A low-swelling and high-strength chitin rod and its preparation method and application

Abstract

The present invention provides a method for preparing a chitin rod with low swelling and high strength, comprising the following steps: First, chitin is treated with a mixed solution of alkali and urea and chemically crosslinked, and then formed at low temperature to obtain a columnar chitin hydrogel; Second, the columnar chitin hydrogel is subjected to a pre-stretching treatment along its axial direction; Third, the pre-stretched chitin hydrogel is subjected to orientation fixation; Finally, the orientation-fixed chitin hydrogel is subjected to dialysis with deionized water and solvent replacement treatment, and then dried to obtain a chitin rod with low swelling and high strength. The chitin rod provided by the present invention is prepared from a natural biodegradable material, has a simple process and is easy to operate, and can be transformed into industrial products. The low-swelling and high-strength chitin rod prepared by the present invention has advantages such as low swelling rate and high mechanical strength, and has broad popularization and application prospects in the fields of bone repair and reconstruction as an auxiliary fixation material.

Description

Technical Field

[0001] The present invention belongs to the technical field of polymer functional materials, and particularly relates to a chitin rod with low swelling and high strength and a preparation method thereof. The present invention also relates to the application of a chitin rod with low swelling and high strength as an auxiliary fixation material in bone repair and reconstruction. Background Art

[0002] The development of materials for sports medical devices is becoming a key research area in the national science and technology and industrial development. The number of fracture cases caused by violent incidents or cumulative strain increases gradually every year globally. Since the self-repair ability of human bone tissue is limited and it is prone to further damage due to external physical stimuli during the process of bone healing and osteogenesis, internal fixation materials with sufficient mechanical strength are required to assist bone tissue in repairing damaged parts and bone reconstruction. The preparation materials for fracture internal fixation medical devices mainly include three categories: metal alloys, inorganic materials, and organic materials. Among them, natural polymer organic materials have great potential in constructing new degradable medical products due to their excellent biocompatibility, biodegradability, and rich sources.

[0003] Currently, the developed natural polymer organic materials include silk fibroin, chitosan, collagen, etc. These materials do not produce other products such as acids that are unfavorable to bone defect healing during the biodegradation process of organisms and can maintain relatively stable mechanical strength. As a natural polymer substance that ranks second only to cellulose in nature, chitin widely exists in the outer shells of shrimps and crabs and the cell walls of fungi. In recent years, there have been many studies on dissolving chitin, which has greatly promoted the application of chitin in material development. However, in fracture internal fixation materials, bone nails further processed from chitin rods have rarely received attention due to the disadvantages of large swelling rates in organisms and unstable mechanical properties.

[0004] Based on this, on the premise of making good use of the advantages of chitin as a natural polymer material, the research on further reducing the swelling rate of chitin bone nails and improving their mechanical strength and mechanical properties has broad promotion prospects and application values, and is also a technical problem that researchers urgently need to solve. Summary of the Invention

[0005] One object of the present invention is to provide a preparation method of a chitin rod with low swelling and high strength.

[0006] Another object of the present invention is to provide a chitin rod with low swelling and high strength.

[0007] A further object of the present invention is to provide the application of a chitin rod with low swelling and high strength as an auxiliary fixation material in bone repair and reconstruction.

[0008] One of the technical solutions adopted by the present invention to achieve its purpose is to provide a method for preparing a chitin rod with low swelling and high strength, comprising the following steps:

[0009] S1. The chitin is first treated with a mixed solution of alkali and urea, and then subjected to freeze-thaw cycles to obtain a chitin solution; a cross-linking agent is added and mixed evenly, and then poured into a mold and treated at a low temperature for a certain period of time to obtain a columnar chitin hydrogel;

[0010] S2. The columnar chitin hydrogel is placed under certain humidity conditions and pre-stretched along its axial direction to increase its axial length by 40% to 200% to obtain a pre-stretched chitin hydrogel;

[0011] S3. The pre-stretched chitin hydrogel is soaked in a curing solution for a certain period of time to obtain an orientation-fixed chitin hydrogel; the curing solution is selected from one or a combination of a mixed solution of ethanol and water, a pre-cooled sulfuric acid solution, or a pre-cooled hydrochloric acid solution;

[0012] S4. The orientation-fixed chitin hydrogel is subjected to dialysis with deionized water and solvent replacement treatment, and then dried to obtain a chitin rod with low swelling and high strength.

[0013] The general idea of the method for preparing a chitin rod with low swelling and high strength provided by the present invention is as follows: First, the chitin solution is chemically cross-linked, so that the molecular chains of chitin fibers are chemically cross-linked with the cross-linking agent, and the cross-linked chitin solution is poured into a mold and formed by low-temperature treatment. Chemical cross-linking points are formed by the chemical cross-linking agent to connect chitin fibers to each other to prepare a chitin hydrogel, and a columnar isotropic chitin hydrogel is obtained for subsequent pre-stretching operations. Secondly, the columnar chitin hydrogel is fixed on a stretching instrument, and the hydrogel is pre-stretched along the axial direction with a certain tensile force and stretching speed to obtain an anisotropic chitin hydrogel; considering that the chitin hydrogel itself has a high water content and good resilience, in order to maintain the pre-stretching effect, the present invention also performs a shaping treatment on the pre-stretched chitin hydrogel, soaking it in the prepared curing solution for a certain period of time. During the soaking process, the alkali / urea water system in the original hydrogel network is destroyed, and the orientation of its molecular chains is fixed; finally, subsequent purification and drying treatments are performed on the orientation-fixed chitin hydrogel. The chitin rod treated by the above preparation method has the characteristics of low swelling rate and high strength.

[0014] Preferably, in step S1, in the treatment with the mixed solution of alkali and urea, the mass ratio of NaOH, urea to chitin is 22:8:(2-12); in the freeze-thaw cycle, the freezing temperature is -40°C, the first freezing time is 2-6 h, the freezing time for the second and subsequent times is 10-12 h, and the number of freeze-thaw cycles is 2-4 times. Preferably, the chitin is selected from natural red crab shells and is obtained as chitin powder through crushing, purification, and bleaching.

[0015] Further, in step S1, the crosslinking agent is selected from one or a combination of more of epichlorohydrin, ethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether, diglycidyl ether, 1,4-butanediol diglycidyl ether, or genipin.

[0016] Preferably, the crosslinking agent is epichlorohydrin, and the volume ratio of epichlorohydrin to the mass of chitin is 0.1-0.3 mL / g. Preferably, the mixing time for adding the crosslinking agent and mixing evenly is 5-10 min, and this mixing operation is carried out under ice-water bath conditions.

[0017] Further, in step S1, the chemical crosslinking reaction of chitin will gradually accelerate with the increase of the environmental temperature. However, excessive chemical crosslinking will lead to a small number of hydrogen bonds formed in the generated hydrogel network. When the hydrogel resists external impact or stretching, the hydrogen bond interaction in the network will be preferentially broken, and then the chemical crosslinking network will be damaged, and finally it will break until fracture. Therefore, by controlling the temperature and time of the crosslinking process, at a lower temperature, while forming chemical crosslinking, hydrogen bond interaction can also be formed, realizing a double crosslinking network of chemistry and physics, and then achieving the effects of strengthening and toughening. Preferably, in step S1, the temperature of the low-temperature treatment is 3-10°C, and the time of the low-temperature treatment is 8-16 h.

[0018] Further, in step S2, the tensile instrument for pre-stretching can be a universal material testing machine (tensile machine). The two ends of the columnar hydrogel are respectively fixed to the tensile fixtures of the testing machine by clamps, and then pre-stretching treatment is carried out. Preferably, the traction force of the pre-stretching treatment is 0.5-2 N, and the stretching speed of the pre-stretching treatment is 50-200 mm / min. In the present invention, by controlling the traction force and stretching speed of the pre-stretching, the arrangement of fiber molecular chains in the chitin hydrogel can be better regulated. Utilizing the good elasticity of the hydrogel, the originally isotropic hydrogel is changed to anisotropic within the elastic range through stretching, and the fiber network as a whole shows an arrangement along the axial direction, and the radial fibers are arranged more closely, thereby realizing a reduction in the axial swelling rate and an enhancement in toughness of the rod.

[0019] In addition, to obtain a better pre-stretching effect, the above pre-stretching treatment can be based on the tensile stress-strain pre-experiment of the hydrogel to determine the appropriate tensile force, tensile speed and elongation at break. At the same time, to complete an effective stretching process, a certain tensile force and tensile speed need to be provided, while ensuring that the hydrogel does not break during fixation and stretching on a universal material testing machine. In step S2 of the present invention, the axial length of the chitin hydrogel is increased by 40% to 200% through pre-stretching, and the degree of pre-stretching can be further determined in combination with the water content of the chitin hydrogel. Preferably, the axial length of the chitin hydrogel is increased by 40% to 110% by pre-stretching.

[0020] Furthermore, it has been found through research that when the surface of the chitin hydrogel is in a state of drying and water loss, its elasticity will decrease to a certain extent. In this case, the effect of pre-stretching is poor and breakage is likely to occur. Preferably, the pre-stretching treatment is carried out in an environment with a relative humidity of 70% to 80%.

[0021] In step S3 of the present invention, the operation of immersing the stretched chitin hydrogel in a curing solution for a certain period of time microscopically shows the fixed orientation of molecular chains, and macroscopically shows the shrinkage of the hydrogel volume, thereby realizing the fixation effect on the pre-stretching effect. Considering that the immersion of the curing solution into the hydrogel is a process from the outside to the inside, when the initial concentration of the curing solution is high, when the internal hydrogel is cured, since the external hydrogel has fixed its volume and surface, as the internal hydrogel cures, the external hydrogel will collapse inward, resulting in the finally prepared rod presenting an irregular cylinder, which will not only cause difficulties for the later processing and treatment of the bone nail, but also reduce the overall mechanical properties of the bone nail. Therefore, preferably, multiple groups (3 to 5 groups) of curing solutions with different concentrations are used to immerse the stretched chitin hydrogel in order from low to high concentration.

[0022] Preferably, the curing solution is selected from a mixed solution of ethanol and water, a pre-cooled sulfuric acid solution or a pre-cooled hydrochloric acid solution.

[0023] Preferably, in the mixed solution of ethanol and water, the volume fraction of ethanol is 30% to 70%; in the pre-cooled sulfuric acid solution, the mass fraction of the sulfuric acid solution is 0.01 to 0.05 wt%; in the pre-cooled hydrochloric acid solution, the mass fraction of the hydrochloric acid solution is 0.04 to 0.1 wt%. The temperature of the pre-cooled sulfuric acid solution and the pre-cooled hydrochloric acid solution is 0 to 10 °C. In the present invention, the treatment of the hydrogel by the immersion method is a process from the outside to the inside. Considering that the acid-base neutralization reaction between hydrochloric acid and sulfuric acid and NaOH in the hydrogel is too fast, which is not conducive to achieving a relatively uniform curing effect, so these two curing solutions are pre-cooled to avoid the problems of surface depression and overall bending deformation of the finally prepared rod.

[0024] Preferably, the cumulative soaking time of the stretched chitin hydrogel in the mixed solution of ethanol and water is 6 - 12 h; the cumulative soaking time of the stretched chitin hydrogel in the pre-cooled sulfuric acid solution is 10 - 60 min; the cumulative soaking time of the stretched chitin hydrogel in the pre-cooled hydrochloric acid solution is 30 - 120 min.

[0025] In some preferred embodiments, the curing solution includes a mixed solution of ethanol and water, and a pre-cooled sulfuric acid solution or a pre-cooled hydrochloric acid solution. The specific operation of step S3 is as follows: First, use 3 - 5 groups of mixed solutions of ethanol and water with different concentrations to soak and cure the stretched chitin hydrogel in sequence from low to high concentration, and then use the pre-cooled sulfuric acid solution or the pre-cooled hydrochloric acid solution to perform secondary curing on the chitin hydrogel to obtain an orientation-fixed chitin hydrogel. When curing with the mixed solution of ethanol and water, most of the water in the hydrogel is removed, destroying the alkali / urea aqueous solution system that dissolves chitin. At the same time, since the swelling degree of ethanol on chitin is small, the chitin molecular chains are further pulled closer to form a physical cross-linked network; on this basis, using the pre-cooled sulfuric acid solution or the pre-cooled hydrochloric acid solution for secondary curing, NaOH in the hydrogel is removed by reaction, and the components in the dissolution system can be better removed, enabling the molecular chains after stretching to be better oriented and shaped, and the stretching effect to be retained to the greatest extent.

[0026] Further, in step S4, the solvent replacement treatment includes: for the chitin hydrogel after dialysis with deionized water, first perform multiple solvent replacements with ethanol, and then perform multiple solvent replacements with acetone or n-hexane.

[0027] Preferably, the solvent replacement treatment specifically includes: first perform solvent replacement with ethanol 3 - 5 times; then, perform solvent replacement with acetone or n-hexane a total of 4 - 6 times. Among them, ethanol has good affinity with water and a very similar structure, and it is very easy to replace the water in the hydrogel and can remove some inorganic salts, with good dehydration effect; then use acetone or n-hexane to replace the ethanol and residual water in the gel multiple times. Such an operation can make the surface of the prepared rod shrink evenly and the shape more regular.

[0028] The technical solution adopted by the present invention to achieve the second object is: to provide a low-swelling and high-strength chitin rod prepared by the preparation method described in the first object of the present invention.

[0029] The chitin rods prepared by the present invention are obtained by subjecting the chemically crosslinked chitin hydrogel to axial stretching and orientation fixation treatments, so that the originally loose chitin crosslinked network is arranged along the axis, and the deformation amount in this direction will be reduced when swelling occurs. Compared with the chitin hydrogel without pre-stretching treatment, the PBS liquid absorption rate of the finally dried chitin hydrogel is reduced by 10-75 wt.%, and the axial elongation rate is reduced by 1%-83%; further, the present invention uses the prepared curing solution to fix and further physically crosslink the pre-stretched chitin hydrogel, and the chitin fibers are more tightly combined by forming hydrogen bonds, and the flexural strength of the finally dried chitin hydrogel is increased by 27%-133%, and the toughness is increased by 2%-34%.

[0030] The technical solution adopted to achieve the third object of the present invention is: to provide an application of a low-swelling and high-strength chitin rod prepared by the preparation method described in the first object of the present invention in bone repair and reconstruction. The application includes: applying the chitin rod to the preparation of bone nails for sports medical devices.

[0031] The low-swelling and high-strength chitin rod prepared by the present invention has the characteristics of lower swelling rate and more stable mechanical properties compared with the bone nails conventionally prepared by processing chitin rods; in addition, the chitin rod of the present invention has a simple process, is easy to operate, can be transformed into industrial products, and has better promotion and application prospects.

[0032] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0033] (1) The preparation method of a low-swelling and high-strength chitin rod provided by the present invention uses natural polymer materials that are abundant and easily available in nature, and has the characteristics of excellent biocompatibility and biodegradability; at the same time, the preparation method has a simple process, is easy to operate, and can be transformed into industrial products.

[0034] (2) The low-swelling and high-strength chitin rod prepared by the present invention adopts the method of subjecting the chemically crosslinked chitin hydrogel to axial stretching and orientation fixation treatments, so that the originally loose chitin crosslinked network is arranged along the axis, and the deformation amount in this direction will be reduced when swelling occurs. Compared with the chitin hydrogel without pre-stretching treatment, the PBS buffer solution (pH 7.4) liquid absorption rate of the finally dried chitin hydrogel is reduced by 10-75 wt.%, and the axial elongation rate is reduced by 1%-83%; further, the present invention uses the solvent replacement method to fix and further physically crosslink the pre-stretched chitin hydrogel, and the chitin fibers are more tightly combined by forming hydrogen bonds, and the flexural strength of the finally dried chitin hydrogel is increased by 27%-133%, and the toughness is increased by 2%-34%.

[0035] (3) The low-swelling and high-strength chitin rods prepared by the present invention not only have the advantages of excellent biocompatibility, biodegradability and rich sources of chitin, but also have the advantages of low swelling rate and stable mechanical properties. They can be used to prepare bone nails for fracture internal fixation medical devices and have broad promotion and application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 It is a schematic flow chart of a preparation method of a low-swelling and high-strength chitin rod provided by an embodiment of the present invention;

[0037] Figure 2 It is the three-point bending method stress-strain curve (a) and the maximum bending strength and toughness (b) of the low-swelling and high-strength chitin rods prepared in Examples 1-3 of the present invention and the chitin rods prepared in Comparative Example 1 after different degrees of stretching;

[0038] Figure 3 It is the liquid absorption rate (a) and axial elongation rate (b) during the swelling process of the low-swelling and high-strength chitin rods prepared in Examples 1-3 of the present invention and the chitin rods prepared in Comparative Example 1 in PBS buffer solution after different degrees of stretching. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0039] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts fall within the protection scope of the present invention.

[0040] It should be noted that, without conflict, the embodiments in the present invention and the features in the embodiments can be combined with each other.

[0041] The present invention will be further described below in conjunction with specific embodiments, but it is not limited to the present invention.

[0042] The main parameters involved in Examples 1-9 and Comparative Examples 1 and 2 of the present invention are shown in Table 1 below:

[0043] Table 1

[0044]

[0045]

[0046] In the examples and comparative examples of the present invention, the chitin raw materials used were purified. The specific purification method included: adding 350 g of chitin raw materials and 4000 g of 5 wt% NaOH(aq) into a 5 L plastic beaker, and mechanically stirring for 12 hours. After the alkali cooking was completed, the chitin was poured into a filter bag (mesh number 60), rinsed with tap water until neutral, wrung dry, and then added into a 5 L plastic beaker containing 4000 g of 7 wt% HCl(aq), and mechanically stirred for 12 hours. After the acid cooking was completed, the chitin was poured into a filter bag (mesh number 60), rinsed with tap water until neutral, wrung dry, and then purified again using the same alkali cooking method. The chitin after the second alkali cooking was dialyzed with deionized water. The dialyzed and purified chitin powder was added into a 5 L glass beaker containing 4000 g of 4 wt% H2O2(aq, pH 9) for bleaching treatment, and reacted in an 80 °C oil bath for three to five hours. The bleached chitin was dialyzed with deionized water, and finally the dialyzed chitin was dried using a blast drying oven. The drying conditions were 24 hours at 50 °C to obtain the purified chitin.

[0047] Example 1

[0048] Step (1): 22 g of NaOH and 8 g of urea were dissolved in a 500 mL plastic beaker containing 161 g of distilled water. After ultrasonic dissolution until complete, 8 g of chitin was added. The beaker was placed in a -30 °C refrigerator and frozen for about 2 h. When ice flowers appeared, the beaker was taken out, stirred until completely thawed, and then placed in a -30 °C refrigerator and frozen for 12 h. After stirring and thawing again, a transparent chitin solution was obtained; the chitin solution was placed in an ice-water bath and mechanically stirred for 10 min. During this period, 0.16 mL of cross-linking agent epichlorohydrin was slowly added dropwise, and then transferred to a high-speed centrifuge (-10 °C, 7000 rpm, 5 min) to remove air bubbles. The supernatant was poured into a cylindrical mold (diameter 24 mm, length 150 mm) for shaping, and placed in a 4 °C environment for 12 hours to obtain a chitin hydrogel;

[0049] Step (2): The chitin hydrogel obtained in step (1) was placed on a stretching fixture and stretched to a strain value of 50% (the traction force was 1.5 N, and the stretching speed was 100 mm / min; the stretching treatment was carried out in an environment with a relative humidity of 75%), so that the axial length had an elongation change of 50%.

[0050] Step (3): The hydrogel together with the stretching fixture was successively soaked in ethanol / water solutions with volume concentrations of 30%, 40%, 50%, and 70% for fixation treatment. The single fixation time was 2 h, and the total was 8 h;

[0051] Step (4): Dialyze the hydrogel obtained in step (3) with deionized water. Then replace it with ethanol 4 times, and then replace it with acetone 4 times. Finally, naturally dry it in the air to obtain a low-swelling and high-strength chitin rod.

[0052] Example 2

[0053] The difference between this example and Example 1 is that in step (2), the chitin hydrogel obtained in step (1) is placed on a stretching fixture and stretched by a strain value of 80% (the traction force is 1.5 N, the stretching speed is 100 mm / min; the stretching treatment is carried out in an environment with a relative humidity of 75%), so that its axial length changes by 80% in elongation. Other steps and operations remain unchanged, and a low-swelling and high-strength chitin rod is prepared.

[0054] Example 3

[0055] The difference between this example and Example 1 is that in step (2), the chitin hydrogel obtained in step (1) is placed on a stretching fixture and stretched by a strain value of 100% (the traction force is 1.5 N, the stretching speed is 100 mm / min; the stretching treatment is carried out in an environment with a relative humidity of 75%), so that its axial length changes by 100% in elongation. Other steps and operations remain unchanged, and a low-swelling and high-strength chitin rod is prepared.

[0056] Example 4

[0057] The difference between this example and Example 3 is that the stretching in step (2) is carried out under conventional humidity conditions (relative humidity of 40% - 50%). Other steps and operations remain unchanged, and a low-swelling and high-strength chitin rod is prepared.

[0058] Example 5

[0059] The difference between this example and Example 3 is that in step (3), the hydrogel together with the stretching fixture is immersed in an ethanol / water solution with a volume concentration of 30% and fixed for 8 h. Other steps and operations remain unchanged, and a low-swelling and high-strength chitin rod is prepared.

[0060] Example 6

[0061] The difference between this example and Example 3 is that in step (3), the hydrogel together with the stretching fixture is immersed in an ethanol / water solution with a volume concentration of 70% and fixed for 8 h. Other steps and operations remain unchanged, and a low-swelling and high-strength chitin rod is prepared.

[0062] Example 7

[0063] The difference between this embodiment and Embodiment 1 lies in that: the parameters in Embodiment 1 are adjusted according to the main parameters shown in Table 1. Among them, step (3) is adjusted to: soak the hydrogel together with the stretching fixture successively in sulfuric acid solutions with a temperature of 4°C and mass fractions of 0.01wt.%, 0.02wt.%, 0.03wt.% and 0.05wt.%, with a single fixation time of 7.5 min and a cumulative soaking time of 30 min. Other steps and operations remain unchanged, and a chitin rod with low swelling and high strength is prepared.

[0064] Embodiment 8

[0065] The difference between this embodiment and Embodiment 1 lies in that: the parameters in Embodiment 1 are adjusted according to the main parameters shown in Table 1. Among them, step (3) is adjusted to: soak the hydrogel together with the stretching fixture successively in hydrochloric acid solutions with a temperature of 5°C and mass fractions of 0.04wt.%, 0.05wt.%, 0.07wt.% and 0.1wt.%, with a single fixation time of 15 min and a cumulative soaking time of 60 min. Other steps and operations remain unchanged, and a chitin rod with low swelling and high strength is prepared.

[0066] Embodiment 9

[0067] Based on Embodiment 3, this embodiment adds the following steps in step (3): take out the chitin hydrogel that has been cumulatively soaked in a gradient concentration of ethanol / water solution for 8 h; then place it in a sulfuric acid solution with a mass fraction of 0.05wt.% for 10 min, repeat this step three times for secondary curing, and the cumulative curing time is 8.5 h; then perform the operation of step (4). Other steps and operations remain unchanged, and a chitin rod with low swelling and high strength is prepared.

[0068] Comparative Example 1

[0069] The difference between this comparative example and Embodiment 1 lies in that: the chitin hydrogel has not undergone the pre-stretching in step (2) and the fixation treatment in step (3) of Embodiment 1. The specific operations in this comparative example are as follows:

[0070] Step (1): Dissolve 22 g of NaOH and 8 g of urea in a 500 mL plastic beaker containing 161 g of distilled water. After ultrasonic treatment until complete dissolution, add 8 g of chitin. Place the beaker in a -30 °C refrigerator and freeze for about 2 h. Take out the beaker when ice flowers appear, stir until completely thawed, then place it back in the -30 °C refrigerator and freeze for 12 h. After stirring and thawing again, a transparent chitin solution is obtained. Place the chitin solution in an ice-water bath and mechanically stir for 10 min. During this period, slowly add 0.16 mL of cross-linking agent epichlorohydrin. Then transfer it to a high-speed centrifuge (-10 °C, 7000 rpm, 5 min) to remove air bubbles. Pour the supernatant into a cylindrical mold (diameter 24 mm, length 150 mm) for shaping, and place it in a 4 °C environment for 12 h to obtain a chitin hydrogel;

[0071] Step (2): Dialyze the chitin hydrogel obtained in step (1) with deionized water. Then replace it with ethanol 4 times, and then replace it with acetone 4 times. Finally, dry it naturally in the air to obtain a chitin rod.

[0072] Comparative Example 2

[0073] The difference between this comparative example and Example 1 is that: the chitin hydrogel was not subjected to the fixation treatment in step (3) of Example 1, and the pre-stretching treatment in step (2) of this comparative example was carried out under conventional humidity conditions. The specific operation is as follows:

[0074] Step (1): Dissolve 22 g of NaOH and 8 g of urea in a 500 mL plastic beaker containing 161 g of distilled water. After ultrasonic treatment until complete dissolution, add 8 g of chitin. Place the beaker in a -30 °C refrigerator and freeze for about 2 h. Take out the beaker when ice flowers appear, stir until completely thawed, then place it back in the -30 °C refrigerator and freeze for 12 h. After stirring and thawing again, a transparent chitin solution is obtained. Place the chitin solution in an ice-water bath and mechanically stir for 10 min. During this period, slowly add 0.16 mL of cross-linking agent epichlorohydrin. Then transfer it to a high-speed centrifuge (-10 °C, 7000 rpm, 5 min) to remove air bubbles. Pour the supernatant into a cylindrical mold (diameter 24 mm, length 150 mm) for shaping, and place it in a 4 °C environment for 12 h to obtain a chitin hydrogel;

[0075] Step (2): Place the chitin hydrogel obtained in step (1) on a stretching fixture and stretch it by a strain value of 50% (the traction force is 1.5 N, and the stretching speed is 100 mm / min; the stretching treatment is carried out in an environment with a relative humidity of 40% - 50%), so that its axial length changes by 50% elongation;

[0076] Step (3): Dialyze the hydrogel treated in step (2) with deionized water. Then replace it with ethanol 4 times, and then replace it with acetone 4 times. Finally, naturally dry it in the air to obtain chitin rods.

[0077] Performance Test

[0078] Test the mechanical properties and swelling ratio of the chitin hydrogels prepared in Examples 1-9 and Comparative Examples 1 and 2. The results are shown in Table 2 below. Among them, the maximum flexural strength was measured by the three-point bending method; the swelling ratio was measured by immersing the sample in PBS buffer solution (0.01M, pH 7.4, 37°C).

[0079] Table 2

[0080]

[0081]

[0082] As can be seen from the above table,

[0083] Comparative Example 1 is a chitin rod that has not been pre-stretched and orientation-fixed, and has the defects of low mechanical strength and high liquid absorption rate. On the basis of Comparative Example 1, Comparative Example 2 added a pre-stretching treatment, but did not undergo orientation fixation. The prepared chitin rod still remains isotropic, and the stretching orientation did not achieve effective results.

[0084] Compared with Comparative Examples 1 and 2, in Examples 1-8, on the basis of pre-stretching the chitin hydrogel, ethanol / aqueous solution immersion was used to fix the orientation of the internal molecular chains. In Example 9, sulfuric acid solution was used for further curing. The mechanical properties of the prepared chitin rods were significantly improved (compared with Comparative Example 1, the maximum flexural strength increased by 27% - 133%, the toughness increased by 2% - 34%, and the maximum liquid absorption rate decreased by 10% - 75%), and the axial elongation rate decreased significantly (decreased by 1% - 83%). This shows that in Examples 1-9 of the present invention, the combination of pre-stretching and immersion setting treatment makes the prepared chitin rods have the advantages of high mechanical strength and low swelling ratio.

[0085] Furthermore, the performance test results of Examples 1-3 show that as the stretching ratio of the hydrogel increases, the toughness and elastic modulus of the prepared rods both increase significantly, and the swelling ratio also decreases significantly, proving that different degrees of stretching treatment can affect the arrangement of internal molecular chains in the hydrogel, and a larger stretching ratio can make the molecular chains arrange more compactly and the orientation degree more obvious.

[0086] Furthermore, by comparing the test results of Example 3 and Example 4, it can be seen that when the pre-stretching is carried out under relatively high humidity conditions, the intact structure of the hydrogel can be maintained, and its elastic structure can be better retained, ensuring the effectiveness during the stretching process. Therefore, the mechanical properties and swelling ratio of the rods prepared in Example 3 are superior to those in Example 4. In addition, by comparing the test results of Example 3 with those of Example 5 and Example 6, it can be seen that during the stage of using ethanol / water solution to fix the orientation of the pre-stretched chitin hydrogel, multiple groups of ethanol / water solutions with different concentrations are used to soak the stretched chitin hydrogel in sequence from low to high concentration. While replacing the water in the hydrogel, alkali and urea are removed at the same time. The concentration gradient replacement helps to achieve uniform shrinkage on the surface of the prepared rods, the rod shape is more regular, the overall structure is more compact, and it can resist deformation caused by greater external forces and has a lower liquid absorption rate, thus realizing stable mechanical properties and obtaining better chitin rods.

[0087] In addition, by comparing the test results of Example 9 and Example 3, it can be seen that using different types of curing solutions to fix the pre-stretched chitin hydrogel can further improve the maximum bending strength of the rods and reduce their swelling ratio. This may be because the pre-cooled sulfuric acid solution performs secondary curing on the chitin hydrogel after gradient ethanol curing, which can better remove the alkali component in the dissolution system. Further hydrogen bonds can be established between the chitin molecular chains, enabling better orientation and shaping of the molecular chains after stretching, and the stretching effect is maximally retained, thereby further enhancing its performance.

[0088] The above are only preferred embodiments of the present invention, and do not limit the implementation manners and protection scope of the present invention. For those skilled in the art, it should be realized that any equivalent replacement and obvious changes made by using the content of the specification of the present invention should be included in the protection scope of the present invention.

Claims

1. A preparation method of a chitin rod with low swelling and high strength, characterized in that, It includes the following steps: S1. Chitin is first treated with a mixed solution of alkali and urea, and then undergoes a freeze-thaw cycle to obtain a chitin solution; a cross-linking agent is added and mixed evenly, and then poured into a mold and treated at a low temperature for a certain time to obtain a columnar chitin hydrogel; S2. The columnar chitin hydrogel is placed in an environment with a relative humidity of 70%-80%, and pre-stretched along its axial direction with a traction force of 0.5-2 N and a stretching speed of 50-200 mm / min to increase its axial length by 40%-110% to obtain a stretched chitin hydrogel; S3. The stretched chitin hydrogel is placed in 3-5 groups of curing solutions with increasing concentrations. The curing solution is selected from a mixed solution of ethanol and water, a pre-cooled sulfuric acid solution, or a pre-cooled hydrochloric acid solution, and soaked in order from low to high concentration to obtain an orientation-fixed chitin hydrogel; Or, the stretched chitin hydrogel is placed in 3-5 groups of mixed solutions of ethanol and water with increasing concentrations, soaked in order from low to high concentration, and then the chitin hydrogel is secondarily cured with a pre-cooled sulfuric acid solution or a pre-cooled hydrochloric acid solution to obtain an orientation-fixed chitin hydrogel; S4. The orientation-fixed chitin hydrogel is subjected to dialysis with deionized water and solvent replacement treatment, and then dried to obtain a low-swelling and high-strength chitin rod.

2. The preparation method according to claim 1, characterized in that, In step S1, the cross-linking agent is selected from one or a combination of more than one of epichlorohydrin, ethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether, diglycidyl ether, 1,4-butanediol diglycidyl ether, or genipin.

3. The preparation method according to claim 1, wherein, In step S1, the temperature of the low-temperature treatment is 3-10°C, and the time of the low-temperature treatment is 8-16 h.

4. The preparation method according to claim 1, characterized in that, In step S3, the cumulative soaking time of the stretched chitin hydrogel in the mixed solution of ethanol and water is 6-12 h; the cumulative soaking time of the stretched chitin hydrogel in the pre-cooled sulfuric acid solution or the pre-cooled hydrochloric acid solution is 10-120 min.

5. The preparation method according to claim 1, characterized in that, In step S4, the solvent replacement treatment includes: for the chitin hydrogel after dialysis with deionized water, first perform multiple solvent replacements with ethanol, and then perform multiple solvent replacements with acetone or n-hexane.

6. A chitin rod with low swelling and high strength, characterized in that, The chitin rod is prepared by the preparation method according to any one of claims 1-5.

7. Use of a chitin rod in bone repair and reconstruction, characterized in that, The chitin rod prepared by the preparation method according to any one of claims 1-5 is applied to the preparation of a bone nail for a sports medical device.

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