HRP20230834T1 - Postupci za proizvodnju personaliziranih krvnih žila - Google Patents

Postupci za proizvodnju personaliziranih krvnih žila Download PDF

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HRP20230834T1
HRP20230834T1 HRP20230834TT HRP20230834T HRP20230834T1 HR P20230834 T1 HRP20230834 T1 HR P20230834T1 HR P20230834T T HRP20230834T T HR P20230834TT HR P20230834 T HRP20230834 T HR P20230834T HR P20230834 T1 HRP20230834 T1 HR P20230834T1
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Croatia
Prior art keywords
whole blood
cell
blood sample
fgf
concentration
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HRP20230834TT
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Raimund Strehl
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VeriGraft AB
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Publication of HRP20230834T1 publication Critical patent/HRP20230834T1/hr

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3604Materials 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 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3616Blood, e.g. platelet-rich plasma
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06Blood vessels
    • A61F2/062Apparatus for the production of blood vessels made from natural tissue or with layers of living cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3604Materials 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 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3625Vascular tissue, e.g. heart valves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3683Materials 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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A61L27/3687Materials 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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/38Materials 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
    • A61L27/3804Materials 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
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    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/38Materials 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
    • A61L27/3839Materials 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
    • A61L27/3882Hollow organs, e.g. bladder, esophagus, urether, uterus
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    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L33/00Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/0005Use of materials characterised by their function or physical properties
    • A61L33/0011Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M21/00Bioreactors or fermenters specially adapted for specific uses
    • C12M21/08Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12M25/00Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/14Scaffolds; Matrices
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
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    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/26Means for regulation, monitoring, measurement or control, e.g. flow regulation of pH
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/34Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/66Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2240/00Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001Designing or manufacturing processes
    • A61F2240/002Designing or making customized prostheses
    • AHUMAN NECESSITIES
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    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/21Acids
    • AHUMAN NECESSITIES
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23Carbohydrates
    • A61L2300/232Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23Carbohydrates
    • A61L2300/236Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents
    • A61L2300/414Growth factors
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/40Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking

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Claims (20)

1. Postupak za proizvodnju personalizirane krvne žile, naznačen time, da obuhvaća stavljanje u doticaj površine bezstaničnog cjevastog postolja sa suspenzijom koja sadrži uzorak pune krvi od pojedinca kojemu je potrebna personalizirana krvna žila, pri čemu se uzorak pune krvi razrjeđuje u fiziološkoj otopini i pritom se stavljanje u doticaj izvršava u vremenu od 3 do 14 dana.
2. Postupak prema patentnom zahtjevu 1, naznačen time, da stanična populacija u uzorku pune krvi nastanjuje bezstanično cjevasto postolje.
3. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da uzorak pune krvi sadrži jedan ili više nestaničnih faktora, pri čemu jedan ili više nestaničnih faktora pune krvi nastanjuje postolje, i time, da nestanični faktori potiču celularizaciju bezstaničnog cjevastog postolja i kompatibilnost domaćina krvne žile nakon usađivanja.
4. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da suspenzija koja sadrži uzorak pune krvi nadalje sadrži antitrombotički faktor.
5. Postupak prema patentnom zahtjevu 4, naznačen time, da antitrombotički faktor sadrži sredstvo protiv zgrušavanja krvi.
6. Postupak prema patentnom zahtjevu 5, naznačen time, da sredstvo protiv zgrušavanja krvi sadrži heparin ili dekstran.
7. Postupak prema patentnom zahtjevu 6, naznačen time, da se heparin nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 0,5 IU/mL +/- 10% do 150 IU/mL +/- 10%, opcionalno pritom heparin se nalazi u nerazrijeđenom uzorku pune krvi ili u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 6,7 IU/mL +/- 10%.
8. Postupak prema patentnom zahtjevu 6, naznačen time, da dekstran je dekstran-40.
9. Postupak prema patentnom zahtjevu 6, naznačen time, da se dekstran nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 1 g/L +/- 10% do 55 g/L +/- 10%.
10. Postupak prema patentnom zahtjevu 4, naznačen time, da antitrombotičko sredstvo sadrži askorbinsku kiselinu.
11. Postupak prema patentnom zahtjevu 10, naznačen time, da se askorbinska kiselina nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 0,2 μg/mL +/- 10% do 200 μg/mL +/- 10%, opcionalno pritom se koncentracija askorbinske kiseline nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 5 μg/mL +/- 10%.
12. Postupak prema patentnom zahtjevu 4, naznačen time, da antitrombotički faktor sadrži acetilsalicilnu kiselinu.
13. Postupak prema patentnom zahtjevu 12, naznačen time, da se acetilsalicilna kiselina nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 0,2 μg/mL +/- 10% do 200 μg/mL +/- 10%, opcionalno pritom se acetilsalicilna kiselina nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 5 μg/mL +/- 10%.
14. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da suspenzija koja sadrži uzorak pune krvi nadalje sadrži jednako ili više od prosječne fiziološke razine populacije faktora rasta odabranog iz skupine koju čine: stimulacijski faktor kolonije granulocita makrofaga (GM-CSF), interleukin (IL)-3, IL-4, neutrofin (NT)-6, pleiotrofin (HB-GAM), midkin (MK), inducirajući protein-10 interferona (IP-10), faktor krvnih pločica (PF)-4, monocitni kemotaktični protein-1 (MCP-1), RANTES (CCL-5, kemokin (C-C-motiv) ligand 5), IL-8, IGF, faktor rasta fibroblasta (FGF)-1, FGF-2, FGF-3, FGF-4, FGF-5, FGF-6, FGF-7, FGF-8, FGF-9, transformacijski faktor rasta (TGF)-β, VEGF, trombocitni faktor rasta (PDGF)-A, PDGF-B, HB-EGF, faktor rasta hepatocita (HGF), faktor nekroze tumora (TNF)-α, faktor rasta nalik na inzulin (IGF)-1, i bilo koja njihova kombinacija ili bilo koje njihove kombinacije, poželjno gdje faktor rasta je faktor rasta fibroblasta (FGF)-2, opcionalno pritom gdje FGF-2 jest ljudski FGF-2.
15. Postupak prema patentnom zahtjevu 1, naznačen time, da je stavljanje u doticaj u vremenskom periodu od 3 do 9 dana, i opcionalno time, da je stavljanje u doticaj u vremenskom periodu od 4 do 9 dana.
16. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da se uzorak pune krvi razrjeđuje u fiziološkoj otopini od najmanje 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, ili 200%, poželjno s time, da se uzorak pune krvi razrjeđuje 1:1.
17. Postupak prema patentnom zahtjevu 14, naznačen time, da se faktor rasta nadopunjava kao izolirana, pročišćena, i/ili sintetička molekula.
18. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da postupak nadalje obuhvaća nadziranje koncentracije nutrijenta u suspenziji, pri čemu nutrijent je D-glukoza, dok se koncentracija D-glukoze neprekidno ili regularno podešava u svrhu održavanja koncentracije D-glukoze na 3 mmol/L +/- 10% do 11 mmol/L +/- 10%, poželjno pritom se koncentracija D-glukoze održava na 5 mmol/L +/- 10% do 8 mmol/L +/- 10%.
19. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da se neprekidno vrši perfuzija bezstaničnog cjevastog postolja suspenzijom, pri čemu se opcionalno vrši perfuzija bezstaničnog cjevastog postolja brzinom od 0,1 mL +/- 10% do 50 mL +/- 10% u minuti, dok se opcionalno vrši perfuzija bezstaničnog cjevastog postolja brzinom od 2 mL +/- 10% u minuti, gdje se opcionalno vrši perfuzija postolja sa zatvorenom recirkulacijom suspenzije, te, opcionalno, time, da neprekidno stavljanje u doticaj jest perfuzija koja se provodi uporabom bioreaktora.
20. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da se bezstanično cjevasto postolje stavlja u doticaj sa suspenzijom koja sadrži uzorak pune krvi, i postupak nadalje obuhvaća nadziranje čitavog niza okolišnih parametara i/ili koncentracije nutrijenta za vrijeme proizvodnje personalizirane krvne žile, s time, da nadalje obuhvaća prilagođavanje čitavog niza okolišnih parametara, dok čitav niz okolišnih parametara uključuje temperaturu, pH vrijednost, kisik, i/ili CO2.
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