A cross-linked esterified modified microcrystalline cellulose and a method for preparing the same

Abstract

The application provides cross-linked esterification modified microcrystalline cellulose and a preparation method thereof, wherein the agglomeration of the microcrystalline cellulose is improved by a double modification method of cross-linking and then esterification, the prepared cross-linked esterification modified microcrystalline cellulose has nanoscale size and high crystallinity, and has good mechanical properties and biocompatibility, and is particularly suitable for the fields of biological stents, tissue repair, drug delivery and biosensors. The application also uses the cross-linked esterification modified microcrystalline cellulose to prepare a collagen composite matrix, and the collagen composite matrix has better mechanical properties, water absorption properties and spatial structure stability, and brings new choices for biomedical material research and application.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medical food, and particularly relates to a cross-linked esterified modified microcrystalline cellulose and a preparation method thereof. BACKGROUND

[0002] Collagen, as one of the main structural proteins in the human body, is widely present in connective tissue and has excellent biocompatibility and biological activity, and thus is widely used in the fields of biomedical materials, cosmetics, food and health products, etc. At present, various collagen composite matrices prepared by taking collagen as the main raw material, such as wound dressings and artificial skin, have been commercialized and entered the market. Such collagen composite matrices have mechanical properties similar to natural skin and can maintain the moisture of the wound, which is conducive to the healing of the wound. However, the collagen composite matrices in the prior art still have problems such as low supportability due to poor mechanical properties, which is not conducive to cell adsorption and proliferation and limits the application range thereof.

[0003] Microcrystalline cellulose is a natural organic polymer material with biodegradability, and its main component is a straight-chain polysaccharide material combined by β-1, 4-glucoside bonds. It is generally obtained by acid hydrolysis of natural cellulose to the limit degree of polymerization, and has the form of extremely fine short rod or powder porous particles. Microcrystalline cellulose has a large specific surface area and also has high Young's modulus and high strength. As a biological material, microcrystalline cellulose also has the characteristics of light weight, biodegradability, biocompatibility and renewability. Therefore, in the prior art, microcrystalline cellulose with high mechanical strength and biodegradability is added to the collagen composite matrix to improve the mechanical properties of the matrix. The patent document with the publication number CN 102886063 B discloses a nano-microcrystalline cellulose reinforced collagen composite matrix. The swelling performance test shows that the composite matrix has a swelling rate of 500% after 500 min at a content of 7wt% of nano-microcrystalline cellulose. The mechanical performance test shows that the mechanical strength of the composite matrix is improved by 30% compared with the pure collagen scaffold.

[0004] Although the above method uses nano-microcrystalline cellulose to improve the performance of the collagen composite matrix, the surface of microcrystalline cellulose has a large number of hydroxyl groups, has good hydrophilicity, and is easy to form hydrogen bonds to cause aggregation, which cannot be uniformly and stably dispersed in water, which is not conducive to the preparation of the collagen composite matrix and further affects the mechanical properties and water absorption of the collagen composite matrix. SUMMARY

[0005] In order to solve the problems of poor dispersibility of microcrystalline cellulose in water and low mechanical property of collagen composite matrix prepared in the prior art, the application provides a cross-linked esterified modified microcrystalline cellulose and a preparation method thereof. The agglomeration of the microcrystalline cellulose is improved by the double modification method of cross-linking and esterification, and the prepared cross-linked esterified modified microcrystalline cellulose has nanoscale size and high crystallinity, thereby providing a new solution for the preparation of the reinforced collagen composite matrix.

[0006] The application provides a preparation method of cross-linked esterified modified microcrystalline cellulose, comprising the following steps:

[0007] S1, after the microcrystalline cellulose suspension is micronized, a cross-linking agent is added to perform cross-linking reaction, and cross-linked modified microcrystalline cellulose is prepared;

[0008] S2, the cross-linked modified microcrystalline cellulose prepared in step S1 is subjected to esterification reaction with soybean oil, and cross-linked esterified modified microcrystalline cellulose is prepared.

[0009] In order to improve the dispersibility of the microcrystalline cellulose, so as to be better applied to the preparation of the collagen composite matrix and further improve the mechanical property and water absorption property of the matrix, the microcrystalline cellulose is subjected to the double modification of cross-linking and esterification in the application. In the application, a dialdehyde compound is used as the cross-linking agent, which generally includes glutaraldehyde and glyoxal. The dialdehyde compound has two symmetrical aldehyde groups (-CHO), can first react with the hydroxyl groups (-OH) in the microcrystalline cellulose to generate hemiacetal, and then cross-link to generate stable acetal compounds. The cross-linking reaction makes the molecules of the microcrystalline cellulose form cross-linking bridges, thereby increasing the cross-linking points between the molecules of the microcrystalline cellulose. On the basis of the cross-linking modification, the esterification reaction is performed between the un-cross-linked hydroxyl groups (-OH) on the microcrystalline cellulose and the fatty acids in the soybean oil. The soybean oil, as a commonly used vegetable oil, is easy to obtain, has good biocompatibility and biodegradability, and contains various fatty acids, including saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids, especially rich in polyunsaturated fatty acids such as linoleic acid and linolenic acid. The introduction of the soybean oil fatty acid group further increases the molecular weight and fiber strength of the cross-linked modified microcrystalline cellulose. The microcrystalline cellulose prepared by the modification of cross-linking and esterification has nanoscale size and high crystallinity, has a larger specific surface area, can be uniformly and stably dispersed in a solution, and the mechanical strength is greatly improved. Meanwhile, the cross-linked esterified modified microcrystalline cellulose has good biocompatibility and low toxicity, and is suitable for the preparation of biomedical materials. Therefore, the cross-linked esterified modified microcrystalline cellulose has important significance for the preparation of the reinforced collagen composite matrix, can further improve the mechanical property of the pure collagen matrix with high water absorption, and expands the application range of the matrix.

[0010] Specifically, in step S1, the concentration of microcrystalline cellulose in the microcrystalline cellulose suspension is 20-30 wt.%; the microcrystalline cellulose can be commercially available or self-made, and the commercially available conventional microcrystalline cellulose, such as nano-microcrystalline cellulose, or its co-processed product, etc., can be suitable for the present application. The microcrystalline cellulose can also be prepared by the following method: mixing wood pulp with dilute sulfuric acid, acid hydrolysis under heating, neutralizing with ammonia water after cooling, and performing pressure filtration, washing, drying, and sieving on the neutralized liquid to obtain the microcrystalline cellulose. The preparation method of the microcrystalline cellulose is further preferably as follows: mixing wood pulp with dilute sulfuric acid with a concentration of 5-20 wt.% at a weight ratio of 1:(10-20), acid hydrolysis under heating to 70-120 °C for 0.5-2 h, neutralizing to pH 5-7 by adding ammonia water with a concentration of 10-30 wt.% after cooling to 50-70 °C; pumping the neutralized liquid into a plate-and-frame filter press for pressure filtration, washing with reverse osmosis water until the conductivity of the washing liquid is less than 200 uS.cm -1 , and drying the filter cake in a flash dryer, with the flash drying parameters set as follows: the inlet air temperature is 130-160 °C, and the outlet air temperature is 60-90 °C. The dried filter cake is sieved using an 80-100 mesh rotary vibrating screen to obtain the microcrystalline cellulose.

[0011] As a preference, in step S1, the crosslinking agent is selected from one or a mixture of both of glutaraldehyde and glyoxal. Among the general dialdehyde crosslinking agents, the number of methylene groups between the two pairs of carbonyl groups has a certain influence on the binding effect of the crosslinking points, and further affects the crystallinity and fiber strength of the microcrystalline cellulose. In addition, the crosslinking modification of the microcrystalline cellulose can also control the crosslinking degree and the formation of crosslinking structure by adjusting the concentration of the crosslinking agent and the reaction conditions, etc.

[0012] As a preference, in step S1, the amount of the crosslinking agent added is 0.1-2 wt.% of the microcrystalline cellulose, and further preferably 0.3-1.5 wt.%.

[0013] As a preference, in step S1, the micronization treatment includes ball milling, high-pressure homogenization, emulsification, etc., and further preferably ball milling.

[0014] As a preference, in step S1, the temperature of the crosslinking reaction is 40-60 °C, and the time is 2-4 h.

[0015] As a preference, in step S2, the amount of soybean oil added is 20-50 wt.% of the microcrystalline cellulose.

[0016] As a preference, in step S2, the esterification reaction uses ethanol as the solvent, and the mass ratio of soybean oil to ethanol is 1:(0.8-1.2), and further preferably 1:1.

[0017] Preferably, in step S2, the esterification reaction is carried out at a temperature of 100-150°C for 3-4 hours.

[0018] Preferably, after the esterification reaction in step S2, the obtained reaction solution is subjected to spray drying, iron removal and sieving to obtain the cross-linked esterification modified microcrystalline cellulose.

[0019] Preferably, the spray drying is carried out by a spray dryer, and the spray dryer is set at an inlet temperature of 170-200°C and an outlet temperature of 60-90°C.

[0020] Preferably, the iron removal is carried out by an iron remover, and the iron remover is set at a magnetic field intensity of 10,000-120,000 Gauss. In the preparation of pharmaceutical excipients, an iron remover is usually used to remove iron impurities in the material to improve the quality of the product and avoid the reaction between active ingredients and iron impurities in the pharmaceutical material.

[0021] Preferably, the material after the iron removal is collected by an 80-100 mesh ultrasonic sieve to obtain the cross-linked esterification modified microcrystalline cellulose.

[0022] The application also provides a cross-linked esterification modified microcrystalline cellulose prepared by the above preparation method. The cross-linked esterification modified microcrystalline cellulose can be applied in the fields of biological scaffolds, three-dimensional printing construction, tissue repair, drug delivery and controlled release systems, etc. Specifically, the cross-linked esterification modified microcrystalline cellulose has good mechanical strength and stable spatial structure, and can be used to prepare biological scaffolds to support cell adhesion, proliferation and differentiation, and promote tissue regeneration and repair. The cross-linked esterification modified microcrystalline cellulose has a large specific surface area, which is beneficial to the adsorption and slow release of drugs, and can be used as a drug carrier to prepare a controlled release drug delivery system to achieve sustained release of drugs. The cross-linked esterification modified microcrystalline cellulose can also be used as a substrate material for biosensors to realize the preparation of high-sensitivity and high-stability biosensors by taking advantage of its highly crystalline characteristics and large surface area.

[0023] The application also provides a collagen composite matrix comprising the cross-linked esterification modified microcrystalline cellulose. Further, the collagen composite matrix comprises 0.05-1 wt% of microcrystalline cellulose. Compared with the prior art, the collagen composite matrix provided by the application has a stable spatial structure, better swelling performance and mechanical properties, and can be applied in the fields of wound dressings, tissue induction regeneration membranes, soft tissue patches, tissue engineering skin and masks, etc.

[0024] The cross-linked esterification modified microcrystalline cellulose provided by the present application has simple preparation method, nanoscale size and high crystallinity, is not easy to agglomerate in aqueous solution, and has good mechanical properties and biocompatibility, and is particularly suitable for the fields of biological stents, tissue repair, drug delivery and biosensors. Compared with the prior art, the collagen composite matrix prepared from the cross-linked esterification modified microcrystalline cellulose has better mechanical properties, water absorption properties and spatial structure stability, and brings new choices for biomedical material research and application. Meanwhile, the modification method of cross-linking first and esterification later provided by the present application also brings a new idea for improving the performance of microcrystalline cellulose. DETAILED DESCRIPTION

[0025] The advantages and effects of the present application can be easily understood by those skilled in the art from the disclosure of the specification. The present application can also be implemented or applied by different specific embodiments, and the details in the specification can be modified or changed based on different views and applications without departing from the spirit of the present application. It should be noted that the following examples and features in the examples can be combined with each other without conflict. The methods used in the examples of the present application are conventional methods, and the reagents used can be obtained from commercial channels.

[0026] Example 1:

[0027] The present embodiment provides a cross-linked esterification modified microcrystalline cellulose, and the preparation method thereof is as follows:

[0028] Preparation of microcrystalline cellulose: 200 kg of wood pulp and 10 wt.% dilute sulfuric acid were mixed in a reaction kettle at a mass ratio of 1:15, and acid hydrolysis was carried out at a temperature of 95-100℃ for 1.5 hours to obtain an acid hydrolysis liquid. The acid hydrolysis liquid was cooled to 65℃, and 15 wt.% ammonia water was added to adjust the pH value to 6.5. The neutralized liquid was pumped into a plate and frame filter press for pressure filtration, and then washed with first-stage reverse osmosis water until the conductivity of the washing liquid was less than 200 uS.cm -1 , and the filter cake was dried in a flash dryer at an inlet air temperature of 150-160℃ and an outlet air temperature of 80-90℃. The dried material was collected and passed through a 100-mesh ultrasonic sieve to obtain the microcrystalline cellulose.

[0029] Cross-linking modification: the microcrystalline cellulose prepared above was prepared into a 20 wt.% suspension with pure water, and micro-pulverized by a ball mill at a speed of 500 r / min for 60 minutes. The slurry was transferred to a cross-linking reaction kettle, and 0.3 wt.% of glutaraldehyde based on the weight of the microcrystalline cellulose was added, and stirred at 55℃ for 3h to obtain the cross-linked modified microcrystalline cellulose.

[0030] Esterification modification: add soybean oil ethanol mixture into the above reaction kettle with crosslinking modification microcrystalline cellulose, the soybean oil ethanol mixture is 20wt.% of microcrystalline cellulose, and the ethanol is 20wt.% of microcrystalline cellulose, stir evenly, and then react at 110-115℃ for 4 hours to obtain a reaction solution.

[0031] Spray drying: pump the reaction solution into the spray dryer, and spray dry under the conditions of inlet air temperature of 190-200℃ and outlet air temperature of 80-90℃. Collect the spray-dried material, remove iron under the condition of 80000 gauss with an iron remover, and sieve to obtain crosslinked esterified modified microcrystalline cellulose, which is sample one.

[0032] Example 2:

[0033] This example provides another crosslinked esterified modified microcrystalline cellulose, and the preparation method is basically the same as that of example 1, the difference is that the addition amount of glutaraldehyde is 0.05wt.% of microcrystalline cellulose, and sample two is prepared.

[0034] Example 3:

[0035] This example provides another crosslinked esterified modified microcrystalline cellulose, and the preparation method is basically the same as that of example 1, the difference is that the addition amount of glutaraldehyde is 1wt.% of microcrystalline cellulose, and sample three is prepared.

[0036] Example 4:

[0037] This example provides another crosslinked esterified modified microcrystalline cellulose, and the preparation method is basically the same as that of example 1, the difference is that the addition amount of glutaraldehyde is 2wt.% of microcrystalline cellulose, and sample four is prepared.

[0038] Example 5:

[0039] This example provides another crosslinked esterified modified microcrystalline cellulose, and the preparation method is basically the same as that of example 1, the difference is that glyoxal is used as a crosslinking agent instead of glutaraldehyde, and sample five is prepared.

[0040] Example 6:

[0041] This example provides another crosslinked esterified modified microcrystalline cellulose, and the preparation method is basically the same as that of example 5, the difference is that the addition amount of glyoxal is 2wt.% of microcrystalline cellulose, and sample six is prepared.

[0042] Example 7:

[0043] This example provides a crosslinked esterified modified microcrystalline cellulose, and the preparation method is as follows:

[0044] Preparation of microcrystalline cellulose: 200 kg of wood pulp was mixed with 10 wt.% dilute sulfuric acid in a mass ratio of 1:15 in a reaction kettle, and acid hydrolysis was carried out at a temperature of 95-100°C for 1.5 hours to obtain an acid hydrolysis solution. The acid hydrolysis solution was cooled to 65°C, and 15 wt.% ammonia water was added to the acid hydrolysis solution to adjust the pH to 6.5. The neutralized solution was pumped into a plate-and-frame filter press for pressure filtration, and then washed with 15 wt.% ammonia water until the conductivity of the washing solution was less than 200 uS.cm -1 , and then dried under pressure to obtain a microcrystalline cellulose filter cake. The filter cake was sent to a flash dryer for drying at an inlet air temperature of 150-160°C and an outlet air temperature of 80-90°C, and the dried material was collected and passed through a 100-mesh ultrasonic sieve to obtain the microcrystalline cellulose.

[0045] Cross-linking modification: The microcrystalline cellulose prepared above was prepared into a 30 wt.% suspension with pure water, and micro-pulverized with a ball mill at a speed of 500 r / min for 60 minutes. The slurry was transferred to a cross-linking reaction kettle, and 0.5 wt.% glutaraldehyde based on the weight of the microcrystalline cellulose was added. The mixture was stirred at 45°C for 4 hours to obtain cross-linked modified microcrystalline cellulose.

[0046] Esterification modification: A mixture of soybean oil and ethanol was added to the reaction kettle containing the cross-linked modified microcrystalline cellulose, wherein the soybean oil accounted for 30 wt.% of the weight of the microcrystalline cellulose, and the ethanol accounted for 24 wt.% of the weight of the microcrystalline cellulose. After stirring, the mixture was reacted at a temperature of 135-140°C for 3 hours to obtain a reaction solution.

[0047] Spray drying: The reaction solution was pumped into a spray dryer, and spray dried at an inlet air temperature of 170-180°C and an outlet air temperature of 60-70°C. The spray-dried material was collected, de-ironed with an iron remover at a magnetic field strength of 100,000 Gauss, and then passed through a 100-mesh ultrasonic sieve to obtain cross-linked and esterified modified microcrystalline cellulose, which was sample seven.

[0048] Example 8:

[0049] This example provides another cross-linked and esterified modified microcrystalline cellulose, which is prepared by the same method as in Example 7, except that the mixture of soybean oil and ethanol added contains 10 wt.% soybean oil based on the weight of the microcrystalline cellulose, and 8 wt.% ethanol based on the weight of the microcrystalline cellulose, to obtain sample eight.

[0050] Example 9:

[0051] This example provides another cross-linked and esterified modified microcrystalline cellulose, which is prepared by the same method as in Example 7, except that the mixture of soybean oil and ethanol added contains 50 wt.% soybean oil based on the weight of the microcrystalline cellulose, and 60 wt.% ethanol based on the weight of the microcrystalline cellulose, to obtain sample nine.

[0052] Comparative Example 1:

[0053] The present comparative example provides a nanocellulose crystal, and the preparation method thereof specifically comprises the following steps: 15 g of microcrystalline cellulose powder is weighed and added into 140 mL of 65 wt.% sulfuric acid, and mechanical stirring is performed under a constant temperature water bath at 45 °C for 6 h. After the reaction is completed, a large amount of distilled water is added to stop the reaction. After cooling to room temperature, ultrasonic dispersion is performed under the condition of a frequency of 45 kHz and a power of 250 W. Subsequently, repeated dialysis is performed three times using pure water until the pH is stable. The dialyzed sample is placed at 4 °C overnight, and then freeze-drying is performed at -60 °C to obtain white nanocellulose crystals, which are sample ten.

[0054] Comparative Example 2:

[0055] The present comparative example provides a cross-linked modified microcrystalline cellulose, and the preparation method thereof is as follows: the cross-linked modified microcrystalline cellulose reaction liquid obtained in Example 1 is pumped into a spray dryer, and spray drying is performed under the condition that the inlet air temperature is 190-200 °C and the outlet air temperature is 80-90 °C. The spray-dried material is collected and de-ironed by an iron remover under the condition of 80000 gauss. After de-ironing is completed, the material is sieved through a 100-mesh ultrasonic sieve to obtain cross-linked modified microcrystalline cellulose, which is sample eleven.

[0056] Comparative Example 3:

[0057] The present comparative example provides an esterified modified microcrystalline cellulose, and the preparation method thereof is as follows: the microcrystalline cellulose obtained in Example 1 is added into a reaction kettle together with a soybean oil-ethanol mixed solution. In the soybean oil-ethanol mixed solution, the soybean oil accounts for 20 wt.% of the weight of the microcrystalline cellulose, and the ethanol accounts for 20 wt.% of the weight of the microcrystalline cellulose. After uniform stirring, esterified modified microcrystalline cellulose reaction liquid is obtained by reacting at a temperature in the range of 110-115 °C for 4 hours. The esterified modified microcrystalline cellulose reaction liquid is pumped into a spray dryer, and spray drying is performed under the condition that the inlet air temperature is 190-200 °C and the outlet air temperature is 80-90 °C. The spray-dried material is collected and de-ironed by an iron remover under the condition of 80000 gauss. After de-ironing is completed, the material is sieved through a 100-mesh ultrasonic sieve to obtain esterified modified microcrystalline cellulose, which is sample twelve.

[0058] Example 10:

[0059] The sample provided in Examples 1-9 and Comparative Examples 1-3 was used to prepare a collagen composite matrix, and the preparation method was as follows: 1wt.% collagen solution was prepared using 1wt.% acetic acid aqueous solution as the solvent, and 1wt.% sample 1-12 solutions were prepared using 1wt.% acetic acid aqueous solution as the solvent. The sample solutions were added dropwise into the collagen solution, and stirred mechanically at room temperature for 6h to obtain a collagen composite solution containing 5 parts by mass of sample solution and 95 parts by mass of collagen solution. The collagen composite solution was degassed in vacuum, and then injected into a polytetrafluoroethylene mold to spread naturally. After standing at 4°C for 12h, the collagen composite matrix was obtained by natural drying at room temperature.

[0060] Performance test

[0061] The collagen composite matrix prepared in Example 10 was subjected to swelling performance test and mechanical performance test.

[0062] Swelling property test:

[0063] The dry collagen composite matrix was weighed and recorded as W d , and then immersed in a phosphate buffer solution. The sample was taken out after 20min, 60min and 250min of immersion, and the surface residual liquid was wiped off. The mass of the sample in the wet state was weighed and recorded as W t . The sample swelling rate (SR%) at different immersion times was calculated using the following formula:

[0064]

[0065] The average value of 5 parallel samples in each group was calculated, and the results are shown in Table 1.

[0066] Mechanical property test:

[0067] The standardized strip samples (2mm x 5mm) were subjected to uniaxial tensile test at room temperature, and the constant tensile rate was 3mm / min. The main properties were tensile modulus, tensile strength and elongation at break. The average value of 5 parallel samples in each group was calculated, and the results are shown in Table 1.

[0068] Table 1. Performance test

[0069]

[0070] It can be seen from Table 1 and Examples 1-6 and Comparative Example 3 that the selection of the crosslinking agent in the crosslinking modification process has certain influence on the crystallinity of the microcrystalline cellulose and the mechanical properties of the collagen composite matrix. At present, glutaraldehyde is the most widely used dialdehyde crosslinking agent, but compared with glyoxal, there are still three methylene groups between the two pairs of carbonyl groups of glutaraldehyde, which have certain binding effect on the crosslinking points after crosslinking, so that the crystallinity of the microcrystalline cellulose crosslinked by glutaraldehyde is slightly lower than that of the microcrystalline cellulose crosslinked by glyoxal, thereby affecting the mechanical strength and the stability of the spatial structure of the collagen composite matrix. At the same time, when the addition amount of the crosslinking agent is 0.1-2 wt.% of the microcrystalline cellulose, the collagen composite matrix prepared has good water absorption performance and mechanical properties. It can be seen from Table 1 and Examples 7-9 and Comparative Example 2 that when the addition amount of the soybean oil is 20-50 wt.% of the microcrystalline cellulose, the esterification modification on the basis of the crosslinking modification has further promoting effect on the mechanical properties of the microcrystalline cellulose.

[0071] The above-described examples only describe the preferred embodiments of the present application, and do not limit the scope of the present application. Without departing from the design spirit of the present application, various modifications and improvements to the technical solutions of the present application made by those skilled in the art shall fall within the protection scope of the present application.

Claims

1. A collagen composite matrix, characterized in that, The cross-linked esterified modified microcrystalline cellulose comprises 0.05-1 wt% cross-linked esterified modified microcrystalline cellulose; the cross-linked esterified modified microcrystalline cellulose is prepared by the following steps: S1, after the microcrystalline cellulose suspension is micronized, a cross-linking agent is added to perform cross-linking reaction to obtain cross-linked modified microcrystalline cellulose; S2, the cross-linked modified microcrystalline cellulose obtained in step S1 is subjected to esterification reaction with soybean oil to obtain cross-linked esterified modified microcrystalline cellulose; In step S1, the cross-linking agent is selected from one or a mixture of two of glutaraldehyde and glyoxal; the cross-linking agent is added in an amount of 0.1-2 wt.% of the microcrystalline cellulose; In step S2, the soybean oil is added in an amount of 20-50 wt.% of the microcrystalline cellulose.

2. The collagen composite matrix of claim 1, wherein, In step S1, the concentration of the microcrystalline cellulose in the microcrystalline cellulose suspension is 20-30 wt.%.

3. The collagen composite matrix of claim 1, wherein, In step S2, the esterification reaction is performed with ethanol as a solvent, and the mass ratio of soybean oil to ethanol is 1:(0.8-1.2).

4. The collagen composite matrix of claim 1, wherein, In step S2, the temperature of the esterification reaction is 100-150℃, and the time is 3-4 h.

5. The collagen composite matrix of claim 1, wherein, In step S2, after the esterification reaction, the obtained reaction solution is subjected to spray drying, iron removal and sieving to obtain cross-linked esterified modified microcrystalline cellulose.

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