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WO2006001778A1 - Formation de tissus de peau humains par genie biologique, utilisant des hpd comme biomateriels - Google Patents

Formation de tissus de peau humains par genie biologique, utilisant des hpd comme biomateriels Download PDF

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Publication number
WO2006001778A1
WO2006001778A1 PCT/SG2005/000208 SG2005000208W WO2006001778A1 WO 2006001778 A1 WO2006001778 A1 WO 2006001778A1 SG 2005000208 W SG2005000208 W SG 2005000208W WO 2006001778 A1 WO2006001778 A1 WO 2006001778A1
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WO
WIPO (PCT)
Prior art keywords
hpd
skin
keratinocytes
fibroblast
tissue engineered
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.)
Ceased
Application number
PCT/SG2005/000208
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English (en)
Inventor
Bt Haji Idrus Ruszymah
B Saim Aminuddin
Abdul Latif Mazlyzam
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
UNIVERSITI KEBANGSAAN MALAYSIA
PINTAS Pte Ltd
Original Assignee
UNIVERSITI KEBANGSAAN MALAYSIA
PINTAS Pte Ltd
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Filing date
Publication date
Application filed by UNIVERSITI KEBANGSAAN MALAYSIA, PINTAS Pte Ltd filed Critical UNIVERSITI KEBANGSAAN MALAYSIA
Publication of WO2006001778A1 publication Critical patent/WO2006001778A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—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
    • 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
    • A61L27/36—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
    • A61L27/3813—Epithelial cells, e.g. keratinocytes, urothelial 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
    • A61L27/36—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
    • A61L27/3886—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 comprising two or more cell types
    • A61L27/3891—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 comprising two or more cell types as distinct cell layers
    • 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
    • A61L27/3895—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 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
    • 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
    • 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
    • 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
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/05—Inorganic components
    • C12N2500/10—Metals; Metal chelators
    • C12N2500/12—Light metals, i.e. alkali, alkaline earth, Be, Al, Mg
    • C12N2500/14—Calcium; Ca chelators; Calcitonin
    • 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
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/70—Undefined extracts
    • C12N2500/80—Undefined extracts from animals
    • C12N2500/84—Undefined extracts from animals from mammals
    • 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
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/09—Coculture with; Conditioned medium produced by epidermal cells, skin cells, oral mucosa cells
    • C12N2502/094—Coculture with; Conditioned medium produced by epidermal cells, skin cells, oral mucosa cells keratinocytes
    • 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
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
    • C12N2502/1323—Adult fibroblasts

Definitions

  • the present invention relates to a method for producing tissue engineered skin, more specifically it relates to a method for producing autologous bilayer tissue engineered skin to be used for skin grafting and cell therapy for various kinds of tissue reconstruction or regenerative medicine.
  • a tissue engineered skin is constructed from a part of a skin structure by in vitro culture of keratinocytes and dermal fibroblasts collected from a piece of healthy skin. It is also called an autologous tissue engineered skin using cells collected from a piece of patient's own healthy skin.
  • the tissue engineered skin can be applied in medical treatments for severe burns, diabetic ulcers, bedsores, treatment of scars, for reconstructive surgery, and so on.
  • the tissue engineered skin is not only effective in simply covering a wounded surface but are also effective in secreting or supplying growth factors or the like required for wound healing.
  • the tissue engineered skin also involves in the reduction of fluid loss, prevention of infections, and reduction of the area for potential scarring.
  • Skin is the largest organ in human body. It has four major function - protection, sensation, thermoregulation and metabolic functions. As mentioned earlier, there are two layers of tissue on the skin, namely the epidermis and dermis.
  • Epidermis layer consists of proliferating keratinocytes cells that will differentiate as they grow outwards to become stratum corneum that later will die and provide the keratin layer at the surface of the skin.
  • the dermis layer mainly consists of fibroblasts cells that secrete various macromolecules including collagen, elastin and fibronectin; main component of extracellular matrix that will provide strength to skin.
  • epithelium cells of the tissues provided as origins of the above cells are those in which cell differentiation and aging have progressed, so that their cell division lifetime may be short and their capacity for differential plasticity may be small.
  • epithelium cells of the tissues provided as origins of the above cells are those in which cell differentiation and aging have progressed, so that their cell division lifetime may be short and their capacity for differential plasticity may be small.
  • problems in the art For instance, there are variations in the collections of cell populations, instability of healthy tissues, dimensions of tissues, and so on. Ethical problems are caused in offering of an extra normal tissue obtained at the time of surgical operation, and so on.
  • biomaterials in skin graft formation are very important in providing the 3 -dimensional structure for the growth of keratinocytes and fibroblasts.
  • Many biomaterials have been used such as bovine collagen type I (Dong YL et al, 2000), hyaluronic acid (Harris et al, 1999), collagen-GAG (Michael et al, 2001) and fibrin glue matrix (Vincent et al, 2000).
  • the objective of the present invention is to provide a cultured reconstructive skin or a tissue engineered skin which cure the aforementioned disadvantage or weaknesses of the prior mentioned cultured skin techniques.
  • One of the object of the present invention is to provide a technique of producing autologous bilayer tissue engineered human skin.
  • Another object of the present invention is to produce autologous human bilayer tissue engineered skin by using human keratinocytes and dermal fibroblasts cultured from a small sample of skin by mixing it with Human Plasma Derivatives (HPD).
  • HPD Human Plasma Derivatives
  • keratinocytes Prior to culture the mentioned skin, skin is obtained from consented patient or any other sources in a sufficient quantity. Consequently, the above-mentioned keratinocytes is isolated from the epidermis layer of the human skin which produces keratinocytes. Later or parallelly, the fibroblast is cultured from the dermis layer of the human skin in order to arrive into a fibroblast monolayer. Consequently, sufficient quantity of human plasma is extracted from human blood to form a Human Plasma Derivatives (HPD). Hence, sufficient number of keratinocytes and fibroblast cultured is mixed with Human Plasma Derivatives (HPD) mentioned to form an autologous bilayer tissue engineered human skin. Tissue engineered skin is very useful in the treatment of burn patient, chronic diabetic ulcer, pressure ulcers e.g.: bedsores, skin disorders, in reconstructive and transplantation surgery and for plastic surgery or any other similar usages.
  • HPD Human Plasma Derivatives
  • a tissue engineered skin is invented through the technique of producing autologous bilayer tissue engineered human skin using human keratinocytes and dermal fibroblasts cultured from a small sample of skin by mixing it with Human Plasma Derivatives (HPD).
  • HPD Human Plasma Derivatives
  • Autologous bilayer tissue engineered human skin is developed by using cultured human keratinocytes and human dermal fibroblasts mixed with human plasma as biomaterials and are ready for clinical application.
  • the autologous bilayer tissue engineered skin construct is similar to native human skin as shown by microscopic analysis.
  • tissue engineered skin according to the present invention is very useful in treatment of irreversible tissue especially for the burn patient, chronic diabetic ulcer, pressure ulcers e.g.: bedsores, skin disorders, in reconstructive and transplantation surgery, plastic surgery and the similar.
  • Example 1 Procedure 1 Separation of the epidermis and dermis layer of the skin. Skin was obtained from consented patient as excessive tissue from surgery. Skin was placed into Defined Keratinocyte - SFM (Gibco/BRL, USA). Skin was rinsed in 70% isopropanol before it was placed into a rinse buffer solution of DPBS (Gibco/BRL, USA) for approximately 1 hour. Skin was cut into small pieces at a size of approximately 0.5 to 2.0 cm 2 and transferred with dermis side down into a 25.0-30.0 caseinolytic units per mL solution of dispase (Sigma- Aldrich Co. ,USA) dissolved in Defined Keratinocyte - SFM and incubated at 2 to 8°C for 18 to 24 hours for epidermal and dermal layer separation.
  • the epidermal layer of human keratinocytes is separated from the dermis using fine forceps.
  • Example 2 Procedure 2 Isolation of keratinocvtes from the epidermis. Epidermal layer was incubated in 0.05 % Trypsin - 0.53mM EDTA (Gibco/BRL, USA) at 37°C for 5-10 minutes. 10 mg/ml of soybean trypsin inhibitor (Gibco/BRL, USA) dissolved in DPBS and sterile filtered was added to stop the trypsin activity. The cell suspension was then centrifuged at 7000 rpm for 5 minutes.
  • Cell pellet was resuspended in 10 ml complete medium and basal keratinocytes were counted using hemacytometer (Weber Scientific International Limited, England) and trypan blue vital dye (Gibco/BRL, USA).
  • Cells were plated in 6 well plate culture dishes (Becton Dickinson, USA) at the density of 4 x 10 5 cell per well in Defined Keratinocyte - SFM medium. Cells were cultured at 37°C in 5% CO 2 (Jouan, France) with medium changed every 2 to 3 days. The keratinocytes monolayer culture was subcultured when the culture reaches 60% to 70% confluence.
  • Example 3 Procedure 3 Isolation of dermal fibroblast from the dermis.
  • Dermis layer was digested with 0.6% collagenase type I enzyme (Gibco/BRL, USA) for 12 to 18 hours in the incubator-shaker.
  • the cell suspension was centrifuged at 6000 rpm for 5 minutes and the resulting pellet was washed with DPBS buffer.
  • Cells were counted using hemacytometer (Weber Scientific International Limited, England) and trypan blue vital dye (Gibco/BRL, USA).
  • Cells were plated in 6 well plate culture dishes (Becton Dickinson, USA) at the density of IxIO 5 cell per well in Ham's F 12: DMEM (1: 1) + 10% HS.
  • Cells were cultured at 37 0 C in 5% CO2 (Jouan, France) with medium changed every 2 to 3 days.
  • the fibroblasts monolayer culture was subcultured when the culture reaches confluence.
  • Example 5 Procedure 5 Formation of autologous bilayer tissue engineered human skin: When the keratinocytes and dermal fibroblast culture reaches sufficient number, they were trypsinized, pooled and centrifuged. For formation of fibroblast layer (10cm 2 ), dermal fibroblasts were mixed with HPD (0.5-5.0 x 10 6 cells : 0.5-5.0 ml HPD) and poured into the culture plate. About 100-300 mmol/L of calcium chloride was added to initialize the polymerization process of the fibroblast layer.
  • HPD 0.5-5.0 x 10 6 cells : 0.5-5.0 ml HPD
  • keratinocytes cells were mixed with HPD (0.5-5.0 x 10 6 cells : 0.5-5.0 ml HPD) and poured on top of the harden fibroblast construct. 100-300 mmol/L of calcium chloride was added to initialize the polymerization process of the keratinocyte layer. This will produce the autologous bilayer tissue engineered skin construct.
  • the autologous bilayer tissue engineered skin construct was cultured in the combination medium of DKSFM: Ham's Fl 2: DMEM (1 : 1) + 10% HS (1 : 1) for 7 days for construct stabilization.
  • tissue engineered human skin construct showed same features as the normal human skin. It is to be understood that the present invention may be embodied in other specific forms and is not limited to the sole embodiment described above. However modification and equivalents of the disclosed concepts such as those which readily occur to one skilled in the art are intended to be included within the scope of the claims which are appended there to.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Botany (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

L'invention porte sur des tissus de peau reconstitués par culture et obtenus au moyen d'une technique produisant de la peau humaine autologue à double couche en utilisant des kératinocytes et des fibroblastes dermiques de peau mis en culture à partir de petits échantillons de peau d'un patient mélangés à des dérivés de plasma humain (HPD). Les tissus ainsi produits s'avèrent très utiles en cas de brûlures, d'ulcères diabétiques chroniques, de plaies de pression (par exemple d'escarres), ou maladies de la peau), et en chirurgie réparatrice ou plastique ou dans d'autres utilisations similaires.
PCT/SG2005/000208 2004-06-29 2005-06-24 Formation de tissus de peau humains par genie biologique, utilisant des hpd comme biomateriels Ceased WO2006001778A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
MYPI20042556A MY137139A (en) 2004-06-29 2004-06-29 Formation of tissue engineered human skin using hpd as biomaterials
MYPI20042556 2004-06-29

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WO2006001778A1 true WO2006001778A1 (fr) 2006-01-05

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9051550B2 (en) 2009-04-09 2015-06-09 Arizona Board Of Regents, On Behalf Of The University Of Arizona Cellular seeding and co-culture of a three dimensional fibroblast construct
US11266766B2 (en) 2015-10-08 2022-03-08 Massachusetts Institute Of Technology Situ expansion of engineered devices for regeneration
US11324858B2 (en) 2012-07-10 2022-05-10 The Trustees Of The University Of Pennsylvania Biomaterials for enhanced implant-host integration
US11890395B2 (en) 2017-06-16 2024-02-06 Avery Therapeutics, Inc. Three dimensional tissue compositions and methods of use

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WO2002046375A1 (fr) * 2000-12-08 2002-06-13 Xgene Corporation Synthese in vitro d'un tissu en couches compose de cellules triees
US6497875B1 (en) * 1996-04-26 2002-12-24 Case Western Reserve University Multilayer skin or dermal equivalent having a layer containing mesenchymal stem cells

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US6497875B1 (en) * 1996-04-26 2002-12-24 Case Western Reserve University Multilayer skin or dermal equivalent having a layer containing mesenchymal stem cells
WO2002046375A1 (fr) * 2000-12-08 2002-06-13 Xgene Corporation Synthese in vitro d'un tissu en couches compose de cellules triees

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Title
CHANG D W ET AL: "Can a tissue-engineered skin graft mprove healing of lower extremitry foot wounds after revascularization", ANN VASC SURG, vol. 14, no. 1, 2000, pages 44 - 49 *
FAUZA DO ET AL: "Videofetoscopically assisted fetal tissue engineering: skin replacement.", J PEDIATR SURG, vol. 33, no. 2, 1998, pages 357 - 361 *
LEE K H ET AL: "Tissue-engineered human living skin substitutes: development and clinical application", YONSEI MED J, vol. 41, no. 6, 2000, pages 774 - 779, XP002198352 *
LLAMES S G ET AL: "Human plasma as a dermal scaffold for the generation of a completely autologous bioengineered skin.", TRANSPLANTATION, vol. 77, no. 3, 2004, pages 350 - 355, XP002428654, DOI: doi:10.1097/01.TP.0000112381.80964.85 *
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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9051550B2 (en) 2009-04-09 2015-06-09 Arizona Board Of Regents, On Behalf Of The University Of Arizona Cellular seeding and co-culture of a three dimensional fibroblast construct
US9976123B2 (en) 2009-04-09 2018-05-22 Arizona Board Of Regents On Behalf Of The University Of Arizona Cellular seeding and co-culture of a three dimensional fibroblast construct
US11345894B2 (en) 2009-04-09 2022-05-31 Arizona Board Of Regents On Behalf Of The University Of Arizona Cellular seeding and co-culture of a three dimensional fibroblast construct
US11324858B2 (en) 2012-07-10 2022-05-10 The Trustees Of The University Of Pennsylvania Biomaterials for enhanced implant-host integration
US11617817B2 (en) 2012-07-10 2023-04-04 The Trustees Of The University Of Pennsylvania Biomaterials for enhanced implant-host integration
US11266766B2 (en) 2015-10-08 2022-03-08 Massachusetts Institute Of Technology Situ expansion of engineered devices for regeneration
US11338065B2 (en) 2015-10-08 2022-05-24 Massachusetts Institute Of Technology In situ expansion of engineered devices for regeneration
US11890395B2 (en) 2017-06-16 2024-02-06 Avery Therapeutics, Inc. Three dimensional tissue compositions and methods of use

Also Published As

Publication number Publication date
MY137139A (en) 2008-12-31

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