CN101381677A - Tissue engineering reactor with torsion and tension-compression functions - Google Patents
Tissue engineering reactor with torsion and tension-compression functions Download PDFInfo
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- CN101381677A CN101381677A CNA2008101120151A CN200810112015A CN101381677A CN 101381677 A CN101381677 A CN 101381677A CN A2008101120151 A CNA2008101120151 A CN A2008101120151A CN 200810112015 A CN200810112015 A CN 200810112015A CN 101381677 A CN101381677 A CN 101381677A
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- 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
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- 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
- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
- C12M35/04—Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
Abstract
The invention provides a tissue engineering reactor with functions of torsioning and drawing, which comprises a tissue culture cavity, a culture fluid perfusion loop, a first maintaining device and a second maintaining device, a drawing driver of tissue culture and a torsioning driver of the tissue culture, wherein the culture fluid perfusion loop passes through the tissue culture cavity; the first maintaining device and the second maintaining device are arranged in the tissue culture cavity for arranging the tissue culture between the first maintaining device and the second maintaining device; the drawing driver of the tissue culture is coupled with at least one of the first maintaining device and the second maintaining device for driving the maintaining device to make reciprocating motion so as to draw the tissue culture; and the torsioning driver of the tissue culture is coupled with at least one of the first maintaining device and the second maintaining device for driving the maintaining device to rotate, so that the tissue culture arranged between the first maintaining device and the second maintaining device can be twisted. The reactor can load periodical axial drawing, twisting and other mechanical loading on the culture while culturing, and has excellent mass transfer performance and regulating and controlling capability.
Description
Technical field
The present invention relates to cell cultures, field of tissue engineering technology, more particularly relate to a kind ofly have tissue culture and reverse tissue engineering reactor with tension-compression functions.
Background technology
Organizational project, be meant with engineering science and life science principle of combining and method, prepare tissue and organ surrogate, to recover, to keep or improve the function of tissue, organ, it is rapid, a far-reaching biomedical engineering Application Areas of development, be a new branch in the biomedical engineering, the appearance of tissue engineering technique and develop into congenital disorders and unprecedented chance has been created in the treatment of acquired disease.
The organizational project bio-reactor is the important component part of organizational project model system, it can regulate and control tissue development and some biological chemistries and the physical signalling kept in the analogue body, multiple controlled condition of in vitro culture such as nutrition, ventilation, stress are provided, provide suitable external environment for the cell-scaffold mixture makes up bud into functional organization.The important means that the organizational project bio-reactor has become research and cultivated tissues such as blood vessel, cardiac muscle, cartilage, bone.So environment such as the mechanics under the body physiological condition of analog cell tissue growth, biochemistry, how to influence the dimensional culture and the functionalization of cell by studying mechanics under the external environment, biochemical factor, how research organization's engineering bio-reactor improves the suitability for industrialized production of inoculation, mass transfer, mechanical environment and the organizational project of cell, and the more advanced used in tissue engineering bio-reactor of research and development is significant for the development of organizational project targetedly.
At present, the research contents of used in tissue engineering bio-reactor mainly comprises:
1. realize and even, the high-density inoculation of control cell in support: the direct filling type bioreactor of discovering in recent years is being better than non-direct filling type bioreactors such as static state, rotation stirring-type aspect cell inoculation density and the homogeneity, this technology has been applied to myocardial cell, vascular tissue and liver cell organizational project
2. improve the mass transfer situation: the rotary bio-reactor of wall provides certain low shear-stress by dynamic rotation Laminar Flow for cell, has improved the mass transfer situation preferably, and culture effect is better than rotation-stirring type bioreactor; The problems such as balance of the shearing stress size that the filling rate of the rotary bio-reactor of wall, pair cell apply, cytotrophy thing and metabolite mass transfer all can exert an influence to culture effect, therefore need be at parameters such as specific organizational controls, adjusting filling rates, with the mass transfer effect that obtains to optimize.
3. in engineered cultivation, apply suitable mechanical force, the control engineering tissue construction: a large amount of studies show that periodically mechanical extension can promote the myocardial cell propagation and framework construction, improve the Skeletal Muscle Cell organization mechanics characteristic of vitro culture, improve the organizational structure's performance of the smooth muscle cell structure that is planted on the polymeric stent material and the expression of elastin; Dynamic compression or shear-stress help the enhancing of the synthetic and cartilaginous tissue mechanical characteristic of chondrocyte GAG; To applying mechanical loading in the engineered culturing process, not only can promote the structure of engineering tissue, and can directly promote cell specific vegetative period to multi-functional differentiation.Therefore, in engineered culturing process, apply mechanical loading, can directly promote cell specific vegetative period to multi-functional differentiation, promote the structure of engineering tissue.
Powell, Courtney A. etc. has designed a kind of bio-reactor that skeletal muscle tissue is cultivated that can be used in, one section on skeletal muscle tissue support is fixing, one section links to each other with stepper-motor, provide constant or periodicity tension and compression stress by stepper-motor, the suffered tensile stress of support detects by pulling force sensor, the tissue culture chamber can not rotate (Mechanical stimulation improves tissue-engineered humanskeletal muscle, Am J Physiol Cell Physiol, 2002; 282 (5): 1557-1565).
Bancroft, Gregory N. etc. carry out the reactor of perfusion culture to the bone support with peristaltic pump, the calcium contents that perfusion culture has improved culture is compared in discovery with static cultivation, cultivate and not load tension and compression simultaneously and mechanical loading (Technical Note:Design of a Flow Perfusion BioreactorSystem for Bone Tissue-Engineering Applications such as to reverse, Tissue Engineering, 2003; 9 (3): 549-554).
Breen, Liam T. etc. have designed the tissue engineering reactor that shearing and tension and compression stress can be provided individually or simultaneously to monolayer cell.Apply shear-stress by the stepper-motor pair cell that links to each other with awl dish mobilometer, apply tension and compression stress by stepper-motor with the pair cell that links to each other on elastic silica gel chassis, the tissue culture chamber can not rotate (Development of a novel bioreactor to apply shear stress and tensilestrain simultaneously to cell monolayers, Review of ScientificInstruments, 2006; 77 (10): 104301-9).
Satish, C.Muluk etc. have designed the vascular reaction device that the enough tension and compression motors of a kind of energy load tension and compression stress and load torsional stress with micro-stepping motors, provide pulsating flow by program-controlled valve, adopt dabbling mode in the blood vessel, no wall rotation (Enhancement of tissue factor expression by veinsegments exposed to coronary arterial hemodynamics.Journal of vascularsurgery:official publication, the Society for Vascular Surgery[and] International Society for Cardiovascular Surgery, North AmericanChapter 1998; 27 (3): 521-527).
Bursac, Nenad etc. are placed on myocardial cell and support the reactor inner suspension cultivation of outer wall rotation, myocardial cell's electric physiology and molecular biology performance have been improved, do not apply stretching in the culturing process and wait mechanical loading (Cultivation in Rotating Bioreactors Promotes Maintenance ofCardiac Myocyte Electrophysiology and Molecular Properties, TissueEngineering, 2003; 9 (6): 1243-1253).
In sum, there is bigger defective in existing tissue engineering reactor: the one, and can't be for organizing periodicity axial tension that approximate physiological status is provided simultaneously, compression, mechanical force such as stretching, distortion load radially; The 2nd, most modes that adopt no wall rotation, at cell evenly, be still waiting improvement aspect high-density inoculation and the mass transfer.Therefore, press for development and can load the required multiple mechanical environment of tissue culture simultaneously, help cell evenly, the high-density inoculation, help mass transfer, have the bio-reactor of good Modulatory character.
Summary of the invention
The present invention is directed to the body interior mechanics environment of tissue growth, a kind of tissue engineering reactor that reverses with the axial push-pull function that has is provided, this reactor has excellent mass transferring performance, can provide nearly good mass transfer for tissue culture.
According to an aspect of the present invention, provide a kind of tissue engineering reactor that reverses with tension-compression functions that has, it comprises: a tissue culture chamber; A nutrient solution perfusion loop, it passes described culture chamber; Be arranged on first holding device and second holding device in the described tissue culture chamber, be used between them, connecting and tissue culture fixedly to be cultivated with removably; In a tissue culture tension and compression drive unit, it and described first holding device and second holding device at least one is coupled, and described holding device is reciprocating that described tissue culture is carried out the tension and compression effect thereby be used to drive; A tissue culture twisting drive unit, in it and described first holding device and second holding device at least one is coupled, be used to drive this holding device and rotate, cause the twisting that is arranged at the described tissue culture between described first holding device and second holding device thus.
As a concrete but infinite embodiment, described have in the tissue engineering reactor that reverses with tension-compression functions, described tissue culture tension and compression drive unit is coupled by a tension and compression shackle rod and described first holding device, to drive described first holding device along axially reciprocating, described second holding device is axially fixed on the fixed support by a steady brace.
As a concrete but infinite embodiment, described have in the tissue engineering reactor that reverses with tension-compression functions, the two ends in described tissue culture chamber are provided with sealing plug, described tension and compression shackle rod passes described sealing plug and is coupled with described first holding device, between described tension and compression shackle rod and the described sealing plug for slidably, rotating coupling, described steady brace passes described sealing plug and is coupled with described second holding device, is rotating coupling between described steady brace and the described sealing plug.
As a concrete but infinite embodiment, described have in the tissue engineering reactor that reverses with tension-compression functions, and described tissue culture twisting drive unit comprises: a rotational drive motor; One rotation transmission device, it and described tension and compression shackle rod or described steady brace are coupled, thereby the rotating drive power of rotational drive motor is passed to described tension and compression shackle rod or described steady brace.
As a concrete but infinite embodiment, described have in the tissue engineering reactor that reverses with tension-compression functions, described rotation transmission device is a gear unit, it and described tension and compression shackle rod are coupled, and this gear unit contains and this reciprocal axially movable mode of the described tension and compression shackle rod of its rotation coupled adopts one of following dual mode:
The first, gear direct-coupled with it and absorbs back and forth moving axially of described tension and compression shackle rod with the endwisely slipping engagement between the gear of described gear unit along axially interfixing in described tension and compression shackle rod and the described gear unit;
It two is, gear direct-coupled with it and makes this gear fixing vertically with a support along axially can sliding mutually in described tension and compression shackle rod and the described gear unit.
As a concrete but infinite embodiment, described have the tissue engineering reactor that reverses with tension-compression functions and also comprise: be arranged on the inlet pressure sensor at upstream inlet place, described tissue culture chamber, be used for detecting the pressure of the ingress in tissue culture chamber, described perfusion loop; Be arranged on the outlet pressure sensor at lower exit place, described tissue culture chamber, be used for detecting the pressure in the exit in tissue culture chamber, described perfusion loop; Displacement sensor is used to detect the displacement that described tension and compression shackle rod takes place; Tension-compression sensor is used for pulling force or the pressure of detection effect on described tissue culture; Signal treatment circuit is used for handling by the detected signal of the sensor.
As a concrete but infinite embodiment, described have in the tissue engineering reactor that reverses with tension-compression functions, shared one draws and turns round integrated electric motor in described tissue culture tension and compression drive unit and the described tissue culture twisting drive unit, described drawing turned round integrated electric motor and drawn by one and turn round transmission rod and described first holding device is coupled, to drive described first holding device along axially reciprocating and around axial rotation, described second holding device is axially fixed on the fixed support by a steady brace; The described output shaft of turning round integrated electric motor that draws is connected with a shaft coupling and a planet gear reducer, and described planetary reducer is coupling in described drawing and turns round on the transmission rod.
As a concrete but infinite embodiment, described have in the tissue engineering reactor that reverses with tension-compression functions, one end of close described first holding device in described tissue culture chamber is provided with gasket, sealing function is played in the nut locking that is locked of described gasket, described draw turn round that transmission rod passes described gasket and with described first holding device coupling, described drawing turned round between transmission rod and the described gasket to slidably, rotating coupling, and an other end in described tissue culture chamber is provided with ripple sealed tube or gasket, sealing function is played in the nut locking that is locked of described ripple sealed tube or gasket, described steady brace pass described ripple sealed tube or gasket and with described second holding device coupling.
As a concrete but infinite embodiment, described have the tissue engineering reactor that reverses with tension-compression functions and also comprise: be arranged on the inlet pressure sensor at upstream inlet place, described tissue culture chamber, be used for detecting the pressure of the ingress in tissue culture chamber, described perfusion loop; Be arranged on the outlet pressure sensor at lower exit place, described tissue culture chamber, be used for detecting the pressure in the exit in tissue culture chamber, described perfusion loop; Displacement sensor is used to detect described drawing and turns round the displacement that transmission rod takes place; Draw and turn round transmitter, be used for detection effect on described tissue culture pulling force, pressure and reverse degree; Signal treatment circuit is used for handling by the detected signal of the sensor; Stopper is used to limit the described amplitude that transmission rod stretches and compresses of turning round of drawing.
As a concrete but infinite embodiment, described have in the tissue engineering reactor that reverses with tension-compression functions, also comprise the culture chamber device of rotation driving, it comprises: culture chamber rotary transmission gear group, a follower gear in this culture chamber rotary transmission gear group is fixedly mounted on the described tissue culture chamber, thereby rotating drive power is passed to described tissue culture chamber, make the rotation of described tissue culture chamber.
As concrete but infinite embodiment, the material in tissue culture chamber for can the withstand high temperatures disinfectant, the glass that does not have bio-toxicity, stainless steel, plastics, polycarbonate, be shaped as right cylinder or symmetric polyhedron, length is for example 5-30cm, and capacity is for example 20-500ml; The tissue culture chamber keeps cultivating cavity airtight by gasket and bolt, but the material of gasket and bolt is the organic and inorganic material of withstand high temperatures disinfectant.As concrete but infinite embodiment, tissue engineering reactor of the present invention is used for bone, muscle, cartilage, the cultivation of engineering tissues such as ligament, comprise by collagen, silk fiber, wool fiber, natural materialss such as hydroxyapatite constitute with or by PLGA, PLA, PLG, sodium alginate, the timbering material that superpolymer such as tetrafluoroethylene constitute, timbering material can be cylindric, sheet, stent diameter thickness for example between the 1-12mm, stent length is for example between the 5-30cm, and the cell on the timbering material comprises osteocyte, the chondrocyte, Skeletal Muscle Cell and myocardial cell.
As concrete but infinite embodiment, the whole priming line of tissue engineering reactor of the present invention is kept 37 ℃, 5-15% CO by putting into the animal cell culture case
2, the culture condition of 95% relative humidity.
Tissue engineering reactor of the present invention, compared following beneficial effect with pre-existing reactors:
1. tissue engineering reactor of the present invention concrete but infinite embodiment, having overcome tissue engineering reactor commonly used can't be for organizing periodicity axial tension that approximate physiological status is provided simultaneously, compression, the shortcoming of mechanical force such as stretching, distortion load radially, can be when cultivating on tissue culture simultaneously or separately loading classes be similar to mechanical loadings such as periodicity axial push-pull that physiological status undertissue is subjected to, distortion, above-mentioned mechanical loading has good Modulatory character;
2. in conduct of tissue engineering reactor of the present invention but among the infinite embodiment, reactor culturing room partly is spirotheca-direct fill-up mode, can realize perfusion culture with regulatable direction and rotating speed rotation, make reactor have excellent mass transferring performance;
3. tissue engineering reactor of the present invention a kind of concrete but infinite embodiment, engineering tissues such as bone, cartilage, muscle, ligament had both been can be used for cultivating, also can be used as the biology of studying described tissue and the instrument of mechanical property, have bigger popularizing application prospect and bigger potential economic results in society.
Description of drawings
Fig. 1 is the structural representation of an illustrative embodiments of tissue engineering reactor of the present invention;
Fig. 2 has shown a kind of distortion of the embodiment of Fig. 1;
Fig. 3 has shown another embodiment of the invention, comprising a kind ofly can and reversing incorporate pair of motion stepper-motor with tension and compression;
Fig. 4 has shown a kind of distortion of the embodiment of Fig. 3;
Fig. 5 has shown a kind of further embodiment of Fig. 1, comprising realizing the part that the tissue culture chamber independently rotates.
Embodiment
Hereinafter provide embodiment to further specify the present invention, but the present invention is not limited only to following embodiment.In the accompanying drawings, identical label is represented identical or corresponding part, and for for purpose of brevity, in the following description these identical or corresponding parts is not made multiple and describe.
As shown in Figure 1, be according to the concrete but tissue engineering reactor of infinite embodiment of the present invention, the details of this reactor is described now.
Of the present invention one concrete but in the infinite embodiment, liquid driving device 102 adopts peristaltic pumps, it provides steady state flow for the perfusion loop.
In another concrete but infinite embodiment, liquid driving device 102 is a kind of linear electric motors, and it provides pulsating flow for the perfusion loop.
The downstream end of tissue culture chamber inlet ductwork 107 is passed upstream seal plug 106 and is entered into tissue culture chamber 103, and upstream extremity and liquid driving device 102 link to each other by pipeline.The upstream extremity of tissue culture chamber export pipeline 115 places in the culture chamber 103, downstream end is passed downstream, tissue culture chamber sealing plug 106 and is reached outside the culture chamber 103, and link to each other, thereby form a complete perfusion fluid loop with the pipeline that is connected to liquid storage bottle 101.
Upstream and downstream sealing plug 106 can provide culture chamber 103 and into and out of the inlet ductwork 107 of culture chamber 103 and the sealing between the export pipeline 115, thereby realizes culture chamber 103 sealing to external world.
One end of tissue culture 109 to be cultivated is fixed by second holding device 108 that comprises anchor clamps, and second holding device 108 is set on the end of steady brace 104; The other end of tissue culture 109 is then fixed by first holding device 108 that comprises anchor clamps, and first holding device 108 is set on the end of the tension and compression electric motor driving bar 111 that is driven by tension and compression motor 114.Steady brace 104 passes upstream seal plug 106, and its other end is fixed on the support 105; Tension and compression electric motor driving bar 111 passes downstream sealing plug 106, and its other end is connected with tension and compression motor 114.
In the embodiment shown in Figure 1, also comprise upstream, tissue culture chamber support 105, be used for fixing and/or keep culture chamber.
In embodiment shown in Figure 1, combining between the sealing plug 106 in tension and compression electric motor driving bar 111 and downstream, tissue culture chamber is slidably, the reciprocal tension and compression of tension and compression electric motor driving bar 111 drive and act on the anchor clamps 108 in downstream, tissue culture chamber, thereby the anchor clamps 108 that drive downstream, tissue culture chamber are along axially reciprocating, thereby realization is to the reciprocal tension and compression of the tissue culture 109 in cultivating.
Further, tension and compression motor 114 is not unique embodiment of realizing the to-and-fro movement generating unit of tissue culture 109, and it can be substituted by other forms of device, as crank-link mechanism, hydro-cylinder etc.These distortion embodiments all belong to scope of the present invention.
It should be noted, the setting of tension and compression mechanism, anchor clamps for the upstream and downstream in tissue culture chamber are reciprocity, promptly, the tension and compression of tension and compression motor 114 drive, both can be coupled to like that as illustrated in fig. 1 on the anchor clamps 108 in downstream in tissue culture chamber, also can be coupled on the anchor clamps 108 of upstream in tissue culture chamber, also can be coupled on the anchor clamps 108 in the anchor clamps 108 of upstream and downstream.These substitute modes all belong to scope of the present invention.
Infinite embodiment has as shown in Figure 1 further comprised the part of the independent twisting that realizes tissue culture: a tissue culture rotational drive motor 203, the rotation axis 204 of motor 203 rotates driving gear set 202 with the downstream and is coupled, and does to rotate synchronously to drive driving gear set 202.Driving gear set 202 is coupled with culture chamber downstream tension and compression electric motor driving bar 111, and tension and compression electric motor driving bar 111 links to each other with the anchor clamps 108 in downstream; One end of tissue culture 109 is fixed on the tension and compression electric motor driving bar 111 by the anchor clamps 108 in downstream, the other end is fixed on the steady brace 104 that links to each other with support by the anchor clamps 108 of upstream, thereby when drive-motor 203 drives rotation driving gear set 202, tissue culture 109 1 ends also are driven and rotate, and the other end is fixed, thereby realizes twisting.
At this, this reciprocal axially movable mode that driving gear set 202 containings and its rotation coupled culture chamber downstream tension and compression electric motor driving bar 111 are rotated in the downstream can have multiple.
The first, gear direct-coupled with it rotated in the driving gear set 202 along axially interfixing in culture chamber downstream tension and compression electric motor driving bar 111 and downstream, and absorbs back and forth moving axially of culture chamber downstream tension and compression electric motor driving bar 111 with the endwisely slipping engagement between the gear of gear unit 202.For this reason, a kind of possibility is, the thickness of one of two gears of the engagement that takes place in the gear unit 202 to slide is obviously greater than another, thereby avoided because the slip between the gear causes the possibility of engagement disengaging.
It two is, gear direct-coupled with it rotated in the driving gear set 202 along axially can sliding mutually in culture chamber downstream tension and compression electric motor driving bar 111 and downstream, and with a support (not shown) this gear fixed vertically.
It should be noted, the setting of twisting mechanism, anchor clamps for the upstream and downstream in tissue culture chamber are reciprocity, promptly, the rotating drive of tissue culture rotational drive motor 203, both can be coupled to like that as illustrated in fig. 1 on the anchor clamps 108 in downstream in tissue culture chamber, also can be coupled on the anchor clamps the 108th of upstream in tissue culture chamber, also can be coupled on the anchor clamps 108 in the anchor clamps 108 of upstream in tissue culture chamber and downstream.These substitute modes all belong to scope of the present invention.
By embodiment shown in Figure 1, can realize simultaneously or individually: the reversing of the tissue culture in the cultivation, the perfusion in culture chamber loop, the tension and compression of tissue culture, and any combination of these function/effects.
Fig. 2 has shown a kind of distortion of embodiment shown in Figure 1.Compare with embodiment shown in Figure 1, embodiment shown in Figure 2 further comprise one be used to gather, handle, the part of demonstration and/or record data.As shown in Figure 2, this is used to gather, handle, one of the part of demonstration and/or the record data concrete but embodiment of indefiniteness comprises: be located at the pressure transmitter 302 of culture chamber ingress, be used for detecting the pressure of the ingress of priming line culture chamber 103; Be located at the pressure transmitter 304 in culture chamber exit, be used for detecting the dynamically pressure in the exit of culture chamber 103 of priming line; Optionally tension-compression sensor 301 is used to detect the pulling force that acts under this embodiment on the tissue culture 109; Displacement sensor 303 is used to detect the displacement that the drop-down piezoelectricity machine of this embodiment driving stem 111 takes place.Concentrator 305; Small signal amplifier 306; Driving mechanism 307; Treater 308, it can be a PC or industrial computer; Indicating meter 309.Transmitter 301,302,303 and 304 output are sent to concentrator 305 and are handled, write down and/or show by part thereafter.
Fig. 3 has shown another infinite embodiment of the present invention, comprising one draw and turn round one motor 407, be used to realize the tension and compression and the twisting function of tissue culture.
As shown in Figure 3, embodiment shown in Figure 3 comprises: a tissue culture twisting tension and compression movement and motor-driven integrative motor 407, shaft coupling 406, planetary reducer 408; Draw and turn round motor 407 and link to each other with planetary reducer 408 by shaft coupling 406, planetary reducer is coupling in and draws on the drive shaft 409 of turning round motor, the other end of drive shaft 409 is connected on the anchor clamps 108 in downstream, tissue culture chamber, the anchor clamps 108 of upstream, tissue culture chamber are connected on the steady brace 104 of upstream, steady brace 104 is fixed on the support 105 of upstream, and tissue culture 109 is fixed between the anchor clamps 108 of tissue culture chamber upstream and downstream; Drive shaft 409 drives anchor clamps 108 rotations in downstream, and the anchor clamps 108 that are connected the upstream of steady brace 104 then do not rotate, thereby the tissue culture 109 that is fixed between the upstream and downstream anchor clamps is twisted; Planetary reducer 406 is used to reduce to draw the twisting speed of turning round motor, thus improve be applied on the tissue culture 109 torsional load.
Drawing combining between the gasket 404 in the drive shaft 409 of turning round motor and downstream, tissue culture chamber is slidably, sealing function is played in gasket 404 nut 402 locking that is locked, the reciprocal tension and compression of drive shaft 409 drive and act on the anchor clamps 108 in downstream, tissue culture chamber, thereby the anchor clamps 108 that drive downstream, tissue culture chamber are along axially reciprocating, thereby realization is to the reciprocal tension and compression of the tissue culture 109 in cultivating.Nut 402 locking that is locked of the ripple sealed tube 403 of upstream, tissue culture chamber realizes the sealing between tissue culture chamber and the steady brace 104.The ripple sealed tube can replace by sealed pad.
It should be noted, draw the setting of turning round mechanism, anchor clamps for the upstream and downstream in tissue culture chamber are reciprocity, promptly, draw and turn round drawing of motor 407 and turn round driving, both can be coupled to like that as illustrated in fig. 3 on the anchor clamps 108 in downstream in tissue culture chamber, also can be coupled on the anchor clamps 108 of upstream in tissue culture chamber.These substitute modes all belong to scope of the present invention.
Fig. 4 has shown a kind of distortion of embodiment shown in Figure 3.Compare with embodiment shown in Figure 3, embodiment shown in Figure 4 further comprise one be used to gather, handle, the part of demonstration and/or record data.As shown in Figure 4, this is used to gather, handle, one of the part of demonstration and/or the record data concrete but embodiment of indefiniteness comprises: be located at the pressure transmitter 302 of culture chamber ingress, be used for detecting the pressure of the ingress of priming line culture chamber 103; Be located at the pressure transmitter 304 in culture chamber exit, be used for detecting the dynamically pressure in the exit of culture chamber 103 of priming line; Optionally draw and turn round transmitter 401, be used to detect and act on pulling force, the pressure on the tissue culture 109 under this embodiment and reverse degree; Displacement sensor 303 is used to detect the drop-down displacement of turning round motor driving shaft 409 generations of this embodiment.Be located at planetary reducer 408 following stoppers 405 and be used to limit the amplitude of turning round motor driving shaft 409 tension and compression and compression of drawing; Concentrator 305; Small signal amplifier 306; Driving mechanism 307; Treater 308, it can be a PC or industrial computer; Indicating meter 309.Transmitter 301,302,303 and 304 output are sent to concentrator 305 and are handled, write down and/or show by part thereafter.
Embodiment shown in Figure 5 has further comprised the part that realizes the rotation of culture chamber, and these parts comprise: culture chamber rotating machine 113; The culture chamber rotary transmission gear group 110 that is coupled with the rotating shaft 112 of motor 113.A follower gear in the gear unit 110 is fixedly mounted on the culture chamber 103, thereby the rotating drive power of motor 113 is passed to culture chamber 103, makes culture chamber 103 rotations.
By embodiment shown in Figure 5, can realize simultaneously or individually: the reversing of the tissue culture in the cultivation, the rotation of culture chamber, the perfusion culture of tissue culture, the tension and compression of tissue culture, and any combination of these function/effects.
It should be understood that above-mentioned gear unit 110,202, just realize the corresponding example that rotates the rotation transmission device that transmits; Also can replace gear unit 110 and/or 202 with other transmission mechanism, these other transmission mechanism can be such as chain gearing, belt transmission, transmission rod or the like.
Should be understood that, though mentioned the tension and compression drive unit hereinbefore respectively, reversed drive unit, rotating driving device etc., these devices might not be mutually complete independent device, and are opposite, they can have the common part, and for example they can be by same electric motor driving.Shown this tension and compression drive unit among Fig. 3 and reversed drive unit by same motor-driven a kind of embodiment.
Embodiment 1 reverses the tension and compression perfusion
1, according to conjunctive tissue culture chamber perfusion shown in Figure 1 loop, wherein liquid driving device is peristaltic pump (Cole-Parmer company, a Masterflex series);
2, reactor is carried out disinfection, conditions for sterilization is: 130 ℃, and 3 normal atmosphere, 1 hour time;
3, osseous tissue culture that will be to be cultivated under sterile state is installed on the anchor clamps in the tissue culture chamber, osseous tissue culture diameter 4mm wherein, and length is 5cm, timbering material is a hydroxyapatite;
4, according to conjunctive tissue culture torsion device shown in Figure 1, wherein tissue culture reverses motor and selects Hayden's 57000 serial stepper-motors for use;
5, according to connection osseous tissue pulling pressing device shown in Figure 1, wherein osseous tissue tension and compression motor is selected Hayden's 57000 serial linear stepping motors for use;
6, require the preparation substratum according to cultivating, aseptic culture medium is injected liquid storage bottle;
7, open the power supply preheating of each equipment;
8, setting irrigation flow is 1.0ml/s;
9, set tissue culture and reverse turning to of motor and windup-degree: reverse 15 degree clockwise;
10, set that the periodicity that osseous tissue is subjected to is drawn, stress is 15N, the tension and compression frequency is 5 times/min;
11, operation reactor.
Embodiment 2 reverses tension and compression perfusion band Controlling System
1, according to conjunctive tissue culture chamber perfusion shown in Figure 2 loop, wherein liquid driving device is peristaltic pump (Cole-Parmer company, a Masterflex series);
2, reactor is carried out disinfection, conditions for sterilization is: 130 ℃, and 3 normal atmosphere, 1 hour time;
3, osseous tissue culture that will be to be cultivated under sterile state is installed on the anchor clamps in the tissue culture chamber, osseous tissue culture diameter 4mm wherein, and length is 5cm, timbering material is a hydroxyapatite;
4, according to conjunctive tissue culture torsion device shown in Figure 2, wherein tissue culture reverses motor and selects Hayden's 57000 serial stepper-motors for use;
5, the pressure transmitter of importing and exporting according to conjunctive tissue culture chamber shown in Figure 2, and signal supervisory instrument;
6, according to connection osseous tissue pulling pressing device shown in Figure 2, wherein osseous tissue tension and compression motor is selected Hayden's 57000 serial linear stepping motors for use;
7, according to the tension-compression sensor and the displacement sensor of conjunctive tissue tension and compression shown in Figure 2;
8, require the preparation substratum according to cultivating, aseptic culture medium is injected liquid storage bottle;
9, open the power supply preheating of each equipment;
10, setting irrigation flow is 1.0ml/s;
11, set tissue culture and reverse turning to of motor and windup-degree: reverse 10 degree clockwise;
12, set that the periodicity that osseous tissue is subjected to is drawn, stress is 15N, the tension and compression frequency is 5 times/min;
13, operation reactor.
Embodiment 3 reverses tension and compression perfusion band Controlling System
1. according to conjunctive tissue culture chamber perfusion shown in Figure 4 loop, wherein liquid driving device is peristaltic pump (Cole-Parmer company, a Masterflex series);
2. reactor is carried out disinfection, conditions for sterilization is: 130 ℃, and 3 normal atmosphere, 1 hour time;
3. osseous tissue culture that will be to be cultivated under sterile state is installed on the anchor clamps in the tissue culture chamber, osseous tissue culture diameter 4mm wherein, and length is 5cm, timbering material is a hydroxyapatite;
4. according to conjunctive tissue culture twisting tension and compression rotary device shown in Figure 4, wherein tissue culture twisting tension and compression rotating motor is selected two motion motors for use;
5. pressure transmitter and the signal supervisory instrument of importing and exporting according to conjunctive tissue culture chamber shown in Figure 4;
6. turn round transmitter and displacement sensor and stopper according to drawing of conjunctive tissue tension and compression shown in Figure 4;
7. require the preparation substratum according to cultivating, aseptic culture medium is injected liquid storage bottle;
8. open the power supply preheating of each equipment;
9. setting irrigation flow is 1.0ml/s;
10. set tissue culture and reverse turning to of motor and windup-degree: reverse 10 degree clockwise; The periodicity that the setting osseous tissue is subjected to is drawn, stress is 15N, and the tension and compression frequency is 5 times/min;
11. operation reactor.
Embodiment 4 reverses tension and compression perfusion inner rotary band Controlling System
1. according to conjunctive tissue culture chamber perfusion shown in Figure 5 loop, wherein liquid driving device is peristaltic pump (Cole-Parmer company, a Masterflex series);
2. reactor is carried out disinfection, conditions for sterilization is: 130 ℃, and 3 normal atmosphere, 1 hour time;
3. osseous tissue culture that will be to be cultivated under sterile state is installed on the anchor clamps in the tissue culture chamber, osseous tissue culture diameter 4mm wherein, and length is 5cm, timbering material is a hydroxyapatite;
4. according to conjunctive tissue culture torsion device shown in Figure 5 and tissue culture chamber swivel arrangement, wherein tissue culture reverses motor and selects Hayden's 57000 serial stepper-motors for use; Tissue culture chamber rotating machine is selected Hayden's 57000 serial stepper-motors for use;
5. the pressure transmitter of importing and exporting according to conjunctive tissue culture chamber shown in Figure 5, and signal supervisory instrument;
6. according to connection osseous tissue pulling pressing device shown in Figure 5, wherein osseous tissue tension and compression motor is selected Hayden's 57000 serial linear stepping motors for use;
7. according to the tension-compression sensor and the displacement sensor of conjunctive tissue tension and compression shown in Figure 5;
8. require the preparation substratum according to cultivating, aseptic culture medium is injected liquid storage bottle;
9. open the power supply preheating of each equipment;
10. setting irrigation flow is 1.0ml/s;
Reverse turning to of motor and windup-degree 11. set tissue culture: reverse 10 degree clockwise;
12. set turning to and rotating speed of tissue culture chamber rotating machine: 10rpm turns clockwise;
13. the periodicity that the setting osseous tissue is subjected to is drawn, stress is 15N, the tension and compression frequency is 5 times/min;
14. operation reactor.
The cross reference of other applications that the applicant submits to simultaneously
The content of the following Chinese patent application that the applicant and the application submit to is simultaneously quoted in full at this:
1, " a kind of tissue engineering reactor " with tissue culture tension and compression and spinfunction
2, " a kind of tissue engineering reactor " with tension and compression and culture chamber spinfunction.
Claims (10)
1, a kind of have a tissue engineering reactor that reverses with tension-compression functions, it is characterized in that comprising:
A tissue culture chamber (103);
A nutrient solution perfusion loop, it passes described culture chamber (103);
Be arranged on first holding device (108) and second holding device (108) in the described tissue culture chamber (103), be used between them, being provided with tissue culture to be cultivated;
In a tissue culture tension and compression drive unit, it and described first holding device and second holding device at least one is coupled, and described holding device is reciprocating that described tissue culture is carried out the tension and compression effect thereby be used to drive;
A tissue culture twisting drive unit, in it and described first holding device and second holding device at least one is coupled, be used to drive this holding device and rotate, cause the twisting that is arranged at the described tissue culture between described first holding device and second holding device thus.
2, according to claim 1 have a tissue engineering reactor that reverses with tension-compression functions, it is characterized in that: described tissue culture tension and compression drive unit is coupled by a tension and compression shackle rod (111) and described first holding device, to drive described first holding device (108) along axially reciprocating, described second holding device is axially fixed on the fixed support (105) by a steady brace (104).
3, according to claim 2 have a tissue engineering reactor that reverses with tension-compression functions, it is characterized in that: the two ends in described tissue culture chamber (103) are provided with sealing plug (106), described tension and compression shackle rod (111) passes described sealing plug (106) and is coupled with described first holding device (108), between described tension and compression shackle rod (111) and the described sealing plug (106) for slidably, rotating coupling, described steady brace (104) passes described sealing plug (106) and is coupled with described second holding device (108), is rotating coupling between described steady brace (104) and the described sealing plug (106).
4, according to claim 2 have a tissue engineering reactor that reverses with tension-compression functions, it is characterized in that: described tissue culture twisting drive unit comprises:
A rotational drive motor (203),
One rotation transmission device (202), it and described tension and compression shackle rod (111) or described steady brace (104) are coupled, thereby the rotating drive power of rotational drive motor (203) is passed to described tension and compression shackle rod (111) or described steady brace (104).
5, according to claim 4 have a tissue engineering reactor that reverses with tension-compression functions, it is characterized in that: described rotation transmission device (202) is a gear unit, it and described tension and compression shackle rod (111) are coupled, and this gear unit contains and the reciprocal axially movable mode of the described tension and compression shackle rod of its rotation coupled (111) adopts one of following dual mode:
The first, gear direct-coupled with it be along axially interfixing in described tension and compression shackle rod (111) and the described gear unit (202), and absorb back and forth moving axially of described tension and compression shackle rod (111) with the endwisely slipping engagement between the gear of described gear unit (202);
It two is, gear direct-coupled with it and makes this gear fixing vertically with a support along axially can sliding mutually in described tension and compression shackle rod (111) and the described gear unit (202).
6, according to claim 2 have a tissue engineering reactor that reverses with tension-compression functions, it is characterized in that: also comprise:
Be arranged on the inlet pressure sensor (302) at upstream inlet place, described tissue culture chamber (103), be used for detecting the pressure of the ingress in tissue culture chamber, described perfusion loop (103);
Be arranged on the outlet pressure sensor (304) at lower exit place, described tissue culture chamber (103), be used for detecting the pressure in the exit in tissue culture chamber, described perfusion loop (103);
Displacement sensor (303) is used to detect the displacement that described tension and compression shackle rod (111) takes place;
Tension-compression sensor (301) is used for pulling force or the pressure of detection effect on described tissue culture;
Signal treatment circuit is used for handling by the detected signal of the sensor.
7, according to claim 1 have a tissue engineering reactor that reverses with tension-compression functions, it is characterized in that: shared one draws and turns round integrated electric motor (407) in described tissue culture tension and compression drive unit and the described tissue culture twisting drive unit, described drawing turned round integrated electric motor (407) and drawn by one and turn round transmission rod (409) and described first holding device (108) and be coupled, to drive described first holding device (108) along axially reciprocating and around axial rotation, described second holding device (108) is axially fixed on the fixed support (105) by a steady brace (104); The described output shaft of turning round integrated electric motor (407) that draws is connected with a shaft coupling (406) and a planet gear reducer (408), and described planetary reducer (408) is coupling in described drawing and turns round on the transmission rod (409).
8, according to claim 7 have a tissue engineering reactor that reverses with tension-compression functions, it is characterized in that: an end of close described first holding device (108) in described tissue culture chamber (103) is provided with gasket (404), sealing function is played in be locked nut (402) locking of described gasket (404), described drawing turned round transmission rod (409) and passed described gasket (404) and be coupled with described first holding device (108), described drawing turned round between transmission rod (409) and the described gasket (404) to slidably, rotating coupling, and an other end in described tissue culture chamber (103) is provided with ripple sealed tube (403) or gasket (404), sealing function is played in be locked nut (402) locking of described ripple sealed tube (403) or gasket (404), and described steady brace (104) passes described ripple sealed tube (403) or gasket (404) and is coupled with described second holding device (108).
9, according to claim 7 have a tissue engineering reactor that reverses with tension-compression functions, it is characterized in that: also comprise:
Be arranged on the inlet pressure sensor (302) at upstream inlet place, described tissue culture chamber (103), be used for detecting the pressure of the ingress in tissue culture chamber, described perfusion loop (103);
Be arranged on the outlet pressure sensor (304) at lower exit place, described tissue culture chamber (103), be used for detecting the pressure in the exit in tissue culture chamber, described perfusion loop (103);
Displacement sensor (303) is used to detect described drawing and turns round the displacement that transmission rod (409) takes place;
Draw and turn round transmitter (401), be used for detection effect on described tissue culture pulling force, pressure and reverse degree;
Signal treatment circuit is used for handling by the detected signal of the sensor;
Stopper is used to limit the described amplitude that transmission rod (409) stretches and compresses of turning round of drawing.
10, according to claim 1 have a tissue engineering reactor that reverses with tension-compression functions, it is characterized in that: also comprise the culture chamber device of rotation driving, it comprises: culture chamber rotary transmission gear group (110), a follower gear in this culture chamber rotary transmission gear group (110) is fixedly mounted on the described tissue culture chamber (103), thereby rotating drive power is passed to described tissue culture chamber (103), make described tissue culture chamber (103) rotation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101120151A CN101381677B (en) | 2008-05-20 | 2008-05-20 | Tissue engineering reactor with torsion and tension-compression functions |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2008101120151A CN101381677B (en) | 2008-05-20 | 2008-05-20 | Tissue engineering reactor with torsion and tension-compression functions |
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| CN101381677B CN101381677B (en) | 2011-05-18 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102943042A (en) * | 2012-12-06 | 2013-02-27 | 天津理工大学 | Combined multifunctional bioreactor |
| CN103525701A (en) * | 2013-09-13 | 2014-01-22 | 杭州电子科技大学 | Tissue engineering cartilago articularis in-vitro construction method and device |
| CN104480009A (en) * | 2014-11-27 | 2015-04-01 | 西安交通大学 | Bioreactor device with double functions of perfusion and tensioning |
| CN112304772A (en) * | 2020-09-28 | 2021-02-02 | 烟台泰悦流体科技有限公司 | Testing device of multifunctional hose |
| CN112656557A (en) * | 2020-12-17 | 2021-04-16 | 湖北工业大学 | Peripheral nerve interface based on tissue engineering |
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2008
- 2008-05-20 CN CN2008101120151A patent/CN101381677B/en active Active
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102943042A (en) * | 2012-12-06 | 2013-02-27 | 天津理工大学 | Combined multifunctional bioreactor |
| CN102943042B (en) * | 2012-12-06 | 2014-08-06 | 天津理工大学 | Combined multifunctional bioreactor |
| CN103525701A (en) * | 2013-09-13 | 2014-01-22 | 杭州电子科技大学 | Tissue engineering cartilago articularis in-vitro construction method and device |
| CN104480009A (en) * | 2014-11-27 | 2015-04-01 | 西安交通大学 | Bioreactor device with double functions of perfusion and tensioning |
| CN112304772A (en) * | 2020-09-28 | 2021-02-02 | 烟台泰悦流体科技有限公司 | Testing device of multifunctional hose |
| CN112656557A (en) * | 2020-12-17 | 2021-04-16 | 湖北工业大学 | Peripheral nerve interface based on tissue engineering |
| CN112656557B (en) * | 2020-12-17 | 2022-09-13 | 湖北工业大学 | Peripheral nerve interface based on tissue engineering |
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| Publication number | Publication date |
|---|---|
| CN101381677B (en) | 2011-05-18 |
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