A hydrogel material for spinal cord nerve repair containing magnetic nanospheres and its preparation method
By preparing hydrogel materials containing magnetic nanospheres and using magnetic fields to guide nerve growth, the problems of mechanical strength and degradation rate of hydrogel materials in spinal cord nerve repair were solved, and effective nerve repair effects were achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- JIANGSU YITONG BIOTECHNOLOGY CO LTD
- Filing Date
- 2026-04-30
- Publication Date
- 2026-07-03
AI Technical Summary
Existing hydrogel materials have insufficient mechanical strength, a degradation rate that does not match the nerve regeneration cycle, and limited nerve regeneration-promoting activity in spinal cord nerve repair, thus failing to meet clinical needs.
A photocurable hydrogel was prepared using chitosan, dimethylaminoethyl methacrylate, methacryloyloxyethyltrimethylammonium chloride, and nano-magnetic iron oxide microspheres. The growth of nerves was guided by a magnetic field to form magnetic channels, thereby synergistically regulating the curing and mechanical properties.
It provides a biocompatible, safe, and non-toxic hydrogel material that can form a stable magnetic channel at the site of spinal cord injury, guide nerve growth, improve nerve repair, avoid incorrect connections, and ensure the effectiveness of nerve repair.
Smart Images
Figure CN122321218A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical materials technology, specifically to a hydrogel material for spinal cord nerve repair containing magnetic nanospheres and its preparation method. Background Technology
[0002] As a key component of the human central nervous system, the spinal cord plays a vital role in transmitting nerve signals between the brain and other parts of the body. Spinal cord injury and defects can lead to the interruption of nerve signal transmission, resulting in serious sequelae such as limb movement disorders and sensory abnormalities, and even lifelong disability, placing a heavy burden on patients' families and society.
[0003] Currently, clinical treatments for spinal cord injuries and defects mainly include drug therapy, surgical treatment, physical therapy, and rehabilitation training. Drug therapy is primarily suitable for mild spinal cord injuries, using neurotrophic drugs such as nerve growth factor and B vitamins to promote nerve repair and regeneration. However, these drugs are easily diffused and inactivated in the body, making it difficult to maintain their effects. Surgical treatment is suitable for severe spinal cord injuries and defects, commonly using methods such as nerve repair surgery, nerve reconstruction surgery, and nerve transplantation. However, surgical procedures are complex, and it is difficult to effectively create a suitable microenvironment for nerve regeneration. Physical therapy and rehabilitation training are mainly used to assist in the recovery of patients' neurological function and daily living abilities, but they cannot fundamentally achieve structural repair and functional reconstruction of the damaged spinal cord.
[0004] Traditional treatments for severe spinal cord injuries and defects have significant limitations and cannot meet clinical repair needs. Therefore, there is an urgent clinical need to develop and explore novel nerve repair materials and sustained-release carriers of nerve-growth-promoting active substances to build a "bridge" for the repair of damaged spinal cord nerves, providing physical support and biological induction for nerve regeneration. Hydrogel materials, due to their good biocompatibility, hydrophilicity, and structural plasticity, can simulate the microenvironment of human tissue and can serve as carriers for the sustained-release delivery of nerve-growth-promoting active substances, showing broad application potential in the field of spinal cord nerve repair. However, existing hydrogel materials still suffer from insufficient mechanical strength, a mismatch between degradation rate and nerve regeneration cycle, and limited nerve-growth-promoting activity, failing to fully meet the clinical needs of spinal cord nerve repair. Therefore, developing a hydrogel material that combines good biocompatibility, suitable mechanical properties, and highly efficient spinal cord regeneration-promoting function has become a pressing technical challenge in the field of spinal cord nerve repair. Summary of the Invention
[0005] To address the shortcomings of existing technologies, the present invention aims to provide a hydrogel material for spinal cord nerve repair containing magnetic nanospheres and its preparation method.
[0006] To achieve the above objectives, the present invention adopts the following technical solution: A method for preparing a hydrogel material for spinal cord nerve repair containing magnetic nanospheres includes the following steps: dissolving chitosan in acetic acid solution, then adding dimethylaminoethyl methacrylate and methacryloyloxyethyltrimethylammonium chloride, stirring evenly, then adding a photoinitiator and magnetic iron oxide nanospheres, stirring evenly, and storing in the dark to obtain the hydrogel material for spinal cord nerve repair.
[0007] In the technical solution disclosed in this invention, the concentration of chitosan in the hydrogel material is 40-60 mg / mL. For example, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, and 60 mg / mL can be selected, but it is not limited to the listed values. Other unlisted values within the range are also applicable.
[0008] In the technical solution disclosed in this invention, the concentration of dimethylaminoethyl methacrylate in the hydrogel material is 20-40 mg / mL, for example, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, or 40 mg / mL can be selected, but it is not limited to the listed values. Other unlisted values within the range are also applicable.
[0009] In the technical solution disclosed in this invention, the concentration of methacryloyloxyethyltrimethylammonium chloride in the hydrogel material is 20-40 mg / mL. For example, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, and 40 mg / mL can be selected, but it is not limited to the listed values. Other unlisted values within the range are also applicable.
[0010] In the technical solution disclosed in this invention, the mass ratio of dimethylaminoethyl methacrylate and methacryloxyethyltrimethylammonium chloride is 1-2:1-2, for example, 1:1, 1:1.5, 1:2, 2:1, 2:1.5 can be selected, but it is not limited to the listed values. Other unlisted values within the range are also applicable.
[0011] In the technical solution disclosed in this invention, the photoinitiator is selected from lithium phenyl (2,4,6-trimethylbenzoyl) phosphate.
[0012] In the technical solution disclosed in this invention, the concentration of the photoinitiator is 1-2 mg / mL, for example, 1 mg / mL, 1.1 mg / mL, 1.2 mg / mL, 1.3 mg / mL, 1.4 mg / mL, 1.5 mg / mL, 1.6 mg / mL, 1.7 mg / mL, 1.8 mg / mL, 1.9 mg / mL, 2 mg / mL, but is not limited to the listed values. Other unlisted values within the range are also applicable.
[0013] In the technical solution disclosed in this invention, the concentration of nano-magnetic iron oxide microspheres in the hydrogel material is 5-10 mg / mL. For example, 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, and 10 mg / mL can be selected, but it is not limited to the listed values. Other unlisted values within the range are also applicable.
[0014] The present invention also provides a hydrogel material for spinal cord nerve repair prepared by the above preparation method.
[0015] Compared with the prior art, the present invention has the following beneficial effects: (1) The hydrogel material provided by this invention is a photocurable hydrogel formulated with chitosan, dimethylaminoethyl methacrylate, methacryloyloxyethyltrimethylammonium chloride, and nano-magnetic iron oxide microspheres. Compared with traditional spinal cord nerve repair materials, the hydrogel material provided by this invention has good biocompatibility, is safe and non-toxic, and has a simple and easy preparation method. When the hydrogel is injected into the spinal cord injury site, photocuring is performed, and a magnetic field is simultaneously added to the injury site. This allows the magnetic nanospheres to rotate according to the magnetic field, forming a series of magnetic channels. As the hydrogel gradually solidifies, the magnetic channels are retained for a long time. During the spinal cord nerve repair process, the magnetic channels guide nerve growth, avoid incorrect nerve connections, and ensure the nerve repair effect.
[0016] (2) This invention innovatively applies two monomers, dimethylaminoethyl methacrylate (DM) and methacryloyloxyethyltrimethylammonium chloride (DMC), to the hydrogel system in a synergistic manner. By using a reasonable ratio, the curing and mechanical properties of the hydrogel can be effectively controlled, thus solving the technical drawbacks of using a single monomer. Among them, methacryloyloxyethyltrimethylammonium chloride (DMC) exists in the solution in the form of quaternary ammonium salt ions, with a faster reaction rate and shorter photocuring time, but the strength of the prepared hydrogel is relatively weak. Dimethylaminoethyl methacrylate (DM) exists in molecular form, with a slower reaction rate and longer photocuring time, and the prepared hydrogel has a compact structure and higher strength. However, using either monomer alone will either fail to guarantee the mechanical strength of the hydrogel to support spinal cord nerve repair, or the improper curing speed will affect the function of the magnetic microspheres. The applicant's research revealed that controlling the mass ratio of dimethylaminoethyl methacrylate (DM) to methacryloyloxyethyltrimethylammonium chloride (DMC) within the range of 1-2:1-2 is crucial to achieving synergistic complementarity between the two. This allows for the regulation of the hydrogel to reach an appropriate curing time and strength, avoiding technical defects caused by excessively fast or slow curing, or excessively high or low strength. It also ensures that the nano-magnetic iron oxide microspheres can smoothly deflect under the influence of a magnetic field, forming a stable magnetic channel. This provides good physical support and guidance for spinal cord regeneration, thereby enhancing the nerve repair effect of the hydrogel material. Attached Figure Description
[0017] Figure 1 Graphs showing BBB score results for different groups; Figure 2 Comparison chart of sensory function recovery results for different groups; Figure 3 A schematic diagram showing the injection of the hydrogel material provided by this invention; Figure 4 A schematic diagram of an applied magnetic field; Figure 5 This is a schematic diagram illustrating the beginning of nerve growth. Figure 6 A schematic diagram illustrating the process of nerve growth; Figure 7 This is a schematic diagram of the complete degradation of the hydrogel. Detailed Implementation
[0018] The present invention will be further described in detail below through specific preferred embodiments, but the present invention is not limited to the following embodiments.
[0019] It should be noted that, unless otherwise specified, all chemical reagents involved in this invention were purchased through commercial channels.
[0020] The nano-magnetic iron oxide microspheres used in this embodiment of the invention have a particle size of 10 nm.
[0021] Example 1 A method for preparing a hydrogel material for spinal cord nerve repair containing magnetic nanospheres includes the following steps: Chitosan was dissolved in acetic acid solution, then dimethylaminoethyl methacrylate and methacryloyloxyethyltrimethylammonium chloride were added and stirred evenly. Then, lithium phenyl (2,4,6-trimethylbenzoyl) phosphate photoinitiator and nano-magnetic iron oxide microspheres were added, stirred evenly, and stored in the dark to obtain the hydrogel material for spinal cord nerve repair. The concentrations of chitosan, dimethylaminoethyl methacrylate, methacryloyloxyethyltrimethylammonium chloride, phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt, and nano-magnetic iron oxide microspheres were 10 mg / mL.
[0022] Example 2 A method for preparing a hydrogel material for spinal cord nerve repair containing magnetic nanospheres includes the following steps: Chitosan was dissolved in acetic acid solution, then dimethylaminoethyl methacrylate and methacryloyloxyethyltrimethylammonium chloride were added and stirred evenly. Then, lithium phenyl (2,4,6-trimethylbenzoyl) phosphate photoinitiator and nano-magnetic iron oxide microspheres were added, stirred evenly, and stored in the dark to obtain the hydrogel material for spinal cord nerve repair. The concentrations of chitosan, dimethylaminoethyl methacrylate, methacryloyloxyethyltrimethylammonium chloride, phenyl (2,4,6-trimethylbenzoyl) lithium phosphate, and nano-magnetic iron oxide microspheres were 5 mg / mL.
[0023] Example 3 A method for preparing a hydrogel material for spinal cord nerve repair containing magnetic nanospheres includes the following steps: Chitosan was dissolved in acetic acid solution, then dimethylaminoethyl methacrylate and methacryloyloxyethyltrimethylammonium chloride were added and stirred evenly. Then, lithium phenyl (2,4,6-trimethylbenzoyl) phosphate photoinitiator and nano-magnetic iron oxide microspheres were added, stirred evenly, and stored in the dark to obtain the hydrogel material for spinal cord nerve repair. The concentrations of chitosan, dimethylaminoethyl methacrylate, methacryloyloxyethyltrimethylammonium chloride, phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt, and nano-magnetic iron oxide microspheres were 10 mg / mL.
[0024] Comparative Example 1 A method for preparing a hydrogel material for spinal cord nerve repair containing magnetic nanospheres includes the following steps: Chitosan was dissolved in acetic acid solution, then dimethylaminoethyl methacrylate was added and stirred evenly. Then, lithium phenyl (2,4,6-trimethylbenzoyl) phosphate photoinitiator and nano-magnetic iron oxide microspheres were added, stirred evenly, and stored in the dark to obtain a hydrogel material for spinal cord nerve repair. The concentrations of chitosan, dimethylaminoethyl methacrylate, lithium phenyl (2,4,6-trimethylbenzoyl) phosphate, and nano-magnetic iron oxide microspheres were 10 mg / mL.
[0025] Compared with Comparative Example 1 and Example 1, an equal amount of dimethylaminoethyl methacrylate was used to replace methacryloyloxyethyltrimethylammonium chloride.
[0026] Comparative Example 2 A method for preparing a hydrogel material for spinal cord nerve repair containing magnetic nanospheres includes the following steps: Chitosan was dissolved in acetic acid solution, then methacryloyloxyethyltrimethylammonium chloride was added and stirred evenly. Then, lithium phenyl (2,4,6-trimethylbenzoyl) phosphate photoinitiator and nano-magnetic iron oxide microspheres were added, stirred evenly, and stored in the dark to obtain a hydrogel material for spinal cord nerve repair. The concentrations of chitosan, methacryloyloxyethyltrimethylammonium chloride, lithium phenyl (2,4,6-trimethylbenzoyl)phosphate, and nano-magnetic iron oxide microspheres were 10 mg / mL.
[0027] Compared with Example 1, Comparative Example 2 uses an equal amount of methacryloyloxyethyltrimethylammonium chloride to replace dimethylaminoethyl methacrylate.
[0028] Comparative Example 3 A method for preparing a hydrogel material for spinal cord nerve repair containing magnetic nanospheres includes the following steps: Chitosan was dissolved in acetic acid solution, then dimethylaminoethyl methacrylate and methacryloyloxyethyltrimethylammonium chloride were added and stirred evenly. Then, lithium phenyl (2,4,6-trimethylbenzoyl) phosphate photoinitiator and nano-magnetic iron oxide microspheres were added, stirred evenly, and stored in the dark to obtain the hydrogel material for spinal cord nerve repair. The concentrations of chitosan, dimethylaminoethyl methacrylate, methacryloyloxyethyltrimethylammonium chloride, phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt, and nano-magnetic iron oxide microspheres were 10 mg / mL.
[0029] Compared with Example 1, the mass ratio of dimethylaminoethyl methacrylate to methacryloyloxyethyltrimethylammonium chloride in Comparative Example 3 was 3:1.
[0030] Comparative Example 4 A method for preparing a hydrogel material for spinal cord nerve repair containing magnetic nanospheres includes the following steps: Chitosan was dissolved in acetic acid solution, then dimethylaminoethyl methacrylate and methacryloyloxyethyltrimethylammonium chloride were added and stirred evenly. Then, lithium phenyl (2,4,6-trimethylbenzoyl) phosphate photoinitiator and nano-magnetic iron oxide microspheres were added, stirred evenly, and stored in the dark to obtain the hydrogel material for spinal cord nerve repair. The concentrations of chitosan, dimethylaminoethyl methacrylate, methacryloyloxyethyltrimethylammonium chloride, phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt, and nano-magnetic iron oxide microspheres were 10 mg / mL.
[0031] Compared with Comparative Example 4 and Example 1, the mass ratio of dimethylaminoethyl methacrylate to methacryloyloxyethyltrimethylammonium chloride was 1:3.
[0032] The hydrogel materials prepared in Examples 1-3 and Comparative Examples 1-4 were photocured at a wavelength of 365 nm. The curing time and gel strength were tested, and the test results are shown in Table 1.
[0033] Table 1 Performance test results for different groups
[0034] As can be seen from Table 1, compared with Comparative Examples 1-4, in the embodiments of the present invention, by controlling the mass ratio of dimethylaminoethyl methacrylate (DM) to methacryloyloxyethyltrimethylammonium chloride (DMC) within the range of 1-2:1-2, the hydrogel can achieve a suitable curing time and curing strength, thus avoiding technical defects caused by curing too fast or too slow, or gel strength that is too high or too low.
[0035] The hydrogel materials prepared in Example 1 and Comparative Example 1 of this invention were used in a spinal cord nerve repair experiment. Example 1 was the experimental group, and Comparative Example 1 was the control group. The specific steps are as follows: Adult female SD rats (200 g) were used to establish a 2 mm hemisection model of spinal cord injury. After anesthetizing the rats with a combined anesthetic, the surgical area on the back was prepared and disinfected with iodine and alcohol. The rat's back was cut along the midline to expose the T9-T10 segment of the spinal cord. A 2 mm section of the right spinal cord was cut using microscissors to establish a right-sided spinal cord hemisection model. Hydrogels from the experimental and control groups were injected into the injury site. The wounds were sutured and disinfected with iodine. The rats were placed on warm blankets and separated into different cages after waking up. Daily urination care was provided to the experimental rats until they could urinate normally. The recovery of sensory and motor functions was assessed at different time points (3, 7, 14, 21, and 28 days) using BBB scores and thermal pain analysis.
[0036] BBB behavioral scores were assessed at 3, 7, 14, 21, and 28 days after the establishment of the spinal cord injury model. Rats were placed in a 100cm × 15cm rectangular track. Three individuals unfamiliar with the experiment were invited to evaluate the rats' hind limb motor behavior without interference from each other, assigning scores according to a scoring system, and the average score was calculated. A score of 0 indicated complete paralysis, and 21 indicated normal motor function; the higher the score, the more normal the hind limb motor function. Results are as follows: Figure 1 As shown, tests were conducted at 3, 7, 14, 21, and 28 days. The BBB scores of the experimental group continuously improved, indicating that the hindlimb motor function of the spinal cord-injured rats was gradually recovering, and was much higher than that of the control group.
[0037] Recovery of sensory function is an important indicator for evaluating the recovery effect of spinal cord injury. Using a thermal pain analyzer, the duration of pain sensation perceived at 40°C on the injured side of the right hind limb of rats was measured at 7, 14, 21, and 28 days post-surgery, with the unaffected side as the baseline. Results are as follows: Figure 2 As shown, the time for pain sensation in the right hind limb of rats gradually shortened over time. On day 28, the experimental group showed a reduced thermal pain response time compared to the control group, which was close to the normal level before surgery.
[0038] This invention also provides a schematic diagram of a process for spinal cord nerve repair using hydrogel materials, wherein... Figure 3 A schematic diagram showing the injection of the hydrogel material provided by this invention; Figure 4 A schematic diagram of an applied magnetic field; Figure 5 This is a schematic diagram illustrating the beginning of nerve growth. Figure 6 A schematic diagram illustrating the process of nerve growth; Figure 7 This is a schematic diagram of the complete degradation of the hydrogel.
[0039] Finally, it should be noted that the above embodiments do not limit the present invention in any way. Those skilled in the art can make modifications and improvements based on the present invention. Therefore, any modifications or improvements made without departing from the spirit of the present invention are within the scope of protection claimed by the present invention.
Claims
1. A method for preparing a hydrogel material for spinal cord nerve repair containing magnetic nanospheres, characterized in that, The process includes the following steps: dissolving chitosan in acetic acid solution, then adding dimethylaminoethyl methacrylate and methacryloyloxyethyltrimethylammonium chloride, stirring until homogeneous, then adding photoinitiator and nano-magnetic iron oxide microspheres, stirring until homogeneous, and storing in the dark to obtain a hydrogel material for spinal cord nerve repair.
2. The preparation method according to claim 1, characterized in that, The concentration of chitosan in the hydrogel material is 40-60 mg / mL.
3. The preparation method according to claim 1, characterized in that, The concentration of dimethylaminoethyl methacrylate in the hydrogel material is 20-40 mg / mL.
4. The preparation method according to claim 1, characterized in that, The concentration of methacryloyloxyethyltrimethylammonium chloride in the hydrogel material is 20-40 mg / mL.
5. The preparation method according to claim 1, characterized in that, The mass ratio of dimethylaminoethyl methacrylate to methacryloyloxyethyltrimethylammonium chloride is 1-2:1-2.
6. The preparation method according to claim 1, characterized in that, The photoinitiator is selected from lithium phenyl (2,4,6-trimethylbenzoyl) phosphate.
7. The preparation method according to claim 1, characterized in that, The concentration of photoinitiator in hydrogel materials is 1-2 mg / mL.
8. The preparation method according to claim 1, characterized in that, The concentration of nano-magnetic iron oxide microspheres in the hydrogel material is 5-10 mg / mL.
9. The hydrogel material for spinal cord nerve repair prepared by the preparation method according to any one of claims 1-8.