JP4292094B2 - Nerve regeneration tube - Google Patents
Nerve regeneration tube Download PDFInfo
- Publication number
- JP4292094B2 JP4292094B2 JP2004048429A JP2004048429A JP4292094B2 JP 4292094 B2 JP4292094 B2 JP 4292094B2 JP 2004048429 A JP2004048429 A JP 2004048429A JP 2004048429 A JP2004048429 A JP 2004048429A JP 4292094 B2 JP4292094 B2 JP 4292094B2
- Authority
- JP
- Japan
- Prior art keywords
- nerve regeneration
- nerve
- tube
- regeneration tube
- covering material
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
Links
- 210000005036 nerve Anatomy 0.000 title claims description 99
- 230000008929 regeneration Effects 0.000 title claims description 82
- 238000011069 regeneration method Methods 0.000 title claims description 82
- 239000000463 material Substances 0.000 claims description 33
- 239000000835 fiber Substances 0.000 claims description 31
- 229920001577 copolymer Polymers 0.000 claims description 14
- 229920000642 polymer Polymers 0.000 claims description 9
- 210000004116 schwann cell Anatomy 0.000 claims description 9
- -1 spiral mesh Substances 0.000 claims description 9
- 239000004744 fabric Substances 0.000 claims description 8
- 230000010261 cell growth Effects 0.000 claims description 6
- 239000003102 growth factor Substances 0.000 claims description 6
- 239000004745 nonwoven fabric Substances 0.000 claims description 6
- 230000021164 cell adhesion Effects 0.000 claims description 5
- 239000002759 woven fabric Substances 0.000 claims description 4
- 239000002131 composite material Substances 0.000 claims description 3
- 102000008186 Collagen Human genes 0.000 description 13
- 108010035532 Collagen Proteins 0.000 description 13
- 210000003050 axon Anatomy 0.000 description 13
- 229920001436 collagen Polymers 0.000 description 13
- 229920001059 synthetic polymer Polymers 0.000 description 9
- 235000015097 nutrients Nutrition 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- 229950003937 tolonium Drugs 0.000 description 7
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 7
- 238000004043 dyeing Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 229920001296 polysiloxane Polymers 0.000 description 6
- 239000002253 acid Substances 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- JJTUDXZGHPGLLC-IMJSIDKUSA-N 4511-42-6 Chemical compound C[C@@H]1OC(=O)[C@H](C)OC1=O JJTUDXZGHPGLLC-IMJSIDKUSA-N 0.000 description 3
- 239000000512 collagen gel Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 229920000117 poly(dioxanone) Polymers 0.000 description 3
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 2
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 2
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 2
- 229920001651 Cyanoacrylate Polymers 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- ZGEYCCHDTIDZAE-BYPYZUCNSA-N L-glutamic acid 5-methyl ester Chemical compound COC(=O)CC[C@H](N)C(O)=O ZGEYCCHDTIDZAE-BYPYZUCNSA-N 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 102000004230 Neurotrophin 3 Human genes 0.000 description 2
- 108090000742 Neurotrophin 3 Proteins 0.000 description 2
- 102000003683 Neurotrophin-4 Human genes 0.000 description 2
- 108090000099 Neurotrophin-4 Proteins 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 150000001277 beta hydroxy acids Chemical class 0.000 description 2
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229920005615 natural polymer Polymers 0.000 description 2
- 210000004126 nerve fiber Anatomy 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 210000000276 neural tube Anatomy 0.000 description 2
- 229940032018 neurotrophin 3 Drugs 0.000 description 2
- 229940097998 neurotrophin 4 Drugs 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000002905 orthoesters Chemical class 0.000 description 2
- 210000000578 peripheral nerve Anatomy 0.000 description 2
- 229920001432 poly(L-lactide) Polymers 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 108700024573 poly-gamma-benzyl-L-glutamate Proteins 0.000 description 2
- 108010054442 polyalanine Proteins 0.000 description 2
- 229920001610 polycaprolactone Polymers 0.000 description 2
- 239000004633 polyglycolic acid Substances 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000003497 sciatic nerve Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000004753 textile Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000007547 Laminin Human genes 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 210000003666 myelinated nerve fiber Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 239000012779 reinforcing material Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Description
本発明は、取扱い性や生産性に優れ、神経再生効果が極めて高く、術後に取り出す必要もない神経再生チューブに関する。 The present invention relates to a nerve regeneration tube that is excellent in handleability and productivity, has a very high nerve regeneration effect, and does not need to be removed after surgery.
末梢神経の再生に関しては、１９８２年に報告されたＬｕｎｄｂｏｒｇらによるシリコーンチューブモデルの発表以来、シリコーンチューブを用いて再生可能な断端間距離を延長するための試みがなされてきた。しかし、シリコーンチューブ内には毛細血管が生成することができない；シリコーンチューブの壁は栄養分が透過することができないため、神経軸索に栄養分が充分に補給されない等の問題点があり、シリコーンチューブを用いても満足のいく神経再生は得られていない。更に、仮に神経が再生できたとしても、いずれは異物であるシリコーンチューブを再手術等により除かなくてはならないという問題点もあった。 With regard to peripheral nerve regeneration, attempts have been made to extend the reproducible stump distance using silicone tubes since the publication of the silicone tube model by Lundberg et al. However, capillaries cannot be formed in the silicone tube; the walls of the silicone tube cannot penetrate the nutrients, so there are problems such as insufficient supply of nutrients to the nerve axons. Satisfactory nerve regeneration has not been obtained even when used. Furthermore, even if the nerve can be regenerated, there is a problem that the silicone tube, which is a foreign substance, must be removed by re-operation.
これに対して、シリコーンチューブの代わりに生体吸収性高分子からなるチューブを用いた末梢神経の再生が試みられている。生体吸収性高分子からなる神経再生チューブを用いれば、神経が再生された後には生体内での加水分解又は酵素の働きにより徐々に神経再生チューブは分解、吸収されることから、改めて手術等の手段により取り出す必要もない。 On the other hand, regeneration of peripheral nerves using a tube made of a bioabsorbable polymer instead of a silicone tube has been attempted. If a nerve regeneration tube made of a bioabsorbable polymer is used, the nerve regeneration tube is gradually decomposed and absorbed by in vivo hydrolysis or enzyme action after the nerve has been regenerated. There is no need to take it out by means.
このような生体吸収性高分子からなる神経再生チューブとしては、例えば、特許文献１には、ラミニンとフィブロネクチンとをコーティングしたコラーゲン繊維の束からなる神経再生補助材が開示されている。特許文献２には、生体分解吸収性材料のチューブと、その内腔に該チューブの軸線にほぼ平行に沿って該チューブを貫通する空隙を有するコラーゲン体からなり、該空隙がコラーゲン、ラミニン等を含むマトリックスゲルで充填されている人工神経管が開示されている。特許文献３には、生体分解吸収性材料のチューブと、その内腔に該チューブの軸線にほぼ平行にラミニンにて被覆されたコラーゲン線維束を挿入した人工神経管が開示されている。特許文献４には、生体内吸収性材料よりなる繊維を束ねた構造を有する神経再建用基材が開示されている。特許文献５には、コラーゲンからなるスポンジ、チューブ、コイル等の支持体が開示されている。特許文献６には、生体分解性材料又は生体吸収性材料からなるスポンジ状の微細なマトリックスと、直線状の生体組織誘導経路又は器官誘導経路とからなる支持体が開示されている。更に、特許文献７には、生体吸収性高分子材料からなるスポンジと、該スポンジより分解吸収期間の長い生体吸収性高分子からなる強化材を含み、その内面がスポンジからなる神経再生チューブが開示されている。 As such a nerve regeneration tube made of a bioabsorbable polymer, for example, Patent Document 1 discloses a nerve regeneration assisting material composed of a bundle of collagen fibers coated with laminin and fibronectin. Patent Document 2 includes a tube of a biodegradable absorbent material and a collagen body having a cavity penetrating the tube along the tube substantially parallel to the axis of the biodegradable absorbent material. The gap contains collagen, laminin, and the like. An artificial neural tube filled with a matrix gel containing is disclosed. Patent Document 3 discloses a tube of biodegradable absorbable material and an artificial neural tube in which a collagen fiber bundle covered with laminin is inserted into the lumen of the tube substantially parallel to the axis of the tube. Patent Document 4 discloses a nerve reconstruction base material having a structure in which fibers made of a bioabsorbable material are bundled. Patent Document 5 discloses a support such as a sponge, tube, or coil made of collagen. Patent Document 6 discloses a support comprising a sponge-like fine matrix made of a biodegradable material or a bioabsorbable material, and a linear biological tissue guide route or organ guide route. Further, Patent Document 7 discloses a nerve regeneration tube including a sponge made of a bioabsorbable polymer material and a reinforcing material made of a bioabsorbable polymer having a longer decomposition and absorption period than that of the sponge, the inner surface of which is made of a sponge. Has been.
これらの神経再生チューブでは、いずれも、神経細胞の軸索の再生を誘導し、神経繊維再生の足場とする材料としてコラーゲンゲルやコラーゲン繊維が用いられている。しかしながら、コラーゲンは生物由来物質であり、安定生産に難があり、また、生物学的感染の可能性が否定できない。また、これらの神経再生チューブは、取扱い性に劣るという問題もあった。 In these nerve regeneration tubes, collagen gel or collagen fiber is used as a material for inducing regeneration of nerve cell axons and as a scaffold for nerve fiber regeneration. However, collagen is a biological material, has difficulty in stable production, and the possibility of biological infection cannot be denied. In addition, these nerve regeneration tubes have a problem that they are inferior in handleability.
本発明は、上記現状に鑑み、取扱い性や生産性に優れ、神経再生効果が極めて高く、術後に取り出す必要もない神経再生チューブを提供することを目的とする。 An object of the present invention is to provide a nerve regeneration tube that is excellent in handleability and productivity, has a very high nerve regeneration effect, and does not need to be removed after surgery.
本発明は、生体吸収性高分子からなる管状被覆材と、前記管状被覆材の管腔内に前記管状被覆材の長手方向に略平行に、管腔占有率が１０〜６０％となるように配置された、Ｌ−ラクチド−ε−カプロラクトン共重合体からなる繊維の束とを含有する神経再生チューブである。
以下に本発明を詳述する。
According to the present invention, a tubular covering material made of a bioabsorbable polymer and a lumen occupation rate within a lumen of the tubular covering material are approximately parallel to the longitudinal direction of the tubular covering material and become 10 to 60%. A nerve regeneration tube containing a bundle of fibers made of L-lactide-ε-caprolactone copolymer .
The present invention is described in detail below.
本発明の神経再生チューブは、生体吸収性高分子からなる管状被覆材と生体吸収性合成高分子からなる繊維の束とを含有する。このように生体吸収性高分子を材料として用いることにより、術後に神経が再生した後には生体内で加水分解され、吸収されることから、手術等により改めて取り出す必要がなく、患者への負担を最小限に抑えることができる。 The nerve regeneration tube of the present invention contains a tubular covering material made of a bioabsorbable polymer and a bundle of fibers made of a bioabsorbable synthetic polymer. By using a bioabsorbable polymer as a material in this way, after nerve regeneration after surgery, it is hydrolyzed and absorbed in vivo, so there is no need to take it out again by surgery, etc. Can be minimized.
上記管状被覆材は、神経が再生される間、侵入した結合組織等により阻まれて神経の再生が停止してしまうのを防ぐ役割を有する。
上記管状被覆材を構成する生体吸収性高分子としては特に限定されず、生体吸収性合成高分子であっても、生体吸収性天然高分子であってもよい。
上記生体吸収性合成高分子としては特に限定されず、例えば、ポリ乳酸、ポリグリコール酸、ポリ−ε−カプロラクトン、乳酸−グリコール酸共重合体、グリコール酸−ε−カプロラクトン共重合体、乳酸−ε−カプロラクトン共重合体、ポリ−p−ジオキサノン、ポリトリメチレンカーボネート、ポリクエン酸、ポリリンゴ酸、ポリ−α−シアノアクリレート、ポリ−β−ヒドロキシ酸、ポリトリメチレンオキサレート、ポリテトラメチレンオキサレート、ポリオルソエステル、ポリオルソカーボネート、ポリエチレンカーボネート、ポリ−γ−ベンジル−Ｌ−グルタメート、ポリ−γ−メチル−Ｌ−グルタメート、ポリ−Ｌ−アラニン等が挙げられる。
上記生体吸収性天然高分子としては特に限定されず、例えば、デンプン、アルギン酸、ヒアルロン酸、キチン、ペクチン酸及びその誘導体等の多糖類や、ゼラチン、コラーゲン、アルブミン、フィブリン等のタンパク質等が挙げられる。
The tubular covering material has a role of preventing nerve regeneration from being stopped by being blocked by an invading connective tissue or the like during nerve regeneration.
The bioabsorbable polymer constituting the tubular covering material is not particularly limited, and may be a bioabsorbable synthetic polymer or a bioabsorbable natural polymer.
The bioabsorbable synthetic polymer is not particularly limited, and examples thereof include polylactic acid, polyglycolic acid, poly-ε-caprolactone, lactic acid-glycolic acid copolymer, glycolic acid-ε-caprolactone copolymer, and lactic acid-ε. -Caprolactone copolymer, poly-p-dioxanone, polytrimethylene carbonate, polycitric acid, polymalic acid, poly-α-cyanoacrylate, poly-β-hydroxy acid, polytrimethylene oxalate, polytetramethylene oxalate, poly Examples include orthoester, polyorthocarbonate, polyethylene carbonate, poly-γ-benzyl-L-glutamate, poly-γ-methyl-L-glutamate, poly-L-alanine and the like.
The bioabsorbable natural polymer is not particularly limited, and examples thereof include polysaccharides such as starch, alginic acid, hyaluronic acid, chitin, pectic acid and derivatives thereof, and proteins such as gelatin, collagen, albumin, and fibrin. .
上記管状被覆材の構造としては特に限定されないが、例えば、スポンジ、組紐、編物、織物、不織布、スパイラルメッシュ、フィルムからなる群より選択される少なくとも１の構造体からなることが好ましい。なかでも、スポンジと、組紐、編物、織物、不織布又はスパイラルメッシュとの複合体が好適である。スポンジは、その孔径を適当に調整すれば、外部からの結合組織等の侵入を防ぐことができるとともに、周囲からの血管のｉｎｇｒｏｗｔｈが期待でき、栄養成分や老廃物等の透過に優れることから、本発明の神経再生チューブを生体内に移植して神経を再生させる場合に、神経再生チューブ内で伸張する神経組織に充分な栄養を供給し、また、老廃物を効率よく除くことができる。更に、本発明の神経再生チューブがシュワン細胞を含有する場合にも、シュワン細胞の足場基材となるうえ、シュワン細胞への栄養の供給に優れる。スポンジ体は強度の点では問題があるものの、組紐、編物、織物、不織布又はスパイラルメッシュとの複合体とすることにより、優れた栄養成分等の透過性を維持したまま、充分な強度を付与することができる。 Although it does not specifically limit as a structure of the said tubular coating material, For example, it is preferable to consist of at least 1 structure selected from the group which consists of sponge, braid, a knitted fabric, a textile fabric, a nonwoven fabric, a spiral mesh, and a film. Especially, the composite_body | complex of sponge and a braid, a knitted fabric, a textile fabric, a nonwoven fabric, or a spiral mesh is suitable. Sponge can prevent the invasion of connective tissue and the like from the outside if the pore diameter is appropriately adjusted, and can expect the blood vessel from the surroundings, and is excellent in permeation of nutritional components and waste products. When the nerve regeneration tube of the present invention is transplanted into a living body to regenerate nerves, sufficient nutrients can be supplied to the nerve tissue extending in the nerve regeneration tube, and waste products can be efficiently removed. Furthermore, when the nerve regeneration tube of the present invention contains Schwann cells, it becomes a scaffold substrate for Schwann cells and is excellent in supplying nutrients to Schwann cells. Although the sponge body has a problem in terms of strength, the composite body with braid, knitted fabric, woven fabric, non-woven fabric or spiral mesh gives sufficient strength while maintaining excellent permeability of nutrients and the like. be able to.
上記管状被覆材がスポンジと組紐、編物、織物、不織布又はスパイラルメッシュとの複合体である場合、スポンジと組紐等とが完全に一体化した１層構造、スポンジからなる管状体の外側に組紐等からなる管状体が配置された２層構造、スポンジからなる管状体の内側に組紐等からなる管状体が配置された２層構造、組み紐等からなる管状体の内側と外側とにスポンジからなる管状体が配置された３層構造、及び、スポンジからなる管状体の内側と外側とに組紐等からなる管状体が配置された３層構造等が考えられる。なかでも、スポンジと組紐等とが完全に一体化した１層構造又はスポンジからなる管状体の内側に組紐等からなる管状体が配置された２層構造が好適である。内層にスポンジからなる管状体が配置されている場合には、分解の進行に伴いスポンジと組紐等との結合性が弱まったときに、支持を失ったスポンジが管状体の管腔を塞いでしまう恐れがあるので、素材の選択や組合せ、或いは、スポンジ層の厚さ等により、これをカバーすることが望ましい。 When the tubular covering material is a composite of sponge and braid, knitted fabric, woven fabric, nonwoven fabric or spiral mesh, a one-layer structure in which the sponge and braid are completely integrated, braid on the outside of the tubular body made of sponge, etc. A two-layer structure in which a tubular body made of a material is arranged, a two-layer structure in which a tubular body made of a braid or the like is arranged inside a tubular body made of a sponge, and a tube made of a sponge on the inside and outside of the tubular body made of a braided string or the like A three-layer structure in which a body is disposed, a three-layer structure in which a tubular body composed of braids or the like is disposed on the inside and the outside of a tubular body composed of sponge, and the like are conceivable. Among these, a one-layer structure in which a sponge and braid are completely integrated, or a two-layer structure in which a tubular body made of braid or the like is arranged inside a tubular body made of sponge is preferable. When a tubular body made of sponge is arranged in the inner layer, the sponge that has lost its support will block the lumen of the tubular body when the connectivity between the sponge and braid is weakened as the decomposition progresses Since there is a fear, it is desirable to cover this by selection or combination of materials, or the thickness of the sponge layer.
上記管状被覆材は、内径の好ましい下限が０．３ｍｍ、好ましい上限が１２ｍｍである。０．３ｍｍであると、縫合時に管腔がふさがることがあり、１２ｍｍを超えると、本発明の神経再生チューブの中心部まで充分に栄養成分が行き渡らないことがある。より好ましい下限は０．５ｍｍ、より好ましい上限は１０ｍｍである。
上記管状被覆材は、外径の好ましい下限が０．４ｍｍ、好ましい上限が１３ｍｍである。０．４ｍｍであると、縫合時に管腔がふさがることがあり、１３ｍｍを超えると、本発明の神経再生チューブの中心部まで充分に栄養成分が行き渡らないことがある。より好ましい下限は０．６ｍｍ、より好ましい上限は１１ｍｍである。
The tubular coating material has a preferable lower limit of the inner diameter of 0.3 mm and a preferable upper limit of 12 mm. If 0.3 mm, the lumen may be blocked during suturing, and if it exceeds 12 mm, nutrient components may not be sufficiently distributed to the center of the nerve regeneration tube of the present invention. A more preferable lower limit is 0.5 mm, and a more preferable upper limit is 10 mm.
The tubular coating material has a preferable lower limit of the outer diameter of 0.4 mm and a preferable upper limit of 13 mm. If it is 0.4 mm, the lumen may be blocked at the time of suturing, and if it exceeds 13 mm, the nutrient component may not sufficiently reach the center of the nerve regeneration tube of the present invention. A more preferable lower limit is 0.6 mm, and a more preferable upper limit is 11 mm.
前記繊維束は、神経軸索の再生を誘導する役割を有するものである。
前記繊維束は、生体吸収性合成高分子からなる。本発明者らは、鋭意検討の結果、生体吸収性合成高分子からなる繊維を用い、かつ、これを一定範囲の管腔占有率となるように上記管状被覆材の管腔に複数本配置した場合には、極めて高い神経再生効果を実現できることを見出した。神経軸索が再生し伸長するためには何らかの足場となるものが必要であるが、コラーゲンゲルは方向性がなく、また、コラーゲン繊維も繊維の直進性に劣るため、神経再生チューブ内を神経軸索が迷走してしまうことがあると考えられる。また、コラーゲンは分解が速く、水溶性分解物が早期にチューブの外へ流失する可能性がある。また、コラーゲンは含水して膨潤するため、特にゲルの場合、物理的にスペースを占有してしまうため、神経軸索の再生スペースがなくなってしまう。更に、従来のコラーゲンゲルやコラーゲン繊維を用いた神経再生チューブでは、周辺組織から応力がかかったときに折れ曲がり等の極端な変形が起こりやすく、そのたびに再生しつつある神経軸索が寸断されてしまう可能性もある。
The fiber bundle has a role of inducing regeneration of nerve axons.
The fiber bundle is made of a bioabsorbable synthetic polymer. As a result of intensive studies, the present inventors have used fibers made of bioabsorbable synthetic polymers, and arranged a plurality of them in the lumen of the tubular covering material so that the lumen occupancy rate is within a certain range. In some cases, it was found that an extremely high nerve regeneration effect can be realized. In order for nerve axons to regenerate and elongate, some kind of scaffolding is necessary, but collagen gel is not directional, and collagen fibers are inferior in the straightness of the fibers, so the nerve axis is inside the nerve regeneration tube. It is thought that the cable may get lost. In addition, collagen decomposes quickly, and water-soluble degradation products may flow out of the tube at an early stage. In addition, since collagen hydrates and swells, especially in the case of gels, it physically occupies space, so that the regeneration space for nerve axons is lost. Furthermore, in a nerve regeneration tube using a conventional collagen gel or collagen fiber, extreme deformation such as bending is likely to occur when stress is applied from surrounding tissues, and the nerve axon that is being regenerated each time is severed. There is also a possibility of end.
かかる点、生体吸収性合成高分子からなる繊維は、一定の柔軟性を有する一方で適度な直進性を有することから、神経軸索が迷走することなく最短距離を通って再生することができる。また、生体内に神経再生チューブを移植した場合、いかに安静にしても日常生活上最低限の動きが必要であるため、一時的に神経再生チューブに大きな応力が加わることがあるが、生体吸収性合成高分子からなる繊維を用いた本発明の神経再生チューブは、このような応力によっても大きくは変形しにくいことから、取扱い性に優れ、効率よい神経の再生を実現できる。更に、生体吸収性合成高分子は極めて紡糸が容易であることから、様々なタイプのものが提供でき、生産性も高い。 In this respect, the fiber made of the bioabsorbable synthetic polymer has a certain degree of flexibility and has a suitable straightness, so that the nerve axon can be regenerated through the shortest distance without straying. In addition, when a nerve regeneration tube is implanted in a living body, no matter how quiet it is, minimal stress is necessary in daily life, so a large stress may be temporarily applied to the nerve regeneration tube. The nerve regeneration tube of the present invention using a fiber made of a synthetic polymer is not easily deformed by such stress, so that it has excellent handleability and can realize efficient nerve regeneration. Furthermore, since the bioabsorbable synthetic polymer is very easy to spin, various types can be provided and the productivity is high.
上記繊維を構成する生体吸収性合成高分子としては、例えば、ポリ乳酸、ポリグリコール酸、ポリ−ε−カプロラクトン、乳酸−グリコール酸共重合体、グリコール酸−ε−カプロラクトン共重合体、乳酸−ε−カプロラクトン共重合体、ポリ−p−ジオキサノン、ポリトリメチレンカーボネート、ポリクエン酸、ポリリンゴ酸、ポリ−α−シアノアクリレート、ポリ−β−ヒドロキシ酸、ポリトリメチレンオキサレート、ポリテトラメチレンオキサレート、ポリオルソエステル、ポリオルソカーボネート、ポリエチレンカーボネート、ポリ−γ−ベンジル−Ｌ−グルタメート、ポリ−γ−メチル−Ｌ−グルタメート、ポリ−Ｌ−アラニン等が挙げられる。なかでも、紡糸が容易で、強度と柔軟性とを兼ね備えた繊維が得られることから、乳酸−ε−カプロラクトン共重合体、グリコール酸−ε−カプロラクトン共重合体、ポリ−p−ジオキサノン等が好適である。なお、共重合比は、所望の機能に応じ適宜選択すればよい。 Examples of the bioabsorbable synthetic polymer constituting the fiber include polylactic acid, polyglycolic acid, poly-ε-caprolactone, lactic acid-glycolic acid copolymer, glycolic acid-ε-caprolactone copolymer, and lactic acid-ε. -Caprolactone copolymer, poly-p-dioxanone, polytrimethylene carbonate, polycitric acid, polymalic acid, poly-α-cyanoacrylate, poly-β-hydroxy acid, polytrimethylene oxalate, polytetramethylene oxalate, poly Examples include orthoester, polyorthocarbonate, polyethylene carbonate, poly-γ-benzyl-L-glutamate, poly-γ-methyl-L-glutamate, poly-L-alanine and the like. Among them, since it is easy to spin and fibers having both strength and flexibility can be obtained, lactic acid-ε-caprolactone copolymer, glycolic acid-ε-caprolactone copolymer, poly-p-dioxanone, etc. are preferable. It is. In addition, what is necessary is just to select a copolymerization ratio suitably according to a desired function.
上記繊維の繊維径としては特に限定されないが、好ましい下限は３μｍ、好ましい上限は３００μｍである。３μｍであると、繊維束に偏りが生じ、繊維が均一に広がらないことがあり、３００μｍを超えると、神経軸索の接着・伸長に供する表面積が小さくなり、神経の再生が遅くなることがある。より好ましい下限は５μｍ、より好ましい上限は２５０μｍである。
また、その断面形状は特に限定されるものでなく、円形、楕円形の他、様々な形状の異形断面糸を用いることができる。
Although it does not specifically limit as a fiber diameter of the said fiber, A preferable minimum is 3 micrometers and a preferable upper limit is 300 micrometers. If it is 3 μm, the fiber bundle may be biased and the fibers may not spread uniformly. If it exceeds 300 μm, the surface area used for adhesion / extension of nerve axons may be reduced, and nerve regeneration may be delayed. . A more preferable lower limit is 5 μm, and a more preferable upper limit is 250 μm.
Moreover, the cross-sectional shape is not particularly limited, and various cross-sectional yarns having various shapes can be used in addition to circular and elliptical shapes.
上記繊維は、上記管状被覆材の管腔内に、管状被覆材の長手方向に略平行に配置されている。
上記繊維による管腔占有率の下限は１０％、上限は６０％である。管腔占有率がこの範囲内にあるときに、極めて高い神経再生率を実現できる。好ましい下限は１２％、好ましい上限は４８％である。
なお、本明細書において管腔占有率とは、本発明の神経再生チューブを長手方向に垂直な断面で見たときに、管腔部分全体の面積に占める繊維部分の面積の総和の割合を意味し、断面部の写真等から測定することができる。
The fibers are arranged in the lumen of the tubular covering material substantially parallel to the longitudinal direction of the tubular covering material.
The lower limit of the lumen occupation rate by the fibers is 10%, and the upper limit is 60%. When the lumen occupancy is within this range, an extremely high nerve regeneration rate can be realized. A preferred lower limit is 12% and a preferred upper limit is 48%.
In this specification, the lumen occupancy rate means the ratio of the total area of the fiber portion to the total area of the lumen portion when the nerve regeneration tube of the present invention is viewed in a cross section perpendicular to the longitudinal direction. It can be measured from a photograph of the cross section.
本発明の神経再生チューブに、更に、細胞接着性因子を含有させることも可能である。細胞接着性因子を含有することにより、神経軸索の接着・伸長を促進し、その再生を促すことができる。
上記細胞接着性因子としては特に限定されず、例えば、コラーゲン、ラミニン、フィブロネクチン、神経細胞の特異抗体等が挙げられる。
上記細胞接着性因子は、例えば、上記繊維の表面や上記管状被覆材の内壁に、コーティング等の方法等により接着させることができる。
The nerve regeneration tube of the present invention can further contain a cell adhesion factor. By containing a cell adhesion factor, it is possible to promote adhesion and elongation of nerve axons and promote their regeneration.
The cell adhesion factor is not particularly limited, and examples thereof include collagen, laminin, fibronectin, and nerve cell specific antibody.
The cell adhesion factor can be adhered to the surface of the fiber or the inner wall of the tubular covering material by a method such as coating.
本発明の神経再生チューブに、更に、細胞成長因子を含有させることも可能である。細胞成長因子を含有することにより、神経軸索の成長を促進し、その再生を促すことができる。
上記細胞成長因子としては特に限定されず、例えば、神経成長因子（ＮＧＦ）、脳由来神経栄養因子（ＢＤＮＦ）、毛様体神経栄養因子（ＣＮＴＦ）、ニューロトロフィン−３（ＮＴ−３）及びニューロトロフィン−４（ＮＴ−４）等が挙げられる。
上記細胞成長因子は、例えば、上記繊維の表面や上記管状被覆材の内壁に、物理的吸着や化学結合等の方法により付着させることができる。
The nerve regeneration tube of the present invention can further contain a cell growth factor. By containing a cell growth factor, the growth of nerve axons can be promoted and the regeneration thereof can be promoted.
The cell growth factor is not particularly limited. For example, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), neurotrophin-3 (NT-3) and Neurotrophin-4 (NT-4) etc. are mentioned.
The cell growth factor can be attached to the surface of the fiber or the inner wall of the tubular covering material by a method such as physical adsorption or chemical bonding.
本発明の神経再生チューブに、更に、シュワン細胞を含有させることも可能である。シュワン細胞は、上述の細胞成長因子等を分泌することから、神経軸索の成長を促進し、その再生を促すことができる。
上記シュワン細胞としては、免疫反応による拒絶を防止する目的から、患者自身の細胞を用いることが好ましい。
上記シュワン細胞は、例えば、適当な培養液に懸濁させたシュワン細胞懸濁液を上記管状被覆材の内壁に播種する方法により、付着させることができる。
The nerve regeneration tube of the present invention can further contain Schwann cells. Since Schwann cells secrete the above-mentioned cell growth factors and the like, they can promote the growth of nerve axons and promote their regeneration.
As said Schwann cell, it is preferable to use a patient's own cell for the purpose of preventing rejection by an immune reaction.
The Schwann cells can be attached by, for example, a method of seeding the Schwann cell suspension suspended in an appropriate culture solution on the inner wall of the tubular covering material.
本発明の神経再生チューブは、極めて高い神経再生効果が得られる。また、適度な強度を有することから取扱い性に優れ、生産性にも優れる。更に、神経が再生した後には分解、吸収されることから、手術等により取り出す必要もない。 The nerve regeneration tube of the present invention can provide an extremely high nerve regeneration effect. Moreover, since it has moderate intensity | strength, it is excellent in handleability and excellent in productivity. Furthermore, since nerves are decomposed and absorbed after regeneration, there is no need to remove them by surgery or the like.
本発明によれば、取扱い性や生産性に優れ、神経再生効果が極めて高く、術後に取り出す必要もない神経再生チューブを提供することができる。 According to the present invention, it is possible to provide a nerve regeneration tube that is excellent in handleability and productivity, has an extremely high nerve regeneration effect, and does not need to be removed after surgery.
以下に実施例を掲げて本発明を更に詳しく説明するが、本発明はこれら実施例のみに限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.
（実施例１）
ポリ−Ｌ−乳酸繊維（８８ｄｔｅｘ、３２ｆ）から構成される内径２．０ｍｍ組紐を内径２．０ｍｍのガラス管の管腔に装着した。次いで、このガラス管の管腔内に、Ｌ−ラクチド−ε−カプロラクトン共重合体（Ｌ−ラクチド成分含有量５０モル％）の５重量％ジオキサン溶液を注入し、直径１．５ｍｍの金属製ロッドをガラス管腔の中心に位置するよう挿入した後、−４０℃にて凍結し、４０℃まで２４時間かけて加温しつつ、凍結乾燥した。このようにして、内層にＬ−ラクチド−ε−カプロラクトン共重合体スポンジ、外層にポリ−Ｌ−乳酸組紐の２層構造からなる、内径１．５ｍｍ、外径２．０ｍｍ、長さ２０ｍｍの管状体を得た。
Example 1
A braid of 2.0 mm inner diameter composed of poly-L-lactic acid fiber (88 dtex, 32f) was attached to the lumen of a glass tube having an inner diameter of 2.0 mm. Next, a 5% by weight dioxane solution of L-lactide-ε-caprolactone copolymer (L-lactide component content 50 mol%) was injected into the lumen of the glass tube, and a metal rod having a diameter of 1.5 mm. Was inserted at the center of the glass lumen, frozen at -40 ° C, and lyophilized while warming to 40 ° C over 24 hours. In this manner, a tubular structure having an inner diameter of 1.5 mm, an outer diameter of 2.0 mm, and a length of 20 mm, comprising a two-layer structure of L-lactide-ε-caprolactone copolymer sponge as the inner layer and poly-L-lactic acid braid as the outer layer. Got the body.
得られた管状体の管腔に、直径８０μｍのＬ−ラクチド−ε−カプロラクトン共重合体（Ｌ−ラクチド成分含有量７５モル％）からなるモノフィラメント糸の束を５０本挿入することにより、密度２８．３本／ｍｍ２、管腔占有率１４．２％である神経再生チューブを得た。 By inserting 50 bundles of monofilament yarn made of L-lactide-ε-caprolactone copolymer (L-lactide component content: 75 mol%) having a diameter of 80 μm into the lumen of the obtained tubular body, a density of 28 A nerve regeneration tube having 3 tubes / mm 2 and a lumen occupation ratio of 14.2% was obtained.
（実施例２）
実施例１で作製した管状体の管腔に、直径８０μｍのＬ−ラクチド−ε−カプロラクトン共重合体（Ｌ−ラクチド成分含有量７５重量％）からなるモノフィラメント糸の束を１５０本挿入することにより、密度８４．９本／ｍｍ２、管腔占有率４２．７％である神経再生チューブを得た。
(Example 2)
By inserting 150 bundles of monofilament yarn made of L-lactide-ε-caprolactone copolymer (L-lactide component content: 75% by weight) having a diameter of 80 μm into the lumen of the tubular body produced in Example 1. A nerve regeneration tube having a density of 84.9 / mm 2 and a lumen occupation rate of 42.7% was obtained.
（比較例１）
実施例１で作製した管状体をそのまま神経再生チューブとして用いた。
(Comparative Example 1)
The tubular body produced in Example 1 was used as it was as a nerve regeneration tube.
（評価）
実施例１、２及び比較例１で作製した神経再生チューブについて以下の方法により評価した。
Ｗｉｓｔａｒラット雄（体重約３００ｇ）の坐骨神経を切除し、神経再生チューブの両末端と神経断端を９・０ナイロン糸にて縫合し、神経断端間が１５ｍｍとなるように神経再生チューブで架橋した。術後１２週間後に坐骨神経を摘出し、移植部の中央及びチューブより末梢側３ｍｍの神経の横断切片を作製し、トルイジンブルー染色を行った。この染色像の光学顕微鏡写真を図１、２（実施例１）、図３、４（実施例２）、及び、図５、６（比較例１）に示した。
(Evaluation)
The nerve regeneration tubes prepared in Examples 1 and 2 and Comparative Example 1 were evaluated by the following methods.
The sciatic nerve of a male Wistar rat (weighing about 300 g) is excised, both ends of the nerve regeneration tube and the nerve stump are sutured with 9.0 nylon thread, and the nerve regeneration tube is used so that the distance between the nerve stumps is 15 mm. Cross-linked. Twelve weeks after the operation, the sciatic nerve was removed, a transverse section of the nerve 3 mm distal to the center of the transplanted part and the tube was prepared, and toluidine blue staining was performed. Optical microscope photographs of this stained image are shown in FIGS. 1, 2 (Example 1), FIGS. 3, 4 (Example 2), and FIGS. 5 and 6 (Comparative Example 1).
図１〜４より、実施例１及び２で作製した神経再生チューブを用いた場合には、神経再生チューブの管腔に配置された繊維間の空隙に、大量の再生有髄神経が観察された。この両者を比較すると、実施例２で作製した神経再生チューブを用いた場合の方が、神経の再生範囲が狭いようであった。
一方、図５、６より、比較例１で作製した神経再生チューブを用いた場合には、管腔の中央に凝集した再生有髄神経群が観察された。
1-4, when the nerve regeneration tube produced in Examples 1 and 2 was used, a large amount of regenerative myelinated nerves was observed in the gaps between the fibers arranged in the lumen of the nerve regeneration tube. . When both were compared, the nerve regeneration range seemed to be narrower when the nerve regeneration tube produced in Example 2 was used.
On the other hand, from FIGS. 5 and 6, when the nerve regeneration tube produced in Comparative Example 1 was used, a regenerated myelinated nerve group aggregated at the center of the lumen was observed.
また、神経再生チューブより末梢側３ｍｍの神経の横断切片の染色像の光学顕微鏡写真から、再生有髄神経の総線維数（本）及び神経の再生範囲（％）を測定した。
結果を表１に示した。かかる結果において、神経線維数の多いほど数多くの再生線維の誘導ができたことを表し、神経の再生範囲が広いほど個々の軸索が太く成長していることを表す。また、太い神経軸索が多いほど再生誘導に優れているといえる。
なお、神経の再生範囲（％）は下記式により算出した。
神経の再生範囲（％）＝（神経内総面積／神経束内総面積）×１００（％）
In addition, the total number of regenerated myelinated nerve fibers (lines) and nerve regeneration range (%) were measured from an optical microscope photograph of a stained image of a nerve cross section 3 mm distal to the nerve regeneration tube.
The results are shown in Table 1. In this result, the greater the number of nerve fibers, the greater the number of regenerated fibers that could be induced, and the wider the nerve regeneration range, the greater the growth of individual axons. Moreover, it can be said that reproduction | regeneration induction | guidance | derivation is excellent, so that there are many thick nerve axons.
The nerve regeneration range (%) was calculated by the following formula.
Nerve regeneration range (%) = (total area in nerve / total area in nerve bundle) × 100 (%)
本発明によれば、取扱い性や生産性に優れ、神経再生効果が極めて高く、術後に取り出す必要もない神経再生チューブを提供することができる。 According to the present invention, it is possible to provide a nerve regeneration tube that is excellent in handleability and productivity, has an extremely high nerve regeneration effect, and does not need to be removed after surgery.
Claims (7)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004048429A JP4292094B2 (en) | 2004-02-24 | 2004-02-24 | Nerve regeneration tube |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004048429A JP4292094B2 (en) | 2004-02-24 | 2004-02-24 | Nerve regeneration tube |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005237476A JP2005237476A (en) | 2005-09-08 |
| JP4292094B2 true JP4292094B2 (en) | 2009-07-08 |
Family
ID=35019844
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004048429A Expired - Fee Related JP4292094B2 (en) | 2004-02-24 | 2004-02-24 | Nerve regeneration tube |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4292094B2 (en) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020095157A1 (en) | 1999-07-23 | 2002-07-18 | Bowman Steven M. | Graft fixation device combination |
| CA2365376C (en) | 2000-12-21 | 2006-03-28 | Ethicon, Inc. | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
| US20040078090A1 (en) | 2002-10-18 | 2004-04-22 | Francois Binette | Biocompatible scaffolds with tissue fragments |
| US7824701B2 (en) | 2002-10-18 | 2010-11-02 | Ethicon, Inc. | Biocompatible scaffold for ligament or tendon repair |
| US8197837B2 (en) | 2003-03-07 | 2012-06-12 | Depuy Mitek, Inc. | Method of preparation of bioabsorbable porous reinforced tissue implants and implants thereof |
| US8226715B2 (en) | 2003-06-30 | 2012-07-24 | Depuy Mitek, Inc. | Scaffold for connective tissue repair |
| US10583220B2 (en) | 2003-08-11 | 2020-03-10 | DePuy Synthes Products, Inc. | Method and apparatus for resurfacing an articular surface |
| US7316822B2 (en) | 2003-11-26 | 2008-01-08 | Ethicon, Inc. | Conformable tissue repair implant capable of injection delivery |
| US7901461B2 (en) | 2003-12-05 | 2011-03-08 | Ethicon, Inc. | Viable tissue repair implants and methods of use |
| US11395865B2 (en) | 2004-02-09 | 2022-07-26 | DePuy Synthes Products, Inc. | Scaffolds with viable tissue |
| US8221780B2 (en) * | 2004-04-20 | 2012-07-17 | Depuy Mitek, Inc. | Nonwoven tissue scaffold |
| CN100382772C (en) * | 2005-09-28 | 2008-04-23 | 南通大学 | Preparation method of medical nerve graft containing silk fibroin |
| JP2007167366A (en) * | 2005-12-22 | 2007-07-05 | Teijin Ltd | Nerve regeneration material |
| JP5702515B2 (en) * | 2007-12-28 | 2015-04-15 | 東洋紡株式会社 | Nerve regeneration induction tube |
| JP2009183575A (en) * | 2008-02-08 | 2009-08-20 | Japan Science & Technology Agency | A structure for forming a neural circuit using a nail wheel-like structure |
| GB2463861B (en) | 2008-09-10 | 2012-09-26 | Univ Manchester | Medical device |
| JP4572996B2 (en) * | 2009-02-02 | 2010-11-04 | 東洋紡績株式会社 | Nerve regeneration induction tube |
| JP6944858B2 (en) * | 2016-12-05 | 2021-10-06 | グンゼ株式会社 | Nerve adhesion prevention wrapping material |
| US12115058B2 (en) | 2019-02-22 | 2024-10-15 | Toray Industries, Inc. | Nerve regeneration-inducing tube |
-
2004
- 2004-02-24 JP JP2004048429A patent/JP4292094B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2005237476A (en) | 2005-09-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4292094B2 (en) | Nerve regeneration tube | |
| US11432922B2 (en) | Biomaterial based on aligned fibers, arranged in a gradient interface, with mechanical reinforcement for tracheal regeneration and repair | |
| JP5763535B2 (en) | Surgical sutures incorporating stem cells or other bioactive materials | |
| US7413575B2 (en) | Nanofibrous biocomposite prosthetic vascular graft | |
| US4712553A (en) | Sutures having a porous surface | |
| CN101945675B (en) | Band coating tissue engineering bracket | |
| US5376118A (en) | Support material for cell impregnation | |
| JP5852655B2 (en) | Implantable cell device with support and radial diffusion scaffolding | |
| US20090069904A1 (en) | Biomaterial including micropores | |
| EP3015089A1 (en) | Implant for parastomal hernia | |
| ES2598300T3 (en) | Synthetic structure for soft tissue repair | |
| EP2174619A1 (en) | Prosthetic material for living organ | |
| HK14495A (en) | Nerve splicing prosthesis | |
| JP2005143979A (en) | Tube for neuroregeneration | |
| KR0165642B1 (en) | Biodegradable shielding membrane for implants and method of manufacturing the same | |
| KR102611664B1 (en) | A medical device for cartilage regeneration-protection by mechanical stimulation and biodegradability | |
| JP6469500B2 (en) | Nerve regeneration tube and method for manufacturing nerve regeneration tube | |
| JP7538306B2 (en) | Tissue regeneration substrate | |
| KR20190066546A (en) | 3-Dimensional fibrous scaffold | |
| JP6722310B2 (en) | Medical patch with spatially arranged fibers | |
| JP2006110184A (en) | Suturing material |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070125 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090106 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090226 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20090226 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090331 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090406 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120410 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120410 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130410 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130410 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140410 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140410 Year of fee payment: 5 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |