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  • 权利要求
  • 类似技术
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    • 专利摘要:
    A bioreactor is proposed for the creation of, in particular, cartilage tissue sets, consisting of a hermetically separated chamber in which the device for the mechanical loading of the cartilage tissue sets is attached. In order to create advantageous construction conditions, it is proposed that the device for the mechanical loading of the culture vessel is provided on a base (8) in the upper part (6) of the culture vessel and at least one rotary pressure inlet (13) connected to a driver (2). comprising, wherein the driver (2), with a linear motor (1) is connected and against the culture vessel (5) slidably mounted.
    公开号:AT13284U1
    申请号:TGM583/2011U
    申请日:2011-10-27
    公开日:2013-09-15
    发明作者:
    申请人:Ceske Vut V Praze Fakulta Strojni Ustav Mechaniky Biomechaniky A Mechatroniky；
    IPC主号:
    专利说明:

    Austrian Patent Office AT13 284U1 2013-09-15
    Description The technical solution relates to the bioreactor for functional tissue engineering, which is composed of a hermetically separated chamber in which a device is mounted, in particular for the mechanical stress of cartilage replacement.
    For a successful production of cartilage replacements, the individual tissue preparations are to complain after occupying the cells mechanically. At the same time, the milieu is to ensure that the given cells can develop further. It comes to meeting such requirements to create a functional tissue implant that is prepared for the implantation of biological stress. The tissue bioreactors are used in the process of cartilage maturation for the simulation of the cycles to be loaded.
    The purpose of current facilities for tissue culture is to mimic in vivo conditions, preferably from a chemical and biological point of view. This environment is formed in the current types of bioreactors depending on the type of tissue desired. In general, it can be said that such devices are those which ensure the chemical and biological sustainability of the nutritional medium, where the incubation temperature of the culture space is regulated and monitored, and where the required pressure and concentration of the mixtures of the planting and culturing media is ensured , Nonetheless, to allow viable tissue to grow, the device must meet the requirements for ease of sterilization, access of the nutritional medium to the cells to be cultured, and their variation.
    One of the most basic designs is the so-called Flask (Piston) system, which contains the culture medium, and may also contain several supporting scaffolds, depending on the size. The piston (s) is (are) operated either static or mixed.
    A special case may be the bioreactors for the growth of the cardiac tissues, which are adapted to the single-lane and two-lobed pulsation flow of the growth medium via the construction of the supporting scaffolds. They are thus adapted to simulate the cardiovascular environment. Representatives of these bioreactors are the FIARV (High Aspect Ratio Vessels) and STLV (Slow Turning Lateral Vessels) systems. The STLV is configured as an annular space between two concentric cylinders, the inner one being the membrane for gas exchange, while the HARV is a cylinder vessel with the membrane for gas exchange in its bottom. Both vessels are in space in the horizontal plane and rotate each other.
    The other system used is the RWPV (Rotating Wall Perfused Vessels) system, which was developed by NASA and was used, inter alia, for cartilage cultivation in the field of microgravity as well as under normal conditions. The medium circulates continuously in the perfused columns. The perfused chambers are designed so that the medium runs continuously between the chamber and the outer membrane.
    So far, the design of the bioreactor for the growth of cartilage replacement, specifically in the field of simulation of realistic loading conditions has not been resolved sufficiently. The existing cartilage reactors complain the individual implants by simple loading with pressure or shear forces. Cartilage in vivo always has a combination of these stresses due to the specific geometry, kinematics and properties of the contact surfaces.
    The disadvantage of the previous solutions is the indirect mechanical stimulation of the tissue, which, although in principle suitable for the appropriate growth of the preparations to be cultivated.
    The invention improves the aforementioned disadvantages with those in the mark of the Austrian Patent Office AT13 284U1 2013-09-15
    Feature 1 specified characteristics. Advantageous developments of the invention can be found in the subclaims. The abovementioned deficiencies are to a large extent eliminated by the bioreactor for functional tissue engineering according to the invention consisting of a hermetically separated chamber in which the device for the mechanical loading, in particular the tissue remnants of the cartilage, is mounted. The invention consists in that the device for the mechanical loading of the cultivation vessel is provided on a base in the upper part of the cultivation vessel and comprises at least one rotary pressure inlet connected to a driver, wherein the carrier is connected to a linear motor and slidably mounted relative to the culture vessel is.
    The device is advantageously formed with a linear motor, connected to the stator of the lower part of the cultivation vessel and the upper part of the cultivation vessel and to the moving part of the linear motor, the driver is connected to at least one rotating roller bearing on the axis Indentor. The axis is slidably embedded in the vertical direction in guides of the vertical webs for the uniform cyclic loading of the cultivation patterns through the indentor.
    Advantageously, at least one relieving tension spring and / or compression spring is coupled to the axis, wherein between the axis and the springs of the voltage sampler is inserted.
    Around the rotary indentor can be girded a pair of fastened to the connection profile brake bands. To the brake bands is a balance bar for ensuring the symmetry of the tensile force in belts for adjusting the rolling, the slip or a complete sliding of the indentor on the pad, linked.
    The upper part of the culture vessel is divided in an advantageous embodiment by elongated partitions and a transverse wall to smaller cultivation spaces for the pad with openings for the cultivation pattern. The underlay is made of material having analogous mechanical properties as are the mechanical properties of the future required fabric for ensuring stability and even distribution of stress on the patterns.
    The basis of the technical solution is the arrangement of the rotating Indentor in the growth chamber of the bioreactor. The chamber is hermetically separated from the surrounding laboratory environment and inside the protective atmosphere is maintained. The bioreactor chamber virtually provides a laminar lab box adapted to the size of the culture well with patterns. In contrast to the technical solutions used, this results in direct mechanical stimulation of the well-tended tissue through the rotary indentor, which simulates the real load on the joint.
    The rotary indentor forms a cylinder with the rotary bearing, which passes over the tissue pattern to be cultivated with different thickness of the set contact pressure. Another contribution is the possibility of unwinding, partial hatching or complete sliding, which not only stimulates a normal load, but also the component in the tangential direction, a sliding load. With this solution, we are expressively approaching the in vivo conditions of tissue growth in the organism. The patterns of the tissue to be cultivated are stored in cylindrical openings. The remainder of the cultivation space is filled with the support of the material, with the analogous mechanical properties, as are the mechanical properties of the future required tissue. The rotary indenter moves after the pad with patterns in a uniform motion and a constant contact pressure, wherein the individual parameters of the movement and the contact pressure during the cultivation can be changed and recorded. The patterns and tub are stored in a small tempered tub. The design solution eliminates any shortcomings of existing standard equipment.
    The technical solution relates to the new furnishing concept, which stimulates the tissue in the course of growth. The bioreactor with the rotary indentor for the functional 2/8 Austrian Patent Office AT 13 284 Ul 2013-09-15
    Tissue Engineering of the cartilage sets and with the continuous supplementation of the nutrients constitutes a three-phase device in which the inner atmosphere is controlled, furthermore the supply of nutrients is regulated and last but not least there is mechanical stimulation by the indentor of the cultured cells.
    The designed technical solution increases the efficiency of mechanical tissue stimulation by their arrangement. This consists mainly in the possible lateral force load under the applied simultaneously normal contact pressure. By using two cylinders with five functional surfaces it is possible to carry out the cultivation of up to 50 samples at the same time, which means an economic contribution and quite a bit of time savings.
    Compared to simpler device types, represented by the above-mentioned "Flask" system, the proposed solution is economically and technically more sophisticated device that is more convenient from the point of view of the technical needs of the controller in their conclusion for the operator. The whole system is equipped with a lot of control and control elements, which make it possible to better track the gears in the interior of the device and more precise settings of the operating parameters. Compared to the more complicated and specialized systems, the mutual comparison is tricky in that the above-mentioned systems "HARV, STLV and RWPV" are primarily intended for the cultivation of tissue types other than our designed bioreactor. Nevertheless, it can be assumed that with regard to the construction, the resulting mechanical effect for mechanical stimulation is lower than in direct contact of the cylinder and tissue.
    The bioreactor is described in more detail by this technical solution to a specific embodiment with the aid of accompanying drawings, where the system of mechanical stimulation in Figure 1 schematically in the axonometric sight, in Figure 2, the embedding of the indentor in detail and on the picture 3 the technical design for the partial slip and complete sliding are shown.
    The device according to the picture 1 and 2 consists of the linear servo motor 1, which is connected in the upper part with screws to the elongated struts 3 and is fixed on the lower surface to the bioreactor chamber. On the movable part of the linear servo motors 1 is fixed with screws of the driver 2 of the rotary indentor 13 and to 4 four vertical webs 11 are fixed by means of screws, which are provided with elongated grooves for the sliding guide. Each pair of webs 11 is, in order to achieve the necessary rigidity, mutually connected to the connection profile 10, which are threads for the adjusting screws 12 for a contact pressure adjustment. The elongated struts 3 are turned on to the lower part of the cultivation vessel 5. The lower part 5 is provided for the passage of the heating medium with an S-shaped groove and is connected to the upper part 6 so that the loss of the heating medium is prevented. The lower part 5 is also provided on the circumference with a groove for the discharge of superfluous nutrition. The upper part 6 of the culture vessel 5 is divided with elongated partitions 7 and the transverse wall 14 into smaller cultivation rooms. In the interior of the cultivation rooms, the base 8 is made of material of analogous mechanical properties, such as the future desired fabrics provided with openings for the storage of the cylindrical cultivation patterns 9. The rotatably bedded with bearings 15 on the axis 16 rotary indentor 13 rolls on the base 8 completely from, if necessary, in partial slippage or he glides perfect.
    In Figure 2, the Anpresssystem used for sizing the contact pressure is shown. With the axis 16 is firmly connected and secured with the nut 17 of the voltage generator 18 train / pressure. On the opposite side of the encoder 18, the support shell 19 of the compression spring 22 is screwed, part of which is also the towing clutch of the tension spring 21. At the opposite side of the compression spring 22 is the towing clutch 20 of the tension spring 21, which also serves as a support pad for the compression spring 22. By the movement of the 3/8 Austrian Patent Office AT13 284U1 2013-09-15
    Screw 12 creates a total of three modes of operation. The home position mode I is that the screw 12 is in the position when the tension spring 21 is raised and the indentor 13 is not in contact with patterns 9. Mode II. Arises when the screw 12 is in such a position Position is when it comes to the contact of the indentor 13 with the pad 8 and the cultivation patterns 9. The Anpressgröße is in this case 0 to the value of Anpressgröße, which is derived by the intrinsic weight of the indentor 13. Mode III. arises when the load of the deformation of the compression spring 22 caused by the screw 12 connects to the contact pressure of the indentor 13. Due to the symmetry of the load, the load must be adjusted by the screws 12 in mutual agreement and this is the information from the encoder 18.
    In Figure 3, the use is shown as a braking system or fully blocked Indentor 13. The Indentor 13 braking is realized by the pair of belts 23, which girdles the gap except functional surfaces. The bands 23 are fixedly connected on one side with the connection profile 10 and on the other side are secured by means of screws 25, nuts 24, lock washers 26 to the rectangular balance beam 27 which is connected to the nut 32 and the screw 33 to the drawbar 31 screwed. It is ensured by the use of the balance beam 27 with the pivot bearing around the screws 25 and 33, the same tensile force in the bands 23. The size of the tensile force in the bands 23 can be regulated by the nut 29 with the washer 30. For the tensile force measurement in the bands 23 can be inserted between the washer 30 and the connection profile 10 of the encoder.
    The rotary indentor 13 including its components - the upper part 6, the elongated partition 7, which come into contact with the tissue to be cultivated, are made of the anticorrosive biocompatible material. The other components are made of anticorrosive steel. The dimensions of the cultivation part are 200x650 mm. The size of the individual cultivation rooms is 30x300 mm. There are 5 patterns to be cultivated in each of them. All at once, up to 50 can be maintained. The stored patterns 9 consist of the matrix occupied with the culture cells of the tissue. The surrounding space is filled, besides the patterns, with the base 8, which is of the analogous material like the collagen, of the specific chemical composition, which ensures the corresponding chemical-mechanical properties.
    The cultivation is carried out in such a way that under exactly defined biological-physical conditions, e.g. Temperature, concentration of the nutrient solution and composition of the protective atmosphere are for mechanical stimulation of the pattern 9 by the rotary indentor 13 comes. The device allows for continuous loading or loads with pauses defined by the user. The adjustment of the contact pressure is selected and adjusted by the operator. Each of the cylinders of the indenter 13 can be set to other load parameters, i. H. So also for different conditions of cultivation. The contact pressure can be adjusted by means of the screws 12 and with the design by means of the encoder 18. The contact pressures can be tracked during cultivation and recorded in terms of data technology.
    The bioreactor for the functional tissue engineering according to this technical solution is used in particular in tissue engineering and medicine. Current trends show that research and development are taking place precisely through this direction. 4.8
    权利要求:
    Claims (5)
    [1]
    Austrian Patent Office AT 13 284 Ul 2013-09-15 Claims 1. A bioreactor for creating in particular cartilaginous tissue sets, consisting of a hermetically separated chamber in which the device for the mechanical loading of the cartilaginous tissue sets is attached, characterized in that the device for the mechanical loading of the cultivation vessel on a base (8) in the upper part (6) of the cultivation vessel and at least one to a driver (2) connected Rotations-Druckindentor (13), wherein the driver (2) with a linear motor (1 ) and slidably mounted opposite the culture vessel (5).
    [2]
    2. bioreactor according to claim 1, characterized in that the stator of the linear motor (1) of the lower part of the cultivation vessel (5) and the upper part (6) of the cultivation vessel (5) and belong to the moving part of the linear motor (1) the driver (2) with at least one rollably mounted rotary indentor (13) listened, which is mounted on a sliding in the guide of the vertical webs (11) mounted axis (16).
    [3]
    3. bioreactor according to claim 1 or 2, characterized in that the axis (16) is assigned at least one relief tension spring (21) and a compression spring (22), wherein between the axis (16) and the springs (21), (22 ) of the voltage generator (18) is inserted.
    [4]
    4. Bioreactor according to one of claims 1 to 3, characterized in that a pair of brake bands (23) girdles the rotary indentor (13) which is fastened to a connecting profile (10), wherein the brake bands (23) of the balance beam (27 ) is assigned for ensuring the symmetry of the tensile force in the brake bands (23).
    [5]
    5. Bioreactor according to one of claims 1 to 4, characterized in that the upper part (6) of the culture vessel is divided by the elongated partitions (7) and the transverse wall (14), wherein the base (8) with openings for the zu cultured preparations (9) is provided. For this 3 sheets drawings 5/8
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    引用文献:
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    US6060306A|1995-06-07|2000-05-09|Advanced Tissue Sciences, Inc.|Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing replacement cartilage tissue constructs|
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    法律状态:
    2015-06-15| MM01| Lapse because of not paying annual fees|Effective date: 20141031 |
    优先权:
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