Novel cross-linked agarose polymer material and preparation method thereof

Abstract

The invention discloses a novel cross-linked agarose polymer material, which relates to the technical field of agarose and comprises an agarose matrix, a cross-linking agent, a nano reinforcing agent and a functional monomer, wherein the agarose matrix is agarose or a derivative thereof, the cross-linking agent is selected from a polyethylene glycol-based cross-linking agent, an aldehyde cross-linking agent, an amide cross-linking agent or a combination thereof, the nano reinforcing agent is selected from a carbon-based nano material, a calcium phosphate nano material or a compound thereof, and the functional monomer is selected from a monomer containing an acrylic acid group or an epoxy group. Through the cross-linking agent and the nano reinforcing agent, the compression resistance and the tensile strength of the agarose gel are remarkably enhanced, the pore structure of the gel is more uniform and adjustable, and cell migration, nutrient substance transfer and drug release are facilitated; the grafting of the functional monomer provides abundant reaction active sites for the agarose matrix, so that the subsequent chemical modification or biological functionalization is facilitated, and the application range of the material in the biomedical field is expanded.

Description

Technical Field

[0001] The present invention relates to the technical field of agarose, in particular to a new cross-linked agarose polymer material and a preparation method thereof. Background Art

[0002] Agarose is a natural polysaccharide extracted from agar. It has excellent biocompatibility, chemical stability, and adjustable gelation properties, and is widely used in biomedicine, drug delivery, tissue engineering, separation and purification, and other fields. However, traditional agarose materials suffer from low mechanical strength, a simple pore structure, and insufficient functionalization, which limits their use in high-performance applications. For example, in tissue engineering scaffolds or drug controlled release carriers, the mechanical properties of agarose gel are insufficient to withstand the stresses of complex physiological environments, and it lacks specific functional groups to achieve precise chemical modification or biological activity regulation. Summary of the Invention

[0003] In order to solve the above technical problems, the present invention provides a new cross-linked agarose polymer material and a preparation method thereof. The specific technical solution is as follows:

[0004] A new cross-linked agarose polymer material comprises the following components, measured by weight: 100 parts of an agarose matrix, 5 to 20 parts of a cross-linking agent, 0.5 to 5 parts of a nano-enhancer, and 1 to 10 parts of a functionalized monomer. The agarose matrix is ​​selected from agarose or a derivative thereof with a molecular weight of 50 to 200 kDa, the cross-linking agent is selected from a polyethylene glycol-based cross-linking agent, an aldehyde cross-linking agent, an amide cross-linking agent, or a combination thereof, the nano-enhancer is selected from a carbon-based nano-material, a calcium phosphate nano-material, or a composite thereof, and the functionalized monomer is selected from a monomer containing an acrylic acid group or an epoxy group.

[0005] Preferably:

[0006] The agarose matrix has a molecular weight of 100 to 150 kDa and is formed into a matrix solution at a concentration of 5 to 10 wt%;

[0007] and / or the cross-linking agent comprises a composite cross-linking system of polyethylene glycol diacrylate and glutaraldehyde, wherein the concentration of glutaraldehyde is 10 to 25 v / v%;

[0008] and / or the nano-enhancer comprises graphene oxide and hydroxyapatite, wherein the sheet diameter of the graphene oxide is 0.5 to 2 μm, the particle size of the hydroxyapatite is 20 to 50 nm, and the mass ratio of the graphene oxide to the hydroxyapatite is 1:(0.2 to 1);

[0009] And / or the functionalized monomer is glycidyl methacrylate, and its added amount is 1-5% of the mass of the agarose matrix.

[0010] Preferably, the cross-linking agent further comprises N,N'-methylenebisacrylamide, and the added amount thereof is 0.5-2% of the total mass of the cross-linking agent.

[0011] Preferably, the invention further comprises 0.05 to 0.3 parts of a catalyst, wherein the catalyst is selected from one or a combination of a photoinitiator and potassium persulfate, the concentration of the photoinitiator is 0.05 to 0.2 wt %, and the concentration of potassium persulfate is 0.01 to 0.1 wt %.

[0012] The present invention also provides a preparation method for preparing the novel cross-linked agarose polymer material as described in any one of the above, the preparation method comprising the following steps:

[0013] a. Prepare agarose matrix solution;

[0014] b. preparing a nanoenhancer dispersion and mixing it with an agarose matrix solution;

[0015] c. adding a crosslinking agent and a catalyst to form a crosslinked network by photopolymerization and / or thermal polymerization to obtain a gel;

[0016] d. The obtained gel is post-processed to adjust the pore structure, thereby obtaining a new cross-linked agarose polymer material.

[0017] Preferably, the agarose matrix is ​​chemically modified to introduce reactive sites, and the modification process comprises the following steps:

[0018] i. Dissolve agarose in deionized water to form a 5-10 wt% solution at 70-90 ° C;

[0019] ii. Cool to 40-60°C, add 0.05-0.2M NaOH and adjust the pH to 7.5-8.5;

[0020] iii. adding glycidyl methacrylate dropwise and reacting at 40-60°C for 2-6 hours to obtain a modified agarose matrix;

[0021] iv. Wash with ethanol / water mixture and freeze-dry.

[0022] Preferably, step b specifically includes the following sub-steps:

[0023] i. dispersing graphene oxide in deionized water and ultrasonically treating the mixture to form a suspension of 0.1 to 2 mg / mL;

[0024] ii. Add hydroxyapatite and continue ultrasonic treatment to form a GO-HAP composite dispersion;

[0025] iii. Mix the composite dispersion and agarose matrix solution in a volume ratio of 1:(5-15) and stir evenly.

[0026] Preferably, step c specifically includes the following sub-steps:

[0027] i. polyethylene glycol diacrylate and glutaraldehyde were added to the mixture, wherein the amount of polyethylene glycol diacrylate added was 5 to 15% by mass of the agarose matrix;

[0028] ii. Add N,N'-methylenebisacrylamide and a photoinitiator, and remove dissolved oxygen through nitrogen;

[0029] iii. irradiating the film with 350-400 nm ultraviolet light for 10-30 min for photopolymerization;

[0030] iv. Heat-initiate glutaraldehyde cross-linking at 50-70°C for 1-3 hours.

[0031] Preferably, step d specifically includes the following sub-steps:

[0032] i. Soak the gel in deionized water for 24 to 72 hours to remove unreacted monomers;

[0033] ii. freeze drying or supercritical CO2 drying is used to control the pore structure, wherein freeze drying is carried out at -20°C to -80°C for 24 to 48 hours, and supercritical CO2 drying is carried out at 10 to 20 MPa for 2 to 6 hours.

[0034] Preferably, potassium persulfate is further added as a thermal initiator in step c, with a concentration of 0.01 to 0.1 wt%.

[0035] The cross-linked agarose novel polymer material provided by the present invention has the following beneficial effects:

[0036] 1. Through the synergistic effect of crosslinkers and nano-enhancers, the compressive and tensile strength of agarose gel is significantly enhanced, enabling it to withstand complex physiological environmental stresses and is suitable for demanding scenarios such as tissue engineering scaffolds and drug controlled release carriers;

[0037] 2. The introduction of cross-linkers and nano-enhancers makes the gel pore structure more uniform and adjustable, which is conducive to the precise regulation of cell migration, nutrient delivery and drug release;

[0038] 3. The grafting of functionalized monomers provides abundant reactive sites for the agarose matrix, facilitating subsequent chemical modification or biological functionalization, thus expanding the application range of the material in the biomedical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] 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 describing the embodiments or the prior art.

[0040] Figure 1This is an SEM image of the new cross-linked agarose polymer material provided by an embodiment of the present invention;

[0041] Figure 2 This is the XRD pattern of the new cross-linked agarose polymer material provided in an embodiment of the present invention. DETAILED DESCRIPTION

[0042] In order to enable those skilled in the art to better understand the technical solution of the present invention, the present invention is described in detail below with reference to the accompanying drawings. The description in this part is only exemplary and explanatory and should not have any limiting effect on the scope of protection of the present invention.

[0043] This embodiment provides a new cross-linked agarose polymer material, which comprises the following components, by weight: 100 parts of an agarose matrix, 5-20 parts of a cross-linking agent, 0.5-5 parts of a nano-enhancer, and 1-10 parts of a functionalized monomer; wherein the agarose matrix is ​​selected from agarose or a derivative thereof having a molecular weight of 50-200 kDa, the cross-linking agent is selected from a polyethylene glycol-based cross-linking agent, an aldehyde cross-linking agent, an amide cross-linking agent, or a combination thereof, the nano-enhancer is selected from a carbon-based nanomaterial, a calcium phosphate nanomaterial, or a composite thereof, and the functionalized monomer is selected from a monomer containing an acrylic acid group or an epoxy group.

[0044] Among them, the agarose matrix uses agarose or its derivatives with a molecular weight of 50 to 200 kDa as the matrix, which not only ensures good solubility and gelation ability, but also avoids the processing difficulty caused by too high molecular weight or insufficient mechanical properties caused by too low molecular weight; the cross-linking agent uses polyethylene glycol-based cross-linking agent, aldehyde cross-linking agent, amide cross-linking agent or a combination thereof. The diversity of cross-linking agents allows flexible regulation of cross-linking density and mechanical properties of the gel according to application requirements. Polyethylene glycol-based cross-linking agents (such as polyethylene glycol diacrylate) have good flexibility and biocompatibility, aldehyde cross-linking agents (such as glutaraldehyde) can provide high cross-linking efficiency, and amide cross-linking agents (such as N,N'-methylenebisacrylamide) enhance chemical stability. The composite cross-linking system makes up for the shortcomings of a single cross-linking agent; nano-enhanced Strengthening agents introduce carbon-based nanomaterials (such as graphene oxide) or calcium phosphate nanomaterials (such as hydroxyapatite) or their complexes, and utilize the excellent mechanical properties and high specific surface area of ​​the nanomaterials to significantly improve the mechanical strength and biological activity of the gel; functional monomers are selected from monomers containing acrylic groups or epoxy groups (such as glycidyl methacrylate), and reactive sites are introduced into the agarose matrix through chemical grafting to facilitate further functional modification, such as grafting bioactive molecules or regulating surface hydrophilicity and hydrophobicity, to meet specific needs in fields such as tissue engineering or drug delivery; new materials can overcome the limitations of traditional agarose gels, such as poor mechanical properties, single pore structure and insufficient functionalization, to achieve comprehensive optimization of mechanical strength, pore structure and biological functionality, and are suitable for high-performance biomedical applications.

[0045] The cross-linked agarose novel polymer material provided in this embodiment has the following beneficial effects:

[0046] 1. Through the synergistic effect of cross-linkers and nano-enhancers, the compressive and tensile strength of agarose gel is significantly enhanced, which can withstand complex physiological environmental stress and is suitable for high-demand scenarios such as tissue engineering scaffolds and drug controlled release carriers.

[0047] 2. The introduction of cross-linkers and nano-enhancers makes the gel pore structure more uniform and adjustable, which is conducive to the precise regulation of cell migration, nutrient delivery and drug release.

[0048] 3. The grafting of functionalized monomers provides abundant reactive sites for the agarose matrix, facilitating subsequent chemical modification or biological functionalization, thus expanding the application range of the material in the biomedical field.

[0049] Further:

[0050] The molecular weight of the agarose matrix is ​​100-150 kDa, and the matrix solution is formed at a concentration of 5-10 wt%.

[0051] The cross-linking agent includes a composite cross-linking system of polyethylene glycol diacrylate and glutaraldehyde, wherein the concentration of glutaraldehyde is 10-25 v / v%.

[0052] The nano-enhancer comprises graphene oxide and hydroxyapatite, wherein the sheet diameter of the graphene oxide is 0.5 to 2 μm, the particle diameter of the hydroxyapatite is 20 to 50 nm, and the mass ratio of the graphene oxide to the hydroxyapatite is 1:(0.2 to 1).

[0053] And / or the functionalized monomer is glycidyl methacrylate, and its added amount is 1-5% of the mass of the agarose matrix.

[0054] Furthermore, the cross-linking agent further comprises N,N'-methylenebisacrylamide, the addition amount of which is 0.5-2% of the total mass of the cross-linking agent.

[0055] Furthermore, the invention further comprises 0.05 to 0.3 parts of a catalyst, wherein the catalyst is selected from one or a combination of a photoinitiator and potassium persulfate, the concentration of the photoinitiator is 0.05 to 0.2 wt %, and the concentration of the potassium persulfate is 0.01 to 0.1 wt %.

[0056] This embodiment also provides a preparation method for preparing the new cross-linked agarose polymer material as described in any one of the above, the preparation method comprising the following steps:

[0057] a. Prepare agarose matrix solution.

[0058] b. Prepare nanoenhancer dispersion and mix with agarose matrix solution.

[0059] c. Add a cross-linking agent and a catalyst to form a cross-linked network through photopolymerization and / or thermal polymerization to obtain a gel.

[0060] d. The obtained gel is post-processed to adjust the pore structure, thereby obtaining a new cross-linked agarose polymer material.

[0061] Furthermore, the agarose matrix is ​​chemically modified to introduce reactive sites, and the modification process includes the following steps:

[0062] i. Dissolve agarose in deionized water to form a 5-10 wt% solution at 70-90°C.

[0063] ii. Cool to 40-60°C and add 0.05-0.2 M NaOH to adjust the pH to 7.5-8.5.

[0064] iii. Glycidyl methacrylate was added dropwise and reacted at 40-60°C for 2-6 hours to obtain a modified agarose matrix.

[0065] iv. Wash with ethanol / water mixture and freeze-dry.

[0066] Furthermore, step b specifically includes the following sub-steps:

[0067] i. Graphene oxide was dispersed in deionized water and ultrasonically treated to form a suspension of 0.1-2 mg / mL.

[0068] ii. Add hydroxyapatite and continue ultrasonic treatment to form a GO-HAP composite dispersion.

[0069] iii. Mix the composite dispersion and agarose matrix solution in a volume ratio of 1:(5-15) and stir evenly.

[0070] Furthermore, step c specifically includes the following sub-steps:

[0071] i. Add polyethylene glycol diacrylate and glutaraldehyde to the mixture, wherein the amount of polyethylene glycol diacrylate added is 5 to 15% of the mass of the agarose matrix.

[0072] ii. Add N,N'-methylenebisacrylamide and photoinitiator, and pass nitrogen to remove dissolved oxygen.

[0073] iii. Irradiate with 350-400 nm ultraviolet light for 10-30 min for photopolymerization.

[0074] iv. Heat-initiate glutaraldehyde cross-linking at 50-70°C for 1-3 hours.

[0075] Furthermore, step d specifically includes the following sub-steps:

[0076] i. Soak the gel in deionized water for 24 to 72 hours to remove unreacted monomers.

[0077] ii. freeze drying or supercritical CO2 drying is used to control the pore structure, wherein freeze drying is carried out at -20°C to -80°C for 24 to 48 hours, and supercritical CO2 drying is carried out at 10 to 20 MPa for 2 to 6 hours.

[0078] Furthermore, potassium persulfate is added as a thermal initiator in step c, with a concentration of 0.01 to 0.1 wt%.

[0079] Specific examples are provided below. The provided examples may enable those skilled in the art to more fully understand the present invention, but are not intended to limit the present invention in any way.

[0080] Example 1

[0081] Weigh 10 g of agarose and add it to 190 mL of deionized water. Place in a thermostatic water bath at 85°C and 500 rpm. Heat for 30 min until completely dissolved, forming a 5 wt% agarose solution. Cool to 50°C and set aside.

[0082] 0.2 g of graphene oxide was added to 100 mL of deionized water and sonicated (400 W, 40 kHz) for 20 minutes to form a 2 mg / mL GO suspension. 0.1 g of hydroxyapatite was added and sonicated for another 10 minutes to form a GO-HAP composite dispersion. This composite dispersion was then mixed with 200 mL of agarose matrix solution at a volume ratio of 1:10 and magnetically stirred at 300 rpm for 15 minutes to obtain a homogeneous mixture.

[0083] To the mixture, add 1.0 g of PEGDA and 0.8 mL of glutaraldehyde (20 v / v%). Add 0.02 g of a photoinitiator (Irgacure 2959, 0.1 wt%) and flow nitrogen through for 10 minutes to remove dissolved oxygen. Pour the mixture into a 10 cm diameter polytetrafluoroethylene mold and place it under a UV curing apparatus. Irradiate with a 365 nm wavelength for 20 minutes to initiate photopolymerization. The mold is then transferred to a constant temperature oven and thermally crosslinked with glutaraldehyde at 60°C for 2 hours to form a gel.

[0084] The gel was immersed in 500 mL of deionized water for 48 hours, with the deionized water replaced every 12 hours to remove unreacted monomers. Half of the gel sample was freeze-dried at -50°C for 36 hours; the other half was dried in a supercritical CO2 dryer at 15 MPa for 4 hours to obtain a cross-linked agarose material.

[0085] Take 5×5×5mm 3The sample was compressed using a universal material testing machine at a rate of 1 mm / min. The maximum stress when the strain was 50% was recorded. The test was repeated three times and the average value was taken.

[0086] The porosity was calculated using the liquid replacement method, using ethanol as the replacement liquid and a sample size of 10 × 10 × 10 mm. 3 , calculation formula: porosity = (wet weight - dry weight) / sample volume × 100%, repeat the test 3 times and take the average value.

[0087] The MTT assay was used to test the survival rate of L929 mouse fibroblasts on the surface of the material for 72 h. The sample size was 10 mm disc and the cell seeding density was 1×10 4 cells / cm 2 , repeat the test 3 times and take the average value.

[0088] The test data is shown in the following table:

[0089]

[0090] Example 2

[0091] Weigh 10g of agarose and add it to 190mL of deionized water. Stir in an 85°C waterbath (500rpm) for 30min to form a 5wt% solution. Cool to 50°C and add 5mL of 0.1M NaOH to adjust the pH to 8.0. Slowly add 0.3g of GMA dropwise and react at 50°C for 4h. Wash three times with 500mL of an ethanol / water mixture and freeze-dry (-50°C for 36h) to obtain the modified agarose matrix.

[0092] Weigh 10g of modified agarose and add it to 190mL of deionized water. Stir at 85°C for 30 minutes to form a 5wt% solution, then cool to 50°C and set aside. Weigh 0.2g of GO and add it to 100mL of deionized water. Ultrasonicate for 20 minutes to form a 2mg / mL suspension. Add 0.1g of HAP and continue ultrasonicating for 10 minutes to form a GO-HAP dispersion. This dispersion was mixed with 200mL of the modified agarose solution at a 1:10 volume ratio and stirred (300rpm) for 15 minutes.

[0093] To the mixture, add 1.0g PEGDA, 0.8mL glutaraldehyde, and 0.018g MBAA. Then, add 0.02g photoinitiator (Irgacure 2959) and 0.01g KPS (0.05wt%). Aerate with nitrogen for 10 minutes to remove dissolved oxygen. Pour the mixture into a polytetrafluoroethylene mold and irradiate with 365nm UV light for 20 minutes to initiate photopolymerization. Thermal initiation is then performed in a 60°C oven for 2 hours to form a gel.

[0094] The gel was immersed in 500 mL of deionized water for 48 h, with the water changed every 12 h. Half of the sample was freeze-dried at -50 °C for 36 h, and the other half was dried at 15 MPa supercritical CO2 for 4 h.

[0095] Take 5×5×5mm 3 The sample was compressed using a universal material testing machine at a rate of 1 mm / min. The maximum stress when the strain was 50% was recorded. The test was repeated three times and the average value was taken.

[0096] The porosity was calculated using the liquid replacement method, using ethanol as the replacement liquid and a sample size of 10 × 10 × 10 mm. 3 , calculation formula: porosity = (wet weight - dry weight) / sample volume × 100%, repeat the test 3 times and take the average value.

[0097] The MTT assay was used to test the survival rate of L929 mouse fibroblasts on the surface of the material for 72 h. The sample size was 10 mm disc and the cell seeding density was 1×10 4 cells / cm 2 , repeat the test 3 times and take the average value.

[0098] The test data is shown in the following table:

[0099]

[0100] Comparative Example

[0101] Weigh 10 g of agarose and add it to 190 mL of deionized water. Place in a thermostatic water bath at 85°C and stir at 500 rpm. Heat for 30 minutes until completely dissolved, forming a 5 wt% agarose solution. Pour the solution into a 10 cm diameter polytetrafluoroethylene mold and cool to room temperature (25°C) for approximately 1 hour to allow for natural gelation.

[0102] The gel was soaked in 500 mL of deionized water for 24 hours, with the deionized water replaced every 8 hours to remove residual impurities. The gel sample was placed in a freeze dryer and freeze-dried at -50°C for 36 hours to obtain an agarose gel.

[0103] Take 5×5×5mm 3 The sample was compressed using a universal material testing machine at a rate of 1 mm / min. The maximum stress when the strain was 50% was recorded. The test was repeated three times and the average value was taken.

[0104] The porosity was calculated using the liquid replacement method, using ethanol as the replacement liquid and a sample size of 10 × 10 × 10 mm. 3 , calculation formula: porosity = (wet weight - dry weight) / sample volume × 100%, repeat the test 3 times and take the average value.

[0105] The MTT assay was used to test the survival rate of L929 mouse fibroblasts on the surface of the material for 72 h. The sample size was 10 mm disc and the cell seeding density was 1×10 4 cells / cm 2 , repeat the test 3 times and take the average value.

[0106] The test data is shown in the following table:

[0107]

[0108] From the above data, it can be seen that the average compressive strength of ordinary agarose gel in the comparative example is 0.83 MPa; the average compressive strength of the freeze-dried sample in Example 1 is 2.47 MPa, and the supercritical CO2 dried sample is 2.63 MPa, which are 2.98 times and 3.17 times that of the comparative example, respectively; the average compressive strength of the freeze-dried sample in Example 2 is 2.89 MPa, and the supercritical CO2 dried sample is 3.05 MPa, which are 3.48 times and 3.67 times that of the comparative example, respectively; the compressive strength of Examples 1 and 2 is significantly better than that of the comparative example, effectively improving the mechanical properties.

[0109] The average porosity of the control group was 85.7%; the average porosity of the freeze-dried sample in Example 1 was 82.3%, and that of the supercritical CO2 dried sample was 78.4%, which were 3.4% and 8.7% lower than those of the control group, respectively. The reduction in porosity was attributed to the introduction of cross-linking agents and nano-enhancers, which made the gel network denser. The post-treatment processes of freeze drying (-50°C, 36h) and supercritical CO2 drying (15MPa, 4h) further regulated the pore structure. Supercritical CO2 drying formed smaller and more uniform pores due to high-pressure conditions. The average porosity of the freeze-dried sample in Example 2 was 80.2%. The porosity of the supercritical CO2 dried sample was 76.3%, which was 5.5% and 10.9% lower than the control example, respectively, and further lower than that of Example 1. The lower porosity was related to the chemical modification and the ternary cross-linking system (PEGDA, glutaraldehyde, MBAA). The modified matrix and additional cross-linking agent increased the cross-linking density, and potassium persulfate promoted the thermal polymerization efficiency to form a tighter network. The porosity of Examples 1 and 2 was lower than that of the control example, and the precise control of the pore structure was achieved through the post-processing process. The porosity of Example 2 was further reduced, indicating that its cross-linked network was denser, which is suitable for applications requiring high strength and fine pores.

[0110] The average cell viability of the control group was 90.2%. In Example 1, the average cell viability of the freeze-dried samples was 92.1%, and that of the supercritical CO2-dried samples was 93.2%, which were 1.9% and 3.0% higher than the control group, respectively. This improvement was attributed to the bioactivity of the nanoenhancer (hydroxyapatite), which promoted cell adhesion and proliferation, and the biocompatibility of the crosslinker (PEGDA). The supercritical CO2-dried samples had a more uniform pore structure (78.4%) that facilitated cell migration and had slightly better biocompatibility than the freeze-dried samples. In Example 2, the average cell viability of the freeze-dried samples was 94.3%, and that of the supercritical CO2-dried samples was 95.2%, which were 4.1% and 5.0% higher than the control group, respectively. This further improvement was related to the chemical modification (GMA grafting). The introduced reactive sites facilitated the subsequent grafting of biomolecules, enhancing cell affinity.

[0111] The principles and implementation methods of the present invention are described herein using specific examples. The description of the above embodiments is only intended to help understand the method and core ideas of the present invention. The above are only preferred implementation methods of the present invention, but the scope of protection of the present invention is not limited thereto. Any person skilled in the art, within the technical scope disclosed by the present invention, can make equivalent replacements or changes based on the technical solutions and inventive concepts of the present invention, and all of these should fall within the scope of protection of the present invention.

Claims

1. A new cross-linked agarose polymer material, characterized in that: The invention comprises the following components in parts by weight: 100 parts of agarose matrix, 5 to 20 parts of a cross-linking agent, 0.5 to 5 parts of a nano-enhancer, and 1 to 10 parts of a functionalized monomer; wherein the agarose matrix is ​​selected from agarose or a derivative thereof with a molecular weight of 50 to 200 kDa, the cross-linking agent is selected from a polyethylene glycol-based cross-linking agent, an aldehyde cross-linking agent, an amide cross-linking agent or a combination thereof, the nano-enhancer is selected from a carbon-based nano-material, a calcium phosphate nano-material or a composite thereof, and the functionalized monomer is selected from a monomer containing an acrylic acid group or an epoxy group.

2. The cross-linked agarose novel polymer material according to claim 1, characterized in that: The agarose matrix has a molecular weight of 100 to 150 kDa and is formed into a matrix solution at a concentration of 5 to 10 wt%; and / or the cross-linking agent comprises a composite cross-linking system of polyethylene glycol diacrylate and glutaraldehyde, wherein the concentration of glutaraldehyde is 10 to 25 v / v%; and / or the nano-enhancer comprises graphene oxide and hydroxyapatite, wherein the sheet diameter of the graphene oxide is 0.5 to 2 μm, the particle size of the hydroxyapatite is 20 to 50 nm, and the mass ratio of the graphene oxide to the hydroxyapatite is 1:(0.2 to 1); And / or the functionalized monomer is glycidyl methacrylate, and its added amount is 1-5% of the mass of the agarose matrix.

3. The cross-linked agarose novel polymer material according to claim 2, characterized in that: The cross-linking agent also includes N,N'-methylenebisacrylamide, the addition amount of which is 0.5-2% of the total mass of the cross-linking agent.

4. The cross-linked agarose novel polymer material according to claim 1, characterized in that The invention also includes 0.05 to 0.3 parts of a catalyst, wherein the catalyst is selected from one or a combination of a photoinitiator and potassium persulfate, the concentration of the photoinitiator is 0.05 to 0.2 wt %, and the concentration of potassium persulfate is 0.01 to 0.1 wt %.

5. A preparation method, characterized in that: For preparing the new cross-linked agarose polymer material according to any one of claims 1 to 4, the preparation method comprises the following steps: a) preparing an agarose matrix solution; b) preparing a nanoenhancer dispersion and mixing it with an agarose matrix solution; c) adding a crosslinking agent and a catalyst to form a crosslinked network by photopolymerization and / or thermal polymerization to obtain a gel; d) performing post-processing on the obtained gel to adjust the pore structure, thereby obtaining a new cross-linked agarose polymer material.

6. The preparation method according to claim 5, characterized in that The agarose matrix is ​​chemically modified to introduce reactive sites, and the modification process includes the following steps: i) dissolving agarose in deionized water to form a 5-10 wt% solution at 70-90° C.; ii) cooling to 40-60° C., adding 0.05-0.2 M NaOH to adjust the pH to 7.5-8.5; iii) adding glycidyl methacrylate dropwise and reacting at 40-60° C. for 2-6 hours to obtain a modified agarose matrix; iv) washing with an ethanol / water mixture and freeze-drying to obtain the product.

7. The preparation method according to claim 5 or 6, characterized in that: Step b) specifically includes the following sub-steps: i) dispersing graphene oxide in deionized water and ultrasonically treating the water to form a suspension having a concentration of 0.1 to 2 mg / mL; ii) adding hydroxyapatite and continuing ultrasonic treatment to form a GO-HAP composite dispersion; iii) mixing the composite dispersion and the agarose matrix solution in a volume ratio of 1:(5-15) and stirring evenly.

8. The preparation method according to claim 5 or 6, characterized in that: Step c) specifically includes the following sub-steps: i) adding polyethylene glycol diacrylate and glutaraldehyde to the mixed solution, wherein the amount of polyethylene glycol diacrylate added is 5-15% of the mass of the agarose matrix; ii) adding N,N'-methylenebisacrylamide and a photoinitiator, and passing nitrogen to remove dissolved oxygen; iii) irradiating the film with 350-400 nm ultraviolet light for 10-30 min to perform photopolymerization; iv) thermally initiating crosslinking with glutaraldehyde at 50-70°C for 1-3 hours.

9. The preparation method according to claim 5 or 6, characterized in that: Step d) specifically includes the following sub-steps: i) soaking the gel in deionized water for 24 to 72 hours to remove unreacted monomers; ii) freeze drying or supercritical CO2 drying is used to control the pore structure, wherein freeze drying is carried out at -20°C to -80°C for 24 to 48 hours, and supercritical CO2 drying is carried out at 10 to 20 MPa for 2 to 6 hours.

10. The preparation method according to claim 5 or 6, characterized in that: In step c), potassium persulfate is also added as a thermal initiator with a concentration of 0.01 to 0.1 wt%.

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