DEVICE FOR THE NON-INVASIVE INDUCTION OF DYNAMIC DEFORMATION OF BODY TISSUE TO DIFFERENTIATE TISSUE CELLS

Abstract

The device is intended for the noninvasive induction of dynamic deformation of body tissue to differentiate tissue cells. It comprises the following components: (i) a suspension of particles suspended in solution; and (ii) an external actuator which is capable of magnetically, electrically, vibrationally, or thermally stimulating the suspended particles.

Claims

1-34. (canceled)

35. A device for noninvasive induction of dynamic deformation of body tissue to differentiate tissue cells, which comprises the following components: (i) a suspension of particles suspended in solution; and (ii) an external actuator; wherein: a) the particles are metallic, magnetic, magnetizable, electrically chargeable, or thermally reactive; b) the average diameter of the particles is greater than 1 nm and less than 5 mm; and c) the external actuator comprises a vibration source or a heat source or is configured to emit electromagnetic waves or to generate an electrical field to stimulate the suspended particles vibrationally, thermally, magnetically or electrically.

36. The device as claimed in claim 35, wherein the suspension further comprises body cells.

37. The device as claimed in claim 35, wherein the particles are nonporous.

38. The device as claimed in claim 35, wherein the particles comprise one or more substances selected from the group consisting of: platinum; titanium; steel; carbon steel; crystalline alloys based on iron; nickel; cobalt; amorphous or nano-crystalline alloys based on iron; nickel; cobalt; soft ferrites; cobalt samarium; neodymium iron-boron; AlNiCo; hard ferrites; martensitic steels; and memory alloys.

39. The device as claimed in claim 35, wherein the particles comprise electrically conductive materials which have a rest potential different from surroundings due to an insulating outer skin.

40. The device as claimed in claim 35, wherein the particles comprise a bioresorbable material.

41. The device as claimed in claim 35, wherein the particles are homogenous to each other at least in their respective cores.

42. The device as claimed in claim 36, wherein the particles are provided with a biocompatible outer skin, which is capable of promoting growth of the body cells.

43. The device as claimed in claim 35, wherein the average diameter of the particles is greater than 5 μm.

44. The device as claimed in claim 35, wherein the average diameter of the particles is less than 50 μm.

45. The device as claimed in claim 35, wherein the average volume of the particles on an individual basis is greater than 125 μm.sup.3.

46. The device as claimed in claim 35, wherein the average volume of the particles on an individual basis is less than 100 mm.sup.3.

47. The device as claimed in claim 35, wherein the particles do not have a fibrous structure.

48. The device as claimed in claim 35, wherein the solution is a body-compatible liquid that contains bone-forming substances and/or tissue components and/or stem cells.

49. The device as claimed in claim 48, wherein at most 106 particles are contained per mm.sup.3 of the body-compatible liquid.

50. The device as claimed in claim 35, wherein the ratio between the volume of the particles in the suspension and the volume of the solution in the suspension is at most 10:1.

51. The device as claimed in claim 35, wherein the ratio between the volume of the particles in the suspension and the volume of the solution in the suspension is at least 1:1000.

52. A method for noninvasive induction of dynamic deformation of a body tissue to reparatively differentiate tissue cells, the method comprising the steps of: a) injecting a body-compatible liquid, in which volume-constant particles are suspended, into the body tissue to be deformed; and b) activating the particles by means of an external actuator without mechanical connection between actuator and the particles; wherein the particles are activated magnetically, electrically, vibrationally, or thermally such that a movement of the particles is generated, which results in deformations in the body tissue, which stimulate the reparative differentiation of the tissue cells.

53. The method as claimed in claim 52, wherein the body-compatible liquid contains, in addition to the particles, body cells which are deformed by the external activation of the particles.

Description

[0059] The figures show:

[0060] An example of a surgical osteosynthesis by means of an implant which corresponds to the prior art and the device for noninvasive induction of dynamic deformation of body tissue.

[0061] FIG. 1a: The bone (a) in the body (b) is broken, the size of the defect (c) prevents, in the case of an operation by means of implants which correspond to the prior art, the healing of the bone due to a lack of bony bridging.

[0062] FIG. 1b: The bone fragments are connected in a frictionally-locked manner with or without screws (d) by means of an implant (e), which corresponds to the prior art, in such a way that little to no movement results between the bone fragments (a).

[0063] FIG. 1c: The solution of suspended particles (f) which can contain body cells is introduced into the defect. This can be performed, for example, by injection.

[0064] FIG. 1d: The actuator (g) is externally attached. Upon its activation, mutual movements and thus strain, which are transmitted to the body cells and/or the body tissue, result in the solution of suspended particles which can contain the body cells. The body cells and/or the body tissue begin to differentiate. In the present case, bone tissue forms in various differentiation stages. One important advantage of the present invention is that the induction can be adapted optimally to the individual progressing healing process.

[0065] FIG. 1e: The bone has connected the two bone fragments again via a bone bridge (h).

[0066] An example of a bone lengthening by severing and surgical osteosynthesis by means of an implant which corresponds to the prior art and the device for noninvasive induction of dynamic deformation of body tissue.

[0067] FIG. 2a: The bone (a) in the body (b) is surgically severed. The two bone fragments are pulled apart and fixed in the desired position by an implant which corresponds to the prior art. The size of the defect (c) prevents the healing of the bone due to a lack of bony bridging in the case of a one-step operation.

[0068] FIG. 2b: The bone fragments are connected in a frictionally-locked manner with or without screws (d) by means of an implant, which corresponds to the prior art, in such a way that little to no movement results between the bone fragments.

[0069] FIG. 2c: The solution of suspended particles which can contain body cells is introduced into the defect. This can be performed, for example, by injection.

[0070] FIG. 2d: The actuator (g) is externally attached. Upon its activation, mutual movements and thus strain, which are transmitted to the body cells and/or the body tissue, result in the solution of suspended particles which can contain the body cells. The body cells and/or the body tissue begin to differentiate. In the present case, bone tissue forms in various differentiation stages. One important advantage of the present invention is that the induction can be adapted optimally to the individual progressing healing process.

[0071] FIG. 2e: The bone has connected the two bone fragments again via a bone bridge (h). The bone has been expanded by the width of the introduced defect. A bone lengthening of up to 50 mm can thus take place in one step.

[0072] An example of tissue regeneration due to induced differentiation in patients by the device for noninvasive induction of dynamic deformation of body tissue.

[0073] FIG. 3a: The solution of suspended particles which can contain body cells is introduced into muscle tissue of the patient. This can be performed, for example, by injection.

[0074] FIG. 3b: The actuator is externally attached. Upon its activation, mutual movements and thus strain, which are transmitted to the body cells and/or the body tissue, result in the solution of suspended particles which can contain the body cells. The body cells and/or the body tissue begin to differentiate.

[0075] FIG. 3c: Different tissue is formed depending on the duration and strength, thus, for example, connective tissue, cartilage, or bone.

[0076] An example of bone restoration in the case of bone defect, for example, due to osteoporosis or as a result of accident, by the device for noninvasive induction of dynamic deformation of body tissue.

[0077] FIGS. 4a/b: The solution of suspended particles which can contain body cells is introduced at the location of the bone defect. This can be performed, for example, by injection.

[0078] FIG. 4c: The actuator is externally attached. Upon its activation, mutual movements and thus strain, which are transmitted to the body cells and/or the body tissue, result in the solution of suspended particles which can contain the body cells. The body cells and/or the body tissue begin to differentiate.

[0079] FIG. 4d: The bone is restored.

[0080] An example of other embodiment types of the particles which can be applied in combination with the above-mentioned examples.

[0081] FIG. 5a: The solution of suspended particles which contain body cells is introduced. This can be performed, for example, by injection. The particles are formed as rods here.

[0082] FIG. 5b: The actuator is externally attached. The rods deform upon its activation. A movement and thus a strain, which are transmitted to the body cells and/or the body tissue, thus result in the solution of suspended particles.

[0083] FIG. 5c: The actuator can also control the particles so that they merge back into the base position. The entire procedure can be repeated so that it is repeated in a frequency range and intensity which are optimum for the body cells and/or the body tissue, so that the optimum/desired differentiation is achieved.

[0084] FIG. 5d: The body cells and/or the body tissue begin to differentiate. The particles can be resorbed by the body or are incorporated into the resulting body tissue. The advantage of the device for the induction of dynamic deformation of body tissue is, firstly, that the differentiation can be fundamentally initiated and, secondly, that the differentiation can be controlled in speed and resulting tissue.

EXAMPLE 1

Pseudoarthrosis Treatment

[0085] The patient suffers from a nonhealing bone fracture of the middle femoral bone after a traffic accident. The fracture consists of many parts. After a series of unsuccessful surgical osteosyntheses, the bone parts remain separate. The bone has partially broken down. One reason for the lack of healing is the absence of stimulation due to insufficient strain stimulus, caused by the geometrical complexity of the fracture. The traditional fixation of the bone parts does not permit a stimulation for the various bone intermediate spaces.

[0086] In this case, the stable traditional connection is left in the patient. A ringer solution admixed with magnetized or magnetically active neodymium particles having endogenous stem cells is injected into the nonhealing bone intermediate spaces.

[0087] The neodymium particles are enclosed by a plastic, so that they are body-compatible. The surface of the particles is formed in such a way that the movement is transferred in accordance with the purpose. The average volume of the neodymium particles used was 1,000,000 μm.sup.3.

[0088] An array of further experiments was carried out using neodymium particles which had an average volume in the range of 1250-4,250,000 μm.sup.3.

[0089] The injected ringer solution contained 50,000 particles per mm.sup.3. An array of further experiments was carried out with endogenous liquid (instead of the ringer solution), having a particle density in the range of 250-200,000 units per mm.sup.3.

[0090] The volume of the injected liquid corresponded to the intermediate space which had resulted in the existing bone fracture, in the specific case 5 cl.

[0091] After completed injection of the solution having the particles, an actuator for these particles was externally attached. It consisted of a fastening component and a technical component. The fastening component was designed as a sleeve made of textile material. The technical component consisted of a control module, an induction module, and a battery. The induction module consisted of two movable coils which were moved forward and backward upon the activation.

[0092] The actuator was set to a frequency of 6 inductions per hour ( 1/600 sec.sup.1 (Hz)) and activated.

[0093] The healing was monitored by radiology, wherein the frequency and amplitude were adapted to the healing progress. The dimension of the amplitude was determined in that the tissue strain transferred by the particles resulted in the dimension of 100-2%.

[0094] The amplitude was reduced during the healing progress.

[0095] After 5 weeks, the healing was completed, the bones were solidly connected and loadbearing. The biochemically inert particles remained in the body until the excretion or were incorporated into the bone. The actuator was removed after completed healing.

EXAMPLE 2

Endogenous Bone Production

[0096] The patient suffered from a bone defect after a trauma as a result of a sports accident. Spongiosa was required as replacement bone. Obtaining the spongiosa represented a significant additional surgical intervention, which caused strong pains for a long time. In this case, the bone defect was filled with bony material by the invention in that a stem cell solution (MSC) enriched with thermally activatable particles was injected into the bone defect by injection.

[0097] The thermally activated particles were constructed so that a tension built up in the particles due to an externally introduced temperature change, which discharged upon reaching a limiting tension and a pulsed movement of the particles was generated. After the relaxation and the reaching of the body temperature, the particles were ready again for a further cycle. The particles used were of oblong shape and were constructed from multiple layers of various thermally reacting metals (in a further experiment, a memory alloy was used for this purpose). The particles were externally coated using an elastic, body-compatible plastic protective layer. The surface was formed so that the movement was transferred appropriately.

[0098] The average size of the particles was 0.1 mm.

[0099] The number of particles per unit of volume of the injected solution was 10 units per mm.sup.3.

[0100] The thermal actuator used in this experiment consisted of a fastening component and a technical component. The fastening component was embodied as a textile sleeve.

[0101] The technical component consisted of a control module, an induction module, and a battery. The induction module was a heat source, which was based on thermal induction and heated the particles in the solution in the bone defect located close to the surface so that they could carry out the provided movement without damaging the surrounding tissue.

[0102] Is externally attached. The frequency set at the actuator was 2 times per hour, i.e., was set to 1/1800 sec.sup.−1 (Hz).

[0103] The power of the actuator was set so that the particles were activated appropriately without damaging the surrounding tissue. The particles were heated enough that the movement was not damaging to tissue.

[0104] The particles exerted a strain on the MSC contained in the solution due to the thermal activation. They began to differentiate and formed endogenous spongiosa bone in a pain-free manner within approximately 6 weeks.

[0105] Upon the activation of the particles, their volume remained constant, only their shape changed from curved to linear, as shown in FIGS. 5a, b, and c.

EXAMPLE 3

Bone Lengthening

[0106] The patient suffered since adolescence from a one-sided shortening of the lower leg of 20 mm due to a growth defect. To counteract foreseeable postural defects, the length of the affected limb was supposed to be adapted. For this purpose, the two lower leg bones of the shortened leg were severed at a suitable point in a surgical invention and stabilized by means of traditional orthopedic fixing methods so that both legs were of equal length. A segment resulted in which the bone was absent. A solution having particles which had a large specific mass was injected into this segment. The particles consisted of a core of high specific mass and a biocompatible jacket. The surface was formed so that the movement was transferred appropriately by adhesion of the tissue. The core of the particles consisted of platinum, the jacket of etched titanium. The mean size of the particles was 0.15 mm. The number of the particles per unit of volume of the injected solution was 8 units per mm.sup.3.

[0107] The quantity of injected solution was 6 ml.

[0108] The actuator adapted to this particle was externally attached to the leg and activated 3 times per hour. ( 1/1200 Hz).

[0109] The actuator functioned according to the principle of resonance and consisted of a fastening component and a technical component. The fastening component was a sleeve made of plastic in this application. The technical component consisted of a control module, an induction module, and a battery. The induction module was a movement source which was based on rotation imbalance and which moved the particles in the solution in the bone defect in relation to the surrounding tissue because of their mass inertia.

[0110] The healing was radiologically monitored. The frequency and amplitude were adapted to the healing progress.

[0111] The tissue cells, on which a strain stimulus acted, began to differentiate, beginning with a cell-containing liquid. This converted approximately in cycles of a week in granulation tissue, into resilient connective tissue.

[0112] After 6 weeks, the healing was completed, the bones were solidly connected and loadbearing. The biochemically inert particles remained in the body until excretion or were incorporated into the bone. The actuator was removed after completed healing.

EXAMPLE 4

Tissue Engineering

[0113] The patient suffered from a sports-related dysfunction in the left shoulder joint, which was painful. A new joint capsule was supposed to be produced for this purpose. It was produced from a connective tissue membrane. The connective tissue membrane was produced in the body using the method according to the invention.

[0114] For this purpose, a flat pocket was produced subcutaneously by surgery in the abdomen region. A solution having particles which had a large specific mass was injected into this pocket. The particles consisted of a core of high specific mass and a biocompatible jacket. The surface was formed so that the movement was transferred appropriately by adhesion of the tissue. The core of the particles consisted of platinum, the jacket of etched titanium.

[0115] For this application, the particles had a mean length of 0.2 mm.

[0116] The number of the particles per unit of volume of the injected solution was 7 units per mm.sup.3.

[0117] The quantity of injected solution was 8 ml.

[0118] The actuator adapted to these particles functioned according to the principle of resonance and consisted of a fastening component and a technical component. The fastening component was a sleeve made of plastic in this application. The technical component consisted of a control module, an induction module, and a battery. The induction module was a movement source which was based on rotation imbalance and which moved the particle in the solution in the bone defect in relation to the surrounding tissue because of their mass inertia.

[0119] The actuator was externally attached to the abdomen and activated 3 times per hour. (1/1200 Hz).

[0120] The healing was radiologically monitored. The frequency and amplitude were adapted to the healing progress. After 3 weeks, the connective tissue membrane had formed in the subcutaneous pocket. This tissue was removed in a surgical intervention and was used to replace the defective tissue capsule. The biochemically inert particles remained in the body until excretion or were incorporated into the bone. The actuator was removed after completed healing.

[0121] Although various embodiments of the present invention exist as described above, these are to be understood so that the various features can be used both individually and also in any arbitrary combination.

[0122] This invention is therefore not simply restricted to the above-mentioned, particularly preferred embodiments.