Temperature-control chamber for controlling the temperature of tissue constructs

EP4655384A1Pending Publication Date: 2025-12-03FRIEDRICH ALEXANDER UNIV ERLANGEN NUERNBERG
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Patent Information

Application Number
EP2024703466
Authority / Receiving Office
EP · EP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-01-27
Filing Date
2024-01-26
Publication Date
2025-12-03

AI Technical Summary

Technical Problem

Current bioreactors are unable to effectively condition hard tissue structures, such as bones, due to the lack of controllable and definable mechanical stimulation, which is crucial for differentiating tissue cells into bone cells, whereas they can only produce soft tissue structures.

Method used

A conditioning chamber with a force transmission section and deformation section that allows for controlled and defined mechanical stimulation of tissue cells within a chamber volume, using a compressive force actuator to apply compressive forces indirectly to the cells, enabling the growth and differentiation of hard tissue structures.

Benefits of technology

Enables the cost-effective and simple growth of hard tissue structures by providing controlled mechanical stimulation, allowing for the development of properties like stability, flexibility, and hardness in tissue constructs, overcoming the limitations of previous bioreactors.

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Abstract

The invention relates to a temperature-control chamber (10) for controlling the temperature of tissue constructs, having chamber walls (20) which enclose a chamber volume (30) for receiving a cellular structure (200). At least one of the chamber walls (20) has a force-transmission section (40), comprising a force-receiving surface (42) on the outer face (22) of said chamber wall (20) for receiving a pressure force (DK) from a pressure-force actuator (110) and a force-transfer surface (44) on the inner face (24) of said chamber wall (20) for transferring the received pressure force (DK) to a cellular structure (200) which can be received in the chamber volume (30). Additionally, the at least one chamber wall (20) has at least one deformation section (50) separately from the force-transmission section (40) for elastically deforming when the pressure force (DK) is acting on the force-transmission section (40).
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Description

[0001] Conditioning chamber for conditioning tissue constructs

[0002] The present invention relates to a conditioning chamber for conditioning tissue constructs and a conditioning method for conditioning bio(artificial) tissue constructs in a conditioning system according to the invention.

[0003] It is generally known that human tissue should be conditioned artificially. For example, this serves to condition tissue cells on a laboratory scale in conjunction with suitable matrix embedding for later use in testing purposes or even for use in humans themselves. In other words, to grow them and expose them to external stimuli in such a way that they can best fulfill their later intended purpose. This already works for soft tissue, such as cartilage structures, skin structures, or similar. However, it is problematic to condition tissue cells so that they can represent hard tissue in a human. In particular, it has so far been difficult or even impossible to artificially condition bones, i.e. to grow them on a laboratory scale and prepare them for biomechanical requirements, and to develop properties such as stability, flexibility, and hardness.This is particularly due to the fact that, in addition to the biological and biochemical prerequisites, external forces also play a crucial role in the conditioning of tissue cells. Especially when generating hard tissue, preferably bone, it is necessary that the growing and conditioned tissue cells within their matrix are subjected to a corresponding compressive or tensile force. Only under the appropriate influence of force are all the biological and biophysical components present for the tissue cells to differentiate into conditioned bone cells as they grow within their matrix.

[0004] With current solutions, this is not possible, or only to a very limited extent. In particular, controllable and definable mechanical stimulation is not possible, so known bioreactors can currently only be used for the creation of soft tissue structures and not for hard tissue.

[0005] The object of the present invention is to at least partially remedy the disadvantages described above. In particular, the object of the present invention is to use bioreactors for the growth of hard tissue structures, in particular artificial bone, in a cost-effective and simple manner.

[0006] The above object is achieved by a conditioning chamber having the features of claim 1, a conditioning system having the features of claim 14, and a conditioning method having the features of claim 17. Further features and details of the invention emerge from the subclaims, the description, and the drawings. Features and details described in connection with the conditioning chamber according to the invention naturally also apply in connection with the conditioning system according to the invention and the conditioning method according to the invention, and vice versa, so that with regard to the disclosure of the individual aspects of the invention, reference is always made to each other.

[0007] According to the invention, a conditioning chamber is used to condition tissue constructs. Such a conditioning chamber has chamber walls that enclose a chamber volume for accommodating a cell scaffold. At least one of the chamber walls is equipped with a force transmission section. This force transmission section has a force absorption surface on the outside of this chamber wall for absorbing a compressive force from a compressive force actuator. Furthermore, the force transmission section is equipped with a force transfer surface on the inside of this chamber wall for transferring the absorbed compressive force to a cell scaffold that can be accommodated in the chamber volume. Furthermore, this at least one chamber wall is equipped, separate from the force transmission section, with at least one deformation section for elastic deformation when the compressive force acts on the force transmission section.

[0008] According to the invention, the conditioning chamber serves to condition tissue cells in a corresponding tissue matrix, which is also referred to as a tissue construct according to the invention, and thus represents a bioreactor or at least part of a bioreactor. The tissue cells can be accommodated by a cell scaffold, which can be referred to as a scaffold structure or also as a scaffold. It is irrelevant whether the cell scaffold is already provided with tissue cells or is introduced into the chamber volume as an empty cell scaffold and whether the tissue cells are later introduced into the cell scaffold via other access points. The cell scaffold can be biomimetic, biological, in particular biologically native or biologically processed, and can already contain tissue cells or be free of them and can be populated with tissue cells at a later time.The core concept of the present invention is that the cell scaffold containing the tissue cells within the chamber volume can be mechanically stimulated repeatedly / continuously in a defined and controlled manner over any desired period of time. Two essential features of the conditioning chamber are designed for this purpose: the force transmission section and the separately formed deformation section. The mode of operation is briefly explained below.

[0009] With the help of a pressure force actuator, as will be explained in more detail later with reference to a conditioning method, but also a conditioning system, a pressure force can be generated, for example, pneumatically, electrically, hydraulically or in a similar manner. It allows this pressure force to be made available in a defined manner. The force transmission section now has two force transmission interfaces. The force transmission section represents a part of the chamber wall or at least one chamber wall, which accordingly has an outer side and an inner side. On the outer side of the force transmission section there is a force absorption surface that acts as an interface for absorbing the pressure force from the pressure force actuator. In other words, in the simplest case, the pressure force actuator can be arranged in force-transmitting contact with the force absorption surface on the outer side of this chamber wall.If the compressive force on the compressive force actuator is subsequently increased, this increasing compressive force is absorbed by the force absorption surface and transferred into the chamber wall. In order to use this applied force in the desired way to mechanically stimulate the cell scaffold accommodated in the chamber volume, this compressive force must be transferred to the cell scaffold. This occurs on the inside of this chamber wall at the force transmission section in the form of the interface of the force transfer surface. In other words, at least in the situation of the applied force, the force transfer surface and thus the inside of this chamber wall lies against the cell scaffold. If the compressive force delivered by the compressive force actuator increases, this increased compressive force is transferred into the chamber wall via the force absorption surface and transferred to the cell scaffold in the same increasing manner via the force transfer surface through the force equilibrium.In other words, it is now possible to apply this compressive force to the cell scaffold in a defined manner mechanically, indirectly, i.e. without direct contact, from the pressure force actuator via the interface functionality of the force transmission section in the hermetically sealable chamber volume.

[0010] To ensure this force transmission, the mobility of this force transmission section is necessary, at least on a small scale, since it must be moved in the direction of reducing the chamber volume. In order to ensure mechanical stimulation in a defined and, above all, directed manner, at least one deformation section is provided separate from the force transmission section. This can be formed, for example, by weakening the material, choosing a different material, or simply a desired deformation point or line. By applying the compressive force, this deformation section can deform elastically and thus reversibly, so that the force transmission section can perform the desired movement to reduce the chamber volume by deforming the deformation section.

[0011] Preferably, when the pressure force is applied, the force transmission section is not deformed or is only deformed to a very small extent, but is moved in the direction of reducing the chamber volume by the corresponding separate deformation of the deformation section.

[0012] Based on the above explanation, it is clear that a defined force can now be applied without requiring direct contact within the chamber volume and thus within the conditioning chamber. It is also evident that the combination of force transmission section and deformation section can be duplicated, thus enabling any multi-axial loading conditions with differently aligned compressive force actuators and correspondingly differently aligned compressive forces. The conditioning chamber itself can hermetically seal the chamber volume, so that contamination from outside is not a problem. Rather, it is possible to indirectly and thus separately couple the compressive force actuator to the force transmission sections of the conditioning chamber, thus providing controlled, mechanical stimulation.Of course, the compressive force can also be varied over different time periods, as will be explained later. This makes it possible to use different profiles of different compressive forces that vary over time for conditioning the tissue constructs.

[0013] It is therefore possible to avoid direct contact between force generation and force application to the cell scaffold, so that the scaffold or graft, i.e. the combination of the cell scaffold and the tissue cells, can be mechanically conditioned unaffected and thus uncontaminated by the environment.

[0014] Plastics, in particular, can be used as materials for the chamber walls. For example, thermoplastics are suitable. The elastic deformation of the deformation section is preferably reversible. This means that the conditioning chamber can be used multiple times and / or different variations with an interim reduction in the compressive force are possible, since a reduction in the compressive force can cause the deformation section to rebound and thus recover.

[0015] For the purposes of the present invention, conditioning of tissue cells and the surrounding matrix means cell differentiation and / or cell growth. However, cell differentiation is at least a part of this conditioning, for example, if tissue cells have grown on the cell scaffold in a separate bioreactor and then only need to be conditioned in the conditioning chamber through mechanical influence and stimulation to mature into hard tissue cells or bone cells. Of course, a conditioning chamber can, as will be explained later, also have additional connections for the introduction of nutrient fluids or the like in order to enable the growth of tissue cells in addition to the differentiation of existing, already grown tissue cells.It can be advantageous if, in a conditioning chamber according to the invention, the force transmission section, in particular the at least one chamber wall with the force transmission section, preferably all chamber walls, have a flat or essentially flat extension. A flat or essentially flat extension brings several advantages. Firstly, the manufacture of the conditioning chamber is simplified, particularly when it is made of a thermoplastic. A further advantage is that this allows for very simple alignment of the forces and correspondingly simple application of the compressive forces. The force distribution across a plane is also easier to predict, which simplifies the control of the applied mechanical stimulation.

[0016] Further advantages can be achieved if, in a conditioning chamber according to the invention, at least two separate deformation sections are arranged for the at least one force transmission section, in particular on different sides of the force transmission section. As already explained, the deformation separate from the force transmission can provide a substantially deformation-free design of the force transmission section. If two or more deformation sections are arranged on different sides of the force transmission section, this leads to a pure translational movement, i.e., a parallel displacement, in particular of the force transfer surface, for the required small movement during the deformation of the deformation sections for the force transmission section.In other words, the preferably symmetrical arrangement of the multiple separate deformation sections allows for even more precise control of the applied compressive force. This offers additional advantages, particularly when bidirectional or multidirectional compressive forces are to be applied. The applied compressive force can also be protected against tilting of the force transmission surface.

[0017] It is furthermore advantageous if, in a conditioning chamber according to the invention, the deformation section has a material weakening of said at least one chamber wall, in particular with a linear or substantially linear extension. For example, this can be a weakening groove or similar, so that although the deformation section is made of the same material as the rest of the chamber wall, it has lower mechanical stability and thus the desired elastic deformability. This applies in particular to identical deformation sections when more than one deformation section is provided on the chamber wall. By designing it as a material weakening, a uniform material can be used for all sections of the respective chamber wall, making production significantly simpler and more cost-effective.

[0018] Further advantages are achieved if, in a conditioning chamber according to the invention, at least two chamber walls have force transmission sections and deformation sections, wherein these chamber walls are arranged at an angle to one another. In particular, these are rectangular arrangements and thus preferably non-parallel arrangements of the force transmission sections. Arranging them at right angles to one another allows for even easier variation, particularly when two or more different pressure force actuators are used, so that by combining two or more pressure force actuators, even complex pressure conditions can be set inside the chamber volume for mechanical stimulation. A particularly simple embodiment is therefore a rectangular or even cubic design of the conditioning chamber.The overlapping edges between two adjacent chamber walls with force transmission sections can have common deformation sections, so that the respective overlapping edge has a double deformation section or a deformation section with double functionality for the two force transmission sections adjacent to different sides.

[0019] It is also advantageous if, in a conditioning chamber according to the invention, one chamber wall has a support section opposite the at least one chamber wall with the force transmission section for supporting the introduced compressive force from a cellular scaffold accommodated in the chamber volume. This means that only a portion of the chamber walls allows active displacement, namely the portion at which the force transmission section is moved or displaced by the introduced compressive force and the correspondingly correlating elastic deformation of the associated deformation section. On the opposite chamber wall, pure support takes place, thus omitting any elastic deformation or translation of this opposite chamber wall. This can also be referred to as a counterbearing or abutment, so that the support section thus provides a passive counterbearing.The two opposing chamber walls formed in this way are preferably aligned parallel or substantially parallel to each other.

[0020] It may also be advantageous if, in a conditioning chamber according to the invention, at least one of the chamber walls has a bio-sensor section with a bio-sensor for detecting at least one bio-parameter of the cells on a cell scaffold accommodated in the chamber volume, in particular for detecting at least one of the following parameters:

[0021] - oxygen concentration,

[0022] - carbon dioxide concentration,

[0023] - PH value.

[0024] The above list is not exhaustive. Of course, combinations of two or more biosensors can also be used. The biosensors are preferably optical sensors, which can carry out a corresponding determination in the interior of the chamber volume without contact through a transparent or at least partially transparent biosensor section. In this way, monitoring and / or regulation and / or control of a media supply is preferably possible if, in addition to differentiation, growth of the tissue cells in the chamber volume is desired. Independently of this, however, it is also possible to determine bioparameters in the form of biomarkers of the cells in order to be able to monitor, for example, the progress of differentiation and thus, for example, the conversion into hard tissue cells.The use of biosensors allows for monitoring and controlling the conditioning process during execution, as well as for detecting growth parameters and / or other conditioning parameters and, accordingly, for displaying the quality and / or quantity of the conditioning. Last but not least, this allows for quality assurance. Another option is contamination monitoring via recorded oxygen consumption.

[0025] It is also advantageous if the biosensor section in a conditioning chamber according to the invention is designed to be transparent at least in sections. For example, transparent glass sections or transparent plastic film sections are conceivable to provide such a biosensor section. Such biosensor sections can thus also form transparent or partially transparent chamber walls. It is also possible for the corresponding biosensors to be designed on the outside, on the inside, or with partial elements of the sensor on the inside. The use of transparent biosensor sections also allows the measurement and thus the monitoring, for example through the use of imaging techniques, to be carried out contactlessly and thus free from contamination of the chamber volume. It is also conceivable that coated glass fibers could be used as spatially high-resolution biosensors.These can, for example, be brought to defined positions in the chamber volume or matrix volume via the chamber lid.

[0026] It is also advantageous if, in a conditioning chamber according to the invention, at least one of the chamber walls has a fastening tab for attaching the bio-sensor section. This means that the bio-sensor section can be attached to this fastening tab, particularly irreversibly. This can, for example, be an adhesive attachment. For example, glass plates and / or glass windows can be glued and / or bonded to such fastening tabs. This can, for example, be the top and / or bottom of such a chamber volume and thus the conditioning chamber.

[0027] Further advantages can be achieved if, in a conditioning chamber according to the invention, at least one of the chamber walls has a force sensor section with a force sensor for detecting the compressive force introduced into the at least one force transmission section. It is also possible to arrange an integrated load cell for force measurement in the force arm of the force actuator. In this case, the monitored compressive forces can, for example, be used to check, monitor, or even regulate the compressive forces actually applied. In particular, when complex compressive force profiles are used for conditioning, this feedback can be used to carry out quality control, but also to check that the end of the conditioning has been reached. In other words, a direct control loop for the mechanical stimulation of the tissue cells is achieved in this way.

[0028] It can also be advantageous if, in a conditioning chamber according to the invention, at least one of the chamber walls has a media connection, in particular with at least one media inlet and at least one media outlet. If tissue cell growth is also desired for conditioning, growth fluids, for example a media supply with nutrients, but also the removal of cellular waste products, can be added and removed here. The growth of tissue cells is thus possible in the same conditioning chamber as the differentiation of the grown tissue cells. It is also conceivable in principle to even introduce the tissue cells themselves through these media connections, so that at the beginning of a conditioning process, an empty cell framework / scaffold is used, which in a subsequent step is supplied with tissue cells or tissue precursor cells via the media connection.During the growth of the introduced cells, the media connections ensure nutrient supply and cell product removal. The sensors discussed above, which are also located in the media lines, can be used to monitor bioparameters of the tissue cells.

[0029] It is further advantageous if, in a conditioning chamber according to the invention, the media connection is spatially correlated with the at least one deformation section, such that at least a part of the media connection protrudes into the deformation section. In particular, if the deformation section is formed by material weakening, it thus essentially forms a groove in the chamber wall. If the media connection protrudes into such a groove, this groove and thus the deformation section can thus ensure the dual function of also providing a receptacle for the respective media connection. This makes it possible to reduce the dead space volume otherwise created by the deformation section and thus further improve the entire conditioning chamber. The dead space volume can in principle be further minimized by encasing the entire length of the media connection in the chamber.

[0030] It is also advantageous if, in a conditioning chamber according to the invention, at least two chamber walls, in particular all chamber walls, are monolithic. For example, the conditioning chamber can be manufactured as an injection-molded part using a thermoplastic material and thus be provided in one piece. This allows for particularly simple production, for example by injection molding, but also by 3D printing or other additive processes. In particular, a subtractive process (CNC milling) from a plastic block (PEEK) can be used here. The monolithic design of the chamber walls also allows the use of identical materials, which further reduces the cost of manufacturing such conditioning chambers.Last but not least, the monolithic design of two or more chamber walls is an advantage, as it ensures 100% leak-tightness and highly predictable mechanical deformability. Last but not least, the materials for the chamber walls are preferably made of an autoclavable material, so that the chamber walls, and thus the conditioning chamber, are sterilizable and thus reusable.

[0031] A further subject of the present invention is a conditioning system for conditioning tissue cells in a tissue matrix, comprising a receiving surface for receiving and positioning at least one conditioning chamber according to the invention. Furthermore, at least one compressive force actuator is provided for introducing a compressive force into the at least one force-receiving surface of the conditioning chamber. Such a conditioning system offers the same advantages as have been explained in detail with reference to a conditioning chamber according to the invention. Preferably, two or more compressive force actuators, two or more media connections, and / or two or more sensor connections are provided, as has already been explained in more detail with reference to the conditioning chambers.Further advantages are achieved if, in a conditioning system according to the invention, the at least one pressure force actuator has one of the following designs:

[0032] - Pneumatics,

[0033] - Hydraulics,

[0034] - Electric, with or without transmission.

[0035] The above list is not exhaustive. Preferably, all pressure force actuators of the conditioning system are identical or essentially identical. More complex or different pressure force actuators, such as piezo pressure force actuators, are also conceivable. Furthermore, the pressure force actuators used are preferably provided with a linear pressure force generation mechanism.

[0036] It is further advantageous if, in a conditioning system according to the invention, a mechanical abutment is provided for each pressure force actuator to absorb the pressure force transmitted through the conditioning chamber. This ensures contact and thus absorption of the pressure force transmitted through the conditioning chambers via the aforementioned and explained support section. The mechanical abutments can be fixed or adjustable. Adjustability can be provided, for example, by a threaded bolt or another type of translational bearing with a locking mechanism.

[0037] Furthermore, the present invention relates to a conditioning method for conditioning tissue constructs in a conditioning system according to the invention, comprising the following steps:

[0038] - Introducing a cell scaffold into the chamber volume of the conditioning chamber,

[0039] - Connecting the at least one pressure force actuator to the conditioning chamber, - Applying a pressure force by means of the at least one pressure force actuator.

[0040] A conditioning method according to the invention offers the same advantages as those explained in detail with reference to a conditioning system according to the invention and with reference to a conditioning chamber according to the invention. The individual steps are preferably monitored, controlled, and / or regulated. In particular, control of the supply and the achievement of targets, for example, the hardness, size, or resistance of the tissue construct, can be provided. Sterility can also be monitored, for example, by detecting bacterial growth using an imaging technique or, for example, by measuring increased CO2 emissions or O2 consumption.

[0041] It is also advantageous if the applied compressive force is varied in a conditioning method according to the invention. This variation can occur over time, for example, in a controlled, defined, frequency-dependent, or other manner. All compressive forces can be identical or varied differently. Different or identical compressive forces can also be used for different sides of the conditioning chamber.

[0042] Furthermore, it is advantageous if, in a conditioning method according to the invention for connecting the compressive force actuator to the conditioning chamber, the compressive force actuator is moved into a position contacting the force-absorbing surface, and then a compressive force is applied, causing a deformation of this chamber wall until contact is made between the cell scaffold in the chamber volume and the force-transfer surface. This is understood to mean deformation until the first resistance is encountered, i.e., until contact is made with the cell scaffold inside the chamber volume. This can also be understood as moving to a starting position for the subsequent conditioning step. Of course, load breaks are also possible, which are ensured, for example, by releasing this contact.

[0043] Further advantages, features, and details of the invention will become apparent from the following description, which describes embodiments of the invention in detail with reference to the drawings. The features mentioned in the claims and in the description may be essential to the invention individually or in any combination. They show schematically:

[0044] Fig. 1 shows an embodiment of a conditioning chamber according to the invention,

[0045] Fig. 2 the embodiment of Figure 1 in a different perspective,

[0046] Fig. 3 shows the embodiment of Figures 1 and 2 in a different perspective,

[0047] Fig. 4 shows the embodiment of Figures 1 to 3 in a different perspective,

[0048] Fig. 5 shows the embodiment of Figures 1 to 4 in exploded view,

[0049] Fig. 6 the cover of the embodiment of Figure 7,

[0050] Fig. 7 the embodiments of Figures 1 to 4 with lid during placement,

[0051] Fig. 8 shows an embodiment of a conditioning system according to the invention,

[0052] Fig. 9 is a partial view of the conditioning system of Figure 8.

[0053] Figures 1 to 4 show a portion of a conditioning chamber 10 from different perspectives. This can subsequently be closed with a lid and a bottom, as will be explained later. The conditioning chamber 10 is essentially cube-shaped here and has four chamber walls 20 in a base body. These four chamber walls 20 define a hollow space, which can be seen here as chamber volume 30.

[0054] Two of these chamber walls 20 are designed for the introduction of a compressive force DK. In Figure 1, these are the two chamber walls 20 pointing to the right, which accordingly have the force-absorbing surfaces 42 of the force-transmitting sections 40 on their outer side 22. If compressive forces DK are now applied to these force-absorbing surfaces 42, the linearly aligned deformation sections 50, formed as material weakenings 52, are deformed. These force-transmitting sections are thus pushed into the chamber volume 30 under the elastic deformation of these deformation sections 50. This occurs when the force-transmitting sections 40 are flat. As soon as a cell framework 200 (not shown in detail in Figures 1 to 4) is reached, the introduced compressive forces DK are transmitted via the force-transmitting surfaces 44 on the inner side 24 of the respective chamber wall 20.

[0055] In order to be able to support the introduced compressive forces DK, the two support sections 60 are provided on the two opposite chamber walls 20, which are each oriented to the left in Figures 1 and 2, and which, as explained later, can interact with abutments 130.

[0056] Furthermore, Figures 1 to 4 show tab-like extensions as fastening tabs 27 on the underside of the conditioning chamber 10. Transparent or glass-like chamber walls 20 can be glued to these to provide a bio-sensor 70 for a bio-sensor section 26. Force sensor sections 28 can also be provided here or integrated into the lateral chamber walls 20.

[0057] Figure 5 shows an exploded view of an assembly situation. In this case, a glass chamber wall is already glued to the underside, thus closing the conditioning chamber 10 from the bottom. To fill the chamber volume, the cell scaffold 200, for example, already with integrated tissue cells, is inserted, and the chamber volume 30 is then closed. The closure is achieved by attaching a bio-sensor section 26 in the form of a glass pane and hermetically sealing it with a chamber wall 20 designed as a lid. A central insert can provide access to the bio-sensors 70 arranged behind the bio-sensor section 26. Figures 6 and 7 show the possibility of supplying media to the chamber volume 30.Media connections 90 are equipped here with a media supply 92 and a media discharge 94, which correlate with corresponding material weakenings 52 of the deformation sections 50 and extend into them, as shown in Figure 7. Figure 7 shows a state during the closing process. After complete closure, the media connections 90 are, of course, only visible and accessible from the outside.

[0058] Figure 8 schematically shows the structure of a conditioning system 100. Figure 9 shows the corresponding representation after recording in detail at the receiving surface 120. As soon as the conditioning chamber 10 has been filled with the tissue cells and the cell scaffold 200 and closed, it can be placed on the receiving surface 120 in the situation shown in Figures 8 and 9. The position is predetermined via the abutments 130. Subsequently, the compression force actuators 110, designed as hydraulic or pneumatic actuators in this embodiment of the conditioning system, can be activated for the conditioning process. The compression force actuators 110 move into contact with the outer side 22 of the chamber walls 20 with the force transmission sections 40 and can then apply the compression forces DK in a bidirectional manner in a targeted and controlled manner for the mechanical stimulation of the tissue cells.

[0059] The above explanation describes the present invention exclusively within the framework of examples. Of course, individual features can be freely combined with one another, provided they are technically feasible, without departing from the scope of the present invention.

[0060] List of reference symbols

[0061] 10 Conditioning chamber

[0062] 20 chamber wall

[0063] 22 Outside

[0064] 24 Inside

[0065] 26 Bio-sensor section

[0066] 27 Mounting tab

[0067] 28 Force sensor section

[0068] 30 chamber volume

[0069] 40 Power transmission section

[0070] 42 force absorption area

[0071] 44 Power transfer area

[0072] 50 deformation section

[0073] 52 Material weakening

[0074] 60 support section

[0075] 70 Bio-Sensor

[0076] 80 force sensor

[0077] 90 Media connection

[0078] 92 Media supply

[0079] 94 Media collection

[0080] 100 conditioning system

[0081] 110 Pressure force actuator

[0082] 120 recording area

[0083] 130 abutments

[0084] 200 cell scaffold

[0085] DK compressive force

Claims

Patent claims 1. Conditioning chamber (10) for conditioning tissue constructs, comprising chamber walls (20) which enclose a chamber volume (30) for receiving a cell scaffold (200), wherein at least one of the chamber walls (20) has a force transmission section (40) with a force absorption surface (42) on the outer side (22) of this chamber wall (20) for receiving a compressive force (DK) from a compressive force actuator (110) and a force transfer surface (44) on the inner side (24) of this chamber wall (20) for transferring the absorbed compressive force (DK) to a cell scaffold (200) which can be received in the chamber volume (30), wherein this at least one chamber wall (20) further has, separate from the force transmission section (40), at least one deformation section (50) for elastic deformation when the compressive force (DK) acts on the force transmission section (40).

2. Conditioning chamber (10) according to claim 1, characterized in that the force transmission section (40), in particular the at least one chamber wall (20) with the force transmission section (40), preferably all chamber walls (20), have a flat or substantially flat extension.

3. Conditioning chamber (10) according to one of the preceding claims, characterized in that for the at least one force transmission section (40) at least two separate deformation sections (50) are arranged, in particular on different sides of the force transmission section (40).

4. Conditioning chamber (10) according to one of the preceding claims, characterized in that the deformation section (50) has a material weakening (52) of this at least one chamber wall (20), in particular with a linear or substantially linear extension.

5. Conditioning chamber (10) according to one of the preceding claims, characterized in that at least two chamber walls (20) have force transmission sections (40) and deformation sections (50), wherein these chamber walls (20) are arranged at an angle to one another.

6. Conditioning chamber (10) according to one of the preceding claims, characterized in that a chamber wall (20) opposite the at least one chamber wall (20) with the force transmission section (40) has a support section (60) for supporting the introduced compressive force (DK) from a cell scaffold (200) accommodated in the chamber volume (30).

7. Conditioning chamber (10) according to one of the preceding claims, characterized in that at least one of the chamber walls (20) has a bio-sensor section (26) with a bio-sensor (70) for detecting at least one bio-parameter of the cells on a cell scaffold (200) accommodated in the chamber volume (30), in particular for detecting at least one of the following parameters: - Oxygen concentration - Carbon dioxide concentration - PH value 8. Conditioning chamber (10) according to claim 7, characterized in that the bio-sensor section (26) is at least partially transparent.

9. Conditioning chamber (10) according to one of claims 7 or 8, characterized in that at least one of the chamber walls (20) has a fastening tab (27) for fastening the bio-sensor section 10. Conditioning chamber (10) according to one of the preceding claims, characterized in that at least one of the chamber walls (20) has a force sensor section (28) with a force sensor (80) for detecting the compressive force (DK) introduced into the at least one force transmission section (40).

11. Conditioning chamber (10) according to one of the preceding claims, characterized in that at least one of the chamber walls (20) has a media connection (90), in particular with at least one media supply (92) and at least one media discharge (94).

12. Conditioning chamber (10) according to claim 11, characterized in that the media connection (90) is locally correlated with the at least one deformation section (50), so that at least a part of the media connection (90) projects into the deformation section (50).

13. Conditioning chamber (10) according to one of the preceding claims, characterized in that at least two chamber walls (20), in particular all chamber walls (20), are monolithic.

14. Conditioning system (100) for conditioning tissue constructs, comprising a receiving surface (120) for receiving and positioning at least one conditioning chamber (10) with the features of one of claims 1 to 13, at least one compressive force actuator (110) for introducing a compressive force (DK) into the at least one force receiving surface (42) of the conditioning chamber (10).

15. Conditioning system (100) according to claim 14, characterized in that the at least one pressure force actuator (110) has one of the following configurations: - Pneumatics - Hydraulics Electric, with or without gearbox 16. Conditioning system (100) according to one of claims 14 or 15, characterized in that for each pressure force actuator (110) a mechanical abutment (130) is formed for receiving the pressure force (DK) guided through the conditioning chamber (10).

17. Conditioning method for conditioning tissue constructs in a conditioning system (100) having the features of one of claims 14 to 16, comprising the following steps: - introducing a cell scaffold (200) into the chamber volume (30) of the conditioning chamber (10), - connecting the at least one pressure force actuator (110) to the conditioning chamber (10), - applying a compressive force (DK) by means of the at least one compressive force actuator (110).

18. Conditioning method according to claim 17, characterized in that the applied compressive force (DK) is varied.

19. Conditioning method according to one of claims 17 or 18, characterized in that for connecting the pressure force actuator (110) to the conditioning chamber (10), the pressure force actuator (110) is moved into a position contacting the force receiving surface (42) and then a pressure force (DK) is applied for a deformation of this chamber wall (20) until contact between the cell framework (200) in the chamber volume (30) and the force transfer surface (44).