CN1635108A - A rotary perfusion bioreactor system - Google Patents
A rotary perfusion bioreactor system Download PDFInfo
- Publication number
- CN1635108A CN1635108A CN 200410073314 CN200410073314A CN1635108A CN 1635108 A CN1635108 A CN 1635108A CN 200410073314 CN200410073314 CN 200410073314 CN 200410073314 A CN200410073314 A CN 200410073314A CN 1635108 A CN1635108 A CN 1635108A
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- bioreactor
- reactor
- cell
- rotary
- peristaltic pump
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- 230000010412 perfusion Effects 0.000 title claims description 5
- 239000012528 membrane Substances 0.000 claims abstract description 10
- 230000002572 peristaltic effect Effects 0.000 claims description 16
- 210000000988 bone and bone Anatomy 0.000 claims description 9
- 238000004113 cell culture Methods 0.000 claims description 7
- 229920002379 silicone rubber Polymers 0.000 claims description 4
- 238000007789 sealing Methods 0.000 claims 1
- 239000004945 silicone rubber Substances 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 9
- 239000001301 oxygen Substances 0.000 abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 abstract description 9
- 230000003915 cell function Effects 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 4
- 239000007789 gas Substances 0.000 abstract description 4
- 238000002513 implantation Methods 0.000 abstract 1
- 238000000338 in vitro Methods 0.000 abstract 1
- 239000007788 liquid Substances 0.000 abstract 1
- 235000008935 nutritious Nutrition 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 20
- 235000015097 nutrients Nutrition 0.000 description 14
- 230000000050 nutritive effect Effects 0.000 description 6
- 230000006870 function Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 210000005009 osteogenic cell Anatomy 0.000 description 3
- 230000004938 stress stimulation Effects 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 230000019522 cellular metabolic process Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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Abstract
The invention discloses a rotating and irrigating type bioreactor system which employs the combination of rotating and irrigating to make the cells distribute more uniformly on the stent surface, promote the transportations of oxygen and nutritious substances into the inner microholes of the stent, keep the activities of the inner cells of the stent. The invention can produce mechanical stress stimulates to the cells by the flow of the culture liquid, regulate the exertion of the cell functions, and realize the real time exchange of the inside and outside gas of the reactor through the semi-permeable membrane on the two ends of the reactor. The invention can provide an excellent, controllable three-dimensional environment for the cell implantation and in vitro culture of cell/stent structural body to realize genuine three-dimensional dynamic culture.
Description
Technical field
The invention belongs to biological plant manufacturing engineering field, relate to a kind of bioreactor system of cell cultures, particularly a kind of rotary pouring type bioreactor system that is applied to biologic medical engineering, organizational project cell cultures.
Background technology
Bioreactor system is a kind of Three-Dimensional Dynamic cell culture system, and it has overcome static cultivation and has had many shortcomings, as oxygen, nutritive substance skewness, can only come to provide oxygen and nutritive substance by diffusion to cell, and institute's cultured cells limited amount.This dynamic culture systems ground major advantage is: (1) can produce in three-dimensional rack effectively, uniform cell seeding, and cell quantity is very big; (2) can promote oxygen and nutritive substance to carry to internal stent, the performance (3) of maintenance internal stent cell activity and function can promote propagation, the differentiation of tactophily cell in the support, secretes more extracellular matrix, promotes osteanagenesis; (4) osteogenic cell can produce the osseous tissue with certain geometrical shape along the growth of three-dimensional rack interior microchannels; (5) can discharge more CO
2, keep the physiological pH value, for the performance of cellular metabolism and function provides more favourable microenvironment; (6) flowing of nutrient solution can produce the mechanical stress stimulation by pair cell, regulates the performance of osteogenic cell function.
The bioreactor system of having developed at present has many kinds, mainly contains rotary flask formula bio-reactor (Spinner-flask bioreactors), rotary container formula bio-reactor (Rotating-wallvessels bioreactors), tubular fibre formula bio-reactor (Hollow-fiberbioreactors), direct filling type bioreactor (Direct perfusion bioreactors), mechanics control type bio-reactor (Bioreactors that apply controlled mechanicalforces) etc.Wherein with rotary comparatively extensive with application filling type bioreactor.
Bioreactor system mainly is by rotation or dabbling mode, makes the cell that is attached on the support be subjected to certain shearing force, improves culture environment simultaneously, promotes the performance of the various functions of cell.Rotary bio-reactor is by rotary container or utilizes the rotation of magnetic force list to impel nutrient solution to flow, realizes the purpose that Three-Dimensional Dynamic is cultivated.The advantage of this mode is to make oxygen and the nutritive substance thorough mixing in the reactor, makes the distribution of cell on support better evenly, is beneficial to the performance of the various functions of cell that are attached to rack surface.Its shortcoming is: the culture environment of internal stent micropore or microchannel does not improve, thereby the cell function performance that is attached in micropore or the microchannel is restricted, and cell quantity is inevitable limited.Filling type bioreactor has then remedied the deficiency of rotary bio-reactor, utilize peristaltic pump continuously nutrient solution to be filled into internal stent micropore or microchannel, culture environment in micropore or the microchannel is well improved, promote the performance of cell function, but the cell of rack surface just is difficult to growth.
Summary of the invention
The objective of the invention is to, a kind of rotary and filling type rotary pouring type bioreactor system of combining of advantage has separately been proposed, promptly, in rotation, utilize peristaltic pump that nutrient solution continuously is transported to internal stent micropore or microchannel, rack surface and inner culture environment are improved simultaneously.
The technical solution that realizes above-mentioned purpose is, a kind of rotary pouring type bioreactor system is characterized in that, this system comprises: a kind of rotary pouring type bioreactor system is characterized in that this system comprises:
A bio-reactor, be used for cell cultures, medical threeway is arranged on this bio-reactor, there is the pump line that is communicated with peristaltic pump at its two ends, the bio-reactor internal fixing is provided with the three-dimensional rack of artificial bone and artificial bone anchor clamps formation, there are micropore or microchannel in this three-dimensional rack inside, by the silicon rubber hose and the outer pump line connection of bio-reactor of an end; Respectively have four fan grooves at the bio-reactor two ends, fan groove is pasted with semi-permeable membranes, and this semi-permeable membranes is used for the inside and outside gaseous interchange of bio-reactor; This bio-reactor two ends external diameter also is provided with bearing, wherein also is inlaid with a gear on the external diameter of an end;
One motor, this motor is connected with the gear of bio-reactor, drives and the rotation of control bio-reactor;
One peristaltic pump, this peristaltic pump is connected with the pump line at bio-reactor two ends, and nutrient solution is by peristaltic pump continuously or being transported in the three-dimensional rack internal capillary or microchannel in the bio-reactor of being interrupted.
Rotary pouring type bioreactor system of the present invention combines by rotation and dabbling method, realizes the Three-Dimensional Dynamic cell cultures, and the content of oxygen and carbonic acid gas is basicly stable in the maintenance nutrient solution.Impel cell better evenly in the distribution of rack surface, promote oxygen and nutritive substance to carry to internal stent micropore or microchannel, keep the internal stent cell activity, mobile pair cell by nutrient solution produces the mechanical stress stimulation, regulate the performance of cell function, pass through the real-time exchange of the inside and outside gas of semi-permeable membranes realization response device at reactor two ends simultaneously.For the vitro culture of cell seeding and cell/supporting structure body provides good, a controlled three-dimensional environment, realize that the Three-Dimensional Dynamic that truly (comprises three-D space structure support and three-dimensional dynamic property vitro culture) cultivates.
Description of drawings
Figure 1 shows that rotary pouring type bio-reaction system structural front view of the present invention; It also is a specific embodiment structure iron of the present invention;
Fig. 2 is the vertical view of Fig. 1;
Fig. 3 is the structural representation of bio-reactor;
Fig. 4 is the fan groove synoptic diagram of end cap and lining among Fig. 2.
Symbolic representation shown in above-mentioned Fig. 1,2 is: 1, base, 2, support, 3, swivel joint, 4, dynamic seal, 5, end ring, 6, bearing, 7, key, 8, gear, 9, left end cap, 10, left lining, 11, clamp-screw, 12, reactor vessel, 13, artificial bone, 14, the artificial bone anchor clamps, 15, lining, 16, right end cap, 17, semi-permeable membranes; 18, peristaltic pump; 19, DC gear reducing motor, 20, medical threeway, 21, nutrient solution, 22 silicon rubber hoses, 23 pump lines.
Embodiment and the principle of the present invention thereof finished below in conjunction with accompanying drawing and applicant are described in further detail.
Embodiment
Referring to Fig. 1, rotary pouring type bioreactor system of the present invention comprises:
One DC gear reducing motor 19 is used to drive and control the rotation of bio-reactor;
Filling system is used for to nutrient solution is provided in the bio-reactor, and this filling system comprises the pump line 23 of the various internal diameters that peristaltic pump 18 and peristaltic pump cooperate;
Bio-reactor, this bio-reactor comprise base 1 and support 2 that reactor vessel 12 is arranged on by bearing 6 and supports on 2, and medical threeway 20 is arranged on the reactor vessel; Be arranged with left lining 10, right lining 15, left end cap 9, right end cap 16, end ring 5, dynamic seal 4, swivel joint 3 at the two ends of reactor vessel 12, respectively have four fan grooves 24 on left and right lining and left and right end cap, fan groove is pasted with semi-permeable membranes 17; This semi-permeable membranes is used for the inside and outside gaseous interchange of bio-reactor;
One end of reactor vessel 12 also is provided with a gear 8, and this gear 8 is embedded on the external diameter by key 7;
Have in the reactor vessel 12 by the three-dimensional rack that has artificial bone 13 and artificial bone anchor clamps 14 to constitute, there are micropore or microchannel in three-dimensional rack inside, and three-dimensional rack is communicated with by the silicon rubber hose and the outer pump line 23 of bio-reactor of an end;
The two ends of bio-reactor are communicated with by pump line 23 and peristaltic pump 18, provide nutrient solution 21 by peristaltic pump 18;
Bio-reactor is connected with DC gear reducing motor 19 by gear 8, is driven and controls revolution by DC gear reducing motor 19.
Certainly, adopt servomotor or interchange reducing motor can control the rotation of bio-reactor equally.
Rotary pouring type bioreactor system of the present invention, can well improve cell culture environment, promote the distribution of cell on three-dimensional rack better evenly, can promote oxygen and nutritive substance to carry to internal stent, the performance that keeps internal stent cell activity and function, the inside and outside gas real-time exchange of realization response device, the content of oxygen and carbonic acid gas is basicly stable in the assurance nutrient solution, keep the physiological pH value, for the performance of cellular metabolism and function provides more favourable microenvironment, and flowing of nutrient solution can produce the mechanical stress stimulation by pair cell, the performance of adjusting osteogenic cell function.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410073314 CN1288235C (en) | 2004-11-25 | 2004-11-25 | Rotary pouring type bioreactor system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410073314 CN1288235C (en) | 2004-11-25 | 2004-11-25 | Rotary pouring type bioreactor system |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1635108A true CN1635108A (en) | 2005-07-06 |
| CN1288235C CN1288235C (en) | 2006-12-06 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410073314 Expired - Fee Related CN1288235C (en) | 2004-11-25 | 2004-11-25 | Rotary pouring type bioreactor system |
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| CN (1) | CN1288235C (en) |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101838610A (en) * | 2010-03-19 | 2010-09-22 | 南方医科大学珠江医院 | Bioreactor and control system and method thereof |
| CN101974404A (en) * | 2010-09-21 | 2011-02-16 | 重庆文理学院 | Experimental device and process for two-way perfusion mechanics |
| CN102154101A (en) * | 2011-01-11 | 2011-08-17 | 王林 | Integrated dynamic inoculation culture method for osteogenous seed cell and matched bioreactor thereof |
| CN102296029A (en) * | 2010-06-28 | 2011-12-28 | 裴国献 | perfusion bioreactor system |
| CN103180431A (en) * | 2010-08-18 | 2013-06-26 | 药物模式有限责任公司 | Bioreactor system |
| CN103614296A (en) * | 2013-11-15 | 2014-03-05 | 汪洋 | Double-chamber three-dimensional pouring bioreactor system |
| CN103789208A (en) * | 2014-02-19 | 2014-05-14 | 上海交通大学医学院附属第九人民医院 | Biaxial rotary bioreactor |
| CN104593258A (en) * | 2015-01-27 | 2015-05-06 | 上海泉众机电科技有限公司 | Device for constructing three-dimensional body tissues |
| CN105483003A (en) * | 2015-12-29 | 2016-04-13 | 北京理工大学 | Biological tissue perfusion culture device |
| CN106010966A (en) * | 2016-06-08 | 2016-10-12 | 中山大学附属第医院 | Multidirectional tissue engineering porous material perfusion system |
| CN106806039A (en) * | 2017-02-22 | 2017-06-09 | 重庆大学 | Rotary cell support planting unit |
| CN112424333A (en) * | 2018-05-21 | 2021-02-26 | 波尔多大学 | System for cell culture in a bioreactor |
| CN112608845A (en) * | 2021-01-11 | 2021-04-06 | 兰州大学第一医院 | Bionic stimulation device for mechanical pressure of stem cells |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101333498B (en) * | 2008-06-13 | 2011-11-23 | 东华大学 | A tissue engineering blood vessel culture device |
| CN101880629A (en) * | 2010-07-22 | 2010-11-10 | 康阳扬 | Rotary tissue stress culture system and method |
-
2004
- 2004-11-25 CN CN 200410073314 patent/CN1288235C/en not_active Expired - Fee Related
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101838610A (en) * | 2010-03-19 | 2010-09-22 | 南方医科大学珠江医院 | Bioreactor and control system and method thereof |
| CN102296029A (en) * | 2010-06-28 | 2011-12-28 | 裴国献 | perfusion bioreactor system |
| CN102296029B (en) * | 2010-06-28 | 2013-01-30 | 裴国献 | Perfusion Bioreactor System |
| CN103180431A (en) * | 2010-08-18 | 2013-06-26 | 药物模式有限责任公司 | Bioreactor system |
| CN101974404A (en) * | 2010-09-21 | 2011-02-16 | 重庆文理学院 | Experimental device and process for two-way perfusion mechanics |
| CN102154101A (en) * | 2011-01-11 | 2011-08-17 | 王林 | Integrated dynamic inoculation culture method for osteogenous seed cell and matched bioreactor thereof |
| CN103614296B (en) * | 2013-11-15 | 2015-05-20 | 汪洋 | Double-chamber three-dimensional pouring bioreactor system |
| CN103614296A (en) * | 2013-11-15 | 2014-03-05 | 汪洋 | Double-chamber three-dimensional pouring bioreactor system |
| CN103789208A (en) * | 2014-02-19 | 2014-05-14 | 上海交通大学医学院附属第九人民医院 | Biaxial rotary bioreactor |
| CN104593258A (en) * | 2015-01-27 | 2015-05-06 | 上海泉众机电科技有限公司 | Device for constructing three-dimensional body tissues |
| CN104593258B (en) * | 2015-01-27 | 2016-11-30 | 上海泉众机电科技有限公司 | A kind of device for setting up said three-dimensional body tissue |
| CN105483003A (en) * | 2015-12-29 | 2016-04-13 | 北京理工大学 | Biological tissue perfusion culture device |
| CN106010966A (en) * | 2016-06-08 | 2016-10-12 | 中山大学附属第医院 | Multidirectional tissue engineering porous material perfusion system |
| CN106010966B (en) * | 2016-06-08 | 2019-03-15 | 中山大学附属第一医院 | Multidirectional tissue engineering porous material perfusion system |
| CN106806039A (en) * | 2017-02-22 | 2017-06-09 | 重庆大学 | Rotary cell support planting unit |
| CN112424333A (en) * | 2018-05-21 | 2021-02-26 | 波尔多大学 | System for cell culture in a bioreactor |
| CN112608845A (en) * | 2021-01-11 | 2021-04-06 | 兰州大学第一医院 | Bionic stimulation device for mechanical pressure of stem cells |
| CN112608845B (en) * | 2021-01-11 | 2023-07-25 | 兰州大学第一医院 | Stem cell mechanical pressure bionic stimulation device |
Also Published As
| Publication number | Publication date |
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| CN1288235C (en) | 2006-12-06 |
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Granted publication date: 20061206 Termination date: 20131125 |