Conditioning chamber for conditioning tissue cells

Abstract

The present invention relates to a conditioning chamber (10) for conditioning tissue cells, 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 wave transfer section (62) for receiving shock waves from a shock wave generator (140) and transferring the received shock waves to the chamber volume (30).

Description

[0001] The present invention relates to a conditioning chamber for conditioning tissue cells and a conditioning method for conditioning tissue cells in a conditioning system according to the invention.

[0002] It is generally known that human tissue should be conditioned artificially. For example, this serves to condition tissue cells on a laboratory scale for later use in testing purposes or even for use in humans themselves, i.e. to grow them in such a way that they can fulfill the 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. This is primarily because, in addition to the biological and biochemical prerequisites, force influences also play a decisive role in the conditioning of tissue cells.Especially when creating hard tissue, preferably bone, it is necessary that the growing and conditioned tissue cells are subjected to an appropriate compressive or tensile force. Only under the appropriate force are all the biological components present to condition the tissue cells into bone cells during growth.

[0003] 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 only be used for the creation of soft tissue structures and not for hard tissue.

[0004] 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.

[0005] The above object is achieved by a conditioning chamber having the features of claim 1, a conditioning system having the features of claim 10, and a conditioning method having the features of claim 11. 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 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.

[0006] The present invention relates to a conditioning chamber for conditioning tissue cells. For this purpose, the conditioning chamber is equipped with chamber walls that enclose a chamber volume. A cell scaffold can be accommodated in the chamber volume, wherein at least one of the chamber walls has a wave transfer section for receiving shock waves from a shock wave generator and transferring the received shock waves to the chamber volume.

[0007] Such a conditioning chamber serves to condition tissue cells. Tissue cell conditioning refers, in particular, to the growth of tissue cells and / or the modification of tissue cells in a targeted manner. A particularly preferred form of conditioning is the creation of bone tissue, i.e., a hardened tissue consisting of individual cells. The cell scaffold forms a basis and serves to keep the cells in a predefined shape and provide a basis for growth.

[0008] In addition to the further conditioning options, as will be explained later, particularly with regard to the supply and removal of media, and in particular with regard to the application of force, the inventive design of the conditioning chamber provides the option of introducing shock waves into the chamber volume. It is already generally known that, within the framework of so-called shock wave therapy on the human body, forms of therapy are provided to, for example, improve blood circulation in human tissue cells. In the inventive design, one or more shock wave generators are provided to generate similar or identical shock waves. Shock waves within the meaning of the present invention can, for example, be in the range of 2 to 4 Hertz, in particular up to 20 or 25 Hertz.Such shock waves can also be designed to be variable, in particular by the shock wave generator, for example with regard to their frequency, their amplitude, their energy content, their method of introduction or with regard to other wave parameters.

[0009] The core concept of the invention is to vary, and in particular improve, the conditioning of tissue cells through the introduction of shock waves. For example, one goal is to positively influence their growth through the targeted introduction of shock waves into the conditioning tissue cells on the cell scaffold in the chamber volume. One possible way of improving and influencing these cells is briefly explained below.

[0010] During the conditioning process in a conditioning method, as will be explained later, the invention provides that the shock waves are introduced into the chamber volume by the shock wave generator. During the conditioning, tissue cells are already located on the cell scaffold and are supplied, for example, by means of a media supply. As the tissue cells grow, they spread across the cell scaffold and grow in whatever place they find an opportunity to grow. By introducing shock waves, these shock waves can lead to at least some of the tissue cells that have already grown on the cell scaffold detaching from it and redistributing themselves within the cell scaffold. In other words, an undesirable agglomeration of tissue cells in partial areas of the cell scaffold is avoided, and at the same time a new distribution or improved redistribution of the cells within the cell scaffold is provided.

[0011] Alternatively or additionally, shock waves can be used to better distribute the media. Particularly when the conditioning procedure is already more advanced, the grown and introduced tissue cells already close off parts of the cell scaffold or even seal it off completely. In such a case, the tissue cells have already grown into a larger tissue structure on the cell scaffold and can therefore block off parts of it or even seal it off completely. The introduction of shock waves can now serve to open the blocked areas or, in the form of active introduction and pulsation, to ensure media supply to the blocked areas. In other words, this makes it possible to ensure the desired media supply even in advanced conditioning situations and thus accelerate and / or improve the further growth of the tissue cells.

[0012] It can be advantageous if, in a conditioning chamber according to the invention, at least one of the chamber walls is designed as a wave damping section for damping the shock waves transferred via the wave transfer section. The wave damping section is arranged, in particular, opposite or substantially opposite the wave transfer section. A wave damping section serves not to reflect shock waves, but to absorb them and compensate for them, for example, through the elastic deformability of the surface of such a wave damping section. While hard surfaces would reflect shock waves, particularly in a chamber volume filled with a liquid or gaseous medium, the wave damping section serves the opposite function.Shock waves introduced into the conditioning chamber via the wave transfer section are thus passed through the chamber volume only once. As soon as they reach the wave damping section, particularly on the opposite side of the chamber wall, the formation of an elastic surface in the wave damping section dampens the introduced and penetrated shock waves there and, in particular, prevents or at least minimizes reflection of the shock waves. This allows the shock waves to be introduced in an even more targeted manner and, in particular, avoids or even completely prevents untargeted reflection or even interference of introduced and reflected shock waves. In particular, this means that the introduced shock waves can be introduced even more precisely, making it possible to positively influence conditioning with the help of the shock waves in a very precisely controlled manner.

[0013] A further advantage can be achieved if, in a conditioning chamber according to the invention, at least one of the chamber walls is designed as a wave reflection section for at least partial reflection of the shock waves transferred via the wave transfer section. A wave reflection section is structurally the opposite of the wave damping section explained in the previous paragraph. Thus, it may be desirable to provide reflection of the shock waves in subregions of the chamber volume. A defined reflection is defined in particular with regard to the direction of reflection and / or the intensity of reflection.This makes it possible to reflect the introduced shock waves in a defined manner and to controllably pre-calculate this reflection, as well as the possible interference between reflected and introduced shock waves, and thus to incorporate the reflected shock waves into the desired conditioning optimization. It can be advantageous if the wave reflection section is designed to be switchable, i.e., switchable with regard to its reflection properties and / or its damping properties. For example, the elasticity of this section can be designed to be flexible, so that, for example, by applying an external voltage, hardening switches the wave damping section into a wave reflection section and vice versa.

[0014] It is also advantageous if, in a conditioning chamber according to the invention, the wave transfer section has a distribution volume on the outside of the chamber wall, in particular one filled with a liquid distribution medium for distributing the shock waves generated by the shock wave generator over the wave transfer section. This means that additional widening or distribution of the shock waves is provided. For example, the distribution volume can be provided as a cushion-like structure which is filled with a liquid distribution medium, for example water. The shock waves are now not applied directly by the shock wave generator to the wave transfer section, but are introduced into the distribution volume. This is where the distribution described takes place, so that the shock waves can be introduced in a correspondingly broadened manner over the entire surface of the wave transfer section.In particular, this serves to introduce the shock waves into the chamber volume in a diffuse or radial manner. This is achieved with this design even when the shock wave generator is designed as a point-type shock wave generator.

[0015] Further advantages can be achieved if, in a conditioning chamber according to the invention, at least two spaced-apart chamber walls each have at least one wave transfer section, wherein each wave transfer section has a defined transfer direction. If two or more wave transfer sections are provided, these preferably also correlate with two or more shock wave generators. In particular, these shock wave generators can be controlled independently of one another, so that multi-axis shock wave situations can be provided to improve conditioning in the conditioning chamber. In particular, when the transfer directions correlate with one another in a defined manner, defined amplification, focusing, interference, or even targeted superposition of different shock waves with different transfer directions can occur.This allows for targeted and, above all, local optimization of individual areas within the chamber volume, while omitting others. In other words, it is now possible to select sub-volumes within the chamber volume that are to be specifically defined, stimulated, and optimized for conditioning using applied shock waves.

[0016] It is also advantageous if, in a conditioning chamber according to the invention, the transfer directions form an acute angle with one another. In particular, when acute or even right angles are formed, targeted coordination of the applied shock waves can be achieved. This allows, preferably, the multi-axial application of the shock waves, as explained several times in the previous paragraph, to be coordinated in such a way that the desired optimization of conditioning is achieved in individual local sub-volumes of the chamber volume. In addition to a superimposed application, a temporally alternating application of the shock waves is also conceivable.For example, the individual shock wave generators can provide the introduction of shock waves at different times, either completely sequentially and / or temporally superimposed, and accordingly also provide complex shock wave patterns to optimize the conditioning of the tissue cells.

[0017] According to the invention, it is advantageous if at least one of the chamber walls is equipped with a force transmission section. This force transmission section has a force-absorbing 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 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.

[0018] According to the invention, the conditioning chamber serves to condition tissue cells 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 core idea of the present invention is that the cell scaffold with the tissue cells inside the chamber volume can be mechanically stimulated in a defined and controlled manner. Two essential features of the conditioning chamber are designed for this purpose: the force transmission section and the deformation section formed separately from it. The mode of operation is briefly explained below.

[0019] 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 way. 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.

[0020] 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.

[0021] 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.

[0022] 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 to condition the tissue cells.

[0023] 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.

[0024] 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.

[0025] For the purposes of the present invention, conditioning of tissue cells means differentiation of the cells and / or growth of the cells. However, 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 by mechanical influence and stimulation toward hard tissue cells or bone cells. Of course, a conditioning chamber, as will be explained later, can also have additional connections for the introduction of nutrient fluids or the like in order to enable growth of tissue cells in addition to differentiation of existing, already grown tissue cells.

[0026] It is further advantageous if, in a conditioning chamber according to the invention, the force transmission section is arranged at a distance from the wave transmission section. Such a force transmission section at a distance from the wave transmission section thus enables the force transmission and the introduction of the shock waves to be independent of each other. Thus, the force transmission and the wave transmission can occur sequentially, alternately, overlapping in time, or completely simultaneously, enabling completely flexible correlation and control of the force transmission as well as the shock wave transmission.

[0027] 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 substantially flat extension. A flat or substantially 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, thereby simplifying the control of the applied mechanical stimulation.

[0028] 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.

[0029] 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 forming 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.

[0030] 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.

[0031] 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 cell 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.

[0032] 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: - oxygen concentration, - carbon dioxide concentration, - PH value.

[0033] 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, thus enabling the quality and / or quantity of the conditioning to be determined accordingly. Last but not least, this allows for quality assurance.

[0034] It is also advantageous if, in a conditioning chamber according to the invention, the bio-sensor section is designed to be transparent at least in sections. For example, transparent glass sections are conceivable to provide such a bio-sensor section. Thus, such bio-sensor sections can also form transparent or partially transparent chamber walls. It is also possible for the corresponding bio-sensors to be designed on the outside, on the inside, or with partial elements of the sensor on the inside. The use of transparent bio-sensor sections also allows measurement and thus monitoring, for example through the use of imaging techniques, to be carried out contactlessly and thus free from contamination of the chamber volume.

[0035] 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.

[0036] 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. For example, the monitored compressive forces can be used to control, monitor, or even regulate the compressive forces actually applied. Particularly when complex compressive force profiles are used for conditioning, this feedback can be used to perform quality control, but also to monitor whether 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.

[0037] 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 the 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 the tissue cells is thus possible in the same conditioning chamber as the differentiation of the grown tissue cells. It is also fundamentally conceivable to even introduce the tissue cells themselves through these media connections, so that at the beginning of a conditioning process, an empty cell scaffold is used, which is then supplied with tissue cells via the media connection in a subsequent step.During the growth of the introduced tissue 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 the bioparameters of the tissue cells.

[0038] 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, so that at least a portion of the media connection protrudes into the deformation section. Particularly when the deformation section is formed by weakening the material, 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.

[0039] 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. 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% tightness and very 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 can be sterilized and thus used multiple times.

[0040] The present invention also relates to a conditioning system for conditioning tissue cells. This conditioning system has a receiving surface for positioning a conditioning chamber according to the present invention on this receiving surface. Furthermore, at least one shockwave generator is provided for generating shockwaves and transmitting the generated shockwaves to the wave transfer section. Such a conditioning system offers the same advantages as those explained in detail with reference to a conditioning chamber according to the invention.

[0041] It may be advantageous if, in a conditioning system according to the invention, at least one pressure force actuator is provided for introducing a pressure force into the at least one force-absorbing surface of the conditioning chamber. Such a conditioning system offers the same advantages as those explained in detail with reference to a conditioning chamber according to the invention. Preferably, two or more pressure force actuators, two or more media connections, and / or two or more sensor connections are provided, as already explained in more detail with reference to the conditioning chambers.

[0042] 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 configurations: - Pneumatics, - Hydraulics, - Electric, with or without transmission.

[0043] 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.

[0044] 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.

[0045] Furthermore, the present invention relates to a conditioning method for conditioning tissue cells in a conditioning system according to the invention, comprising the following steps: - Introducing a cell scaffold into the chamber volume of the conditioning chamber, - Connecting at least one shock wave generator to the wave transfer section, - Applying shock waves to the wave transfer section by means of the at least one shock wave generator.

[0046] By using a conditioning system according to the invention and a conditioning chamber according to the invention, a conditioning system according to the invention brings about the same advantages as have been explained in detail with reference to a conditioning chamber according to the invention.

[0047] It may also be advantageous if, in a conditioning method according to the invention, the shock waves are applied over at least one shock period, followed by at least one rest period free from the application of shock waves. Thus, it is possible for rest periods and shock periods to be arranged alternately one after the other, and, in particular, depending on the actual conditioning situation, the shock waves may be applied or not applied. Intermediate measurements and adjustments to the method of applying the shock waves are also conceivable in principle.

[0048] It can also be advantageous if, in a conditioning method according to the invention, the shock wave generator varies the shock waves with respect to at least one parameter, in particular with respect to one of the following: - radial, diffuse or focused shock waveform, - Frequency of shock waves, - Energy of the shock waves, - Amplitude of the shock waves, - Rate of rise of the shock waves.

[0049] The above list is not exhaustive. Of course, these various parameters can also be adjusted based on measured values or other information to further improve conditioning optimization over the course of tissue cell conditioning.

[0050] It is also advantageous if, in a conditioning method according to the invention, the shock waves are introduced as a function of at least one conditioning parameter, in particular at least one of the following: - Media supply, - Media disposal, - temperature, - Application of force.

[0051] The above list is also not exhaustive. Of course, additional information about the actual conditioning situation of the tissue cells can also be used to further optimize conditioning.

[0052] Further advantages can be achieved if, in a conditioning method according to the invention, at least one transmission element is arranged in the chamber volume for targeted transmission of the applied shock waves. In particular, a metallic transmission element, for example, made of metal, can be used. In this way, the applied shock waves can be guided specifically into one or more sub-areas of the chamber volume to achieve targeted and local effects.

[0053] Furthermore, it is advantageous if a conditioning method according to the invention for conditioning tissue cells in a conditioning system according to the invention comprises the following steps: - Connecting at least one pressure force actuator to the conditioning chamber, - Applying a compressive force by means of the at least one compressive force actuator.

[0054] 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, regulation of the supply and regulation of target achievement, for example, the hardness, size, or resistance of the tissue cells, can be provided. Sterility can also be monitored, for example, by detecting bacterial growth using an imaging method or, for example, by measuring increased CO2 emissions.

[0055] 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.

[0056] 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.

[0057] 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: Fig. 1 an embodiment of a conditioning chamber according to the invention, Fig. 2 the embodiment of the Fig. 1 in a different perspective, Fig. 3 the design of the Fig. 1 and Fig. 2 in a different perspective, Fig. 4 the design of the Fig. 1 to 3 in a different perspective, Fig. 5 the embodiment of the Fig. 1 to 4 in exploded view, Fig. 6 the cover of the embodiment for Fig. 7, Fig. 7 the embodiments of the Fig. 1 to 4 with lid during assembly, Fig. 8 an embodiment of a conditioning system according to the invention, Fig. 9 a partial representation of the conditioning system of the Fig. 8, Fig. 10 an embodiment of a conditioning chamber according to the invention, Fig. 11 shows a further embodiment of a conditioning chamber according to the invention, Fig. 12 another embodiment of a conditioning chamber according to the invention Fig. 13 another embodiment of a conditioning chamber according to the invention Fig. 14 an embodiment of a conditioning system according to the invention.

[0058] Regarding the Fig. 1 to 9, it should be noted that these deal with the embodiment with force transmission sections 40. For reasons of clarity, the shaft transfer sections 62 are not shown and described in these figures. However, these embodiments represent technical combinations with the embodiments of the Fig. 10 to 14, which include different variations of the shaft transfer sections 62.

[0059] The Fig. Figures 1 to 4 show a portion of a conditioning chamber 10 from different perspectives. This chamber 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.

[0060] Two of these chamber walls 20 are designed for the introduction of a compressive force DK. This is Fig. 1 around the two right-facing chamber walls 20, which accordingly have on their outer side 22 the force absorption surfaces 42 of the force transmission sections 40. If compressive forces DK are now applied to these force absorption surfaces 42, a deformation of the linearly aligned deformation sections 50, which are designed as material weakenings 52, takes place. Thus, these force transmission sections are pushed into the chamber volume 30 under the elastic deformation of these deformation sections 50. This happens when the force transmission sections 40 are flat. As soon as a Fig. 1 to 4, the introduced compressive forces DK are transmitted via the force transfer surfaces 44 on the inner side 24 of the respective chamber wall 20.

[0061] In order to be able to support the applied compressive forces DK, the two opposite, in the Fig. 1 and Fig. 2 chamber walls 20, each directed to the left, the two support sections 60 are provided, which, as explained later, can interact with abutments 130.

[0062] In addition, the Fig. 1 to 4 tab-like projections serve 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 biosensor 70 for a biosensor section 26. Force sensor sections 28 can also be provided here or integrated into the lateral chamber walls 20.

[0063] The Fig. 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 underside. To fill the chamber volume, the cell scaffold 200, for example, already with integrated tissue cells, is inserted, and then the chamber volume 30 is closed. The closure is achieved by placing 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. Fig. 6 and Fig. 7 show the possibility of a media supply of 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 into these, as the Fig. 7 shows, protrudes. The Fig. Figure 7 shows the state during the closing process. After complete closure, the media connections 90 are, of course, only visible and accessible from the outside.

[0064] The Fig. 8 shows schematically a structure of a conditioning system 100. The Fig. Figure 9 shows the corresponding representation after the recording in detail on the recording 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 recording surface 120 in the situation according to the Fig. 8 and Fig. 9. The position is predetermined by 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 targeted and controlled manner in a bidirectional manner for the mechanical stimulation of the tissue cells.

[0065] The Fig. 10 shows a variant of a conditioning chamber 10 according to the invention, which in particular is provided with one of the embodiments of the Fig. 1 to 9. However, a design without a power transmission section 40 is also conceivable in principle, as is the case with Fig. 10. Here, too, a conditioning chamber 10 is designed such that one of the chamber walls 20, namely the left front, has a wave transfer section 62. This is now designed such that from the outside, as shown in the Fig. 14, a shock wave generator 140 can be attached to introduce shock waves into the chamber volume 30 via this wave transfer section 62.

[0066] The Fig. 11 shows a variant that allows for additional influence on the shock waves. For example, a wave damping section 64 is provided on the opposite chamber wall 20 of the chamber volume 30, opposite the wave transfer section 20. This section can be formed, for example, by an elastically designed inner side 24 so that the shock waves can be dampened there. If a shock wave generator 140 is attached to the wave transfer section 62, shock waves are introduced and introduced into the chamber volume 30 via the wave transfer section 62. The introduced shock waves propagate through the internal medium and, after penetrating the chamber volume 30, hit the opposite inner side 24 and there, among other things, the wave damping section 64.Due to the partially elastic or fully elastic design of the wave damping section 64, this leads to damping, in particular complete damping of the introduced and impinging shock waves, so that reflection is avoided or at least minimized.

[0067] In the Fig. 12 shows a variant having a distribution volume 63. This distribution volume 63 is filled, for example, with a liquid distribution medium (not shown) and serves to be placed between the shock wave generator 64 and the wave transfer section 63. Shock waves are thus further generated by the shock wave generator 140 and can subsequently be introduced into the distribution volume 63. There, the shock waves are spatially distributed over the wave transfer section 62 and accordingly introduced into the chamber volume 30.

[0068] Also the Fig. Figure 13 shows a further development of such a conditioning chamber 10. Two separate wave transfer sections 62 are provided here, each configured with transmission directions UR at an acute angle to one another, in particular perpendicularly aligned. Opposite one of the two transfer sections 62, a wave reflection section 66 is provided, which is configured in a defined manner with a hard and reflective surface for reflecting the shock waves.

[0069] In the Fig. Figure 14 shows another variant of the conditioning system 100, which is combined here with the pressure force actuators 110. The shock wave generator 140 is also integrated into the conditioning system 100.

[0070] 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. List of reference symbols 10 Conditioning chamber 20 chamber wall 22 Outside 24 Inside 26 Bio-sensor section 27 Mounting tab 28 Force sensor section 30 chamber volume 40 Power transmission section 42 force absorption area 44 Power transfer area 50 deformation section 52 Material weakening 60 support section 62 shaft transfer section 63 distribution volume 64 Wave damping section 66 Wave reflection section 70 Bio-Sensor 80 force sensor 90 Media connection 92 Media supply 94 Media collection 100 conditioning system 110 Pressure force actuator 120 recording area 130 abutments 140 shock wave generator 200 cell scaffold DK compressive force UR transfer direction

Claims

[1] Conditioning chamber (10) for conditioning tissue cells, 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 wave transfer section (62) for receiving shock waves from a shock wave generator (140) and transferring the received shock waves to the chamber volume (30). [2] Conditioning chamber (10) according to claim 1, characterized by that at least one of the chamber walls (20) is designed as a wave damping section (64) for damping the shock waves transferred via the wave transfer section (62), wherein the wave damping section (64) is arranged in particular opposite or substantially opposite the wave transfer section (62). [3] Conditioning chamber (10) according to one of the preceding claims, characterized bythat at least one of the chamber walls (20) is designed as a wave reflection section (66) for at least partial reflection of the shock waves transferred via the wave transfer section (62). [4] Conditioning chamber (10) according to one of the preceding claims, characterized by that the wave transfer section (62) has on the outer side (22) of the chamber wall (20) a distribution volume (63), in particular filled with a liquid distribution medium, for distributing the shock waves generated by the shock wave generator (140) via the wave transfer section (62). [5] Conditioning chamber (10) according to one of the preceding claims, characterized by that at least two spaced-apart chamber walls (20) each have at least one wave transfer section (62), wherein each wave transfer section (62) has a defined transfer direction (UR). [6] Conditioning chamber (10) according to claim 5, characterized bythat the transfer directions (UR) form an acute angle with each other. [7] Conditioning chamber (10) according to one of the preceding claims, characterized by in that 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 absorbing 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 framework (200) that can be accommodated 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). [8] Conditioning chamber (10) according to claim 7, characterized bythat the force transmission section (40) is arranged at a distance from the shaft transmission section (62). [9] Conditioning chamber (10) according to one of the preceding claims, characterized by 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). [10] Conditioning system (100) for conditioning tissue cells, comprising a receiving surface (120) and positioning of a conditioning chamber (10) with the features of one of claims 1 to 9, at least one shock wave generator (140) for generating shock waves and transferring the generated shock waves to the wave transfer section (62). [11] Conditioning method for conditioning tissue cells in a conditioning system (100) having the features of claim 10, comprising the following steps: - introducing a cell scaffold (200) into the chamber volume (40) of the conditioning chamber (10), - connecting at least one shock wave generator (140) to the wave transfer section (62), - applying shock waves to the wave transfer section (62) by means of the at least one shock wave generator (140). [12] Conditioning method according to claim 11, characterized by that the shock waves are introduced over at least one shock period, followed by at least one rest period which is free from the introduction of shock waves. [13] Conditioning method according to one of claims 11 or 12, characterized by that the shock wave generator (140) varies the shock waves with respect to at least one parameter, in particular with respect to one of the following: - Radial, diffuse or focused shock waveform - Frequency of shock waves - Energy of the shock waves - Amplitude of the shock waves - Rate of rise of the shock waves [14] Conditioning method according to one of claims 11 to 13, characterized by that the shock waves are introduced depending on at least one conditioning parameter, in particular at least one of the following: - Media supply - Media disposal - Temperature - Application of force [15] Conditioning method according to one of claims 11 to 14, characterized by that at least one transmission element is arranged in the chamber volume (40) for a targeted transmission of the applied shock waves.

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