WO2024082416A1 - Collagenous fiber composite membrane for repairing nerve injuries - Google Patents

Collagenous fiber composite membrane for repairing nerve injuries Download PDF

Info

Publication number
WO2024082416A1
WO2024082416A1 PCT/CN2022/139668 CN2022139668W WO2024082416A1 WO 2024082416 A1 WO2024082416 A1 WO 2024082416A1 CN 2022139668 W CN2022139668 W CN 2022139668W WO 2024082416 A1 WO2024082416 A1 WO 2024082416A1
Authority
WO
WIPO (PCT)
Prior art keywords
layer
regeneration
nerve
fiber composite
composite membrane
Prior art date
Application number
PCT/CN2022/139668
Other languages
French (fr)
Chinese (zh)
Inventor
钱运
严至文
范存义
Original Assignee
上海市第六人民医院
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 上海市第六人民医院 filed Critical 上海市第六人民医院
Publication of WO2024082416A1 publication Critical patent/WO2024082416A1/en

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02W—CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO WASTEWATER TREATMENT OR WASTE MANAGEMENT
    • Y02W90/00—Enabling technologies or technologies with a potential or indirect contribution to greenhouse gas [GHG] emissions mitigation
    • Y02W90/10—Bio-packaging, e.g. packing containers made from renewable resources or bio-plastics

Definitions

  • the invention relates to the technical field of medical devices, and in particular to a collagen fiber composite membrane for repairing nerve damage.
  • Peripheral nerve injury can lead to motor and sensory dysfunction of the patient's limbs.
  • the commonly used clinical treatment methods are autologous nerve transplantation and nerve catheter bridging.
  • slow nerve regeneration and implant adhesion seriously affect the prognosis.
  • Slow nerve regeneration can lead to long-term denervation of the target organ, resulting in irreversible atrophy or even fibrosis, leading to lifelong disability.
  • the peripheral nerves will slide freely in the original cavity. After peripheral nerve injury, local inflammatory factors accumulate, which can lead to abnormal activation of fibroblasts around the injury, causing nerve adhesion.
  • This phenomenon is also one of the important reasons for the poor quality of life of patients after autologous nerve transplantation or nerve stent bridging, because nerve adhesion can cause nerves that can move freely with limb movement to adhere to fixed parts, causing nerve pulling pain when the patient's limbs move. Severe nerve adhesion may even cause nerve compression, resulting in nerve swelling, limited motor function of the affected limb, and chronic pain.
  • the purpose of the present invention is to provide a collagen fiber composite membrane for nerve damage repair in view of the deficiencies in the prior art.
  • the first aspect of the present invention is to provide a collagen fiber composite membrane for nerve damage repair, comprising: an anti-adhesion layer, an elastic connecting layer chemically cross-linked with the anti-adhesion layer, and a regeneration-promoting layer chemically cross-linked with the elastic connecting layer; wherein:
  • the anti-adhesion layer and the regeneration promoting layer can slide relative to each other within 20% of their lengths in the axial direction.
  • the anti-adhesion layer is made of type I collagen by casting in a mold.
  • the elastic connecting layer is made of methacrylated gelatin by casting in a mold.
  • the regeneration-promoting layer is an axially oriented layer made of type I collagen by electrospinning.
  • the anti-adhesion layer and the elastic connecting layer are chemically cross-linked by dopamine hydrochloride.
  • the elastic connecting layer and the regeneration promoting layer are chemically cross-linked by dopamine hydrochloride.
  • the second aspect of the present invention is to provide a use of the collagen fiber composite membrane as described above in the preparation of nerve damage repair products.
  • the nerve injury repair product is a nerve sheath
  • the anti-adhesion layer is an outer tube of the nerve sheath
  • the regeneration promoting layer is an inner tube of the nerve sheath.
  • the nerve injury repair product is a barrier membrane
  • the anti-adhesion layer is the outer layer of the barrier membrane
  • the regeneration promoting layer is the inner layer of the barrier membrane
  • the present invention adopts the above technical solution, and has the following technical effects compared with the prior art:
  • the collagen fiber composite membrane of the present invention is divided into an anti-adhesion layer and a pro-regeneration layer by an elastic connecting layer.
  • the anti-adhesion layer made of type I collagen by mold casting has a smooth surface and is difficult for cells to adhere to, so it can prevent abnormally activated fibroblasts from depositing into adhesion bands;
  • the pro-regeneration layer made of type I collagen by electrospinning has an axial orientation, and nerve supporting cells (for example, Schwann cells and vascular endothelial cells) can adhere to the nanofiber structure for axial regeneration; the relative sliding between the anti-adhesion layer and the pro-regeneration layer can avoid abnormal pain caused by nerve traction; and for nerve rupture injuries and nerve non-rupture injuries, the present invention provides nerve sheaths and barrier membranes respectively to match different situations of clinical peripheral nerve injuries.
  • FIG1 is a schematic diagram of the structure of a nerve sheath in the present invention.
  • FIG2 is a schematic diagram of the structure of the barrier film of the present invention.
  • FIG3 is a schematic diagram of the axial orientation structure of the regeneration-promoting layer in the present invention.
  • FIG4 is a cell experiment diagram of the neural sheath in the present invention.
  • Figures 5-6 are animal experiment diagrams of the nerve sheath tube of the present invention.
  • Anti-adhesion layer 1 elastic connection layer 2; regeneration-promoting layer 3; nerve sheath 4a; barrier membrane 4b.
  • this embodiment provides a nerve sheath tube 4a for repairing nerve damage, comprising:
  • An anti-adhesion layer 1 i.e., an outer tube
  • the anti-adhesion layer 1 is made of type I collagen (Sigma Aldrich, C3867, the same below) by mold casting;
  • An elastic connecting layer 2 wherein the elastic connecting layer 2 is made of methacrylated gelatin (Aladdin Company, M299511, the same below) by mold casting, and the elastic connecting layer 2 and the anti-adhesion layer 1 are chemically cross-linked by dopamine hydrochloride;
  • a pro-regeneration layer 3 (i.e., inner tube), wherein the pro-regeneration layer 3 is an axially oriented layer made of type I collagen by electrospinning, the pro-regeneration layer 3 and the elastic connecting layer 2 are chemically cross-linked by dopamine hydrochloride (MACKLIN Company, D806618, the same below), and the pro-regeneration layer 3 and the anti-adhesion layer 1 can slide relative to each other within 20% of their lengths in the axial direction.
  • dopamine hydrochloride MACKLIN Company, D806618, the same below
  • the average diameter of the axially oriented fibers in the regeneration promoting layer 3 is 5 ⁇ m.
  • This embodiment also provides a method for preparing the nerve sheath tube 4a as described above, the steps comprising:
  • the nano-scale collagen fibers obtained by electrospinning are received by cylindrical molds of different diameters to obtain an axially oriented pro-regeneration layer 3 (as shown in FIG3 ); the anti-adhesion layer 1 and the elastic connection layer 2 are obtained by direct coating and drying using cylindrical molds of different diameters;
  • Dopamine hydrochloride is coated on the inner wall of the anti-adhesion layer 1 , the inner and outer walls of the elastic connection layer 2 , and the outer wall of the regeneration-promoting layer 3 to chemically cross-link the anti-adhesion layer 1 and the elastic connection layer 2 , and the elastic connection layer 2 and the regeneration-promoting layer 3 .
  • This embodiment further provides an application of the nerve sheath tube 4a as described above in nerve damage repair, including:
  • the nerve sheath 4a Before repairing the damaged nerve, the nerve sheath 4a is placed on the nerve segment, followed by autologous nerve transplantation or sheath bridging, and then the nerve sheath 4a is moved to cover the nerve repair site.
  • this embodiment provides a barrier membrane 4b for nerve damage repair, comprising:
  • An anti-adhesion layer 1 (i.e., an outer layer), wherein the anti-adhesion layer 1 is made of type I collagen by casting through a mold;
  • An elastic connecting layer 2 wherein the elastic connecting layer 2 is made of methacrylated gelatin by mold casting, and the elastic connecting layer 2 and the anti-adhesion layer 1 are chemically cross-linked by dopamine hydrochloride;
  • a regeneration-promoting layer 3 (i.e., inner layer), wherein the regeneration-promoting layer 3 is an axially oriented layer made of type I collagen by electrospinning, the regeneration-promoting layer 3 and the elastic connecting layer 2 are chemically cross-linked by dopamine hydrochloride, and the regeneration-promoting layer 3 and the anti-adhesion layer 1 can slide relative to each other within 20% of their lengths in the axial direction.
  • This embodiment further provides an application of the barrier membrane 4b as described above in nerve damage repair, including:
  • the inner side of the third porous structure 3 is covered toward the damaged nerve and fixed with sutures.
  • FIG4a is an immunofluorescence staining of primary peripheral nerve fibroblasts on the surface of the anti-adhesion layer and the surface of the pro-regeneration layer (blue represents the cell nucleus, green represents ⁇ -SMA, a fibroblast activation marker, and red represents Col I (collagen I), which is secreted by activated fibroblasts to form scars).
  • FIG4b is a Schwann Immunofluorescence staining of Schwann cells (glial cells in peripheral nerves, which are important supporting cells for promoting peripheral nerve regeneration) on the surface of the anti-adhesion layer and the pro-regeneration layer (blue represents the cell nucleus, green represents factin, factin is the cytoskeleton and can characterize the cell adhesion, PH3 is a cell proliferation index and can characterize the cell proliferation).
  • This embodiment provides an animal experiment and its results. As shown in Figure 5, Smooth represents that both the inner and outer surfaces are anti-adhesion layers, and Fibrosis represents that the outer surface is an anti-adhesion layer and the inner surface is a pro-regeneration layer.
  • FIG. 5a is a transmission electron microscope image of the regenerated peripheral nerve in the implant to show the axon and myelin structure of the peripheral nerve
  • Figure 5b is a statistical graph showing that the design of the inner surface as a pro-regeneration layer can increase the diameter of the peripheral nerve axon, thereby promoting the reconstruction of the microstructure of the peripheral nerve (Avg. is the abbreviation of average)
  • Figure 5c is a statistical graph showing that the design of the inner surface as a pro-regeneration layer can increase the thickness of the peripheral nerve myelin sheath, thereby achieving a better therapeutic effect.
  • Figure 5d is the pathological detection result of the gastrocnemius innervated by the damaged nerve.
  • Figure 5e shows that the diameter of the gastrocnemius of rats treated with a design stent with an inner surface as a pro-regeneration layer is larger, indicating that the design of the inner surface as a pro-regeneration layer can reduce the atrophy of the gastrocnemius muscle after nerve injury.
  • Figure 5f shows that the fibrosis rate of the gastrocnemius muscle of rats treated with a stent designed with a pro-regeneration layer on the inner surface is smaller, indicating that the design of the inner surface with a pro-regeneration layer can reduce the fibrosis of the gastrocnemius muscle caused by nerve damage.
  • Figure 5g shows that the average muscle fiber area of the gastrocnemius muscle of rats treated with a stent designed with a pro-regeneration layer on the inner surface is larger, indicating that the design of the inner surface with a pro-regeneration layer can improve the recovery of muscle function after nerve damage.
  • the above experiments prove that the design of the inner surface with a pro-regeneration layer can promote the regeneration of peripheral nerves, demonstrating the rationality of this application.
  • This embodiment also provides another animal experiment and its results.
  • Smooth represents that both the inner and outer surfaces are anti-adhesion layers
  • Fibrosis represents that both the inner and outer surfaces are pro-regeneration layers.
  • This experiment uses a 1 cm sciatic nerve defect model of SD rats to verify the effectiveness of this application, and the sampling time point is 4 months after implantation;
  • Figure 6a is a pathological section staining image of the outer surface of the nerve stent;
  • Figure 6b is a statistical analysis showing that the design of the anti-adhesion layer can significantly reduce the thickness of the fiber layer on the surface of the neural implant, thereby achieving the effect of anti-fibrosis and anti-scar formation, proving the rationality of this application.
  • the collagen fiber composite membrane of the present invention is separated into an anti-adhesion layer and a pro-regeneration layer by an elastic connecting layer.
  • the anti-adhesion layer made of type I collagen by mold casting has a smooth surface and is difficult for cells to adhere to, so it can prevent abnormally activated fibroblasts from depositing into adhesion bands;
  • the pro-regeneration layer made of type I collagen by electrospinning has an axial orientation, and the supporting cells of the nerves (for example, Schwann cells and vascular endothelial cells) can adhere to the nanofiber structure for axial regeneration; the relative sliding between the anti-adhesion layer and the pro-regeneration layer can avoid abnormal pain caused by nerve traction; and for nerve rupture injuries and nerve non-rupture injuries, the present invention provides nerve sheaths and barrier membranes respectively to match different situations of clinical peripheral nerve injuries.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dermatology (AREA)
  • Public Health (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Composite Materials (AREA)
  • Materials Engineering (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)

Abstract

The present invention relates to a collagenous fiber composite membrane for repairing nerve injuries. The collagenous fiber composite membrane comprises: an anti-adhesion layer, an elastic connection layer chemically cross-linked with the anti-adhesion layer, and a regeneration-promoting layer chemically cross-linked with the elastic connection layer, wherein the anti-adhesion layer and the regeneration-promoting layer can slide relative to each other within 20% of the lengths thereof along the axial direction. The collagenous fiber composite membrane of the present invention is divided into the anti-adhesion layer and the regeneration-promoting layer by means of the elastic connection layer. The anti-adhesion layer, which is made from type I collagen by means of mold casting, has a smooth surface, and it is difficult for cells to attach thereto, so that abnormally activated fibroblasts can be prevented from deposition in an adhesion zone; the regeneration-promoting layer, which is made from type I collagen by means of electrospinning, has an axial orientation, and supporting cells of the nerves can attach to the nanofiber structure for axial regeneration; and the relative sliding between the anti-adhesion layer and the regeneration-promoting layer can avoid abnormal pain caused by nerve stretching.

Description

一种用于神经损伤修复的胶原纤维复合膜A collagen fiber composite membrane for repairing nerve damage 技术领域Technical Field
本发明涉及医疗器械技术领域，尤其涉及一种用于神经损伤修复的胶原纤维复合膜。The invention relates to the technical field of medical devices, and in particular to a collagen fiber composite membrane for repairing nerve damage.
背景技术Background technique
围神经损伤可导致患者肢体运动与感觉功能障碍，目前临床常用的治疗手段为自体神经移植与神经导管桥接。然而，神经再生速度过慢及植入物粘连严重影响了预后。神经再生速度过慢可导致靶器官失神经支配过长，从而发生不可逆萎缩甚至纤维化，从而导致终生残疾。在肢体进行正常活动时，周围神经会在原有腔隙中自由滑动，而在周围神经损伤后，局部炎症因子积聚，可导致损伤周围成纤维细胞异常激活，造成神经粘连。此现象也是导致自体神经移植手术或神经支架桥接术后患者生活质量不佳的重要原因之一，因为神经粘连会导致原本可以随着肢体活动自由活动的神经粘连在固定部位，从而在患者肢体活动时导致神经牵扯痛，严重的神经粘连甚至可能导致神经卡压，从而使得神经肿胀，患肢运动功能受限，出现慢性疼痛。Peripheral nerve injury can lead to motor and sensory dysfunction of the patient's limbs. Currently, the commonly used clinical treatment methods are autologous nerve transplantation and nerve catheter bridging. However, slow nerve regeneration and implant adhesion seriously affect the prognosis. Slow nerve regeneration can lead to long-term denervation of the target organ, resulting in irreversible atrophy or even fibrosis, leading to lifelong disability. When the limbs are in normal activity, the peripheral nerves will slide freely in the original cavity. After peripheral nerve injury, local inflammatory factors accumulate, which can lead to abnormal activation of fibroblasts around the injury, causing nerve adhesion. This phenomenon is also one of the important reasons for the poor quality of life of patients after autologous nerve transplantation or nerve stent bridging, because nerve adhesion can cause nerves that can move freely with limb movement to adhere to fixed parts, causing nerve pulling pain when the patient's limbs move. Severe nerve adhesion may even cause nerve compression, resulting in nerve swelling, limited motor function of the affected limb, and chronic pain.
因此，亟需一种用于神经损伤修复的胶原纤维复合膜。Therefore, there is an urgent need for a collagen fiber composite membrane for repairing nerve damage.
发明内容Summary of the invention
本发明的目的是针对现有技术中的不足，提供一种用于神经损伤修复的胶原纤维复合膜。The purpose of the present invention is to provide a collagen fiber composite membrane for nerve damage repair in view of the deficiencies in the prior art.
为实现上述目的，本发明采取的技术方案是：To achieve the above object, the technical solution adopted by the present invention is:
本发明的第一方面是提供一种用于神经损伤修复的胶原纤维复合膜，包括：抗粘连层、与所述抗粘连层化学交联的弹性连接层以及与所述弹性连接层化学交联的促再生层；其中，The first aspect of the present invention is to provide a collagen fiber composite membrane for nerve damage repair, comprising: an anti-adhesion layer, an elastic connecting layer chemically cross-linked with the anti-adhesion layer, and a regeneration-promoting layer chemically cross-linked with the elastic connecting layer; wherein:
所述抗粘连层与所述促再生层能够沿轴向方向在其长度的20％之内发生相对滑动。The anti-adhesion layer and the regeneration promoting layer can slide relative to each other within 20% of their lengths in the axial direction.
优选地，所述抗粘连层由I型胶原经模具浇筑制得。Preferably, the anti-adhesion layer is made of type I collagen by casting in a mold.
优选地，所述弹性连接层由甲基丙烯酸酰化明胶经模具浇筑制得。Preferably, the elastic connecting layer is made of methacrylated gelatin by casting in a mold.
优选地，所述促再生层为由I型胶原经静电纺丝制得的轴向取向层。Preferably, the regeneration-promoting layer is an axially oriented layer made of type I collagen by electrospinning.
优选地，所述抗粘连层与所述弹性连接层之间由盐酸多巴胺化学交联。Preferably, the anti-adhesion layer and the elastic connecting layer are chemically cross-linked by dopamine hydrochloride.
优选地，所述弹性连接层与所述促再生层之间由盐酸多巴胺化学交联。Preferably, the elastic connecting layer and the regeneration promoting layer are chemically cross-linked by dopamine hydrochloride.
本发明的第二方面是提供一种如前所述胶原纤维复合膜在制备神经损伤修复产品中的应用。The second aspect of the present invention is to provide a use of the collagen fiber composite membrane as described above in the preparation of nerve damage repair products.
优选地，所述神经损伤修复产品为神经鞘管，所述抗粘连层为所述神经鞘管的外管，所述促再生层为所述神经鞘管的内管。Preferably, the nerve injury repair product is a nerve sheath, the anti-adhesion layer is an outer tube of the nerve sheath, and the regeneration promoting layer is an inner tube of the nerve sheath.
优选地，所述神经损伤修复产品为屏障膜，所述抗粘连层为所述屏障膜的外层，所述促再生层为所述屏障膜的内层。Preferably, the nerve injury repair product is a barrier membrane, the anti-adhesion layer is the outer layer of the barrier membrane, and the regeneration promoting layer is the inner layer of the barrier membrane.
本发明采用以上技术方案，与现有技术相比，具有如下技术效果：The present invention adopts the above technical solution, and has the following technical effects compared with the prior art:
本发明的胶原纤维复合膜被弹性连接层分隔为抗粘连层和促再生层，由I型胶原经模具浇筑制得的抗粘连层表面光滑，难以被细胞附着，故能够防止异常激活的成纤维细胞沉积成粘连带；由I型胶原经静电纺丝制得的促再生层具有轴向取向，神经的支持细胞(例如：施旺细胞和血管内皮细胞)能够贴附于纳米纤维结构进行轴向再生；抗粘连层与促再生层之间的相对滑动能够避免神经牵扯引起的异常痛感；且针对神经断裂伤与神经非断裂伤，本发明分别针对性地提供神经鞘管与屏障膜，匹配临床周围神经损伤的不同情况。The collagen fiber composite membrane of the present invention is divided into an anti-adhesion layer and a pro-regeneration layer by an elastic connecting layer. The anti-adhesion layer made of type I collagen by mold casting has a smooth surface and is difficult for cells to adhere to, so it can prevent abnormally activated fibroblasts from depositing into adhesion bands; the pro-regeneration layer made of type I collagen by electrospinning has an axial orientation, and nerve supporting cells (for example, Schwann cells and vascular endothelial cells) can adhere to the nanofiber structure for axial regeneration; the relative sliding between the anti-adhesion layer and the pro-regeneration layer can avoid abnormal pain caused by nerve traction; and for nerve rupture injuries and nerve non-rupture injuries, the present invention provides nerve sheaths and barrier membranes respectively to match different situations of clinical peripheral nerve injuries.
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
图1为本发明中神经鞘管的结构示意图；FIG1 is a schematic diagram of the structure of a nerve sheath in the present invention;
图2为本发明中屏障膜的结构示意图；FIG2 is a schematic diagram of the structure of the barrier film of the present invention;
图3为本发明中促再生层的轴向取向结构示意图；FIG3 is a schematic diagram of the axial orientation structure of the regeneration-promoting layer in the present invention;
图4为本发明中神经鞘管的细胞实验图；FIG4 is a cell experiment diagram of the neural sheath in the present invention;
图5-6为本发明中神经鞘管的动物实验图；Figures 5-6 are animal experiment diagrams of the nerve sheath tube of the present invention;
其中，附图标记包括：The reference numerals include:
抗粘连层1；弹性连接层2；促再生层3；神经鞘管4a；屏障膜4b。Anti-adhesion layer 1; elastic connection layer 2; regeneration-promoting layer 3; nerve sheath 4a; barrier membrane 4b.
具体实施方式Detailed ways
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动的前提下所获得的所有其他实施例，都属于本发明保护的范围。The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
需要说明的是，在不冲突的情况下，本发明中的实施例及实施例中的特征可以相互组合。It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments may be combined with each other.
下面结合附图和具体实施例对本发明作进一步说明，但不作为本发明的限定。The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, but they are not intended to limit the present invention.
实施例1Example 1
如图1所示，本实施例提供一种用于神经损伤修复的神经鞘管4a，包括：As shown in FIG1 , this embodiment provides a nerve sheath tube 4a for repairing nerve damage, comprising:
抗粘连层1(即外管)，所述抗粘连层1由I型胶原(Sigma Aldrich公司，C3867，下同)经模具浇筑制得；An anti-adhesion layer 1 (i.e., an outer tube), wherein the anti-adhesion layer 1 is made of type I collagen (Sigma Aldrich, C3867, the same below) by mold casting;
弹性连接层2，所述弹性连接层2由甲基丙烯酸酰化明胶(Aladdin公司，M299511，下同)经模具浇筑制得，所述弹性连接层2与所述抗粘连层1之间由盐酸多巴胺化学交联；An elastic connecting layer 2, wherein the elastic connecting layer 2 is made of methacrylated gelatin (Aladdin Company, M299511, the same below) by mold casting, and the elastic connecting layer 2 and the anti-adhesion layer 1 are chemically cross-linked by dopamine hydrochloride;
以及促再生层3(即内管)，所述促再生层3为由I型胶原经静电纺丝制得的轴向取向层，所述促再生层3与所述弹性连接层2之间由盐酸多巴胺(MACKLIN公司，D806618，下同)化学交联，所述促再生层3与所述抗粘连层1能够沿轴向方向在其长度的20％之内发生相对滑动。And a pro-regeneration layer 3 (i.e., inner tube), wherein the pro-regeneration layer 3 is an axially oriented layer made of type I collagen by electrospinning, the pro-regeneration layer 3 and the elastic connecting layer 2 are chemically cross-linked by dopamine hydrochloride (MACKLIN Company, D806618, the same below), and the pro-regeneration layer 3 and the anti-adhesion layer 1 can slide relative to each other within 20% of their lengths in the axial direction.
作为一个优选的实施方式，所述促再生层3轴向取向的纤维平均直径为5μm。As a preferred embodiment, the average diameter of the axially oriented fibers in the regeneration promoting layer 3 is 5 μm.
本实施例还提供一种如前所述神经鞘管4a的制备方法，步骤包括：This embodiment also provides a method for preparing the nerve sheath tube 4a as described above, the steps comprising:
采用不同直径的柱状模具对静电纺丝制得的纳米级胶原纤维进行接收，以制得轴向取向的促再生层3(如图3所示)；采用不同直径的柱状模具通过直接涂抹干燥法以制得抗粘连层1以及弹性连接层2；The nano-scale collagen fibers obtained by electrospinning are received by cylindrical molds of different diameters to obtain an axially oriented pro-regeneration layer 3 (as shown in FIG3 ); the anti-adhesion layer 1 and the elastic connection layer 2 are obtained by direct coating and drying using cylindrical molds of different diameters;
于抗粘连层1的内侧壁、弹性连接层2的内外侧壁以及促再生层3的外侧壁上涂覆盐酸多巴胺，以化学交联抗粘连层1与弹性连接层2以及弹性连接层2与促再生层3。Dopamine hydrochloride is coated on the inner wall of the anti-adhesion layer 1 , the inner and outer walls of the elastic connection layer 2 , and the outer wall of the regeneration-promoting layer 3 to chemically cross-link the anti-adhesion layer 1 and the elastic connection layer 2 , and the elastic connection layer 2 and the regeneration-promoting layer 3 .
本实施例再提供一种如前所述神经鞘管4a在神经损伤修复中的应用，包括：This embodiment further provides an application of the nerve sheath tube 4a as described above in nerve damage repair, including:
在神经损伤处修复前，将神经鞘管4a套设于神经节段之上，随后行自体神经移植术或鞘管桥接术，随后将神经鞘管4a移位至覆盖神经修补部位。Before repairing the damaged nerve, the nerve sheath 4a is placed on the nerve segment, followed by autologous nerve transplantation or sheath bridging, and then the nerve sheath 4a is moved to cover the nerve repair site.
实施例2Example 2
如图2所示，本实施例提供一种用于神经损伤修复的屏障膜4b，包括：As shown in FIG. 2 , this embodiment provides a barrier membrane 4b for nerve damage repair, comprising:
抗粘连层1(即外层)，所述抗粘连层1由I型胶原经模具浇筑制得；An anti-adhesion layer 1 (i.e., an outer layer), wherein the anti-adhesion layer 1 is made of type I collagen by casting through a mold;
弹性连接层2，所述弹性连接层2由甲基丙烯酸酰化明胶经模具浇筑制得，所述弹性连接层2与所述抗粘连层1之间由盐酸多巴胺化学交联；An elastic connecting layer 2, wherein the elastic connecting layer 2 is made of methacrylated gelatin by mold casting, and the elastic connecting layer 2 and the anti-adhesion layer 1 are chemically cross-linked by dopamine hydrochloride;
以及促再生层3(即内层)，所述促再生层3为由I型胶原经静电纺丝制得的轴向取向层，所述促再生层3与所述弹性连接层2之间由盐酸多巴胺化学交联，所述促再生层3与所述抗粘连层1能够沿轴向方向在其长度的20％之内发生相对滑动。And a regeneration-promoting layer 3 (i.e., inner layer), wherein the regeneration-promoting layer 3 is an axially oriented layer made of type I collagen by electrospinning, the regeneration-promoting layer 3 and the elastic connecting layer 2 are chemically cross-linked by dopamine hydrochloride, and the regeneration-promoting layer 3 and the anti-adhesion layer 1 can slide relative to each other within 20% of their lengths in the axial direction.
本实施例的制备步骤与实施例1相似，此处不再赘述。The preparation steps of this embodiment are similar to those of embodiment 1 and will not be repeated here.
本实施例再提供一种如前所述屏障膜4b在神经损伤修复中的应用，包括：This embodiment further provides an application of the barrier membrane 4b as described above in nerve damage repair, including:
将第三多孔结构3的内侧面朝向损伤神经处进行包覆，采用缝线固定即可。The inner side of the third porous structure 3 is covered toward the damaged nerve and fixed with sutures.
实施例3Example 3
本实施例提供一种细胞实验及其结果，如图4所示，图4a为原代周围神经成纤维细胞在抗粘连层表面和促再生层表面的免疫荧光染色(蓝色代表细胞核，绿色代表α-SMA，一种成纤维细胞激活标志物，红色代表Col I(胶原I)，胶原I由成激活纤维细胞分泌从而构成瘢痕)，由统计图(MFI为平均荧光强度mean fluorescent intensity的缩写)可看出，培养在抗粘连层表面的周围神经原代成纤维细胞展现出更少的α-SMA与胶原I表达，说明抗粘连层表面更有利于阻止成纤维细胞激活与瘢痕形成；图4b为施旺细胞(周围神经中的胶质细胞，是促进周围神经再生的重要支持细胞)在抗粘连层表面和促再生层表面的免疫荧光染色(蓝色代表细胞核，绿色代表f actin，f actin是细胞骨架，可表征细胞贴附情况，PH3为细胞增殖指标，可以表征细胞的增殖情况)，由统计图可以看出，培养在促再生层表面的施旺细胞展现出更高的f actin与PH3表达，表示促再生层更利于施旺细胞贴附与增殖，从而体现其促周围神经再生的功能；图4c为使用western blot实验进一步认证上述结果，当培养在抗粘连层表面上时，原代周围神经成纤 维细胞的α-SMA与Col I表达下降；而当培养在促再生层表面上时，施旺细胞的N-Cad(全称为N-Cadherin，细胞粘附指标)与Ki-67(细胞增殖指标)表达上升；上述实验使用GAPDH为内参，以进行蛋白表达变化的相对定量。The present embodiment provides a cell experiment and its results, as shown in FIG4 , FIG4a is an immunofluorescence staining of primary peripheral nerve fibroblasts on the surface of the anti-adhesion layer and the surface of the pro-regeneration layer (blue represents the cell nucleus, green represents α-SMA, a fibroblast activation marker, and red represents Col I (collagen I), which is secreted by activated fibroblasts to form scars). It can be seen from the statistical graph (MFI is the abbreviation of mean fluorescent intensity) that the primary peripheral nerve fibroblasts cultured on the surface of the anti-adhesion layer show less α-SMA and collagen I expression, indicating that the surface of the anti-adhesion layer is more conducive to preventing fibroblast activation and scar formation; FIG4b is a Schwann Immunofluorescence staining of Schwann cells (glial cells in peripheral nerves, which are important supporting cells for promoting peripheral nerve regeneration) on the surface of the anti-adhesion layer and the pro-regeneration layer (blue represents the cell nucleus, green represents factin, factin is the cytoskeleton and can characterize the cell adhesion, PH3 is a cell proliferation index and can characterize the cell proliferation). It can be seen from the statistical graph that Schwann cells cultured on the surface of the pro-regeneration layer showed higher expression of factin and PH3, indicating that the pro-regeneration layer is more conducive to the adhesion and proliferation of Schwann cells, thereby reflecting its function of promoting peripheral nerve regeneration; Figure 4c is a western blot experiment to further verify the above results. When cultured on the surface of the anti-adhesion layer, the expression of α-SMA and Col I of primary peripheral nerve fibroblasts decreased; while when cultured on the surface of the pro-regeneration layer, the expression of N-Cad (full name N-Cadherin, cell adhesion index) and Ki-67 (cell proliferation index) of Schwann cells increased; the above experiment used GAPDH as an internal reference to perform relative quantification of protein expression changes.
实施例4Example 4
本实施例提供一种动物实验及其结果，如图5所示，Smooth代表内外表面均为抗粘连层，Fibrosis代表外表面为抗粘连层，内表面为促再生层。本实验使用SD大鼠坐骨神经缺损1cm模型以验证本申请的有效性，取材时间点为植入后4月；图5a为植入物中再生周围神经的透射电镜图，以展示周围神经的轴突与髓鞘结构；图5b为统计图显示内表面为促再生层的设计可以提高周围神经轴突的直径，从而促进周围神经微观结构的重建(Avg.为average的缩写)；图5c为统计图显示内表面为促再生层的设计可以提高周围神经髓鞘的厚度，从而达到更好的治疗效果。图5d为损伤神经支配的腓肠肌的病理学检测结果。图5e为使用内表面为促再生层的设计支架治疗的大鼠的腓肠肌直径更大，表示内表面为促再生层的设计可以减轻神经损伤后的腓肠肌萎缩。图5f为使用内表面为促再生层的设计支架治疗的大鼠的腓肠肌纤维化率更小，表示内表面为促再生层的设计可以减轻神经损伤导致的腓肠肌纤维化。图5g为使用内表面为促再生层的设计支架治疗的大鼠的腓肠肌的平均肌纤维面积更大，表示内表面为促再生层的设计可以提升神经损伤的肌肉功能恢复。上述实验证明了内表面为促再生层的设计可促进周围神经再生，展示了本申请的合理性。This embodiment provides an animal experiment and its results. As shown in Figure 5, Smooth represents that both the inner and outer surfaces are anti-adhesion layers, and Fibrosis represents that the outer surface is an anti-adhesion layer and the inner surface is a pro-regeneration layer. This experiment uses a 1cm sciatic nerve defect model of SD rats to verify the effectiveness of this application, and the sampling time point is 4 months after implantation; Figure 5a is a transmission electron microscope image of the regenerated peripheral nerve in the implant to show the axon and myelin structure of the peripheral nerve; Figure 5b is a statistical graph showing that the design of the inner surface as a pro-regeneration layer can increase the diameter of the peripheral nerve axon, thereby promoting the reconstruction of the microstructure of the peripheral nerve (Avg. is the abbreviation of average); Figure 5c is a statistical graph showing that the design of the inner surface as a pro-regeneration layer can increase the thickness of the peripheral nerve myelin sheath, thereby achieving a better therapeutic effect. Figure 5d is the pathological detection result of the gastrocnemius innervated by the damaged nerve. Figure 5e shows that the diameter of the gastrocnemius of rats treated with a design stent with an inner surface as a pro-regeneration layer is larger, indicating that the design of the inner surface as a pro-regeneration layer can reduce the atrophy of the gastrocnemius muscle after nerve injury. Figure 5f shows that the fibrosis rate of the gastrocnemius muscle of rats treated with a stent designed with a pro-regeneration layer on the inner surface is smaller, indicating that the design of the inner surface with a pro-regeneration layer can reduce the fibrosis of the gastrocnemius muscle caused by nerve damage. Figure 5g shows that the average muscle fiber area of the gastrocnemius muscle of rats treated with a stent designed with a pro-regeneration layer on the inner surface is larger, indicating that the design of the inner surface with a pro-regeneration layer can improve the recovery of muscle function after nerve damage. The above experiments prove that the design of the inner surface with a pro-regeneration layer can promote the regeneration of peripheral nerves, demonstrating the rationality of this application.
本实施例还提供另一种动物实验及其结果，如图6所示Smooth代表内外表面均为抗粘连层，Fibrosis代表内外表面均为促再生层。本实验使用SD大鼠坐骨神经缺损1cm模型以验证本申请的有效性，取材时间点为植入后4月；图6a为神经支架外表面的病理切片染色图；图6b为统计分析显示抗粘连层的设计可以显著减少神经植入物表面的纤维层厚度，从而达到抗纤维化，抗瘢痕形成的效果，证明了本申请的合理性。This embodiment also provides another animal experiment and its results. As shown in Figure 6, Smooth represents that both the inner and outer surfaces are anti-adhesion layers, and Fibrosis represents that both the inner and outer surfaces are pro-regeneration layers. This experiment uses a 1 cm sciatic nerve defect model of SD rats to verify the effectiveness of this application, and the sampling time point is 4 months after implantation; Figure 6a is a pathological section staining image of the outer surface of the nerve stent; Figure 6b is a statistical analysis showing that the design of the anti-adhesion layer can significantly reduce the thickness of the fiber layer on the surface of the neural implant, thereby achieving the effect of anti-fibrosis and anti-scar formation, proving the rationality of this application.
综上所述，本发明的胶原纤维复合膜被弹性连接层分隔为抗粘连层和促再生层，由I型胶原经模具浇筑制得的抗粘连层表面光滑，难以被细胞附着，故能够防止异常激活的成纤维细胞沉积成粘连带；由I型胶原经静电纺丝制得的促再生层具有轴向取向，神经的支持细胞(例如：施旺细胞和血管内皮细胞)能够贴附 于纳米纤维结构进行轴向再生；抗粘连层与促再生层之间的相对滑动能够避免神经牵扯引起的异常痛感；且针对神经断裂伤与神经非断裂伤，本发明分别针对性地提供神经鞘管与屏障膜，匹配临床周围神经损伤的不同情况。In summary, the collagen fiber composite membrane of the present invention is separated into an anti-adhesion layer and a pro-regeneration layer by an elastic connecting layer. The anti-adhesion layer made of type I collagen by mold casting has a smooth surface and is difficult for cells to adhere to, so it can prevent abnormally activated fibroblasts from depositing into adhesion bands; the pro-regeneration layer made of type I collagen by electrospinning has an axial orientation, and the supporting cells of the nerves (for example, Schwann cells and vascular endothelial cells) can adhere to the nanofiber structure for axial regeneration; the relative sliding between the anti-adhesion layer and the pro-regeneration layer can avoid abnormal pain caused by nerve traction; and for nerve rupture injuries and nerve non-rupture injuries, the present invention provides nerve sheaths and barrier membranes respectively to match different situations of clinical peripheral nerve injuries.
以上所述仅为本发明较佳的实施例，并非因此限制本发明的实施方式及保护范围，对于本领域技术人员而言，应当能够意识到凡运用本发明说明书及图示内容所作出的等同替换和显而易见的变化所得到的方案，均应当包含在本发明的保护范围内。The above description is only a preferred embodiment of the present invention, and does not limit the implementation mode and protection scope of the present invention. For those skilled in the art, it should be aware that all solutions obtained by equivalent substitutions and obvious changes made using the description and illustrations of the present invention should be included in the protection scope of the present invention.

Claims (9)

  1. 一种用于神经损伤修复的胶原纤维复合膜，其特征在于，包括：抗粘连层(1)、与所述抗粘连层(1)化学交联的弹性连接层(2)以及与所述弹性连接层(2)化学交联的促再生层(3)；其中，A collagen fiber composite membrane for nerve damage repair, characterized in that it comprises: an anti-adhesion layer (1), an elastic connection layer (2) chemically cross-linked with the anti-adhesion layer (1), and a regeneration-promoting layer (3) chemically cross-linked with the elastic connection layer (2); wherein:
    所述抗粘连层(1)与所述促再生层(3)能够沿轴向方向在其长度的20％之内发生相对滑动。The anti-adhesion layer (1) and the regeneration promoting layer (3) can slide relative to each other within 20% of their lengths in the axial direction.
  2. 根据权利要求1所述的胶原纤维复合膜，其特征在于，所述抗粘连层(1)由I型胶原经模具浇筑制得。The collagen fiber composite membrane according to claim 1 is characterized in that the anti-adhesion layer (1) is made of type I collagen by casting through a mold.
  3. 根据权利要求1所述的胶原纤维复合膜，其特征在于，所述弹性连接层(2)由甲基丙烯酸酰化明胶经模具浇筑制得。The collagen fiber composite membrane according to claim 1 is characterized in that the elastic connecting layer (2) is made of methacrylated gelatin by mold casting.
  4. 根据权利要求1所述的胶原纤维复合膜，其特征在于，所述促再生层(3)为由I型胶原经静电纺丝制得的轴向取向层。The collagen fiber composite membrane according to claim 1 is characterized in that the regeneration-promoting layer (3) is an axially oriented layer made of type I collagen by electrospinning.
  5. 根据权利要求1所述的胶原纤维复合膜，其特征在于，所述抗粘连层(1)与所述弹性连接层(2)之间由盐酸多巴胺化学交联。The collagen fiber composite membrane according to claim 1 is characterized in that the anti-adhesion layer (1) and the elastic connecting layer (2) are chemically cross-linked by dopamine hydrochloride.
  6. 根据权利要求1所述的胶原纤维复合膜，其特征在于，所述弹性连接层(2)与所述促再生层(3)之间由盐酸多巴胺化学交联。The collagen fiber composite membrane according to claim 1 is characterized in that the elastic connecting layer (2) and the regeneration promoting layer (3) are chemically cross-linked by dopamine hydrochloride.
  7. 一种如权利要求1-6任一项所述胶原纤维复合膜在制备神经损伤修复产品中的应用。A use of the collagen fiber composite membrane as claimed in any one of claims 1 to 6 in the preparation of nerve damage repair products.
  8. 根据权利要求7所述的应用，其特征在于，所述神经损伤修复产品为神经鞘管(4a)，所述抗粘连层(1)为所述神经鞘管(4a)的外管，所述促再生层(3)为所述神经鞘管(4a)的内管。The use according to claim 7 is characterized in that the nerve injury repair product is a nerve sheath (4a), the anti-adhesion layer (1) is the outer tube of the nerve sheath (4a), and the regeneration promoting layer (3) is the inner tube of the nerve sheath (4a).
  9. 根据权利要求7所述的应用，其特征在于，所述神经损伤修复产品为屏障膜(4b)，所述抗粘连层(1)为所述屏障膜(4b)的外层，所述促再生层(3)为所述屏障膜(4b)的内层。The use according to claim 7 is characterized in that the nerve damage repair product is a barrier membrane (4b), the anti-adhesion layer (1) is the outer layer of the barrier membrane (4b), and the regeneration promoting layer (3) is the inner layer of the barrier membrane (4b).
PCT/CN2022/139668 2022-10-20 2022-12-16 Collagenous fiber composite membrane for repairing nerve injuries WO2024082416A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202211283595.7 2022-10-20
CN202211283595.7A CN115634317B (en) 2022-10-20 2022-10-20 Collagen fiber composite membrane for nerve injury repair

Publications (1)

Publication Number Publication Date
WO2024082416A1 true WO2024082416A1 (en) 2024-04-25

Family

ID=84944771

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/139668 WO2024082416A1 (en) 2022-10-20 2022-12-16 Collagenous fiber composite membrane for repairing nerve injuries

Country Status (3)

Country Link
CN (1) CN115634317B (en)
LU (1) LU503769B1 (en)
WO (1) WO2024082416A1 (en)

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1604696A1 (en) * 2001-06-27 2005-12-14 Ethicon, Inc. Porous ceramic/porous polymer layered scaffolds for the repair and regeneration of tissue
CN101912318A (en) * 2010-07-30 2010-12-15 东华大学 Three-layer electrostatic spinning ordered fiber nerve conduit and preparation and application thereof
US20130095167A1 (en) * 2011-10-11 2013-04-18 Bond University Ltd Customized compositions and uses thereof
CN103920194A (en) * 2011-03-25 2014-07-16 广州迈普再生医学科技有限公司 Nerve conduit and preparation method thereof
CN107205809A (en) * 2014-12-16 2017-09-26 巴伦西亚理工大学 The biological mixture regenerated for nerve tract
WO2018225076A1 (en) * 2017-06-09 2018-12-13 Collplant Ltd. Additive manufacturing using recombinant collagen-containing formulation
CN109224133A (en) * 2018-09-21 2019-01-18 浙江大学 A kind of bion multilayer nerve trachea preparation method containing mescenchymal stem cell
CN109260520A (en) * 2018-11-01 2019-01-25 北京航空航天大学 A kind of multi-functional endocranium repair materials and preparation method thereof based on Bionic Design
CN114558173A (en) * 2022-03-02 2022-05-31 青岛大学 Multilayer bioactive nanofiber artificial dura mater and preparation method thereof

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100479785C (en) * 2005-04-07 2009-04-22 首都医科大学北京神经科学研究所 Producing method for double-layer artificial nerve catheter
US8093027B2 (en) * 2006-09-13 2012-01-10 University Of South Florida Method for producing biocomposite comprising collagen and polymer
US8728817B2 (en) * 2007-05-04 2014-05-20 University Of Virginia Patent Foundation Compositions and methods for making and using laminin nanofibers
CN101579247B (en) * 2009-06-23 2012-02-29 许和平 I-type collagen peripheral nerve sheath keeping the peculiar triple helical structure of collagen, preparation method and applications thereof
CN104645412B (en) * 2015-01-28 2016-09-21 南方医科大学 A kind of preparation method of the biomimetic prosthetic Nerve Scaffold built by collagen protein
CN112870451B (en) * 2021-03-02 2022-09-06 山东奥精生物科技有限公司 Nerve sheath tube and preparation method and application thereof

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1604696A1 (en) * 2001-06-27 2005-12-14 Ethicon, Inc. Porous ceramic/porous polymer layered scaffolds for the repair and regeneration of tissue
CN101912318A (en) * 2010-07-30 2010-12-15 东华大学 Three-layer electrostatic spinning ordered fiber nerve conduit and preparation and application thereof
CN103920194A (en) * 2011-03-25 2014-07-16 广州迈普再生医学科技有限公司 Nerve conduit and preparation method thereof
US20130095167A1 (en) * 2011-10-11 2013-04-18 Bond University Ltd Customized compositions and uses thereof
CN107205809A (en) * 2014-12-16 2017-09-26 巴伦西亚理工大学 The biological mixture regenerated for nerve tract
WO2018225076A1 (en) * 2017-06-09 2018-12-13 Collplant Ltd. Additive manufacturing using recombinant collagen-containing formulation
CN109224133A (en) * 2018-09-21 2019-01-18 浙江大学 A kind of bion multilayer nerve trachea preparation method containing mescenchymal stem cell
CN109260520A (en) * 2018-11-01 2019-01-25 北京航空航天大学 A kind of multi-functional endocranium repair materials and preparation method thereof based on Bionic Design
CN114558173A (en) * 2022-03-02 2022-05-31 青岛大学 Multilayer bioactive nanofiber artificial dura mater and preparation method thereof

Also Published As

Publication number Publication date
LU503769B1 (en) 2024-04-23
CN115634317A (en) 2023-01-24
CN115634317B (en) 2023-09-08

Similar Documents

Publication Publication Date Title
Quigley et al. Engineering a multimodal nerve conduit for repair of injured peripheral nerve
Santos et al. PEOT/PBT guides enhance nerve regeneration in long gap defects
CN114377204A (en) Bioerodible coverings and uses thereof
Wilson Coordinated modulation of corneal scarring by the epithelial basement membrane and Descemet's basement membrane
EP2493418A2 (en) Bioerodible wraps and uses therefor
CA2580349A1 (en) Methods and apparatus for enhanced growth of peripheral nerves and nervous tissue
Zhang et al. A long-term retaining molecular coating for corneal regeneration
WO2024082416A1 (en) Collagenous fiber composite membrane for repairing nerve injuries
Hayashida et al. Transplantation of tissue-engineered epithelial cell sheets after excimer laser photoablation reduces postoperative corneal haze
Liang et al. A modified symblepharon ring for sutureless amniotic membrane patch to treat acute ocular surface burns
CN105311679A (en) Complex hernia patch and preparing method and application thereof
Wang et al. The morphological regeneration and functional restoration of bladder defects by a novel scaffold and adipose-derived stem cells in a rat augmentation model
US20220257831A1 (en) Method and device for in vivo bronchus regeneration
Sato et al. Biodegradable polymer coating promotes the epithelization of tissue-engineered airway prostheses
Kenyon et al. Regeneration of corneal epithelial basement membrane following thermal cauterization.
CN113425908A (en) Novel foreign body amnion composite material repair catheter and preparation method thereof
Li et al. Applications of hydrogel materials in different types of corneal wounds
JP2023535979A (en) fiber composite
Kajbafzadeh et al. Tissue-engineered external anal sphincter using autologous myogenic satellite cells and extracellular matrix: functional and histological studies
Droutsas et al. Equine pericardium for tectonic globe repair
Sato et al. Replacement of the left main bronchus with a tissue-engineered prosthesis in a canine model
CN215915828U (en) High-strength degradable regenerated silk protein tissue repairing piece
CN114681106B (en) Implant for promoting wound repair of endometrium
Wu et al. The healing effect of the collagen-glycosaminoglycan copolymer on corneal thinning
CN109276759B (en) Bionic antibacterial abdominal wall repair material