CN101372665B - Tissue engineering reactor having tension-compression and cultivation cavity rotation functions - Google Patents
Tissue engineering reactor having tension-compression and cultivation cavity rotation functions Download PDFInfo
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Abstract
本发明提供一种具有拉压和培养腔旋转功能的组织工程反应器，其包括：一个组织培养腔(103)；一个培养液灌注回路，它穿过所述培养腔(103)；设置在所述组织培养腔(103)内的第一保持装置(108)和第二保持装置(108)，用于在它们之间设置待培养的组织培养物；一个组织培养物拉压驱动装置，它与所述第一保持装置(108)耦合，用于驱动所述第一保持装置(108)作往复运动从而对所述组织培养物进行拉压作用；与所述组织培养腔(103)耦合的培养腔旋转驱动装置，用于使所述组织培养腔(103)转动。本发明的组织工程反应器能够在培养的同时在组织培养物上加载周期性轴向拉压等力学载荷，培养室为旋壁-直接灌注模式，具有良好的传质性能。
The present invention provides a tissue engineering reactor with the functions of tension, compression and culture chamber rotation, which comprises: a tissue culture chamber (103); a culture fluid perfusion circuit, which passes through the culture chamber (103); The first holding device (108) and the second holding device (108) in the tissue culture cavity (103) are used to set the tissue culture to be cultivated between them; The first holding device (108) is coupled, and is used to drive the first holding device (108) to reciprocate so as to perform tension and compression on the tissue culture; the culture chamber coupled with the tissue culture chamber (103) The chamber rotation driving device is used to rotate the tissue culture chamber (103). The tissue engineering reactor of the present invention can load mechanical loads such as periodic axial tension and compression on the tissue culture while culturing, and the culture chamber is in a rotating wall-direct perfusion mode, and has good mass transfer performance.
Description
Technical field
The present invention relates to cell cultures, field of tissue engineering technology, more particularly relate to a kind of tissue engineering reactor with tension and compression and culture chamber spinfunction.
Background technology
Organizational project; Be meant with engineering science and life science principle of combining and method; Preparing tissue and organ surrogate, to recover, to keep or improve the function of tissue, organ, 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, suitable external environment are provided 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 through 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 superior to 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 is that cell provides certain low shear-stress through dynamic rotation Laminar Flow, has improved the mass transfer situation preferably, and culture effect is superior to rotation-stirring type bioreactor; The problems such as balance of shearing stress size, cytotrophy thing and metabolite mass transfer that the filling rate of the rotary bio-reactor of wall, pair cell apply all can exert an influence to culture effect; Therefore need to 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 research show 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, and one section links to each other with stepper-motor, provides constant or periodicity tension and compression stress through stepper-motor; The suffered tensile stress of support detects through pulling force sensor; The tissue culture chamber can not rotate (Mechanical stimulation improves tissue-engineered human skeletal muscle, Am J Physiol Cell Physiol, 2002; 282 (5): 1557-1565).
Bancroft; Gregory N. etc. carry out the reactor drum 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 Bioreactor System forBone Tissue-Engineering Applications, Tissue Engineering, 2003 such as to reverse; 9 (3): 549-554).
Breen, Liam T. etc. have designed the tissue engineering reactor that shearing and tension and compression stress can be provided monolayer individually or simultaneously.Apply shear-stress through the stepper-motor pair cell that links to each other with awl dish mobilometer; Apply tension and compression stress through 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 tensile strainsimultaneously to cell monolayers; Review of Scientific Instruments, 2006; 77 (10): 104301-9).
Satish; C.Muluk etc. have designed that the enough tension and compression motor of a kind of ability loads tension and compression stress and have loaded the vascular reaction device of torsional stress with micro-stepping motors; Through program-controlled valve pulsating flow is provided; Adopt dabbling mode in the blood vessel; No wall rotation (Enhancement of tissue factor expression by vein segmentsexposed to coronary arterial hemodynamics.Journal of vascular surgery:official publication; The Society for Vascular Surgery [and] International Societyfor Cardiovascular Surgery, North American Chapter 1998; 27 (3): 521-527).
Bursac; Nenad etc. are placed on myocardial cell and support the reactor drum inner suspension cultivation of outer wall rotation; Myocardial cell's electric physiology and molecular biology performance have been improved; Do not apply mechanical loading (Cultivation in Rotating Bioreactors Promotes Maintenance ofCardiac Myocyte Electrophysiology and Molecular Properties, TissueEngineering, 2003 such as tension and compression in the culturing process; 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 push-pull 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 with axial push-pull and culture chamber spinfunction is provided, this reactor drum has excellent mass transferring performance, can nearly good mass transfer be provided for tissue culture.
According to an aspect of the present invention, a kind of tissue engineering reactor with tension and compression and culture chamber spinfunction is provided, it comprises: a tissue culture chamber; A nutrient solution perfusion loop, it passes said culture chamber; Be arranged on first holding device and second holding device in the said tissue culture chamber, be used between them, connecting and tissue culture fixedly to be cultivated with removably; A tissue culture tension and compression drive unit, the coupling of it and said first holding device, said first holding device is reciprocating that said tissue culture is carried out the tension and compression effect thereby be used to drive; With said tissue culture chamber coupled culture chamber rotating driving device, be used to make said tissue culture chamber to rotate.Wherein, a kind of implementation of said holding device is anchor clamps.
As a concrete but infinite embodiment; In the described tissue engineering reactor with tension and compression and culture chamber spinfunction; Tissue culture tension and compression drive unit is coupled through a tension and compression shackle rod and said first holding device; To drive said first holding device along axially reciprocating, said second holding device is axially fixed on the fixed support through a steady brace.
As a concrete but infinite embodiment; In the described tissue engineering reactor with tension and compression and culture chamber spinfunction; The two ends in said tissue culture chamber are provided with sealing plug; Said tension and compression shackle rod passes said sealing plug and is coupled with said first holding device; Between said tension and compression shackle rod and the said sealing plug for slidably, rotating coupling, said steady brace pass said sealing plug and with the coupling of said second holding device, be rotating coupling between said steady brace and the said sealing plug.
As a concrete but infinite embodiment; In the described tissue engineering reactor with tension and compression and culture chamber spinfunction; Said culture chamber rotating driving device comprises a culture chamber rotary actuator; A slave unit in the said culture chamber rotary actuator is fixedly mounted on the said tissue culture chamber, thereby passes to said tissue culture chamber to the rotating drive power of propulsion source, makes the rotation of said tissue culture chamber.
As a concrete but infinite embodiment; Described tissue engineering reactor with tension and compression and culture chamber spinfunction also comprises: be arranged on the inlet pressure sensor at upstream inlet place, said tissue culture chamber, be used for detecting the pressure of the ingress in tissue culture chamber, said perfusion loop; Be arranged on the outlet pressure sensor at lower exit place, said tissue culture chamber, be used for detecting the pressure in the exit in tissue culture chamber, said perfusion loop; Displacement sensor is used to detect the displacement that said tension and compression shackle rod takes place; Tension-compression sensor is used for pulling force or the pressure of detection effect on said tissue culture; Signal treatment circuit is used for handling by the detected signal of the sensor.
As a concrete but infinite embodiment; Described tissue engineering reactor with tension and compression and culture chamber spinfunction also comprises a tissue culture rotating driving device that is used to make said tissue culture rotation; It comprises: one first rotation transmission device and one second rotation transmission device, and the same output shaft of said two rotation transmission devices and propulsion source is coupled and rotates synchronously; Said first rotation transmission device and said tension and compression shackle rod are coupled; Second rotation transmission device and said steady brace are coupled; Thereby the rotation of said two rotation transmission devices has driven said tension and compression shackle rod respectively and said steady brace rotates synchronously, thereby the two ends that are arranged on the tissue culture between said tension and compression shackle rod and the said steady brace are rotated synchronously.
As a concrete but infinite embodiment; In the described tissue engineering reactor with tension and compression and culture chamber spinfunction, said culture chamber rotary actuator, said first rotation transmission device and second rotation transmission device adopt one of gear unit, chain gearing, belt transmission or transmission rod respectively.
As a concrete but infinite embodiment; In the described tissue engineering reactor with tension and compression and culture chamber spinfunction; Adopt same rotational drive motor as propulsion source in said tissue culture chamber rotating driving device and the said tissue culture rotating driving device, and adopt a clutch/transmission rig to realize the independent rotation in said tissue culture and said tissue culture chamber is driven and/or the different rotation drive pattern.
As a concrete but infinite embodiment; In the described tissue engineering reactor with tension and compression and culture chamber spinfunction; Parts direct-coupled with it are along axially interfixing in said tension and compression shackle rod and said first rotation transmission device, and absorb back and forth moving axially of said tension and compression shackle rod with the endwisely slipping engagement between the parts in said first rotation transmission device.
As a concrete but infinite embodiment; In the described tissue engineering reactor with tension and compression and culture chamber spinfunction; Parts direct-coupled with it be along axially can sliding each other in said tension and compression shackle rod and said first rotation transmission device, and make these parts fixing vertically with a stationary installation.
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 through 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 the cultivation of engineering tissues such as bone, muscle, cartilage, ligament; Comprise constitute by natural materialss such as collagen, silk fiber, wool fiber, Win 40350s with or the timbering material that constitutes by superpolymer such as PLGA, PLA, PLG, sodium-alginate, tetrafluoroethylene; 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, 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 through 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, reactor assembly installation of the present invention, convenient disassembly; Whole reactor, comprise that perfusion channel pipeline and joint are detachable, can sterilize that exemplary conditions for sterilization is for for example: 130 ℃, 3 normal atmosphere, 1 hour time.
2, in conduct of tissue engineering reactor of the present invention but among the infinite embodiment; Reactor drum culturing room partly is spirotheca-direct fill-up mode; Can realize perfusion culture with regulatable direction and rotating speed rotation, make reactor drum have excellent mass transferring performance;
3, tissue engineering reactor of the present invention concrete but infinite embodiment; Having overcome tissue engineering reactor commonly used can't be for organizing the shortcoming of mechanical force load such as periodicity axial tension that approximate physiological status is provided simultaneously, compression; Can be when cultivating on tissue culture simultaneously or separately loading classes be similar to the mechanical loadings such as periodicity axial push-pull that physiological status undertissue receives, above-mentioned mechanical loading has good Modulatory character;
4, in conduct of tissue engineering reactor of the present invention but among the infinite embodiment, tissue culture can be with regulatable direction and rotating speed rotation, thereby realizes contacting more fully with perfusion fluid;
5, 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 said 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 a further embodiment of the present invention, comprising realizing the part of the independent rotation of tissue culture.
Embodiment
Further specify the present invention below in conjunction with embodiment, but the present invention is not limited only to the embodiment of following description.In the accompanying drawings, identical label is represented identical or corresponding part, and for for purpose of brevity, in following explanation, 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 drum 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 its upstream extremity and liquid driving device 102 link to each other through pipeline.The upstream extremity of tissue culture chamber export pipeline 115 places in the culture chamber 103; Its 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 engages with culture chamber 103 with the mode of rotatable (relatively rotating with culture chamber 103) sealing, thereby realizes culture chamber 103 sealing to external world.And upstream and downstream sealing plug 106 also provides culture chamber 103 and into and out of the inlet ductwork 107 of culture chamber 103 and the sealing between the export pipeline 115.
In the embodiment shown in Figure 1, also comprise the upper reaches, tissue culture chamber support 105, be used for fixing and/or keep culture chamber.
As shown in Figure 1, an 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 embodiment shown in Figure 1; Engaging between the sealing plug 106 in tension and compression electric motor driving bar 111 and downstream, tissue culture chamber is slidably; Tension and compression electric motor driving bar 111 reciprocatings are on the anchor clamps 108 in downstream, tissue culture chamber; Thereby the anchor clamps 108 in driven organization culture chamber downstream are reciprocating along axially, thereby realize the reciprocal tension and compression to the tissue culture 109 in cultivating.
It should be noted; The setting of tension and compression mechanism is reciprocity for the anchor clamps of the upstream and downstream in tissue culture chamber, promptly; The tension and compression of tension and compression motor 114 drive; On the anchor clamps 108 in both can be the as illustrated in fig. 1 such downstream that be coupled to the tissue culture chamber, also can be coupled on the anchor clamps 108 at the upper reaches in tissue culture chamber, also can be coupled to simultaneously on the anchor clamps 108 in anchor clamps 108 and downstream at the upper reaches.These replace embodiment, all belong to scope of the present invention.
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, like crank-link mechanism, hydro-cylinder etc.These distortion embodiments all belong to scope of the present invention.
Embodiment shown in Figure 1 has further comprised the part that realizes the rotation of culture chamber, and these parts comprise: culture chamber rotating machine 113; Culture chamber rotary transmission gear group 110, it is coupled through the rotating shaft of rotating machine transmission rod 112 with motor 113.In the embodiment of Fig. 1, a follower gear in the gear unit 110 is fixedly mounted in the neck portion 116 of culture chamber 103 evaginations, thereby passes to culture chamber 103 to the rotating drive power of motor 113, makes culture chamber 103 rotations.
It is understandable that; The rotation of culture chamber rotating machine 113 drives; In the neck portion 116 of the culture chamber in both can be the as illustrated in fig. 1 such downstream that be coupled to the tissue culture chamber; Also can be coupled in the neck portion of culture chamber at the upper reaches in tissue culture chamber, also can be coupled on other parts of culture chamber.These replace embodiment, all belong to scope of the present invention.
By embodiment shown in Figure 1, can realize simultaneously or individually: the tension and compression of the circumfusion of nutrient solution, tissue culture 109 in the rotation in tissue culture chamber 103, the culture chamber 103, 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; Optional tension-compression sensor 301 is used to detect the pulling force or the pressure that act 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 IPC; 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 a further embodiment of the present invention, has wherein further comprised the part that realizes the independent rotation of tissue culture 109.
Embodiment as shown in Figure 3 further comprises: a tissue culture rotational drive motor 203; The rotation axis 204 of motor 203 is coupled with upper reaches driving gear set 201 and downstream driving gear set 202, does to rotate synchronously to drive driving gear set 201 and 202.Driving gear set 201 also is coupled with the steady brace 104 at the culture chamber upper reaches; And driving gear set 202 also is coupled with culture chamber downstream tension and compression electric motor driving bar 111; Thereby the rotation of driving gear set 201 and 202 has driven the rotation of the steady brace 104 and the culture chamber downstream tension and compression electric motor driving bar 111 at the culture chamber upper reaches respectively; And because the rotation of driving gear set 201 and 202 is synchronous; Under their drive; The steady brace 104 at the culture chamber upper reaches also is synchronized with each other with the rotation of culture chamber downstream tension and compression electric motor driving bar 111, thereby is arranged on the steady brace 104 at the culture chamber upper reaches and the rotation of treating cultured tissue 109 two ends between the culture chamber downstream tension and compression electric motor driving bar 111 is synchronous, treats that cultured tissue 109 can not twist.
Though it should be noted that two motors 113 and 203 that shown the tissue culture that is respectively applied in drive cultivating and culture chamber among Fig. 3, the present invention is not limited to this.On the contrary, can adopt single motor to add a clutch/transmission rig, realize the independent rotation in tissue culture 109 and tissue culture chamber 103 is driven and/or the different rotation drive pattern.This distortion also belongs to scope of the present invention.
At this, downstream driving gear set 202 contains and this reciprocal axially movable mode of its rotation coupled culture chamber downstream tension and compression electric motor driving bar 111 can have multiple.
The first; Gear direct-coupled with it be along axially interfixing in culture chamber downstream tension and compression electric motor driving bar 111 and the downstream driving gear set 202, and absorb 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 that sliding engaged takes place in the gear unit 202 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 and fixes this gear with a support (not shown) along axially can sliding each other vertically in culture chamber downstream tension and compression electric motor driving bar 111 and the downstream driving gear set 202.
By embodiment shown in Figure 3, can realize simultaneously or individually: the nutrient solution perfusion in the rotation of tissue culture, the rotation of culture chamber, tissue culture chamber, the tension and compression of tissue culture, and any combination of these function/effects.
It should be understood that above-mentioned gear unit 110,201,202, just realize the corresponding example that rotates the rotation transmission device that transmits; Also can replace gear unit 110,201 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 noted that; Though mentioned the tension and compression drive unit hereinbefore respectively, reversed drive unit, rotating driving device, these devices might not be each other complete independent device, and are opposite; They can have the common part, and for example they can be by same electric motor driving.
Embodiment 1 inner rotary 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 drum 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 Win 40350;
4. according to conjunctive tissue culture chamber swivel arrangement shown in Figure 1, wherein tissue culture chamber rotating machine is selected 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 preparing culture medium according to cultivation, 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 turning to and rotating speed of tissue culture chamber rotating machine: turn clockwise 10rpm;
10. set that the periodicity that osseous tissue receives is drawn, stress is 15N, the tension and compression frequency is 5 times/min;
11. operation reactor drum;
Embodiment 2 inner rotary tension and compression perfusion band 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 drum 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 Win 40350;
4. according to conjunctive tissue culture chamber swivel arrangement shown in Figure 2, wherein 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 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 connection tension-compression sensor shown in Figure 2 and displacement sensor;
8. require preparing culture medium according to cultivation, 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 turning to and rotating speed of tissue culture chamber rotating machine: turn clockwise 10rpm;
12. the periodicity that the setting osseous tissue receives is drawn, stress is 15N, the tension and compression frequency is 5 times/min;
13. operation reactor drum;
Embodiment 3 inner rotary tension and compression perfusion internal rotation band 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 drum 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 Win 40350;
4. according to conjunctive tissue culture swivel arrangement shown in Figure 3 and tissue culture chamber swivel arrangement, wherein the tissue culture rotating machine is selected 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 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 connection tension-compression sensor shown in Figure 2 and displacement sensor;
8. require preparing culture medium according to cultivation, 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 turning to and rotating speed of tissue culture chamber rotating machine: turn clockwise 10rpm;
12. the periodicity that the setting osseous tissue receives is drawn, stress is 15N, the tension and compression frequency is 5 times/min;
13. operation reactor drum.
The cross reference of other applications that the applicant submits to simultaneously
The content of the following one 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 have the tissue engineering reactor that reverses with tension-compression functions "
Claims (7)
1. tissue engineering reactor with tension and compression and culture chamber spinfunction is characterized in that comprising:
A tissue culture chamber (103);
A nutrient solution perfusion loop, it passes said culture chamber (103);
Be arranged on first holding device (108) and second holding device (108) in the said tissue culture chamber (103), be used between them, being provided with tissue culture to be cultivated;
A tissue culture tension and compression drive unit; In it and said first holding device (108) and second holding device (108) at least one is coupled, and is used for the said tissue culture that is arranged between said first holding device (108) and second holding device (108) is carried out the tension and compression effect; Said tissue culture tension and compression drive unit comprises a tension and compression shackle rod (111); Said tension and compression shackle rod and said first holding device (108) are coupled; To drive said first holding device (108) along axially reciprocating; Said second holding device (108) is axially fixed on the fixed support (105) through a steady brace (104)
With said tissue culture chamber (103) coupled culture chamber rotating driving device; Comprise a culture chamber rotary actuator (110); A slave unit in the said culture chamber rotary actuator (110) is fixedly mounted on the said tissue culture chamber (103); Thereby pass to said tissue culture chamber (103) to the rotating drive power of propulsion source, make said tissue culture chamber (103) rotation;
Be used to make the tissue culture rotating driving device of said tissue culture rotation; Comprise one first rotation transmission device (202) and one second rotation transmission device (201), said first rotation transmission device (202) and second rotation transmission device (201) are coupled with the same output shaft (204) of propulsion source; Said first rotation transmission device (202) is coupled with said tension and compression shackle rod (111), and said second rotation transmission device (201) is coupled with said steady brace (104).
2. tissue engineering reactor according to claim 1 is characterized in that further comprising:
Be arranged on the sealing plug (106) at the two ends in said tissue culture chamber (103); Said tension and compression shackle rod (111) passes said sealing plug (106) and is coupled with said first holding device (108); Between said tension and compression shackle rod (111) and the said sealing plug (106) with slidably, rotating mode engages; Said steady brace (104) pass said sealing plug (106) and with said second holding device (108) coupling, engage with rotating mode between said steady brace (104) and the said sealing plug (106).
3. the tissue engineering reactor with tension and compression and culture chamber spinfunction according to claim 1 is characterized in that also comprising:
Be arranged on the inlet pressure sensor (302) at upstream inlet place, said tissue culture chamber (103), be used for detecting the pressure of the ingress in tissue culture chamber, said perfusion loop (103);
Be arranged on the outlet pressure sensor (304) at lower exit place, said tissue culture chamber (103), be used for detecting the pressure in the exit in tissue culture chamber, said perfusion loop (103);
Displacement sensor (303) is used to detect the displacement that said tension and compression shackle rod (111) takes place;
Tension-compression sensor (301) is used for pulling force or the pressure of detection effect on said tissue culture;
Signal treatment circuit is used for handling by the detected signal of the sensor.
4. the tissue engineering reactor with tension and compression and culture chamber spinfunction according to claim 1 is characterized in that said culture chamber rotary actuator (110), said first rotation transmission device (202) and second rotation transmission device (201) adopt one of gear unit, chain gearing, belt transmission or transmission rod respectively.
5. the tissue engineering reactor with tension and compression and culture chamber spinfunction according to claim 1; It is characterized in that adopting in said tissue culture chamber rotating driving device and the said tissue culture rotating driving device same rotational drive motor as propulsion source, and adopt a clutch/transmission rig to realize the independent rotation in said tissue culture and said tissue culture chamber is driven and/or the different rotation drive pattern.
6. the tissue engineering reactor with tension and compression and culture chamber spinfunction according to claim 1; It is characterized in that in said tension and compression shackle rod (111) and said first rotation transmission device (202) parts direct-coupled along axially interfixing, and absorb back and forth moving axially of said tension and compression shackle rod (111) with the endwisely slipping engagement between the parts in said first rotation transmission device (202) with it.
7. the tissue engineering reactor with tension and compression and culture chamber spinfunction according to claim 1; It is characterized in that; Parts direct-coupled with it be along axially can sliding each other in said tension and compression shackle rod (111) and said first rotation transmission device (202), and make these parts fixing vertically with a stationary installation.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2008101117869A CN101372665B (en) | 2008-05-16 | 2008-05-16 | Tissue engineering reactor having tension-compression and cultivation cavity rotation functions |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2008101117869A CN101372665B (en) | 2008-05-16 | 2008-05-16 | Tissue engineering reactor having tension-compression and cultivation cavity rotation functions |
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| CN101372665A CN101372665A (en) | 2009-02-25 |
| CN101372665B true CN101372665B (en) | 2012-12-26 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103525701B (en) * | 2013-09-13 | 2015-02-04 | 杭州电子科技大学 | Tissue engineering cartilago articularis in-vitro construction method and device |
| 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 |
| CN104342370B (en) * | 2014-05-28 | 2016-08-10 | 中国科学院力学研究所 | Biomechanical system for three-dimensional perfusion stretching and compression culture of cells |
| CN110982696B (en) * | 2020-01-02 | 2021-09-07 | 北京理工大学 | A directional stimulation system and method for artificial neuromuscular tissue |
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|---|---|---|---|---|
| EP0320239A2 (en) * | 1987-12-08 | 1989-06-14 | Mitsui Petrochemical Industries, Ltd. | Method of preparation of plant tissue strips for plant tissue culture |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0320239A2 (en) * | 1987-12-08 | 1989-06-14 | Mitsui Petrochemical Industries, Ltd. | Method of preparation of plant tissue strips for plant tissue culture |
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| Title |
|---|
| BORIS A. NASSERI et al..Dynamic Rotational Seeding and Cell Culture System for Vascular Tube Formation.《TISSUE ENGINEERING》.2003,第9卷(第2期),291-299. * |
| Gregory H. Altman et al..Advanced Bioreactor with Controlled Application of Multi-Dimensional Strain For Tissue Engineering.《J. Biomech. Eng.》.2002,第124卷(第6期),742-749. * |
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| CN101372665A (en) | 2009-02-25 |
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