CN-118576762-B - Double-layer core-shell structure artificial fiber dura mater for spinal cord injury and preparation method thereof

Abstract

The invention belongs to the technical field of medical instruments, relates to medical consumables for treating spinal cord injury, and in particular relates to a double-layer core-shell structure artificial fiber dura mater for spinal cord injury and a preparation method thereof. The membrane-shaped structure is formed by double-layer core-shell structure artificial fibers, the double-layer core-shell structure artificial fibers are formed by an outer-layer shell structure and an inner-layer core structure, the material of the outer-layer shell structure is formed by PLGA and PEG, NM is loaded in the outer-layer shell structure, the material of the inner-layer core structure is PLA, and NT3 is loaded in the inner-layer core structure. The artificial fiber dura mater with the double-layer core-shell structure has the advantages of relieving spinal cord edema, preventing fiber adhesion, improving microenvironment, promoting spinal cord injury repair and the like.

Inventors

• FENG SHIQING
• WANG WENCHAO
• Zhou hengxing
• ZHANG XINGSHUANG
• HAN SHUWEI
• ZHANG DAPENG
• SHI GUIDONG
• Shang Shenghui

Assignees

• 山东大学齐鲁医院
• 山东大学

Dates

Publication Date

20260512

Application Date

20240424

Claims (10)

1. 1. The utility model provides a double-deck core-shell structure artificial fiber dura mater for spinal cord injury, its characterized in that comprises membranous structure by double-deck core-shell structure artificial fiber, double-deck core-shell structure artificial fiber comprises outer shell structure and inlayer core structure, outer shell structure's material comprises PLGA and PEG, just load Nafamostat Mesylate (NM) in the outer shell structure, inlayer core structure's material is PLA, just load neurotrophic factor 3 (NT 3) in the inlayer core structure.
2. 2. The artificial fibrous dura mater with a double-layer core-shell structure for spinal cord injury according to claim 1, wherein the PEG is 5-20% of the total weight of PLGA and PEG.
3. 3. The artificial fibrous dura mater with a double-layer core-shell structure for spinal cord injury according to claim 1, wherein the molar ratio of lactic acid units to glycolic acid in PLGA is 1:0.8-1.2; or the weight average molecular weight of PLGA is 880000-117000; Or, the weight average molecular weight of PLA is 100000-130000.
4. 4. The artificial fibrous dura mater with a double-layer core-shell structure for spinal cord injury according to claim 1, wherein the weight of NM is 8-12% of the weight of the outer-layer shell structure; or the ratio of the addition amount of NT3 to the weight of the inner layer core structure is 0.8-1.2:0.1, and mu L is g; Or the weight ratio of the outer shell structure to the inner core structure is 3.5-4.5:1.
5. 5. The artificial fibrous dura mater with a double-layer core-shell structure for spinal cord injury according to claim 1, wherein the thickness is 0.1-0.5 mm.
6. 6. A method for preparing the artificial fibrous dura mater with a double-layer core-shell structure for spinal cord injury according to any one of claims 1 to 5, comprising the following steps: Dissolving PLGA, PEG and NM to prepare shell solution; Dissolving PLA and NT3 to prepare a nucleating solution; Coaxially spinning the shell liquid and the core liquid, and then freeze-drying to obtain the composite fiber.
7. 7. The method for preparing a double-layer core-shell structured artificial fibrous dura mater for spinal cord injury according to claim 6, wherein the solvent of the shell fluid is hexafluoroisopropanol; Or, in the shell solution, the volume ratio of the total weight of PLGA and PEG to the solvent is 0.8-1.2:5, and g is ml.
8. 8. The method for preparing a double-layer core-shell structured artificial fiber dura mater for spinal cord injury according to claim 6, wherein the solvent of the nuclear fluid is hexafluoroisopropanol; Or, in the nuclear liquid, the volume ratio of the weight of PLA to the solvent is 0.8-1.2:8, g: ml.
9. 9. The method for preparing the artificial fibrous dura mater with the double-layer core-shell structure for spinal cord injury according to claim 6, wherein in the coaxial spinning process, the flow rate ratio of the shell liquid to the core liquid is 3.8-4.2:1; Or in the coaxial spinning process, the ratio of the diameter of the inner pipe of the spinning nozzle to the diameter of the outer pipe of the spinning nozzle is 1:1.5-2.0.
10. 10. The method for preparing the artificial fibrous dura mater with the double-layer core-shell structure for spinal cord injury according to claim 6, wherein the time of freeze drying is 45-50 hours.

Description

Double-layer core-shell structure artificial fiber dura mater for spinal cord injury and preparation method thereof Technical Field The invention belongs to the technical field of medical instruments, relates to medical consumables for treating spinal cord injury, and in particular relates to a double-layer core-shell structure artificial fiber dura mater for spinal cord injury and a preparation method thereof. Background The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art. Spinal Cord Injury (SCI) is serious damage to the central nervous system, has the characteristics of high disability rate, high death rate and the like, can cause loss of motor and sensory functions, and can even cause multiple organ failure of human bodies to cause death. External compression caused by fracture and dislocation can be treated by surgical operation, but the simple laminectomy neglects the restriction of dura mater and cannot block the above-mentioned vicious circle, effectively reducing the intramedullary pressure. Therefore, early-stage thoracotomy removal of the dural restraint is a necessary means to block the above-described vicious circle, and is a key to effective repair of spinal cord injury. The local microenvironment is unbalanced after the spinal cord injury, and the induced waterfall type inflammatory response is one of the most main reasons for the reconstruction of the surgical treatment recovery structure but the function is difficult to recover. The imbalance in microenvironment is a major cause of impeding SCI regeneration and recovery. There is bleeding and ischemia at the tissue level, glial scarring, demyelination and demyelination imbalance, imbalance at the cellular level involving differentiation of endogenous stem cells and microglial imbalance, imbalance at the molecular level including neurotrophins and their propeptides, cytokines, inflammatory factors and chemokines. Disclosure of Invention In order to solve the defects of the prior art, the invention aims to provide the double-layer core-shell structure artificial fiber dura mater for spinal cord injury and the preparation method thereof. In order to achieve the above purpose, the technical scheme of the invention is as follows: in a first aspect, a membrane-like structure is formed by a double-layer core-shell structure artificial fiber for spinal cord injury, the double-layer core-shell structure artificial fiber is formed by an outer-layer shell structure and an inner-layer core structure, the material of the outer-layer shell structure is formed by polylactic acid-glycolic acid (PLGA) and polyethylene glycol (PEG), and the outer-layer shell structure is internally loaded with Nafamostat Mesylate (NM), the material of the inner-layer core structure is polylactic acid (PLA), and the inner-layer core structure is internally loaded with neurotrophic factor 3 (NT 3). The inventors have studied that restoring function after reconstruction of the surgical treatment restoration structure by medication is mainly problematic in that (1) the blood-spinal barrier impedes the entry of the drug into the cerebrospinal fluid. The blood-spinal cord barrier can provide stable microenvironment for central nerves, prevent bacteria, viruses and the like from invading, bring great difficulty to the application of medicines, and increase the dosage of systemic administration to ensure that the medicines in cerebrospinal fluid reach effective therapeutic concentration, so that the medicines pass through the blood-spinal cord barrier more, and bring a great number of side effects to patients. (2) The oral medicine is absorbed by the mucosa of digestive tract and then enters into blood circulation system, so that the effective medicine concentration is hard to reach locally, besides, the medicine is cleared by kidney, so that the medicine has too short residence time and too fast metabolism rate in vivo, and the local injection administration mode has the obvious defects that the medicine cannot be gathered and released at the damaged part. For this reason, the present invention loads the drug to the artificial dura mater so that the drug acts on the affected area in situ, thereby bypassing the blood-spinal barrier and circumventing the systemic side effects of oral administration. According to the invention, firstly, PLA and PLGA with anti-adhesion property are selected, so that not only can the fibrous adhesion be prevented, but also the thickness and mechanical property of the artificial membrane prepared by the method can meet the requirement of the dura mater. Secondly, PLGA and PEG are adopted as the materials of the outer shell structure, the preparation method has the advantages of high degradation speed and