Patent Grant
11344721
The present invention relates generally to therapeutic electrical stimulation techniques, and specifically to apparatus and methods for therapeutic electrical stimulation of joints.
Articular cartilage is an avascular structure composed of predominantly type II collagen mixed with proteoglycans and relatively few cells. Because it lacks vascularity, articular cartilage is dependent on diffusion of nutrients and oxygen at its surface from synovial fluid.
The structure and function of articular cartilage is controlled by chondrocytes that regulate extracellular matrix (ECM) turnover and maintain tissue homeostasis. An imbalance in ECM function may lead to degenerative diseases, such as osteoarthritis.
Known cartilage repair approaches include boric marrow stimulation, such as subchondral drilling or microfracturing, and implantation of cellular or acellular scaffolds.
In some embodiments of the present invention, a cartilage treatment system is provided for treating hyaline cartilage of a subject. The cartilage treatment system comprises a first exposed electrode surface, which is configured to be implanted in osteochondral tissue, and a second exposed electrode surface, which is configured to be implanted in the subject's body. The cartilage treatment system further comprises control circuitry that is configured to promote regeneration of the hyaline cartilage by driving the first and the second exposed electrode surfaces to drive nutrients toward the first exposed electrode surface.
The system restores the natural negative charge of the hyaline cartilage and reestablishes the natural cartilage function, thereby reviving the cartilage and reducing pain. The system may be useful for treating injuries to the cartilage, as well as osteoarthritis, which is generally characterized by damage distributed over a large portion of the cartilage. Many conventional techniques for treating cartilage are generally appropriate for treating only focal damage, such as caused by an injury, and cannot practically be used for wide-spread damage. By contrast, the system of some embodiments of the present invention is appropriate for treating osteoarthritis, because the first exposed electrode surface can be used to apply a charge to a large area of the cartilage.
There is therefore provided, in accordance with an Inventive Concept 1 of the present invention, a method of treating hyaline cartilage of a subject, the method including:
implanting a first exposed electrode surface in osteochondral tissue of the subject;
implanting a second exposed electrode surface in a body of the subject; and
promoting regeneration of the hyaline cartilage by activating control circuitry to drive the first and the second exposed electrode surfaces to drive nutrients toward the first exposed electrode surface.
Inventive Concept 2. The method according to Inventive Concept 1, wherein implanting the first exposed electrode surface includes implanting the first exposed electrode surface in physical contact with an external surface of subchondral bone of the osteochondral tissue.
Inventive Concept 3. The method according to Inventive Concept 1, wherein implanting the first exposed electrode surface includes implanting the first exposed electrode surface within subchondral bone of the osteochondral tissue.
Inventive Concept 4. The method according to Inventive Concept 1, wherein implanting the first exposed electrode surface includes implanting the first exposed electrode surface within the hyaline cartilage of the osteochondral tissue.
Inventive Concept 5. The method according to Inventive Concept 1, wherein implanting the first exposed electrode surface includes implanting the first exposed electrode surface in the osteochondral tissue such that at least a portion of the first exposed electrode surface is under a chondral defect of the hyaline cartilage.
Inventive Concept 6. The method according to Inventive Concept 1, wherein implanting the first exposed electrode surface includes implanting the first exposed electrode surface in the osteochondral tissue such that at least a portion of the first exposed electrode surface is not under a chondral defect of the hyaline cartilage.
Inventive Concept 7. The method according to Inventive Concept 1, wherein the first exposed electrode surface has a surface area of 1-30 cm2.
Inventive Concept 8. The method according to Inventive Concept 1, wherein implanting the second exposed electrode surface includes implanting the second exposed electrode surface in physical contact with synovial fluid in a joint cavity of a joint capsule of the subject.
Inventive Concept 9. The method according to Inventive Concept 1, wherein implanting the second exposed electrode surface includes implanting the second exposed electrode surface in physical contact with a capsular ligament of a joint capsule of the subject.
Inventive Concept 10. The method according to Inventive Concept 1, further including implanting at least a portion of the control circuitry within the body.
Inventive Concept 11. The method according to Inventive Concept 1, wherein activating the control circuitry includes activating the control circuitry to configure the first exposed electrode surface to be a cathode and the second exposed electrode surface to be an anode.
Inventive Concept 12. The method according to Inventive Concept 1, wherein activating the control circuitry includes activating the control circuitry to drive direct current between the first and the second exposed electrode surfaces.
Inventive Concept 13. The method according to Inventive Concept 1, wherein activating the control circuitry includes activating the control circuitry to drive the first and the second exposed electrode surfaces to apply a constant current.
Inventive Concept 14. The method according to Inventive Concept 1, wherein activating the control circuitry includes activating the control circuitry to drive the first and the second exposed electrode surfaces to apply current as a series of pulses.
Inventive Concept 15. The method according to Inventive Concept 1, wherein activating the control circuitry includes activating the control circuitry to apply a voltage between the first and the second exposed electrode surfaces.
Inventive Concept 16. The method according to Inventive Concept 15, wherein the voltage is 0.1-1.1 V.
Inventive Concept 17. The method according to Inventive Concept 1, wherein activating the control circuitry includes activating the control circuitry to drive the first and the second exposed electrode surfaces to electroosmotically drive fluid containing the nutrients toward the first exposed electrode surface.
Inventive Concept 18. The method according to Inventive Concept 17, wherein activating the control circuitry includes activating the control circuitry to cyclically:
drive the first and the second exposed electrode surfaces to electroosmotically drive the nutrient-containing fluid toward the first exposed electrode surface, and
provide rest periods during which the nutrient-containing fluid is not electroosmotically driven toward the first exposed electrode surface.
Inventive Concept 19. The method according to Inventive Concept 1, wherein the method further includes identifying that the subject suffers from osteoarthritis, and wherein implanting the first and the second exposed electrode surfaces includes implanting the first and the second exposed electrode surfaces responsively to identifying that the subject suffers from the osteoarthritis.
Inventive Concept 20. The method according to Inventive Concept 1, wherein implanting the first exposed electrode surface in the osteochondral tissue includes implanting a chondral implant that includes the first exposed electrode surface, the chondral implant configured to stimulate the hyaline cartilage regeneration in a chondral defect of the hyaline cartilage.
Inventive Concept 21. The method according to Inventive Concept 20, wherein implanting the second exposed electrode surface includes implanting the second exposed electrode surface at a non-zero distance from the chondral implant.
Inventive Concept 22. The method according to Inventive Concept 20, wherein the chondral implant includes one or more synthetic materials that are configured to stimulate the hyaline cartilage regeneration.
Inventive Concept 23. The method according to Inventive Concept 22, wherein the chondral implant includes a synthetic scaffold that is configured to stimulate the hyaline cartilage regeneration.
Inventive Concept 24. The method according to Inventive Concept 23, wherein the synthetic scaffold includes an electrically-conductive material that serves as the first exposed electrode surface.
Inventive Concept 25. The method according to Inventive Concept 24, wherein the electrically-conductive material includes carbon fiber.
Inventive Concept 26. The method according to Inventive Concept 25, wherein the carbon fiber is hollow carbon fiber.
Inventive Concept 27. The method according to Inventive Concept 24, wherein the electrically-conductive material includes a biocompatible bioresorbable conductive porous material.
Inventive Concept 28. The method according to Inventive Concept 24, wherein the electrically-conductive material is shaped as a thin layer.
Inventive Concept 29. The method according to Inventive Concept 23, wherein the first exposed electrode surface is coupled to the synthetic scaffold, and wherein implanting the chondral implant includes implanting the chondral implant such that the first exposed electrode surface is located deeper within the osteochondral tissue than the synthetic scaffold.
Inventive Concept 30. The method according to Inventive Concept 29, wherein the synthetic scaffold is shaped as a thin layer.
Inventive Concept 31. The method according to Inventive Concept 23, wherein the synthetic scaffold includes a layer of fibrin glue.
Inventive Concept 32. The method according to Inventive Concept 23, wherein the synthetic scaffold is biphasic.
Inventive Concept 33. The method according to Inventive Concept 20, wherein the chondral implant includes a biological tissue graft that is configured to stimulate the hyaline cartilage regeneration.
Inventive Concept 34. The method according to Inventive Concept 33, wherein the first exposed electrode surface is coupled to the biological tissue graft, and wherein implanting the chondral implant includes implanting the chondral implant such that the first exposed electrode surface is located deeper within the osteochondral tissue than the biological tissue graft.
Inventive Concept 35. The method according to Inventive Concept 20, wherein implanting the chondral implant includes implanting the chondral implant in a chondral defect of the hyaline cartilage.
Inventive Concept 36. The method according to Inventive Concept 35, wherein the chondral implant includes an osteochondral plug that is configured to stimulate the hyaline cartilage regeneration in the chondral defect.
Inventive Concept 37. The method according to Inventive Concept 36, wherein the first exposed electrode surface is located in a transition zone of the osteochondral plug between a chondral layer of the osteochondral plug and a subchondral bone layer of the osteochondral plug.
Inventive Concept 38. The method according to Inventive Concept 36, wherein the osteochondral plug includes naturally-derived cartilage.
Inventive Concept 39. The method according to Inventive Concept 36, wherein the osteochondral plug includes a biocompatible, artificial material.
There is further provided, in accordance with an Inventive Concept 40 of the present invention, apparatus for treating hyaline cartilage of a subject, the apparatus including:
a first exposed electrode surface, which is configured to be implanted in osteochondral tissue of the subject;
a second exposed electrode surface, which is configured to be implanted in a body of the subject; and
control circuitry, which is configured to promote regeneration of the hyaline cartilage by driving the first and the second exposed electrode surfaces to drive nutrients toward the first exposed electrode surface.
Inventive Concept 41. The apparatus according to Inventive Concept 40, wherein the first exposed electrode surface is configured to be implanted in physical contact with an external surface of subchondral bone of the osteochondral tissue.
Inventive Concept 42. The apparatus according to Inventive Concept 40, wherein the first exposed electrode surface is configured to be implanted within subchondral bone of the osteochondral tissue.
Inventive Concept 43. The apparatus according to Inventive Concept 40, wherein the first exposed electrode surface is configured to be implanted in the hyaline cartilage of the osteochondral tissue.
Inventive Concept 44. The apparatus according to Inventive Concept 40, wherein the first exposed electrode surface has a surface area of 1-30 cm2.
Inventive Concept 45. The apparatus according to Inventive Concept 40, wherein the second exposed electrode surface is configured to be implanted in physical contact with synovial fluid in a joint cavity of a joint capsule of the subject.
Inventive Concept 46. The apparatus according to Inventive Concept 40, wherein the second exposed electrode surface is configured to be implanted in physical contact with a capsular ligament of a joint capsule of the subject.
Inventive Concept 47. The apparatus according to Inventive Concept 40, wherein at least a portion of the control circuitry is configured to be implanted within the body.
Inventive Concept 48. The apparatus according to Inventive Concept 40, wherein the control circuitry is configured to drive direct current between the first and the second exposed electrode surfaces.
Inventive Concept 49. The apparatus according to Inventive Concept 40, wherein the control circuitry is configured to drive the first and the second exposed electrode surfaces to apply a constant current.
Inventive Concept 50. The apparatus according to Inventive Concept 40, wherein the control circuitry is configured to drive the first and the second exposed electrode surfaces to apply current as a series of pulses.
Inventive Concept 51. The apparatus according to any one of Inventive Concepts 40-50, wherein the control circuitry is configured to configure the first exposed electrode surface to be a cathode and the second exposed electrode surface to be an anode.
Inventive Concept 52. The apparatus according to any one of Inventive Concepts 40-51, wherein the control circuitry is configured to apply a voltage between the first and the second exposed electrode surfaces.
Inventive Concept 53. The apparatus according to Inventive Concept 52, wherein the voltage is 0.1-1.1 V.
Inventive Concept 54. The apparatus according to any one of Inventive Concepts 40-53, wherein the control circuitry is configured to drive the first and the second exposed electrode surfaces to electroosmotically drive fluid containing the nutrients toward the first exposed electrode surface.
Inventive Concept 55. The apparatus according to Inventive Concept 54, wherein the control circuitry is configured to cyclically:
drive the first and the second exposed electrode surfaces to electroosmotically drive the nutrient-containing fluid toward the first exposed electrode surface, and
provide rest periods during which the nutrient-containing fluid is not electroosmotically driven toward the first exposed electrode surface.
Inventive Concept 56. The apparatus according to any one of Inventive Concepts 40-53, further including a chondral implant, which includes the first exposed electrode surface, the chondral implant configured to stimulate the hyaline cartilage regeneration in a chondral defect of the hyaline cartilage.
Inventive Concept 57. The apparatus according to Inventive Concept 56, wherein the chondral implant includes one or more synthetic materials that are configured to stimulate the hyaline cartilage regeneration.
Inventive Concept 58. The apparatus according to Inventive Concept 57, wherein the chondral implant includes a synthetic scaffold that is configured to stimulate the hyaline cartilage regeneration.
Inventive Concept 59. The apparatus according to Inventive Concept 58, wherein the synthetic scaffold includes an electrically-conductive material that serves as the first exposed electrode surface.
Inventive Concept 60. The apparatus according to Inventive Concept 59, wherein the electrically-conductive material includes carbon fiber.
Inventive Concept 61. The apparatus according to Inventive Concept 60, wherein the carbon fiber is hollow carbon fiber.
Inventive Concept 62. The apparatus according to Inventive Concept 59, wherein the electrically-conductive material includes a biocompatible bioresorbable conductive porous material.
Inventive Concept 63. The apparatus according to Inventive Concept 59, wherein the electrically-conductive material is shaped as a thin layer.
Inventive Concept 64. The apparatus according to Inventive Concept 58, wherein the first exposed electrode surface is coupled to the synthetic scaffold, and wherein the chondral implant is configured to be implanted such that the first exposed electrode surface is located deeper within the osteochondral tissue than the synthetic scaffold.
Inventive Concept 65. The apparatus according to Inventive Concept 64, wherein the synthetic scaffold is shaped as a thin layer.
Inventive Concept 66. The apparatus according to Inventive Concept 58, wherein the synthetic scaffold includes a layer of fibrin glue.
Inventive Concept 67. The apparatus according to Inventive Concept 58, wherein the synthetic scaffold is biphasic.
Inventive Concept 68. The apparatus according to Inventive Concept 56, wherein the chondral implant includes a biological tissue graft that is configured to stimulate the hyaline cartilage regeneration.
Inventive Concept 69. The apparatus according to Inventive Concept 68, wherein the first exposed electrode surface is coupled to the biological tissue graft, and the chondral implant is configured to be implanted such that the first exposed electrode surface is located deeper within the osteochondral tissue than the biological tissue graft.
Inventive Concept 70. The apparatus according to Inventive Concept 56, wherein the chondral implant is configured to be implanted in a chondral defect of the hyaline cartilage.
Inventive Concept 71. The apparatus according to Inventive Concept 70, wherein the chondral implant includes an osteochondral plug that is configured to stimulate the hyaline cartilage regeneration in the chondral defect.
Inventive Concept 72. The apparatus according to Inventive Concept 71, wherein the first exposed electrode surface is located in a transition zone of the osteochondral plug between a chondral layer of the osteochondral plug and a subchondral bone layer of the osteochondral plug.
Inventive Concept 73. The apparatus according to Inventive Concept 71, wherein the osteochondral plug includes naturally-derived cartilage.
Inventive Concept 74. The apparatus according to Inventive Concept 71, wherein the osteochondral plug includes a biocompatible, artificial material.
The present invention will be more fully understood from the following detailed description of embodiments thereof, taken together with the drawings, in which:
As used in the present application, including in the claims, “nutrients” are substances used by cells (chondrocytes) within hyaline cartilage 22 to survive and reproduce. As used in the present application, including in the claims, oxygen is considered a nutrient, because oxygen is essential for the survival and reproduction of cells.
For some applications, first exposed electrode surface 26 is the external surface of a non-insulated portion of a wire of first electrode 24, such as shown in
Alternatively or additionally, for some applications, second exposed electrode surface 32 is the external surface of a non-insulated portion of a wire of second electrode 30, such as shown in
Typically, control circuitry 36 is configured to drive first and second exposed electrode surfaces 26 and 32 to electroosmotically drive fluid containing the nutrients toward first exposed electrode surface 26.
For some applications, first exposed electrode surface 26 is configured to be implanted:
For some applications, first exposed electrode surface 26 has a surface area of at least 1 cm2, no more than 30 cm2 (e.g., no more than 10 cm2), and/or 1-30 cm2, e.g., 1-10 cm2.
For some applications, second exposed electrode surface 32 is configured to be implanted:
For some applications, at least a portion of control circuitry 36 is configured to be implanted within body 34 (e.g., by injection), such as shown in
For some applications, cartilage treatment system 20 comprises an implantable controller 42, which comprises at least a portion of control circuitry 36, optionally all of control circuitry 36. Optionally, control circuitry 36 does not comprise any active electronic components; for example, control circuitry 36 may comprise one or more passive diodes that are configured to rectify the current generated in the coil of control circuitry 36. Alternatively, for some applications, control circuitry 36 comprises a battery configured to be implanted in body 34.
For some applications, cartilage treatment system 20 further comprises an external unit 38, which is configured to be disposed external to body 34, such as against the skin of the body, and which is configured to wirelessly transmit power (via a coil) to a coil of implantable controller 42, and optionally to wirelessly submit control signals. Optionally, external unit 38 comprises a portion of control circuitry 36.
Typically, control circuitry 36 is configured to configure first exposed electrode surface 26 to be a cathode and second exposed electrode surface 32 to be an anode. (The plus and minus signs in
For some applications, control circuitry 36 is configured to apply a voltage between first and second exposed electrode surfaces 26 and 32. Typically, the voltage is at least 0.1 V, no more than 1.1 V, and/or 0.1-1.1 V).
For some applications, control circuitry 36 is configured to drive first and second exposed electrode surfaces 26 and 32 to apply a constant current.
For some applications, control circuitry 36 is configured to drive direct current between first and second exposed electrode surfaces 26 and 32. For some applications, control circuitry 36 is configured to drive the direct current as a series of pulses.
For some applications in which control circuitry 36 is configured to drive first and second exposed electrode surfaces 26 and 32 to electroosmotically drive fluid containing the nutrients toward first exposed electrode surface 26, control circuitry 36 is configured to cyclically:
The rest periods may allow any excess fluid driven toward first exposed electrode surface 26 to flow in the opposite direction. For example, control circuitry 36 may be configured to electroosmotically drive the nutrient-containing fluid toward first exposed electrode surface 26 for periods of time having a duration of between 3 and 10 minutes, e.g., 5 minutes, and to provide the rest periods having respective durations of between 1 and 3 minutes, e.g., 2 minutes.
Optionally, control circuitry 36 is configured to sense a voltage between first and second exposed electrode surfaces 26 and 32 during each rest period, and upon detection of a reduction to below a threshold value, again begin electroosmotically driving the nutrient-containing fluid toward first exposed electrode surface 26.
Reference is still made to
For some applications, the method further comprises identifying that the subject suffers from osteoarthritis, and first and second exposed electrode surfaces 26 and 32 are implanted responsively to identifying that the subject suffers from the osteoarthritis.
For some applications, first exposed electrode surface 26 is implanted:
For some applications, first exposed electrode surface 26 is implanted in osteochondral tissue 28 such that at least a portion of first exposed electrode surface 26 is under a chondral defect 56 of hyaline cartilage 22. Alternatively or additionally, for some applications, first exposed electrode surface 26 is implanted in osteochondral tissue 28 such that at least a portion of first exposed electrode surface 26 is not under a chondral defect 56.
For some applications, second exposed electrode surface 32 is implanted:
For some applications, the method further comprises implanting at least a portion of control circuitry 36 within body 34.
Reference is now made to
Cartilage treatment system 120 further comprises a chondral implant 154, which comprises a first exposed electrode surface 126. Chondral implant 154 is configured to stimulate hyaline cartilage regeneration in a chondral defect 56 of hyaline cartilage 22. Control circuitry 36 may implement all of the features described hereinabove with reference to
For some applications, first exposed electrode surface 126 has a surface area of at least 1 cm2, no more than 30 cm2 (e.g., no more than 10 cm2), and/or 1-30 cm2, e.g., 1-10 cm2.
Optionally, cartilage treatment system 120 further comprises first exposed electrode surface 26, described hereinabove with reference to
For some applications, chondral implant 154 comprises one or more synthetic materials that are configured to stimulate hyaline cartilage regeneration. For some of these applications, chondral implant 154 comprises a synthetic scaffold 160 that is configured to stimulate hyaline cartilage regeneration. For example, synthetic scaffold 160 may comprise an electrically-conductive material (e.g., comprising carbon fiber (e.g., a nanomaterial), such as hollow carbon fiber) that serves as first exposed electrode surface 126. For some applications, the electrically-conductive material comprises a biocompatible bioresorbable conductive porous material (e.g., arranged as a membrane). Optionally, the electrically-conductive material is shaped as a thin layer and/or as a mesh.
For some applications, first exposed electrode surface 126 is coupled to synthetic scaffold 160, and wherein chondral implant 154 is configured to be implanted such that first exposed electrode surface 126 is located deeper within osteochondral tissue 28 than synthetic scaffold 160.
For some applications, synthetic scaffold 160 is shaped as a thin layer (e.g., 0.1-2 mm thick, e.g., 1 mm thick).
For some applications, synthetic scaffold 160 comprises an outer layer of fibrin glue 162. Outer layer of fibrin glue 162 may be added to synthetic scaffold 160 during the implantation procedure, or pre-attached to the synthetic scaffold. Fibrin is permeable to nutrients, including oxygen, and thus does not interfere with the driving of the nutrients toward first exposed electrode surface 26.
For some applications, synthetic scaffold 160 is biphasic (i.e., comprises first and second regions, e.g., layers, specific for the growth of respective particular tissue types, such as cartilage and bone, respectively).
For some applications, chondral implant 154 comprises a biological tissue graft that is configured to stimulate hyaline cartilage regeneration. For example, the biological tissue graft may be autologous, e.g., implementing osteochondral allograft transplantation (OATS) or matrix-associated autologous chondrocyte implantation (MACI), as are known in the cartilage repair art.
For some of these applications, first exposed electrode surface 126 is coupled to the biological tissue graft, and chondral implant 154 is configured to be implanted such that first exposed electrode surface 126 is located deeper within osteochondral tissue 28 than the biological tissue graft.
For some applications, chondral implant 154 is configured to be implanted in chondral defect 56 of hyaline cartilage 22. For some of these applications, chondral implant 154 comprises an osteochondral plug that is configured to stimulate hyaline cartilage regeneration in chondral defect 56. Optionally, first exposed electrode surface 126 is located in a transition zone of the osteochondral plug between a chondral layer of the osteochondral plug and a subchondral bone layer of the osteochondral plug. For some applications, the osteochondral plug comprises naturally-derived cartilage. Alternatively, the osteochondral plug comprises a biocompatible, artificial material. Optionally, the osteochondral plug is cylindrical. The osteochondral plug may or may not comprise cells, as is known in the osteochondral plug art. For example, the osteochondral plug may implement techniques described in U.S. Pat. No. 6,632,246 to Simon et al.
Reference is still made to
For some applications, second exposed electrode surface 32 is implanted at a non-zero distance from chondral implant 154.
For some applications in which first exposed electrode surface 126 is coupled to synthetic scaffold 160, and implanting chondral implant 154 is implanted such that first exposed electrode surface 126 is located deeper within osteochondral tissue 28 than synthetic scaffold 160.
For some applications in which first exposed electrode surface 126 is coupled to the biological tissue graft, and chondral implant 154 is implanted such that first exposed electrode surface 126 is located deeper within osteochondral tissue 28 than the biological tissue graft.
For some applications, chondral implant 154 is implanted in chondral defect 56 of hyaline cartilage 22.
Reference is now made to
Optionally, cartilage treatment system 220 further comprises a knee brace 272, into which external unit 38 is incorporated.
Although cartilage treatment systems 20, 120, and 120 are illustrated as treating a knee joint, the systems may also be used to treat other synovial joints, such a hip joint, a shoulder joint, a finger joint (e.g., a knuckle joint), a toe joint, an ankle joint, an elbow joint, or a wrist. In addition, the cartilage treatment systems may be configured to treat other tissues, such as meniscus of the knee.
It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.
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