High-strength collagen rotator cuff patch and method of making same

Abstract

The application discloses a high-strength collagen shoulder muscle repair patch and a preparation method thereof, and adopts an acid enzymolysis method to treat animal tissues, and high-purity type I collagen protein fibers are extracted through variable-speed stirring; the collagen protein solution is prepared into a single-layer sample with a thickness of 1-10 mm through gradient freeze-drying; the single-layer sample is placed in a salt solution for physical crosslinking, the strength of the collagen film is enhanced through ionic electrostatic interaction and hydrogen bond, and no chemical crosslinking agent is introduced; after washing, the single-layer sample is dried again, and finally, a plurality of single-layer samples are laminated under specific humidity and normal temperature to obtain a multilayer composite patch. The shoulder muscle repair patch prepared by the application completely retains the natural triple-helix conformation and biological activity of the collagen protein, has no chemical reagent residue, has a tensile strength of 207 N, a suture strength of 7.8 N, has a good pore structure to promote cell adhesion and tissue regeneration, has excellent biocompatibility, can be completely degraded and absorbed, and is suitable for the repair of load-bearing tendons such as shoulder muscles.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to a high-strength collagen rotator cuff patch and its preparation method. Background Technology

[0002] Tendons are dense connective tissues connecting muscles and bones, with type I collagen making up up to 95% of their extracellular matrix, forming the main mechanical load-bearing structure. However, due to their low cell density and poor blood vessels, tendons have extremely limited self-regenerative and repair capabilities. The tendon repair process after injury often leads to tissue structural disorder, forming scar tissue with significantly reduced mechanical properties, its tensile strength being only about 30% of that of a normal tendon. The incidence of tendon injuries continues to rise, with more than 1.5 million patients worldwide undergoing repair surgery annually for tendon and bone injuries such as rotator cuff and cruciate ligament injuries. This huge clinical demand has made the development of tendon repair materials a key focus in the field of tissue engineering.

[0003] Surgical repair remains the mainstream treatment for tendon injuries, but high re-tear rates and poor functional recovery remain core challenges in clinical practice. Patch-enhanced repair strategies, which provide mechanical support by covering the suture site with a patch, have been proven to strengthen the repaired area and improve healing outcomes. Currently, clinically used patches are mainly divided into two categories: synthetic polymer materials and bio-based materials. Synthetic polymer materials (such as polylactic acid and polycaprolactone) have good mechanical strength, but poor biocompatibility, and their degradation products may trigger inflammatory reactions. Bio-based materials (such as autologous or allogeneic tissue-derived materials) have good biocompatibility, but suffer from limited availability and insufficient mechanical strength.

[0004] Collagen-based repair materials have become a research hotspot due to their excellent biocompatibility and low immunogenicity. Various collagen patches or their preparation methods have been disclosed in existing technologies. For example, Chinese patent application CN202210860210.2 discloses a three-layer composite collagen-based artificial skin, which prepares a collagen membrane layer and a collagen sponge layer using a gradient temperature freeze-drying method and performs chemical cross-linking using EDC / NHS. However, this technology uses a chemical cross-linking agent, posing a risk of cytotoxicity from residual cross-linking agent, and its tensile strength is only 50.78 kPa, far from meeting the mechanical strength requirements for tendon repair. Another example is Chinese patent application CN202511666661.2, which discloses a composite rotator cuff patch that forms a porous structure by alternately stacking structural layers (hot-pressing) and biological layers (gel), avoiding chemical cross-linking agents. However, its hot-pressing temperature (110-130℃) may cause partial denaturation of collagen, thus losing the repair function of collagen.

[0005] In addition, the preparation of rotator cuff patches using electrospinning technology has also been reported. For example, Chinese patent application CN202310077942.9 discloses a rotator cuff patch containing exosomes, which uses coaxial electrospinning to prepare a core-shell nanofiber membrane, with the core layer encapsulating exosomes to promote healing. However, this process requires the use of organic solvents such as hexafluoroisopropanol, which can easily lead to collagen denaturation, and the source, batch consistency, and long-term safety of exosomes still face challenges. Chinese patent application CN201210457521.0 discloses a fiber membrane for tissue repair, which obtains a fluffy porous structure through electrospinning combined with solvent dissolution or stretching, and can be used for artificial rotator cuffs. However, this technology also relies on organic solvents and synthetic polymer materials (such as polylactic acid, polycaprolactone, polyvinylidene fluoride, etc.), making it difficult to achieve high mechanical strength in a pure collagen system. Chinese patent application CN202080076183.9 discloses a medical device containing poly(butylene succinate) and its copolymers, which has an extended strength retention rate, but is a synthetic polymer material and lacks the cell recognition signals and bioactive microenvironment of natural collagen.

[0006] The current technology faces the following technical problems:

[0007] 1) Although collagen patches prepared by freeze-drying have high porosity and good cell infiltration, their mechanical strength is generally low and their tensile and tear resistance is poor, which cannot meet the long-term mechanical support required for tendon repair.

[0008] 2) Chemical cross-linking methods (such as EDC / NHS) can enhance the mechanical properties of collagen, but they can also irreversibly damage the natural triple helix structure of collagen, leading to a significant decrease in bioactivity. Furthermore, the residues of cross-linking agents have potential cytotoxicity, affecting the biosafety of the patch.

[0009] 3) Collagen patches prepared by electrospinning, to compensate for the insufficient mechanical properties of pure collagen, usually need to be blended or co-spun with synthetic polymers (such as polylactic acid, polycaprolactone, polyurethane, etc.) to form multi-component composite patches. Organic solvent residues, collagen's susceptibility to denaturation, and uncontrollable degradation behavior are all problems.

[0010] 4) The preparation of multilayer patches involves biological and structural layers. Although chemical cross-linking agents are avoided, the hot pressing temperature (110-130℃) may cause partial denaturation of collagen, thereby losing the repair function of collagen.

[0011] Therefore, developing a method for preparing rotator cuff patches that can preserve the natural triple helix structure of collagen, leave no chemical residues, and achieve high mechanical strength (especially the tensile and suture strength required for rotator cuff repair) is of great clinical significance. Summary of the Invention

[0012] The purpose of this invention is to provide a high-strength collagen rotator cuff patch and its preparation method, thereby solving the problems of easy damage to the triple helix structure and biosafety hazards caused by residual chemical cross-linking agents during the preparation of collagen patches in the prior art. This invention is achieved through the following technical solution:

[0013] This invention discloses a method for preparing a high-strength collagen rotator cuff patch, comprising the following steps:

[0014] S1: Animal tissues were treated with acid enzymatic hydrolysis, and collagen was extracted by controlling the stirring speed during digestion. A self-assembled collagen solution was then prepared using self-assembly technology.

[0015] S2: A gradient freeze-drying process is used to prepare a collagen membrane from the self-assembled collagen solution. The thickness of the collagen membrane is 1~10mm.

[0016] S3: The prepared collagen membrane is immersed in a salt solution for cross-linking, washed after physical cross-linking, and then dried again;

[0017] S4: Using a pressing process, multiple physically cross-linked collagen membranes are pressed into an independent patch to obtain the final high-strength collagen shoulder and cuff patch.

[0018] As a further improvement, in step S1 of the present invention, the enzyme used in the acid enzymatic hydrolysis method is pepsin, and the acid used is acetic acid; the stirring speed in the digestion method is controlled at high speed of 100~500 rpm first, and then at low speed of 10~40 rpm, and the collagen is type I collagen with a collagen purity of 90%~99.9%.

[0019] As a further improvement, in step S2 of the present invention, the gradient vacuum drying process specifically includes: a first stage of pre-freezing at -80℃ to -40℃ for 5 to 6 hours; a second stage of gradually increasing the temperature at -40℃ to 0℃ for 24 to 48 hours; and a third stage of maintaining the temperature at 20 to 30℃ for 1 to 4 hours, resulting in a drying weight loss of 2 to 15% for the obtained sample.

[0020] As a further improvement, in step S3 of the present invention, the salt contained in the salt-containing solution is selected from one or more of the following salts: sodium chloride, potassium chloride, calcium chloride, sodium sulfate, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium acetate, calcium acetate, sodium citrate, calcium citrate, sodium bicarbonate, and sodium carbonate, and the salt concentration of the salt-containing solution is 0.5~2M.

[0021] As a further improvement, the specific steps of washing after physical cross-linking in this invention are as follows: after physical cross-linking, the collagen membrane is washed with 0.9% physiological saline to remove excess salt ions, thus obtaining a physically cross-linked collagen membrane; in step S3, physical cross-linking enhances the strength of the collagen membrane through physical interactions such as electrostatic interactions and hydrogen bonds between ions in the salt solution and the side chain groups of collagen molecules, preserving the natural triple helix structure of collagen, and leaving no chemical residue.

[0022] As a further improvement, in step S4 of the present invention, the temperature of the pressing process is 20-40°C, the ambient humidity is required to be 40-80%, the pressure is 2-10 MPa, and the pressing time is 120-360 minutes to ensure that the collagen does not undergo thermal denaturation.

[0023] As a further improvement, the pressing process described in this invention has a temperature of 25-30°C and an ambient humidity requirement of 50-70%.

[0024] The present invention also discloses a high-strength collagen rotator cuff patch prepared by the preparation method of the present invention. The patch is made of one or more layers of collagen membrane laminated together. Its elongation at break is 6-30%, its tensile strength is 10-210N, and its suture strength is 1-8N. This allows the patch to undergo elastic deformation along the tendon axis while maintaining structural integrity, thereby adapting to the dynamic mechanical environment of tendons in different locations.

[0025] Based on this, compared with the prior art, the present invention has the following beneficial effects:

[0026] (1) This invention proposes for the first time a method for preparing high-strength collagen shoulder and sleeve patches by "physical cross-linking + compression molding". It forms a complete technical solution from material selection and structural design to molding process, and solves the contradiction between "preserving the natural structure" and "obtaining high strength" that has long existed in the prior art. Its core innovations are: ① Abandoning the conventional path of chemical cross-linking and synthetic polymer complexes, it uses only pure collagen as raw material and physically cross-links the monolayer collagen membrane through a salt solution to form a dense physical cross-linking network, perfectly preserving the triple helix conformation and bioactivity of collagen; ② Introducing a gradient freeze-drying process, controlling the pre-freezing temperature and the stepwise heating curve. The first stage is at -80℃ to -40℃ for 5 to 6 hours; the second stage is at -40℃ to 0℃, with stepwise heating and a holding time of 24 to 48 hours; the third stage is at 20 to 30℃ for 1 to 4 hours, forming a microporous network structure with uniform pore size (100 to 200 μm) and high interconnection inside the collagen membrane, providing a favorable microenvironment for cell ingrowth and tissue regeneration; ③ The multilayer collagen membrane does not rely on adhesives or chemical cross-linking for interlayer bonding. It achieves the one-time compression molding of the multilayer collagen membrane purely through physical pressure, without the introduction of any foreign substances. By adjusting parameters such as salt type (e.g., potassium chloride, calcium chloride, sodium sulfate, disodium hydrogen phosphate, etc.) / concentration (e.g., 0.5~2M), number of layers, and pressure (2-10MPa), the mechanical properties of the patch can be precisely controlled (tensile strength can reach over 207.15 N, significantly higher than the approximately 90 N reported in previous studies), while retaining the microporous structure (pore size 100~200 μm, highly interconnected) that facilitates cell ingrowth.

[0027] (2) This invention uses pure collagen throughout the process and does not add synthetic polymers such as polylactic acid, polycaprolactone, and poly(butylene succinate) (CN202080076183.9, CN202310077942.9, and CN201210457521.0 all rely on synthetic polymers or organic solvents), thus avoiding the risk of inflammatory reactions caused by degradation products of synthetic materials and collagen denaturation caused by residual organic solvents, and thus has higher biosafety.

[0028] (3) This invention innovatively employs a salt solution to physically crosslink the collagen membrane. The core mechanism lies in the fact that the anions and cations in the salt solution effectively shield the electrostatic repulsion between the oppositely charged amino and carboxyl groups on the collagen molecular chain. Simultaneously, through ion bridging and enhanced hydrogen bonding, it promotes the formation of a denser and more ordered physical crosslinking network between collagen molecules. This treatment method is fundamentally different from the chemical crosslinking in existing technologies (EDC / NHS in CN202210860210.2). It does not form new covalent bonds, does not introduce any exogenous chemical substances, thus perfectly preserving the natural triple helix conformation of collagen and its inherent biological activity. Furthermore, excess salt ions can be removed with simple washing, leaving no cytotoxic residues and exhibiting extremely high biosafety.

[0029] (4) The gradient freeze-drying process used in this invention, through precise control of the pre-freezing temperature and the stepwise heating curve, involves pre-freezing at -80℃ to -40℃ for 5 to 6 hours in the first stage; gradually heating at -40℃ to 0℃ for 24 to 48 hours in the second stage; and gradually heating at 20 to 30℃ for 1 to 4 hours in the third stage, forming a highly interconnected microporous network structure with uniform pore size (100-200 μm). This microporous network structure provides strong support for cell migration and adhesion, enhancing tissue regeneration.

[0030] (5) When pressed under humidity of 40%-80% and temperature of 20-40℃, the multilayer collagen membranes are firmly bonded through the "pore-fiber" interlocking mechanism, which is far superior to the composite method that relies on adhesives or simple hot pressing. The tensile strength of the final patch reaches 207.15N, which is significantly higher than the composite rotator cuff patch (about 90N) reported in CN202511666661.2 and the artificial skin (about 0.05 MPa) reported in CN202210860210. At the same time, the microporous structure that facilitates cell ingrowth is retained, realizing the unity of mechanical and biological properties, and effectively preserving the natural triple helix conformation and biological activity of collagen.

[0031] (5) Cytotoxicity test ( Figure 5 This study confirmed that the patch of the present invention exhibits grade 1 cytotoxicity and good biocompatibility. Cell adhesion assay (…) Figure 4 The results showed that cells could adhere well and grow on the surface and in the pores of the patch, indicating that it can provide a favorable microenvironment for tissue regeneration. In vitro degradation experiments ( Figure 6 This study confirmed that the patch can be degraded by collagenase and eventually completely absorbed, avoiding the need for secondary surgery and achieving true tissue functional repair.

[0032] (6) This method does not require complex electrospinning equipment (CN202310077942.9, CN201210457521.0), 3D printing equipment (CN202511666661.2) or chemical crosslinking agent (CN202210860210.9). The process is short, the batch consistency is good, it is suitable for industrial production, and has good industrialization prospects. Attached Figure Description

[0033] Figure 1 This is a tensile strength curve of the high-strength collagen patch in Example 8;

[0034] Figure 2 This is a suture strength curve of the high-strength collagen patch in Example 8;

[0035] Figure 3 The images show the micropore structure (left) and pore wall structure (right) of the high-strength collagen patch in Example 1 using scanning electron microscopy.

[0036] Figure 4 This is a microscopic image of cell adhesion fluorescence staining in the high-strength collagen patch from Example 1;

[0037] Figure 5 This is a graph showing the relative proliferation rate of cells in the high-strength collagen patch from Example 1.

[0038] Figure 6 This is an in vitro degradation curve of the high-strength collagen patch in Example 1. Detailed Implementation

[0039] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are merely illustrative of the present invention and are not intended to limit the scope of the present invention. The scope of protection of the present invention shall be determined by the appended claims.

[0040] The following detailed description of some embodiments of the present invention is provided in conjunction with the accompanying drawings. Unless otherwise specified, the following embodiments and features can be combined with each other.

[0041] Example 1

[0042] This embodiment provides the preparation of a single-layer high-strength collagen rotator cuff patch, and the specific steps are as follows:

[0043] 1.1 Preparation of Collagen Solution

[0044] First, the bovine Achilles tendon was cleaned and placed in an acidic enzymatic hydrolysis solution. The stirring speed was set to 100 rpm and the stirring time to 24 hours. Then, the stirring speed was adjusted to 10 rpm and the stirring time to 40 hours. After salting out and dialysis, a 0.8% collagen solution was obtained.

[0045] 1.2 Freeze-drying

[0046] Pour a certain amount of collagen solution into a freeze-drying pan and pre-freeze at -80℃ for 5-6 hours; in the second stage, gradually increase the temperature from -40℃ to 0℃ and hold for 24-48 hours; in the third stage, hold at 30℃ for 1-4 hours.

[0047] 1.3 Crosslinking

[0048] The freeze-dried intermediate was immersed in a 2M phosphate solution. The salt-crosslinked sample was then removed and immersed in PBS buffer. After stirring at low speed for 10-30 minutes, it was transferred to a freeze-drying tray, and the freeze-drying steps in 1.2 were repeated. The resulting physically crosslinked collagen membrane had a thickness of 10 mm.

[0049] 1.4 Pressing process

[0050] The humidity of the pressing environment is set to 60-70%. The cross-linked freeze-dried monolayer collagen membrane is placed on the pressing equipment, and the pressure parameter is set to 10MPa and the holding time is set to 360 minutes.

[0051] Example 2

[0052] This embodiment provides a high-strength collagen shoulder and cuff patch. The preparation method of this patch differs from that of Embodiment 1 in that, in step 1.1, it is placed in an acidic enzymatic hydrolysate, the stirring speed is set to 500 rpm, the stirring time is set to 24 hours, and the stirring speed is adjusted to 40 rpm.

[0053] Example 3

[0054] This embodiment provides a high-strength collagen shoulder and cuff patch. The difference between its preparation method and that of Embodiment 1 is that the pre-freezing temperature in step 1.2 is -40℃.

[0055] Example 4

[0056] This embodiment provides a high-strength collagen shoulder and cuff patch, the preparation method of which differs from that of Example 1 in that sodium chloride is used as the salt in step 1.3.

[0057] Example 5

[0058] This embodiment provides a high-strength collagen shoulder and cuff patch. The difference between its preparation method and that of Embodiment 1 is that, in step 1.4, the pressure holding time is 120 minutes.

[0059] Example 6

[0060] This embodiment provides a high-strength collagen rotator cuff patch. The difference between its preparation method and that of Embodiment 1 is that, in step 1.4, the pressure parameter is set to 2 MPa.

[0061] Example 7

[0062] This embodiment provides a high-strength collagen shoulder and cuff patch. The difference between its preparation method and that of Embodiment 1 is that, in step 1.4, the cross-linked freeze-dried double-layer collagen membrane is placed on a pressing device.

[0063] Example 8

[0064] This embodiment provides a high-strength collagen shoulder and cuff patch. The difference between its preparation method and that of Embodiment 1 is that, in step 1.4, the cross-linked freeze-dried multilayer collagen film is placed on a pressing device.

[0065] Comparative Example 1

[0066] Unlike Example 1, the pressing process in step 1.4 is not performed.

[0067] Comparative Example 2

[0068] Unlike Example 1, the crosslinking in step 1.3 is not performed.

[0069] Comparative Example 3

[0070] Unlike Example 1, in step 1.2, gradient freeze-drying is not performed; the entire process is freeze-dried at -40°C.

[0071] Comparative Example 4

[0072] Unlike Example 1, in step 1.1, the digestion method of adjusting the stirring speed uses a stirring speed of 500 rpm throughout the digestion process.

[0073] Verification 1

[0074] The tensile strength and stitching strength of the shoulder and cuff patches obtained in Examples 1-6 and Comparative Example 1 were tested according to standards GB / T3923.1 and YY / T 1788. The test results are shown in Table 1. The data for Example 8 are as follows: Figure 1 , 2 Demonstration. Test results showed that the mechanical properties of the cross-linked patch were significantly improved compared to the pure collagen patch.

[0075] Table 1. Mechanical property test results of the patches in each embodiment.

[0076]

[0077] Verification 2

[0078] The high-strength collagen rotator cuff patch prepared using the method in Example 1 has a clean, white appearance. The patch exhibits a porous structure with high pore connectivity and a pore size of approximately 100-200 μm. Furthermore, cross-linking results in denser pore walls, providing the patch with higher strength. (See [link to example]). Figure 3 .

[0079] Verification 3

[0080] Simultaneously, the highly porous collagen rotator cuff patch should possess excellent cell adhesion-promoting ability. The sample prepared in Example 8 was cut into 1cm × 1cm pieces and fully swollen using complete culture medium. The swollen patch was transferred to a 24-well plate, and 293T cells were seeded onto the patch. After incubation at 37°C and 5% CO2 for 24 hours, the cells were stained with calcein and observed under a fluorescence inverted microscope. (See [link to relevant documentation]). Figure 4 The image shows a large number of cells (green dots) migrating into the patch.

[0081] Verification 4

[0082] Meanwhile, cytotoxicity testing was performed according to GB / T 16886.5, and the results are as follows: the relative cell proliferation rate of the test sample is, for example... Figure 5 As shown in Table 2, the relative cell proliferation rates of the different concentrations of test solution groups were 102.5%, 100.9%, 98.0%, and 100.9% respectively. Therefore, the cytotoxicity of the sample was grade 1, indicating that the sample did not have cytotoxicity.

[0083] Table 2 Survival Rate Results

[0084]

[0085] Verification 5

[0086] In vitro degradation assay: Preparation of degradation solution: Phosphate buffer was used to simulate the degradation environment in the human body. 8.0g NaCl, 0.2g KH2PO4, 1.56g Na2HPO4·H2O, and 0.2g KCl were weighed in sequence to prepare phosphate buffer. Collagenase was added to the phosphate buffer at a concentration of 1U / mL. After thorough stirring, the volume was adjusted to 1000ml for testing.

[0087] The sample was cut into 4×3cm strips, weighed, and placed in a stoppered conical flask. The prepared degradation solution was added until the strips were submerged. The flask was then placed in a 37°C constant temperature shaking incubator. Samples were taken at regular intervals, freeze-dried, and weighed. The mass loss rate of the patch was calculated based on the mass change before and after degradation. See [link to relevant documentation]. Figure 6Experimental results show that as the degradation time increases, the mass loss rate of the patch gradually increases, eventually achieving complete degradation (mass loss rate of over 95%), indicating that the collagen rotator cuff patch prepared in this invention has good biodegradability.

[0088] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the collagen shoulder and cuff patch of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions described in the foregoing embodiments, and such modifications or substitutions do not depart from the essence of the technical solutions of the present invention. The above embodiments are only descriptions of preferred embodiments of the present invention, and are not intended to limit the scope of the present invention. Any modifications and improvements without departing from the spirit of the present invention fall within the protection scope of the present invention.

Claims

1. A method for preparing a high-strength collagen rotator cuff patch, characterized in that, Includes the following steps: S1: Animal tissues were treated with an acid-enzymatic hydrolysis method, and collagen was extracted by controlling the stirring speed during digestion. A self-assembled collagen solution was then prepared using self-assembly technology. The acid-enzymatic hydrolysis method used pepsin as the enzyme and acetic acid as the acid. The stirring speed in the controlled-speed digestion method was initially high (100-500 rpm) followed by a low speed (10-40 rpm). The collagen was type I collagen with a purity of 90%-99.9%. S2: A gradient freeze-drying process is used to prepare a collagen membrane from the self-assembled collagen solution. The thickness of the collagen membrane is 1-10 mm. The gradient freeze-drying process specifically includes: a first stage of pre-freezing at -80℃ to -40℃ for 5-6 hours; a second stage of gradually increasing the temperature at -40℃ to 0℃ for 24-48 hours; and a third stage of holding at 20-30℃ for 1-4 hours. The resulting sample has a drying weight loss of 2-15%. S3: The prepared collagen membrane is immersed in a salt solution for cross-linking. After physical cross-linking, it is washed to obtain a physically cross-linked collagen membrane, which is then dried again. The salt in the salt solution is selected from one or more of the following: sodium chloride, potassium chloride, calcium chloride, sodium sulfate, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium acetate, calcium acetate, sodium citrate, calcium citrate, sodium bicarbonate, and sodium carbonate. The salt concentration of the salt solution is 0.5~2M. The specific steps for washing after physical cross-linking are as follows: after physical cross-linking, the collagen membrane is washed with 0.9% physiological saline to remove excess salt ions, resulting in a physically cross-linked collagen membrane. In step S3, physical cross-linking enhances the strength of the collagen membrane through electrostatic interactions and hydrogen bonding between ions in the salt solution and the side chain groups of collagen molecules, preserving the natural triple helix structure of collagen without chemical residue. S4: Using a pressing process, multiple physically cross-linked collagen membranes are pressed into an independent patch to obtain the final high-strength collagen shoulder and sleeve patch; the pressing process temperature is 20-40℃, the ambient humidity is 40-80%, the pressure is 2-10MPa, and the pressing time is 120-360 minutes to ensure that the collagen does not undergo thermal denaturation.

2. The method for preparing the high-strength collagen rotator cuff patch according to claim 1, characterized in that, The pressing process requires a temperature of 25–30°C and an ambient humidity of 50–70%.

3. A high-strength collagen rotator cuff patch prepared by the method described in claim 1, characterized in that, The patch is made of one or more layers of collagen membrane laminated together. It has a microporous structure with a pore size of 100-200 μm, which is conducive to cell ingrowth. The elongation at break is 6-30%, the tensile strength is 10-210 N, and the suture strength is 1-8 N. This allows the patch to undergo elastic deformation along the tendon axis while maintaining structural integrity, thereby adapting to the dynamic mechanical environment of tendons in different locations.

Images