Skull repair material and preparation method thereof

Abstract

The present invention relates to the technical field of skull repair materials, and more particularly to a skull repair material and its preparation method. The method comprises: dissolving collagen and a water-soluble polymer compound in a phosphate buffer solution to obtain a prepolymer solution; and subjecting the prepolymer solution to synchrotron radiation treatment to obtain a skull repair material in a hydrogel form. Embodiments of the present invention provide a method for preparing a skull repair material that can provide a skull repair material that prevents excessive intracranial pressure.

Description

Technical Field

[0001] The present invention relates to the technical field of skull repair materials, and in particular to a skull repair material and a preparation method thereof. Background Art

[0002] When the skull defect is large, skull repair materials are needed to repair the skull.

[0003] Most skull repair materials are rigid. Therefore, in clinical practice, large skull defects associated with craniocerebral injury are primarily treated with a two-step approach: craniectomy and cranioplasty. In the early stages of injury, intracranial hemorrhage and brain edema are prone to occur, leading to an increase in intracranial tissue volume. However, the skull is rigid and inelastic, causing a sharp rise in intracranial pressure, resulting in intracranial hypertension. Increased intracranial pressure reduces brain perfusion. When perfusion falls below the minimum required to maintain normal brain function, further ischemic brain damage can occur. Therefore, early craniectomy can reduce intracranial pressure and prevent secondary brain damage caused by intracranial hypertension. Later cranioplasty can be performed 2-6 months later to repair large skull defects. During this period, the soft tissues lack the protection of the skull, making secondary damage more likely. Furthermore, undergoing two surgeries increases the physical, emotional, and financial burden on patients. However, skull defects are prone to secondary intracranial hemorrhage and brain edema, which can increase the volume of intracranial tissue. Using hard materials to repair the skull can lead to excessive intracranial pressure. When intracranial pressure increases, blood perfusion to the brain tissue decreases. When the perfusion blood flow is lower than the minimum value to maintain normal physiological function of the brain tissue, it will further cause ischemic brain damage.

[0004] Therefore, in view of the above shortcomings, a skull repair material and a preparation method thereof are urgently needed. Summary of the Invention

[0005] The embodiment of the present invention provides a skull repair material and a preparation method thereof, which can provide a skull repair material that prevents excessive intracranial pressure.

[0006] In a first aspect, an embodiment of the present invention provides a method for preparing a skull repair material, comprising:

[0007] dissolving collagen and a water-soluble polymer compound in a phosphate buffer solution to obtain a prepolymer solution;

[0008] The prepolymerized solution is subjected to synchrotron radiation treatment to obtain a hydrogel-like skull repair material.

[0009] Preferably, after obtaining the hydrogel-like skull repair material, the method further comprises:

[0010] The skull repair material is freeze-dried to obtain a hydrogel freeze-dried material.

[0011] Preferably, after obtaining the hydrogel freeze-dried material, the method further comprises:

[0012] mixing the hydrogel freeze-dried material with water to swell the hydrogel freeze-dried material to obtain a swollen hydrogel;

[0013] uniformly mixing the swollen hydrogel and mineralized collagen particles to obtain a mineralized hydrogel;

[0014] The mineralized hydrogel is freeze-dried to obtain a mineralized hydrogel freeze-dried material.

[0015] Preferably, the step of uniformly mixing the swollen hydrogel and the mineralized collagen particles comprises:

[0016] The swollen hydrogel and the mineralized collagen particles are uniformly mixed in a mass ratio of 1: (0.2-1).

[0017] Preferably, the particle size of the mineralized collagen particles is 300-500 μm.

[0018] Preferably, the water-soluble polymer compound includes at least one of polyvinyl pyrrolidone and polyethylene glycol.

[0019] Preferably, the water-soluble polymer compound is polyethylene glycol, and in the prepolymerization solution, the concentration of collagen is 0.3-0.4 mg / mL, and the concentration of the polyethylene glycol is 45-55 mg / mL.

[0020] Preferably, the water-soluble polymer compound is polyvinyl pyrrolidone, and in the prepolymerization solution, the concentration of collagen is 0.3-0.4 mg / mL, and the concentration of polyvinyl pyrrolidone is 20-30 mg / mL.

[0021] Preferably, the water-soluble polymer compound is polyethylene glycol and polyvinyl pyrrolidone. In the prepolymerization solution, the concentration of collagen is 0.3-0.4 mg / mL, the concentration of polyethylene glycol is 25-75 mg / mL, and the concentration of polyvinyl pyrrolidone is 50-150 mg / mL.

[0022] In a second aspect, a skull repair material is prepared according to any one of the preparation methods described in the first aspect.

[0023] Compared with the prior art, the present invention has at least the following beneficial effects:

[0024] In this embodiment, collagen and a water-soluble polymer compound are dissolved in a phosphate buffer solution to obtain a prepolymer solution, and the prepolymer solution is subjected to synchrotron radiation treatment to crosslink the collagen and the water-soluble polymer to obtain a hydrogel-like skull repair material. The hydrogel-like skull repair material has a high water content, good permeability, and strong adaptability. The hydrogel is also elastic and can undergo a certain degree of stretching under intracranial pressure, thereby being able to adapt to different intracranial pressures. A certain degree of stretching can prevent excessive intracranial pressure. Therefore, the hydrogel-like skull repair material provided by the present invention can repair skull damage in one go. The collagen in the skull repair material has excellent biocompatibility, collagen can promote skull repair, and improve the efficiency of skull repair. The synchrotron radiation method can crosslink collagen and water-soluble polymer compounds at room temperature without the need for crosslinking agents or initiators, and monomers remain after crosslinking. In addition, during the preparation process of the radiation-synthesized hydrogel, high-energy rays can not only trigger the crosslinking reaction but also have a sterilizing effect, without the need to add preservatives. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0026] Figure 1a This is an infrared spectrum of a skull repair material provided by an embodiment of the present invention;

[0027] Figure 1b This is an infrared spectrum of another skull repair material provided by an embodiment of the present invention;

[0028] Figure 2 is a swelling rate curve diagram of a skull repair material provided by an embodiment of the present invention;

[0029] Figure 3 is a tensile stress-strain curve diagram of a skull repair material provided by an embodiment of the present invention;

[0030] Figure 4 This is a histogram of strain variables of a skull repair material provided by an embodiment of the present invention. DETAILED DESCRIPTION

[0031] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0032] In the description of the embodiments of the present invention, unless otherwise expressly specified or limited, the terms "first" and "second" are used for descriptive purposes only and are not to be understood as indicating or implying relative importance; unless otherwise specified or explained, the term "plurality" refers to two or more; the terms "connected" and "fixed" should be understood in a broad sense. For example, "connected" can mean a fixed connection, a detachable connection, an integral connection, or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium. For those skilled in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0033] In the description of this specification, it should be understood that the directional terms such as "upper" and "lower" described in the embodiments of the present invention are described from the perspectives shown in the accompanying drawings and should not be understood as limiting the embodiments of the present invention. In addition, in the context, it should be understood that when it is mentioned that an element is connected "upper" or "lower" of another element, it can not only be directly connected "upper" or "lower" of the other element, but also indirectly connected "upper" or "lower" of the other element through an intermediate element.

[0034] Figure 1, Figure 2 As shown, an embodiment of the present invention provides a method for preparing a skull repair material, comprising:

[0035] dissolving collagen and a water-soluble polymer compound in a phosphate buffer solution to obtain a prepolymer solution;

[0036] The prepolymerized solution is treated with synchrotron radiation to obtain a hydrogel-like skull repair material.

[0037] In this embodiment, collagen and a water-soluble polymer compound are dissolved in a phosphate buffer solution to obtain a prepolymer solution, and the prepolymer solution is subjected to synchrotron radiation treatment to crosslink the collagen and the water-soluble polymer to obtain a hydrogel-like skull repair material. The hydrogel-like skull repair material has a high water content, good permeability, and strong adaptability. The hydrogel is also elastic and can undergo a certain degree of stretching under intracranial pressure, thereby being able to adapt to different intracranial pressures. A certain degree of stretching can prevent excessive intracranial pressure. Therefore, the hydrogel-like skull repair material provided by the present invention can repair skull damage in one go. The collagen in the skull repair material has excellent biocompatibility, collagen can promote skull repair, and improve the efficiency of skull repair. The synchrotron radiation method can crosslink collagen and water-soluble polymer compounds at room temperature without the need for crosslinking agents or initiators, and monomers remain after crosslinking. In addition, during the preparation process of the radiation-synthesized hydrogel, high-energy rays can not only trigger the crosslinking reaction but also have a sterilizing effect, without the need to add preservatives.

[0038] In this embodiment, the pH of the phosphate buffer solution is 7.2-7.6, and M is 0.1. Collagen is preferably type I collagen, which is prepared by the following method:

[0039] (1) Remove excess fascia, fat, muscle, etc. from the Achilles tendon, rinse with tap water, place neatly in a freezer, and freeze at -20°C for at least 12 hours;

[0040] (2) Cut the frozen beef Achilles tendon into slices of about 1 mm and place them in a strainer and wash until the liquid is clear;

[0041] (3) Enzymatic hydrolysis: The cleaned bovine Achilles tendon slices were enzymatically hydrolyzed with sufficient stirring for no less than 72 h; the mass ratio of the enzymatic hydrolyzate to the bovine Achilles tendon was 130:1, the volume ratio of purified water to acetic acid in the enzymatic hydrolyzate was 25:1, and the mass ratio of purified water to pepsin was 15:1.

[0042] (4) Salting out: Centrifuge the solution after enzymatic hydrolysis, take the supernatant, add the supernatant into sodium chloride solution to precipitate white flocculent collagen, filter and wash it, and drain the water.

[0043] (5) Dialysis: Pour the salted-out material into a dialysis bag with a volume of about 1 / 3 of the bag; place the dialysis bag in a 0.057 mol / L acetic acid solution for 6 days at a temperature of 10-20°C, and replace the dialysis solution every 3 days; then place the dialysis bag in a 0.00057 mol / L acetic acid solution for 5 days at a temperature of 10-20°C, and replace the dialysis solution every day; from the 12th day, place the bag in a 0.0000057 mol / L acetic acid solution for dialyzation until the pH is between 5.5-5.5 and the dialysis temperature is 10-20°C. The dialysis solution can be replaced once a day as needed.

[0044] (6) Freeze-drying

[0045] The samples were freeze-dried according to the following process, which includes a pre-freezing stage, a first sublimation stage, a second sublimation stage, and a cooling stage. The process conditions of each stage are as follows:

[0046] Pre-freezing stage: target temperature is -12~-8℃, rate is 3~4.0℃ / min, constant temperature time is 280~320min;

[0047] The first sublimation stage: vacuum, gas injection 90-110Pa, target temperature -4-2°C, rate 0.6-0.8°C / min, constant temperature time 1300-1340min;

[0048] The second sublimation stage is vacuuming and gasification of 90-110Pa, including five temperature rising steps, namely:

[0049] -1~1℃, rate is 0.2~0.3℃ / min, constant temperature time is 110~130min;

[0050] 8-12℃, rate is 1.0-1.2℃ / min, constant temperature time is 110-130min;

[0051] 18-22°C, rate 1.0-1.2°C / min, constant temperature time 110-130min;

[0052] 28-32°C, rate 1.0-1.2°C / min, constant temperature time 110-130min;

[0053] 38~42℃, rate is 1.0~1.2℃ / min, constant temperature time: endpoint judgment is performed every 10 minutes until the endpoint is qualified; endpoint judgment is ≤0.9Pa / 10min;

[0054] Cooling stage: cooling to room temperature at a rate of 1.4-1.6°C / min;

[0055] The collagen sponge raw material is obtained.

[0056] It should be noted that the above freeze-drying process is applicable to all freeze-drying treatments in the present invention.

[0057] In this embodiment, nitrogen was introduced to deaerate the prepolymer solution before irradiation, and the prepolymer solution was subjected to a dose rate of 3.4 to 3.8 kgy / h and a dose of 50 kgy (measured by a Fricke dosimeter) in air. 60 Irradiation with Co-γ radiation source (γ beam 651PT).

[0058] In some embodiments of the present invention, after obtaining the hydrogel-like skull repair material, the process further comprises:

[0059] The skull repair material is freeze-dried to obtain a hydrogel freeze-dried material.

[0060] In this embodiment, the skull repair material is freeze-dried to facilitate storage.

[0061] In some embodiments of the present invention, after obtaining the hydrogel freeze-dried material, the method further comprises:

[0062] mixing the hydrogel freeze-dried material with water to swell the hydrogel freeze-dried material to obtain a swollen hydrogel;

[0063] uniformly mixing the swollen hydrogel and the mineralized collagen particles to obtain a mineralized hydrogel;

[0064] The mineralized hydrogel is freeze-dried to obtain a mineralized hydrogel freeze-dried material.

[0065] In this example, the swollen hydrogel and mineralized collagen particles are uniformly mixed to produce a mineralized hydrogel containing mineralized collagen. The mineralized collagen contained in the mineralized hydrogel can promote bone tissue growth and accelerate the rate of skull repair. Specifically, purified water is slowly added to allow the freeze-dried hydrogel to slowly swell. A certain amount of mineralized collagen particles is then added and kneaded to form a uniform mixture.

[0066] In some embodiments of the present invention, the swollen hydrogel and the mineralized collagen particles are mixed uniformly, comprising:

[0067] The swollen hydrogel and the mineralized collagen particles were mixed uniformly in a mass ratio of 1: (0.2-1).

[0068] In this embodiment, if the mass ratio of the swollen hydrogel to the mineralized collagen particles is greater than 1:0.2, the obtained mineralized hydrogel cannot significantly improve the repair rate of the skull; if the mass ratio of the swollen hydrogel to the mineralized collagen particles is less than 1:0.2, the water absorption and mechanical properties of the hydrogel will be weakened.

[0069] In some embodiments of the present invention, the particle size of the mineralized collagen particles is 300-500 μm.

[0070] In this embodiment, the particle size of the mineralized collagen particles is 300-500 μm. The above particle size range makes it easy for the mineralized collagen particles to be mixed evenly with the swollen hydrogel. The preparation method of the mineralized collagen particles is as follows:

[0071] Step 1: dissolving collagen in any one of hydrochloric acid, nitric acid or acetic acid to prepare a collagen acid solution, wherein the collagen concentration is 0.01 to 0.2 g / ml;

[0072] Step 2: adding a calcium salt solution dropwise to the collagen acid solution, wherein the amount of calcium ions added is 0.1 to 2 mol per gram of collagen;

[0073] Step 3, adding phosphoric acid solution dropwise to the solution obtained in step 2, wherein the molar ratio of the added amount of phosphate ions to the amount of calcium ions added in step S1-2 is Ca / P=1 / 1 to 2 / 1;

[0074] Step 4: Add NaOH solution dropwise to the solution obtained in step 3 to form a mixed solution, and adjust the pH value to 6-8;

[0075] Step 5: After the mixed solution obtained in step 4 is allowed to stand for 4 to 12 hours, the precipitate is centrifuged at a speed of 3000 to 6000 r / min and then dried at 50-70° C. for 24 to 72 hours to obtain mineralized collagen particles;

[0076] Step 6: crush the mineralized collagen particles obtained in step 5, and then sieve them to retain the mineralized collagen particles with a particle size of 300 to 500 microns.

[0077] In some embodiments of the present invention, the water-soluble polymer compound includes at least one of polyvinyl pyrrolidone and polyethylene glycol.

[0078] In this embodiment, polyvinyl pyrrolidone and polyethylene glycol have the general properties of water-soluble polymer compounds, such as colloid protection, film-forming property, adhesion, hygroscopicity, solubilization or coagulation. In addition, polyvinyl pyrrolidone also has excellent solubility and physiological compatibility.

[0079] In some embodiments of the present invention, the water-soluble polymer compound is polyethylene glycol, and the concentration of collagen in the prepolymer solution is 0.3-0.4 mg / mL (for example, it can be 0.3 mg / mL, 0.31 mg / mL, 0.32 mg / mL, 0.33 mg / mL, 0.34 mg / mL, 0.35 mg / mL, 0.36 mg / mL, 0.37 mg / mL, 0.38 mg / mL, 0.39 mg / mL or 0.4 mg / mL), and the concentration of polyethylene glycol is 45-55 mg / mL (for example, it can be 45 mg / mL, 46 mg / mL, 47 mg / mL, 48 mg / mL, 49 mg / mL, 50 mg / mL, 51 mg / mL, 52 mg / mL, 53 mg / mL, 54 mg / mL or 55 mg / mL).

[0080] In this embodiment, collagen with a concentration of 0.3 to 0.4 mg / mL and polyethylene glycol with a concentration of 45 to 55 mg / mL can form a hydrogel after cross-linking.

[0081] In some embodiments of the present invention, the water-soluble polymer compound is polyvinyl pyrrolidone, and in the prepolymerization solution, the concentration of collagen is 0.3-0.4 mg / mL (for example, it can be 0.3 mg / mL, 0.31 mg / mL, 0.32 mg / mL, 0.33 mg / mL, 0.34 mg / mL, 0.35 mg / mL, 0.36 mg / mL, 0.37 mg / mL, 0.38 mg / mL, 0.39 mg / mL or 0.4 mg / mL), and the concentration of polyvinyl pyrrolidone is 20-30 mg / mL (for example, it can be 20 mg / mL, 21 mg / mL, 22 mg / mL, 23 mg / mL, 24 mg / mL, 25 mg / mL, 26 mg / mL, 27 mg / mL, 28 mg / mL, 29 mg / mL or 30 mg / mL).

[0082] In this embodiment, collagen with a concentration of 0.3 to 0.4 mg / mL and polyvinyl pyrrolidone with a concentration of 20 to 30 mg / mL can form a hydrogel after cross-linking.

[0083] In some embodiments of the present invention, the water-soluble polymer compound is polyethylene glycol and polyvinyl pyrrolidone, and in the prepolymer solution, the concentration of collagen is 0.3-0.4 mg / mL (for example, 0.3 mg / mL, 0.31 mg / mL, 0.32 mg / mL, 0.33 mg / mL, 0.34 mg / mL, 0.35 mg / mL, 0.36 mg / mL, 0.37 mg / mL, 0.38 mg / mL, 0.39 mg / mL or 0.4 mg / mL), and the concentration of polyethylene glycol is 25-75 mg / mL (for example, 25 mg / mL L, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL or 75 mg / mL), and the concentration of polyvinyl pyrrolidone is 50-150 mg / mL (for example, it can be 50 mg / mL, 60 mg / mL, 70 mg / mL, 80 mg / mL, 90 mg / mL, 100 mg / mL, 110 mg / mL, 120 mg / mL, 130 mg / mL, 140 mg / mL or 150 mg / mL).

[0084] In this embodiment, collagen is simultaneously cross-linked with polyethylene glycol and polyvinyl pyrrolidone to produce a skull repair material with a higher degree of cross-linking. This higher degree of cross-linking significantly improves the tensile properties of the skull repair material. Furthermore, the three cross-linking allows the same mass of collagen to be cross-linked with a greater amount of polyethylene glycol and polyvinyl pyrrolidone, resulting in a skull repair material with a higher swelling capacity. While maintaining the same collagen content, the higher the amount of polyethylene glycol and polyvinyl pyrrolidone, the higher the water absorption swelling capacity and the better the mechanical properties. The preferred collagen concentration is 0.35 mg / mL, the polyethylene glycol concentration is 75 mg / mL, and the polyvinyl pyrrolidone concentration is 150 mg / mL.

[0085] A skull repair material is prepared according to any of the above-mentioned preparation methods.

[0086] The skull repair material provided in the embodiment of the present invention and the preparation method of the skull repair material described above are based on the same inventive concept and therefore can achieve the same beneficial effects. Therefore, their beneficial effects will not be described in detail here.

[0087] It should be noted that at least one is any one or a mixture of any several in any proportion.

[0088] In order to more clearly illustrate the technical solutions and advantages of the present invention, a method for preparing a skull repair material is described in detail below through several embodiments.

[0089] Example 1

[0090] Dissolving collagen and polyethylene glycol in a phosphate buffer solution to obtain a prepolymerization solution; wherein the concentration of collagen is 0.35 mg / mL and the concentration of polyethylene glycol is 50 mg / mL;

[0091] The prepolymerized solution is treated with synchrotron radiation to obtain a hydrogel-like skull repair material;

[0092] The skull repair material is freeze-dried to obtain a hydrogel freeze-dried material.

[0093] Example 2

[0094] Dissolving collagen and polyvinyl pyrrolidone in phosphate buffer solution to obtain a prepolymerization solution; wherein the concentration of collagen is 0.35 mg / mL and the concentration of polyvinyl pyrrolidone is 25 mg / mL;

[0095] The prepolymerized solution is treated with synchrotron radiation to obtain a hydrogel-like skull repair material;

[0096] The skull repair material is freeze-dried to obtain a hydrogel freeze-dried material.

[0097] Example 3

[0098] Dissolve collagen, polyethylene glycol, and polyvinyl pyrrolidone in phosphate buffer solution to obtain a prepolymerization solution; wherein the concentration of collagen is 0.35 mg / mL, the concentration of polyvinyl pyrrolidone is 50 mg / mL, and the concentration of polyethylene glycol is 25 mg / mL;

[0099] The prepolymerized solution is treated with synchrotron radiation to obtain a hydrogel-like skull repair material;

[0100] The skull repair material is freeze-dried to obtain a hydrogel freeze-dried material.

[0101] Example 4

[0102] Dissolve collagen, polyethylene glycol, and polyvinyl pyrrolidone in phosphate buffer solution to obtain a prepolymerization solution; wherein the concentration of collagen is 0.35 mg / mL, the concentration of polyvinyl pyrrolidone is 125 mg / mL, and the concentration of polyethylene glycol is 50 mg / mL;

[0103] The prepolymerized solution is treated with synchrotron radiation to obtain a hydrogel-like skull repair material;

[0104] The skull repair material is freeze-dried to obtain a hydrogel freeze-dried material.

[0105] Example 5

[0106] Dissolve collagen, polyethylene glycol, and polyvinyl pyrrolidone in phosphate buffer solution to obtain a prepolymerization solution; wherein the concentration of collagen is 0.35 mg / mL, the concentration of polyvinyl pyrrolidone is 150 mg / mL, and the concentration of polyethylene glycol is 75 mg / mL;

[0107] The prepolymerized solution is treated with synchrotron radiation to obtain a hydrogel-like skull repair material;

[0108] The skull repair material is freeze-dried to obtain a hydrogel freeze-dried material.

[0109] Example 6

[0110] Dissolve collagen, polyethylene glycol, and polyvinyl pyrrolidone in phosphate buffer solution to obtain a prepolymerization solution; wherein the concentration of collagen is 0.35 mg / mL, the concentration of polyvinyl pyrrolidone is 150 mg / mL, and the concentration of polyethylene glycol is 75 mg / mL;

[0111] The prepolymerized solution is treated with synchrotron radiation to obtain a hydrogel-like skull repair material;

[0112] freeze-drying the skull repair material to obtain a hydrogel freeze-dried material;

[0113] mixing the hydrogel freeze-dried material with water to swell the hydrogel freeze-dried material to obtain a swollen hydrogel;

[0114] The swollen hydrogel and the mineralized collagen particles were mixed uniformly at a mass ratio of 1:0.5 to obtain a mineralized hydrogel;

[0115] The mineralized hydrogel is freeze-dried to obtain a mineralized hydrogel freeze-dried material.

[0116] Comparative Example 1

[0117] Dissolving collagen in phosphate buffer solution to obtain a mixed solution; wherein the concentration of collagen is 0.35 mg / mL;

[0118] The mixed solution is freeze-dried to obtain a hydrogel freeze-dried material.

[0119] The materials obtained in Examples 1-6 are respectively recorded as M1, M2, M3, M4, M5, and M6, and the material obtained in Comparative Example 1 is recorded as M0.

[0120] Infrared spectrum test:

[0121] Spectral tests were performed on M1, M2, M3, M4, M5, M0, polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) to obtain Fourier transform infrared spectra FTIR (see Figure 1). Figure 1a As shown, PVP spectrum 3000-2800cm-1 、1651cm -1 , 1436cm -1 and 1282cm -1 The signals at 1493-1423 cm correspond to the CH stretching peak, carbonyl absorption peak, and characteristic CH stretching vibration peak of PVP. -1 ) and CN stretching peaks. The PEG spectrum also shows a hydroxyl signal (3445cm -1 ) and PEG backbone vibration (1100cm -1 Collagen M0 shows a broad band at 3290 cm -1 Labeled as amide A ( Figure 1a and b). 3274cm -1 and 2941cm -1 The stretching vibration at 1628 cm is associated with amide B. -1 The signal at (amide I) plays a key role in evaluating conformational changes. -1 and 1229cm -1 Two additional peaks were observed at 400 nm and were attributed to amide II (bending) and amide III (stretching) vibrations. Figure 1a The shift of M1 to higher wave numbers, for example, from 1628 cm -1 to 1641cm -1 , revealing evidence of cross-linking between collagen and polyethylene glycol. The most notable features of the M2 sample are the decrease in bending vibration (CN) and the shift of amide I (1628-1658 cm -1 ). The M3-M5 spectra correspond to the prepared terpolymer (collagen-polyvinyl pyrrolidone-polyethylene glycol). As shown in the figure, they follow the same trend as the M1 and M2 samples, indicating that the polymers are cross-linked. In addition, a decrease in the relative intensity of amides II and III and a broadening of amides A and B can be observed. This result indicates that polyvinyl pyrrolidone and polyethylene glycol form intermolecular interactions with the hydrogen bonds of collagen, and that the collagen backbone undergoes a chemical reaction with these polymers.

[0122] Swelling test:

[0123] Cut M1, M2, M3, M4, M5, M6, and M0 into strips, and cut the freeze-dried hydrogel sample into strips. After accurately weighing (m0), immerse it in about 10 mL of purified water and keep it warm at 37°C. At regular intervals, use tweezers to pick up the gel sample and place it on a moistened filter paper. After absorbing the surface moisture, quickly weigh it (mt). After weighing, continue to place the sample in a centrifuge tube to swell until the swelling is balanced. Set up 3 parallel samples for each test sample. The swelling degree of the hydrogel at t can be calculated by the following formula. According to the calculation fitting, the swelling degree of the hydrogel is plotted against time ( Figure 2), the swelling curves of collagen-polyvinyl pyrrolidone-polyethylene glycol composite hydrogels with different ratios were plotted. The swelling degree formula of collagen-polyvinyl pyrrolidone-polyethylene glycol composite hydrogel is:

[0124] SR / %=(mt-m0) / m0*100%,

[0125] The swelling rate and swelling degree of collagen-polyvinyl pyrrolidone-polyethylene glycol (M3-M6) are higher than those of collagen (M0), collagen-polyvinyl pyrrolidone (M2), and collagen-polyethylene glycol (M1). Moreover, the equilibrium swelling degree increases with the increase of polyethylene glycol and polyvinyl pyrrolidone content. This indicates that polyvinyl pyrrolidone and polyethylene glycol form an interpenetrating structure with collagen, which increases the flexibility of the cross-linked network. At the same time, the increase of hydrophilic groups in the system makes it easier for water molecules to enter and diffuse, thus improving the swelling performance. Figure 2 It can be seen that the sample with the addition of mineralized collagen particles (M6) has little effect on the water absorption of the hydrogel.

[0126] Tensile mechanics testing:

[0127] The prepared hydrogel materials and composite materials were cut into standard specimens using a standard sample knife, and the tensile properties were tested according to GB / T 1040-1992. The test process is as follows:

[0128] a) Prepare M5 and M6 hydrogel blocks into rectangular blocks 3 cm long, 6 mm wide, and 2 mm thick for later use;

[0129] b) Use 502 glue to glue the two ends of the prepared rectangular blocks M5 and M6 to one end of two glass slides, leaving a distance of 1.5 cm between the two glass slides.

[0130] C) Prepare the force sensor and fixture of the universal mechanical testing machine, open the test software, and set the stretching speed parameter to 2 mm / min;

[0131] e) Fixing the two glass slides bonded with the hydrogel cuboids to the upper and lower clamps of a universal mechanical testing machine;

[0132] f) Turn on the switch and slowly stretch until the rectangular hydrogel breaks. Repeat the test for three samples in each group.

[0133] The tensile properties of M5 and M6 were investigated by using a universal mechanical testing machine (see Figure 3 、 4As the stress applied to M5 and M6 continued to increase, the hydrogel continued to stretch. The maximum tensile stress that M6 could withstand was 6.53 kPa, with an elongation of 28.63%. Meanwhile, the maximum tensile stress that M5 could withstand was 11.95 kPa, with an elongation of 340.2%. This indicates that both M5 and M6 possess good stretchability.

[0134] Clinical studies have shown that when a skull defect is accompanied by a craniocerebral injury, the volume of intracranial tissue increases by 10%, leading to an increase in intracranial pressure to 3 kPa. Quantitative analysis of the elongation ratio at a tensile stress of 3 kPa revealed that the tensile strain in the M6 ​​group was 13.71%, while the tensile strain in the M5 group was as high as 16.96%. When experiencing intracranial hypertension, the stress and tensile strain levels in the M6 ​​group most closely resemble physiological changes in the human body. This demonstrates that the M6 ​​craniocerebral prosthesis exhibits excellent tensile properties and is more adaptable to changes in intracranial pressure when intracranial pressure increases. A skull support with excellent extensibility can adapt to changes in intracranial pressure and maintain normal intracranial pressure. When intracranial pressure increases and intracranial tissue volume increases, the skull repair material gradually expands, increasing the volume of the cranial cavity, alleviating the elevated intracranial pressure and maintaining it within a normal range. The tensile stress-strain curve shows that when a stress of 3 kPa is applied, the tensile strain of the M6 ​​is 13.71%, which is consistent with clinical statistical data on intracranial pressure-volume changes during craniocerebral injury. The skull repair material provided by the present invention can not only adapt to changes in intracranial pressure, but also alleviate the pain and economic burden of repairing large-area skull defects using a two-step method.

[0135] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A method for preparing a skull repair material, characterized in that: include: dissolving collagen and a water-soluble polymer compound in a phosphate buffer solution to obtain a prepolymer solution; The prepolymer solution was subjected to a dosage of 50 kgy at a dosage rate of 3.4 to 3.8 kgy / h. 60 Irradiation with a Co-γ radiation source yields a hydrogel-like skull repair material; The water-soluble polymer compound includes at least one of polyvinyl pyrrolidone and polyethylene glycol; The water-soluble polymer compound is polyethylene glycol, and in the prepolymerization solution, the concentration of collagen is 0.3-0.4 mg / mL, and the concentration of the polyethylene glycol is 45-55 mg / mL; or, The water-soluble polymer compound is polyvinyl pyrrolidone. In the prepolymerization solution, the concentration of collagen is 0.3-0.4 mg / mL, and the concentration of polyvinyl pyrrolidone is 20-30 mg / mL. or, The water-soluble polymer compounds are polyethylene glycol and polyvinyl pyrrolidone. In the prepolymerization solution, the concentration of collagen is 0.3-0.4 mg / mL, the concentration of polyethylene glycol is 25-75 mg / mL, and the concentration of polyvinyl pyrrolidone is 50-150 mg / mL.

2. The preparation method according to claim 1, characterized in that After obtaining the hydrogel-like skull repair material, the method further comprises: The skull repair material is freeze-dried to obtain a hydrogel freeze-dried material.

3. The preparation method according to claim 2, characterized in that After obtaining the hydrogel freeze-dried material, the method further comprises: mixing the hydrogel freeze-dried material with water to swell the hydrogel freeze-dried material to obtain a swollen hydrogel; uniformly mixing the swollen hydrogel and mineralized collagen particles to obtain a mineralized hydrogel; The mineralized hydrogel is freeze-dried to obtain a mineralized hydrogel freeze-dried material.

4. The preparation method according to claim 3, characterized in that The step of uniformly mixing the swollen hydrogel and the mineralized collagen particles comprises: The swollen hydrogel and the mineralized collagen particles are uniformly mixed in a mass ratio of 1: (0.2-1).

5. The preparation method according to claim 3, characterized in that The particle size of the mineralized collagen particles is 300-500 μm.

6. A skull repair material, characterized in that: Prepared according to the preparation method described in any one of claims 1-5.

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