WO2016107108A1 - 一种聚乳酸神经支架及其制备方法 - Google Patents
一种聚乳酸神经支架及其制备方法 Download PDFInfo
- Publication number
- WO2016107108A1 WO2016107108A1 PCT/CN2015/082159 CN2015082159W WO2016107108A1 WO 2016107108 A1 WO2016107108 A1 WO 2016107108A1 CN 2015082159 W CN2015082159 W CN 2015082159W WO 2016107108 A1 WO2016107108 A1 WO 2016107108A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- polylactic acid
- stent
- nerve
- metal wire
- film
- Prior art date
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
- A61L27/02—Inorganic materials
- A61L27/04—Metals or alloys
-
- 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
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
Definitions
- the invention relates to the technical field of nerve stents, in particular to a polylactic acid nerve stent and a preparation method thereof.
- Peripheral nerve damage or breakage due to various trauma causes a decrease or loss of sensory and motor function. Severe peripheral nerve injury often leads to paralysis or permanent loss of labor. Peripheral nerve injury has a high incidence in China. According to statistics, in trauma patients, nerve injury of the extremities accounts for about 10% of the total number of trauma, and about 60% of the fractures of firearm injuries have neurological injuries. To this end, we need to find the ideal treatment for peripheral nerve injury. For peripheral nerve fractures, if the fracture gap is large, the fractured peripheral nerve must be regenerated and repaired by bridging the graft.
- Polylactic acid is a kind of polyester material. It is the most commonly used material in tissue engineering. It has good biocompatibility, degradability and no toxic side effects on human body. However, the cell affinity of polylactic acid is poor. After the three-dimensional nerve tissue engineering scaffold constructed by polylactic acid is implanted into the human body, Schwann cells can not grow well on the scaffold, thus limiting the polylactic acid in the nerve tissue engineering scaffold. Application on.
- the present invention provides a polylactic acid nerve scaffold and a preparation method thereof.
- the artificial nerve scaffold prepared by the method is filled with fibronectin on polylactic acid, so that Schwann cells can grow on the scaffold.
- Biodegradable, with the three-dimensional structure required for nerve regeneration, has far-reaching significance for nerve repair.
- a polylactic acid nerve stent comprising a stent film and a degradable metal wire wrapped by a stent film, and the main component of the stent film is polylactic acid.
- the stent is in the form of a sheet, a strip or a cylinder.
- the degradable wires are distributed along the lateral and longitudinal directions of the stent.
- the main component of the degradable metal wire is magnesium, zinc, calcium, iron or an alloy thereof.
- the preparation method of the polylactic acid nerve stent comprises the following steps:
- the precursor of the obtained polylactic acid nerve scaffold is trimmed into a strip of 10-30 mm, and a fibronectin solution of 30-80 ug/ml is perfused from the top of the strip to allow the fibronectin solution to flow down the pores in the strip. , stationary 0.5-3h, disinfected under ultraviolet irradiation for 15-35min, to obtain the polylactic acid nerve stent.
- the three-dimensional structure of the polylactic acid scaffold is a longitudinal tubular arrangement with a pore diameter of 10-100 ⁇ m, which is advantageous for cell regeneration. Infusion of fibronectin into the scaffold film of polylactic acid helps the Schwann cells to grow between them, thereby facilitating nerve regeneration.
- Degradable metals and their alloys can guide the growth of nerve cells, which is beneficial to the repair of nerve cells.
- the beneficial effects of the invention are: the polylactic acid nerve scaffold of the invention perfuse the fibronectin on the polylactic acid, so that the Schwann cells can grow on the scaffold, biodegradable, and have nerve regeneration
- the required three-dimensional structure, and the setting of degradable metal wire to guide the nerve growth in the stent, has far-reaching significance for nerve repair.
- FIG. 1 is a schematic view showing the structure of a polylactic acid nerve stent according to the present invention.
- a polylactic acid nerve stent comprises a stent film 1 and a degradable metal wire 2 wrapped by a stent film 1.
- the degradable wires 2 are distributed along the lateral and longitudinal directions of the stent.
- the stent can be prepared into various shapes according to the needs of use, and is generally cylindrical or sheet-shaped.
- the main component of the stent film 1 is polylactic acid, and the main component of the degradable metal wire 2 is magnesium, zinc, calcium, iron or an alloy thereof.
- Example 1 A method for preparing a polylactic acid nerve, comprising the following specific steps:
- the precursor of the obtained polylactic acid nerve scaffold was trimmed into a 20 mm strip, and 50 ⁇ g/ml of fibronectin solution was perfused from the top of the strip to allow the fibronectin solution to flow down the pores in the strip, and stood still for 1.5 h.
- the polylactic acid nerve scaffold was obtained by disinfecting for 30 minutes under ultraviolet irradiation.
- Example 2 A method for preparing a polylactic acid nerve, comprising the following specific steps:
- the precursor of the obtained polylactic acid nerve scaffold was trimmed into a strip of 10 mm, and a 30 ug/ml fibronectin solution was perfused from the top of the strip to allow the fibronectin solution to flow down the pores in the strip, and was allowed to stand for 3 hours.
- the polylactic acid nerve scaffold was obtained by sterilizing for 15 minutes under ultraviolet irradiation.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Materials For Medical Uses (AREA)
Abstract
一种聚乳酸神经支架,包括支架膜料(1)以及支架膜料(1)包裹的可降解金属丝(2),所述支架膜料(1)的主要成份为聚乳酸。该方法制备的人工神经支架在聚乳酸上灌注了纤维粘连蛋白,从而使得雪旺细胞可以在支架上生长,生物可降解,具有神经再生所需要的三维结构,对神经修复具有深远的意义。
Description
本发明涉及神经支架技术领域,具体地,涉及一种聚乳酸神经支架及其制备方法。
由于各种外伤原因导致的周围神经损伤或断裂造成伤者感觉和运动功能的下降或丧失。严重的外周神经损伤往往导致患者瘫痪或永久丧失劳动力。外周神经损伤在我国发病率较高,据统计,在外伤患者中,四肢神经伤约占外伤总数的10%,火器伤骨折中约有60%的合并神经伤。为此,需寻找理想的外周神经伤治疗手段。对于外周神经断裂类损伤,若断裂缺口较大,就须借助对缺口进行桥接移植手术才能使断裂的周围神经得到再生修复。
目前,常用的移植体有自体移植体和人工神经支架。自体移植体来源有限且会带来供体后遗症。人工神经支架方面,由于非降解导管材料可能导致神经压迫和二次手术的风险,近年来研究的主要趋向于生物可降解支架材料的开发和研究。当前,美国已经批准多种品牌,如,NeuraGen、SaluBridge,Neurolac等的神经导管用于临床。然而,我国在神经支架方面的研究较为落后,并没有开发出具有自主知识产权的神经导管。
聚乳酸是一种聚酯材料,是目前组织工程中应用的最多最常用的材料,具有良好的生物相容性,可降解性,并对人体无毒副作用。然而,聚乳酸的细胞亲和性能较差,用聚乳酸构建的三维立体神经组织工程支架植入人体后,雪旺细胞在支架上不能良好的生长,因而,限制了聚乳酸在神经组织工程支架上的应用。
发明内容
为了克服现有技术的不足,本发明提供了一种聚乳酸神经支架及其制备方法,该方法制备的人工神经支架在聚乳酸上灌注了纤维粘连蛋白,从而使得雪旺细胞可以在支架上生长,生物可降解,具有神经再生所需要的三维结构,对神经修复具有深远的意义。
本发明的技术方案如下:一种聚乳酸神经支架,包括支架膜料以及支架膜料包裹的可降解金属丝,所述支架膜料的主要成分为聚乳酸。
所述支架为片状,长条状或圆柱状。
所述可降解金属丝沿所述支架的横向和纵向分布。
所述可降解金属丝的主要成分为镁,锌,钙,铁或其合金。
所述聚乳酸神经支架的制备方法,包括如下步骤:
1)取消旋聚乳酸R206,其分子量50X103,溶解在5%的二氧杂环乙烷得到聚乳酸R206二氧杂环乙烷溶液,而后转入制膜模具的模具腔中,模具腔中沿支架成型方向的横向和纵向放置有可降解金属丝,而后将模具浸入液氮中2h,取出置于0℃的真空环境下让溶剂初步挥发,再在室温下让溶剂彻底挥发,使得聚乳酸形成支架膜料并包裹所述可降解金属丝,即聚乳酸神经支架的前体;
2)将所得的聚乳酸神经支架的前体修剪成10-30mm的长条,用30-80ug/ml的纤维粘连蛋白溶液从长条顶端灌注,使纤维粘连蛋白溶液顺长条内的孔隙流下,静止0.5-3h,紫外线照射下消毒15-35min,得到所述聚乳酸神经支架。
所述聚乳酸支架的三维结构为纵行管状排列,孔径为10-100μm,这种结构利于细胞再生。在聚乳酸行的支架膜料中灌注纤维粘连蛋白,有助于雪旺细胞在之间上生长,从而有利于神经再生。
可降解金属及其合金可以引导神经细胞生长,从而有利于神经细胞的修复。
本发明的有益效果为:本发明所述聚乳酸神经支架在聚乳酸上灌注了纤维粘连蛋白,从而使得雪旺细胞可以在支架上生长,生物可降解,具有神经再生
所需要的三维结构,并设置了可降解金属丝引导神经在支架内生长,对神经修复具有深远的意义。
图1为本发明所述聚乳酸神经支架的结构示意图。
下面结合附图和优选实施例对本发明作进一步的描述,但本发明的实施方式不限于此。
参照图1,一种聚乳酸神经支架,包括支架膜料1以及支架膜料1包裹的可降解金属丝2。所述可降解金属丝2沿所述支架的横向和纵向分布。所述支架可以根据使用需要制备成各种形状,一般为圆筒形,也可以是片状。
所述支架膜料1的主要成分为聚乳酸,所述可降解金属丝2的主要成分为镁,锌,钙,铁或其合金。
实施例1:一种聚乳酸神经之间的制备方法,包括如下具体步骤:
1)取消旋聚乳酸R206,其分子量50X103,溶解在5%的二氧杂环乙烷得到聚乳酸R206二氧杂环乙烷溶液,而后转入制膜模具的模具腔中,模具腔中沿支架成型方向的横向和纵向放置有可降解金属丝,而后将模具浸入液氮中2h,取出置于0℃的真空环境下让溶剂初步挥发,再在室温下让溶剂彻底挥发,使得聚乳酸形成支架膜料并包裹所述可降解金属丝,即聚乳酸神经支架的前体;
2)将所得的聚乳酸神经支架的前体修剪成20mm的长条,用50ug/ml的纤维粘连蛋白溶液从长条顶端灌注,使纤维粘连蛋白溶液顺长条内的孔隙流下,静止1.5h,紫外线照射下消毒30min,得到所述聚乳酸神经支架。
实施例2:一种聚乳酸神经之间的制备方法,包括如下具体步骤:
1)取聚乳酸,其分子量50X103,溶解在5%的二氧杂环乙烷得到聚乳酸二氧杂环乙烷溶液,而后转入制膜模具的模具腔中,模具腔中沿支架成型方向的横向和纵向放置有可降解金属丝,而后将模具浸入液氮中2h,取出置于0℃的真空环境下让溶剂初步挥发,再在室温下让溶剂彻底挥发,使得聚乳酸形成支架膜料并包裹所述可降解金属丝,即聚乳酸神经支架的前体;
2)将所得的聚乳酸神经支架的前体修剪成10mm的长条,用30ug/ml的纤维粘连蛋白溶液从长条顶端灌注,使纤维粘连蛋白溶液顺长条内的孔隙流下,静止3h,紫外线照射下消毒15min,得到所述聚乳酸神经支架。
以上内容是结合具体的优选实施方式对本发明所作的进一步详细说明,不能认定本发明的具体实施只局限于这些说明。对于本发明所属技术领域的普通技术人员来说,在不脱离本发明构思的前提下,其架构形式能够灵活多变,可以派生系列产品。只是做出若干简单推演或替换,都应当视为属于本发明由所提交的权利要求书确定的专利保护范围。
Claims (5)
- 一种聚乳酸神经支架,其特征在于,包括支架膜料以及支架膜料包裹的可降解金属丝,所述支架膜料的主要成分为聚乳酸,支架膜料上粘附有纤维粘连蛋白。
- 如权利要求1所述的聚乳酸神经支架,其特征在于,所述支架为片状,长条状或圆柱状。
- 如权利要求1所述的聚乳酸神经支架,其特征在于,所述可降解金属丝沿所述支架的横向和纵向分布。
- 如权利要求1所述的聚乳酸神经支架,其特征在于,所述可降解金属丝的主要成分为镁,锌,钙,铁或其合金。
- 如权利要求1-4任一项所述的聚乳酸神经支架的制备方法,其特征在于,包括如下步骤:1)取消旋聚乳酸R206,其分子量50X103,溶解在5%的二氧杂环乙烷得到聚乳酸R206二氧杂环乙烷溶液,而后转入制膜模具的模具腔中,模具腔中沿支架成型方向的横向和纵向放置有可降解金属丝,而后将模具浸入液氮中2h,取出置于0℃的真空环境下让溶剂初步挥发,再在室温下让溶剂彻底挥发,使得聚乳酸形成支架膜料并包裹所述可降解金属丝,即聚乳酸神经支架的前体;2)将所得的聚乳酸神经支架的前体修剪成10-30mm的长条,用30-80ug/ml的纤维粘连蛋白溶液从长条顶端灌注,使纤维粘连蛋白溶液顺长条内的孔隙流下,静止0.5-3h,紫外线照射下消毒15-35min,得到所述聚乳酸神经支架。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410833446.2 | 2014-12-29 | ||
CN201410833446.2A CN104645409B (zh) | 2014-12-29 | 2014-12-29 | 一种聚乳酸神经支架及其制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2016107108A1 true WO2016107108A1 (zh) | 2016-07-07 |
Family
ID=53237370
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2015/082159 WO2016107108A1 (zh) | 2014-12-29 | 2015-06-24 | 一种聚乳酸神经支架及其制备方法 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN104645409B (zh) |
WO (1) | WO2016107108A1 (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN204394742U (zh) * | 2014-12-29 | 2015-06-17 | 东莞颠覆产品设计有限公司 | 一种内置可降解金属丝的实芯神经支架 |
CN104645409B (zh) * | 2014-12-29 | 2017-06-23 | 东莞颠覆产品设计有限公司 | 一种聚乳酸神经支架及其制备方法 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1562383A (zh) * | 2004-03-16 | 2005-01-12 | 武汉理工大学 | 复合型聚乳酸缓释人工神经导管材料及制备方法 |
CN1589913A (zh) * | 2003-09-02 | 2005-03-09 | 中国人民解放军第四军医大学口腔医学院 | 用于修复周围神经缺损的组织工程化周围神经及制备方法 |
US20100047310A1 (en) * | 2008-08-21 | 2010-02-25 | Taipei Medical University | Bio-acceptable conduits and method providing the same |
CN102149859A (zh) * | 2009-06-25 | 2011-08-10 | 三维生物科技有限公司 | 用于制备三维多孔管状支架的方法及设备 |
CN104107096A (zh) * | 2014-07-18 | 2014-10-22 | 上海交通大学 | 可弯曲全降解镁合金神经导管及其制备方法 |
CN104645409A (zh) * | 2014-12-29 | 2015-05-27 | 东莞颠覆产品设计有限公司 | 一种聚乳酸神经支架及其制备方法 |
-
2014
- 2014-12-29 CN CN201410833446.2A patent/CN104645409B/zh active Active
-
2015
- 2015-06-24 WO PCT/CN2015/082159 patent/WO2016107108A1/zh active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1589913A (zh) * | 2003-09-02 | 2005-03-09 | 中国人民解放军第四军医大学口腔医学院 | 用于修复周围神经缺损的组织工程化周围神经及制备方法 |
CN1562383A (zh) * | 2004-03-16 | 2005-01-12 | 武汉理工大学 | 复合型聚乳酸缓释人工神经导管材料及制备方法 |
US20100047310A1 (en) * | 2008-08-21 | 2010-02-25 | Taipei Medical University | Bio-acceptable conduits and method providing the same |
CN102149859A (zh) * | 2009-06-25 | 2011-08-10 | 三维生物科技有限公司 | 用于制备三维多孔管状支架的方法及设备 |
CN104107096A (zh) * | 2014-07-18 | 2014-10-22 | 上海交通大学 | 可弯曲全降解镁合金神经导管及其制备方法 |
CN104645409A (zh) * | 2014-12-29 | 2015-05-27 | 东莞颠覆产品设计有限公司 | 一种聚乳酸神经支架及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN104645409A (zh) | 2015-05-27 |
CN104645409B (zh) | 2017-06-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Cao et al. | Recent advances in regenerative biomaterials | |
CN104195369B (zh) | 一种Zn-Ca系锌合金及其制备方法与应用 | |
US20070207186A1 (en) | Tear and abrasion resistant expanded material and reinforcement | |
JPS62161375A (ja) | 生体適合性のエラストマ−性物品及びその製造法 | |
EP1275405A1 (de) | Implantat mit poröser Proteinmatrix und Verfahren zu seiner Herstellung | |
CN107778446A (zh) | 降解时间可控、断裂伸长率可调的医用可降解聚氨酯 | |
WO2009092294A1 (en) | Implant for tissue engineering | |
WO2015188403A1 (zh) | 用于神经缺损修复的可降解镁合金神经导管及其制备方法 | |
CN107456601A (zh) | 一种Zn-Cu系锌合金及其制备方法与应用 | |
Goncalves et al. | Biomedical implants for regenerative therapies | |
WO2016107109A1 (zh) | 一种胶原蛋白-羟基磷灰石神经支架及其制备方法 | |
Sarvari et al. | Shape-memory materials and their clinical applications | |
WO2016107108A1 (zh) | 一种聚乳酸神经支架及其制备方法 | |
CN111317867A (zh) | 一种神经导管及其制备方法 | |
Lin et al. | Nerve growth factor released from a novel PLGA nerve conduit can improve axon growth | |
WO2016107106A1 (zh) | 一种内置可降解金属丝的实芯神经支架 | |
WO2016107107A1 (zh) | 一种动物源神经支架及其制备方法 | |
WO2016107112A1 (zh) | 一种富含胶原蛋白的人工神经支架及其制备方法 | |
JP2017519565A (ja) | in situティッシュ・エンジニアリング | |
Grundfest‐Broniatowski | What would surgeons like from materials scientists? | |
WO2016107110A1 (zh) | 一种羟基磷灰石神经支架及其制备方法 | |
Wang et al. | Progress in the research and development of nerve conduits | |
WO2016107111A1 (zh) | 一种基于肌肉的神经支架及其制备方法 | |
Freire | Anti-Bacterial Surface Protection for Prostheses | |
CN107773781B (zh) | 可弯曲全降解锌合金神经导管的制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 15874798 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
32PN | Ep: public notification in the ep bulletin as address of the adressee cannot be established |
Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205 DATED 16/11/2017) |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 15874798 Country of ref document: EP Kind code of ref document: A1 |