JP5529918B2 - 人工真皮 - Google Patents
人工真皮 Download PDFInfo
- Publication number
- JP5529918B2 JP5529918B2 JP2012107526A JP2012107526A JP5529918B2 JP 5529918 B2 JP5529918 B2 JP 5529918B2 JP 2012107526 A JP2012107526 A JP 2012107526A JP 2012107526 A JP2012107526 A JP 2012107526A JP 5529918 B2 JP5529918 B2 JP 5529918B2
- Authority
- JP
- Japan
- Prior art keywords
- plasma
- gel
- cells
- skin
- artificial
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0697—Artificial constructs associating cells of different lineages, e.g. tissue equivalents
- C12N5/0698—Skin equivalents
-
- 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
- A61L27/60—Materials for use in artificial skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/10—Hair or skin implants
- A61F2/105—Skin implants, e.g. artificial skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/33—Fibroblasts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/36—Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Cell Biology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Immunology (AREA)
- Developmental Biology & Embryology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Materials For Medical Uses (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Description
動物起源のコラーゲンI型、これは真皮中に存在するタンパク質のうち最も豊富にあるから用いられる(マラグチT等のPlast. Reconstr. Surg, 93:537〜544(1994)、ムハルツ等のArch Dermatol, 135:913〜918(1999))。
(イ) 原料は入手するのが容易である。血漿は通常キレート化してあるカルシウムの存在下に、血管の穿刺により抽出したヒトの全血から生成される。全血から血漿を得るのに遠心法のみが必要とされる。ヒトの血漿はまたアフェレーシス法を用いて全血から得られる。
1) 同類の線維芽細胞。包茎手術で得られた包皮から培養するか及び/又は健康な成人からの真皮の線維芽細胞から培養される。患者又は患者の法定代理人はそれらの同意を与えねばならない。
一方では、線維芽細胞を培地又は0.9%塩化ナトリウム溶液に再懸濁する。或る容量の血漿をこの溶液に添加し、続いて抗フィブリノーゲン分解剤を添加する。この溶液が用意された時、2通りの異なる仕方で凝血させる:
i) 0.9%塩化ナトリウムに溶かした1%塩化カルシウム溶液を添加する。
培地である0.9%の塩化ナトリウム溶液とヒトの線維芽細胞(3)(30,000個と250,000個との間の細胞)とを基本的に含有する溶液を調製した。必要ならば、抗−フィブリノーゲン分解剤(10,000Uのアプロチニン、5〜20mgのトランキサム酸又は200〜300mgのイプシロン−アミノカプロン酸)を添加し、最後に2〜4IUのトロンビンを前もって溶解させておいた1mlの0.04M CaCl2溶液を添加した。これらの諸成分を混合した時、フィブリノーゲン濃度に応じて3〜6mlの血小板入り血漿(2)を添加した。用いた血漿の量に応じて、多少の塩化ナトリウムを用いて最終容量を15mlに仕上げた。該溶液を培養皿中に迅速に装入し、皿の表面上に均質に分布した。凝血が生起し、ゲルが重合されるまで培養皿を37℃でCO2の炉中に放置した。
培地である0.9%塩化ナトリウム溶液とヒトの線維芽細胞(3)(30,000個と250,000個との間の細胞)とを基本的に含有する溶液を調製した。必要ならば、抗−フィブリノーゲン分解剤(10,000Uのアプロチニン、5〜20mgのトランキサム酸又は200〜800mgのイプシロン−アミノカプロン酸)を添加し、最後に0.9%塩化ナトリウムに溶解した1%CaCl2溶液の1mlを添加した。これらの成分を混合した後に、血小板入りの血漿(2)を添加した。用いた血漿の量に応じて多少とも塩化ナトリウムで最終容量を15mlに仕上げた。該溶液を培養皿に迅速に装入し、皿の表面上に均質に分布させた。凝血が生起しゲルが重合されるまで37℃でCO2の炉中に培養皿を放置した。この方法を用いると、ゲルはきわめて徐々に重合する。
最後の培地を取出し、培養皿を開放する。ゲルを無菌ガーゼ(ワセリン被覆した又は被覆されていない)で被覆し、こうしてガーゼはゲル表面全体を正確に被覆する。メスを用いて培養皿からゲルの側面を分離する。この操法が完了したからには、無機接着剤(シアノアクリレート、ヒストアクリル(商標名)、ブラウム又は同様な特性の別の接着剤)の使用によりゲルの上表面(角化細胞である場合には側面)にガーゼを固定する。シアノアクリレートはゲルの端縁に数滴施用して用いるものであり、別の数滴の接着剤はゲル中央に施用できる。接着剤が乾燥したからには、スパチラを用いて培養皿からゲルを分離する。ガーゼは真皮基材と培養した角化細胞の上層とを含有するゲルを一体に維持するのに役立つ。この原型はその保全性を失うことなく又は破断することなく16時間以上運搬し得る。
2 自己の血小板入り血漿
3 線維芽細胞
4 全血
5 皮膚の生検
6 角化細胞
7 人工皮膚
8 患者
9 人工皮膚のシート
Claims (5)
- 凝血したヒトの血漿と、血小板と、培養した線維芽細胞とのゲルを包含してなる人工真皮。
- 線維芽細胞は相同性の線維芽細胞又は自家線維芽細胞である請求項1記載の人工真皮。
- 角化細胞を更に含有してなる請求項1又は2記載の人工真皮。
- 請求項3記載の人工真皮が層状化した上皮を更に包含してなる、人工皮膚。
- 層状化した上皮細胞の上部と、線維芽細胞を密に分布した細胞外(extracellular)基質よりなる下部とを含有してなる請求項4記載の人工皮膚。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ESP200100494 | 2001-03-01 | ||
ES200100494A ES2173812B1 (es) | 2001-03-01 | 2001-03-01 | Dermis artificial y metodo de obtencion. |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008118300A Division JP5047047B2 (ja) | 2001-03-01 | 2008-04-30 | 人工真皮 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012187412A JP2012187412A (ja) | 2012-10-04 |
JP5529918B2 true JP5529918B2 (ja) | 2014-06-25 |
Family
ID=8496947
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2002571856A Expired - Fee Related JP4235452B2 (ja) | 2001-03-01 | 2002-02-28 | 人工真皮及びその製造方法 |
JP2008118300A Expired - Fee Related JP5047047B2 (ja) | 2001-03-01 | 2008-04-30 | 人工真皮 |
JP2012107526A Expired - Fee Related JP5529918B2 (ja) | 2001-03-01 | 2012-05-09 | 人工真皮 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2002571856A Expired - Fee Related JP4235452B2 (ja) | 2001-03-01 | 2002-02-28 | 人工真皮及びその製造方法 |
JP2008118300A Expired - Fee Related JP5047047B2 (ja) | 2001-03-01 | 2008-04-30 | 人工真皮 |
Country Status (14)
Country | Link |
---|---|
US (3) | US7244552B2 (ja) |
EP (2) | EP2165678A1 (ja) |
JP (3) | JP4235452B2 (ja) |
AR (1) | AR032916A1 (ja) |
AT (1) | ATE448295T1 (ja) |
AU (1) | AU2002235958B2 (ja) |
CA (1) | CA2439387C (ja) |
DE (1) | DE60234323D1 (ja) |
DK (1) | DK1375647T3 (ja) |
EG (1) | EG23321A (ja) |
ES (2) | ES2173812B1 (ja) |
PT (1) | PT1375647E (ja) |
TW (1) | TWI258506B (ja) |
WO (1) | WO2002072800A1 (ja) |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7144729B2 (en) | 2000-09-01 | 2006-12-05 | Dfb Pharmaceuticals, Inc. | Methods and compositions for tissue regeneration |
ES2173812B1 (es) * | 2001-03-01 | 2003-12-16 | Ct Investig Energeticas Ciemat | Dermis artificial y metodo de obtencion. |
JP2004075661A (ja) * | 2002-06-18 | 2004-03-11 | Shiseido Co Ltd | 表皮基底膜ケアを特徴とする皮膚外用剤、皮膚基底膜構造形成促進剤および人工皮膚の製造方法 |
GB0224986D0 (en) | 2002-10-28 | 2002-12-04 | Smith & Nephew | Apparatus |
US11298453B2 (en) | 2003-10-28 | 2022-04-12 | Smith & Nephew Plc | Apparatus and method for wound cleansing with actives |
US8765169B2 (en) * | 2004-02-13 | 2014-07-01 | Smith & Nephew, Inc. | Wound healing profile |
WO2005084223A2 (en) * | 2004-02-27 | 2005-09-15 | The General Hospital Corporation | Methods and compositions for hair growth |
US7753894B2 (en) | 2004-04-27 | 2010-07-13 | Smith & Nephew Plc | Wound cleansing apparatus with stress |
GB0505202D0 (en) | 2005-03-14 | 2005-04-20 | Intercytex Ltd | Skin equivalent culture |
ES2263382B1 (es) * | 2005-05-16 | 2007-11-16 | Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Marañon | Matriz artificial de gel de fibrina endotelizada superproductora de factores proangiogenicos. |
EP1885280A1 (en) | 2005-05-26 | 2008-02-13 | Intercytex Limited | Tissue repair using allogenic dermal fibroblasts |
CA2644525A1 (en) * | 2006-03-03 | 2007-09-07 | Ciemat | A mouse model comprising an engrafted human skin having hypersensitivity to uv-light |
US8709081B2 (en) | 2006-10-23 | 2014-04-29 | Stemedica Cell Technologies, Inc. | Cellular scaffold |
US8105380B2 (en) * | 2006-10-23 | 2012-01-31 | Stemedica Cell Technologies, Inc. | Cellular scaffold |
US20100303770A1 (en) * | 2006-12-28 | 2010-12-02 | John Maslowski | Methods for culturing dermal cells for treatment of skin injuries such as burns |
JP5253749B2 (ja) * | 2007-03-19 | 2013-07-31 | 肇 井上 | 表皮シートの作製方法および初代培養時における培養容器への上皮幹細胞の接着性付与方法 |
WO2009051701A2 (en) * | 2007-10-15 | 2009-04-23 | Wake Forest University Health Sciences | Methods and compositions for printing biologically compatible nanotube composites of autologous tissue |
CA2716752A1 (en) * | 2008-02-29 | 2009-09-03 | Showa University | Method for producing artificial skin |
CN102341130B (zh) | 2009-01-27 | 2017-11-10 | 雷德德莱斯有限公司 | 创伤敷料、用于制造创伤敷料的方法和设备以及其储存和用途 |
PT2471902T (pt) * | 2009-08-25 | 2018-08-02 | Univ Granada | Produção de tecidos artificiais por meio da engenharia de tecidos utilizando biomateriais de agarose-fibrina |
JP5737860B2 (ja) * | 2010-04-30 | 2015-06-17 | テルモ株式会社 | ゲル状細胞組成物およびその製造方法 |
CL2011001870A1 (es) * | 2011-08-03 | 2012-01-27 | U Tecnica Federico Santa Maria 28 71% | Proceso de preparacion de un gel de fibrina autologo o desde sangre compatible para proliferacion y vehiculizacion celular; gel de fibrina o de sangre compatible; uso del gel de fibrina o de sangre compatible para uso quirurgico. |
TWI448310B (zh) * | 2012-05-23 | 2014-08-11 | Medical dressings and their coating methods for frozen freeze - dried platelets | |
TWI448312B (zh) * | 2012-05-23 | 2014-08-11 | An implant of freeze - dried platelets and its coating method | |
GB201303485D0 (en) | 2013-02-27 | 2013-04-10 | Alcyomics Ltd | Skin model |
MX342233B (es) * | 2014-02-04 | 2016-08-24 | Alvaro Galue Eduardo | Proceso de obtencion de un compuesto de aspersion celular de fibroblastos y queratinocitos humanos en solucion y su uso como agente regenerativo de lesiones cutáneas. |
ES2551143B1 (es) * | 2014-05-13 | 2016-07-01 | Fundación Tekniker | Dermis artificial, piel artificial, métodos para su preparación y sus usos |
CN105505855A (zh) * | 2016-02-04 | 2016-04-20 | 关志广 | 一种具备增殖能力的自体表皮细胞apg凝胶的制作方法 |
CN109789245B (zh) * | 2016-05-31 | 2022-10-18 | 瑞士奥克特珐玛公司 | 基于血浆的膜及其制造和使用方法 |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
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US4485096A (en) * | 1982-02-26 | 1984-11-27 | Massachusetts Institute Of Technology | Tissue-equivalent and method for preparation thereof |
JPS6379588A (ja) * | 1986-09-25 | 1988-04-09 | Yasuo Moriya | 細胞培養用基材およびその製造方法 |
DK475386D0 (da) * | 1986-10-03 | 1986-10-03 | Weis Fogh Ulla Sivertsen | Fremgangsmaade og apparat til fremstilling af biologiske stoffer |
FR2639958B1 (fr) * | 1988-12-06 | 1992-08-21 | Lille Transfusion Sanguine | Support biologique pour cultures cellulaires constitue de proteines plasmatiques coagulees par la thrombine, son utilisation pour la culture des keratinocytes, leur recuperation et leur transport a des fins d'utilisation therapeutique |
ES2194013T3 (es) * | 1992-05-29 | 2003-11-16 | Univ North Carolina | Plaquetas de sangre humana de secado fijo farmaceuticamente aceptables. |
JP3091113B2 (ja) * | 1994-11-22 | 2000-09-25 | 科学技術振興事業団 | 生理活性物質分泌性のハイブリッド型ゲル |
US5733545A (en) * | 1995-03-03 | 1998-03-31 | Quantic Biomedical Partners | Platelet glue wound sealant |
WO1997001533A1 (fr) | 1995-06-27 | 1997-01-16 | The Green Cross Corporation | Derives d'acide thiocarbamique |
WO2000062828A1 (en) * | 1996-04-30 | 2000-10-26 | Medtronic, Inc. | Autologous fibrin sealant and method for making the same |
ES2117573B1 (es) * | 1996-07-19 | 1999-02-16 | Comunitario De Transfusion Del | Base dermica especialmente diseñada para el cultivo de queratinocitos. |
JP3333108B2 (ja) * | 1997-04-08 | 2002-10-07 | 学校法人東海大学 | 上皮性組織移植片およびその製造方法 |
ES2132027B1 (es) * | 1997-07-04 | 2000-04-01 | Comunitario De Transfusion Del | Desarrollo de una piel artificial mediante cultivo de queratinocitos sobre una base de fibrina y fibroblastos humanos y metodo de preparacion de esta piel para trasplante. |
JPH11239609A (ja) * | 1998-02-26 | 1999-09-07 | Sekisui Chem Co Ltd | 血小板含有生体組織用接着剤 |
JPH11246420A (ja) * | 1998-02-26 | 1999-09-14 | Sekisui Chem Co Ltd | 創傷治癒促進剤 |
ES2173812B1 (es) * | 2001-03-01 | 2003-12-16 | Ct Investig Energeticas Ciemat | Dermis artificial y metodo de obtencion. |
ES2184623B1 (es) * | 2001-06-29 | 2004-09-16 | Centro De Investigaciones Energeticas, Medioambientales Y Tecnologicas (C.I.E.M.A.T.) | Piel artificial autologa secretora de leptina y metodo de obtencion. |
AU2002343738A1 (en) * | 2001-11-15 | 2003-05-26 | University Of Medicine And Dentistry Of New Jersey | A three-dimensional matrix for producing living tissue equivalents |
US20040126881A1 (en) * | 2002-09-06 | 2004-07-01 | Vincent Ronfard | Fibrin cell supports and methods of use thereof |
-
2001
- 2001-03-01 ES ES200100494A patent/ES2173812B1/es not_active Expired - Fee Related
-
2002
- 2002-02-27 TW TW091103519A patent/TWI258506B/zh not_active IP Right Cessation
- 2002-02-28 JP JP2002571856A patent/JP4235452B2/ja not_active Expired - Fee Related
- 2002-02-28 AR ARP020100722A patent/AR032916A1/es not_active Application Discontinuation
- 2002-02-28 WO PCT/ES2002/000087 patent/WO2002072800A1/es active IP Right Grant
- 2002-02-28 DK DK02702424.9T patent/DK1375647T3/da active
- 2002-02-28 AU AU2002235958A patent/AU2002235958B2/en not_active Ceased
- 2002-02-28 EP EP09014041A patent/EP2165678A1/en not_active Withdrawn
- 2002-02-28 ES ES02702424T patent/ES2336430T3/es not_active Expired - Lifetime
- 2002-02-28 EP EP02702424A patent/EP1375647B1/en not_active Expired - Lifetime
- 2002-02-28 CA CA2439387A patent/CA2439387C/en not_active Expired - Fee Related
- 2002-02-28 US US10/469,554 patent/US7244552B2/en not_active Expired - Fee Related
- 2002-02-28 AT AT02702424T patent/ATE448295T1/de active
- 2002-02-28 PT PT02702424T patent/PT1375647E/pt unknown
- 2002-02-28 DE DE60234323T patent/DE60234323D1/de not_active Expired - Lifetime
- 2002-03-02 EG EG20020229A patent/EG23321A/xx active
-
2007
- 2007-05-31 US US11/809,665 patent/US20070275461A1/en not_active Abandoned
-
2008
- 2008-04-30 JP JP2008118300A patent/JP5047047B2/ja not_active Expired - Fee Related
-
2012
- 2012-02-07 US US13/367,548 patent/US9168125B2/en not_active Expired - Fee Related
- 2012-05-09 JP JP2012107526A patent/JP5529918B2/ja not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
AU2002235958B2 (en) | 2007-05-10 |
JP2008253788A (ja) | 2008-10-23 |
US9168125B2 (en) | 2015-10-27 |
ES2173812A1 (es) | 2002-10-16 |
JP2012187412A (ja) | 2012-10-04 |
JP5047047B2 (ja) | 2012-10-10 |
PT1375647E (pt) | 2010-02-18 |
DE60234323D1 (de) | 2009-12-24 |
DK1375647T3 (da) | 2010-03-15 |
EP1375647B1 (en) | 2009-11-11 |
US20040171145A1 (en) | 2004-09-02 |
US7244552B2 (en) | 2007-07-17 |
ES2173812B1 (es) | 2003-12-16 |
EP1375647A1 (en) | 2004-01-02 |
TWI258506B (en) | 2006-07-21 |
ES2336430T3 (es) | 2010-04-13 |
CA2439387C (en) | 2012-04-24 |
US20120183505A1 (en) | 2012-07-19 |
AR032916A1 (es) | 2003-12-03 |
ATE448295T1 (de) | 2009-11-15 |
US20070275461A1 (en) | 2007-11-29 |
JP4235452B2 (ja) | 2009-03-11 |
JP2004522545A (ja) | 2004-07-29 |
CA2439387A1 (en) | 2002-09-19 |
EG23321A (en) | 2004-12-29 |
WO2002072800A1 (es) | 2002-09-19 |
EP2165678A1 (en) | 2010-03-24 |
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