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CN1126515C - Medical artificial nerve graft and preparation process thereof - Google Patents

Medical artificial nerve graft and preparation process thereof Download PDF

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Publication number
CN1126515C
CN1126515C CN01108208A CN01108208A CN1126515C CN 1126515 C CN1126515 C CN 1126515C CN 01108208 A CN01108208 A CN 01108208A CN 01108208 A CN01108208 A CN 01108208A CN 1126515 C CN1126515 C CN 1126515C
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chitosan
nerve graft
artificial nerve
medical artificial
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CN1319379A (en
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顾晓松
周赤
张沛云
杨宇民
丁斐
王晓冬
曹涌
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Nantong University
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NANTONG MEDICAL COLLEGE
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Abstract

本发明公开了一种医用人造神经移植物及制备方法,包括生物导管,生物导管内嵌有纤维支架。制备方法包括用壳聚糖或聚乙醇酸、聚乳酸制备生物导管、用聚乙醇酸或聚乳酸制备纤维支架、将纤维支架嵌入生物导管中。本发明所制备的医用人造神经移植物有利于神经生长,使神经损伤后恢复好,制备方法方便、可靠。The invention discloses a medical artificial nerve graft and a preparation method thereof, which comprises a biological conduit, and a fiber support is embedded in the biological conduit. The preparation method includes preparing biological conduits with chitosan, polyglycolic acid, and polylactic acid, preparing fiber scaffolds with polyglycolic acid or polylactic acid, and embedding the fiber scaffolds in the biological conduits. The medical artificial nerve graft prepared by the invention is beneficial to the growth of the nerve, and makes the recovery of the damaged nerve better, and the preparation method is convenient and reliable.

Description

医用人造神经移植物及其制备方法Medical artificial nerve graft and preparation method thereof

本发明涉及一种用于桥接缺损神经的移植物。The present invention relates to a graft for bridging defective nerves.

周围神经缺损是骨科、显微外科、创伤外科、战伤外科治疗的一个难题,虽然现代显微外科技术已高度精确,但目前周围神经损伤修复后的功能恢复率仍不尽人意,人们将进一步提高周围神经康复水平的希望寄托于基础研究的突破。国外将聚乙醇酸(PGA)、聚乳酸(PLA)及其共聚物在组织工程中应用的主要形式有纤维支架、管状结构等。Peripheral nerve defect is a difficult problem in the treatment of orthopedics, microsurgery, trauma surgery, and war wound surgery. Although modern microsurgery techniques are highly accurate, the functional recovery rate after peripheral nerve injury repair is still unsatisfactory. People will further Hopes for improving peripheral nerve rehabilitation rest on breakthroughs in basic research. The main forms of applying polyglycolic acid (PGA), polylactic acid (PLA) and their copolymers in tissue engineering abroad are fibrous scaffolds and tubular structures.

本发明的目的在于提供一种有利于神经生长,使神经损伤后恢复好的医用人造神经移植物及其制备方法。The purpose of the present invention is to provide a kind of medical artificial nerve graft and its preparation method which is beneficial to the growth of nerves and recovers the damaged nerves.

本发明的技术解决方案是:Technical solution of the present invention is:

一种医用人造神经移植物,包括生物导管,生物导管内嵌有纤维支架。A medical artificial nerve graft includes a biological conduit, and a fiber support is embedded in the biological conduit.

生物导管材料为壳聚糖或聚乙醇酸、聚乳酸,纤维支架材料为聚乙醇酸或聚乳酸。生物导管是聚乙醇酸或聚乳酸材料的泡沫状管。医用人造神经移植物直径为2.0~4.0mm。医用人造神经移植物长度为3.0~6.0cm。The bioconduit material is chitosan, polyglycolic acid, polylactic acid, and the fiber scaffold material is polyglycolic acid or polylactic acid. Biological catheters are foam-like tubes of polyglycolic acid or polylactic acid material. The diameter of the medical artificial nerve graft is 2.0-4.0mm. The length of the medical artificial nerve graft is 3.0-6.0cm.

一种医用人造神经移植物的制备方法,包括下列步骤:A method for preparing a medical artificial nerve graft, comprising the following steps:

1)用壳聚糖或聚乙醇酸、聚乳酸制备生物导管;1) prepare biological conduit with chitosan or polyglycolic acid, polylactic acid;

2)用聚乙醇酸或聚乳酸制备纤维支架;2) preparing fiber scaffolds with polyglycolic acid or polylactic acid;

3)将经2)制得的纤维支架嵌入经1)制得的生物导管中。3) Embedding the fiber scaffold prepared in 2) into the biological catheter prepared in 1).

其中制造壳聚糖生物导管的方法是:Wherein the method for making chitosan biological conduit is:

1)将壳聚糖溶于醋酸溶液中;1) chitosan is dissolved in acetic acid solution;

2)加入戊二醛进行交联反应;2) adding glutaraldehyde to carry out cross-linking reaction;

3)加入表面活性剂进行活化处理;3) add surfactant to carry out activation treatment;

4)将经上述步骤得到的溶液倒入模具中成型。4) Pour the solution obtained through the above steps into a mold for molding.

上述制造壳聚糖生物导管的方法中步骤1)的具体步骤是:将脱乙酰度为80~85%的壳聚糖溶于1~3%的醋酸溶液中溶解;步骤2)的具体步骤是:将溶液升温至70~90℃,加入0.5~3倍于壳聚糖量的戊二醛,进行交联反应0.5~3小时,降温至常温;步骤3)的具体步骤是:加入相当于壳聚糖量0.5~1.5倍的表面活性剂斯本85和相当于壳聚糖量0.5~1.5倍的吐温20,将溶液充分搅拌,静置;步骤4)的具体步骤是:将经上述步骤得到的溶液倒入模具中成型,并干燥除去易挥发物质。The specific steps of step 1) in the above-mentioned method for manufacturing chitosan biological conduits are: the chitosan with a deacetylation degree of 80-85% is dissolved in 1-3% acetic acid solution; the specific steps of step 2) are : solution is heated up to 70~90 ℃, adds the glutaraldehyde of 0.5~3 times of chitosan amount, carries out cross-linking reaction 0.5~3 hours, cools down to normal temperature; Step 3) concrete steps are: Surfactant Siben 85 with 0.5 to 1.5 times the amount of polysaccharide and Tween 20 equivalent to 0.5 to 1.5 times the amount of chitosan, the solution is fully stirred and left to stand; the specific steps of step 4) are: The resulting solution is poured into molds and dried to remove volatile substances.

制备聚乙醇酸或聚乳酸泡沫状生物导管的方法是:将聚乙醇酸或聚乳酸先通过常规成型加工成管状结构,然后将其置于3~10MPa二氧化碳高压气体中,至二氧化碳气体在聚乙醇酸或聚乳酸中溶解饱和,再将气压下降,形成泡沫状的管状结构。The method for preparing polyglycolic acid or polylactic acid foamed biological catheter is: polyglycolic acid or polylactic acid is processed into a tubular structure through conventional molding, and then placed in 3-10MPa carbon dioxide high-pressure gas, until the carbon dioxide gas is in the polyethanol It is dissolved and saturated in acid or polylactic acid, and then the air pressure is lowered to form a foamy tubular structure.

本发明所制备的医用人造神经移植物采用壳聚糖、聚乙醇酸、聚乳酸材料,均为生物可降解材料,与人体有着良好的生物相容性,无任何不良反应,且其降解速度较慢,为神经损伤的修复提供了充分的时间保证;结构上采用PGA、PLA管和纤维支架结合的形式,使复合管具有一定的机械强度和韧性,为神经细胞的生长提供了畅通的空间,同时为指导神经细胞有序生长提供了必要的诱导作用;管壁采用泡沫状多孔结构,为神经细胞生长过程中所需的营养物质的输送,提供了必需的途径,神经损伤恢复好。本发明制备方法方便、可靠。The medical artificial nerve graft prepared by the present invention adopts chitosan, polyglycolic acid, and polylactic acid materials, all of which are biodegradable materials, have good biocompatibility with the human body, have no adverse reactions, and have a relatively fast degradation rate. Slow, which provides sufficient time guarantee for the repair of nerve damage; the structure adopts the combination of PGA, PLA tube and fiber scaffold, so that the composite tube has certain mechanical strength and toughness, and provides a smooth space for the growth of nerve cells. At the same time, it provides the necessary induction to guide the orderly growth of nerve cells; the tube wall adopts a foam-like porous structure, which provides a necessary way for the delivery of nutrients required for the growth of nerve cells, and the recovery of nerve damage is good. The preparation method of the invention is convenient and reliable.

下面结合实施例对本发明作进一步说明。The present invention will be further described below in conjunction with embodiment.

实施例1:Example 1:

1)用壳聚糖制备生物导管:将脱乙酰度为80~85%(例80%、28%、85%)的壳聚糖溶于1~3%(例1%、2%、3%)的醋酸溶液中溶解,将上述溶液升温至70~90℃(例70℃、80℃、90℃),加入0.5~3倍(例0.5、1、2、3倍)于壳聚糖量的戊二醛,进行交联反应0.5~3小时(例0.5、1、2、3小时),降温至常温;再加入相当于壳聚糖量0.5~1.5倍(例0.5、1、1.5倍)的斯本85和相当于壳聚糖量0.5~1.5倍(例0.5、1、1.5倍)的吐温20,将溶液充分搅拌,静置24小时以上;将经上述步骤得到的溶液倒入准备好的管状模具(2.0~4.0mm×3.0cm~6cm)中成型,并干燥除去易挥发物质。1) prepare biological conduit with chitosan: the chitosan that the deacetylation degree is 80~85% (example 80%, 28%, 85%) is dissolved in 1~3% (example 1%, 2%, 3% ) in the acetic acid solution, the above solution is heated to 70 ~ 90 ℃ (example 70 ℃, 80 ℃, 90 ℃), add 0.5 ~ 3 times (example 0.5, 1, 2, 3 times) to the amount of chitosan Glutaraldehyde, carry out cross-linking reaction 0.5~3 hours (example 0.5, 1, 2, 3 hours), cool down to normal temperature; Siben 85 and Tween 20 equivalent to 0.5 to 1.5 times the amount of chitosan (for example, 0.5, 1, 1.5 times), fully stir the solution, and let it stand for more than 24 hours; pour the solution obtained through the above steps into the prepared Shaped in a tubular mold (2.0 ~ 4.0mm × 3.0cm ~ 6cm), and dried to remove volatile substances.

2)用聚乙醇酸(PGA)制备纤维支架:用现有技术的常规方法通过挤压成型加工成10~15μm的纤维,并制成不同形状、不同粗细的支架。2) Fabrication of fiber scaffolds with polyglycolic acid (PGA): Extrusion into fibers of 10-15 μm by conventional methods in the prior art, and scaffolds of different shapes and thicknesses.

3)将经2)制得的纤维支架用常规显微操作方法嵌入经1)制得的生物导管中。3) Embedding the fibrous scaffold prepared in 2) into the biological conduit prepared in 1) by conventional micromanipulation methods.

实施例2:Example 2:

纤维支架采用聚乳酸(PLA)材料,用现有技术的常规方法通过挤压成型加工成10~15μm的纤维,并制成不同形状、不同粗细的支架。其余同实施例1。The fiber scaffold is made of polylactic acid (PLA) material, processed into fibers of 10-15 μm by extrusion molding by conventional methods in the prior art, and made into scaffolds of different shapes and thicknesses. All the other are with embodiment 1.

实施例3:Example 3:

采用聚乙醇酸或聚乳酸制造泡沫状生物导管:将聚乙醇酸或聚乳酸先通过常规方法塑料成型加工成管状结构(2.0~4.0mm×3.0cm~6cm),然后将其置于3~10MPa(例3、5、7、10MPa)二氧化碳高压气体中,至二氧化碳气体在聚乙醇酸或聚乳酸中溶解饱和,再将气压下降至一个大气压左右,聚合物中二氧化碳溶解度迅速下降,产生大量的气腔,最终形成泡沫状的管状结构。其余均同实施例1。Polyglycolic acid or polylactic acid is used to manufacture foam-shaped biological catheters: polyglycolic acid or polylactic acid is plastic-molded into a tubular structure (2.0-4.0mm×3.0cm-6cm) by conventional methods, and then placed at 3-10MPa (Example 3, 5, 7, 10MPa) In the carbon dioxide high-pressure gas, until the carbon dioxide gas is dissolved and saturated in polyglycolic acid or polylactic acid, and then the air pressure drops to about one atmospheric pressure, the solubility of carbon dioxide in the polymer drops rapidly, producing a large amount of gas cavities, eventually forming a foamy tubular structure. All the other are the same as in Example 1.

实施例4:Example 4:

纤维支架采用聚乳酸(PLA)材料,用现有技术的常规方法通过挤压成型加工成10~15μm的纤维,并制成不同形状、不同粗细的支架。其余同实施例3。The fiber scaffold is made of polylactic acid (PLA) material, processed into fibers of 10-15 μm by extrusion molding by conventional methods in the prior art, and made into scaffolds of different shapes and thicknesses. All the other are with embodiment 3.

Claims (7)

1、一种医用人造神经移植物,其特征是:包括壳聚糖材料制成的生物导管,生物导管内嵌有纤维支架。1. A medical artificial nerve graft, characterized in that: it includes a biological conduit made of chitosan material, and the biological conduit is embedded with a fiber support. 2、根据权利要求1所述的医用人造神经移植物,其特征是:纤维支架材料为聚乙醇酸或聚乳酸。2. The medical artificial nerve graft according to claim 1, characterized in that: the fiber scaffold material is polyglycolic acid or polylactic acid. 3、根据权利要求1或2所述的医用人造神经移植物,其特征是:医用人造神经移植物直径为2.0~4.0mm。3. The medical artificial nerve graft according to claim 1 or 2, characterized in that the diameter of the medical artificial nerve graft is 2.0-4.0 mm. 4、根据权利要求1或2所述的医用人造神经移植物,其特征是:医用人造神经移植物长度为3.0~6.0cm。4. The medical artificial nerve graft according to claim 1 or 2, wherein the length of the medical artificial nerve graft is 3.0-6.0 cm. 5、一种医用人造神经移植物的制备方法,其特征是:包括下列步骤:5. A method for preparing a medical artificial nerve graft, characterized in that it comprises the following steps: 1)用壳聚糖制备生物导管;1) prepare biological conduit with chitosan; 2)用聚乙醇酸或聚乳酸制备纤维支架;2) preparing fiber scaffolds with polyglycolic acid or polylactic acid; 3)将经2)制得的纤维支架嵌入经1)制得的生物导管中。3) Embedding the fiber scaffold prepared in 2) into the biological catheter prepared in 1). 6、根据权利要求5所述的医用人造神经移植物的制备方法,其特征是:制造壳聚糖生物导管的方法是:6, the preparation method of medical artificial nerve graft according to claim 5 is characterized in that: the method for manufacturing chitosan biological conduit is: 1)将壳聚糖溶于醋酸溶液中;1) chitosan is dissolved in acetic acid solution; 2)加入二戊醛进行交联反应;2) adding diperaldehyde to carry out cross-linking reaction; 3)加入表面活性剂进行活化处理;3) add surfactant to carry out activation treatment; 4)将经上述步骤得到的溶液倒入模具中成型。4) Pour the solution obtained through the above steps into a mold for molding. 7、根据权利要求6所述的医用人造神经移植物的制备方法,其特征在于:步骤1)的具体步骤是:将脱乙酰度为80~85%的壳聚糖溶于1~3%的醋酸溶液中溶解;步骤2)的具体步骤是:将溶液升温至70~90℃,加入0.5~3倍于壳聚糖量的二戊醛,进行交联反应0.5~3小时,降温至常温;步骤3)的具体步骤是:加入相当于壳聚糖量0.5~1.5倍的表面活性剂斯本85和相当于壳聚糖量0.5~1.5倍的吐温20,将溶液充分搅拌,静置;步骤4)的具体步骤是:将经上述步骤得到的溶液倒入模具中成型,并干燥除去易挥发物质。7. The preparation method of medical artificial nerve graft according to claim 6, characterized in that: the specific step of step 1) is: dissolving chitosan with a degree of deacetylation of 80-85% in 1-3% Dissolving in the acetic acid solution; the specific steps of step 2) are: heating the solution to 70-90° C., adding 0.5-3 times the chitosan amount of dipentaldehyde, performing a cross-linking reaction for 0.5-3 hours, and cooling to normal temperature; The specific steps of step 3) are: adding surfactant Siben 85 equivalent to 0.5 to 1.5 times the amount of chitosan and Tween 20 equivalent to 0.5 to 1.5 times the amount of chitosan, fully stirring the solution, and standing; The specific steps of step 4) are: pour the solution obtained through the above steps into a mold for molding, and dry to remove volatile substances.
CN01108208A 2001-02-19 2001-02-19 Medical artificial nerve graft and preparation process thereof Expired - Lifetime CN1126515C (en)

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CN1298298C (en) * 2004-05-14 2007-02-07 清华大学 Preparation method of chitosan tubular bracket
CN100355405C (en) * 2004-06-24 2007-12-19 同济大学 Production of porous stand for tissue engineering
CN100388911C (en) * 2005-09-09 2008-05-21 南方医科大学 Preparation method and application of poultry feather root artificial nerve bridge tube and bridge wire

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CN100382772C (en) * 2005-09-28 2008-04-23 南通大学 Preparation method of medical nerve graft containing silk fibroin
CN100358589C (en) * 2006-04-28 2008-01-02 武汉理工大学 Tubular material and preparation method for repairing human peripheral nerve defect
CN101732760A (en) * 2009-12-31 2010-06-16 扬州大学 Chitosan non-vessel stent and preparation method thereof
CN102526811B (en) * 2010-12-16 2013-10-09 上海其胜生物制剂有限公司 Preparation method and application of degradable carboxymethyl chitosan composite nerve conduit
CN102908207B (en) * 2012-10-30 2015-04-22 南通大学 Tissue engineering nerve graft prepared by biological printing technology and preparation method thereof
CN103230623A (en) * 2013-05-10 2013-08-07 南通大学 Method for in-vitro construction of tissue engineered nerves
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CN106729980B (en) * 2016-12-30 2019-11-12 清华大学 A kind of bionic nerve graft for peripheral nerve repair and its preparation method

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1298298C (en) * 2004-05-14 2007-02-07 清华大学 Preparation method of chitosan tubular bracket
CN100355405C (en) * 2004-06-24 2007-12-19 同济大学 Production of porous stand for tissue engineering
CN100388911C (en) * 2005-09-09 2008-05-21 南方医科大学 Preparation method and application of poultry feather root artificial nerve bridge tube and bridge wire

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