TW200400811A - Tissue engineering scaffold material, artificial vessel, cuff member and coating for implants - Google Patents

Tissue engineering scaffold material, artificial vessel, cuff member and coating for implants Download PDF

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Publication number
TW200400811A
TW200400811A TW92106841A TW92106841A TW200400811A TW 200400811 A TW200400811 A TW 200400811A TW 92106841 A TW92106841 A TW 92106841A TW 92106841 A TW92106841 A TW 92106841A TW 200400811 A TW200400811 A TW 200400811A
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TW
Taiwan
Prior art keywords
porous
patent application
resin
scope
network structure
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TW92106841A
Other languages
Chinese (zh)
Inventor
Yasuhide Nakayama
Yasushi Nemoto
Eisuke Tatsumi
Original Assignee
Nat Cardiovascular Ct ;
Bridgestone Corp
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Priority claimed from JP2002091793A external-priority patent/JP2003284767A/en
Priority claimed from JP2002259849A external-priority patent/JP2004097268A/en
Priority claimed from JP2002259848A external-priority patent/JP2004097267A/en
Application filed by Nat Cardiovascular Ct ;, Bridgestone Corp filed Critical Nat Cardiovascular Ct ;
Publication of TW200400811A publication Critical patent/TW200400811A/en

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    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • 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
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
    • 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
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • 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
    • A61L27/56—Porous materials, e.g. foams or sponges

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Botany (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Dispersion Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)

Abstract

It is intended to provide a scaffold material for tissue engineering uses, an artificial vessel, a cuff member and a coating for implants, which can easily and stably organize the take and culture of cells, and an artificial blood vessel small in diameter and good in rate of patency. The scaffold material for tissue engineering uses is made of a thermoplastic resin and has an open cell porous three-dimensional network structure with an average pore size of 100 to 650 μ m and an apparent density of 0.01 to 0.5 g/cm3. The artificial vessel is made of the scaffold material. The cuff member and the coating for implants are each made of a thermoplastic resin or a thermosetting resin and have a part of an open cell porous three-dimensional network structure with an average pore size of 100 to 1000 μ m and an apparent density of 0.01 to 0.5 g/cm3.

Description

(1) (1)200400811 【發明所屬之技術領域】 本發明係有關組織工學瘢痕把持材料，人造血管，環 帶材料及植入活體材料被覆材料。 【先前技術】 首先本發明係有關細胞繁殖培養容易且安定可組織化 的多孔性之組織工學用瘢痕把持材料，及使用此瘢痕材料 之人造血管。 · 本發明的組織工學用瘢痕把持材料及人造血管，不僅 生物工程學的基礎趼究，作爲人造器官的取代醫療、組織 工程學的再生醫療相關之人造骨骼基材使用之有用醫用材 料，特別是，利用與血管內皮細胞內壁全面繁殖的性質， 小至6 mm內徑的口徑亦爲有用之良好開存率的人造血管 〇 向來，組織工學用瘢痕把持材料廣泛的利用聚苯乙烯 製細菌培殖器，聚酯製網狀物等的基材以膠原等的細胞外 φ 的母體塗覆之單層培養爲中心。單層培養以外的培養形態 ，有振盪培養之球體形態或利用膠原之殖包培養，特別是 ，利用膠原之殖包培養，係如活體培養，即可由三次元形 ' 態繁殖，可補救單培養不充分的細胞機能之基礎硏究。 ' 向來的人造血管爲聚酯樹脂或P T F E樹脂製之網狀物 所成之軟管，自古即已實用化，以小口徑化或開存率之提 昇等爲課題之硏究已有進展。至今檢討的主流，係使用抗 血栓材料有實績的段節化聚氨基甲酸酯軟管，利用接枝鏈 (2) (2)200400811 等以肝素等的抗血栓物質固定於表面之人造血管材料等。 殖包培養用之膠原凝膠非爲如三次元網狀構造體之多 孔構造體，細胞不能全面得到均勻之繁殖，或不能調整繁 殖分布的問題。具有三次元網狀構造之多孔性材料的製作 方法，已知之含鹽法或氣泡法，嚴密且任意的調整孔徑或 密度有困難，尙未得到適當由三次元構造物所成之瘢痕把 持材料。 由膠原凝膠殖包培養而得之細胞繁殖構造物，瘢痕 把持材料之膠原凝膠自身並無物理強度，細胞機能之評價 爲可使用，若機械的負荷較大的用途，例如利用於人造血 管則爲不可行。 作爲自身血管之代替材料之人造血管，既已廣泛應用 於臨床之小口徑之人造血管，由於開存率差，冠狀動脈之 分流術、末梢動脈再建術有關之必要小口徑血管，現狀仍 採用自身靜脈之移植術。如現在主流之小口徑化檢討技術 ’僅追求抗血栓性，此等向來的人造血管內壁僅由纖維性 膠原形成擬內膜，亦尙未達到形成內皮。此結果，成爲開 存率低的小口徑人造血管。又，不存在細胞可侵入內壁之 孔，例如由吻合部侵延至血管翳亦不與內壁接合而浮游， 此爲多數報告症例閉塞之要因。(1) (1) 200400811 [Technical field to which the invention belongs] The present invention relates to a tissue engineering scar holding material, a vascular prosthesis, an annulus material, and a covering material for implanted living materials. [Prior art] Firstly, the present invention relates to a porous tissue scar scar holding material which is easy to stably and can be organized and cultured, and an artificial blood vessel using the scar material. · The scar-holding material and artificial blood vessel for tissue engineering of the present invention are not only the basis of bioengineering, but also useful medical materials for the replacement of artificial organs with artificial bones related to medical and tissue engineering, In particular, due to its ability to fully reproduce with the inner wall of vascular endothelial cells, a caliber as small as 6 mm is also a useful artificial blood vessel with a good survivability. In the past, polystyrene has been widely used as a scarring material for tissue engineering Substrates such as bacterial culture vessels and polyester nets are centered on a single-layer culture coated with a matrix of extracellular φ, such as collagen. Culture forms other than monolayer culture include spheroidal culture with shaking culture or colony culture with collagen, in particular, collagen colony culture, such as living culture, can be multiplied by the three-dimensional form, which can remedy single culture Research on the basis of insufficient cellular function. '' Conventional artificial blood vessels are hoses made of polyester resin or P T F E resin mesh. They have been put into practical use since ancient times, and research has been progressed on the subject of smaller diameters and improvement in deposit rate. The mainstream of review so far is the use of segmented polyurethane hoses with proven performance in antithrombotic materials, and grafted chains (2) (2) 200400811 and other artificial blood vessel materials fixed to the surface with antithrombotic substances such as heparin Wait. The collagen gel used for colonization culture is not a porous structure such as a three-dimensional network structure, and the cells cannot reproduce uniformly or adjust the distribution of reproduction. The method for producing a porous material having a three-dimensional network structure is known by the salt-containing method or the bubble method, and it is difficult to adjust the pore diameter or density rigorously and arbitrarily. Therefore, a scar-holding material made of a three-dimensional structure is not obtained properly. Cell proliferation structures obtained from collagen gel colonization culture. The collagen gel of the scar-holding material does not have physical strength by itself, and it can be used for evaluation of cell function. If the mechanical load is large, such as for artificial blood vessels It is not feasible. As artificial blood vessel substitute materials, artificial blood vessels have been widely used in clinical small-caliber artificial blood vessels. Due to the poor preserving rate, necessary small-caliber blood vessels related to coronary shunt surgery and peripheral arterial reconstruction, the status quo still uses itself Vein transplantation. For example, the mainstream small-diameter review technology is only pursuing antithrombotic properties. The inner wall of these conventional artificial blood vessels is formed only by fibrous collagen to form an intimal membrane, and it has not reached the endothelium formation. As a result, a small-caliber artificial blood vessel with a low survival rate was obtained. In addition, there are no holes through which the cells can invade the inner wall, for example, the anastomosis part spreads to the blood vessel loops and does not engage with the inner wall and float, which is the cause of occlusion in most reported cases.

第二，本發明係有關可由活體組織侵入細胞，得到與 活體組織頑強的癒合的環帶材料，特別是，由套管或導管 類以皮下剌入之療法之補助人造心臟之血液循環法、腹膜 透析療法、中心靜脈營養法、經套管D D S及經導管D D S (3) (3)200400811 等的活體皮膚部有用之環帶材料。 近年發達之補助人造心臟或腹膜透析等的療法使用之 套管或導管係與尿導液管、經消化管的營養法及氣管確保 術等相異’必要進行皮下剌入留置於活體內。當於活體內 長期間留置時，於活體內與外界相隔，爲防止細菌侵入活 體內或爲防止體液水分的揮發，利用環帶材料（亦稱表皮 環帶材料）進行剌入部的擬似密閉。向來，由補助人造心 臟之血液循環法，主要由聚酯纖維所成纖維棉絨纏附於剌 入套管’相關之剌入部該纖維棉絨與皮下組織以縫合固定 ’留置導管。相關之腹膜透析療法，亦由以聚酯纖維所成 纖維棉絨等作爲環帶材料固定於套管剌入皮膚之位置，此 環帶材料以壓迫的與皮下組織縫合留置套管。此等的纖維 棉絨係以膠原浸漬，以頑強的癒合爲目標。又，亦有由活 體適合性優之材料所成之環帶材料固定於剌入部的皮下組 織的方法。 但是’由補助人造心臟的血液循環法，係於患者體外 設置之脈動泵補助血液循環的療法。約相當於1 . 5Hz脈動 泵的振動傳達至套管’即套管的剌入部經常承受由振動的 力學負荷。更因患者自身的體位的變化，剌入部的消毒作 業時等動到套管時，皮下組織與環帶材料的接合界面亦產 生剝離的應力。因此判斷爲由此等的應力負荷環帶材料與 皮下組織的癒合性降低的要因問題，其代表例有隧道感染 等的感染問題，補助人造心臟療法的症例中，此隧道問題 的經驗數非常的多。現狀多數的症例非因心不全，而係由 -10- (4) (4)200400811 細菌感染停止療法’本療法的急務爲開發可防止感染的環 帶材料。 有關套管施以皮下剌入，長期間留置之腹膜透析療法 ’環帶材料亦爲大課題。即，此療法係由於以透析液爲注 排法將套管留置於腹腔內，套管由於被活體認定爲異物而 作排除的運作’皮下組織與套管不能癒合，產生表皮沿著 套管鑽入腹腔之向下生長的袋狀，成爲消毒液困難到達的 情形，成爲表皮炎或隧道感染的要因，最終與引發腹膜炎 有關。考慮有頻繁經驗的綠膿菌性的腹膜炎患者SEp (硬 化性皮繭性腹膜炎）的發症率高的報告，由改良環帶材料 防止感染爲腹膜透析療法的一大課題。 如上述，以膠原爲主成分之環帶材料等的開發，如此 狀之ϊ哀帶材料，因吸收生理食鹽水、酒精、Isodine、血液 '體液而減少體積，套管剌入部困難繁殖皮下組織，其結 果，不能得到抑制向下生長的效果。 本發明第三，係有關被覆人造閥、人造閥套環、人造 血管、人造乳房、人造骨、人造關節及人造心臟等及附帶 零件類等的植入活體材料的表面，緩和由活體之異物反應 之植入活體材料被覆材料。 向來，有關人造閥、人造閥套環、人造血管、人造乳 房、人造骨、人造關節及人造心臟等及附帶零件類等的植 入活體材料的構成材料，硏究以檢討無或較少溶出物，對 週邊組織剌激少或無剌激之化學惰性，免疫學上爲活體勿 視的材料爲中心。此等的材料如鈦' 不繡鋼、白金等的金 -11 - (5) (5)200400811 屬材料’羥基磷灰石等的陶瓷材料及聚四氟乙烯、聚酯及 、 聚丙烧等的高分子材料，種種用途已實用化。金屬材料， 例如利用於留置血管中的移植片固定模、骨固定用螺絲、 人造關節。陶瓷材料，例如利用於人造關節、作爲塡充關 節或骨的缺損之人造骨、或取代者。高分子材料，已實用 化於動脈瘤切除後確保血流的人造血管、需再度進行切開 無法折線部位縫合用之縫合線。人造氣管、因乳癌切除乳 房之補綴術或整型外科的豐胸術使用之人造乳房等。 鲁 植入活體內之金屬材料，例如留置血管中的移植片固 定模，以防繡性良好的不鏽鋼爲主成分，長期間留於血管 內，由於常時間曝露於含有種種電解質、蛋白質、脂質之 血液中而生鏽，成爲剌激週邊組織的要因。 現在已實用化之人造乳房的主流，係以生理食鹽水塡 充之矽膠包，此等植入皮下後，其表層被包化膠原組織肥 厚而拘縮者多，此時，矽膠包於活體內變形，壓迫週邊組 織，引起炎症反應，成爲乳癌再發的問題。 · 人造氣管，以矽膠管所成者已實用化，此與活體氣管 之間無親和性，由於長期的植入而脫離，引起界面感染的 問題。 植入型人造心臟之情形，例如由於驅動馬達的振動慣 性，與活體組織之境界面引起炎症、感染的袋狀感染問題 【發明內容】 ZO j气 -12- (6) (6)200400811 【發明之揭示】 ' 發明相關的第一觀點，係提供由具三次元網狀構造的 均質多孔體所成，其多孔體構造內部之全面由均勻細胞繁 殖所得之組織工學用瘢痕把持材料，其物理強度優，不僅 活體組織工學領域的基礎硏究，且人造血管，特別是，適 用於6 mm內徑以下的小口徑人造血管，可長期維持高開 存率構成人造血管之組織工學用瘢痕把持材料，及使用此 組織工學用瘢痕把持材料之人造血管爲目的。 · 本發明之組織工學用瘢痕把持材料，係熱可塑性樹脂 製之組織工學用瘢痕把持材料，該熱可塑性樹脂爲平均孔 徑100〜65 Ομηΐ，表觀密度爲0.0 1〜0.5 g / cm3之具連 通性多孔性形成三次元網狀構造之組織工學用瘢痕把持材 料爲其特徵。 本發明之組織工學用瘢痕把持材料，由於係具有上述 特定之平均孔徑及表觀密度之具有多孔性三次元狀構造之 熱可塑性樹脂，此多孔性三次元網狀構造部之空孔部份容 φ 易以細胞或膠原懸浮液浸透而得。因此，多孔性三次元網 狀構造部的整體可均句的播種細胞，例如可得到中皮細胞 與纖維芽細胞的二層所成的人造腹膜，亦期得使用於腹膜 — 透析之糖基化之機構之解析或透析之基礎檢討。又，此組 · 織工學用瘢痕把持材料使用爲人造血管時，人造血管內壁 可存在血管內皮細胞，不易引起閉塞，其結果可實現小口 徑人造血管。 本發明之人造血管係由本發明組織工學用瘢痕把持材 -13 _ (7) (7)200400811 料所成者，內徑6 m m以下之小口徑開存率亦高，可有效 的適用於冠狀動脈之分流術末梢動脈再建術等。 有關本發明的第2觀點，係提供容易由活體皮下組織 侵入細胞，繁殖，構築毛細血管與皮下組織得到頑強的癒 合’其結果，抑制向下生長之進行，由隧道感染爲始的各 種感染之問題少的環帶材料爲目的。 本發明之環帶材料由熱可塑性樹脂或熱硬化型樹脂所 成之平均孔徑100〜ΙΟΟΟμιτί，表觀密度爲0.01〜0.5 g / cm 3之具連通性多孔性三次元網狀構造爲其特徵。 本發明之環帶材料係具有上述特定之平均孔徑及表觀 密度之具有多孔性三次元狀構造之熱可塑性樹脂，此多孔 性三次元網狀構造部之空孔部份容易由活體皮下組織侵入 細胞’繁殖’構築毛細血管與皮下組織得到頑強的癒合。 有關本發明第三觀點，提供由於容易由活體皮下組織 侵入細胞’繁殖而組織化，其結果，可防止植入活體材料 植A活體之對活體的不良影響之植入活體材料被覆材料爲 目的。 本發明的植入活體材料被覆材材，係以熱可塑性樹脂 或熱硬化型樹脂所成之平均孔徑丨〇 〇〜1 〇 〇 〇 μ m，表觀密 度爲0.0 1〜0.5 g / cm 3之具有連通性多孔性三次元網狀 構造爲其特徵。 本0月t ii帶材料係具有上述特定之平均孔徑及表觀 抵'度之具有多孔性三次元狀構造之熱可塑性樹脂，此多孔 t生=/欠7C ϋ #彳冓^部之空孔部份容易由活體皮下組織侵入 (8) (8)200400811 細胞’繁殖’又可能構築毛細血管，可得到與活體組織頑 ' 強的癒合。 本發明的植入活體材料被覆材料，係可具有細胞侵入 繁殖及構築毛細血管之多孔性三次元網狀構造層。 因此’使用本發明的植入活體材料被覆材料，被覆人 造閥、人造閥套環、人造血管、人造乳房、人造骨、人造 關節及人造心臟等及附帶零件類等的植入活體材料的構成 材料，相對於此材料可緩和由週邊組織之異物反應。 · 植入活體材料係可植入活體內者，包含由各種零件類 所構築的系統。例如，有關人造心臟系統，體內驅動單位 之執行元件（能量轉換器），作爲泵的左右血液泵心房環 帶’心房聯結器，動脈接枝及動脈聯結器，經皮的能量傳 送系統內之體內二次線圈，經皮的資訊傳遞系統內之體內 單兀’容積置換（V 〇丨u m e d i s p丨a c e m e n t )系統則爲順度艙 '容積匱換艙、排氣管，其他與體內單元連接的線路及聯 結器等多點零件所成者。本發明槪以植入活體材料稱之。 · 本發明的植入活體材料被覆材料，係臨床之目的以外 ’爲動物生態調查而植入動物體內的發信機時，可被覆於 該發信機外表面以緩和異物反應者。 胃 【發明之最佳實施形態】 以下詳細檢討本發明之瘢痕把持材料及人造血管之形 言g 0 Μ、ι、 構成本發明之瘢痕把持材料之熱可塑性樹脂所成三次 200400811 Ο) 元網狀構造部，爲平均孔徑1 〇〇〜6 5 0 μ m，表觀密度爲 0.01〜0.5 g / cm3之具連通性多孔性形成三次元網狀構 造即可，由內壁至外壁具有類似之構造亦可，由內壁附近 至外壁附近相異之構造亦可。又，部份之平均孔徑或表觀 密度爲變化者亦可，例如，由內壁至外壁之方向其平均孔 徑緩緩變化，所謂具有異方性亦可。 由此熱可塑性樹脂所成多孔性三次元網狀構造之平均 孔徑爲100〜65 Ομηΐ，表觀密度爲0.01〜0.5 g / cm3 ’ 理想的之平均孔徑爲100 ~ 400μιη，更理想爲之平均孔徑 爲100〜300μηΊ。表觀密度的範圍爲〇.〇1〜0.5 g / cm3 者，細胞繁殖性良好，維持優物理強度，可得到近似活體 的彈性特性，理想爲〇. 〇 1〜〇. 2 g / c m3者，更理想爲 0.01 ~ 0.1 g / cm3 者。 又，有關平均孔徑之槪念，以單向分散之孔徑分佈者 爲理想，細胞侵入之重要孔徑尺寸，孔徑150〜3 00μιη孔 的寄予率高者爲理想。孔徑1 5 0〜3 0 0 μ m孔的寄予率爲 1 0%以上，理想爲20%以上，更理想爲30%以上，再理想 爲40%以上，特別理想爲50%以上時，細胞容易侵入，又 ，由於侵入之細胞容易接合、成長，對於作爲瘢痕把持材 料及人造血管之用途有效。 又，有關多孔性三次元網狀構造之平均孔徑之孔徑 1 5 0〜3 00 μ m之寄予率，指依下述實施例有關之平均孔徑 的測定方法，其相對於全孔數該孔徑1 50〜3 ΟΟμηι的孔數 之比例。Secondly, the present invention relates to annulus material that can invade cells from living tissue to obtain a stubborn healing with living tissue. In particular, the blood circulation method and peritoneum of artificial heart supplemented by cannula or catheter for subcutaneous infusion therapy. Diaphragm therapy, central venous nutrition, transcatheter DDS, and transcatheter DDS (3) (3) 200400811 are useful ring material for living skin. In recent years, sleeves or catheters used to supplement artificial heart or peritoneal dialysis are different from urinary catheters, digestive tract nutrition methods, and tracheal assimilation surgery. It is necessary to infiltrate subcutaneously into the body. When left in the living body for a long period of time, it is separated from the outside in the living body. In order to prevent bacteria from invading the body or to prevent the volatilization of body fluids, the entrapment material (also known as the epidermal lining material) is used to make the entry portion appear to be closed. Conventionally, the blood circulation method of assisting the artificial heart is mainly made of polyester fiber made of cotton wool entangled in the introductory portion of the intubation cannula. The fiber wool and the subcutaneous tissue are sutured and fixed. Relevant peritoneal dialysis therapy is also fixed at the position where the cannula penetrates the skin by using a cotton linter made of polyester fiber as an annulus material. This annulus material is used to compress the suture with the subcutaneous tissue to indwell the cannula. These fiber linters are impregnated with collagen and targeted for tenacious healing. There is also a method in which a belt material made of a material suitable for living body is fixed to the subcutaneous tissue of the insertion portion. However, the method of assisting blood circulation by artificial heart is a method of assisting blood circulation by a pulse pump provided outside the patient's body. It is approximately equivalent to 1.5 Hz that the vibration of the pulsating pump is transmitted to the casing ', that is, the entry portion of the casing is often subjected to a mechanical load due to vibration. In addition, due to changes in the patient's own body position, when the sterilization operation of the implanted part waits for the sleeve to move, the joint interface between the subcutaneous tissue and the annulus material also generates peeling stress. Therefore, it is judged that the cause of the decrease in the healing properties of the stress-loaded annulus material and the subcutaneous tissue is a representative example of an infection problem such as a tunnel infection. Among the cases of subsidized artificial heart therapy, the experience of this tunnel problem is very large. many. Most of the current cases are not due to heart failure, but -10- (4) (4) 200400811 Stop Bacterial Infection Therapy 'The urgent task of this therapy is to develop a band material that can prevent infection. The peritoneal dialysis therapy for the long-term indwelling of peritoneal dialysis using a cannula for subcutaneous invasion is also a major issue. That is, this therapy is based on the use of dialysate as a drainage method to leave the cannula in the abdominal cavity. The cannula is excluded because it is recognized as a foreign body by the living body. 'Subcutaneous tissue and cannula cannot heal, and the epidermis is drilled along the cannula The bag-shaped bag that grows downward into the abdominal cavity becomes a situation where the disinfectant solution is difficult to reach, it becomes the cause of epidermatitis or tunnel infection, and it is ultimately related to the peritonitis. Considering reports of a high incidence of SEp (sclerosing cocoon peritonitis) in patients with Pseudomonas aeruginosa peritonitis with frequent experience, it is a major issue for peritoneal dialysis therapy to prevent infection by improving the material of the annulus. As mentioned above, the development of zonal band materials with collagen as the main component, such sorrow band materials, reduce the volume due to the absorption of physiological saline, alcohol, Isodine, blood and body fluids, and it is difficult to reproduce the subcutaneous tissue in the canal invasion. As a result, the effect of suppressing downward growth cannot be obtained. The third aspect of the present invention relates to the surface of an implanted living material that covers artificial valves, artificial valve collars, artificial blood vessels, artificial breasts, artificial bones, artificial joints, artificial hearts, and accessories, and alleviates the reaction of foreign bodies in the living body. It is implanted with a living material covering material. In the past, research has been conducted on the composition of artificial valve, artificial valve collar, artificial blood vessel, artificial breast, artificial bone, artificial joint, artificial heart, and other components of implanted living materials. It is chemically inert to surrounding tissues with little or no irritation, and immunologically focuses on materials that are ignored by living bodies. Such materials as titanium 'stainless steel, platinum and other gold-11-(5) (5) 200400811 belong to the material' ceramic materials such as hydroxyapatite and polytetrafluoroethylene, polyester and polypropylene, etc. Polymer materials have been put into practical use for various purposes. The metal material is used, for example, as a graft fixation tool in an indwelling blood vessel, a bone fixing screw, or an artificial joint. Ceramic materials are used, for example, in artificial joints, artificial bones that serve as joints or bone defects, or substitutes. High-molecular materials have been applied to artificial blood vessels that ensure blood flow after aneurysm removal, and need to be cut again. Artificial trachea, artificial breasts used for breast cancer resection of the breast, or breast augmentation for plastic surgery. Lu metal materials implanted in the body, such as the implantation molds in the blood vessels, are made of stainless steel with good anti-embroidery properties. They are left in the blood vessels for a long period of time, because they are exposed to all kinds of electrolytes, proteins, and lipids for a long time. Rust in the blood becomes the cause of irritating surrounding tissues. The mainstream of artificial breasts that have been put into practical use today is silicone gel packs filled with physiological saline solution. After implantation into the skin, the surface layer is covered with collagen and the tissue is thick and constricted. At this time, the silicone gel is packed in the living body. Deformation, compresses surrounding tissues, causes inflammation, and becomes a recurrence problem of breast cancer. · Artificial trachea, made of silicone tube, has been put into practical use. There is no affinity with living trachea. It is detached due to long-term implantation, which causes interface infection. In the case of an implanted artificial heart, for example, the problem of bag infection caused by inflammation and infection due to the vibration inertia of the driving motor and the interface with living tissue [Abstract] ZO j 气 -12- (6) (6) 200400811 [Invention [Disclosure] The first aspect related to the invention is to provide a homogeneous porous body with a three-dimensional network structure. The inside of the porous body structure is a tissue engineering scar holding material obtained by uniform cell proliferation. Excellent strength, not only basic research in the field of biological tissue engineering, but also artificial blood vessels, especially for small-caliber artificial blood vessels with an inner diameter of 6 mm or less, which can maintain a high retention rate for a long period of time to form artificial blood vessel scars for tissue engineering The purpose is to hold the material and the artificial blood vessel using the tissue engineering scar control material. · The scar holding material for tissue engineering of the present invention is a scar holding material for tissue engineering made of a thermoplastic resin. The thermoplastic resin has an average pore diameter of 100 to 65 Ομηΐ and an apparent density of 0.0 1 to 0.5 g / cm3. It is characterized by a three-dimensional network structure with interconnected porosity and a scar holding material for tissue engineering. Since the scar-holding material for tissue engineering of the present invention is a thermoplastic resin having a porous three-dimensional structure having the above-mentioned specific average pore diameter and apparent density, the pore portion of the porous three-dimensional network structure portion Volume φ is easily obtained by soaking cells or collagen suspension. Therefore, the whole of the porous three-dimensional network structure can be seeded uniformly. For example, an artificial peritoneum formed by two layers of mesothelial cells and fibroblasts can be obtained. It is also expected to be used for peritoneal dialysis-glycosylation The basic analysis of the organization's analysis or dialysis. Also, when this group uses a scar holding material for weaving as a vascular prosthesis, vascular endothelial cells can be present on the inner wall of the vascular prosthesis, which is less likely to cause occlusion. As a result, a small-caliber vascular prosthesis can be realized. The artificial blood vessel system of the present invention is made of the scar holding material for tissue engineering of the present invention -13 _ (7) (7) 200400811. It also has a high opening rate of small calibers with an inner diameter of 6 mm or less, which can be effectively applied to coronary Arterial shunt surgery and peripheral arterial reconstruction. A second aspect of the present invention is to provide a variety of infections starting from tunnel infections, as a result of which it is easy to invade cells from living subcutaneous tissues, reproduce, build capillaries and subcutaneous tissues, and achieve tenacious healing. The endless belt material is less problematic. The endless belt material of the present invention is characterized by an interconnected porous three-dimensional network structure with an average pore diameter of 100 to 100 μm and an apparent density of 0.01 to 0.5 g / cm 3 made of a thermoplastic resin or a thermosetting resin. The endless belt material of the present invention is a thermoplastic resin having a porous three-dimensional structure having the above-mentioned specific average pore diameter and apparent density. The pores of the porous three-dimensional network structure portion are easily penetrated by living subcutaneous tissue. Cells 'multiply' build capillaries and subcutaneous tissues for tenacious healing. A third aspect of the present invention is to provide an implanted living material covering material that prevents tissues from implanting a living body and prevents adverse effects on the living body from being implanted in the living body, as it is easily organized by invading cells ' The implanted living material covering material of the present invention is an average pore diameter formed by a thermoplastic resin or a thermosetting resin, and the apparent density is between 0.01 and 0.5 g / cm3. It is characterized by a connected three-dimensional porous network structure. The material of this month t ii is a thermoplastic resin with a porous three-dimensional structure having the above-mentioned specific average pore size and apparent resistance. This porous material is = / owed to 7C ϋ # 彳 冓 ^ 部 的 void Part of it is easily invaded by subcutaneous tissue of living body (8) (8) 200400811 Cells 'proliferate' may also build capillaries, which can get strong healing with living tissue. The implanted living material covering material of the present invention is a porous three-dimensional network structure layer that can have cell invasion, reproduction, and capillary formation. Therefore, using the implanted living material covering material of the present invention, the artificial valve, artificial valve collar, artificial blood vessel, artificial breast, artificial bone, artificial joint, artificial heart, and other components of the implanted living material are covered. Compared with this material, it can ease the foreign body reaction from surrounding tissues. · Implantable materials are those that can be implanted in a living body, and include systems constructed from various parts. For example, the artificial heart system, the actuator (energy converter) of the body's driving unit, the left and right blood pumps as the pump, the atrial annulus, the atrial coupler, the arterial graft and the arterial coupler, the body within the percutaneous energy delivery system The secondary coil, the internal unit's volume replacement (V 〇 丨 umedisp 丨 acement) system in the percutaneous information transmission system is the smooth cabin 'volume replacement cabin, exhaust pipe, other lines connected to the internal unit and Couplings made of multi-point parts. The present invention is referred to as implanted living material. · The implanted living material covering material of the present invention is other than a clinical purpose ′ When a transmitter is implanted into an animal body for animal ecological survey, it can be covered on the outer surface of the transmitter to relieve foreign body responders. Stomach [Best Embodiment of the Invention] The following is a detailed review of the scar holding material and vascular prosthesis of the present invention: g 0 M, ι, three times formed by the thermoplastic resin constituting the scar holding material of the present invention 200400811 〇) The structural part is a three-dimensional network structure with interconnected porosity with an average pore diameter of 100-650 μm and an apparent density of 0.01-0.5 g / cm3, and it has a similar structure from the inner wall to the outer wall. The structure may be different from the vicinity of the inner wall to the vicinity of the outer wall. It is also possible to change the average pore diameter or apparent density of a part, for example, the average pore diameter of the inner wall to the outer wall gradually changes, and the so-called anisotropy may be used. The average pore size of the porous three-dimensional network structure formed from the thermoplastic resin is 100 ~ 65 Ομηΐ, and the apparent density is 0.01 ~ 0.5 g / cm3 'The ideal average pore size is 100 ~ 400μιη, and the more preferable average pore size is It is 100 to 300 μηΊ. Those with an apparent density in the range of 0.01 to 0.5 g / cm3 have good cell reproduction properties, maintain excellent physical strength, and can obtain elastic characteristics similar to living organisms. Ideally, they are 0.01 to 0.2 g / c m3. , More preferably 0.01 ~ 0.1 g / cm3. In addition, regarding the average pore diameter, a unidirectionally dispersed pore diameter distribution is ideal, an important pore size for cell invasion, and a high pore diameter of 150 to 300 μm is ideal. Cells with a pore size of 150 to 300 μm are more than 10%, ideally 20% or more, more preferably 30% or more, more preferably 40% or more, and particularly preferably 50% or more. Invasion, and because the invading cells are easy to join and grow, it is effective for use as a scar holding material and a vascular prosthesis. In addition, the ratio of the average pore diameter of the porous three-dimensional network structure with a pore diameter of 150 to 3 00 μm refers to the method for measuring the average pore diameter according to the following examples. The pore diameter is 1 relative to the total number of pores. The ratio of the number of pores of 50 ~ 3 OOμηι.

-16- (10) (10)200400811 具如此之平均孔徑、表觀密度及孔徑分佈之多孔性三 次元網狀構造者，細胞•膠原浮游培養液等容易侵透空孔 部份’得到細胞與多孔構造層β接合，容易生長的良好癒 痕把持材料。因此，將此成形爲管狀時，由於由內壁至外 周全體繁殖細胞，閉塞之危險性低，可實現高開存率的人 造血管。 構成本發明之組織工學用瘢痕把持材料之熱可塑性樹 脂，可舉例如聚氨基甲酸酯樹脂、聚醯胺樹脂、聚乳酸樹 脂、聚烯烴樹脂、聚酯樹脂、氟素樹脂、丙烯酸樹脂、甲 基丙烯酸樹脂及此等的衍生物，此等單獨使用亦可，2種 以上倂用亦可，理想爲聚氨基甲酸酯樹脂，其中依抗血栓 性及物理特性優之觀點由段節化聚氨基甲酸酯樹脂得到之 人造血管爲理想。 段節化聚氨基甲酸酯樹脂係由多元醇、二異氰酸酯及 鏈延長劑之3成分所合成，由於具有由分子內具有所謂硬 段節部份與軟段節部份之嵌段聚合物構造之彈性物特性， 使用如此段節化聚氨基甲酸酯時所得之瘢痕把持材料及人 造血管’顯示具有近似活體血管之彈性力學的s - S曲線 (低血壓範圍具有高高順應性之低彈性，高血壓範圍具有 比低血壓範圍低順應性之高彈性）可成形爲抗血栓性或物 理特性優之管狀構造物。 又，熱可塑性樹脂爲具有加水分解或生分解性者，人 造血管之活體移植後緩緩分解，被吸收，最終如原樣殘留 繁殖之細胞，樹脂製之基材自身可由活體排除。 -17 - (11) 200400811 如此由熱可塑性樹脂所構成之多孔性三次元網狀構造 部，係保持1種或2種以上選自第I型膠原、第II型膠 原、第III型膠原、第IV型膠原 '粥型膠原、纖維結合 素、明膠、透明質酸、肝素 硫酸 '軟骨素硫酸B、羥基 基甲基丙烯酸酯共聚物、羥 烯酸的共聚物、藻朊酸、聚 醯胺及聚乙烯脒咯烷酮所成 選自纖維芽細胞繁殖因子、 卢、上皮繁殖因子及二倍體 之細胞分裂類亦可，更接合 胞、管內皮細胞、中胚葉性 細胞及中皮細胞所成群者亦 可〇 又，本發明之組織工學 性三次元網狀構造層之熱可 設置微細的孔。此微細孔係 係具複雜的凹凸表面，有效 ，其結果細胞之繁殖性可提 導入本發明之所謂多孔性三 槪念。 本發明之組織工學用瘢 制，例如管狀構造物時，可 此時，此管狀構造物爲 、角質素酸、軟骨素、軟骨素 乙基甲基丙烯酸酯與二甲基乙 基乙基甲基丙烯酸酯與甲基丙 丙烯酸醯胺、聚二甲基丙烯酸 群者，更保持1種或2種以上 內白細胞素-1、腫瘍繁殖因子 纖維芽細胞繁殖因子所成群者 1種或2種以上選自胚性幹細 細胞、平滑筋細胞、末梢血管 可。胚性幹細胞爲被分化者亦 用瘢痕把持材料，其構築多孔 塑性樹脂所成之骨骼自身亦可 使骨骼表面不爲平滑的表面而 於保持膠原或細胞繁殖因子等 昇。但是，此時之微細孔，不 次元構造部之平均孔徑的計算 痕把持材料的形狀無特別的限 使用於人造血管。 內徑 0.3〜15 mm 而外徑爲 (12) (12)200400811 0.4〜20 mm，理想爲內徑0.3〜10 mm 而外徑爲0.4〜 ]5 mm，更理想爲內徑0.3 ~ 6 mm而外徑爲0.4〜]0 mm ，特別理想爲內徑〇 . 3〜2.5 m m 而外徑爲0.4〜1 0 m m， 尤其理想爲內徑〇 . 3〜1 . 5 m m 而外徑爲〇 . 4〜1 0 m m。此 小口徑之人造血管經長時期亦可維持高開存率。 由本發明之瘢痕把持材料所成之人造血管，外側爲個 別之管狀構造物被覆者亦可，由設置此被覆層，對本發明 之瘢痕把持材料之膠原浸漬密度低時，或瘢痕把持材料的 厚度薄時等，移植後的一定期間可防止血液的溢漏，細胞 的接合，繁殖充分進行，血液溢漏的可能性下降時由活體 吸收，可賦與所謂消滅的效果。此被覆用之構造物無特別 的限制，例如可爲1種或2種以上選自殻聚糖、聚乳酸樹 脂、聚酯樹脂、聚醯胺樹脂、聚氨基甲酸酯樹脂、纖維結 合素、明膠、透明質酸、角質素酸、軟骨素、軟骨素硫酸 、軟骨素硫酸B、羥基乙基甲基丙烯酸酯與二甲基乙基甲 基丙烯酸酯共聚物、羥基乙基甲基丙烯酸酯與甲基丙烯酸 的共聚物、藻朊酸、聚丙烯酸醯胺、聚二甲基丙烯酸醯胺 及聚乙烯脒咯烷酮、交聯膠原及絲纖朊所成群者所形成之 軟管，此種殻聚糖等之被覆用管狀構造物的厚度（外徑與 內徑之差）爲5〜5 0 0 μ m者爲理想。 本發明的人造血管，對向來技術不能達成的小口徑亦 具高開存率’依可確保安定的血流亦爲新穎者。例如超越 6 mm之大口徑亦無問題的可適用。 以下’列舉構成本發明瘢痕把持材料或人造血管的管 (13) (13)200400811 狀構造物之熱可塑性樹脂聚氨基甲酸酯樹脂所成的多孔性 · 三次元網狀構造之製造方法的一例，有關本發明的多孔性 三次元網狀構造的熱可塑性樹脂製構造物之製造方法並不 限定於以下的方法。又，依以下的方法爲準可製造平面狀 基材等的組織工學用的瘢痕把持材料之要求的種種形狀之 三次元網狀構造的熱可塑性樹脂製的基材。 製造由熱可塑性聚氨基甲酸酯樹脂所成之多孔性三次 元網狀構造物，首先，聚氨基甲酸酯樹脂，與後述之水溶 φ 性高分子之孔形成劑，與聚氨基甲酸酯樹脂的良溶媒之有 機溶媒混合製造聚合物膠漿。具體的，聚氨基甲酸酯樹脂 以有機溶媒混合成爲均勻的溶液後，此溶液中以水溶性高 分子化合物混合分散之。有機溶媒有Ν,Ν-二甲基甲醯胺 ，Ν-甲基-2-脒咯基二酮，四氫呋喃等，可溶解聚氨基甲 酸酯樹脂者不限定於此，又，減量使用或不使用有機溶媒 ，而以熱的作用融解聚氨基甲酸酯樹脂，在此情況下混合 孔形成劑。 籲 作爲孔形成劑的水溶性高分子化合物，可列舉如聚乙 二醇、聚丙二醇、聚乙烯醇、聚乙烯脒咯烷酮、藻朊酸、 羧基甲基纖維素、羥基丙基纖維素、甲基纖維素、乙基纖 ^ 維素等，可與熱可塑性樹脂均勻的分散形成膠漿者無特別 限制。又，依熱可塑性樹脂的種類，亦可使用非水溶性高 分子，例如對苯二甲酸酯、液腊等的親油性化合物或氯化 鋰、碳酸鈣等的無機鹽類。又，利用高分子用的結晶核劑 等，於凝固時生成二次粒子，即，可助長多孔物的骨骼形 -20- (14) (14)200400811 成。 由熱可塑性聚氨基甲酸醋樹脂，有機溶媒及水溶性高 分子化合物等所製造的聚合物膠漿，接著於含有熱可塑性 聚氨基甲酸酯樹脂的貧溶媒的凝固浴中浸漬，於凝固液中 萃取除去有機溶媒及水溶性高分子化合物。由此除去—部 份或全部的有機溶媒或水溶咼分子化合物，可得到由熱可 塑性聚氨基甲酸酯樹脂而成的多孔性三次元網狀構造物。 此處使用的貧溶媒可例示如水、低級醇、低碳數之酮類等 。凝固之熱可塑性聚氨基甲酸酯樹脂，最後以水等淸洗， 除去殘留之有機溶媒形成劑即可。 【實施方式】 以下以實施例及比較例說明，不超越本發明之要旨者 ，不限定於以下之實施例。 [實施例1 ] 熱可塑性聚氨基甲酸酯樹脂（日本MIRAKUTORANE 公司製Miraku- torane E98 0 PNAT )以N-甲基-2-脒咯基 一酮（日本關東化學公司製縮氨酸合成用試藥，NMP )使 用溶解器（約2000 rpm )於室溫下溶解得到5.0% (重量 /重量）溶液。秤取約1. 〇 kg此NMP溶液放入星型混合 機（日本井上製作所製，2.0L容量，PLM-2型），以相當 於聚氨基甲酸酯樹脂同重量的甲基纖維素（日本關東化學 公司製’試藥，25 cp級）於401混合4〇分鐘後，其後 (15) ZUUWU511 繼續攪拌1 0分鐘 到聚合物膠漿。 減壓至20 mm Hg ( 2.7 kp〇 脫泡-16- (10) (10) 200400811 Porous three-dimensional network structure with such average pore size, apparent density, and pore size distribution. Cells and collagen floating culture fluid, etc., can easily penetrate the pores to obtain cells and The porous structure layer is a β-bonded, easy-to-grow good healing material. Therefore, when this tube is shaped into a tube, since the entire cell is propagated from the inner wall to the outer periphery, the risk of occlusion is low, and an angiogenesis with a high survival rate can be realized. Examples of the thermoplastic resin constituting the scar holding material for tissue engineering of the present invention include, for example, polyurethane resin, polyamide resin, polylactic acid resin, polyolefin resin, polyester resin, fluorine resin, acrylic resin, Methacrylic resins and these derivatives may be used alone or in combination of two or more kinds. Polyurethane resins are preferred. Among them, polyurethane is reduced in terms of excellent antithrombotic properties and physical properties. An artificial blood vessel obtained from a polyurethane resin is desirable. Segmented polyurethane resins are synthesized from the three components of a polyol, a diisocyanate, and a chain extender. They have a block polymer structure with a so-called hard segment and soft segment in the molecule. The elastic properties of the scar holding material and vascular prosthesis obtained when using such a segmented polyurethane show an s-S curve with elasticity similar to that of living blood vessels (low elasticity in the low blood pressure range with high and high compliance and low elasticity) The high blood pressure range has higher flexibility than the low blood pressure range. It can be formed into a tubular structure with excellent antithrombotic properties or physical properties. In addition, the thermoplastic resin is hydrolyzed or biodegradable. After being transplanted into a living body, an artificial blood vessel slowly decomposes, is absorbed, and eventually reproduces cells as it is. The resin-made substrate itself can be eliminated by the living body. -17-(11) 200400811 The porous three-dimensional network structure composed of a thermoplastic resin as described above retains one or two or more selected from the group consisting of type I collagen, type II collagen, type III collagen, and Type IV collagen 'porridge collagen, fibronectin, gelatin, hyaluronic acid, heparin sulfate' chondroitin sulfate B, hydroxymethacrylate copolymer, copolymer of hydroxyenoic acid, alginic acid, polyamidine and Polyvinylpyrrolidone can also be made from cell divisions selected from the group consisting of fibroblast proliferation factors, rhodamine, epithelial reproduction factors, and diploids. It can also be composed of conjugated cells, endothelial cells, mesoderm cells, and mesothelial cells. Those who are in the group can also provide fine holes in the heat of the tissue engineering three-dimensional network structure layer of the present invention. This fine pore system has a complicated concave-convex surface and is effective. As a result, the cell's reproduction ability can be introduced into the so-called porous triple concept of the present invention. In the case of scar formation for tissue engineering of the present invention, for example, in the case of a tubular structure, the tubular structure may be: keratin acid, chondroitin, chondroitin ethylmethacrylate, and dimethylethylethylformate. Those with methacrylic acid ester, methacrylic acid methacrylate, and polydimethacrylic acid group, more than one or two kinds of endoleukin-1, tumor reproduction factor, fibroblast reproduction factor, or one group The above may be selected from embryonic stem fine cells, smooth muscle cells, and peripheral blood vessels. Embryonic stem cells are the materials used by differentiated individuals to hold scars. The construction of bones made of porous plastic resin can also make the bone surface not a smooth surface and maintain collagen or cell proliferation factors. However, the calculation of the average pore diameter of the fine pores and the dimension structure at this time is not particularly limited to the shape of the material to be used for artificial blood vessels. The inner diameter is 0.3 to 15 mm and the outer diameter is (12) (12) 200400811 0.4 to 20 mm, ideally the inner diameter is 0.3 to 10 mm and the outer diameter is 0.4 to 5 mm, and more preferably the inner diameter is 0.3 to 6 mm. The outer diameter is 0.4 ~] 0 mm, and the inner diameter is particularly preferably 0.3 ~ 2.5 mm and the outer diameter is 0.4 ~ 10 mm, and the inner diameter is particularly preferably 0.3 ~ 1.5 mm and the outer diameter is 0.4. ~ 10 mm. This small caliber vascular prosthesis can also maintain a high deposit rate over a long period of time. The artificial blood vessel formed by the scar holding material of the present invention may also be covered by an individual tubular structure on the outer side. By setting this coating layer, the collagen impregnation density of the scar holding material of the present invention is low, or the thickness of the scar holding material is thin. In a certain period of time, blood leakage can be prevented for a certain period of time after transplantation, and cell splicing and reproduction are fully performed. When the possibility of blood leakage decreases, it is absorbed by the living body, and the so-called elimination effect can be imparted. The structure used for this coating is not particularly limited, and may be, for example, one or two or more kinds selected from chitosan, polylactic acid resin, polyester resin, polyamide resin, polyurethane resin, fibronectin, Gelatin, hyaluronic acid, keratin acid, chondroitin, chondroitin sulfate, chondroitin sulfate B, copolymer of hydroxyethyl methacrylate and dimethylethyl methacrylate, hydroxyethyl methacrylate and Hose formed by a group of copolymers of methacrylic acid, alginic acid, polyacrylamide, polyammonium dimethacrylate and polyvinylpyrrolidone, crosslinked collagen, and silk fibroin. The thickness (the difference between the outer diameter and the inner diameter) of the coating tubular structure such as chitosan is preferably 5 to 50 μm. The artificial blood vessel of the present invention has a high survival rate for small calibers that have not been achieved with conventional technology, and it is a novelty that can ensure stable blood flow. For example, it can be applied without any problem beyond the large diameter of 6 mm. The following is an example of a method for manufacturing the porous and three-dimensional network structure of the thermoplastic resin polyurethane resin constituting the tube (13) (13) 200400811-like structure constituting the scar holding material or vascular prosthesis of the present invention. The method for producing a thermoplastic resin structure having a porous three-dimensional network structure according to the present invention is not limited to the following method. In addition, a thermoplastic resin substrate having a three-dimensional network structure having various shapes required for a tissue engineering scar holding material such as a planar substrate can be manufactured by the following method. To produce a porous three-dimensional network structure made of a thermoplastic polyurethane resin, first, a polyurethane resin, a pore-forming agent of a water-soluble φ polymer described later, and a polyurethane Polymer solvents are produced by mixing organic solvents with good resins. Specifically, after the polyurethane resin is mixed with an organic solvent to form a homogeneous solution, the solution is mixed and dispersed with a water-soluble polymer compound. Organic solvents include Ν, Ν-dimethylformamide, N-methyl-2-pyrrolyl dione, tetrahydrofuran, etc. The ones which can dissolve polyurethane resin are not limited to this, and are used in a reduced amount or not. The organic resin is used to melt the polyurethane resin by the action of heat. In this case, the pore former is mixed. Examples of water-soluble polymer compounds that can be used as pore-forming agents include polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, alginic acid, carboxymethyl cellulose, hydroxypropyl cellulose, There is no particular limitation on methyl cellulose, ethyl cellulose, etc., which can be uniformly dispersed with a thermoplastic resin to form a glue. Also, depending on the type of the thermoplastic resin, water-insoluble polymers such as lipophilic compounds such as terephthalate and liquid wax, or inorganic salts such as lithium chloride and calcium carbonate may be used. In addition, the use of a crystalline nucleating agent for a polymer generates secondary particles during solidification, that is, it promotes the skeletal shape of a porous material. -20- (14) (14) 200400811. A polymer dope made of a thermoplastic polyurethane resin, an organic solvent, and a water-soluble polymer compound is immersed in a coagulation bath of a poor solvent containing a thermoplastic polyurethane resin, and then immersed in the coagulation solution. Extraction removes organic solvents and water-soluble polymer compounds. In this way, a part or all of the organic solvent or the water-soluble hydrazone molecular compound is removed, and a porous three-dimensional network structure made of a thermoplastic polyurethane resin can be obtained. Examples of the lean solvent used herein include water, lower alcohols, and low-carbon ketones. The solidified thermoplastic polyurethane resin may be finally washed with water or the like to remove the remaining organic solvent-forming agent. [Embodiments] Examples and comparative examples are described below, and those that do not exceed the gist of the present invention are not limited to the following examples. [Example 1] Thermoplastic polyurethane resin (Miraku-torane E98 0 PNAT manufactured by MIRAKUTORANE, Japan) using N-methyl-2-pyrrolyl monoketone (peptide synthesis test manufactured by Kanto Chemical Co., Japan) (NMP) using a dissolver (about 2000 rpm) at room temperature to obtain a 5.0% (w / w) solution. About 1.0 kg of this NMP solution was weighed into a star mixer (2.0L capacity, PLM-2 type manufactured by Japan Inoue Manufacturing Co., Ltd.), and methyl cellulose equivalent to the weight of polyurethane resin (Japan (Kanto Chemical Co., Ltd.'s test reagent, 25 cp grade) was mixed in 401 for 40 minutes, and then (15) ZUUWU511 continued to stir for 10 minutes to the polymer cement. Decompression to 20 mm Hg (2.7 kp)

以化學實驗用據紙（日本東洋爐紙公司製，定性用， 2號）作成內徑3 . 5 m 外 _ 介 ^ 4.6 mm 0 ’長 6〇 mm 的 商狀紙曾，及S U S 4 4 〇製的直_ 1 9 m υ衣H J祖f工〗.2 m m 0的芯棒，及可 疋此L·柃方、紙目的中心部份之醫用聚丙烯樹脂製之圓柱 密栓所構成之軟管成形夾具中，上述聚合物膠獎使用23 5虎針射出注入後密检，将< 人；費、〉太肿亩 ^ ^又人通/凡狀態之甲醇中繼續還流 72小時’卒取除去從紙管面至內部的NMP溶媒，凝固聚 氨基甲酸酯樹脂。此時，甲醇於持續維持還流狀態下，隨 時更換新液。72小時後，軟管成型夾具由還流狀態的甲 醇中移至室溫下不會乾燥的甲醇溶中，於浴中由成型夾具 取出容內物’於日本藥局方精製水中淸洗72小時，將甲 基纖維素、甲醇及殘留的NMP萃取除去。隨時供給新的 淸洗用水。於室溫下減壓2 0 m m H g ( 2.7 k P a )乾燥2 4小 時，得到本發明的實施形態之可作爲人造血管使用之管狀 多孔性三次元網狀構造的瘢痕把持材料。 圖1〜4係此瘢痕把握材料以掃瞄型電子顯微鏡（ JEOL公司製 SEM，HMS -5 800 LV )或實體顯微鏡（ KEY AN CE公司製，VH-6300)攝影之圖像，由圖1〜4可 知，所得之瘢痕把持材料的基材，孔徑約20 Ομ m，內徑 爲1.2 mm 0 ，外徑爲3.2 mm 0 ，構造物內部（圖2)， 內壁表層（圖3)及外周表層（圖4)約略爲同一構造之 多孔性三次元網狀構造’整體爲均質的多孔質物。Chemical test paper (made by Toyo Furnace Paper Co., Ltd., qualitative, No. 2) was used to make a commercial paper with an inner diameter of 3.5 m and a diameter of 4.6 mm 0 and a length of 60 mm, and SUS 4 4 0 Straight _ 1 9 m υ clothing HJ Zu Fong〗. 2 mm 0 mandrel, and can be formed by a cylindrical plug made of medical polypropylene resin which can be used as the central part of the paper and paper In the fixture, the above-mentioned polymer glue award was used for close inspection after injection with 23 5 tiger needles, and the <person; fee,> too swollen acres ^ ^ again in the normal / normal state of methanol for 72 hours, NMP solvent from the surface of the paper tube to the inside, solidifying the polyurethane resin. At this time, the methanol was continuously replaced with a new solution while maintaining the flow-through state. After 72 hours, the hose molding jig was moved from the methanol in the reflux state to methanol that would not dry at room temperature. The contents were taken out from the molding jig in the bath and rinsed in the purified water of the Japanese Drug Administration for 72 hours. Methyl cellulose, methanol and residual NMP were extracted and removed. Fresh water is always available. It was decompressed at room temperature under a pressure of 20 mm Hg (2.7 kPa) and dried for 24 hours to obtain a scar holding material having a tubular porous three-dimensional network structure which can be used as a vascular prosthesis according to the embodiment of the present invention. Figures 1 to 4 are images of this scar grasping material taken with a scanning electron microscope (SEM manufactured by JEOL, HMS-5800 LV) or a solid microscope (made by KEY AN CE, VH-6300). 4 It can be seen that the base material of the obtained scar holding material has a pore diameter of about 20 μm, an inner diameter of 1.2 mm 0 and an outer diameter of 3.2 mm 0. The inside of the structure (Figure 2), the inner surface layer (Figure 3) and the outer peripheral surface layer (Fig. 4) A porous three-dimensional network structure with approximately the same structure is a homogeneous porous material as a whole.

-22- (16) (16)200400811 所得之瘢痕把持材料，依下述方法進行測定平均孔徑 及表觀密度。又’有關平均孔徑及表觀密度的測定，試料 的切斷使用兩面刮鬍刀（Feather公司製，High Stainless )於室溫下進行。 [平均孔徑之測定] 以兩面刮鬍刀切斷之試樣平面（切斷面）使用實體顯 微鏡（KEYANCE公司製，VH-63 00 )攝影之圖像，同一 平面上的各個孔作爲由三次元網狀構造之骨骼包圍之圖型 作圖像處理（圖像處理裝置使用 NILECO公司製之 LUZEX AP，圖像的取得CCD相機係使用SONY之LE N 5 0)，測定各個圖形的面積。以此作爲真画面積，求取對 應圓之直徑作爲孔徑。勿視多孔物的骨骼部份之穿孔之微 細孔，僅測定同一平面上之連通孔的結果，平均孔徑計測 爲169 ± 5 5μπι。同時，有關之孔徑分佈之孔徑150〜 3〇〇μηι計測之寄予率爲71.2 %，確認其爲細胞有效接合 尺寸之孔爲主體的多孔物。 [表觀密度的測定] 同樣以兩面刮鬆刀切斷約1 〇 m m長之上述試料’以 投影機（Nikon，V-12 )測定所得之尺寸求取體積，其重 量以體積除之値求得的結果，計算出 0.077 ± 0.002 g / cm3 〇 本發明特徵之三次元網狀構造，爲孔與孔之連通性優 (17) (17)200400811 之構造，此連通性之指標之透水性依以下方法進行評價。 [透水性的評價] 首先，1 0 m m長與上述同樣切斷之試料片一側之末 端部密栓之’由另一端之開孔，以內徑0.3 m m 0，外徑 1 .2 m m ·0 ，長4 0 m m之針，插入試料之管狀構造物調整 至0.5〇 mm管長之有效穿透面。此針以長50 mm，直徑5 mm 0之砍膠軟管，及直徑20 mm Θ，長90 mm裝入25 g水之圓筒連接，測定於25 °C時蒸餾水之穿透率。透水量 爲 13.47± 0_33 g/ 60 秒、，24.64± 0.35 / 120 秒、。無裝載此 試料之無負荷狀態之透水量爲1 3.70 ± 0.33 g / 60秒， 24.8 7± 0.3 5 / 1 20秒，確認此瘢療把持材料係透水性良好 ，連通性高的三次元網狀構造物。 [實施例2] 牛血管來源之平滑筋細胞（細胞密度：6 X 1 0 6 c e 11 s / mL )之DMEM (培養原成分）溶液（含1 〇%FCS (牛胎 兒血淸））及等量第I型膠原溶液（〇. 3 %酸性溶液，曰本 高硏製）邊於冰上冷卻邊混合，調製爲平滑筋細胞的懸浮 液（細胞密度：3 X 1 0 6 c e 11 s / m L)。 實施例1所製作之管狀之多孔性三次元網狀構造之瘢 痕把ί寸材料（內徑爲1.2 mm0 ’外徑爲3.2 mm0 ，長2 c m )之一端以挾具縛緊，由他端將上述之平滑筋細胞的 懸浮液（1 mL )注入至瘢痕把持材料的管狀構造之側壁滲 -24 - (18) 200400811 出爲止’注入的操作全數於冰上進行，重複數回至管 造物之內部充滿含平滑筋細胞之膠原溶液。其後，將 鬆開，瘢痕把持材料之管狀物的中心通以 S U S 4 4 0 1 . 2 m m 0芯棒，於3 7 °C之恆溫箱內進行培養，得到 胞之多孔性三次元網狀構造材料。 如此所得之含細胞之多孔性三次元網狀構造材料 3曰後以光學顯微鏡觀察之剖面組織圖像如圖5所示 圖5 ’可知製作之構造材料之內部全面分佈細胞。此 胞之構造物進行1週的追加培養，觀察到內部組織繁 無壞死（圖6)。 [實施例3 ] 實施例1所製作之管狀之多孔性三次元網狀構造 痕把持材料（內徑爲1 .2 mm 0 ，外徑爲3.2 mm 0 ， cm )之一端以挾具縛緊，由他端將第I型膠原水溶 〇 . 1 5重量％ )注入，至構造物內部充滿膠原溶液。其 將挾具鬆開，瘢痕把持材料之管狀物的中心通以SUS 製之1 .2 mm 0芯棒，放置於37°C之恆溫箱內，使膠 液凝固，製作網狀構造充滿膠原之管狀構造物。 老鼠的腹部大動脈剝離約3 cm，其兩端以挾具 ，遮斷血流後，由動脈的中央部切斷，其間以上述管 造物接合兩端。將挾具除開後，血液重新流通，產生 ，成爲人造血管的機能（圖7)。此人造血管於1週 出，觀察管狀組織物之內腔面，內腔面全無形成附著 狀構 挾具 製之 含細 培養 。由 含細 殖亦 之瘢 長2 液（ 後， 440 原溶 縛緊 狀構 脈動 後摘 血栓 -25- (19) (19)200400811 ，極爲平滑（圖8)。 [比較例1 ] 熱可塑性聚氨基甲酸酯樹脂（日本MIRAKUTORANE 公司製Miraku- torane E 980 PNAT)以四氫呋喃（日本和 光純藥工業公司製，T H F )於6 〇 °C加熱溶解得到5.0 % ( 重量/重量）溶液。1 6 mL此THF以12 g之氯化鈉粒 子（由飾選處理爲一致的100〜2〇〇μηι粒子徑）分散調 製爲懸浮液。以S U S 4 4 0製之1 . 2 m m 0芯棒浸漬於此懸 浮液中，取出乾燥，芯棒之周圍被含氯化鈉粒子之聚氨基 甲酸酯軟管狀皮膜化。將此充分乾燥後，以離子交換水充 分淸洗，將埋於軟管內的氯化鈉溶解除去。於室溫下減壓 (20 mm Hg(2.7kPa))乾燥24小時，得到內徑爲12 m m 0 ’外徑爲3.2 m m 0之多孔性管狀構造物。 此多孔性管狀構造物，以實施例I同樣的方法測定平 均孔徑及表觀密度’平均孔徑計測爲i 2 1 ± 6 5 μ m，孔徑 1 5 0〜3 0 0 μ m計測之寄予率爲3丨8 %。又，表觀密度爲 0.086 ± 0.004 g / cm3 。-22- (16) (16) 200400811 The average pore diameter and apparent density of the scar-holding material obtained are measured in the following manner. The measurement of the average pore diameter and the apparent density was performed by cutting the sample using a double-sided razor (Feather Co., High Stainless) at room temperature. [Measurement of average pore diameter] An image taken with a solid microscope (manufactured by KEYANCE Corporation, VH-63 00) of a sample plane (cut surface) cut by a two-sided razor, and each hole on the same plane is taken as a three-dimensional element. The mesh-enclosed pattern was used for image processing (the image processing device used LUZEX AP manufactured by NILECO Corporation, and the image acquisition CCD camera used SONY LE N 50) to measure the area of each figure. Take this as the true drawing area, and find the diameter of the corresponding circle as the aperture. Regardless of the perforated pores of the porous part of the porous body, only the connected pores on the same plane were measured. The average pore diameter was 169 ± 5 5 μm. At the same time, the estimated pore size of the pore size distribution of 150 to 300 μm was 71.2%, and it was confirmed that it was a porous body mainly composed of pores of effective cell size. [Measurement of Apparent Density] Similarly, the above-mentioned sample 'about 10 mm in length' was cut with a double-sided spatula to measure the size obtained with a projector (Nikon, V-12) to obtain the volume, and the weight was divided by the volume. The obtained result calculated 0.077 ± 0.002 g / cm3. The characteristic three-dimensional network structure of the present invention is a structure with excellent connectivity between pores and pores (17) (17) 200400811. The permeability of this connectivity indicator depends on Evaluation was performed by the following method. [Evaluation of Water Permeability] First, a 10 mm-long specimen cut in the same manner as described above was tightly plugged at one end of the test piece, with an opening of 0.3 mm 0 and an outer diameter of 1.2 mm · 0. For a 40 mm long needle, the tubular structure inserted into the sample was adjusted to an effective penetration surface of 0.5 mm tube length. This needle is connected by a 50 mm length rubber cutting hose with a diameter of 5 mm 0 and a cylinder with a diameter of 20 mm Θ and a length of 90 mm filled with 25 g of water. The penetration of distilled water at 25 ° C was measured. The water permeability is 13.47 ± 0_33 g / 60 seconds, and 24.64 ± 0.35 / 120 seconds. The amount of water permeated in the unloaded state without this sample is 1 3.70 ± 0.33 g / 60 seconds, 24.8 7 ± 0.3 5/1 20 seconds. It is confirmed that this scar treatment holding material is a three-dimensional mesh with good water permeability and high connectivity. Structure. [Example 2] A solution of bovine vascular smooth muscle cells (cell density: 6 X 10 6 ce 11 s / mL) in a DMEM (original culture) solution (containing 10% FCS (bovine fetal hemorrhage)) and the like A type I collagen solution (0.3% acidic solution, made in Japan) was mixed while cooling on ice to prepare a suspension of smooth tendon cells (cell density: 3 X 1 0 6 ce 11 s / m L). The scar of the tubular porous three-dimensional net-like structure made in Example 1 was fastened at one end with a harness, and the other end was fastened with a harness. The above-mentioned smooth muscle cell suspension (1 mL) was injected into the side wall of the tubular structure of the scar-holding material to infiltrate -24-(18) 200400811. The injection operation was performed on ice, and repeated to the inside of the tube product. Filled with collagen solution containing smooth tendon cells. After that, the tube of the scar holding material was loosened, and the center of the tubular material with SUS 4 0 0 1.2 mm was inserted into a constant temperature box at 37 ° C to obtain a porous three-dimensional network. Construction materials. The porous three-dimensional network structure material containing cells thus obtained is shown in Fig. 5 in the cross-section structure observed with an optical microscope. Fig. 5 'shows that the inside of the produced construction material is completely distributed. The cell structure was subjected to additional culture for one week, and the internal tissues were observed to have no necrosis (Figure 6). [Example 3] One end of the tubular porous three-dimensional net-like structure mark holding material (inner diameter of 1.2 mm 0 and outer diameter of 3.2 mm 0, cm) produced in Example 1 was fastened with a harness, Type I collagen (water-soluble 0.15% by weight) was injected from the other end until the inside of the structure was filled with a collagen solution. The tool is loosened, and the center of the tubular material of the scar holding material is passed through a 1.2 mm 0 core rod made of SUS and placed in a 37 ° C incubator to solidify the glue to produce a mesh structure filled with collagen. Tubular structure. The abdominal aorta of the rat was detached by about 3 cm, and its two ends were braced. After the blood flow was cut off, it was cut off by the central part of the artery, and the two ends were joined with the tube structure. After the harness is removed, the blood circulates again, producing the function of an artificial blood vessel (Figure 7). The artificial blood vessel emerged at 1 week, and the inner cavity surface of the tubular tissue was observed. The inner cavity surface did not form an adherent structure. Thrombosis was removed from the spore-long 2 fluid containing fine colony and 440 (post, 440 original lysed tight structure pulsations-25- (19) (19) 200400811), which is extremely smooth (Figure 8). [Comparative Example 1] Thermoplastic polymerization A urethane resin (Miraku-torane E 980 PNAT manufactured by MIRAKUTORANE, Japan) was dissolved in tetrahydrofuran (manufactured by Wako Pure Chemical Industries, Ltd., THF) at 60 ° C to obtain a 5.0% (w / w) solution. 16 mL This THF is prepared by dispersing 12 g of sodium chloride particles (a uniform particle diameter of 100 to 2000 μm from the decoration treatment) into a suspension. A 1.2 mm 0 core rod made of SUS 4 40 is immersed in this. The suspension was taken out and dried, and a polyurethane hose-like film containing sodium chloride particles was formed around the core rod. After this was sufficiently dried, it was thoroughly rinsed with ion-exchanged water, and the Sodium chloride was dissolved and removed. It was dried under reduced pressure (20 mm Hg (2.7kPa)) at room temperature for 24 hours to obtain a porous tubular structure with an inner diameter of 12 mm 0 'and an outer diameter of 3.2 mm 0. This porous tube Structure, the average pore diameter and apparent density were measured in the same manner as in Example I. Measurement of i 2 1 ± 6 5 μ m, pore size 15 00 0~3 placed the measured count rate of 3 μ m Shu 8% and an apparent density of 0.086 ± 0.004 g / cm3.

以SEM觀察外觀’相對於表層及內部爲具有相同三 次元網狀構造之實施例1，本比較例表層部生成細緻層（ 圖9)，表層部份與內部爲完全不同的構造，內部構造爲 集合的球狀孔’鄰接的孔與孔之接觸部份孔壁有貫通，不 是二次兀網狀構造（圖1 〇 ) D 以實施例1同樣的方法測定透水性，爲】丨2 2 ± 0.4 6 g -26- (20) (20)200400811 / 6 0秒，2 0 . 〇 8 ± 〇 . 9 6 / 1 2 0秒，顯示的値低於實施例1。 此原因係表層部份的孔與孔之間之連通性低，推定爲受表 層部存在細緻層的影響。 [比較例2 ] 與實施例2同樣調製成平滑筋細胞的懸浮液（細胞密 度：3 X 1 〇 6 cells / mL)，以比較例1所製作之多孔性管 狀構造物（內徑：1 .2 mm 0 ，外徑：3.2 mm 0 ，長：2 c m )，依實施例2同樣注入後，進行培養，得到含細胞之 管狀構造物。 如此所得之含細胞之管狀構造物培養3日後以光學顯 微鏡觀察之剖面組織圖像如圖1 1所示。由圖1 1，可知製 作之構造材料之內部幾乎無細胞存在，僅存在於內壁面。 如以上詳述，依本發明，可提供由具有三次元網狀構 造之均質多孔體所成，該多孔構造的內部之全面繁殖均勻 的細胞而得之組織工學用瘢療把持材料，其物理特性優， 不僅適用於活體組織工學領域的基礎硏究，用於人造血管 ’特別是6 mm以下的小口徑之人造血管時，可構成長期 維持尚開存率之人造血管之組織工學用瘢療把持材料，及 使用此組織工學用瘢療把持材料之人造血管》 以下詳細說明本發明之環帶材料。 本發明之環帶材料，係由熱可塑性樹脂或熱硬化性樹 脂所成之基材樹脂所形成，具連通性之三次元網狀構造部 爲平均孔徑爲100〜1〇〇〇μηι，表觀密度爲0.01〜0.5 g / -27- (21) (21)200400811 cm 3之多孔性三次元網狀構造部者即可，有關之厚度方 向之切斷剖面，全面具有類似之構造，或一邊之面側與他 邊之面側具有不同的構造亦可。又，部份之平均孔徑或表 觀密度爲有變化者亦可，例如，由內壁至外壁之方向其平 均孔徑緩緩變化，所謂具有異方性亦可。又，與活體組織 之接觸面側存在大於平均孔徑的大口徑亦沒有關係。此種 孔以5 0 0〜2 0 0 0 μ m左右爲理想，此等存在於活體組織側 的表層時，容易均質的浸漬至膠原等細胞外網之深部，又 ，有利於由組織侵入細胞或毛細血管的構築等的作用。但 是，此種大口徑並不導入本發明所謂之多孔性三次元構造 的平均孔徑的計算槪念。 多孔性三次元構造的平均孔徑爲100〜ΙΟΟΟμιη，表 觀密度爲〇.〇 1〜5 g / cm 3 ，理想的平均孔徑爲200 ~ 600μηΐ，更理想爲200〜500μιτι。表觀密度範圍爲0.01〜 0.5 g / cm 3之內者，細胞繁殖性良好，維持優物理的強 度，細胞侵入，繁殖，組織化時可得到近似皮下組織的彈 性特性，理想爲〇.〇5〜0.3 g / cm 3，更理想爲0.05〜0.2 g / c m 3。 平均孔徑爲相同者其相關之孔徑分佈，亦以細胞侵入 之重要孔徑尺寸1 5 0〜3 0 0 μ m孔的寄予率高者爲理想，孔 徑1 5 0〜3 0 0 μ m孔的寄予率爲1 〇 %以上，理想爲2 0%以上 ，更理想爲30%以上，再理想爲4〇%以上，特別理想爲 5 0%以上時，細胞容易侵入，又，由於侵入之細胞容易接 合、成長爲理想。Observation of the appearance by SEM. Compared to Example 1 with the same three-dimensional network structure as the surface layer and the interior, the surface layer of this comparative example generates a detailed layer (Figure 9). The surface layer and the interior are completely different structures. The internal structure is The aggregated spherical hole 'adjacent hole and the contact part of the hole penetrated through the hole wall, not a secondary network structure (Fig. 10) D. The water permeability was measured in the same manner as in Example 1, and was 2] ± 2 2 ± 0.4 6 g -26- (20) (20) 200400811/60 seconds, 20 .08 ± 0.96 / 120 seconds, and the displayed radon is lower than that in Example 1. This is because the connectivity between the pores in the surface layer is low, and it is presumed to be affected by the presence of a fine layer in the surface layer. [Comparative Example 2] A suspension of smooth tendon cells (cell density: 3 X 106 cells / mL) was prepared in the same manner as in Example 2, and a porous tubular structure (inner diameter: 1. 2 mm 0, outer diameter: 3.2 mm 0, length: 2 cm). After being injected in the same manner as in Example 2, the cells were cultured to obtain a tubular structure containing cells. The cross-sectional tissue image observed by the optical microscope after culturing the tube-containing tubular structure thus obtained for 3 days is shown in FIG. 11. From Fig. 11, it can be seen that almost no cells exist in the manufactured construction material, and only the inner wall surface exists. As described in detail above, according to the present invention, a tissue engineering scar treatment holding material made of a homogeneous porous body having a three-dimensional network structure can be provided. Excellent characteristics, not only suitable for basic research in the field of biotissue engineering. When used in artificial blood vessels, especially small-caliber artificial blood vessels of less than 6 mm, it can constitute the tissue engineering of long-term maintenance of artificial blood vessels. Scar treatment holding material and artificial blood vessel using the tissue engineering scar treatment holding material "The cuff material of the present invention will be described in detail below. The endless belt material of the present invention is formed of a base resin made of a thermoplastic resin or a thermosetting resin, and the connected three-dimensional network structure portion has an average pore diameter of 100 to 1000 μηι, and has an apparent appearance. The density is 0.01 ~ 0.5 g / -27- (21) (21) 200400811 cm 3 for the porous three-dimensional network structure part. The cut-off section in the thickness direction has a similar structure on the whole, or one side. The surface side may have a different structure from the other side. It is also possible to change the average pore diameter or the apparent density of some parts. For example, the average pore diameter changes gradually from the inner wall to the outer wall, and the so-called anisotropy may be used. It is also irrelevant that a large diameter larger than the average pore diameter exists on the contact surface side with the living tissue. Such pores are preferably about 500 to 2000 μm. When present in the surface layer on the side of living tissue, it is easy to homogeneously impregnate into the deep part of the extracellular network such as collagen, and it is also conducive to invasion of cells by tissues. Or the construction of capillaries. However, such a large caliber does not introduce the calculation concept of the average pore diameter of the so-called porous three-dimensional structure of the present invention. The average pore diameter of the porous three-dimensional structure is 100 to 100 μm, the apparent density is 0.01 to 5 g / cm 3, and the ideal average pore diameter is 200 to 600 μηΐ, more preferably 200 to 500 μιτι. Those with an apparent density in the range of 0.01 to 0.5 g / cm 3 have good cell reproduction properties and maintain excellent physical strength. Cell invasion, reproduction, and organization can obtain elastic properties similar to those of subcutaneous tissue, ideally 0.05. ~ 0.3 g / cm 3, more preferably 0.05 ~ 0.2 g / cm 3. The average pore diameter is the same pore size distribution, and the important pore size of the cell invasion is 1 50 ~ 3 0 0 μm. The higher the rate is, the better the pore size is 15 0 ~ 3 0 0 μm. When the rate is 10% or more, it is preferably 20% or more, more preferably 30% or more, and even more preferably 40% or more, and particularly preferably 50% or more, the cells easily invade, and the invaded cells are easy to join. And grow as an ideal.

-28- (22) (22)200400811 有關多孔性三次元網狀構造之平均孔徑之孔徑1 5 0〜 400μ m之寄予率，係指依下述實施例1相關之平均孔徑的 測定方法，其相對於全孔數該孔徑150〜400μπΐ的孔數之 比例。 具如此之平均孔徑、表觀密度及孔徑佈之多孔性三次 元網狀構造者，細胞容易浸透空孔部份，其多孔性三次元 網狀構造部細胞容易接合，成長，構築毛細血管，可得到 剌入部皮下組織與套管或導管頑強的癒合之良好環帶材料 〇 多孔性三次元網狀構造可使用之厚度爲0.2〜500 mm ，理想爲〇 . 2〜1 0 0 m m ’更理想爲〇 . 2〜5 0 m m，特別理 想爲0.2〜10 mm，尤其理想爲0.2 ~ 5 mm，爲此厚度者 ’可高水準的滿足作爲環帶材料必要之物理強度，細胞的 侵入、組織化，與皮下組織的癒合性、抗細菌性等。 構成本發明之三次元網狀構造部之熱可塑性樹脂或熱 硬化性樹脂，可舉例如聚氨基甲酸酯樹脂、聚醯胺樹脂、 聚乳酸樹脂、聚烯烴樹脂、聚酯樹脂、氟素樹脂、丙烯酸 樹脂、甲基丙烯酸樹脂及此等的衍生物的1種或2種以上 ’理想爲聚氨基甲酸酯樹脂’其中亦以段節化聚氨基甲酸 酯樹脂爲合適。 段節化聚氨基甲酸酯樹脂係由多元醇、二異氰酸酯及 鏈延長劑之3成分所合成’由於具有由分子內具有所謂硬 段節部份與軟段節部份之嵌段聚合物構造之彈性物特性， 使用如此段節化聚氨基甲酸酯時所得之彈性，期待可衰減 -29- (23) 200400811 患者動到套管或導管時，或消毒作業等動到剌入部眉 皮膚時，皮下組織與環帶材料的界面所產生之應力。 本發明的環帶材料，可爲由上述特定之多孔性三 網狀構造所成的層作爲第1層，更與此第1層相異的 的第2層層合者。此第2層可爲纖維集合物或可撓色 ，更可使用與第1層之多孔性三次元網狀構造不同耳 徑或表觀密度之多孔性三次元網狀構造層。 纖維集合物可例示如不織布或織布，其厚度爲 1 0 0 m m，理想爲0. 1〜5 0 m m，更理想爲〇.丨〜i 0 尤其理想爲0. 1〜5 m m，爲此厚度範圍者，與多孔性 兀網狀構造層層合時可得到良好可撓性，與皮下組_ 合強度亦頑強爲理想。 不織布或織布之有孔性爲100〜5〇〇〇 cc / cm2 的範圍者，依可撓性、與皮下組織的縫合觀點爲理f ’此有孔性係依JIS L 1 004而測定之値，亦具通氣性 氣Μ。 纖維集合物爲1種或2種以上選自聚氨基甲酸酯 、聚醯胺樹脂、聚乳酸樹脂 '聚烴樹脂、聚酯樹脂、 脂、丙烯酸樹脂、甲基丙烯酸樹脂與由此等之衍生牧 群所成之合成樹脂者亦可，或可使用1種或2種以上 絲纖阮、甲殼素、殼聚糖及纖維素與由此等之衍生物 然物來源之纖維所成者。亦可倂用合成纖維與天然物 的纖維。 可撓性薄膜爲熱可塑性樹脂薄膜，具體可例示如 丨邊的 :次元 丨構造 :薄膜 :均口 0.1〜 mm， :三次 丨的縫 / min !。又 :或通 i樹脂 氟樹 '所成 選自 之天 來源 1種 -30- (24) (24)200400811 或2種以上選自聚氨基甲酸酯樹脂 '聚醯胺樹脂、聚乳酸 樹脂、聚烴樹脂、聚酯樹脂、氟樹脂、尿素樹脂、酚樹脂 、環氧樹脂、聚醯亞胺樹脂、矽樹脂 '丙烯酸樹脂、甲基 丙烯酸樹脂與由此等之衍生物所成群所成薄膜，理想爲1 種或2種以上選自聚酯樹脂、氟樹脂、聚氨基甲酸酯樹脂 、丙烯酸樹脂、氯乙烯、氟樹脂及矽樹脂所成群之薄膜。 此種可燒性薄膜之厚度爲0 . 1〜5 0 0 m m者，可得至jj 有利於可撓性、物理強度之環帶材料，理想爲〇 . 1〜1 0 〇 m m，更理想爲0 . 1〜5 0 m m，尤其理想爲〇 . 1〜1 〇 m m。 可撓性薄膜不僅實心的薄膜亦可使用多孔膜或發泡膜 。與實心的可撓性薄膜層合時細菌隔離性大，可得到有利 於感染管理的環帶材料。 以平均口徑或表觀密度與第1層之多孔性三次元網狀 構造不同之多孔性三次元網狀構造爲第2層時，此多孔性 三次元網狀構造，可用使平均孔徑爲〇 . 1〜2 0 0 μ m而表觀 密度爲〇. 0 1〜1.0 g / c m 3之多孔性三次元網狀構造。此 第2層之多孔性三次元網狀構造層的厚度以ο」〜2〇 mm 爲理想。 此等第2層之多孔性三次元網狀構造層的層合方法 ，可列舉如該第2層爲纖維集合物，可撓性薄膜，與平 均口徑或表觀密度與第丨層之多孔性三次元網狀構造不同 之多孔性三次元網狀構造層時，使用粘合劑接合的方法， 特別是以熱溶不織布挾於第1層與第2層之間層合，加熱 下壓合的方法。該熱溶不織布可使用如日本日東紡公司製 (25) (25)200400811 之P A 1 0 0 1的聚醯胺型熱粘合薄片等。其他如，使用溶劑 溶解接觸表面的表層部之接合方法，以熱溶融表層部的接 合方法，利用超音波或高週波的方法等。又，製造第1層 時’聚合物膠獎與纖維集合物或可撓性薄膜層合形成等， 可由連續的層合形成。 第2層亦可設置2層以上纖維集合物、可撓性薄膜， 多孔性二次兀網狀構造層，又，亦可介入第2層而層合第 1層的多孔性三次元網狀構造層成爲3層構造。 本發明的環帶材料的多孔性三次元網狀構造部，係保 持1種或2種以上選自第I型膠原、第π型膠原、第m 型膠原、第IV型膠原、粥型膠原、纖維結合素、明膠、 透明質酸、肝素、角質素酸、軟骨素、軟骨素硫酸、軟骨 素硫酸B、彈性素、肝素硫酸、昆布寧 '凝血海綿硬蛋白 、vitronectin' osteonectin、entactin、經基乙基甲基丙嫌 酸酯與二甲基胺基乙基甲基丙烯酸酯的共聚物、羥基乙基 甲基丙烯酸酯與甲基丙烯酸酯的共聚物、藻朊酸、聚丙烯 醯胺、聚二甲基烯醯胺及聚乙烯脒咯烷酮所成群者亦可， 更可保持1種或2種以上選自血小板來源繁殖因子、上皮 繁殖因子、形質轉換繁殖因子α、胰島素樣繁殖因子、胰 島素樣繁殖因子結合蛋白、肝細胞繁殖因子、血管內皮繁 殖因子、血管生長素、神經繁殖因子、腦來源神經營養因 子' 毛樣體神經營養因子、形質轉換繁殖因子石、潛在型 形質轉換繁殖因子/?、苯丙酸諾龍、骨形質蛋白、纖維芽 細胞繁殖因子、腫瘍繁殖因子沒、二倍體纖維芽繁殖因子 -32- (26) (26)200400811 肝素結恰性上皮繁殖因子樣繁殖因子、神經腫瘤來源繁殖 因子、兩性邊條曲菌素、/5動物纖維素' 7 -甲基鳥嘌呤、 淋巴毒素、細細胞生成素、腫瘍壞死因子α 、內白細胞 素-1 /5 、內白細胞素-6 '內白細胞素_8、內白細胞素_ i 7、 內黴蛋白、抗病毒劑、抗菌劑、及抗生物所成群者亦可， 更接合1種或2種以上選自胚性幹細胞、血管內皮細胞' 中胚葉性細胞、平滑筋細胞、末梢血管細胞及中皮細胞所 成群之細胞亦可。 本發明的環帶材料’可設置由構成該多孔性三次元網 狀構造層之熱可塑性樹脂或熱硬化性樹脂所成的較骨骼自 身細微的孔。此細微的孔，非使骨骼表面平滑而爲複雜的 凹凸表面，有效的保持膠原或細胞繁殖因子等。但是，此 細微的孔’不列入本發明所謂的該多孔性三次元網狀構造 層的平均孔徑之計算。 以下列舉構成本發明環帶材料的由熱可塑性聚氨基甲 酸醋所成之該多孔性三次元網狀構造物的製造方法之一例 ’本發明的環帶材料的製造方法不限於以下方法。 由熱可塑性聚氨基甲酸酯製造該多孔性三次元網狀構 造物時’首先’聚氨基甲酸酯樹脂，與後述作爲孔形成劑 的水溶性高分子化合物，與聚氨基甲酸酯的良溶媒之有機 溶媒混合製造成聚合物膠漿。具體的，聚氨基甲酸酯樹脂 以有機溶媒混合成爲均勻的溶液後，此溶液中以水溶性高 分子化合物混合分散之。有機溶媒可爲N，N_二甲基甲醯 胺’ N-甲基-2-脉咯基二酮，四氫呋喃等，凡可溶解聚氧 -33 - (27) (27)200400811 基甲酸酯樹脂者不限定於此，又，減量使用或不使用有機 溶媒，而以熱的作用融解聚氨基甲酸酯樹脂，亦可於此狀 態混合孔形成劑。 作爲孔形成劑的水溶性高分子化合物，可列舉如聚乙 二醇、聚丙二醇、聚乙烯醇、聚乙烯脒咯烷酮、藻朊酸、 羧基甲基纖維素、羥基丙基纖維素、甲基纖維素、乙基纖 維素等，可與熱可塑性樹脂均勻分散形成膠漿者無特別限 制。又，依熱可塑性樹脂的種類，亦可使用非水溶性高分 子化合物，例如對苯二甲酸酯 '液腊等的親油性化合物或 氯化鋰、碳酸鈣等的無機鹽類。又’利用高分子用的結晶 核劑等在凝固時生成二次粒子，即’可助長多孔物的骨骼 形成。 由熱可塑性聚氨基甲酸酯樹脂，有機溶媒及水溶性高 分子化合物等所製造的聚合物膠漿，接著於含有熱可塑性 聚氨基甲酸酯樹脂的貧溶媒的凝固浴中浸漬，於凝固液中 萃取除去有機溶媒及水溶性高分子化合物。由此除去一部 份或全部的有機溶媒或水溶性高分子化合物，可得到由熱 可塑性聚氨基甲酸酯樹脂而成的多孔性三次元網狀構造物 。此處使用的貧溶媒可例示如水、低級醇、低碳數之酮類 等。凝固之熱可塑性聚氨基甲酸酯樹脂，最後以水等淸洗 ’除去殘留之有機溶媒或孔形成劑即可。 以下詳細說明本發明之植入活體材料被覆材料。 本發明之植入活體材料被覆材料係由熱可塑性樹脂或 熱硬化性樹脂所成成，具連通性之三次元網狀構造部其平 -34- (28) (28)200400811 均孔徑爲100 ~ ΐ〇〇〇μΐΉ ’表觀密度爲o.oi〜0.5 g / cm 3 之多孔性三次元網狀構造部者即可，有關之厚度方向之切 斷剖面，全面具有類似之構造，或一邊之面側與他邊之面 側具有不同的構造亦可。又’部份之平均孔徑或表觀密度 爲有變化者亦可，例如，由內壁至外壁之方向其平均孔徑 緩緩變化’所謂具有異方性亦可。又，與活體組織之接觸 面側存在大於平均孔徑的大口徑亦沒有關係。此種孔以 5 0 0〜20 ΟΟμηΐ左右爲理想，此等存在於活體組織側的表 層時，容易均質的浸漬至膠原等之細胞外網深部，又，有 利於由組織侵入細胞或毛細血管的構築等的作用。但是， 此種大口徑並不導入本發明所謂之多孔性三次元構造的平 均孔徑的計算槪念。 多孔性三次元構造的平均孔徑爲1 0 0〜1 0 0 0 μ m，表 觀密度爲0.01〜0.5 g / cm 3 ’理想的平均孔徑爲200〜 600μηΐ，更理想爲200〜500μπΐ。表觀密度範圍爲〇.〇1〜 0.5 g / cm 3之內者，細胞繁殖性良好，維持優物理的強 度，細胞侵入，繁殖，組織化時可得到近似皮下組織的彈 性特性，理想爲0.05〜0.3 g / cm 3，更理想爲0.05〜0.2 •2 g / cm 。 平均孔徑爲相同者其相關之孔徑分佈，以細胞侵入之 重要孔徑尺寸1 5 0〜4 0 0 μ m孔的寄予率高者爲理想，孔徑 150 ~ 400μηι孔的寄予率爲10%以上，理想爲2〇%以上， 更理想爲30%以上，再理想爲4 0%以上’特別理想爲5 0% 以上時，細胞容易侵入，又，由於侵入之細胞容易接合、 -35- (29) 200400811 成長爲理想。 有關多孔性三次元網狀構造之平均孔徑之孔 4 00μ m之寄予率，指依下述實施例1相關之平均 定方法，其相對於全孔數該孔徑1 5 〇〜4 0 0 μ m的 例。 具如此之平均孔徑、表觀密度及孔徑佈之多 元網狀構造者，細胞容易浸透空孔部份，多孔性 狀構造部細胞容易接合，成長，構築毛細血管， 入活體材料之植入部份活體可得到頑強的癒合。 多孔性三次元網狀構造可使用之厚度爲〇 5 ，理想爲0.5〜100 mm，更理想爲0.5〜50 mrr 想爲0.5〜10 mm，尤其理想爲0.5 ~ 5 mm，爲 ，可高水準的滿足作爲植入活體材料被覆材料必 強度，細胞的侵入、組織化，與活體組織的癒合 構成本發明之三次元網狀構造部之熱可塑性 硬化性樹脂，可舉例如聚氨基甲酸酯樹脂、聚醯 聚乳酸樹脂、聚烯烴樹脂、聚酯樹脂、氟素樹脂 樹脂、甲基丙烯酸樹脂及此等的衍生物的1種或 ，理想爲聚氨基甲酸酯樹脂，其中亦以段節化聚 酯樹脂爲合適。 段節化聚氨基甲酸酯樹脂係由多元醇、二異 鏈延長劑之3成分所合成，由於具有由分子內具 段節部份與軟段節部份之嵌段聚合物構造之彈性 使用如此段節化聚氨基甲酸酯時所得之彈性，期 徑 1 5 0 ~ 孔徑的測 孔數之比 孔性三次 三次元網 相關的植 〜5 0 0 m m i，特別理 此厚度者 要之物理 性等。 樹脂或熱 胺樹脂、 、丙烯酸 2種以上 氨基甲酸 氰酸酯及 有所謂硬 物特性， 待可衰減 (30) (30)200400811 活體組織與植入活體材料的界面所產生之應力。 本發明的植入活體材料被覆材料’可爲由上述特定之 多孔性三次元網狀構造所成的層作爲第1層，更與此第】 層相異的構造的第2層層合者。此第2層可爲纖維集合物 或可撓性薄膜，更可使用與第1層之多孔性三次元網狀構 造不同平均口徑或表觀密度之多孔性三次元網狀構造層。 本發明的植入活體材料被覆材料的多孔性三次元網狀 構造部，係保持1種或2種以上選自第I型膠原、第Π 型膠原 '第III型膠原、第IV型膠原、粥型膠原、纖維 結合素、明膠、透明質酸、肝素 '角質素酸、軟骨素、軟 骨素硫酸、軟骨素硫酸B、彈性素、肝素硫酸、昆布寧、 凝血海綿硬蛋白、vitronectin、osteonectin、entactin、經 基乙基甲基丙烯酸酯與二甲基胺基乙基甲基丙烯酸酯的共 聚物、羥基乙基甲基丙烯酸酯與甲基丙烯酸酯的共聚物、 藻朊酸、聚丙烯醯胺、聚二甲基烯醯胺及聚乙烯脒咯烷酮 所成群者亦可，更可保持丨種或2種以上選自血小板來源 繁殖因子' 上皮繁殖因子、形質轉換繁殖因子α、胰島素 樣繁殖因子、胰島素樣繁殖因子結合蛋白、肝細胞繁殖因 子、血管內皮繁殖因子、血管生長素、神經繁殖因子、腦 來源神經營養因子、毛樣體神經營養因子、形質轉換繁殖 因子/?、潛在型形質轉換繁殖因子A、苯丙酸諾龍、骨形 質蛋白、纖維芽細胞繁殖因子、腫瘍繁殖因子点、二倍體 纖維芽繁殖因子、肝素結恰性上皮繁殖因子樣繁殖因子、 血管生長素來源繁殖因子 '兩性邊條曲菌素、Θ動物纖維 -37- (31) (31)200400811 素' 7 -甲基鳥嘌玲、淋巴毒素、細細胞生成素、腫瘍壞 死因子α 、內白細胞素-1点、內白細胞素-6、內白細胞 素-8、內白細胞素-1 7、內黴蛋白、抗病毒劑、抗菌劑' 及抗生物所成群者亦可’更接合1種或2種以上選自胚性 幹細細胞' 血管內皮細胞、中胚葉性細胞、平滑筋細胞、 末梢血管細胞及中皮細胞所成群之細胞亦可。 又，本發明的植入活體材料被覆材料，可設置由構成 該多孔性三次元網狀構造層之熱可塑性樹脂或熱硬化性樹 脂所成的較骨骼自身細微的孔。此細微的孔，非使骨骼表 面平滑而爲複雜的凹凸的表面，有效的保持膠原或細胞繁 殖因子等。但是，此細微的孔，不列入本發明所謂的該多 孔性三次元網狀構造層的平均孔徑之計算。 以下列舉構成本發明環帶材料的由熱可塑性聚氨基甲 酸酯所成之該多孔性三次元網狀構造物的製造方法的一例 ’本發明的環帶材料的製造方法不限於以下方法。 由熱可塑性聚氨基甲酸酯製造該多孔性三次元網狀構 造物時’首先，聚氨基甲酸酯樹脂，與後述作爲孔形成劑 的水丨谷性局分子化合物，與聚氨基甲酸酯的良溶媒之有機 溶媒混合製造成聚合物膠漿。具體的，聚氨基甲酸酯樹脂 以有機溶媒混合成爲均勻的溶液後，此溶液中以水溶性高 分子化合物混合分散之。有機溶媒可爲Ν，Ν_二甲基甲醯 胺，Ν -甲基-2-脒咯基二酮，四氫呋喃等，舉凡可溶解聚 熱基甲酸酯樹脂者不限定於此，又，減量使用或不使用有 機溶媒，以熱的作用融解聚氨基甲酸酯樹脂，亦可於此狀 -38- (32) (32)200400811 態混合孔形成劑。 作爲孔形成劑的水溶性高分子化合物，可列舉如聚乙 二醇、聚丙二醇、聚乙烯醇、聚乙烯脒咯烷酮、藻朊酸、 羧基甲基纖維素、羥基丙基纖維素、甲基纖維素、乙基纖 維素等，可與熱可塑性樹脂均勻的分散形成膠漿者無特別 限制。又，依熱可塑性樹脂的種類，亦可使用非水溶性高 分子化合物，例如對苯二甲酸I旨、液腊等的親油性化合物 或氯化鋰、碳酸鈣等的無機鹽類。又，利用高分子用的結 晶核劑等於凝固時生成二次粒子，即，可助長多孔物的骨 骼形成。 由熱可塑性聚氨基甲酸酯樹脂，有機溶媒及水溶性高 分子化合物等所製造的聚合物膠漿，接著於含有熱可塑性 聚氨基甲酸酯樹脂的貧溶媒的凝固浴中浸漬，於凝固液中 萃取除去有機溶媒及水溶性高分子化合物。由此除去一部 份或全部的有機溶媒或水溶高分子化合物，可得到由熱可 塑性聚氨基甲酸酯樹脂而成的多孔性三次元網狀構造物。 此處使用的貧溶媒可例示如水、低級醇、低碳數之酮類等 。凝固之熱可塑性聚氨基甲酸酯樹脂，最後以水等淸洗， 除去殘留之有機溶媒形成劑即可。 如以上詳述，依本發明的植入活體材料被覆材料，由 細胞容易由活體組織侵入、繁殖器質化，得到與活體組織 頑強的癒合，其結果，可防止因植入活體材料植入活體而 對活體的不良影響。 以下以實施例具體的說明本發明的環帶材料及構成其 ^ ODi -39- (33) (33)200400811 表面的植入活體材料被覆材料，在不超越本發明的要旨下 ，不限定於以下的實施例。 [實施例4 ] 熱可塑性聚氨基甲酸酯樹脂（日本MIRAKUTORANE 公司製Miraku- torane E9 80 PNAT)以N-甲基-2-吡咯基 二酮（日本關東化學公司製縮氨酸合成用試藥，NMP )使 用溶解器（約2000 rpm)於室溫下溶解得到5.0% (重量 /重量）溶液。秤取約1.0 kg此NMP溶液放入星型混合 機（日本井上製作所製，2.0L容量，PLM-2型），以相當 於聚氨基甲酸酯樹脂同重量的甲基纖維素（日本關東化學 公司製，試藥，25 cp級）於40 °C混合40分鐘後，其後 繼續攪拌10分鐘，減壓至20 mm Hg ( 2.7 kPa)脫泡，得 到聚合物膠漿。 另外，以厚度3 mm，150 mm X 150 mm 的鐵夫龍， 沖出內14〇 mm X 140 mm 的四角外框二片重疊，其間挾 入15〇 mm X 150 mm角型之化學實驗用濾紙（日本東洋 濾紙，定量分析用，1號）。用上述聚合物膠漿流延，以 玻璃板括平膠液後，承載於1 5 0 mm X 1 5 0 mm角型的化 學實驗用濾紙（日本東洋濾紙，定量分析用，1號）。投 入還流狀態之甲醇中繼續還流72小時，萃取除去化學實 驗用濾紙上下兩面的NMP溶媒，凝固聚氨基甲酸酯樹脂 。此時，甲醇於持續維持還流狀態下，隨時更換新液。 7 2小時後，由鐵夫龍框取出凝固的聚氨基甲酸酯樹 -40- (34) 200400811 月曰’於日本藥局方精製水中淸洗72小時， 、甲轉及殘留的NMP萃取除去。隨時供給 再知室溫下減壓20 mm Hg ( 2.7 kPa)乾隹 到熱可塑性樹脂製之多孔性三次元網狀構造 次元網狀構造物爲本發明之植入活體材料被 其次，以1 4 0 m m x 1 4 0 m m聚酯製纖糸| 公司，穿孔打擊•雙•棉絨•纖維，有孔性 / min ’厚度1.5 mm )以四氫呋喃（日本關 特級試藥）浸漬’以雙輥軋擰使浸漬量爲（ g / cm2 ’上述多孔性三次元網狀構造材料 料被覆材料）重疊，以1. 〇 leg / cm2壓合得 帶材料。 圖1及圖2爲此環帶材料的表面之植入 材料之掃瞄型電子顯微鏡（TOPCON公司製 拍攝的相片，所得之環帶材料的表面之植入 材料’知其孔徑約爲3 5 〇 μ m之多孔性三次元 有關所得之環帶材料之厚度2.3 m m之 狀構造部份（即，植入活體材料被覆材料） 測定平均孔徑及表觀密度，其結果如表1所 之平均孔徑及表觀密度之測定，試料的切斷 刀（Feather 公司製，High Stainless)於室结 [平均孔徑之測定] 以兩面刮鬍刀切斷之試樣平面（切斷面 將甲基纖維素 新的淸洗用水 | 24小時，得 物。多孔性三 覆材料。 "帛絨(BADO 3800 cc / cm2 東化學公司， 3.104 土 0.002 (植入活體材 到本發明之環 活體材料被覆 ，SM200 )所 活體材料被覆 >網狀構造。 多孔三次元網 ，依下述方法 示。又，相關 使用兩面刮鬍 I下進行。 )使用電子顯 -41 - (35) 200400811 微鏡CTOPCON公司製，SM200)所拍攝的相片，同一平 面上的各個孔作爲由三次元網狀構造之骨骼包圍之圖型作 圖像處理（圖像處理裝置使用NILEC0公司製之LUZEX AP，圖像的取得CCD相機係使用SONY之LE N50) ’測 定各個圖形的面積。以此作爲真圓面積，求取對應圓之直 徑作爲孔徑。勿視多孔物的骨骼部份之穿孔之微細孔，僅 測定同一平面上之連通孔。同時測定有關之孔徑分佈，如 圖3之圖示。由孔徑分佈的測定結果，計測孔徑1 5 0〜 4 〇 〇 μ m之寄予率。 [表觀密度的測定] 實施例4製造之層合第2層前之三次元網狀構造物約 10 mm X 1 〇 m m x 3 mm的直方體以兩面刮鬍刀切斷。此 試料以投影機（Nikon，V-12 )測定所得之尺寸求取體積 ’由其重量除以體積之値求得。 表1 平均 孔徑 (μ 111 ) 孔徑 1 5 0 ~ 4 0 0 μ m之寄予率 (%) 表觀密度 (g / cm3) 厚度 (mm) 作爲第1 層的多孔 性三次元 _網構造部 3 29土 160 66.2 0.1 17± 〇 . 1 1 8 2.3 -42- (36) (36)200400811 由表1，可知第丨層的多孔性三次元網構造部，係以 細胞有效接合之尺寸孔爲主體的多孔性三次元網構造。 [實施例5 ] 使用成羊爲檢體（雌，體重54 kg)，以刹毛之左側胸 部之腹部表皮㈣難1手„，檢㈣左麵位，以 通常的手法迅速進行氣管內插管’以異氟院維持全身麻醉 。胸腹部周圍表面以IS0dine消毒後，表皮切開20 mm， 以實施例4所成之環帶材料的試驗片植入一半，縫合皮下 *織貫通固定（圖4)。該環帶材料係使用切斷爲〗〇 mm X 1 0 mm之試驗片，以環氧乙烷施予減菌者。手術後， »式驗位置以酸性水或I s 〇 (Π n e進行1日2次的消毒。檢體 自由給水’一日5回適量（約1 kg )供給壓縮飼料。手術 2週後’於全身麻醉下將先前植入之試驗片及周圍的組織 摘出。該試驗片與周圍的組織繁殖密合，相互的剝離有困 難。又’周圍沒有發現感染、發炎等。 圖5 a所示爲此環帶材料表面（即植入活體材料被覆 材料）之繁殖部份以放大鏡擴大之相片。圖5 a的中央之 指標所示爲境界不明的乳白色層爲與環帶材料的內部連接 著’又’環帶材料內部充滿透明的組織確認爲浸潤之肉芽 組織。 圖5 b所不爲使用織布（實施例4使用之聚酯製纖維 棉絨（BADO公司，穿孔打擊.雙.棉絨•纖維））單體 -43- (37) (37)200400811 與上述進行同樣的試驗時以放大鏡擴大之相片。沿著織布 表面乳白色的層向深的方向浸潤’確認所謂的向下成長現 象。 相對於此，本發明的環帶材料’乳白色層連續存在至 表皮附近，確認可抑制向下成長的現象。 上述試驗後，摘出的試料片’迅速以I 〇%中性緩衝福 馬林固定，以常法作成HE染色標本，以光學顯微鏡觀察 之。其結果，本發明的環帶材料的表面之植入活體材料被 覆材料多孔性三次元網構造層，浸潤著由周圍組織伸展的 線維芽細胞，巨噬細胞及膠原線維等的細胞外基質爲主體 的肉芽組織，又確認有新生的血管。 又，同樣手法四週後所得的標本，植入的試驗片內伸 展多量的肉芽細胞，辨識形成成熟的結合組織，確認更向 器質化前進。 由以上，本發明的環帶材料由細胞浸潤多孔性三次元 構造層而器質，隔離外界與創傷部，唆使防禦有關治癒機 智的細胞感染的增惡因子。 如以上詳述，依本發明的環帶材料，可提供容易由活 體皮下組織浸入、繁殖細胞’構築毛細血管得到與皮下組 織頑強的癒合，其結果，創傷部與外界隔離，防禦有關治 癒機能的細胞感染的增惡因子，抑制向下成長的進行，以 隧道感染爲首的各種感染問題少的環帶材料。 如此之本發明環帶材料，可適合於由套管或導管類以 皮下剌入療法之補助人造心臟之血液循環法，腹膜透析療 (38) (38)200400811 法，中心靜脈營養法，經套管D D s及經導管D D S等的活 體皮膚剌入部使用。 【圖式簡單說明】 圖1係實施例1所製造之瘢痕把持材料之管狀構造物 之全體SEM圖像（20倍）。 圖2係貫施例1所製造之癒痕把持材料之管狀構造物 內部之微細構造之實體顯微鏡圖像（1 0 〇倍）。 圖3係實施例1所製造之瘢痕把持材料之管狀構造物 之內壁表層之SEM圖像（20倍）。 圖4係實施例1所製造之瘢痕把持材料之管狀構造物 之外周表層之SEM圖像（20倍）。 圖5係實施例2所製造之含細胞之多孔性三次元網狀 構造材料之三日培養後之光學顯微鏡圖像（1 〇倍）。 圖6係實施例2追加一培養後顯示內部全體繁殖之光 學顯微鏡圖像（1 0倍）。 圖7係實施例3，由人造血管確保血流生拍動場面之 相片。 圖8係實施例3，移植一週後人造血管內部無顯示生 成血栓之相片。 ffl 9係比較例丨所製造之環狀構造物的表層部之 s E Μ圖像（5 〇倍）。 圖〗〇係比較例1所製造之環狀構造物內部之·微細構 造之SEM圖像（50倍）。 (39) 200400811 ® 1 1係比較例2所製造之含細胞之管狀構造材料之 三日培養後之光學顯微鐃圖像（1 〇倍）。 圖12係實施例4製造之環帶材料之組織接觸側之表 面之SEM圖像（50倍）。 圖13係實施例4製造之環帶材料之內部斷面之SEM 圖像（5 0倍）。-28- (22) (22) 200400811 The average pore diameter of the porous three-dimensional network structure with a pore diameter of 150 to 400 μm refers to the method for measuring the average pore diameter according to Example 1 below. The ratio of the number of pores having a pore diameter of 150 to 400 μπΐ with respect to the total number of pores. With a porous three-dimensional network structure with such average pore size, apparent density and pore size cloth, the cells are easy to permeate the pores, and the cells in the porous three-dimensional network structure are easy to join, grow, and build capillaries. A good annulus material that obtains a stubborn healing of the subcutaneous tissue of the invaded region and the cannula or catheter. The porous three-dimensional network structure can be used with a thickness of 0.2 ~ 500 mm, ideally 0.2 ~ 100 mm. It is 0.2 to 50 mm, particularly preferably 0.2 to 10 mm, and particularly preferably 0.2 to 5 mm. For this thickness, a high level of physical strength, cell invasion and organization necessary for the belt material can be satisfied. , And subcutaneous tissue healing, antibacterial and so on. Examples of the thermoplastic resin or thermosetting resin constituting the three-dimensional network structure portion of the present invention include polyurethane resin, polyamide resin, polylactic acid resin, polyolefin resin, polyester resin, and fluorine resin. One or two or more of acrylic resins, methacrylic resins, and derivatives thereof are 'ideally polyurethane resins'. Among them, segmented polyurethane resins are also suitable. Segmented polyurethane resin is synthesized from the three components of polyol, diisocyanate and chain extender. 'Because it has a block polymer structure with a so-called hard segment and soft segment in the molecule. The elastic properties of this type of polyurethane are expected to reduce the elasticity of -29- (23) 200400811 when the patient moves to the cannula or catheter, or disinfection operations, etc. , The stress generated at the interface between the subcutaneous tissue and the annulus material. The endless belt material of the present invention may be a layer formed of the specific porous tri-mesh structure described above as the first layer, or a second layer laminated different from the first layer. This second layer may be a fiber assembly or a flexible color, and a porous three-dimensional network structure layer having a different ear diameter or apparent density than the porous three-dimensional network structure of the first layer may be used. The fiber assembly can be exemplified as a non-woven fabric or a woven fabric, and its thickness is 100 mm, ideally 0.1 to 50 mm, more preferably 0.1 to 5 i, and especially 0.1 to 5 mm, for this purpose. For thickness ranges, good flexibility can be obtained when laminated with a porous mesh structure layer, and the combined strength with the subcutaneous group is also ideal. Non-woven or woven fabrics with a porosity in the range of 100 to 5000 cc / cm2 are based on the viewpoint of flexibility and suture with subcutaneous tissue. F 'This porosity is measured in accordance with JIS L 1 004 Alas, it also has a breathable gas M. The fiber assembly is one or two or more kinds selected from polyurethane, polyamide resin, polylactic acid resin, polyalkylene resin, polyester resin, grease, acrylic resin, methacrylic resin, and derivatives derived therefrom. Herds can also be made of synthetic resin, or one or two or more kinds of silk fiber, chitin, chitosan, cellulose and fibers derived from these derivatives and natural materials can be used. Synthetic and natural fibers can also be used. The flexible film is a thermoplastic resin film, which can be specifically exemplified as: 丨 edge: dimension 丨 structure: film: average mouth 0.1 ~ mm,: three times 丨 slit / min !. Also: Or one of the resins made of fluorine resin 'is selected from the group consisting of one source of -30- (24) (24) 200400811 or two or more selected from polyurethane resins' polyamine resin, polylactic acid resin, Films made of hydrocarbon resins, polyester resins, fluororesins, urea resins, phenol resins, epoxy resins, polyimide resins, silicone resins, acrylic resins, methacrylic resins, and derivatives thereof Preferably, it is one or two or more kinds of films selected from the group consisting of polyester resin, fluororesin, polyurethane resin, acrylic resin, vinyl chloride, fluororesin, and silicone resin. The thickness of such a sinterable film is 0.1 ~ 500 mm, and the jj is an endless belt material which is favorable for flexibility and physical strength, and is preferably 0.1 ~ 100 mm, more preferably 1 ~ 50 mm, particularly preferably 0.1 ~ 10 mm. As the flexible film, not only a solid film but also a porous film or a foamed film can be used. When laminated with a solid flexible film, it has high bacterial isolation, and an endless belt material that is favorable for infection management can be obtained. When the average pore diameter or apparent density is different from the porous three-dimensional network structure of the first layer as the second layer, the porous three-dimensional network structure can be used to make the average pore size of 0. A porous three-dimensional network structure with an apparent density of 0.1 to 1.0 g / cm 3 and a thickness of 1 to 2 0 0 μm. The thickness of the porous three-dimensional network structure layer in the second layer is preferably from 0 mm to 20 mm. The lamination method of the porous three-dimensional network structure layer of the second layer may include, for example, the second layer is a fiber assembly, a flexible film, an average caliber or an apparent density, and the porosity of the first layer. When the porous three-dimensional network structure layer with different three-dimensional network structure is bonded by an adhesive, especially a hot-melt non-woven fabric is laminated between the first layer and the second layer, and laminated under heating. method. As the hot-melt non-woven fabric, for example, a polyamine-type thermal adhesive sheet of P A 1 0 0 1 (25) (25) 200400811 manufactured by Nittobo Co., Ltd. can be used. Other methods include a method of bonding the surface layer portion of the contact surface with a solvent, a method of bonding the surface layer portion by thermal fusion, a method using an ultrasonic wave or a high frequency. In the production of the first layer, the 'polymer gel award' may be formed by laminating a fiber aggregate or a flexible film, etc., and may be formed by continuous lamination. The second layer can also be provided with two or more fiber aggregates, flexible films, porous secondary mesh structure layers, and also can interpose the second layer and laminate the porous three-dimensional network structure of the first layer. The layer has a three-layer structure. The porous three-dimensional network structure of the annulus material of the present invention holds one or two or more selected from the group consisting of type I collagen, type π collagen, type m collagen, type IV collagen, porridge type collagen, Fibronectin, Gelatin, Hyaluronic Acid, Heparin, Keratinic Acid, Chondroitin, Chondroitin Sulfate, Chondroitin Sulfate B, Elastin, Heparin Sulfate, Kunbuning's Coagulation Sponge Hard Protein, Vitronectin 'Osteonectin, Enactin, Meridian Copolymer of ethyl methylpropionate and dimethylaminoethyl methacrylate, copolymer of hydroxyethyl methacrylate and methacrylate, alginic acid, polyacrylamide, polymer Dimethylketamine and polyvinylpyrrolidone can be grouped, and one or two or more species can be selected from the group consisting of platelet-derived reproduction factor, epithelial reproduction factor, form-shifting reproduction factor α, and insulin-like reproduction factor. , Insulin-like reproduction factor binding protein, hepatocyte reproduction factor, vascular endothelial reproduction factor, angiogenin, nerve reproduction factor, brain-derived neurotrophic factor ' Factor Stone, Latent Form-Conversion Reproductive Factor / ?, Nandrolone Phenylpropionate, Bone Morphoprotein, Fibroblast Reproductive Factor, Tumor Reproductive Factor, Diploid Fibrous Reproductive Factor-32- (26) (26) 200400811 Heparin knot just epithelial reproduction factor-like reproduction factor, neurotumor-derived reproduction factor, amphoteric edge aspergillin, / 5 animal cellulose '7-methylguanine, lymphotoxin, cytokinin, tumor necrosis factor α, Interleukin-1 / 5, Interleukin-6 'Interleukin_8, Interleukin_i 7, Endomycin, antiviral agents, antibacterial agents, and groups of antibiotics are also available One or two or more kinds of cells selected from the group consisting of embryonic stem cells, vascular endothelial cells' mesoderm cells, smooth tendon cells, peripheral vascular cells, and mesothelial cells may be used. The endless belt material of the present invention may be provided with finer pores formed by the thermoplastic resin or the thermosetting resin constituting the porous three-dimensional network structure layer. These fine pores do not make the surface of the bone smooth but have complex uneven surfaces, and effectively retain collagen or cell proliferation factors. However, the fine pores' are not included in the calculation of the average pore diameter of the porous three-dimensional network structure layer in the present invention. The following is an example of a method for producing the porous three-dimensional network structure made of thermoplastic polyurethane which constitutes the endless belt material of the present invention. 'The method for producing the endless belt material of the present invention is not limited to the following method. When the porous three-dimensional network structure is produced from a thermoplastic polyurethane, the polyurethane resin is "first", a water-soluble polymer compound as a pore-forming agent described later, and a good polyurethane resin. The organic solvent of the solvent is mixed to make a polymer cement. Specifically, after the polyurethane resin is mixed with an organic solvent to form a homogeneous solution, the solution is mixed and dispersed with a water-soluble polymer compound. The organic solvent may be N, N-dimethylformamide, N-methyl-2-pulsolyl dione, tetrahydrofuran, etc., where soluble polyoxy-33-(27) (27) 200400811 carbamate The resin is not limited to this, and the polyurethane resin is melted by the action of heat with or without the use of an organic solvent, and a pore-forming agent may be mixed in this state. Examples of the water-soluble polymer compound of the pore-forming agent include polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, alginic acid, carboxymethyl cellulose, hydroxypropyl cellulose, and formazan. There are no particular restrictions on the base cellulose, ethyl cellulose, and the like that can be uniformly dispersed with a thermoplastic resin to form a dope. Depending on the type of the thermoplastic resin, a water-insoluble polymer compound such as a lipophilic compound such as terephthalate or liquid wax or an inorganic salt such as lithium chloride or calcium carbonate may be used. In addition, the use of a crystallization nucleating agent for a polymer generates secondary particles during solidification, that is, it promotes the formation of bones in porous materials. A polymer dope made of a thermoplastic polyurethane resin, an organic solvent, and a water-soluble polymer compound is immersed in a coagulation bath of a poor solvent containing a thermoplastic polyurethane resin, and dipped in the coagulation solution Extraction and removal of organic solvents and water-soluble polymer compounds. By removing a part or all of the organic solvent or the water-soluble polymer compound, a porous three-dimensional network structure made of a thermoplastic polyurethane resin can be obtained. Examples of the lean solvent used herein include water, lower alcohols, and low-carbon ketones. The cured thermoplastic polyurethane resin may be finally washed with water or the like to remove the remaining organic solvent or pore former. The implanted living material covering material of the present invention will be described in detail below. The implanted living material covering material of the present invention is made of a thermoplastic resin or a thermosetting resin, and the connected three-dimensional network structure has a flat pore diameter of -34- (28) (28) 200400811 with an average pore diameter of 100 ~ ΐ〇〇〇〇ΐΉ '' apparent density is o.oi ~ 0.5 g / cm 3 porous three-dimensional network structure part can be, the relevant thickness direction of the cut section, the entire structure has a similar structure, or one side The surface side may have a different structure from the other side. It is also possible that the average pore diameter or apparent density of the portion is changed. For example, the average pore diameter is gradually changed from the inner wall to the outer wall. In addition, it does not matter if there is a large diameter larger than the average pore diameter on the contact surface side with the living tissue. Such pores are preferably about 500 to 20 OOμη ，. When these pores are present in the surface layer of the living tissue side, they are easily and homogeneously impregnated into the deep part of the extracellular network of collagen and the like, and it is beneficial for tissues to invade cells or capillaries. Construction and so on. However, such a large caliber does not introduce the calculation idea of the average pore diameter of the so-called porous three-dimensional structure of the present invention. The average pore diameter of the porous three-dimensional structure is 100 to 100 μm, and the apparent density is 0.01 to 0.5 g / cm 3 ′. The ideal average pore diameter is 200 to 600 μηΐ, and more preferably 200 to 500 μπΐ. Apparent density ranges from 0.001 to 0.5 g / cm3, cell reproduction is good, maintains excellent physical strength, cell invasion, reproduction, and organization can obtain elastic characteristics similar to subcutaneous tissue, ideally 0.05 ~ 0.3 g / cm 3, more preferably 0.05 ~ 0.2 • 2 g / cm. The average pore diameter is the same and its related pore size distribution. The important pore size of the cell invasion is 150 ~ 400 μm. The higher the prevalence rate is, the better the prevalence rate is 150% to 400μηι. It is more than 20%, more preferably 30% or more, and even more preferably 40% or more. Especially when it is 50% or more, cells easily invade, and because the invaded cells are easy to join, -35- (29) 200400811 Grow to Ideal. The ratio of the average pore size of the porous three-dimensional network structure with a pore size of 400 μm refers to the average determination method according to the following Example 1. The pore size is 150 to 400 μm with respect to the total number of pores. Case. With such an average pore size, apparent density, and pore size of a multi-dimensional network structure, cells can easily penetrate the pores, and cells with porous traits can easily join and grow, building capillaries, and implanting parts into living materials. Can get tenacious healing. The porous three-dimensional network structure can be used with a thickness of 0, preferably 0.5 to 100 mm, more preferably 0.5 to 50 mrr, 0.5 to 10 mm, and especially 0.5 to 5 mm. The thermoplastic hardening resin that satisfies the necessary strength as a covering material for implanted living materials, the invasion and organization of cells, and the healing of living tissues that constitute the three-dimensional network structure part of the present invention, such as polyurethane resin, Polylactic acid resin, polyolefin resin, polyester resin, fluororesin resin, methacrylic resin, or one of these derivatives, or preferably a polyurethane resin, which is also polymerized in segments. Ester resins are suitable. Segmented polyurethane resins are synthesized from the three components of a polyhydric alcohol and a diisochain extender. They have the flexibility to use a block polymer structure with a segmented portion and a soft segmented portion in the molecule. The elasticity obtained when this section is polyurethane-reduced, the ratio of the number of holes measured from 150 to the diameter of the pores is 3 to 3, which is related to the three-dimensional three-dimensional network. The physical properties of those who want to care about this thickness are particularly important. Sex, etc. Resin or thermal amine resin, acrylic acid, 2 or more types of urethane cyanate, and so-called hard properties, which can be attenuated (30) (30) 200400811 Stress generated at the interface between living tissue and implanted living material. The implantable living material coating material 'of the present invention may be a layer formed of the above-mentioned specific porous three-dimensional network structure as the first layer, and a second layer laminate having a structure different from this first layer. The second layer may be a fiber assembly or a flexible film, and a porous three-dimensional network structure layer having a different average diameter or apparent density from the porous three-dimensional network structure of the first layer may be used. The porous three-dimensional network structure part of the implanted living material covering material of the present invention holds one or two or more types selected from the group consisting of type I collagen, type II collagen, type III collagen, type IV collagen, and porridge. Type collagen, fibronectin, gelatin, hyaluronic acid, heparin 'keratanic acid, chondroitin, chondroitin sulfate, chondroitin sulfate B, elastin, heparin sulfate, kumbutin, coagulation sponge hard protein, vitronectin, osteonectin, enteractin , Copolymers of methyethyl methacrylate and dimethylaminoethyl methacrylate, copolymers of hydroxyethyl methacrylate and methacrylate, alginic acid, polypropylene amine, Polydimethyleneamide and polyvinylpyrrolidone can also be grouped, and they can also maintain one or two or more selected from platelet-derived reproduction factors' epithelial reproduction factor, shape conversion reproduction factor α, and insulin-like reproduction. Factor, insulin-like reproduction factor binding protein, hepatocyte reproduction factor, vascular endothelial reproduction factor, angiogenin, nerve reproduction factor, brain-derived neurotrophic factor, hairy body neurotrophic factor , Morphogenetic reproductive factor / ?, latent morphogenic reproductive factor A, nandrolone phenylpropionate, osteomorphin, fibroblast proliferation factor, tumor growth factor point, diploid fibroblast reproduction factor, heparin knot correct epithelium Reproductive factor-like reproductive factor, angiogenin-derived reproductive factor 'amphizotoxin, Θ animal fiber-37- (31) (31) 200400811', 7-methylguanine, lymphotoxin, cytokinin , Tumor Necrosis Factor Alpha, Endoleukin-1, Endoleukin-6, Endoleukin-8, Endoleukin-1 7, Endomycin, Antiviral Agents, Antibacterial Agents, and Antibiotics It is also possible to 'join more than one type or two or more types of cells selected from embryonic stem and fine cells' vascular endothelial cells, mesodermal cells, smooth muscle cells, peripheral vascular cells, and mesothelial cells. Further, the implanted living material covering material of the present invention may be provided with finer holes made of a thermoplastic resin or a thermosetting resin constituting the porous three-dimensional network structure layer than the bone itself. These fine pores do not smooth the surface of the bones, but have complicated uneven surfaces, and effectively retain collagen or cell proliferation factors. However, these fine pores are not included in the calculation of the average pore diameter of the porous three-dimensional network structure layer in the present invention. An example of a method for producing the porous three-dimensional network structure made of a thermoplastic polyurethane constituting the endless belt material of the present invention is given below. 'The endless belt production method of the present invention is not limited to the following method. When the porous three-dimensional network structure is produced from a thermoplastic polyurethane, first of all, a polyurethane resin and water, which is a pore-forming agent described later, and a local molecular compound, and polyurethane A good solvent is mixed with an organic solvent to make a polymer cement. Specifically, after the polyurethane resin is mixed with an organic solvent to form a homogeneous solution, the solution is mixed and dispersed with a water-soluble polymer compound. The organic solvent may be Ν, Ν_dimethylformamide, N-methyl-2-pyrrolyl dione, tetrahydrofuran, etc. The ones which can dissolve the polythermate resin are not limited to this, and the weight reduction With or without an organic solvent, the polyurethane resin is melted by the action of heat, and the pore-forming agent can also be mixed in this state -38- (32) (32) 200400811. Examples of the water-soluble polymer compound of the pore-forming agent include polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, alginic acid, carboxymethyl cellulose, hydroxypropyl cellulose, and formazan. Base cellulose, ethyl cellulose, etc. are not particularly limited as long as they can be uniformly dispersed with a thermoplastic resin to form a dope. Depending on the type of the thermoplastic resin, water-insoluble high molecular compounds such as lipophilic compounds such as terephthalic acid I, liquid wax, and inorganic salts such as lithium chloride and calcium carbonate may also be used. In addition, the use of a crystal nucleating agent for a polymer is equivalent to the formation of secondary particles during solidification, that is, it can promote the formation of bones in porous materials. A polymer dope made of a thermoplastic polyurethane resin, an organic solvent, and a water-soluble polymer compound is immersed in a coagulation bath of a poor solvent containing a thermoplastic polyurethane resin, and dipped in the coagulation solution Extraction and removal of organic solvents and water-soluble polymer compounds. By removing some or all of the organic solvent or the water-soluble polymer compound, a porous three-dimensional network structure made of a thermoplastic polyurethane resin can be obtained. Examples of the lean solvent used herein include water, lower alcohols, and low-carbon ketones. The solidified thermoplastic polyurethane resin may be finally washed with water or the like to remove the remaining organic solvent-forming agent. As described in detail above, the implanted living material covering material according to the present invention can be easily invaded by living tissues and multiplied by the living organisms to obtain stubborn healing with living tissues. As a result, it is possible to prevent the implantation of living materials from living organisms Adverse effects on the living body. The following specifically explains the endless belt material of the present invention and the constituents of the living body material covering material on the surface of the present invention by using examples. Examples. [Example 4] Thermoplastic polyurethane resin (Miraku-torane E9 80 PNAT manufactured by MIRAKUTORANE, Japan) using N-methyl-2-pyrrolidinedione (a reagent for peptide synthesis produced by Kanto Chemical Co., Ltd.) (NMP) using a dissolver (about 2000 rpm) at room temperature to obtain a 5.0% (w / w) solution. Weigh about 1.0 kg of this NMP solution into a star mixer (2.0L capacity, PLM-2, manufactured by Japan Inoue Manufacturing Co., Ltd.), and use methyl cellulose equivalent to the weight of polyurethane resin (Kanto Chemical, Japan). The company's test reagent (25 cp grade) was mixed at 40 ° C for 40 minutes, and then stirring was continued for 10 minutes. The pressure was reduced to 20 mm Hg (2.7 kPa) to defoam to obtain a polymer cement. In addition, with a thickness of 3 mm, 150 mm X 150 mm, the outer frame of the four corners with a diameter of 140 mm X 140 mm punched out overlapped, and a 150 mm X 150 mm angle type chemical filter paper ( Japan Toyo Filter Paper, for quantitative analysis, No. 1). The polymer cement was cast and the glass glue was used to flatten the glue solution, and then it was loaded on a 150 mm X 150 mm angle type chemical filter paper (Japan Toyo Filter Paper, for quantitative analysis, No. 1). The methanol fed into the reflux state was further refluxed for 72 hours, and the NMP solvent on the upper and lower sides of the filter paper for chemical experiments was extracted and removed, and the polyurethane resin was solidified. At this time, the methanol is continuously replaced with a new liquid while the flow is continuously maintained. 7 After 2 hours, the solidified polyurethane tree was taken out from the Teflon frame. -40- (34) 200400811, said, ‘washed in the purified water of the Japanese Pharmacy for 72 hours, and the formazan and residual NMP were extracted and removed. It is provided at any time to decompress 20 mm Hg (2.7 kPa) at room temperature to dryness to a porous three-dimensional network structure made of thermoplastic resin. The second-dimensional network structure is the implanted living material of the present invention, followed by 1 4 0 mmx 1 4 0 mm polyester fiber reed | company, perforated blow • double • cotton wool • fiber, porous / min 'thickness 1.5 mm) impregnated with tetrahydrofuran (Japanese special test reagent)' rolled with two rolls The impregnation amount (g / cm2 'of the above-mentioned porous three-dimensional network structure material coating material) was overlapped, and the tape material was pressed at 1.0 leg / cm2. Figures 1 and 2 are scanning electron microscopes (photographs taken by TOPCON Corporation) of the implant material on the surface of the annulus material. The implant material on the surface of the obtained annulus material has a pore size of about 3 5. The porous three-dimensional structure of μ m is about 2.3 mm in thickness of the obtained ring-shaped material (ie, the implanted living material covering material). The average pore diameter and apparent density were measured. The results are shown in Table 1 The apparent density is measured by a cutting knife (High Stainless, manufactured by Feather Co., Ltd.) at the cell junction. [Measurement of the average pore diameter] The plane of the sample cut with a two-sided razor (the cut surface will be methyl cellulose new Washing water | 24 hours, obtained. Porous triple-covered material. &Quot; Fleece (BADO 3800 cc / cm2 Toka Chemical Co., 3.104 soil 0.002 (implanted living material into the ring living material coating of the present invention, SM200)) Living material coating> Reticulated structure. A porous three-dimensional net is shown in the following method. Moreover, it is performed using a double-sided shave I.) Using an electronic display -41-(35) 200400811 Microscope CTOPCON, SM200) Captured Images, each hole on the same plane is used for image processing as a pattern surrounded by a three-dimensional mesh structure of bones (the image processing device uses LUZEX AP manufactured by NILEC0 company, and the image acquisition CCD camera uses SONY LE N50 ) 'Measure the area of each figure. Use this as the area of a true circle and find the diameter of the corresponding circle as the pore diameter. Do not look at the fine pores of the perforation of the skeletal part of the porous material, only measure the connected holes on the same plane. The pore size distribution is shown in Fig. 3. From the measurement result of the pore size distribution, the aperture ratio of 150 to 400 μm is measured. [Measurement of Apparent Density] The second layer of the laminate produced in Example 4 The previous three-dimensional mesh structure was approximately 10 mm X 10 mm x 3 mm with a razor cut on both sides. This sample was measured by a projector (Nikon, V-12) to obtain the volume. Calculated by dividing the weight by the volume. Table 1 Average pore diameter (μ 111) Possibility rate (%) of pore diameter 15 0 ~ 4 0 0 μm Apparent density (g / cm3) Thickness (mm) As the first layer Porous three-dimensional_Net Structure Department 3 29 soil 160 66.2 0.1 17 ± 〇 1 1 8 2.3 -42- (36) (36) 200400811 From Table 1, it can be seen that the porous three-dimensional network structure part of the first layer is a porous three-dimensional network structure mainly composed of pores with effective cell junctions. [Example 5] An adult sheep was used as the specimen (female, weighing 54 kg), and the epidermis of the left chest and abdomen of the bristles was difficult to handle with one hand. The left position was examined, and the endotracheal intubation was performed quickly by ordinary methods. 'Maintain general anesthesia with isoflurane. After disinfecting the peripheral surface of the thorax and abdomen with ISOdine, the epidermis was cut 20 mm, and the test piece of the annulus material made in Example 4 was implanted in half and sutured subcutaneously and woven through and fixed (Fig. 4). The endless belt material is a test piece cut to a size of 0 mm × 10 mm, and the sterilizer is administered with ethylene oxide. After the operation, the sterilization site was sterilized twice a day with acidic water or Is 〇 (Π ne. The specimens were freely supplied with water 5 times a day (approximately 1 kg) and supplied with compressed feed. 2 weeks after the operation Under general anesthesia, the previously implanted test piece and surrounding tissues were removed. The test piece reproduced closely with the surrounding tissues and had difficulty peeling off each other. Also, no infection, inflammation, etc. were found around it. Figure 5a shows this. The reproduction part of the surface of the annulus material (that is, the implanted living material covering material) is enlarged with a magnifying glass. The indicator in the center of Figure 5a shows that the milky white layer of unknown level is connected to the inside of the annulus material. The transparent tissue inside the endless belt material is confirmed to be an infiltrated granulation tissue. Figure 5b does not use a woven fabric (polyester fiber linter used in Example 4 (BADO, perforated blow. Double. Lint • fiber) ) Monomer-43- (37) (37) 200400811 A photo enlarged with a magnifying glass when the same test was performed as described above. Wetting in the deep direction along the milky white layer on the surface of the woven fabric 'confirmed the so-called downward growth phenomenon. This, this The bright ring-shaped material 'the milky white layer continuously exists near the epidermis, and it is confirmed that the phenomenon of downward growth can be suppressed. After the above test, the extracted sample piece' was quickly fixed with 100% neutral buffered formalin, and HE staining was performed by a conventional method. The specimen was observed with an optical microscope. As a result, the porous three-dimensional network structure layer of the living material covering material implanted on the surface of the annulus material of the present invention was impregnated with linear dimension bud cells, macrophages, and collagen stretched from the surrounding tissue. The extracellular matrix, such as line dimension, is the main granulation tissue, and new blood vessels have been confirmed. In addition, the specimen obtained four weeks after the same method, a large number of granulation cells were stretched in the implanted test piece to identify the formation of mature binding tissue, and it was confirmed that From the above, from the above, the endless belt material of the present invention infiltrates the porous three-dimensional structural layer and organs by the cells, isolates the outside world from the wounded area, and instigates defense-related malignant cell-increasing factors. As detailed above, The cuff material according to the present invention can provide capillaries to be easily constructed by infiltrating and reproducing cells from subcutaneous tissue of a living body. As a result of the stubborn healing with the subcutaneous tissue, as a result, the wounded part is isolated from the outside, and the malignant factor of the cell infection related to the healing function is prevented, and the progress of the downward growth is inhibited. Such an annulus material of the present invention can be suitable for blood circulation methods of artificial heart assisted by cannula or catheter by subcutaneous infusion therapy, peritoneal dialysis (38) (38) 200400811 method, central vein nutrition method, Cannula DD s and transcatheter DDS are used for living skin insertions. [Brief Description of the Drawings] Figure 1 is an overall SEM image (20 times) of the tubular structure of the scar holding material manufactured in Example 1. Figure 2 This is a solid microscope image (100 times) of the fine structure inside the tubular structure of the scarring holding material manufactured in Example 1. Fig. 3 is a SEM image (20 times) of the inner wall surface layer of the tubular structure of the scar holding material manufactured in Example 1. Fig. 4 is a SEM image (20 times) of the outer surface layer of the tubular structure of the scar-gripping material manufactured in Example 1. Fig. 5 is an optical microscope image (10 times) of a three-day culture of a porous three-dimensional network structure containing cells produced in Example 2. Fig. 6 is an optical microscope image (10 times) showing the entire internal reproduction after additional culture in Example 2. Fig. 7 is a photograph of a scene in which blood flow is ensured by an artificial blood vessel in Embodiment 3; Fig. 8 is Example 3, and there is no picture showing thrombus formation inside the artificial blood vessel after one week of transplantation. ffl 9 is a SEM image (50 times) of the surface layer portion of the annular structure manufactured in Comparative Example 丨. Figure 〇 is a SEM image (50 times) of the microstructure inside the ring structure manufactured in Comparative Example 1. (39) 200400811 ® 1 1 is an optical microscope image (10 times) of a cell-containing tubular structural material manufactured in Comparative Example 2 after three days of culture. Fig. 12 is an SEM image (50 times) of the surface of the tissue contact side of the endless belt material produced in Example 4. FIG. 13 is a SEM image (50 times) of an internal cross section of the endless belt material manufactured in Example 4. FIG.

圖1 4係實施例4製造之環帶材料之測定孔徑分佈所 得之分佈圖。 圖1 5係貫施例4製造之環帶材料植入羊胸部切開部 位，縫合皮下組織貫通囿定手術終了當時之相片。 圖1 6 a係實施㈣4製造之環帶材料植入羊胸部切開部 位二週，摘出時的試驗炸墓細織七1 〜斤週邊過織之擴大相片，圖1 6係 爲比較之使用織布進行间# p & a ]fee S式驗時的試驗片週邊組織之擴 大相片之擴大相片。Fig. 14 is a distribution diagram obtained by measuring the pore diameter distribution of the endless belt material manufactured in Example 4. Fig. 15 is a photograph taken at the time of implantation of the cuff material manufactured in Example 4 into the incision site of the thorax of the sheep, and suture the subcutaneous tissue through the lumbar region. Fig. 16a is an enlarged photo of the lap 4 made of ㈣4 implanted into the incision site of the sheep's chest for two weeks, and the experimental fried grave fine weaving VII ~ 1 kg of overweaving was taken out. Fig. 16 is a comparison using woven cloth. Enlarged photographs of the surrounding tissues of the test strips during the # p & a] ee S test.

-46 --46-

Claims (1)

(1) (1)200400811 拾、申請專利範圍 1. 一種組織工學用瘢痕把持材料，其特徵爲熱可塑性 樹脂製之組織工學用瘢痕把持材料，該熱可塑性樹脂形成 之平均孔徑爲100〜650μηΐ，表觀密度爲0.01〜0.5 g / cm3之具連通性之多孔性三次元網狀構造者。 2. 如申請專利範圍第丨項之組織工學用瘢痕把持材料 ’其中該多孔性三次元網狀構造之平均孔徑1 〇〇〜400 μ m ，表觀密度爲0.01〜0.5 g / cm3者。 3 .如申請專利範圍第2項之組織工學用瘢痕把持材料 ，其中該多孔性三次元網狀構造之平均孔徑1 00〜3 00 μ 111 者。 4 .如申請專利範圍第1至第3項中任一項之組織工學 用瘢痕把持材料，其中該多孔性三次元網狀構造之表觀密 度爲 0.01 〜0.2 g / cm3 者。 5 .如申請專利範圍第4項之組織工學用瘢痕把持材料 ，其中該多孔性三次元網狀構造之表觀密度爲0.01〜0.1 g / cm3 者。 6. 如申請專利範圍第1至第5項中任一項之組織工學 用瘢痕把持材料，其中多孔性三次元網狀構造之平均孔徑 相關於孔徑〗5〇〜3 00 μηι之孔的之寄予率爲1〇 %以上者 〇 7. 如申請專利範圍第6項之組織工學用瘢痕把持材料 ，其中多孔性三次元網狀構造之平均孔徑相關於孔徑150 ~ 3 0 0 μ m之孔的寄予率爲2 0 %以上者。 (2) (2)200400811 8. 如申請專利範圍第7項之組織工學用瘢痕把持材料 ，其中多孔性三次元網狀構造之平均孔徑相關於孔徑150 〜3 Ο 0 μ m之孔的寄予率爲3 〇 %以上者。 9. 如申請專利範圍第8項之組織工學用瘢痕把持材料 ，其中多孔性三次元網狀構造之平均孔徑相關於孔徑150 〜3 00 μηι之孔的寄予率爲1 2 3 4〇%以上者。 1 〇.如申請專利範圍第9項之組織工學用瘢痕把持材 料，其中多孔性三次元網狀構造之平均孔徑相關於孔徑 1 50〜3 00 μηι之孔的寄予率爲50%以上者。 Π .如申請專利範圍第1至第1 0項中任一項之組織工 學用瘢痕把持材料，其中熱可塑性樹脂爲〗種或2種以上 選自聚氨基甲酸酯樹脂、聚醯胺樹脂、聚乳酸樹脂、聚烴 樹脂、聚酯樹脂、氟樹脂、丙烯酸樹脂及甲基丙烯酸樹脂 與由此等之衍生物所成群者。 1 2 .如申請專利範圍第π項之組織工學用瘢痕把持材 料’其中該熱可塑性樹脂爲聚氨基甲酸酯樹脂者。 1 3 .如申請專利範圍第〗2項之組織工學用瘢痕把持材 料’其中該氨基甲酸酯樹脂爲段節化聚氨基甲酸酯樹脂者 〇 -48- 1 4 .如申請專利範圍第1至第1 3項中任一項之組織工 學用瘢痕把持材料’其中該多孔性三次元網狀構造部保持 2 1種或2種以上選自第I型膠原、第π型膠原、第ΠΙ型 3 膨原、第IV型膠原、粥型膠原、纖維結合素、明膠、透 4 月質酸、肝素、角質素酸、軟骨素、軟骨素硫酸、軟骨素 (3) (3) 200400811 ^酸B '經基乙基甲基丙烯酸酯與二甲基乙基甲基丙烯酸 酉旨共聚物、羥基乙基甲基丙烯酸酯與甲基丙烯酸的共聚物 '澡It酸、聚丙烯酸醯胺、聚二甲基丙烯酸醯胺及聚乙烯 脒咯烷酮所成群者。 1 5 .如申請專利範圍第1 4項之組織工學用瘢痕把持材 料· ’其中該多孔性三次元網狀構造部更保持1種或2種以 上選自纖維芽細胞繁殖因子、內白細胞素_ i、腫瘍繁殖因 子'/5、上皮繁殖因子及二倍體纖維芽細胞繁殖因子所成群 有。 1 6 .如申請專利範圍第1 5項之組織工學用瘢痕把持材 料’其中該多孔性三次元網狀構造部接合著細胞者。 1 7 .如申請專利範圍第1 6項之組織工學用瘢痕把持材 料’其中該細胞爲1種或2種以上選自胚性幹細胞、血管 內皮細胞、中胚葉性細胞、平滑筋細胞、末梢血管細胞及 中皮細胞所成群者。 1 8 .如申請專利範圍第1 7項之組織工學用瘢痕把持材 料，其中該胚性幹細胞爲被分化者。 1 9 .如申請專利範圍第1至第1 8項中任一項之組織工 學用瘢痕把持材料，其中形狀爲管狀構造者。 2 〇 .如申請專利範圍第1 9項之組織工學用瘢痕把持材 料’其中該管狀構造物的內徑爲〇 . 3〜1 5 m ιώ，而外徑爲 0.4 〜20 mm 者。 2 1 .如申請專利範圍第20項之組織工學用瘢痕把持材 料，其中該管狀構造物的內徑爲〇. 3〜1 0 m m，而外徑爲 -49- (4) (4)200400811 Ο 4 〜1 5 m m 者。 2 2 .如申請專利範圍第2 1項之組織工學用瘢痕把持材 料’其中該管狀構造物的內徑爲0.3〜6 m m，而外徑爲 0.4 〜1 0 m m 者。 23. 如申請專利範圍第22項之組織工學用瘢痕把持材 料’其中該管狀構造物的內徑爲0.3〜2.5 mm，而外徑爲 0.4 〜10 mm 者。 24. 如申請專利範圍第23項之組織工學用瘢痕把持材 料’其中該管狀構造物的內徑爲〇.3〜15 mm，而外徑爲 0 4 〜1 0 m m 者0 2 5 . —種人造血管’其特徵爲由如申請專利範圍第〗〜 2 4項中任一項之瘢痕把持材料所成者。 2 6 .如申請專利範圍第2 5項之人造血管，其中該瘢痕 把持材料的外側更以別的管狀構造物被覆者。 2 7 .如申請專利範圍第2 6項之人造血管，其中該瘢痕 把持材料的外側被覆管狀構造物爲1種或2種以上選自殻 聚糖 '聚乳酸樹脂、聚酯樹脂 '聚醯胺樹脂、聚氨基甲酸 酯樹脂、纖維結合素、明膠、透明質酸、角質素酸、軟骨 素、軟骨素硫酸、軟骨素硫酸B、羥基乙基甲基丙烯酸酯 與二甲基乙基甲基丙烯酸酯共聚物、羥基乙基甲基丙烯酸 酯與甲基丙烯酸的共聚物、藻朊酸、聚丙烯酸醯胺、聚二 甲基丙烯酸醯胺及聚乙烯脒咯烷酮、交聯膠原及絲纖朊所 成群者所形成之軟管。 2 8 . —種環帶材料，其特徵爲由熱可塑性樹脂或熱硬 -50- (5) (5)200400811 化性樹脂所成之基材樹脂所形成，平均孔徑爲1〇〇、 ΙΟΟΟμηΐ，表觀密度爲〇.〇1〜0.5 g / cm3之具連通性之多 孔性三次元網狀構造部者。 29.如申請專利範圍第28項之環帶材料，其中該多孔 性二次兀網狀構造之平均Λ徑爲2 〇 〇〜6 〇 〇 μ m，表觀密度 爲 0.01 〜0.5 g / cm3 者。 3 0 .如申請專利範圍第2 9項之環帶材料，其中該多孔 性三次元網狀構造之平均孔徑爲200〜50 〇μηι，表觀密度 爲 0.01 〜0.5 g / cm3 者。 3 1.如申請專利範圍第28至30項中任―項之環帶材 料，其中表觀密度爲〇.〇5〜0.3 g/ cm3者。 3 2 .如申請專利範圍第3 1項之環帶材料，其中該多孔 性二次兀網狀構造之表觀密度爲0.0 5〜. 2 g / c m 3者。 3 3 .如申請專利範圍第2 8〜3 2項中任—項之環帶材料 ’其中該多孔性三次元網狀構造之平均孔徑相關於孔徑 1 5 0〜4 0 0 μ m之孔的寄予率爲1 0 %以上者。 3 4 .如申請專利範圍第3 3項之環帶材料，其中該多孔 性三次元網狀構造之平均孔徑相關於孔徑15〇〜40 〇 μ nl之 孔的寄予率爲20%以上者。 3 5 .如申請專利範圍第3 4項之環帶材料，其中該多孔 性三次元網狀構造之平均孔徑相關於孔徑丨50〜40〇μη1之 孔的寄予率爲30%以上者。 3 6 .如申請專利範圍第3 5項之環帶材料，其中該多孔 性三次元網狀構造之平均孔徑相關於孔徑丨5 〇〜4 〇〇μ m之 (6) 200400811 孔的寄予率爲40%以上者。 3 7 .如申請專利範圍第3 6項之環帶材料 性三次元網狀構造之平均孔徑相關於孔徑1 5 孔的寄予率爲5 0 %以上者。 3 8 .如申請專利範圍第2 8〜3 7項中任一 ’其中該多孔性三次元網狀構造之厚度爲（ 者。 3 9 .如申請專利範圍第3 8項之環帶材料 性三次元網狀構造之之厚度爲0.2〜1 0 0 mm 4〇.如申請專利範圍第39項之環帶材料 性三次元網狀構造之厚度爲〇 . 2〜5 0 m m者 4 1 .如申請專利範圍第40項之環帶材料 性三次元網狀構造之之厚度爲〇 . 2〜1 〇 mm : 4 2 .如申請專利範圍第4 1項之環帶材料 性三次元網狀構造之之厚度爲〇. 2〜5 mm者 4 3 .如申請專利範圍第2 8〜4 2項中任一 ’其中該基材樹脂爲1種或2種以上選自聚 脂、聚醯胺樹脂、聚乳酸樹脂 '聚烴樹脂、 樹脂、尿素樹脂、酚樹脂、環氧樹脂 '聚醯 烯酸樹脂、甲基丙烯酸樹脂與由此等之衍生 44.如申請專利範圍第43項之環帶材料 塑性樹脂爲聚氨基甲酸酯樹脂者。 4 5 .如申請專利範圍第4 4項之環帶材料 基甲酸酯樹脂爲段節化聚氨基甲酸酯樹脂者 ，其中該多孔 0 〜400μΐη 之 項之環帶材料 ).2 ~ 5 0 0 mm ，其中該多孔 者。 ，其中該多孔 〇 ，其中該多孔 萏。 ，其中該多孔 〇 項之環帶材料 氨基甲酸酯樹 聚酯樹脂、氟 亞胺樹脂、丙 物所成群者。 ，其中該熱可 ’其中該聚氨 -52- (7) (7)200400811 4 6 '如申請專利範圍第2 8〜4 5項中任一項之環帶材料 ’其中爲該多孔性三次元網狀構造所成之第1層，與不同 於第1層的第2層之層合物。 47'如申請專利範圍第46項之環帶材料，其中該第2 層爲1種或2種以選自纖維集合物 '可撓性薄膜、及與上 述第1層多孔性三次元網狀構造不同之平均孔徑及/或 表觀密度之多孔性三次元網狀構造層所成群者。 4 8 .如申請專利範圍第4 7項之環帶材料，其中該纖維 集合物爲不織布或織布者。 4 9 .如申請專利範圍第4 8項之環帶材料，其中不織布 或織布之厚度爲〜1〇〇 〇1„1者^ 5 0 .如申請專利範圍第4 9項之環帶材料，其中不織布 或織布之厚度爲0.1〜50 mm者。 5 1 .如申請專利範圍第5 0項之環帶材料，其中不織布 或織布之厚度爲0.1〜1〇.〇 mm者。 5 2.如申請專利範圍第5][項之環帶材料，其中不織布 或織布之厚度爲0.1〜5.0 mm者。 5 3 .如申請專利範圍第4 8〜5 2項中任一項之環帶材料 ’其中該不織布或織布之有孔性爲1〇〇〜50〇〇 cC / cm 2 / m i η 者。 5 4 .如申請專利範圍第4 6〜5 3項中任一項之環帶材料 ’其中該纖維集合物爲1種或2種以上選自聚氨基甲酸酯 樹脂、聚醯胺樹脂、聚乳酸樹脂、聚烴樹脂、聚酯樹脂' 氟樹脂 '丙烯酸樹脂 '甲基丙稀酸樹脂與由此等之衍生物 -53- (8) (8)200400811 所成群者所構成。 5 5.如申請專利範圍第Μ〜53項中任—項之環帶材料 ,其中該纖維集合物爲1種或2種以上選自絲纖朊、甲殻 素、殼聚糖及纖維素與由此等之衍生物所成群者。 5 6 如申請專利範圍第46〜5 5項中任一項之環帶材料 ，其中該可撓性薄膜爲熱可塑性樹脂薄膜者。 5 7 .如申請專利範圍第5 6項之環帶材料，其中該熱可 塑性樹脂爲1種或2種以上選自聚氨基甲酸酯樹脂、聚釀 胺樹脂、聚乳酸樹脂、聚烴樹脂、聚酯樹脂、氟樹脂、尿 素樹脂、酚樹脂、環氧樹脂 '聚醯亞胺樹脂、矽樹脂、丙 烯酸樹脂、甲基丙烯酸樹脂與由此等之衍生物所成群者。 5 8 .如申請專利範圍第5 7項之環帶材料，其中該熱可 塑性樹脂爲1種或2種以上選自聚氯乙烯樹脂、聚氨基甲 酸酯樹脂、氟樹脂、矽樹脂所成群者。 5 9.如申請專利範圍第4 6〜5 8項中任—項之環帶树料 ，其中可撓性薄膜之厚度爲0.1〜500 mm者。 60.如申請專利範圍第59項之環帶材料，其中可辕性 薄膜之厚度爲0.1〜100 mm者。 6 1 .如申請專利範圍第60項之環帶材料，其中可捧个生 薄膜之厚度爲0.1〜50 mm者。 6 2 .如申請專利範圍第6 1項之環帶材料，其中可辕个生 薄膜之厚度爲0.1 ~ 10mm者。 6 3.如申請專利範圍第46〜62項中任一項之環帶材料 ，其中該第2層多孔性三次元網狀構造層的平均孔徑爲 -54- (9) 200400811 0.1〜200μιτι，表觀密度爲〇.01〜i〇g/cm3者。 6 4 如申請專利範圍第4 6〜6 3項中任一項之環帶材料 ，其中第2層多孔性三次元網狀構造層的厚度爲〇. 2〜2 〇 m m者。 6 5 ·如申請專利範圍第2 8〜6 4項中任一項之環帶材料， 其中該多孔性三次元網狀構造部保持1種或2種以上選自 第Ϊ型膠原、第II型膠原、第ΙΠ型膠原、第〗、型膠原、 粥型膠原、纖維結合素、明膠、透明質酸、肝素、角質素 酸、軟骨素、軟骨素硫酸、軟骨素硫酸B、彈性素、肝素 硫酸、昆布寧、凝血海綿硬蛋白、vitronectin、 osteonectin ' entactin '羥基乙基甲基丙烯酸酯與二甲基 月女基乙基甲基丙烯酸酯的共聚物、經基乙基甲基丙嫌酸酯 與甲基丙烯酸酯的共聚物、藻朊酸、聚丙烯醯胺、聚二甲 基丙烯基醯胺及聚乙烯脒咯烷酮所成群者。 66.如申請專利範圍第65項之環帶材料，其中該多孔 丨生一;人兀網狀構造部更保持1種或2種以上選自血小板來 源繁殖因子、上皮繁殖因子、形質轉換繁殖因子α、胰島 素樣繁殖因子、胰島素樣繁殖因子結合蛋白、肝細胞繁殖 因子、血管內皮繁殖因子、血管生長素 '神經繁殖因子、 月a來源神經營養因子、毛樣體神經營養因子、形質轉換繁 殖因子/5、潛在型形質轉換繁殖因子万、苯丙酸諾龍、骨 形質蛋白、纖維芽細胞繁殖因子、腫瘍繁殖因子万、二倍 體纖維芽繁殖因子、肝素結合性上皮繁殖因子樣繁殖因子、 神經腫瘤來源繁殖因子、兩性邊條曲菌素 ' 万動物纖維素 -55- 287? (10) (10)200400811 、7 -甲基鳥嚷哈、淋巴毒素、細細胞生成素、腫瘍壞死 因子α 、內白細胞素、內白細胞素-6、內白細胞素_8、 內白細胞素-1 7、內黴蛋白、抗病毒劑、抗菌劑、及抗生 物所成群者。 6 7 .如申請專利範圍第6 6項之環帶材料，其中該多孔 三次元網狀構造部接合著細胞者。 6 8 .如申請專利範圍弟6 7項之ϊ哀帶材料，其中該細胞 爲1種或2種以上選自胚性幹細胞、血管內皮細胞、中胚 葉性細胞、平滑筋細胞、末梢血管細胞及中皮細胞所成群 者。 6 9 .如申請專利範圍第6 8項之環帶材料，其中該胚性 幹細胞爲被分化者。 7 〇. —種植入活體材料被覆材料，其特徵爲由熱可塑 性樹脂或熱硬化性樹脂而成之基材所形成，平均孔徑爲 100〜ΙΟΟΟμίη，表觀密度爲0.01〜0.5 g/cm3之具有連 通性多孔三次元網狀構造部者。 7 1 .如申請專利範圍第7 0項之植入活體材料被覆材料 ，其中該多孔性三次元網狀構造之平均孔徑爲200〜600μ m ’表觀密度爲0.01〜〇.5g/cm3 者。 72.如申請專利範圍第7 1項之植入活體材料被覆材料 ’其中該多孔性三次元網狀構造之平均孔徑爲200〜500 μηι ’表觀密度爲0.01〜0.5 g / cm3者。 7 3 .如申請專利範圍第7 0至7 2項中任一項之植入活 體材料被覆材料，其中表觀密度爲〇.〇5〜0.3 g / cm3者 -56 - (11) (11)200400811 7 4 .如申請專利範圍第7 3項之植入活體材料被覆材料 ’其中该多孔性三次元網狀構造之表觀密度爲0.0 5〜0.2 g / c m3 者。 7 5 .如申a靑專利範圍第7 〇至7 4項中任一項之植入 、活II材' f斗被覆材料，其中該多孔性三次元網狀構造之平均 孔徑相關於孔徑丨5 〇〜4〇〇 μ m之孔的寄予率爲〗以上者 〇 7 6 .如申請專利範圍第7 5項之植入活體材料被覆材料 ，其中該多孔性三次元網狀構造之平均孔徑相關於孔徑 150〜400μηΐ之孔的寄予率爲2〇%以上者。 7 7 .如申請專利範圍第7 6項之植入活體材料被覆材料 ，其中該多孔性三次元網狀構造之平均孔徑相關於孔徑 1 5 0 ~ 4 0 0 μ m之孔的寄予率爲3 0 %以上者。 78.如申請專利範圍第77項之植入活體材料被覆材料 ，其中該多孔性三次元網狀構造之平均孔徑相關於孔徑 1 5 0〜4 0 0 μ ill之孔的寄予率爲4 0 %以上者。 7 9 .如申請專利範圍第7 8項之植入活體材料被覆材料 ，其中該多孔性三次元網狀構造之平均孔徑相關於孔徑 150~40(^111之孔的寄予率爲50%以上者。 8〇.如申請專利範圍第70至 79項中任一項之植入 活體材料被覆材料’其中該多孔性三次元網狀構造之厚度 爲 0.5 ~ 5 00 mm 者。 8 1 .如申請專利範圍第80項之植入活體材料被覆材料 -57- (12) (12)200400811 ’其中該多孔性三次元網狀構造之之厚度爲〇. 5〜100 mm 者。 8 2 .如申請專利範圍第8 1項之植入活體材料被覆材料 ，其中該多孔性三次元網狀構造之之厚度爲〇 . 5〜5 〇 m m 者。 83. 如申請專利範圍第82項之植入活體材料被覆材料 ’其中該多孔性三次元網狀構造之之厚度爲0.5〜1 〇 m m 者。 84. 如申請專利範圍第83項之植入活體材料被覆材料 ’其中該多孔性三次元網狀構造之之厚度爲0.5〜5 mm 者。 8 5 .如申請專利範圍第7 〇至 8 4項中任一項之植入 活體材料被覆材料，其中該基材樹脂爲1種或2種以上選 自聚氨基甲酸酯樹脂、聚醯胺樹脂、聚乳酸樹脂、聚烴樹 脂、聚酯樹脂、氟樹脂、尿素樹脂、酚樹脂、環氧樹脂' 聚醯亞胺樹脂、丙烯酸樹脂、甲基丙烯酸樹脂與由此等之 衍生物所成群者。 8 6 .如申請專利範圍第8 5項之植入活體材料被覆材料 ，其中該熱可塑性樹脂爲聚氨基甲酸酯樹脂者。 8 7 .如申請專利範圍第8 6項之植入活體材料被覆材料 ，其中該聚氨基甲酸酯樹脂爲段節化聚氨基甲酸酯樹脂者 〇 8 8 .如申請專利範圍第7 〇項至第8 7項中任一項之植 入活體材料被覆材料，其中由爲該多孔性三次元網狀構造 (13) (13)200400811 所成之第1層’與不同於第1層的第2層之層合物。 8 9 .如申請專利範圍第7 0項至第8 8項中任一項之植 入活體材料之被覆材料，其中係該多孔性三次元網狀構造 部保持1種或2種以上選自第I型膠原、第II型膠原、 第III型膠原、第IV型膠原 '粥型膠原、纖維結合素、 明膠、透明質酸、肝素、角質素酸、軟骨素、軟骨素硫酸、 軟骨素硫酸B、彈性素、肝素硫酸、昆布寧、凝血海綿硬 蛋白、vitronectin、osteonectin、entactin、經基乙基甲基 丙烯酸酯與二甲基胺基乙基甲基丙烯酸酯的共聚物、羥基 乙基甲基丙烯酸酯與甲基丙烯酸酯的共聚物、藻朊酸、聚 丙烯基醯胺、聚二甲基丙烯基醯胺及聚乙烯脒咯烷酮所成 群者。 90.如申請專利範圍第89項之植入活體材料之被覆材 料’其中該多孔性三次元網狀構造部更保持1種或2種以 上選自血小板來源繁殖因子、上皮繁殖因子、形質轉換繁 殖因子a、胰島素樣繁殖因子、胰島素樣繁殖因子結合蛋 白、肝細胞繁殖因子、血管內皮繁殖因子、血管生長素、 神經繁殖因子、腦來源神經營養因子、毛樣體神經營養因 子、形質轉換繁殖因子万、潛在型形質轉換繁殖因子泠、 本丙酸s若龍、骨形質蛋白、纖維芽細胞繁殖因子、腫瘍繁 口子沒一倍體纖維芽繁殖因子、肝素結恰性上皮繁殖 因子樣繁殖因子、神經腫瘤來源繁殖因子、兩性邊條曲菌 素点動物纖維素、7 -甲基烏嘌呤、淋巴毒素、細細胞 生成素、腫瘍壞死因子〇 、內白細胞素、內白細胞 -59- (14) (14)200400811 素-6、內白細胞素-8、內白細胞素-1 7、內黴蛋白、抗病 毒劑、抗菌劑、及抗生物所成群者。 9 1 .如申請專利範圍第9〇項之植入活體材料之被覆材 料，其中該多孔三次元網狀構造部結合著細胞者。 9 2 .如申請專利範圍第9 1項之植入活體材料之被覆材 _ 料，其中該細胞爲】種或2種以上選自胚性幹細胞、血管 內皮細胞、中胚葉性細胞、平滑筋細胞、末梢血管細胞及 中皮細胞所成群者。 籲 9 3 .如申請專利範圍第9 2項之植入活體材料之被覆材 料，其中該胚性幹細胞爲被分化者。 -60-(1) (1) 200400811 Scope of application and patent application 1. A scar holding material for tissue engineering, characterized by a thermoplastic resin scar holding material, the average diameter of which is formed by the thermoplastic resin is 100 ~ 650 μηΐ, an interconnected porous three-dimensional network structure with an apparent density of 0.01 to 0.5 g / cm3. 2. For the tissue engineering scar holding material according to item 丨 of the application, the average pore diameter of the porous three-dimensional network structure is 100-400 μm and the apparent density is 0.01-0.5 g / cm3. 3. The tissue engineering scar holding material according to item 2 of the patent application, wherein the porous three-dimensional network structure has an average pore diameter of 100 to 3 00 μ 111. 4. The scar-holding material for tissue engineering according to any one of claims 1 to 3, wherein the apparent density of the porous three-dimensional network structure is 0.01 to 0.2 g / cm3. 5. The scar holding material for tissue engineering according to item 4 of the patent application, wherein the apparent density of the porous three-dimensional network structure is 0.01 to 0.1 g / cm3. 6. The scar holding material for tissue engineering according to any one of the claims 1 to 5, wherein the average pore diameter of the porous three-dimensional network structure is related to the pore diameter of 50 to 3 00 μηι. The deposit rate is 10% or more. 7. For the tissue engineering scar holding material such as the scope of patent application No. 6, the average pore diameter of the porous three-dimensional network structure is related to the pores with a pore diameter of 150 to 300 μm. The deposit rate is above 20%. (2) (2) 200400811 8. If the tissue engineering scar holding material of item 7 of the patent application scope, the average pore diameter of the porous three-dimensional network structure is related to the pores with a pore diameter of 150 ~ 3 0 0 μm Those with a rate of more than 30%. 9. For the tissue engineering scar holding material such as the item No. 8 of the application, the average pore diameter of the porous three-dimensional network structure is related to the pore diameter of 150 ~ 3 00 μηι, and the deposit rate is 1 2 3 40% or more. By. 10. The scar holding material for tissue engineering according to item 9 of the scope of the patent application, in which the average pore diameter of the porous three-dimensional network structure is related to the deposit rate of pores with a pore size of 150 to 300 μm, and the rate is more than 50%. Π. The tissue engineering scar holding material according to any one of claims 1 to 10, wherein the thermoplastic resin is one or more than two kinds selected from polyurethane resin and polyamide resin , Polylactic acid resin, polyhydrocarbon resin, polyester resin, fluororesin, acrylic resin and methacrylic resin, and a group of derivatives thereof. 1 2. The tissue engineering scar holding material according to item π of the patent application, wherein the thermoplastic resin is a polyurethane resin. 1 3. If the tissue engineering scar holding material according to item 2 of the scope of the patent application, 'wherein the urethane resin is a segmented polyurethane resin, 0-48-14. The tissue engineering scar holding material according to any one of items 1 to 13, wherein the porous three-dimensional network structure portion holds 21 or more selected from the group consisting of type I collagen, type π collagen, and Type III III Ploogen, Type IV Collagen, Porcine Collagen, Fibronectin, Gelatin, Trans-April Acid, Heparin, Keratin Acid, Chondroitin, Chondroitin Sulfate, Chondroitin (3) (3) 200400811 ^ Acid B 'copolymer of methyl ethyl methacrylate and dimethyl ethyl methacrylic acid, copolymer of hydroxy ethyl methacrylate and methacrylic acid' Groups of ammonium dimethacrylate and polyvinylpyrrolidone. 1 5. According to the tissue engineering scar holding material according to item 14 of the scope of the patent application, 'wherein the porous three-dimensional network structure part further retains one or more than one selected from the group consisting of fibroblast reproduction factor and endoleukin. _ i. Tumor reproduction factor '/ 5, epithelial reproduction factor and diploid fibroblast proliferation factor. 16. A tissue holding scar material according to item 15 of the scope of the patent application, wherein the porous three-dimensional network structure is connected to the cell. 17. If the tissue engineering scar holding material according to item 16 of the scope of the application for patent, wherein the cell is one or more than one selected from embryonic stem cells, vascular endothelial cells, mesodermal cells, smooth muscle cells, and peripherals Groups of vascular cells and mesothelial cells. 18. The tissue engineering scar holding material according to item 17 of the patent application scope, wherein the embryonic stem cells are differentiated. 19. The tissue engineering scar holding material according to any one of claims 1 to 18 in the scope of patent application, wherein the shape is a tubular structure. 20. For the tissue engineering scar holding material of item 19 in the scope of the application for patent, wherein the inner diameter of the tubular structure is 0.3 to 15 m, and the outer diameter is 0.4 to 20 mm. 2 1. The tissue engineering scar holding material as claimed in item 20 of the patent application scope, wherein the inner diameter of the tubular structure is 0.3 to 10 mm and the outer diameter is -49- (4) (4) 200400811 Ο 4 to 15 mm. 2 2. The tissue engineering scar holding material according to item 21 of the patent application, wherein the tubular structure has an inner diameter of 0.3 to 6 mm and an outer diameter of 0.4 to 10 mm. 23. For example, the tissue engineering scar holding material of item 22 of the application, wherein the tubular structure has an inner diameter of 0.3 to 2.5 mm and an outer diameter of 0.4 to 10 mm. 24. For the tissue engineering scar holding material according to item 23 of the patent application, where the inner diameter of the tubular structure is 0.3 to 15 mm and the outer diameter is 0 4 to 10 mm, 0 2 5. — This type of artificial blood vessel is characterized in that it is made of a scar-holding material as described in any one of the scope of the patent application Nos. 26. The artificial blood vessel according to item 25 of the scope of patent application, wherein the outer side of the scar holding material is covered with another tubular structure. 27. The artificial blood vessel according to item 26 of the patent application scope, wherein the outer covering tubular structure of the scar holding material is one or more than one selected from chitosan 'polylactic acid resin, polyester resin' polyamine Resin, polyurethane resin, fibronectin, gelatin, hyaluronic acid, keratin acid, chondroitin, chondroitin sulfate, chondroitin sulfate B, hydroxyethyl methacrylate and dimethylethylmethyl Acrylate copolymer, copolymer of hydroxyethyl methacrylate and methacrylic acid, alginic acid, polyacrylamide, polyammonium dimethacrylate and polyvinylpyrrolidone, cross-linked collagen and silk fiber软管 hoses formed by groups. 2 8. An endless belt material, which is characterized in that it is formed of a base resin made of thermoplastic resin or thermosetting-50- (5) (5) 200400811 chemical resin, with an average pore diameter of 100, 100 μηΐ, Those with an apparent density of 0.01 to 0.5 g / cm3 and a porous three-dimensional network structure with connectivity. 29. The belt material according to item 28 of the scope of patent application, wherein the average secondary diameter of the porous secondary network structure is 2000-600 μm, and the apparent density is 0.01-0.5 g / cm3 . 30. The annular material according to item 29 of the patent application, wherein the porous three-dimensional network structure has an average pore diameter of 200 to 50 μm and an apparent density of 0.01 to 0.5 g / cm3. 3 1. The belt material in any one of items 28 to 30 of the scope of patent application, wherein the apparent density is 0.05 ~ 0.3 g / cm3. 32. The belt material according to item 31 of the scope of patent application, wherein the apparent density of the porous secondary network structure is 0.0 5 ~. 2 g / c m 3. 3 3. As in any of the scope of application for patent No. 2 8 ~ 3 2-the ring material of the item 'where the average pore diameter of the porous three-dimensional network structure is related to the pores with a pore diameter of 1 50 ~ 4 0 0 μm The deposit rate is above 10%. 34. The annulus material according to item 33 of the scope of patent application, wherein the average pore diameter of the porous three-dimensional network structure is related to the deposit rate of pores with a pore size of 15-40 μnl, which is more than 20%. 35. The annulus material according to item 34 of the scope of the patent application, wherein the average pore diameter of the porous three-dimensional network structure is related to the deposit rate of pores with a pore size of 50 to 40 μη1 or more. 36. The belt material according to item 35 of the scope of patent application, wherein the average pore diameter of the porous three-dimensional network structure is related to the pore diameter. (6) 200400811 Pore rate of pores 40% or more. 37. If the average pore diameter of the three-dimensional network structure of the material of the annulus of item 36 in the scope of patent application is related to the deposit rate of 15 holes, the deposit rate is 50% or more. 38. If the thickness of the porous three-dimensional network structure is any one of items 2-8 to 37 in the scope of patent application, the thickness of the porous three-dimensional network structure is (or.). The thickness of the elementary mesh structure is 0.2 ~ 100 mm 4 0. If the thickness of the material three-dimensional mesh structure of the endless belt of item 39 of the patent application is 0.2 to 5 0 mm 4 1. The thickness of the material three-dimensional network structure of the annular zone in the scope of the patent item is 0.2 to 10 mm: 42. For example, the material of the three-dimensional network structure of the annular zone material in the scope of patent application No. 41 A thickness of 0.2 to 5 mm is 4 3. As in any one of 2 to 8 to 2 of the scope of patent application, wherein the substrate resin is one or more than one selected from the group consisting of polyester, polyamide resin, and polymer Lactic resin 'Polyhydrocarbon resin, resin, urea resin, phenol resin, epoxy resin' polypinenoic acid resin, methacrylic resin and derivatives derived therefrom 44. For example, the plastic material of the belt material in the 43rd patent application range Those who are polyurethane resins. 4 5. For example, the belt material based on the scope of patent application No. 4 4 is based on the polyurethane resin. Those of the urethane resin, wherein the porous material of the endless belt of Paragraph 0 ~400μΐη) .2 ~ 5 0 0 mm, wherein the porous person. , Where the porous 〇, where the porous 萏. Among them, the porous ○ ring material is a group of urethane tree polyester resin, fluoroimide resin, and propylene. Where the heat may be 'wherein the polyurethane-52- (7) (7) 200400811 4 6' as the belt material of any one of the scope of patent application No. 2 8 ~ 4 5 'where is the porous three-dimensional The layered structure of the first layer formed by the network structure and the second layer different from the first layer. 47 'The belt material according to item 46 of the patent application scope, wherein the second layer is one or two selected from a fiber assembly' flexible film 'and a porous three-dimensional network structure with the first layer Groups of porous three-dimensional network structures with different average pore sizes and / or apparent densities. 48. The belt material according to item 47 of the patent application scope, wherein the fiber assembly is a non-woven fabric or a woven fabric. 49. If the belt material of item 48 in the scope of the patent application, the thickness of the non-woven fabric or woven fabric is ~ 100001 „1 ^ 5 0. If the belt material of the area 49 in the patent application, Among them, the thickness of the non-woven fabric or woven fabric is 0.1 to 50 mm. 5 1. As for the belt material of the 50th scope of the patent application, the thickness of the non-woven fabric or woven fabric is 0.1 to 10.0 mm. 5 2. For example, the belt material in item 5 of the scope of application [in which the thickness of the non-woven fabric or woven fabric is 0.1 to 5.0 mm. 5 3. The belt material in any one of areas 4 to 8 of the scope of patent application 'Where the non-woven fabric or woven fabric has a porosity of 100 to 50 00 cC / cm 2 / mi η. 5 4. The belt material according to any one of the scope of patent application No. 4 6 to 5 3 'Wherein the fiber assembly is one or two or more kinds selected from polyurethane resin, polyamide resin, polylactic acid resin, polyhydrocarbon resin, polyester resin' fluoro resin 'acrylic resin' methyl acrylic acid Resin and its derivatives -53- (8) (8) 200400811 Group of people. 5 5. If any one of the scope of the patent application scope M ~ 53 An endless belt material, in which the fiber assembly is one or two or more selected from the group consisting of silk fibroin, chitin, chitosan, cellulose and derivatives thereof. 5 6 46 ~ 5 The endless belt material of any one of 5 items, wherein the flexible film is a thermoplastic resin film. 5 7. The endless belt material according to item 56 of the patent application scope, wherein the thermoplastic resin is 1 One or two or more kinds selected from polyurethane resin, polyamine resin, polylactic acid resin, polyhydrocarbon resin, polyester resin, fluororesin, urea resin, phenol resin, epoxy resin, polyimide resin, Groups of silicone resins, acrylic resins, methacrylic resins, and derivatives thereof. 5 8. The belt material according to item 57 of the patent application scope, in which the thermoplastic resin is one or more than one. It is selected from the group consisting of polyvinyl chloride resin, polyurethane resin, fluororesin, and silicone resin. 5 9. According to any of the items in the scope of application for patents No. 4 6 ~ 5 8-the cirrus tree material, among which The thickness of the flexible film is 0.1 ~ 500 mm. 60. Such as the scope of patent application No. 59 For the belt material, the thickness of the flexible film is 0.1 to 100 mm. 6 1. For the belt material of the patent application No. 60, the thickness of the raw film can be 0.1 to 50 mm. 6 2. If the belt material of item 61 of the scope of patent application, among which the thickness of the raw film can be 0.1 to 10mm. 6 3. If the belt material of any of the scope of patent application, 46 to 62, The average pore diameter of the second porous three-dimensional network structure layer is -54- (9) 200400811 0.1 to 200 μm, and the apparent density is 0.01 to 10 g / cm3. 6 4 As claimed in any of the scope of patent applications No. 4 to 6 of the ring material, wherein the thickness of the second layer of the three-dimensional porous network structure layer is 0.2 ~ 2 0 mm. 6 5 · The annulus material according to any one of claims 2 8 to 64, wherein the porous three-dimensional network structure portion maintains one or more types selected from type VII collagen and type II Collagen, collagen type I, collagen type I, collagen type, atheroma type collagen, fibronectin, gelatin, hyaluronic acid, heparin, keratin acid, chondroitin, chondroitin sulfate, chondroitin sulfate B, elastin, heparin sulfate , Cumunin, coagulation spongidin, vitronectin, osteonectin 'entactin' hydroxyethyl methacrylate and copolymer of dimethyl ethyl methacrylate ethyl methacrylate, Copolymers of methacrylic acid esters, alginic acid, polypropylene amidamine, polydimethylacrylamide, and polyvinylpyrrolidone. 66. The belt material according to item 65 of the patent application scope, wherein the porous structure generates one or more human reticular structures and one or two or more selected from platelet-derived reproduction factors, epithelial reproduction factors, and morphogenetic conversion reproduction factors. α, insulin-like reproduction factor, insulin-like reproduction factor binding protein, hepatocyte reproduction factor, vascular endothelial reproduction factor, angiogenin 'nerve reproduction factor, month-derived neurotrophic factor, hairy body neurotrophic factor, shape-shifting reproduction factor / 5, Potential morphomorphic transformation factor 10,000, Nandrolone phenylpropionate, bone morphogen protein, fibroblast proliferation factor, tumor growth factor 10,000, diploid fibroblast reproduction factor, heparin-binding epithelial reproduction factor-like reproduction factor, Neurotumor-derived reproductive factor, amphibian amphotericin '10,000 animal cellulose-55- 287? (10) (10) 200400811, 7-methyl ornithine, lymphotoxin, cytokinin, tumor necrosis factor alpha , Endoleukin, endoleukin-6, endoleukin_8, endoleukin-1 7, endomycin, antiviral agent, antibacterial agent, and anti Crowds of living things. 67. The belt material according to item 6 of the patent application, wherein the porous three-dimensional network structure is connected with cells. 6.8. According to the sorrowful band material of item 67 in the scope of the patent application, the cell is one or more than one selected from embryonic stem cells, vascular endothelial cells, mesodermal cells, smooth muscle cells, peripheral vascular cells, and Groups of mesothelial cells. 69. The ring material according to item 68 of the patent application scope, wherein the embryonic stem cells are differentiated. 7 〇. — Living material coating material implanted, characterized by a substrate made of thermoplastic resin or thermosetting resin, with an average pore diameter of 100 ~ ΙΟΟΟμίη and an apparent density of 0.01 ~ 0.5 g / cm3. Those with connected porous three-dimensional network structure. 71. The implanted living material covering material according to item 70 of the application for a patent, wherein the average pore diameter of the porous three-dimensional network structure is 200 to 600 μm, and the apparent density is 0.01 to 0.5 g / cm3. 72. The implanted living material covering material according to item 71 of the application for patent, wherein the average pore diameter of the porous three-dimensional network structure is 200 ~ 500 μηι, and the apparent density is 0.01 ~ 0.5 g / cm3. 7 3. The implanted living material covering material according to any one of the scope of patent application Nos. 70 to 72, wherein the apparent density is from 0.05 to 0.3 g / cm3 -56-(11) (11) 200400811 7 4. If the implanted living material covering material of item 73 of the patent application 'is one in which the apparent density of the porous three-dimensional network structure is 0.0 5 ~ 0.2 g / c m3. 75. The implanted, live II material 'f bucket coating material according to any one of claims 70 to 74 in the patent scope, wherein the average pore diameter of the porous three-dimensional network structure is related to the pore diameter. 5 The deposit rate of pores of 〇 ～ 400μm is more than the above. 〇 7 6. If the implanted living material covering material in the scope of patent application No. 75, the average pore diameter of the porous three-dimensional network structure is related to The deposit rate of pores with a pore diameter of 150 to 400 μηΐ is more than 20%. 7 7. The implanted living material covering material according to item 76 of the patent application scope, wherein the average pore diameter of the porous three-dimensional network structure is related to the deposit rate of pores with a pore diameter of 150 to 400 μm, which is 3 Above 0%. 78. The covering material for implanted living materials according to item 77 of the application, wherein the average pore diameter of the porous three-dimensional network structure is related to the pore size of 150% ~ 4 0 0 μ ill. The deposit rate is 40%. The above. 79. The implanted living material covering material according to item 78 of the scope of patent application, wherein the average pore diameter of the porous three-dimensional network structure is related to the pore diameter of 150 to 40 (^ 111, and the deposit rate is more than 50%) 80. If the implanted living material covering material according to any one of claims 70 to 79 is applied, wherein the thickness of the porous three-dimensional network structure is 0.5 to 5000 mm. 8 1. If a patent is applied Implanted living material covering material in the range of item 80-57- (12) (12) 200400811 'Where the thickness of the porous three-dimensional network structure is 0.5 to 100 mm. 8 2. If the scope of patent application The implanted living material covering material according to item 81, wherein the thickness of the porous three-dimensional network structure is 0.5 to 50 mm. 83. The implanted living material covering material according to item 82 of the patent application scope 'Where the thickness of the porous three-dimensional network structure is 0.5 to 10 mm. 84. The implanted living material covering material such as the scope of application for the patent No. 83' where the thickness of the porous three-dimensional network structure Those with a thickness of 0.5 to 5 mm. 8 5. If applying for a patent The implanted living material covering material according to any one of the items 70 to 84, wherein the base resin is one or more than one selected from the group consisting of a polyurethane resin, a polyamide resin, a polylactic acid resin, Polyhydrocarbon resins, polyester resins, fluororesins, urea resins, phenol resins, epoxy resins, polyimide resins, acrylic resins, methacrylic resins, and their derivatives. 8 6. The living body material covering material for which the scope of the patent application is No. 85, wherein the thermoplastic resin is a polyurethane resin. 8 7. The living body material covering material for which the patent scope of the application is No. 86, where the Polyurethane resin is a segmented polyurethane resin 088. For example, the application of any one of the scope of 70 to 87 of the patent application for the implanted living material coating material, wherein Porous three-dimensional network structure (13) (13) 200400811 Laminated layer 1 'and a second layer different from the first layer. 8 9. Such as the scope of the patent application No. 70 to 8 The covering material for implanting living material according to any one of 8 items, wherein The porous three-dimensional network structure holds one or two or more selected from the group consisting of type I collagen, type II collagen, type III collagen, type IV collagen 'porridge collagen, fibronectin, gelatin, hyaluronic acid , Heparin, keratin acid, chondroitin, chondroitin sulfate, chondroitin sulfate B, elastin, heparin sulfate, cumunin, coagulation sponge hard protein, vitronectin, osteonectin, entactin, transethyl ethyl methacrylate and dimethyl Copolymer of aminoamino ethyl methacrylate, copolymer of hydroxyethyl methacrylate and methacrylate, alginic acid, polyacrylamide, polydimethylacrylamide and polyethylene A group of rolrolidone. 90. The covering material for implanting a living material according to the scope of the patent application No. 89, wherein the porous three-dimensional network structure portion maintains one or two or more selected from the group consisting of platelet-derived reproduction factor, epithelial reproduction factor, and shape conversion reproduction. Factor a, insulin-like reproduction factor, insulin-like reproduction factor binding protein, hepatocyte reproduction factor, vascular endothelial growth factor, angiogenin, nerve reproduction factor, brain-derived neurotrophic factor, hairy body neurotrophic factor, shape-shifting reproduction factor Potential morphogenesis-transforming reproduction factors, benzoic acid sauron, osteoprotein, fibroblast reproduction factor, ulcerative fibroblast reproduction factor, heparin-knotted epithelial reproduction factor-like reproduction factor, Neurotumor-derived reproduction factor, amphoteric edge aspergillin point animal cellulose, 7-methyl uridine, lymphotoxin, cytokinin, tumor necrosis factor 0, endoleukin, endoleukin-59- (14) ( 14) 200400811 -6, interleukin-8, interleukin-1 7, endomycin, antiviral agent, antibacterial agent, The hordes who antibiotic. 91. The covering material for implanting a living material according to item 90 of the patent application scope, wherein the porous three-dimensional network structure is combined with cells. 9 2. The covering material for implanting living material according to item 91 of the scope of patent application, wherein the cell is one or more than two kinds selected from embryonic stem cells, vascular endothelial cells, mesodermal cells, and smooth muscle cells Groups of peripheral vascular cells and mesothelial cells. Call 93. For example, the covering material for implanting living material in item 92 of the patent application scope, wherein the embryonic stem cells are differentiated. -60-
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