One-needle injection type gel and preparation method thereof

Abstract

The present invention proposes a needle-type injection gel, comprising a developing component and a constituent monomer, wherein the constituent monomer comprises at least one of a photocrosslinking gel monomer, a temperature-responsive gel monomer, and a microgel monomer, wherein the photocrosslinking gel monomer is used to crosslink under light conditions to form a gel skeleton, the curing temperature of the temperature-responsive gel monomer is 32-37°C, and the particle size of the microgel monomer is 1-100µm, wherein, in terms of weight percentage, the photocrosslinking gel monomer accounts for 40-60w%, the temperature-responsive gel monomer accounts for 10-20wt%, the microgel monomer accounts for 10-20wt%, and the developing component accounts for 5-15wt%. The constituent materials of the needle-type injection gel have excellent biocompatibility, can provide stable support at the bone defect or fracture site, and provide a good growth environment for bone cells to promote bone integration.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and in particular relates to a one-needle injection gel and a preparation method thereof. Background Art

[0002] With the continuous development of society as a whole, the global aging rate is increasing year by year. Fractures in the elderly have become an important challenge for health management. Osteoporosis is an important cause of fractures in the elderly. Osteoporosis is a systemic metabolic bone disease characterized by decreased bone mass, damage to bone tissue microstructure, and increased bone fragility, which often leads to brittle fractures.

[0003] Osteoporotic fractures are essentially caused by the imbalance between osteoblast bone formation and osteoclast bone resorption. Currently, the prevention and treatment of osteoporotic fractures are mainly achieved through drug intervention and bone implant material intervention. Drug intervention includes anti-bone resorption drugs (bisphosphonates, selective estrogen receptor modulators, estrogens, calcitonins, etc.), bone formation promoting drugs (parathyroid hormone PTH1-34) and dual-action drugs. However, long-term periodic treatment by oral or injection may cause serious complications such as hypercalcemia or chronic kidney damage, and the high price brings inconvenience to life.

[0004] Filling the fracture area with bone implant materials is another important means of treating osteoporotic fractures, including autologous bone, allogeneic bone, artificial ceramics, polymer materials, etc. For example, PMMA (polymethyl methacrylate) bone cement has problems such as mismatched mechanical properties, lack of biological activity, and weak ability to promote new bone formation; although biodegradable CPC (calcium phosphate bone cement) bone fillers improve bone integration ability, CPC needs a certain amount of time to gradually solidify after implantation, and CPC that is not completely solidified is prone to displacement, causing serious complications. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide a one-needle injection gel and a preparation method thereof, aiming to solve the problem that bone implant materials are difficult to maintain support and easily cause displacement under the premise of ensuring bone integration ability.

[0006] To solve the above technical problems, the present invention is implemented as follows: the present invention proposes a needle-injectable gel agent, including a developing component and a constituent monomer, wherein the constituent monomer includes at least one of a photocrosslinking gel monomer, a temperature-responsive gel monomer, and a microgel monomer, wherein the photocrosslinking gel monomer is used to crosslink under light conditions to form a gel skeleton, the curing temperature of the temperature-responsive gel monomer is 32-37° C., and the particle size of the microgel monomer is 1-100µm, wherein, in terms of weight percentage, the photocrosslinking gel monomer accounts for 40-60w%, the temperature-responsive gel monomer accounts for 10-20wt%, the microgel monomer accounts for 10-20wt%, and the developing component accounts for 5-15wt%.

[0007] In some embodiments of the present invention, the photo-crosslinked gel monomer comprises a polymer and / or a small molecule containing an acryloyl group and a photoinitiator, the polymer containing an acryloyl group comprises at least one of methacrylated gelatin, methacrylated gelatin, methacrylated sodium alginate, methacrylated polyethylene glycol, polyethylene glycol diacrylate, and poly-N-acryloyl glycinamide, and the small molecule containing a methacrylate group comprises at least one of N-acryloyl glycinamide, methyl methacrylate, and acrylamide;

[0008] The photoinitiator includes at least one of 2-hydroxy-2-methyl-1-phenylpropanone, 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, and phenyl-2,4,6-trimethylbenzoyl lithium phosphonate.

[0009] In some embodiments of the present invention, the temperature-responsive gel monomer includes at least one of poly (N-isopropylacrylamide), block copolymer, and methacrylated gelatin.

[0010] In some embodiments of the present invention, the microgel monomer includes at least one of polyethylene glycol diacrylate microgel, hydroxyapatite microgel, and sodium alginate microgel.

[0011] In some embodiments of the present invention, the developing component includes at least one of iohexol, sodium diatrizoate, and barium sulfate.

[0012] In some embodiments of the present invention, the needle-injectable gel includes functional components, which include load cells, anti-osteoporosis drugs, antibiotics and bioactive factors, wherein the load cells include at least one of bone marrow mesenchymal stem cells, osteoblasts and bone marrow mononuclear cells; the anti-osteoporosis drugs include at least one of bisphosphonates, parathyroid hormones, denosumab and traditional Chinese medicine with anti-osteoporosis effects; the antibiotics include at least one of gentamicin, tobramycin and streptomycin; and the bioactive factors are used to promote bone regeneration or inhibit bone resorption.

[0013] The present invention provides a preparation method for preparing the above-mentioned one-needle injectable gel, the preparation method comprising the steps of:

[0014] S1, modulation of constituent monomers;

[0015] S2, adding a developing component to the constituent monomers to obtain a gel mixture;

[0016] S3, adding functional components to the gel mixture, vacuum degassing, mixing and packaging in a needle-type syringe to obtain a needle-type injection gel.

[0017] In some embodiments of the present invention, when the constituent monomers include photo-crosslinked gel monomers, the step S1 includes:

[0018] S1.1, adding acryloyl polymer and / or small molecule and photoinitiator to a solvent, stirring evenly, to obtain a photo-crosslinked gel precursor solution, wherein the solvent comprises at least one of deionized water, physiological saline, and phosphate buffer, and calculated by mass percentage, the acryloyl polymer and / or small molecule accounts for 5-20wt%, the photoinitiator comprises 0.05-1wt%, and the balance is the solvent;

[0019] S1.2, vacuum degassing the photo-crosslinked gel precursor solution;

[0020] S1.3, placing the degassing photo-crosslinked gel precursor solution under a light source with a wavelength of 365nm or 405nm to perform a polymerization reaction to obtain the photo-crosslinked gel monomer.

[0021] Compared with the prior art, the needle-type injection gel and its preparation method in the present invention have the following beneficial effects:

[0022] The constituent materials of the one-needle injectable gel all have excellent biocompatibility. Through the synergistic effect of the photocrosslinking gel monomer and the temperature-responsive gel monomer, the one-needle injectable gel can quickly crosslink and precisely solidify after being injected into the bone defect or fracture site, forming a stable support structure to avoid the loss or uneven distribution of the material after injection. In addition, the introduction of microgel monomers not only improves the injectability of the material, but also enhances the mechanical strength of the gel, enabling it to provide lasting support at the bone defect site and prevent secondary collapse or displacement of the fracture site.

[0023] The addition of the developing component allows the distribution of the gel to be monitored in real time under X-ray or CT imaging, ensuring that the one-needle injection gel is accurately injected into the bone defect or fracture site, greatly reducing operational risks and avoiding the misdispersion of the material into the surrounding soft tissue or blood vessels, greatly improving the accuracy of the surgery and reducing complications caused by material misplacement, such as infection, vascular compression or nerve damage. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 is a CT scan image of a needle-type injectable gel according to an embodiment of the present invention;

[0025] Figure 2a is a CT scan image of a blank control group of a needle-type injection gel in one embodiment of the present invention;

[0026] Figure 2b It is a CT scan image of an experimental group of a needle injection type gel in one embodiment of the present invention. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0028] The present invention provides a needle-injectable gel, comprising a developing component and constituent monomers, wherein the constituent monomers comprise at least one of a photocrosslinking gel monomer, a temperature-responsive gel monomer, and a microgel monomer, wherein the photocrosslinking gel monomer is used to form a gel skeleton by crosslinking under light conditions, the curing temperature of the temperature-responsive gel monomer is 32-37° C., and the particle size of the microgel monomer is 1-100 μm, wherein, in terms of weight percentage, the photocrosslinking gel monomer accounts for 40-60wt%, the temperature-responsive gel monomer accounts for 10-20wt%, the microgel monomer accounts for 10-20wt%, and the developing component accounts for 5-15wt%.

[0029] In the one-needle injectable gel, the photocrosslinking gel monomer, the temperature-responsive gel monomer, the microgel monomer, and the developing component can be freely combined to achieve specific functions. Through the synergistic effect of the photocrosslinking gel monomer and the temperature-responsive gel monomer, the one-needle injectable gel can quickly crosslink and precisely solidify after being injected into the bone defect or fracture site, forming a stable support structure to avoid the loss or uneven distribution of the material after injection. In addition, the introduction of the microgel monomer not only improves the injectability of the material, but also enhances the mechanical strength of the gel, enabling it to provide long-lasting support at the bone defect site and prevent secondary collapse or displacement of the fracture site.

[0030] The addition of the developing component allows the distribution of the gel to be monitored in real time under X-ray or CT imaging, ensuring that the one-needle injection gel is accurately injected into the bone defect or fracture site, greatly reducing operational risks and avoiding the misdispersion of the material into the surrounding soft tissue or blood vessels, greatly improving the accuracy of the surgery and reducing complications caused by material misplacement, such as infection, vascular compression or nerve damage.

[0031] In summary, the constituent materials of the one-needle injectable gel have excellent biocompatibility, can provide stable support at the site of bone defect or fracture, and at the same time provide a good growth environment for bone cells and promote bone integration.

[0032] Specifically, the photo-cross-linked gel monomers can account for 40wt%, 50wt%, and 60wt%. The filling system of the needle-injectable gel includes a light source. The photo-cross-linked gel monomers can quickly cross-link under light conditions to form a stable gel skeleton. This rapid cross-linking property helps to quickly provide mechanical support after injection, prevent further collapse or compression of bone cavities, and effectively support the repair of bone tissue.

[0033] The temperature-responsive gel monomer can account for 10wt%, 15wt%, and 20wt%, and the curing temperature can be designed at 32°C, 35°C, and 37°C. The temperature-responsive gel monomer allows a needle-injectable gel to remain liquid at room temperature, which is convenient for injection operation, but it quickly solidifies after entering the body. This temperature-responsive characteristic ensures that the material can accurately control the gelation process in the body according to the ambient temperature, providing a reliable local filling effect.

[0034] The microgel monomer can account for 10wt%, 15wt%, 20wt%, and the particle size of the microgel monomer can be 10µm, 30µm, 80µm. The addition of microgel monomer significantly improves the injectability and fluidity of the material, ensuring that the gel can be smoothly injected through a fine needle and evenly distributed in the bone cavity or bone defect area. This design makes the material more suitable for minimally invasive filling operations, reduces wound damage and improves the accuracy of the operation.

[0035] The developing component can account for 5wt%, 10wt%, and 15wt%. The presence of the developing component allows a needle-injectable gel to be monitored in real time through imaging techniques such as X-ray, CT or MRI, which greatly improves the visualization of the filling operation, reduces uncertainty in the operation, and reduces the risk of complications.

[0036] In some embodiments of the present invention, the photo-crosslinked gel monomer includes a polymer and / or small molecule containing an acryl group and a photoinitiator, the polymer containing an acryl group includes at least one of methacrylated gelatin, methacrylated gelatin, methacrylated sodium alginate, methacrylated polyethylene glycol, polyethylene glycol diacrylate, and poly N-acryloyl glycinamide, the small molecule containing a methacrylate group includes at least one of N-acryloyl glycinamide, methyl methacrylate, and acrylamide, and the photoinitiator includes at least one of 2-hydroxy-2-methyl-1-phenylpropanone, 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, and phenyl-2,4,6-trimethylbenzoyl lithium phosphonate.

[0037] In some embodiments of the present invention, the temperature-responsive gel monomer includes at least one of poly (N-isopropylacrylamide), block copolymer, and methacrylated gelatin.

[0038] In some embodiments of the present invention, the microgel monomer includes at least one of polyethylene glycol diacrylate microgel, hydroxyapatite microgel, and sodium alginate microgel.

[0039] In some embodiments of the present invention, the developing component includes at least one of iohexol, sodium diatrizoate, and barium sulfate.

[0040] In some embodiments of the present invention, a needle-injectable gel includes functional components, which include load cells, anti-osteoporosis drugs, antibiotics and bioactive factors, wherein the load cells include at least one of bone marrow mesenchymal stem cells, osteoblasts and bone marrow mononuclear cells, the anti-osteoporosis drugs include at least one of bisphosphonates, parathyroid hormones, denosumab and traditional Chinese medicine with anti-osteoporosis effects, the antibiotics include at least one of gentamicin, tobramycin and streptomycin, and the bioactive factors are used to promote bone regeneration or inhibit bone absorption.

[0041] The present invention provides a preparation method for preparing a needle-type injection gel, and the preparation method comprises the following steps:

[0042] S1. Modulate the constituent monomers.

[0043] When the constituent monomers include photogel monomers, step S1 includes:

[0044] S1.1. Add acryloyl polymer and / or small molecules and photoinitiator to the solvent, stir evenly, and obtain a photo-crosslinked gel precursor solution, wherein the solvent includes at least one of deionized water, physiological saline, and phosphate buffer, and calculated by mass percentage, the acryloyl polymer and / or small molecules account for 5~20wt%, the photoinitiator includes 0.05~1wt%, and the remainder is solvent.

[0045] Acryloyl polymers and / or small molecules can account for 5wt%, 10wt%, 15wt%, and photoinitiators can account for 0.1wt%, 0.5wt%, 1wt%. Through precise mass percentages, the mechanical properties and cross-linking speed of the needle-injectable gel can be adjusted to ensure that the material has suitable fluidity and curing properties under different bone filling requirements. Deionized water, saline or phosphate buffer provide good biocompatibility, ensuring that the solution will not induce immune response or cytotoxicity when used in vivo. The solvent also ensures that all components are fully dissolved so that the photocross-linking reaction can proceed smoothly.

[0046] S1.2. Vacuum degassing the photo-crosslinked gel precursor solution.

[0047] After removing the bubbles, the formation of pores or uneven areas during the gel curing process can be avoided, ensuring that the gel has consistent physical properties and mechanical strength after injection. The bubble-free gel precursor solution can pass through the needle more smoothly during the injection process, avoiding blockage or uneven material distribution caused by bubbles, thereby reducing the occurrence of intraoperative complications.

[0048] S1.3. Place the degassed photo-crosslinked gel precursor solution under a light source with a wavelength of 365nm or 405nm to perform a polymerization reaction to obtain a photo-crosslinked gel monomer. The light intensity of the light source can be 10~100mW / cm², such as 30mW / cm², 50mW / cm², 80mW / cm², and the illumination time can be 1~5min, such as 1min, 2min, 3min. The higher the light intensity, the shorter the required illumination time, and the specific time can also be adjusted according to the response speed of the photoinitiator to light.

[0049] Illumination with a specific wavelength can quickly trigger a cross-linking reaction between acryloyl monomers to form a stable gel network structure, ensuring that the material solidifies quickly after injection and providing good mechanical support. By controlling the wavelength of the light source and the irradiation time, the degree of cross-linking and the final mechanical properties of the gel can be precisely adjusted, so that the curing time and strength of the material can be customized according to different surgical needs to ensure its effective filling and support at the bone defect site. By partially irradiating the light before filling, a certain degree of cross-linking network can be formed before injection, thereby improving the initial mechanical strength of the gel. This pre-cross-linking can help the material maintain its shape during the filling process and avoid leakage or overflow caused by excessive fluidity. During the irradiation, only slight pre-cross-linking is performed to keep the gel in a semi-fluid state. This can provide a certain mechanical strength without significantly increasing the flow resistance.

[0050] When the constituent monomer is a temperature-responsive monomer, for example, poly (N-isopropylacrylamide) is selected as the temperature-responsive monomer, the pH of the solvent is first adjusted, and then the solution containing the temperature-responsive monomer reaches a pH close to 7 by adding acid-base regulators such as dilute hydrochloric acid and dilute sodium hydroxide, so as to optimize the curing rate and biocompatibility of the material.

[0051] When the constituent monomer is a microgel monomer, the microgel monomer is prepared by a double emulsion method. The steps are as follows:

[0052] The prepared polymer solution (such as PEGDA or sodium alginate) is used as the inner phase, and then slowly injected into the outer oil phase (such as liquid paraffin or silicone oil), maintaining strong stirring to form an emulsion.

[0053] The microgel monomer is formed by adding glutaraldehyde or N,N'-methylenebisacrylamide for cross-linking, wherein the particle size of the microgel is controlled within the range of 1 to 100 µm by adjusting the stirring rate and the ratio of the inner and outer phases.

[0054] The prepared microgel monomer is surface modified by chemical treatment or physical adsorption, such as introducing carboxyl or amino groups on the microgel surface to enhance its biocompatibility in the in vivo environment. The surface modification can be performed by immersing in carboxymethyl chitosan (CMC) or polyethylene glycol (PEG) solution, with the treatment temperature controlled at 25-30°C and the treatment time being 1-2 hours.

[0055] S2. Adding developing components to the constituent monomers to obtain a gel mixture.

[0056] S3, adding functional components to the gel mixture, vacuum degassing, mixing and packaging in a needle-type syringe to obtain a needle-type injection gel.

[0057] Furthermore, the functional components are arranged as a multilayer microsphere structure, which includes an outer polymer membrane, a middle polymer membrane and an inner polymer microsphere which are stacked in sequence, antibiotics are placed between the outer polymer membrane and the middle polymer membrane, loaded cells and bioactive factors are placed between the middle polymer membrane and the outer surface of the inner polymer microsphere, and anti-osteoporosis drugs are placed in the inner polymer microsphere.

[0058] The outer polymer film can be made of rapidly degradable water-soluble polymers, such as gelatin and hyaluronic acid. This layer dissolves rapidly after contacting body fluids, releasing antibiotics for short-term control of infection and pain. The outer polymer film can also be a pH-responsive material, such as polyacrylic acid, chitosan, polyvinyl pyrrolidone-acrylic acid copolymer, etc. pH-responsive materials are usually stable in a neutral environment and release drugs more slowly. In an acidic environment, such as infected or inflamed bone tissue, the material senses the local acidic environment and swells, dissociates or degrades, prompting the rapid release of the encapsulated antibiotics and reducing the risk of infection.

[0059] The middle polymer membrane can be made of biodegradable synthetic materials, such as PLGA (poly(lactic-co-glycolic acid)), which can gradually degrade over a period of days to weeks, releasing loaded cells and bioactive factors to promote bone regeneration and bone aggregation.

[0060] The material of the inner layer of polymer microspheres can be an enzyme-responsive material. Enzyme-responsive materials refer to materials that degrade, dissolve or change structure in the presence of specific enzymes, and are usually used for drug delivery to specific tissues or lesions. For example, it can be gelatin, polyethylene glycol-peptide copolymer enzyme. Enzyme-responsive materials can be used for long-term treatment of bone healing, and growth factors or anti-osteoporosis drugs are released through the action of enzymes in bone tissue to achieve good integration with bone tissue. The release time can last for several months, which is used to play a long-term anti-osteoporosis effect.

[0061] Specifically, the steps for preparing the multilayer microsphere structure include:

[0062] An outer polymer solution containing antibiotics, a middle polymer solution containing loaded cells and bioactive factors, and an inner polymer solution containing anti-osteoporosis drugs are prepared respectively.

[0063] The inner polymer solution is injected into an electrospinner to be sprayed into nanofibers, and then the nanofibers are transferred to a collector containing a crosslinking agent solution and solidified to form inner polymer microspheres. The crosslinking agent can be glutaraldehyde or N,N'-dimethylenebisacrylamide, and gelatin, chitosan, etc. in the inner polymer solution can be crosslinked and solidified with the crosslinking agent, and the internal shape of the collector can be spherical. The electric field strength is usually 2~3kV / cm.

[0064] The middle layer polymer solution is injected into the electrospinner and sprayed onto the inner layer polymer microspheres for solidification to obtain inner layer polymer microspheres covered with the middle layer polymer film. The electric field strength can be maintained at 1-2 kV / cm.

[0065] The outer layer polymer solution is injected into the electrospinner and sprayed onto the inner layer polymer microspheres covered with the middle layer polymer film, and then solidified to obtain a multi-layer microsphere structure. The electric field strength can be 0.5~1kV / cm.

[0066] During the electrospinning process, improvements are made to the electrospinning process by inserting a conductivity meter during the spinning process. The specific structure of the conductivity meter is well known to those skilled in the art and will not be described in detail here.

[0067] In electrospinning, the presence of an electric field causes ions or charged molecules in the solution to move under the action of the electric field. When these charged ions or molecules move in the solution, they are hindered by the internal resistance of the solution, which will produce Joule heating effect. The generation of Joule heating effect will cause the solution temperature to rise, especially when a higher electric field strength is applied.

[0068] The increase in temperature will increase the kinetic energy of ions in the solution. According to the principles of thermodynamics, the increase in temperature makes the thermal motion of ions more intense, thereby increasing the mobility of ions (i.e. the speed at which ions move in an electric field). The increase in ion mobility will directly increase the conductivity of the solution, thereby increasing the conductivity.

[0069] The influence of temperature on conductivity is corrected by the correction formula. The correction formula for conductivity is: ,in, is the conductivity at the preset temperature, is the conductivity measured by the conductivity meter, is the temperature coefficient, with a value of 0.02~0.03 / ℃, The preset temperature can be a reference standard temperature, such as 20~25℃. The temperature detected by the conductivity meter.

[0070] During the electrospinning process, the calculation formula for the electric field strength is: , where E is the electric field intensity and J is the current density. Different electric field intensities were used for the inner, middle and outer polymer solutions during the electrospinning process. The electric field intensity of the inner polymer solution was set at 2~3kV / cm, the electric field intensity of the middle polymer was set at 1~2kV / cm, and the electric field intensity of the outer polymer was set at 0.5~1kV / cm. This change in electric field intensity is mainly based on the characteristics of the polymer solutions at different levels, the diameter of the required fibers, and the forming effect of the target layer. For the inner layer, a larger electric field intensity is required to ensure a stronger tensile force to form a stable inner fiber structure, while for the middle and outer layers, the electric field intensity gradually decreases to meet the needs of forming a thinner coating.

[0071] During the preparation process, if the corrected conductivity Compared with standard value If the current density is too high, the current density will increase accordingly, resulting in excessive stretching of the generated material and even unstable injection. At this time, in order to maintain suitable fiber-forming conditions, the electric field strength should be reduced to avoid excessive current density.

[0072] If the corrected conductivity Compared with standard value If the conductivity is too low, the current density will decrease accordingly, resulting in insufficient electric field tensile force, making it difficult to form the fiber or making the diameter thicker. At this time, in order to maintain suitable fiber-forming conditions, the electric field strength should be increased to compensate for the insufficient tensile force caused by the decrease in conductivity.

[0073] Figure 1 The CT scan images of the one-needle injectable gel when the addition amount of different developing components is 0mg / ml, 60mg / ml, 120mg / ml, 180mg / ml, 240mg / ml, and 300mg / ml respectively, show that with the increase of the concentration of the developing component, the CT development effect of the gel is effectively improved. When it is not added or at a low concentration, there is a lack of clear contrast in the CT image, indicating that the developing component fails to fully show the distribution and morphology of the one-needle injectable gel. At a high concentration, a stronger development contrast is shown in the CT image, which means that the developing component can make the one-needle injectable gel appear more clearly under CT scanning.

[0074] Figure 2a It is a blank control group, which is not filled with a needle-type injection gel. Figure 2b This is a CT scan after filling with a needle-type injection gel, which shows the effect of filling the bone cavity with a needle-type injection gel. Figure 2a It is an untreated cavity or early stage. Figure 2b The distribution of the gel in the bone cavities and its integration into the bone tissue are shown.

[0075] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A one-needle injection type gel, characterized in that: It comprises a developing component and a constituent monomer, wherein the constituent monomer comprises a photo-crosslinking gel monomer, a temperature-responsive gel monomer and a microgel monomer, wherein, in terms of weight percentage, the developing component accounts for 5-15wt%, the photo-crosslinking gel monomer accounts for 40-60w%, the temperature-responsive gel monomer accounts for 10-20wt%, the microgel monomer accounts for 10-20wt%, the photo-crosslinking gel monomer is used to crosslink under light conditions to form a gel skeleton, the curing temperature of the temperature-responsive gel monomer is 32-37° C., the particle size of the microgel monomer is 1-100µm, and the microgel monomer comprises at least one of hydroxyapatite microgel and sodium alginate microgel; The one-needle injection gel further includes functional components, which include load cells, anti-osteoporosis drugs, antibiotics and bioactive factors, wherein the load cells include at least one of bone marrow mesenchymal stem cells, osteoblasts and bone marrow mononuclear cells, the anti-osteoporosis drugs include at least one of bisphosphonates, parathyroid hormones, denosumab and traditional Chinese medicine with anti-osteoporosis effects, the antibiotics include at least one of gentamicin, tobramycin and streptomycin, the bioactive factors are used to promote bone regeneration or inhibit bone absorption, and the functional components are arranged in a multilayer microsphere structure; The preparation steps of the functional component include: Separately preparing an outer polymer solution containing antibiotics, a middle polymer solution containing loaded cells and bioactive factors, and an inner polymer solution containing anti-osteoporosis drugs; The inner layer polymer solution is injected into an electrospinner to be sprayed into nanofibers, and then the nanofibers are transferred to a collector containing a crosslinking agent solution and solidified to form inner layer polymer microspheres; The middle layer polymer solution is injected into an electrospinner and sprayed onto the inner layer polymer microspheres for solidification to obtain inner layer polymer microspheres covered with the middle layer polymer film; The outer layer polymer solution is injected into an electrospinner and sprayed onto the inner layer polymer microspheres covered with the middle layer polymer film, and solidified to obtain a multilayer microsphere structure; The correction formula for the conductivity of the inner layer polymer solution, the middle layer polymer solution and the outer layer polymer solution during the electrospinning process is: ,in, is the conductivity at the preset temperature, is the conductivity measured by the conductivity meter, is the temperature coefficient, with a value of 0.02~0.03 / ℃, is the preset temperature, The temperature detected by the conductivity meter; During the preparation process, if the corrected conductivity Compared with standard value high, reduce the electric field strength, if the corrected conductivity Compared with standard value Low, increase the electric field strength.

2. The one-needle injection type gel according to claim 1, characterized in that: The photo-crosslinked gel monomer includes a polymer and / or a small molecule containing an acryl group, wherein the polymer containing an acryl group includes at least one of methacryloyl gelatin, methacryloyl sodium alginate, methacryloyl polyethylene glycol, and polyethylene glycol diacrylate, and the small molecule containing an acryl group includes at least one of N-acryloyl glycinamide, methyl methacrylate, and acrylamide.

3. The one-needle injection type gel according to claim 1, characterized in that: The temperature responsive gel monomer includes at least one of poly (N-isopropylacrylamide) and block copolymer.

4. The one-needle injection type gel according to claim 1, characterized in that: The developing component includes at least one of iohexol, sodium diatrizoate and barium sulfate.

5. A preparation method, characterized in that: For preparing a needle-type injection gel according to any one of claims 1 to 4, the preparation method comprises the following steps: S1, modulation of constituent monomers; S2, adding a developing component to the constituent monomers to obtain a gel mixture; S3, adding functional components to the gel mixture, vacuum degassing, mixing and packaging in a needle-type syringe to obtain a needle-type injection gel.

Images