation period, improve the tear resistance and mechanical support of patch, effectively reduce the risk of inflammatory response, improve the biocompatibility and safety of patch, finally realize the applicability and effect of improving composite rotator cuff patch in clinical application.

Description

Technical Field

[0001] This invention belongs to the field of biomaterials technology, and relates to a composite rotator cuff patch, its preparation method, and its application. Background Technology

[0002] Rotator cuff tears are one of the most common tendon injuries in orthopedics, primarily causing shoulder pain and limited range of motion. Currently, treatment for rotator cuff tears mainly includes conservative treatment and surgical treatment. Conservative treatment has limited effectiveness, especially for patients with large-area rotator cuff tears or those that fail to heal over a long period; in these cases, surgical repair becomes the only option.

[0003] Rotator cuff patches are medical devices used in surgery to reinforce and assist in the repair of rotator cuff tears. They are sheet-like structures made of biomaterials or synthetic materials, used to enhance repair, promote healing, fill defects, and reduce the rate of re-tears. Currently, commonly used rotator cuff patch materials mainly include collagen, decellularized matrix materials, and electrospun materials. However, these materials still need improvement in terms of mechanical properties, biocompatibility, and degradation performance. For example, while pure collagen has good biocompatibility, its mechanical properties are poor, and its degradation time is short, limiting its clinical application. Therefore, developing a rotator cuff patch material that can provide good mechanical support, promote cell migration and healing, and has a controllable degradation cycle has become a key research focus and challenge.

[0004] For example, CN116899015A discloses a composite material rotator cuff patch and its preparation method, which improves mechanical properties by combining polylactic acid / silk fibroin warp-knitted fabric with collagen. However, it suffers from dependence on synthetic materials, poses a risk of inflammation with long-term use, and has insufficient pore uniformity, failing to meet both mechanical support and cell migration requirements. CN115551564A discloses a composite material rotator cuff patch using a composite structure of synthetic materials (such as polyester) and collagen, but it suffers from non-degradable material residues, long-term retention of the synthetic layer leading to chronic inflammation, and a contradiction between mechanical properties and biocompatibility, where synthetic materials enhance mechanical properties but inhibit cell infiltration.

[0005] Existing rotator cuff patch materials suffer from poor mechanical properties, short degradation cycles, unreasonable pore structures, and unsafe interlayer bonding methods. These problems lead to poor rotator cuff repair outcomes, slow postoperative recovery, and even the potential for secondary injury. Therefore, there is an urgent need to develop novel materials that can provide durable mechanical support, achieve controlled degradation, optimize pore structure to promote cell migration and regeneration, ensure strong interlayer bonding, and reduce the risk of inflammation. Summary of the Invention

[0006] In response to the shortcomings of existing technologies and practical needs, this invention provides a composite rotator cuff patch, its preparation method, and its application, aiming to provide a rotator cuff patch material that can provide good mechanical support, promote cell migration and healing, and has a controllable degradation cycle.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] In a first aspect, the present invention provides a composite rotator cuff patch, the composite rotator cuff patch comprising alternatingly stacked structural layers and biological layers; the material of the structural layer includes at least one of collagen, gelatin, collagen fiber or silk fibroin, and the structural layer is prepared by hot pressing the material of the structural layer; the material of the biological layer includes at least one of collagen, gelatin, chitosan or silk fibroin, and the structural layer and the biological layer have a porous structure.

[0009] This invention presents a composite rotator cuff patch with a specific structure and composition. The biolayer acts as an adhesive, bonding the structural layer to enhance strength and simultaneously delivering nutrients and providing space for cell growth. The structural layer also provides a cell growth environment, while its dense structure improves the patch's mechanical support. Both the structural and biolayers are fully biomedical materials with excellent biocompatibility and a porous structure that promotes cell growth. Furthermore, the absence of cross-linking agents eliminates the need for cleaning these agents, reducing time and costs. The alternating composite design of the structural and biolayers enhances the patch's tear resistance and mechanical support. Its in vivo degradation period is approximately 3-6 months, avoiding the problems of non-degradability or short degradation cycles associated with traditional synthetic materials. This effectively reduces the risk of inflammatory reactions and improves the material's biocompatibility and safety.

[0010] In this invention, the material of the structural layer can be the same as that of the biological layer. At the same time, the structural layer has a fibrous material, which is heat-treated to further improve the bonding between fibers, further enhance mechanical properties and form a specific structure, play a key supporting role, and work synergistically with the biological layer.

[0011] In this invention, the tensile strength of the composite patch is 4.0-10.0 MPa. If the tensile strength is too low, it cannot provide adequate mechanical support and fails to meet the patch's tear resistance and mechanical support requirements. If it is too high, it may lead to atrophy and degeneration of the natural tendon.

[0012] Preferably, the structural layer material further includes hydroxyapatite.

[0013] In this invention, the addition of hydroxyapatite to the structural layer further enhances its strength. Simultaneously, as the structural layer degrades, hydroxyapatite acts as a calcium and phosphorus ion reservoir, releasing calcium ions (Ca²⁺). ＋ ) and phosphate ions (PO4³ -It can promote cell proliferation and differentiation.

[0014] Preferably, the thickness of the structural layer is 0.02-0.6 mm, for example, it can be 0.03, 0.04, 0.05, 0.1, 0.15, 0.2, 0.3, 0.4 or 0.5 mm.

[0015] Preferably, the pore size of the structural layer is 10~50 μm, for example, it can be 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 46, 47, 48 or 49 μm.

[0016] In this invention, specific pore sizes in the structural layers are controlled to maintain a specific shape and mechanical support while meeting the pore size requirements for fibroblast growth.

[0017] Preferably, the porosity of the structural layer is 30% to 50%, for example, it can be 31%, 32%, 33%, 34%, 35%, 40%, 45%, 46%, 47%, 48% or 49%, etc.

[0018] In this invention, the specific porosity of the structural layer is controlled to meet the growth needs of fibroblasts while also having a dense structure, providing strength support for damage repair.

[0019] Preferably, the biolayer material further includes hyaluronic acid and / or sodium alginate.

[0020] In this invention, hyaluronic acid and / or sodium alginate are added to the biological layer. Hyaluronic acid or sodium alginate can interweave with the biological layer material to form a microfiber network, and a porous (porosity of up to 80%) fiber-interwoven sponge morphology can be obtained by freeze drying.

[0021] Preferably, the thickness of the biological layer is 0.1~0.3 mm, for example, it can be 0.12, 0.13, 0.15, 0.2, 0.25, 0.26, 0.27, 0.28 or 0.29 mm.

[0022] Preferably, the pore size of the biological layer is 50~200 μm, for example, it can be 55, 60, 70, 80, 100, 150, 160, 170, 180, 190 or 195 μm.

[0023] In this invention, specific pore sizes of the biological layer are controlled to maintain a specific shape and mechanical support while meeting the pore size requirements for fibroblast growth.

[0024] Preferably, the porosity of the biological layer is 50% to 90%, for example, it can be 51%, 52%, 53%, 54%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, or 89%, etc.

[0025] In this invention, the porosity of the biological layer is controlled to be greater than that of the structural layer, resulting in a loose structure that reduces the resistance to nutrient transport and enables efficient delivery of nutrients for tissue healing. At the same time, the high porosity provides sufficient space for the growth of proliferating and differentiating cells.

[0026] In this invention, the alternating composite structure layer and biological layer, along with their specific pore sizes and porosities, form a specific gradient pore structure that can simultaneously meet the needs of mechanical support and cell migration.

[0027] Preferably, the total number of structural layers and biological layers is 4 to 8.

[0028] The multi-layered alternating stacked structure (4-8 composite units) of this invention significantly improves the tear resistance and mechanical support of the patch through interlayer fiber interlacing reinforcement. During the fabrication process, the bottom layer of the composite rotator cuff patch is designed as a structural layer, which adheres to the damaged area. A schematic diagram of the two-layer structure consisting of the structural layer and the biological layer is shown below. Figure 1 As shown, 4-8 layers of composite units are repeatedly stacked on this basis.

[0029] Preferably, the thickness of the composite shoulder and sleeve patch is 0.6~3.0 mm, for example, it can be 0.7, 0.8, 0.9, 1, 1.5, 1.6, 1.7, 1.8, 2, 2.5, 2.6, 2.7, 2.8 or 2.9 mm.

[0030] Preferably, the tensile strength of the composite rotator cuff patch is 4.0~10.0 MPa; if the tensile strength is too low, it cannot provide mechanical support and cannot meet the tear resistance and mechanical support requirements of the patch; if it is too high, it may cause atrophy and degeneration of the tissue itself.

[0031] In a second aspect, the present invention provides a method for preparing the composite rotator cuff patch described in the first aspect, the method comprising:

[0032] The material of the structural layer is hot-pressed to obtain the structural layer. The material of the biological layer is then laid on the structural layer to form the biological layer. The structural layer and the biological layer are alternately stacked to obtain the composite shoulder and sleeve patch.

[0033] This invention is prepared through a thermal crosslinking physical bonding process, which eliminates the need for chemical crosslinking agents and avoids the cytotoxic risks that may be caused by chemical additives such as glutaraldehyde, thereby further improving the biocompatibility and safety of the patch.

[0034] Preferably, the hot pressing treatment is performed at a temperature of 110~130℃ (e.g., 112, 113, 114, 115, 120, 125, 126, 127, 128 or 129℃, etc.), for a time of 30~60 min (e.g., 35, 40, 45, 50 or 55 min, etc.), and at a pressure of 0.5~1 MPa (e.g., 0.6, 0.7, 0.8 or 0.9 MPa, etc.).

[0035] In this invention, specific hot-pressing conditions are designed to obtain a structural layer that can achieve the target effect. If the temperature is too low, the cross-linking effect will be insufficient; if the temperature is too high, the material will be deformed. If the time is too short, effective cross-linking bonds cannot be formed; if the time is too long, the time will increase the time cost, and excessively increasing the time under suitable temperature and pressure will cause the material to deform. If the pressure is too high, the pore size will be too small; if the pressure is too low, the spacing between reactive groups cannot be effectively increased, effective cross-linking bonds cannot be formed, and the strength is not easy to meet the requirements.

[0036] Preferably, the method for preparing the structural layer specifically includes:

[0037] The material of the structural layer is dissolved to obtain a structural layer gel. The structural layer gel is dried to obtain a structural layer patch. The structural layer patch is hot-pressed and cooled to obtain a structural layer.

[0038] Preferably, the mass percentage of the structural layer material in the structural layer gel is 1 to 6 wt%, for example, it can be 2 wt%, 2.5 wt%, 3.5 wt%, 4 wt%, 4.5 wt%, or 5.5 wt%.

[0039] Preferably, the solvent for the structural layer gel is a volatile solvent capable of dissolving the structural layer material, such as acetic acid, hexafluoroisopropanol, or water. Specifically, collagen and collagen fibers can be dissolved using an acetic acid solution; silk fibroin can be dissolved using a hexafluoroisopropanol solution (8%-12%); gelatin can be dissolved using water (e.g., first soaking in cold water for 10 minutes, then heating the water to 40-60°C to completely dissolve it); hydroxyapatite can be dissolved using an acetic acid solution, and then mixed evenly with the dissolved structural layer gel.

[0040] In this invention, designing the concentration of a specific structural layer gel is beneficial for obtaining a structural layer with the target porosity.

[0041] Preferably, the method for preparing the biological layer specifically includes:

[0042] The material of the biological layer is dissolved to obtain a biological layer gel, which is then laid on the structural layer to form the biological layer.

[0043] Preferably, the biolayer material in the biolayer gel has a mass percentage of 0.5 to 4 wt%, for example, it can be 0.6 wt%, 0.7 wt%, 0.8 wt%, 1 wt%, 1.5 wt%, 2 wt%, 2.5 wt%, 3 wt%, 3.5 wt%, 3.6 wt%, 3.8 wt%, or 3.9 wt%.

[0044] Preferably, the solvent for the biolayer gel is a volatile solvent capable of dissolving the biolayer material, such as acetic acid, sodium hydroxide solution, or water. Specifically, collagen and chitosan can be dissolved using acetic acid solution; silk fibroin can be dissolved using hexafluoroisopropanol solution; gelatin and sodium alginate can be dissolved using water; and hyaluronic acid can be dissolved using sodium hydroxide solution.

[0045] In this invention, designing a specific concentration of the biolayer gel is beneficial for obtaining a biolayer with the target porosity.

[0046] Preferably, the alternating stacked structural layers and biological layers are followed by a drying process.

[0047] As a preferred technical solution, the preparation method of the composite shoulder and cuff patch includes the following steps:

[0048] (1) Dissolve the material of the structural layer to prepare a structural layer gel with a mass fraction of 1~6 wt%, and dry it at 25~30℃ for 4~8 h to obtain a structural layer patch;

[0049] (2) Place the structural layer patch into a hot press and hot press it at 110~130℃ and 0.5~1 MPa for 30~60 min to obtain a thermally cross-linked sheet. Cool the thermally cross-linked sheet to obtain a structural layer with a thickness of 0.02~0.6 mm.

[0050] (3) Dissolve the material of the biolayer to prepare a biolayer gel with a mass fraction of 0.5~4 wt%, and lay the biolayer gel on the structural layer obtained in step (2), with a biolayer gel thickness of 0.1~0.3 mm;

[0051] (4) Alternately stack structural layers and biological layers to prepare 4-8 layer composite units with a total thickness of 0.6-3.0 mm;

[0052] (5) The composite unit is dried to obtain the composite shoulder and sleeve patch.

[0053] This invention designs a thermal crosslinking physical bonding process that eliminates the need for chemical crosslinking agents, avoids the cytotoxic risks that chemical additives such as glutaraldehyde may bring, and further improves the biocompatibility and safety of the patch.

[0054] Thirdly, the present invention provides the application of the composite rotator cuff patch in the preparation of products for rotator cuff repair surgery.

[0055] The composite rotator cuff patch designed based on this invention can be further developed into related products for rotator cuff repair surgery.

[0056] Compared with the prior art, the present invention has at least the following beneficial effects:

[0057] This invention presents a novel composite rotator cuff patch with a new composition and structure, along with its preparation method. The structural and biological layers are made entirely of biomedical materials, eliminating the need for cross-linking agents. Furthermore, the alternating composite design of the structural and biological layers avoids the problems of non-degradability or short degradation cycles associated with traditional synthetic materials. This results in a controllable degradation cycle, improved tear resistance and mechanical support, effectively reduced risk of inflammatory reactions, and enhanced biocompatibility and safety. Ultimately, this invention improves the applicability and efficacy of composite rotator cuff patches in clinical applications. Attached Figure Description

[0058] Figure 1 A schematic three-dimensional diagram of a two-layer structural unit for a composite shoulder and sleeve patch.

[0059] Figure 2 The image shows a scanning electron microscope cross-sectional view of the composite shoulder and sleeve patch structure layer prepared in Example 1.

[0060] Figure 3 The image shows a scanning electron microscope cross-sectional view of the biological layer of the composite shoulder and cuff patch prepared in Example 3.

[0061] Figure 4 The image shows the appearance of the composite shoulder and sleeve patch prepared in Example 3.

[0062] Figure 5 The image shows the fracture strength test result of the composite shoulder and sleeve patch prepared in Example 5.

[0063] Figure 6 The image shows the strength test of the supraspinatus tendon rupture in rabbits 8 weeks after implantation of the composite rotator cuff patch prepared in Example 3. Detailed Implementation

[0064] The technical solution of the present invention will be further described below with reference to the accompanying drawings and specific embodiments. However, the following examples are merely simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention is determined by the claims.

[0065] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased from legitimate channels.

[0066] In a specific embodiment of the present invention, the collagen fiber, collagen protein, silk fibroin and gelatin are branded as Adamas Life, the hydroxyapatite is branded as Sigma-Aldrich, and the hyaluronic acid, chitosan and sodium alginate are branded as Adamas. All of the above raw materials were purchased from Shanghai Titan Technology Co., Ltd.

[0067] In a specific embodiment of the present invention, the method for testing the tensile strength of the shoulder and cuff patch is as follows:

[0068] The samples were cut into strips (width 10 mm ± 0.5 mm, length 2.5-3 cm), and the tensile rate was 100 mm / min. The tensile strength was determined according to GB / T3923.1-2013 "Textiles - Tensile Properties of Fabrics - Part 1: Determination of Breaking Strength and Elongation at Break (Strip Method)". The equipment used was a fabric tensile testing machine, model YG026Q. Tensile strength (σ) refers to the ability of the patch to resist breakage during stretching, and the calculation formula is σ = F / A, where F is the maximum tensile force (in N) that the patch can withstand when it breaks, and A is the cross-sectional area of ​​the patch (in mm²).

[0069] The method for detecting the pore size and porosity of the structural layer and the biological layer is as follows:

[0070] The pore size and porosity of the structural layer and biological layer were determined using scanning electron microscopy (SEM).

[0071] Example 1

[0072] This embodiment provides a composite rotator cuff patch, the preparation method of which includes the following steps:

[0073] (1) Collagen fibers with a mass fraction of 3% were prepared by dissolving them in 0.5% acetic acid solution to obtain structural layer gel. The gel was placed in a vacuum drying oven and dried at 25°C for 5 h to obtain structural layer patch.

[0074] (2) Place the structural layer patch into a hot press and hot press it at 110°C for 40 min, with the pressure controlled at 0.5 MPa, to obtain a thermally cross-linked sheet;

[0075] (3) Cool the thermally cross-linked sheet to room temperature to obtain a high-strength structural layer with a thickness of 0.2 mm and a pore size of 20~30 μm.

[0076] (4) Collagen was dissolved in 0.5% acetic acid solution to obtain 1.5 wt% biolayer gel;

[0077] (5) The biolayer gel is laid on the structural layer obtained in step (3) to obtain the biolayer. The biolayer gel has a thickness of 0.2 mm and a pore size of 100~150 μm.

[0078] (6) Alternately stack structural layers and biological layers to prepare a 4-layer composite unit with a total thickness of 0.8 mm;

[0079] (7) The composite unit was freeze-dried at -20℃ for 8 h to obtain a high tensile strength rotator cuff patch. The scanning electron microscope cross-sectional image of the composite rotator cuff patch structure is shown below. Figure 2 As shown, the tensile strength of the obtained shoulder sleeve patch is 5.5 MPa.

[0080] Example 2

[0081] This embodiment provides a composite rotator cuff patch, the preparation method of which includes the following steps:

[0082] (1) Silk fibroin with a mass fraction of 4% was prepared by dissolving it in hexafluoroisopropanol solution to obtain structural layer gel. The gel was placed in a vacuum drying oven and dried at 30°C to obtain structural layer patch.

[0083] (2) Place the structural layer patch into a hot press and hot press it at 120°C for 60 min, with the pressure controlled at 0.8 MPa, to obtain a thermally cross-linked sheet;

[0084] (3) Cool the thermally cross-linked sheet to room temperature to obtain a high-strength structural layer with a thickness of 0.3 mm and a pore size of 20-35 μm.

[0085] (4) Dissolve gelatin slowly in warm water to obtain 2wt% biolayer gel;

[0086] (5) The biolayer gel is laid on the structural layer obtained in step (3) to obtain the biolayer. The biolayer gel has a thickness of 0.1 mm and a pore size of 120-200 μm.

[0087] (6) Alternately stack structural layers and biological layers to prepare a 6-layer composite unit with a total thickness of 1.2 mm;

[0088] (7) The composite unit was freeze-dried at -20℃ for 10 h to obtain a high tensile strength composite shoulder sleeve patch. The tensile strength of the obtained shoulder sleeve patch was 8.0 MPa.

[0089] Example 3

[0090] This embodiment provides a composite rotator cuff patch, the preparation method of which includes the following steps:

[0091] (1) A 6 wt% structural layer gel was prepared by dissolving collagen fibers and hydroxyapatite in a 5:1 ratio using a 0.5% acetic acid solution. The gel was placed in a vacuum drying oven and dried at 25°C to obtain a structural layer patch.

[0092] (2) Place the structural layer patch into a hot press and hot press it at 130°C for 50 min, with the pressure controlled at 1.0 MPa, to obtain a thermally cross-linked sheet;

[0093] (3) Cool the thermally cross-linked sheet to room temperature to obtain a high-strength structural layer with a thickness of 0.2 mm and a pore size of 25~40 μm;

[0094] (4) Collagen was dissolved in 0.5% acetic acid solution to obtain 2 wt% biolayer gel;

[0095] (5) The biolayer gel is laid on the structural layer obtained in step (3) to obtain the biolayer. The biolayer gel has a thickness of 0.4 mm and a pore size of 85~176 μm.

[0096] (6) By alternating the structural layer and the biological layer, an 8-layer composite unit was prepared with a total thickness of 2.4 mm;

[0097] (7) The composite unit was freeze-dried at -20℃ for 12 h to obtain a high tensile strength composite rotator cuff patch. The scanning electron microscope cross-sectional image of the composite rotator cuff patch structure is shown below. Figure 3 As shown in the diagram, the composite shoulder and sleeve patch has the following appearance. Figure 4 As shown, the tensile strength of the obtained shoulder sleeve patch is 8.5 MPa.

[0098] Example 4

[0099] This embodiment provides a composite rotator cuff patch, the preparation method of which includes the following steps:

[0100] (1) Collagen with a mass fraction of 3% was prepared by dissolving it in 0.5% acetic acid solution to obtain structural layer gel. The gel was placed in a vacuum drying oven and dried at 30°C to obtain structural layer patch.

[0101] (2) Place the structural layer patch into a hot press and hot press it at 115°C for 50 min, with the pressure controlled at 0.8 MPa, to obtain a thermally cross-linked sheet;

[0102] (3) Cool the thermally cross-linked sheet to room temperature to obtain a high-strength structural layer with a thickness of 0.2 mm and a pore size of 32~50 μm.

[0103] (4) First, dissolve the gelatin in water to prepare 6% gelatin, then dissolve it in 0.1 M sodium hydroxide solution to prepare 6% sodium hyaluronate gel, and then mix the two in a mass ratio of 1:1 to obtain a biolayer gel with a total mass fraction of 3%.

[0104] (5) The biolayer gel is laid on the structural layer obtained in step (3) to obtain the biolayer. The biolayer gel has a thickness of 0.3 mm and a pore size of 135~190 μm.

[0105] (6) Alternately stack structural layers and biological layers to prepare a 6-layer composite unit with a total thickness of 1.5 mm;

[0106] (7) The composite unit was freeze-dried at -10℃ for 11 h to obtain a high tensile strength shoulder sleeve patch. The tensile strength of the obtained shoulder sleeve patch was 6.5 MPa.

[0107] Example 5

[0108] This embodiment provides a composite rotator cuff patch, the preparation method of which includes the following steps:

[0109] (1) Dissolve and prepare collagen fibers with a mass fraction of 5% to obtain structural layer gel, place it in a vacuum drying oven and dry it at 25°C to obtain structural layer patch.

[0110] (2) Place the structural layer patch into a hot press and hot press it at 120°C for 40 min, with the pressure controlled at 0.9 MPa, to obtain a thermally cross-linked sheet;

[0111] (3) Cool the thermally cross-linked sheet to room temperature to obtain a high-strength structural layer with a thickness of 0.13 mm and a pore size of 28~45 μm.

[0112] (4) Prepare a biolayer gel with a total mass fraction of 2wt% by dissolving chitosan and collagen fibers in a 1:1 mass ratio using a 0.5% acetic acid solution;

[0113] (5) The biolayer gel is laid on the structural layer obtained in step (3) to obtain the biolayer. The biolayer gel has a thickness of 0.2 mm and a pore size of 105~200 μm.

[0114] (6) Alternately stack structural layers and biological layers to prepare a 6-layer composite unit with a total thickness of 0.99 mm;

[0115] (7) The composite unit was freeze-dried at -15℃ for 20 h to obtain a high tensile strength rotator cuff patch. The tensile strength of the obtained rotator cuff patch was 9.0 MPa. The fracture strength test diagram of the composite rotator cuff patch is shown below. Figure 5 As shown.

[0116] Example 6

[0117] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that step (1) prepares collagen fibers with a mass fraction of 0.5%.

[0118] Example 7

[0119] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that step (1) prepares collagen fibers with a mass fraction of 1%.

[0120] Example 8

[0121] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that step (1) prepares collagen fibers with a mass fraction of 6%.

[0122] Example 9

[0123] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that collagen fibers with a mass fraction of 6.5% are prepared in step (1).

[0124] Example 10

[0125] This embodiment provides a composite shoulder and cuff patch, which differs from Example 1 only in that the pressure is controlled at 0.3 MPa in step (2).

[0126] Example 11

[0127] This embodiment provides a composite shoulder and cuff patch, which differs from Example 1 only in that the pressure is controlled at 1 MPa in step (2).

[0128] Example 12

[0129] This embodiment provides a composite shoulder and cuff patch, which differs from Example 1 only in that the pressure is controlled at 1.2 MPa in step (2).

[0130] Example 13

[0131] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that the hot pressing temperature in step (2) is 90°C.

[0132] Example 14

[0133] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that the hot pressing temperature in step (2) is 130°C.

[0134] Example 15

[0135] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that the hot pressing temperature in step (2) is 140°C.

[0136] Example 16

[0137] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that the hot pressing time in step (2) is 25 min.

[0138] Example 17

[0139] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that the hot pressing time in step (2) is 30 min.

[0140] Example 18

[0141] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that the hot pressing time in step (2) is 60 min.

[0142] Example 19

[0143] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that the hot pressing time in step (2) is 65 min.

[0144] Example 20

[0145] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that step (4) prepares collagen fibers with a mass fraction of 0.4%.

[0146] Example 21

[0147] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that step (4) prepares collagen fibers with a mass fraction of 0.5%.

[0148] Example 22

[0149] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that step (4) prepares collagen fibers with a mass fraction of 4%.

[0150] Example 23

[0151] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 1 only in that collagen fibers with a mass fraction of 4.1% are prepared in step (4).

[0152] Example 24

[0153] This embodiment provides a composite shoulder and cuff patch, which differs from Example 1 only in that a 3-layer composite unit (structural layer → biological layer → structural layer) is prepared in step (6).

[0154] Example 25

[0155] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 3 only in that hydroxyapatite is replaced with an equal amount of collagen fibers in step (1).

[0156] Example 26

[0157] This embodiment provides a composite shoulder and sleeve patch, which differs from Example 4 only in that hyaluronic acid is replaced with an equal amount of gelatin in step (4).

[0158] Test case

[0159] The composite shoulder and cuff patches prepared in each embodiment were tested and analyzed.

[0160] (1) Tensile strength and pore size determination

[0161] The tensile strength, pore size, and porosity of the composite rotator cuff patch are shown in Table 1. It can be seen that the high tensile strength composite rotator cuff patch designed and prepared by the present invention has different pore sizes and porosities in the alternating superimposed structural layers and biological layers, forming a gradient distribution. The large pores are conducive to stress dispersion, and the micropores are conducive to the directional migration of cells. At the same time, it meets the needs of mechanical support and cell migration, which is beneficial to tendon regeneration.

[0162] Table 1

[0163]

[0164] Furthermore, the results of Examples 1 and 6-9 show that by controlling the mass percentage of the structural layer material in the specific structural layer gel, the present invention can effectively control the porosity of the structural layer while meeting the requirements of mechanical support and cell growth. The results of Examples 1 and 10-12 show that by controlling the pressure of the specific hot-pressing treatment, the present invention can effectively control the porosity of the structural layer while meeting the requirements of mechanical support and cell growth. The results of Examples 1 and 13-15 show that by controlling the temperature of the specific hot-pressing treatment, the present invention can prepare an effective structural layer; if the temperature is too low, the cross-linking effect is insufficient, and if the temperature is too high, the material will denature. The results of Examples 1 and 16-19 show that by controlling the time of the specific hot-pressing treatment, the present invention can prepare an effective structural layer. Too short a time interval prevents the formation of effective cross-linking bonds, while too long a time increases time costs, and excessively increasing the time under suitable temperature and pressure can cause material denaturation. As shown in Examples 1 and 20-23, controlling the mass percentage of the biolayer material in the biolayer gel in this invention is beneficial for obtaining a biolayer with the target porosity and tensile strength. As shown in Examples 1 and 24, controlling a specific multilayer alternating stacked structure in this invention enables the composite shoulder and sleeve patch to possess suitable tensile strength. As shown in Examples 3 and 25, adding hydroxyapatite to the structural layer in this invention can further improve the tensile strength of the structural layer. As shown in Examples 4 and 26, adding hyaluronic acid to the biolayer in this invention is more conducive to preparing a biolayer with high porosity.

[0165] (2) Performance test of composite shoulder and cuff patch:

[0166] I. Animal Model Establishment: New Zealand rabbits were selected as experimental animals and anesthetized via intravenous injection of 3% sodium pentobarbital (30 mg / kg) via the ear. The rabbits were fixed on the operating table, and hair on the right shoulder was removed with a depilatory agent. A 3-4 cm incision was made along the lateral aspect of the acromion, and the skin, subcutaneous tissue, and fascia were dissected layer by layer to expose the insertion point of the supraspinatus tendon. The supraspinatus tendon insertion point was severed with a scalpel, causing an injury of approximately 2 mm.

[0167] II. Composite Rotator Cuff Patch Implantation: Using the composite patch prepared in Example 3 as an example, the patch was sutured and fixed to the surrounding healthy tissue with non-absorbable sutures. Finally, the fascia, subcutaneous tissue, and skin were sutured layer by layer, the incision was disinfected with iodine, and bandaged.

[0168] III: Tendon Repair Performance Test

[0169] a. Degradation cycle test: Image analysis was used to measure the residual area of ​​the patch using software, calculate the residual rate (residual area / initial area × 100%), and evaluate the degradation rate. The results showed that the complete degradation time of the rotator cuff patch was about 6 months.

[0170] b. Biocompatibility test: Through gross observation and histological analysis, no adverse reactions such as foreign body reaction, fibrosis, or abscess were observed around the composite patch, indicating good compatibility with autologous tendon tissue.

[0171] c. Tendon repair capacity test: 8 weeks post-surgery, no wound infection was observed, and the implanted composite rotator cuff patch was encapsulated by new tissue. The healed New Zealand rabbit supraspinatus tendon was removed, and its maximum tensile strength was tested to be 185 N. Figure 6 The normal tensile strength of the supraspinatus tendon in rabbits is 220-270N. After 8 weeks, the tendon healing strength is close to the normal strength of the tendon, indicating that the multilayer composite rotator cuff patch prepared using bio-based materials has a significant repair effect. It can prevent the tendon from tearing again during the healing process by providing additional mechanical support, and promote the generation of new tendons by promoting the proliferation and differentiation of fibroblasts.

[0172] In summary, this invention provides a high-mechanical-strength composite rotator cuff patch and its preparation method. The structural layer and biological layer are made of fully biomedical materials. Through the alternating composite design of thermally cross-linked sheets and gel layers, the tear resistance and mechanical support of the patch are significantly improved, avoiding the problems of non-degradability or short degradation cycles of traditional synthetic materials. This effectively reduces the risk of inflammatory reactions and improves the biocompatibility and safety of the patch. Furthermore, the porosity and pore size are designed to meet the requirements of both mechanical support and cell migration. The thermal cross-linking physical bonding process eliminates the need for chemical cross-linking agents, avoiding the cytotoxic risks that may be caused by chemical additives such as glutaraldehyde, further improving the biocompatibility and safety of the patch.

[0173] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A composite rotator cuff patch, characterized in that, The composite shoulder and cuff patch comprises alternating structural layers and biological layers; The structural layer is made of at least one of collagen, gelatin, collagen fibers, or silk fibroin; and the structural layer is prepared by hot pressing the material of the structural layer. The material of the biolayer includes at least one of collagen, gelatin, chitosan, or silk fibroin; The structural layer and the biological layer have a porous structure; The pore size of the structural layer is 10~50 μm; the porosity of the structural layer is 30%~50%. The pore size of the biolayer is 50~200 μm; the porosity of the biolayer is 50%~90%; Furthermore, the porosity of the biological layer is greater than that of the structural layer, and the pore size of the biological layer is greater than that of the structural layer. The structural layer and the biological layer are obtained by the following method: dissolving the material of the structural layer to obtain a structural layer gel, drying the structural layer gel to obtain a structural layer patch, hot-pressing the structural layer patch and cooling it to obtain the structural layer; dissolving the material of the biological layer to obtain a biological layer gel, and laying the biological layer gel on the structural layer to form the biological layer.

2. The composite rotator cuff patch of claim 1, wherein, The structural layer material also includes hydroxyapatite.

3. The composite rotator cuff patch of claim 1, wherein, The biolayer material also includes hyaluronic acid and / or sodium alginate.

4. The composite rotator cuff patch of claim 1, wherein, The total number of structural and biological layers is 4 to 8.

5. The composite rotator cuff patch of claim 1, wherein, The thickness of the composite shoulder and sleeve patch is 0.6~3.0 mm.

6. A method of preparing the composite rotator cuff patch of any one of claims 1-5, wherein, The preparation method includes: The material of the structural layer is hot-pressed to obtain the structural layer. The material of the biological layer is then laid on the structural layer to form the biological layer. The structural layer and the biological layer are alternately stacked to obtain the composite shoulder and sleeve patch.

7. The method for preparing the composite shoulder and cuff patch according to claim 6, characterized in that, The hot pressing treatment is performed at a temperature of 110~130℃ for 30~60 min and a pressure of 0.5~1 MPa.

8. The method of claim 6, wherein the composite rotator cuff patch is prepared by, The biolayer gel contains 0.5 to 4 wt% of the biolayer material, and / or the structural layer gel contains 1 to 6 wt% of the structural layer material.

9. The use of the composite rotator cuff patch according to any one of claims 1-5 in the preparation of products for rotator cuff repair surgery.

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