Fibroin PLCL functionalized self-curling nerve conduit
By preparing silk fibroin PLCL functionalized self-coiling nerve conduits and utilizing electrospinning technology and conductive anti-inflammatory materials, the problems of infection risk and slow regeneration speed in peripheral nerve injury repair were solved, achieving efficient nerve repair and regeneration.
Patent Information
- Application Number
- CN202511326937.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-17
- Publication Date
- 2025-12-05
AI Technical Summary
Existing technologies for repairing peripheral nerve injuries carry risks of infection, have slow nerve regeneration rates and limited effectiveness, and drug treatments have poor targeting and are difficult to effectively promote nerve repair.
We used silk fibroin PLCL to functionalize self-coiled nerve conduits, prepared nanofiber membranes through electrospinning, and added conductive graphene oxide and anti-inflammatory cerium dioxide to promote nerve cell migration and differentiation and inhibit inflammatory responses.
It improves nerve repair efficiency, promotes nerve cell migration and differentiation, inhibits post-implantation rejection, and enhances nerve regeneration capacity.
Smart Images
Figure CN121059902A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of tissue engineering in biomedical technology, and particularly relates to a silk fibroin PLCL functionalized self-curling nerve conduit. BACKGROUND
[0002] Peripheral nervous system injury is a common disease, and there are about 20 million cases of peripheral nerve injury in China. Peripheral nervous system injury often leads to nerve dysfunction, which manifests as loss of motor and sensory function in the corresponding nerve innervation area, reduces the quality of life of patients, and even leads to long-term disability of patients, which brings heavy disease burden to patients and society. Nerve injury can be caused by various reasons, including trauma, ischemia, infection, etc., and even loss of sensation. The regeneration ability of adult nervous system is limited. Therefore, the non-regeneration of nerve sprouts in vivo makes nerve repair a difficult problem.
[0003] The common methods for repairing the nervous system at present include surgical repair, drug treatment and rehabilitation intervention. Surgical repair includes nerve suture and transplantation, but there is a risk of infection, slow nerve regeneration and difficulty in completely repairing severe injury. The existing nerve growth drugs for drug treatment have poor targeting, and it is difficult to break through the blood nerve barrier. Physical therapy and rehabilitation training need to be adhered to for a long time and have limited effect on severe injury, so a silk fibroin PLCL functionalized self-curling nerve conduit is proposed. SUMMARY
[0004] In view of the problems in the prior art, the present application provides a silk fibroin PLCL functionalized self-curling nerve conduit, which can limit the ingrowth of surrounding tissues, more effectively promote the migration, differentiation and transplantation of nerve cells to guide nerve regeneration, and improve the efficiency of repairing nerve injury.
[0005] The technical scheme adopted by the present application to solve the technical problem is a silk fibroin PLCL functionalized self-curling nerve conduit, which comprises a functional material, a spinning solution and an organic solvent, the functional material and the spinning solution are processed into a nanofiber membrane by electrospinning, and the nanofiber membrane is obtained by a heat setting treatment equipment to obtain a nerve conduit with a lumen structure. The spinning solution is made of PLCL and silk fibroin.
[0006] Specifically, the functional material is a conductive material, the conductive material is graphene oxide (GO), and the concentration of graphene oxide is 1-4 mg / ml, the mass concentration of PLCL in the spinning solution is 50-70%, and the nanofiber membrane containing graphene oxide (GO) is soaked in an ascorbic acid solution before heat setting treatment, and the graphene oxide is reduced to reduced graphene oxide (RGO).
[0007] Specifically, the functional material is an anti-inflammatory material, and the anti-inflammatory material is cerium dioxide (CeO2).
[0008] Specifically, the organic solvent is hexafluoroisopropanol (HFIP).
[0009] Specifically, the process parameters of the electrospinning are as follows: the sample volume of the spinning solution for the nanofiber membrane is 6-10 mL, the voltage is 9-11 kV, the advancing speed of the spinning solution is 1.0-1.5 mL / h, the distance between the needle of the syringe and the receiving device during spinning is 8-15 cm, and the speed of the drum receiving is 300-400 rpm.
[0010] Specifically, the heat setting treatment device comprises a stainless steel rod and a constant temperature drying oven, the nanofiber membrane is wrapped around the stainless steel rod of a predetermined size after being cut to a predetermined size, and the heat setting is performed in the constant temperature drying oven.
[0011] Specifically, the heat setting temperature of the constant temperature drying oven is 100-140 DEG C, and the heat setting time is 2-6 h.
[0012] The present application has the following advantages: the addition of silk fibroin and PLCL can make the nerve conduit have good biocompatibility and mechanical properties, the addition of reduced graphene oxide in the electrospun nanofiber can create a nerve conduit, transmit electrical signals from the fiber to the neuron, and thus promote the better adsorption and proliferation of nerve cells. After the addition of the anti-inflammatory material CeO2 in the electrospun nanofiber, the nerve conduit can inhibit the rejection reaction and inflammatory reaction after implantation. BRIEF DESCRIPTION OF DRAWINGS
[0013] Figure 1 The flow chart of the self-curling nerve conduit manufacturing method of Example 1 is shown in the figure. Figure 2 The SEM image and fiber diameter statistical diagram of Example 1 are shown in the figure. Figure 3 The flow chart of the self-curling nerve conduit manufacturing method of Example 2 is shown in the figure. Figure 4 The SEM image and fiber diameter statistical diagram of Example 2 are shown in the figure. Figure 5 The flow chart of the self-curling nerve conduit manufacturing method of Example 3 is shown in the figure. Figure 6 The SEM image and fiber diameter statistical diagram of Example 3 are shown in the figure.
[0014] Figure 7 The mechanical properties of the electrospun nanofiber membranes prepared in Example 1, Example 2 and Example 3 are compared. DETAILED DESCRIPTION
[0015] In order to make the technical means, creative features, purposes and effects of the present application easy to understand, the present application is further described below in conjunction with specific embodiments.
[0016] As an embodiment of the present application, the silk fibroin PLCL functionalized self-curling nerve conduit of the present application comprises a functional material, a spinning solution and an organic solvent, the functional material and the spinning solution are processed into a nanofiber membrane by electrospinning, and the nanofiber membrane is obtained by a heat setting treatment device to obtain a nerve conduit with a lumen structure. The spinning solution is made of PLCL and silk fibroin.
[0017] Exemplarily, the present application further comprises that the functional material is a conductive material, the conductive material is graphene oxide (GO), and the concentration of graphene oxide is 1-4 mg / ml, the mass concentration of PLCL in the spinning solution is 50-70%, and the nanofiber membrane containing graphene oxide (GO) is soaked in an ascorbic acid solution before heat setting treatment, and the graphene oxide is reduced to reduced graphene oxide (RGO).
[0018] Exemplarily, the present application further comprises that the functional material is an anti-inflammatory material, the anti-inflammatory material is cerium dioxide (CeO2).
[0019] Exemplarily, the present application further comprises that the organic solvent is hexafluoroisopropanol (HFIP).
[0020] Exemplarily, the present application further comprises that the process parameters of electrospinning are as follows: the sample volume of the spinning solution used for the nanofiber membrane is 6-10 mL, the voltage is 9-11 kV, the pushing speed of the spinning solution is 1.0-1.5 mL / h, the distance between the syringe needle and the receiving device during spinning is 8-15 cm, and the speed of the drum receiving is 300-400 rpm.
[0021] Exemplarily, the present application further comprises that the heat setting treatment device comprises a stainless steel rod and a constant temperature drying oven, the nanofiber membrane is wrapped around the stainless steel rod after being cut to a predetermined size, and the heat setting is performed in the constant temperature drying oven. Example 1
[0022] (1) Spinning solution preparation: 0.5 g of PLCL and 0.5 g of silk fibroin were dispersed in 10 ml of hexafluoroisopropanol (HFIP), stirred for three days to mix, and a spinning solution was obtained.
[0023] (2) Electrospun nanofiber membrane: Take 10 ml of spinning solution and push the spinning solution through a blunt-ended needle with an inner diameter of 0.18 mm at a spinning voltage of 10 kV and a speed of 1 ml / h. The receiving speed of the spinning roller is 300 rpm and the distance between the needle and the receiving roller is 12 cm to prepare an electrospun nanofiber membrane.
[0024] (3) Nerve conduit shaping: The electrospun nanofiber membrane was cut into rectangles of 1.2cm×2.0cm and wrapped around a stainless steel rod. After wrapping twice, it was heat-set in a drying oven at 120℃ for 6 hours to prepare a self-curling nerve conduit with a tubular structure.
[0025] like Figure 2 As shown in the electron microscope image, the outer layer of the electrospun nanofiber membrane consists of random nanofibers with a smooth surface and fine filaments. The analyzed fiber diameter is 0.74±0.14μm.
[0026] like Figure 7 As shown, the mechanical properties were measured using a tensile testing machine, and the stress-strain curves were obtained. Example 2
[0027] (1) Preparation of spinning solution: Weigh 0.02g of graphene oxide (GO) powder and disperse it in 10ml of hexafluoroisopropanol (HFIP). Stir and mix well, then add 0.5g of PLCL and 0.5g of silk fibroin. Stir with a magnetic stirrer until completely dissolved.
[0028] (2) Electrospun nanofiber membrane: Take 10 ml of spinning solution and push the spinning solution through a blunt-ended needle with an inner diameter of 0.18 mm at a spinning voltage of 10 kV and a speed of 1 ml / h. The receiving speed of the spinning roller is 300 rpm and the distance between the needle and the receiving roller is 12 cm to prepare an electrospun nanofiber membrane.
[0029] (3) Reduction of GO fiber membrane: Under normal temperature conditions, the electrospun nanofiber membrane was immersed in 20 mg / mL ascorbic acid solution and soaked for 3 days for reduction oxidation treatment.
[0030] (4) Nerve conduit shaping: The electrospun nanofiber membrane after reduction and oxidation treatment was cut into rectangles of 1.2cm×2.0cm and wrapped around a stainless steel rod. It was then heat-set in a drying oven at 120℃ for 4 hours to prepare a self-curling nerve conduit with a tubular structure.
[0031] like Figure 4 As shown in the electron micrograph, the outer layer of the electrospun nanofiber membrane consists of random nanofibers with a smooth surface. The fiber diameter is analyzed to be 1.16 ± 0.25 μm.
[0032] likeFigure 7 As shown, the mechanical properties were measured using a tensile testing machine, and the stress-strain curves were obtained. Example 3
[0033] (1) Preparation of spinning solution: Use a pipette to transfer 200 μL of cerium dioxide (CeO2) and disperse it in 10 ml of hexafluoroisopropanol (HFIP). Stir and mix well, then add 0.5 g of PLCL and 0.5 g of silk fibroin. Stir with a magnetic stirrer until completely dissolved.
[0034] (2) Electrospun nanofiber membrane: Take 10 ml of spinning solution and push the spinning solution through a blunt-ended needle with an inner diameter of 0.18 mm at a spinning voltage of 10 kV and a speed of 1 ml / h. The receiving speed of the spinning roller is 300 rpm and the distance between the needle and the receiving roller is 12 cm to prepare an electrospun nanofiber membrane.
[0035] (3) Nerve conduit shaping: The electrospun nanofiber membrane was cut into rectangles of 1.2cm×2.0cm and wrapped around a stainless steel rod. After wrapping twice, it was heat-set in a drying oven at 120℃ for 4 hours to prepare a self-coiling nerve conduit with a tubular structure.
[0036] like Figure 6 As shown in the electron micrograph, the outer layer of the electrospun nanofiber membrane consists of random nanofibers with a smooth surface. The fiber diameter is analyzed to be 0.57 ± 0.15 μm.
[0037] like Figure 7 As shown, the mechanical properties were measured using a tensile testing machine, and the stress-strain curves were obtained.
[0038] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of protection claimed by the present invention. The scope of protection of the present invention is defined by the appended claims and their equivalents.
Claims
1. A silk fibroin PLCL functionalized self-curling nerve conduit, characterized in that, The application relates to a nerve conduit with a lumen structure, which comprises functional materials, a spinning solution and an organic solvent, the functional materials and the spinning solution are processed into a nanofiber membrane through electrospinning, and the nanofiber membrane is subjected to heat setting treatment by a heat setting treatment device. The spinning solution is made of PLCL and silk fibroin.
2. The silk fibroin PLCL functionalized self-curling nerve conduit according to claim 1, wherein, The functional materials are conductive materials, the conductive materials are graphene oxide (GO), the concentration of the graphene oxide is 1-4 mg / ml, the mass concentration of the PLCL in the spinning solution is 50-70%, and the nanofiber membrane containing the graphene oxide (GO) is subjected to immersion treatment by an ascorbic acid solution before heat setting treatment, and the graphene oxide is reduced into reduced graphene oxide (RGO).
3. The silk fibroin PLCL functionalized self-curling nerve conduit according to claim 1, wherein, The functional materials are anti-inflammatory materials, the anti-inflammatory materials are cerium dioxide (CeO2).
4. The silk fibroin PLCL functionalized self-curling nerve conduit according to claim 1, wherein, The organic solvent is hexafluoroisopropanol (HFIP).
5. The silk fibroin PLCL functionalized self-curling nerve conduit according to claim 1, wherein, The process parameters of the electrospinning are as follows: the sample volume of the spinning solution for the nanofiber membrane is 6-10 mL, the voltage is 9-11 kV, the pushing speed of the spinning solution is 1.0-1.5 mL / h, the distance between the needle of the injector and the receiving device is 8-15 cm during spinning, and the speed of the drum receiving device is 300-400 rpm.
6. The silk PLCL functionalized self-curling nerve conduit according to claim 1, wherein, The heat setting treatment device comprises a stainless steel rod and a constant temperature drying box, the nanofiber membrane is wrapped around the stainless steel rod with a predetermined size after being cut to a predetermined size, and heat setting is carried out in the constant temperature drying box.
7. The silk fibroin PLCL functionalized self-curling nerve conduit according to claim 6, wherein, The heat setting temperature of the constant temperature drying box is 100 DEG C-140 DEG C, and the heat setting time is 2 h-6 h.