EP2729558A1 - Bioreaktor - Google Patents
BioreaktorInfo
- Publication number
- EP2729558A1 EP2729558A1 EP12724932.4A EP12724932A EP2729558A1 EP 2729558 A1 EP2729558 A1 EP 2729558A1 EP 12724932 A EP12724932 A EP 12724932A EP 2729558 A1 EP2729558 A1 EP 2729558A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- liquid
- interior
- housing
- hollow organ
- bioreactor
- 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- Withdrawn
Links
- 239000007788 liquid Substances 0.000 claims abstract description 34
- 210000000056 organ Anatomy 0.000 claims description 47
- 238000003756 stirring Methods 0.000 claims description 9
- 238000013019 agitation Methods 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 2
- 238000012544 monitoring process Methods 0.000 claims description 2
- 239000000523 sample Substances 0.000 claims 1
- 238000011010 flushing procedure Methods 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 8
- 239000006285 cell suspension Substances 0.000 description 6
- 210000000130 stem cell Anatomy 0.000 description 4
- 210000003437 trachea Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 210000000621 bronchi Anatomy 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000002629 repopulating effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0236—Mechanical aspects
- A01N1/0242—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components
- A01N1/0247—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M21/00—Bioreactors or fermenters specially adapted for specific uses
- C12M21/08—Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
- C12M25/14—Scaffolds; Matrices
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/02—Stirrer or mobile mixing elements
- C12M27/06—Stirrer or mobile mixing elements with horizontal or inclined stirrer shaft or axis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/10—Rotating vessel
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/12—Pulsatile flow
Definitions
- the invention relates to a bioreactor according to the preamble of claim 1.
- the technical article of MA Asnaghi at AI "A double-chamber rotation bioreactor for the development of tissue-engineered hollow organs: From concept to clinical trial" from Biomaterials 30, 2009, 5260-9, 1-10 disclose bioreactors for administering the exterior and interior of hollow organs with a liquid
- the need for such exposure of hollow organs to a liquid is particularly evident in the field of transplantation medicine and regenerative medicine,
- the artificial replacement organs (scaffolds) or the donor organs must be colonized with stem cells of the patient, which differentiate themselves by the addition of chemicals and certain growth factors Stem cells or frameworks are necessary to ensure the functionality of the organ and to prevent contamination with other cells, bacteria or fungi, thus minimizing rejection reactions.
- the replacement organ is the donor organ of another human, it must also be cleared of any cells of the donor person prior to treatment with the subject's stem cells.
- Bioreactors are used for these purposes. If the organs or replacement organs are hollow organs such as tracheas, bronchi, blood vessels, ureters, etc., special bioreactors are used which allow both the outside of the organ and the interior to be charged with a liquid. Such a special bioreactor is described in the above-mentioned article.
- the liquid which is applied to the hollow organ may contain chemicals for destroying cells which are still present and consists in repopulating the organ with the stem cells of the organ recipient from a cell suspension.
- FIG. 1 shows a cross section through a bioreactor according to the invention from above
- Fig. 2 is a section along the line A-B of Fig. 1;
- FIG. 3 shows a side view of the bioreactor from FIG. 1.
- the bioreactor shown in cross section in FIG. 1 has a cylindrical housing 2, which receives a rotary device 3 along its longitudinal axis.
- This rotary device 3 is rotatably mounted in the housing 2 with bearings and seals not shown in detail.
- the housing 2 has on its side ports 11 and a window 12 for a camera, wherein monitoring of the cell suspension by suitable biochemical measures is possible through the ports 11 and monitored and recorded by the window 12 of the entire process of bioreaction with an external camera can be here, and here also an infrared camera can be used to monitor the temperature and to monitor the settlement of the cells on the hollow organ 1.
- the rotary device 3 within the bioreactor has two receiving devices 8 and 10, between which the hollow organ 1 or replacement organ to be treated is clamped in a suitable manner. For example, the hollow member 1 is pushed over corresponding tubular ends of the receiving devices 8 and 10 and fixed there in a conventional manner, as shown in Fig. 1.
- the first receiving device 8 is connected to the second receiving device 10 via two stirring rods 7, which run parallel to the longitudinal axis of the hollow organ 1 and thus also the entire device.
- the two stirring rods 7 serve once in the illustrated embodiment, the rotation of the first receiving device 8 on the second recording device 10 to transmit. Furthermore, the stirring rods 7 serve to agitate the liquid, in particular the cell suspension within the housing 2 and thus to prevent a clumping or accumulation of cells at the bottom of the housing 2.
- the second receiving device 10 has a scooping chamber, which is shown particularly well in FIG. 2.
- This scoop chamber 5 extends tangentially to the longitudinal axis 4 of the clamped hollow organ 1 and thus to the axis of rotation of the rotary device 3.
- the scoop chamber 5 is open on one side and closed on the other side, thus forming a blind hole.
- the end of this blind hole, as seen along the longitudinal axis of this scooping chamber 5, extends beyond the longitudinal axis 4 of the clamped hollow organ 1.
- the scoop chamber 5 is also connected via a flow channel 6 of smaller diameter with the interior of the hollow organ 1, namely the shape that this flow channel 6 branches off laterally from the scoop chamber 5 and ends in the axis of rotation or in the longitudinal axis 4 of the hollow organ 1.
- the described bioreactor works as follows:
- the rotation device 3 is removed from the housing 2. Then, the hollow organ 1 or replacement organ to be processed is clamped between the first receiving device 8 and the second receiving device 10 of the rotary device 3, which takes place in a manner known per se and described above. The aim is a reasonably liquid-tight connection between the ends of the hollow organ 1 and the first receiving device 8 and second receiving device 10. Subsequently, the rotary device 3 is used with the hollow organ 1 again in the housing 2 and the housing 2 with liquid, such as a cell suspension until filled to the height of the axis of rotation.
- liquid such as a cell suspension
- the rotary device 3 After reaching the correct chemical parameters and the correct temperature, the rotary device 3 is set in motion, for example by the left in the drawing over the housing 2 protruding shaft part is driven.
- the first receiving device 8 thus also rotates, and the second receiving device 10 is also driven for rotation via the stirring rods 7.
- the housing 2 is about half filled with liquid (cell suspension)
- the scooping chamber 5 immerses each time, when the outer opening of the scooping chamber 5 is below the liquid level by the rotation of the second receiving device 10, into the liquid and takes this liquid especially during the phase of emergence.
- the liquid As soon as the scooping chamber is above the liquid level and continues to rotate, the liquid enters the flow channel 6, which connects the scooping chamber 5 to the interior of the second receiving device 10 and thus to the interior of the hollow organ 1.
- the liquid then exits via the first receiving device 8 and the drainage channels 9 back into the interior of the housing 2.
- the opening of the scooping chamber 5 is at the top, no further flow of the hollow organ 1 with liquid takes place. Only in the next cycle, ie the next appearance of the opening of the scooping chamber 5 from the mirror of the liquid is again a flow through the interior of the hollow organ 1 with liquid.
- this intermittent supply has proven to be sufficient to always provide the interior of the hollow organ 1 with fresh liquid and new cells.
- the housing may also have other shapes, e.g. box-shaped or trough-shaped forms.
- the liquid level may take other heights, if so desired, e.g. if the outside of the hollow organ is not or not so strong or permanently wetted with the liquid.
- the housing 2 also has a special, not shown in the drawing, transport cover for the purpose of transporting the entire bioreactor to the operating room.
- This transport cover is removable, sterilizable and can be placed tightly and serves to maintain the sterility of the interior of the housing 2 in a non-sterile environment.
- another cover can be placed for normal operation, which then rests only on the housing 2 and allows gas exchange with the environment, whereby in the interior of the housing 2 an optimal concentration of oxygen and carbon dioxide and thus a correspondingly optimal partial pressure of these gases in the liquid is complied with.
- agitators can take the form of paddles 13, which are attached to the stirring bars 7 and / or to the rotating part, eg to the first receiving device 8 or to the second receiving device 10.
- the paddles act as stirring spoons, which run as close as possible to the bottom of the bioreactor housing and cause a vortex to appear there, which possibly dissolves detached cells.
- the bioreactor according to the invention can be built.
- the adaptation to the different forms of scaffolding then takes place via appropriate inserts, e.g. a Y-shape for a trachea with two bronchi or an L-shape for a trachea with a bronchia can be used.
- inserts e.g. a Y-shape for a trachea with two bronchi or an L-shape for a trachea with a bronchia can be used.
- These inserts also have different diameters, as do the natural organs.
- the scaffolds are tied to the holder by surgical suture.
- the hollow organ 1 can also be mounted on the receiving devices 8 and 10.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Sustainable Development (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Thermal Sciences (AREA)
- Mechanical Engineering (AREA)
- Dentistry (AREA)
- Environmental Sciences (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102011107400A DE102011107400B3 (de) | 2011-07-07 | 2011-07-07 | Bioreaktor |
PCT/EP2012/059560 WO2013004431A1 (de) | 2011-07-07 | 2012-05-23 | Bioreaktor |
Publications (1)
Publication Number | Publication Date |
---|---|
EP2729558A1 true EP2729558A1 (de) | 2014-05-14 |
Family
ID=46201583
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP12724932.4A Withdrawn EP2729558A1 (de) | 2011-07-07 | 2012-05-23 | Bioreaktor |
Country Status (9)
Country | Link |
---|---|
US (1) | US9918463B2 (zh) |
EP (1) | EP2729558A1 (zh) |
JP (1) | JP2014518076A (zh) |
CN (1) | CN103946365A (zh) |
AU (1) | AU2012280664A1 (zh) |
CA (1) | CA2841033A1 (zh) |
DE (1) | DE102011107400B3 (zh) |
RU (1) | RU2014103343A (zh) |
WO (1) | WO2013004431A1 (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2841010B1 (en) | 2012-04-24 | 2023-08-23 | Harvard Apparatus Regenerative Technology, Inc. | Supports for engineered tissue scaffolds |
WO2014004746A2 (en) | 2012-06-26 | 2014-01-03 | Harvard Bioscience, Inc. | Methods and compositions for promoting the structural integrity of scaffolds for tissue engineering |
US9040921B2 (en) | 2012-07-28 | 2015-05-26 | Harvard Apparatus Regenerative Technology, Inc. | Analytical methods |
WO2014110300A1 (en) | 2013-01-09 | 2014-07-17 | Harvard Apparatus Regenerative Technology | Synthetic scaffolds |
CN105349423B (zh) * | 2015-09-30 | 2018-04-06 | 重庆大学 | 一种独立腔室的血管流体平台使用方法 |
RU2645455C1 (ru) * | 2017-04-27 | 2018-02-21 | Рубен Вагеевич Оганесян | Биореактор для выращивания тканеинженерных конструкций |
JP7144958B2 (ja) * | 2018-03-30 | 2022-09-30 | 株式会社エビデント | 観察装置および観察システム |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2938668C2 (de) * | 1979-09-25 | 1982-06-24 | Bergwerksverband Gmbh, 4300 Essen | Mechanischer Entschäumer für Gas-/Flüssigkeitsreaktoren |
DE3826455A1 (de) * | 1988-08-04 | 1990-02-22 | Kernforschungsanlage Juelich | Vorrichtung zur entnahme von fluessigkeitsproben |
US5248613A (en) * | 1991-07-08 | 1993-09-28 | Roubicek Rudolf V | Nonhomogeneous centrifugal film bioreactor |
GB9116036D0 (en) * | 1991-07-25 | 1991-09-11 | Univ Leicester | Preparing grafts for implantation |
US5846498A (en) * | 1996-02-27 | 1998-12-08 | Praxair Technology, Inc. | Reactor system |
DK0916390T3 (da) * | 1997-11-14 | 2003-01-06 | Kansai Chem Eng | Fremgangsmåde ved ejektion af væske og indretning til udøvelse af fremgangsmåden |
US6720178B1 (en) * | 2000-06-29 | 2004-04-13 | University Of Louisville Research Foundation, Inc. | Self-feeding roller bottle |
KR20020088848A (ko) * | 2001-05-21 | 2002-11-29 | (주)코아바이오텍 | 세포배양관 및 이를 이용한 대량 세포배양기 |
US7348175B2 (en) * | 2002-03-15 | 2008-03-25 | St3 Development Corporation | Bioreactor with plurality of chambers for conditioning intravascular tissue engineered medical products |
WO2003089566A1 (en) * | 2002-04-22 | 2003-10-30 | Tufts University | Multi-dimensional strain bioreactor |
US6841384B2 (en) * | 2002-08-08 | 2005-01-11 | Becton Dickinson Company | Advanced roller bottle system for cell and tissue culturing |
CN1974750A (zh) * | 2006-11-16 | 2007-06-06 | 华东理工大学 | 用于组织工程软骨体外构建的两相生物反应器系统 |
KR100932863B1 (ko) * | 2007-11-30 | 2009-12-21 | 코아스템(주) | 세포배양을 위한 회전 구동 장치 |
CN101372664B (zh) * | 2008-05-16 | 2012-01-11 | 北京航空航天大学 | 一种具有组织培养物拉压和旋转功能的组织工程反应器 |
CN101486966B (zh) * | 2008-09-12 | 2012-12-26 | 广州齐志生物工程设备有限公司 | 一种动物细胞贴壁培养的生物反应器和方法 |
US8507263B2 (en) * | 2009-08-07 | 2013-08-13 | Maria Adelaide Asnaghi | Rotating bioreactor |
-
2011
- 2011-07-07 DE DE102011107400A patent/DE102011107400B3/de not_active Expired - Fee Related
-
2012
- 2012-05-23 CN CN201280033728.3A patent/CN103946365A/zh active Pending
- 2012-05-23 JP JP2014517545A patent/JP2014518076A/ja active Pending
- 2012-05-23 EP EP12724932.4A patent/EP2729558A1/de not_active Withdrawn
- 2012-05-23 US US14/130,953 patent/US9918463B2/en active Active
- 2012-05-23 WO PCT/EP2012/059560 patent/WO2013004431A1/de active Application Filing
- 2012-05-23 RU RU2014103343/10A patent/RU2014103343A/ru not_active Application Discontinuation
- 2012-05-23 CA CA2841033A patent/CA2841033A1/en not_active Abandoned
- 2012-05-23 AU AU2012280664A patent/AU2012280664A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO2013004431A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO2013004431A1 (de) | 2013-01-10 |
CN103946365A (zh) | 2014-07-23 |
AU2012280664A1 (en) | 2014-01-23 |
CA2841033A1 (en) | 2013-01-10 |
JP2014518076A (ja) | 2014-07-28 |
US9918463B2 (en) | 2018-03-20 |
DE102011107400B3 (de) | 2012-10-04 |
RU2014103343A (ru) | 2015-08-20 |
US20140377848A1 (en) | 2014-12-25 |
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Legal Events
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RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: HARVARD APPARATUS REGENERATIVE TECHNOLOGY, INC. |
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Effective date: 20150708 |