EP2809366A1 - Matrice pour colonisation cellulaire - Google Patents

Matrice pour colonisation cellulaire

Info

Publication number
EP2809366A1
EP2809366A1 EP13702345.3A EP13702345A EP2809366A1 EP 2809366 A1 EP2809366 A1 EP 2809366A1 EP 13702345 A EP13702345 A EP 13702345A EP 2809366 A1 EP2809366 A1 EP 2809366A1
Authority
EP
European Patent Office
Prior art keywords
matrix
mixture
polymers
layer
solvent
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.)
Withdrawn
Application number
EP13702345.3A
Other languages
German (de)
English (en)
Inventor
Martin GÖRNE
Thomas Kordick
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.)
Bioenergy Capital AG
Original Assignee
Bioenergy Capital AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Bioenergy Capital AG filed Critical Bioenergy Capital AG
Priority to EP13702345.3A priority Critical patent/EP2809366A1/fr
Publication of EP2809366A1 publication Critical patent/EP2809366A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • 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
    • 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
    • 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
    • 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
    • A61L27/58—Materials at least partially resorbable by the body

Definitions

  • the present application relates to porous matrixes for cell colonization for therapeutic or diagnostic purposes.
  • Cell implants based on porous matrices of biocompatible polymers are known from WO 2004/108810 AI.
  • the pores are cross-linked and serve as a template for the location of cells in vivo (eg, therapeutically) or in vitro (eg, diagnostically).
  • a bioresorbable matrix can serve for the temporary localization of the graft.
  • the invention therefore sets itself the goal of achieving an improvement in the clinical performance of the template.
  • the invention proposes to provide on one side of the usually disc-shaped template a surface with less than 20% of the average pore content of the other side (s).
  • This asymmetric structure allows the template to be placed in the body so that the implanted vital cells stay in it longer.
  • the invention provides methods of making porous bioresorbable matrices, initially forming a polymer layer without a pore former, followed by coating a mixture of at least two polymers, a solvent for one of the polymers, and a water-soluble pore former, followed by evaporation of the solvent and then water to remove the pore-forming agent. Between these last two steps, in one variant, pressurization for compacting may still take place. Both methods lead to highly porous polymer matrix disks, but one side of which has a pore-free or at least low-pore membrane. Despite this membrane, the supply of the cells in use in the case of the application is sufficient, the However, loss rates due to emigration are considerably reduced. If, in one variant, such a template serves as connective tissue support, the continuous polymer layer can have sufficient hold for z. B. Provide suture for fixation of the template.
  • the porous matrix is hydrophilic, e.g. B. coated with (meth) acrylic acid polymer. This is followed by a plasma coating step followed by a plasma-free
  • Coating step whereby the required layer thicknesses of more than one micrometer can be achieved.
  • matrices are provided for colonization with functional cells, for example hepatocytes and / or Langerhans' islet cells.
  • functional cells for example hepatocytes and / or Langerhans' islet cells.
  • Such biochemical function cells attach to the inner walls of the pores of the foamy matrix (attachment rates over 80% or, suitably coated, over 95%) and can be transplanted with the matrix into mesothelial pockets, ideally the cell donor itself In this case, no rejection reaction takes place, but only a comparatively mild, for the therapeutic process favorable foreign body stimulus is exercised.
  • the matrix becomes vascularized and the implanted cells no longer rely on diffusive supply.
  • the matrices are placed so that the low-pore (or -free) side is inside and the pore-rich side is outward, through the rate of loss To keep brain drainage low.
  • a gradual dissolution of part of the degradable matrix occurs (within 3-4 months, or at least 2 and / or less than 7 months), thereby affecting the physiological milieu in a manner which is also conducive to therapeutic success. It is useful if a portion of the polymer mixture erodes more slowly (ratio of degradation times at least 5) and the structural cohesion longer time, z. B. 2.5-3 years (or at least 2 and / or less than 5 years) guaranteed.
  • Such polymers are useful based on -hydroxy- carboxylic acids such as lactic acid and / or glycolic acid, eg. PLA or PLGA. Manufacturers of such polymers approved for use in the human body indicate the nominal degradation times that are relevant here.
  • coated matrices namely those which in a combined PECVD / CVD process are first plasma-coated with a thin (eg 20-30 nm) PAA layer and subsequently with a thicker PAA layer (eg 20-30 pm) without plasma exposure.
  • This upper layer forms a crystalline, hydrophilic layer.
  • Particle size distribution mixed mixed with a solution of one of the polymers in chloroform and then added to the already prepared polymer layer.
  • the solvent evaporates at slightly elevated temperature (45 ° C-65 ° C) and this can then be compacted if desired by applying pressure. Subsequently, the compact is watered to provide the desired porosity by removing the salt. However, the initially produced polymer layer remains pore-free. Depending on the application, the thickness of the low-pore layer can be adjusted by the amount and concentration of the initial solution.
  • the resulting membrane has a thickness of about 10-20 pm, in the latter case about 0.5-1 mm.
  • the saline particles of the mixture to be coated are somewhat coarser (median at 350-370 pm) than the polymer particles (median of the slower degradable polymer between 210 pm and 230 pm, that of the faster degradable polymer between 150 pm and 170 pm).
  • the distribution widths (5% / 95%) are similar, namely about ⁇ 85-95 pm for salt or polymer in total.
  • the distribution form can be bi- or trimodal.
  • the composition of the layer mixture is about 96% salt, 1-1.5% solid polymer and another about 3-5% dissolved polymer, wherein the volume fractions of solids and liquid are about the same. Overall, the proportion of the rapidly degradable polymer is only about 5-20% of the polymer.
  • the total thickness of the pore-forming layer is 5-6 mm.
  • the salt can be chosen a little coarser (median about 400-420 pm).
  • the total thickness of the pore-forming layer 4-5 mm can be dispensed with the compaction with pressure.
  • the water lasts about 24 h and is followed by drying at 45-50 ° C. If a coating is made, the matrix is on the low-pore side and therefore is predominantly the open-pore side coated.
  • the polymers used here are z. Available from the company Evonik and bear the designations L210s, L210, L09s, L207s, L206s (slower degradable PLGA polymers) and RG502, RG502H, RG505 (faster degradable PLGA polymers).
  • a matrix as described above may serve to fix cells exposed to agents in a bioreactor.
  • defined cell types can be this way whether or not they respond to eligible drugs, and the therapy may be scheduled in response to such assay results.
  • drug development can be simplified because toxicity is detected early.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Botany (AREA)
  • Dispersion Chemistry (AREA)
  • Biotechnology (AREA)
  • Virology (AREA)
  • Immunology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Materials For Medical Uses (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)

Abstract

Matrice d'implantation de cellules qui présente une porosité, à connectivité des pores, supérieure à 80 % et qui est constituée principalement d'un mélange de polymères biorésorbables, la matrice présentant une forme de plaque, et une couche de surface située sur une face de la plaque présentant moins de 20 % de la densité moyenne des pores des autres faces. Ladite matrice est fabriquée à partir d'une couche polymère bio-résorbable, par application d'une couche d'un mélange constitué d'une matière solide hydrosoluble, d'au moins deux polymères différents pour ce qui est de leur vitesse de résorption et d'un solvant pour un des polymères, sur la couche polymère; par évaporation du solvant, éventuellement suivie par un compactage du mélange; et par lavage à l'eau du corps compact pour éliminer le sel.
EP13702345.3A 2012-02-01 2013-02-01 Matrice pour colonisation cellulaire Withdrawn EP2809366A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP13702345.3A EP2809366A1 (fr) 2012-02-01 2013-02-01 Matrice pour colonisation cellulaire

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP12000650.7A EP2628490B1 (fr) 2012-02-01 2012-02-01 Matrice de colonisation cellulaire
PCT/EP2013/000324 WO2013113514A1 (fr) 2012-02-01 2013-02-01 Matrice pour colonisation cellulaire
EP13702345.3A EP2809366A1 (fr) 2012-02-01 2013-02-01 Matrice pour colonisation cellulaire

Publications (1)

Publication Number Publication Date
EP2809366A1 true EP2809366A1 (fr) 2014-12-10

Family

ID=47632975

Family Applications (2)

Application Number Title Priority Date Filing Date
EP12000650.7A Not-in-force EP2628490B1 (fr) 2012-02-01 2012-02-01 Matrice de colonisation cellulaire
EP13702345.3A Withdrawn EP2809366A1 (fr) 2012-02-01 2013-02-01 Matrice pour colonisation cellulaire

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP12000650.7A Not-in-force EP2628490B1 (fr) 2012-02-01 2012-02-01 Matrice de colonisation cellulaire

Country Status (9)

Country Link
US (1) US9381165B2 (fr)
EP (2) EP2628490B1 (fr)
JP (2) JP5784249B2 (fr)
CN (1) CN104245002A (fr)
ES (1) ES2474121T3 (fr)
PL (1) PL2628490T3 (fr)
RU (1) RU2014135278A (fr)
SG (1) SG11201404478WA (fr)
WO (1) WO2013113514A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103908701B (zh) * 2014-03-27 2017-03-08 杭州市第三人民医院 一种基于不对称膜的人体黑素细胞的培养方法
CN109289090A (zh) * 2018-10-31 2019-02-01 陈津 一种胰岛移植微环境及其构建方法

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9914616D0 (en) * 1999-06-23 1999-08-25 Univ Sheffield Attachment surface
US20020183858A1 (en) * 2001-06-05 2002-12-05 Contiliano Joseph H. Attachment of absorbable tissue scaffolds to scaffold fixation devices
JP4975432B2 (ja) * 2003-06-06 2012-07-11 ヒューマンオートセル ゲーエムベーハー マトリクス、細胞インプラント並びにそれらの調製方法及び使用方法
JP4529410B2 (ja) * 2003-10-23 2010-08-25 株式会社ジェイ・エム・エス 培養担体、該培養担体を使用した培養物と培養物の作製方法
DE102004059169A1 (de) 2004-12-08 2006-06-22 Humanautocell Gmbh Verfahren zum Testen von Substanzen an Biomatrices
ATE446060T1 (de) * 2004-12-23 2009-11-15 Novus Scient Pte Ltd Gewebeimplantat zur verwendung in der rekonstruktion von weichgewebedefekten
JP5552690B2 (ja) 2006-09-13 2014-07-16 ディーエスエム アイピー アセッツ ビー．ブイ． 被覆された医療装置
US7763456B2 (en) 2006-09-28 2010-07-27 University Of Washington 3D micro-scale engineered tissue model systems
DK2252661T3 (en) 2008-03-12 2017-01-16 Dsm Ip Assets Bv HYDROPHIL COATING
US20100297675A1 (en) * 2008-11-24 2010-11-25 Huayun Deng Substrate and method for culturing breast cells

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2013113514A1 *

Also Published As

Publication number Publication date
JP2015226811A (ja) 2015-12-17
SG11201404478WA (en) 2014-10-30
US9381165B2 (en) 2016-07-05
EP2628490B1 (fr) 2014-04-02
EP2628490A1 (fr) 2013-08-21
WO2013113514A1 (fr) 2013-08-08
JP5784249B2 (ja) 2015-09-24
ES2474121T3 (es) 2014-07-08
PL2628490T3 (pl) 2014-09-30
US20150010611A1 (en) 2015-01-08
RU2014135278A (ru) 2016-03-27
CN104245002A (zh) 2014-12-24
JP2015505491A (ja) 2015-02-23

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