Method and apparatus for cartilage growth stimulation
Abstract
A kit for ultrasonically stimulating cartilage growth (10, 200, 300, 500), comprising: an assembly of ultrasonic transducers (16), which have at least one ultrasonic transducer; a positioner module (14), configured to be used by a patient, wherein said positioner module (14) is configured to receive said transducer assembly (16) such that when said positioner module (14) is used, said Ultrasonic transducer, at least one, is located near the lesion and / or the cartilaginous and / or osteocartilaginous defect, for the treatment of the lesion; an ultrasonic signal generator located in said assembly of ultrasonic transducers (16); and a main operating unit (12), characterized in that the positioning module (14) comprises a positioning support (20) that includes channels (22), each of which has an extension (24) there mounted to support an ultrasonic transducer assembly (16).

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Projected expiry passed 6 February 2018, 8.6 years ago.
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7 claims: 1 independent, 6 dependent
- 1REIVINDICACIONES 1. Un kit para estimular ultrasónicamente el crecimiento del cartílago (10, 200, 300, 500), que comprende:un montaje de transductores ultrasónicos (16), que tienen al menos un transductor ultrasónico;un módulo posicionador (14), configurado para ser usado por un paciente, donde dicho módulo posicionador (14) está configurado para recibir a dicho montaje de transductores (16) de manera tal que cuando el mencionado módulo posicionador (14) es usado, dicho transductor ultrasónico, uno como mínimo, se ubique cerca de la lesión y/o del defecto cartilaginoso y/u osteocartilaginoso, para el tratamiento de la lesión;un generador de señales ultrasónicas ubicado en dicho montaje de transductores ultrasónicos (16);y una unidad operativa principal (12), caracterizado porque el módulo posicionador (14) comprende un soporte posicionador (20) que incluye canales (22), cada uno de los cuales tiene una extensión (24) allí montada para sostener un montaje de transductores ultrasónicos (16).
- 2El kit de acuerdo con la reivindicación 1, en el cual dicho generador de señales ultrasónicas incluye un sistema de circuitos del generador de señales y una fuente de alimentación interna conectada al citado sistema de circuitos del generador de señales, una pantalla conectada a dicho sistema de circuitos del generador de señales para presentar los datos de secuencia del tratamiento, y dicho sistema de circuitos del generador de señales incluye un procesador y medios para generar una señal de RF pulsada.
- 3El kit de acuerdo con la reivindicación 1, que comprende, además, medios de enclavamiento de seguridad para evitar la excitación inadvertida de dicho único transductor ultrasónico como mínimo.
- 4El kit de acuerdo con la reivindicación 1, en el cual dicho módulo posicionador incluye un mecanismo inmovilizador que el paciente puede ponerse y que evita que este flexione o extienda las extremidades.
- 5El kit de acuerdo con la reivindicación 1, en el cual el módulo posicionador (14) se fabrica a partir de un material conductor y dicho transductor ultrasónico, uno como mínimo, provisto en dicho módulo posicionador (14) está conectado eléctricamente a la citada unidad de operación principal (12) mediante el citado material conductor.
- 6El kit de acuerdo con la reivindicación 1, en el cual el módulo posicionador (14) se moldea especialmente para una articulación en particular del paciente.
- 7El kit de acuerdo con la reivindicación 1, en el cual al menos un transductor ultrasónico incluye medios para recibir los datos de diagnóstico reflejados. � Fig. 13:A) Se obtuvo la exposición del surco patelar. B) Se usó un taladro para crear el defecto. C) Después de la irrigación, el lugar se cerró en capas. Figura 14. A) El aspecto por estudio macroscópico después de cuatro semanas de realizada la cirugía del animal H156, derecho, terapia con el SAFHS. Este defecto recibió una puntuación de 8, de los 8 puntos posibles. B) El aspecto por estudio macroscópico después de cuatro semanas de efectuada la cirugía del animal H 156, izquierdo, sin tratar. Este defecto recibió una puntuación de 6, de los 8 puntos posibles. C) El aspecto por estudio macroscópico después de cuatro semanas de efectuada la cirugía del animal G217, derecha, terapia con SAFHS. Este defecto recibió una puntuación de 7, de los 8 puntos posibles. D) El aspecto por estudio macroscópico después de cuatro semanas de la cirugía del animal G217, izquierdo, sin tratar. Este defecto recibió una puntuación de 3, de los 8 puntos posibles. Figura 15. A) El aspecto por estudio macroscópico después de ocho semanas de efectuada la cirugía del animal G201;derecho, terapia con SAFHS. Este defecto recibió una puntuación de 7,5 de los 8 puntos posibles. B) El aspecto por estudio macroscópico después de ocho semanas de efectuada la cirugía del animal G201;izquierdo, sin tratar. Este defecto recibió una puntuación de 5, de los 8 puntos posibles. C) El aspecto por estudio macroscópico después de ocho semanas de efectuada la cirugía del animal H153;derecho, terapia con SAFHS. Este defecto recibió una puntuación de 8, de los 8 puntos posibles. D) El aspecto por estudio macroscópico después de ocho semanas de efectuada la cirugía del animal H153;izquierdo, sin tratar. Este defecto recibió una puntuación de 7, de los 8 puntos posibles. Figura 16. A) El aspecto por estudio macroscópico después de doce semanas de efectuada la cirugía del animal H164;derecho;terapia con SAFHS. Este defecto recibió una puntuación de 8, de los 8 puntos posibles. B) El aspecto por estudio macroscópico después de doce semanas de efectuada la cirugía del animal H 164;izquierdo, sin tratar. Este defecto recibió una puntuación de 6, de los 8 puntos posibles. C) El aspecto por estudio macroscópico después de doce semanas de efectuada la cirugía del animal H 157;derecho, terapia con SAFHS. Este defecto recibió una puntuación de 8, de los 8 puntos posibles. D) El aspecto por estudio macroscópico después de doce semanas de efectuada la cirugía del animal H 157;izquierdo, sin tratar. Este defecto recibió una puntuación de 3, de los 8 puntos posibles. Figure 17. A) Una vista de baja potencia de un defecto tratado con ultrasonido después de cuatro semanas de la operación. (Safranina O y verde rápido, aumento 8x. G217 derecho, EXI095-1R). En comparación con los defectos no tratados, hay un aumento muy marcado en la tinción de safranina O en todo el tejido reparado, lo cual indica la producción de proteoglicanos de la matriz. Hay una significativa actividad de condroblastos y evidencia precoz de disposición en columna de los condrocitos en las interfaces del defecto. También hubo cierta restauración del hueso subcondral. Figura 17 C) Una vista de baja potencia de un defecto tratado por ultrasonido después de cuatro semanas de la operación. (Safranina O y verde rápido, aumento 8x. H156, derecho, EXI095-01R). De un modo similar a lo observado en G217, derecho, la tinción intensa con safranina O en todo el tejido reparado indica la producción de proteoglicanos de la matriz. Hay una significativa actividad de los condroblastos y evidencias precoces de disposición en columna de los condrocitos en todo el defecto. El hueso subcondral está restaurado casi por completo. Pese a que la interfaz entre el cartílago reparado y el cartílago adyacente intacto ha soportado ciertos cambios degenerativos, el cartílago reparado está bien unido en la interfaz. (El desgarro grande del centro del defecto se produjo durante el seccionamiento).
Independent claims7
220 paragraphs in 6 sections, as filed
Kit to stimulate cartilage growth.
Field of the Invention
The present invention relates to methods and apparatus for treating lesions therapeutically, using ultrasound. More particularly, the present invention relates to methods and apparatus that use an ergonomic construction ultrasonic transducer assembly, configured to cooperate with a positioning module, to locate it near a cartilaginous and / or osteocartilaginous lesion and / or defect, with the purpose of stimulating cartilage growth.
Description of the related technique
The use of ultrasound to treat therapeutically and evaluate bone lesions is known. It has been determined that the collision of ultrasonic pulses having the appropriate parameters - for example, frequency, repetition of pulses and amplitude - during adequate periods and at an appropriate external location, adjacent to a bone lesion, accelerates natural healing, for example, of tears and bone fractures.
U.S. Patent Document UU. with the number 4,530,360 granted to Duarte, it describes a basic, non-invasive therapeutic technique, and an apparatus for applying ultrasonic pulses from an operating surface placed on the skin, in a place adjacent to a bone lesion. To apply the ultrasound pulses during the treatment, the operator must manually hold the applicator in place, until the treatment is completed.
The Duarte patent, as well as the US patent document. UU. With the number 5,520,612 granted to Winder et al., it describes intervals of RF signals to create the ultrasound, levels of ultrasound power density, duration intervals for each ultrasonic pulse and frequency ranges of ultrasonic pulses.
U.S. Patent Document UU. No. 5,003,965 issued to Talish et al. refers to an ultrasonic treatment system for the body, which has an applicator unit for the body connected to a remote control unit, by means of coated fiber optic lines. The signal that controls the duration of the ultrasonic pulses and the repetition frequency of the pulses are generated separately from the applicator unit for the body. Talish et al. Also describe a assembly for connecting the applicator unit for the body to a patient, so that the operating surface is adjacent to the skin site.
U.S. Patent Document UU. 5,556,372 describes a suitable kit to stimulate cartilage growth, which comprises a module of the therapeutic head with an ultrasonic transducer, an accessory that the patient can be placed adjacent to the lesion and that can be configured to accommodate at least a portion of the module of the therapeutic head with an ultrasonic transducer, an ultrasonic signal generator and a main operating unit.
Although the systems described in these patents refer to therapeutic methods and an apparatus for the ultrasonic treatment of injuries and defects in hard and soft tissues, there is a need to find transducers and signal generators configured for the treatment of lesions and / or cartilaginous and / or osteocartilaginous defects. In addition, it is necessary to find an apparatus that optimizes the treatment of lesions and / or cartilaginous and / or osteocartilaginous defects.
A cartilaginous and / or osteocartilaginous lesion and / or defect usually involves damage to the cartilage that covers the bone joints (articular cartilage), such as the bones of the knee, elbow, shoulder and ankle. Osteocartilaginous or osteochondral lesions can be treated by chondral and / or osteochondral perforation, causing blood flow to the site. The goal of chondral perforation is to stimulate the regeneration of cartilage, as part of the healing process. However, the resulting non-hyaline or fibrocartilage membrane produced is biomechanically inferior to articular cartilage, has no comparable proteoglycan content and can basically consist of a thin and disorganized layer of collagen. On the other hand, it has been observed that, generally, with the passage of time, degeneration of the new tissue occurs, which necessitates an additional reconstructive surgical treatment.
Other methods of treatment include: transplanting cartilage without weight load in the lesion and / or defective place; induce a fracture in the place where the lesion and / or defect is found; place a carbon fiber matrix to induce cartilage formation and perform an autologous chondrocyte implant (ACI). ICA involves removing chondrocytes capable of regenerating hyaline type cartilage from the body and cultivating it for several weeks. During the culture process, the amount of cells increases approximately 15 times more than the original tissue sample. Cultured cells are then transplanted through an arthrotomy. A small piece of periosteum is taken, the skin that lines the patient's tibia bone. The periosteum is then sutured over the defect, to provide a protective cover to the cultured cells. Cultured cells are injected under the periosteum in the defect, where they continue to multiply and produce lasting repair tissue. However, ICA increases healing time, because chondrocytes have to be cultured before being transplanted to the patient.
Therefore, there is also a need to find a method and an apparatus to stimulate the regeneration of cartilage that produces fibrocartilage, which is biomechanically equal to or better than articular cartilage, which has a comparable proteoglycan content and which consists of a thick layer. and organized collagen. Moreover, there is also a need to find an apparatus that stimulates the regeneration of cartilage and where the regenerated cartilage does not degenerate over time, demanding additional treatment or reconstructive surgery. In addition, an apparatus that stimulates cartilage regeneration and that significantly reduces healing time is also required.
SUMMARY OF THE INVENTION
The ultrasonic treatment apparatus such as that described herein is used to therapeutically treat lesions and / or cartilaginous and / or osteocartilaginous (osteochondral) defects using ultrasound. The apparatus includes an ergonomic locator module, configured to install at least one ultrasonic transducer assembly with an integral signal generator, which provides excitation signals to an ultrasonic transducer - at least one - within the transducer assembly. The synchronization control circuit system, as well as the monitoring circuit system for the proper connection and operation of the transducer assembly, are housed inside a portable main operating unit, which can be equipped with a bag that The patient gets. During operation, the positioning module is located against a part of the patient's body, so that at least one transducer is positioned on the cartilage and / or the lesion and / or the osteocartilaginous defect. Then, at least one transducer is excited for a predetermined period, to measure ultrasonic waves against the damaged cartilage area, in order to stimulate the regeneration of the new articular cartilage.
Preferably, the main operating unit has: an internal power supply to power the signal generator circuit system; a screen connected to the circuit system of the signal generator to present the sequence data of the treatment; a keyboard connected to the circuit system of the signal generator to allow user operation and / or data entry. The signal generator circuit system includes a processor, means for generating a pulsed control signal and a switch connected to the processor to regulate the pulsed control signal. A communication interface may be connected between a communication port and the processor, to provide a communication link between the ultrasonic signal generator and an external computer or modem. Preferably, the communication interface is a serial communication interface; however, a parallel interface is also contemplated. An alarm is provided to indicate to the user that the treatment time has expired. The alarm is connected to the processor in such a way that when the ultrasonic treatment is completed, the processor activates the alarm and terminates the ultrasound generation.
The present invention, as defined in claim 1, provides a kit for ultrasound treating the lesions and / or defects of the cartilage and / or osteocartilaginous. The kit includes an ultrasonic transducer assembly, a positioner module configured to be used by a patient and to receive the ultrasonic transducer assembly, an integrated ultrasonic signal generator, located in the ultrasonic transducer assembly, and a main operating unit (MOU , main operating unit) or controller, where the positioning module comprises a positioning support, which includes channels, each of which consists of an extension mounted there to hold an assembly of ultrasonic transducers.
The MOU has an internal power supply, which allows mobility for the patient. The MOU contemplated for use with the present invention is described in US Pat. UU. with the number 5,556,372 granted to Talish and collaborators.
The MOU is electrically connected to at least one transducer that is fixed to the positioner module. The activation of the signal generator that corresponds to each transducer excites at least one ultrasonic transducer, so that it emits ultrasonic waves to the cartilage and / or to the lesion and / or to the osteocartilaginous defect.
A method is also provided to treat lesions and / or cartilaginous and / or osteocartilaginous defects with ultrasound. Once the location of the lesion and / or the cartilaginous and / or osteocartilaginous defect is determined, the natural healing processes, typical of the organism adjacent to the lesion, are stimulated. This can be achieved by means of a chondral perforation in the defect, to form a series of channels designed to stimulate blood flow and induce the biological reconstructive healing response of the underlying area, in the place where the cartilage is located. Other methods of stimulating this response include: laser drilling, inducing a fracture, scraping, applying chemical or biochemical treatments, etc. Once the healing response has been sufficiently facilitated, a positioning module is placed, which contains an assembly of ultrasonic transducers that have at least one transducer and a signal generator adjacent to the injured part of the organism, so that at least one transducer is near the lesion and / or the cartilaginous and / or osteocartilaginous defect for the treatment of the lesion. The signal generator is then activated to excite the only transducer at least, so that it emits ultrasonic waves to the lesion and / or to the cartilaginous and / or osteocartilaginous defect. Ultrasonic waves impact the site of the lesion to stimulate and accelerate the biological healing properties of the organism, in order to regenerate the cartilaginous material. The present method can also be used in conjunction with autologous cultured chondrocyte transplantation to the site of injury to increase healing time.
In an alternative embodiment, a positioning module is provided for fixing there a plurality of transducers in a plurality of configurations. The positioning module is then fixed to the place where the lesion and / or the cartilaginous and / or osteocartilaginous defect is found, for example, in the ankle or wrist, to stimulate cartilage regeneration. In addition, the present invention also provides an embodiment that has a positioning module that contains an interlocking structure to immobilize the bones that articulate in a particular position. This embodiment prevents the patient from moving his limbs, for example, moving the femur with respect to the tibia, during treatment.
BRIEF DESCRIPTION OF THE DRAWINGS
Preferred embodiments of the invention are described below, with reference to the drawings, which are explained as follows:
Figure 1 is a perspective view of a patient, wearing a portable ultrasonic treatment apparatus of a first embodiment, in accordance with the present invention, which has a main operating unit or controller and a positioning module.
Figure 2A is an exploded view of the positioning module of the portable ultrasonic treatment apparatus, illustrated in Figure 1.
Figure 2B is a rear and bottom view of the positioning module of the portable ultrasonic treatment apparatus, which is illustrated by Figure 1.
Figure 3 is a cross-sectional view illustrating the assembly of transducers that emit ultrasonic waves towards the articular cartilage inside the knee, where an ultrasonic conductive gel is placed between the transducer assembly and the patient's knee.
Figure 4 is a block diagram of an embodiment of the circuit system for mounting ultrasonic transducers.
Figure 4A is a block diagram of an alternative embodiment of the circuit system for mounting ultrasonic transducers.
Figure 5 is a perspective view of a second embodiment of the portable ultrasonic treatment apparatus, illustrating a main operating unit or controller and a positioning module for treating osteocartilaginous lesions within the elbow region.
Figure 6 is a perspective view of a third embodiment of the portable ultrasonic treatment apparatus, illustrating a main operating unit or controller and a positioning module for treating osteocartilagonous lesions within the shoulder region.
Figure 7 is a perspective view of a configuration that is not in accordance with the invention, of the ultrasonic treatment apparatus, illustrating a main operating unit or controller and a positioning module.
Figure 8 is a perspective view of the portable ultrasonic treatment apparatus illustrated by Figure 7 mounted on the ankle of a patient.
Figure 9 is a perspective view of a fifth embodiment of the portable ultrasonic treatment apparatus, illustrating a main operating unit or controller and a positioning module for treating osteocartilaginous lesions within the knee region.
Figure 10A is an exploded view of the portable ultrasonic treatment apparatus, which is illustrated by Figure 9.
Figure 10B is a perspective view of a support piece of the portable ultrasonic treatment apparatus illustrated by Figure 9.
Figure 11 is a flow chart illustrating the steps required to stimulate a healing response at the site of an osteocartilaginous lesion in accordance with the present invention.
Figure 12A is a perspective view showing the perforation of channels within the articular walls of the femur and tibia.
Figure 12B is a cross-sectional view showing the ultrasonic waves "bouncing" from the channels within the articular walls of the femur and tibia.
And Figures 13A-19D are photographs that illustrate the postoperative aspect of cartilaginous and / or ostoecartilaginous defects of the patellar groove region of rabbits, according to a study carried out to show that daily ultrasound therapy accelerated healing. of cartilaginous and / or osteocartilaginous defects already at four weeks, both in histological analysis and in the macroscopic study.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The ultrasonic treatment apparatus is used for the non-invasive use of ultra-high frequency acoustic energy surgically, in the treatment of cartilaginous and / or osteocartilaginous lesions and / or defects. Although this detailed description analyzes the treatment of cartilaginous and / or osteocartilaginous lesions and / or defects caused by an injury, the ultrasound treatment apparatus can be used to treat osteocartilaginous defects caused by other means, such as medication, a infection or metabolic processes.
The apparatus includes the ergonomic locator module, which has a strap or other fastening means to fix it adjacent to an injured part of the patient's body. At least one assembly of ultrasonic transducers is placed or embedded within the positioning module and is properly located in the vicinity of the cartilage and / or the lesion and / or the osteocartilaginous defect. It is possible to provide different types of ultrasonic transducers and signals, such as those described and illustrated schematically in US Pat. UU. with the number 5.520.612 granted to Winder and collaborators. Particularly, the transducers and arrangements schematically illustrated in Figures 7-11 of the patent, where at least one transducer is used to provide acoustic energy to the site of the injury. The device can also use a portable main operating unit (MOU), ergonomically constructed, which the patient puts on and controls the signals sent to the ultrasonic transducers. The MOU used is preferably the one described in US Pat. UU. with the number 5,556,372 granted to Talish and collaborators.
Turning to the figures, in particular to figure 1, an embodiment of the portable ultrasonic treatment apparatus 10 of the present invention is shown. The ultrasonic treatment apparatus 10 includes an MOU 12, a positioning module 14 and the assemblies of ultrasonic transducers 16.
The positioning module 14 comprises a positioning support 20, which includes at least two or three channels 22, each of which has an extension 24 mounted thereon. Each extension has a pocket of the transducer 26, at one end, to support an assembly of ultrasonic transducers 16. It is contemplated that each extension 24 has several ranges of movements, in addition to the longitudinal movement, such as, for example, the joint movement transverse to the longitudinal movement .
The positioning module 14 also includes a positioning band 28 that cooperates with a slot 30 to fix the positioning support 20 in the patient. The positioning band 28 is configured to firmly fix the positioning module 14 on the patient. A material of the sponge type 32 preferably covers the inner surface of the positioning support 20 to provide comfort to the patient (Figures 2A and 2B). The positioning support 20 can be constructed of hard plastic, which can be molded specifically for a particular body part of the patient.
With reference to Figures 2A and 2B, the extensions 24 are mounted on the positioning bracket 20 by means of the screws 33 and thumb screws 34. The screws 33 pass through the slots 35 and holes 36, in the extensions 24 and they are screwed with the thumb screws 34. Extensions 24 can be moved to different positions to accommodate patients of all types of physical build, by unscrewing the butterfly screws 34 and sliding the screws 33 through the slots 35 and screwing the screws 33 to the butterfly screws 34 in the new position.
The transducer assembly 16 may include a circuit system, which is schematically illustrated in Figures 4 and 4A and described below, to excite there at least one transducer and is coupled to the MOU by means of cable 37 and wires 39 The wires 39 are connected to the positioning bracket 20. The cable 37 is preferably a multiconductor cable capable of transmitting relatively low frequency optical or RF signals, as well as digital signals. Cable 37 may include a coaxial cable or other suitable shielded cable. Alternatively, cable 37 may include a fiber optic cable for transmitting optical signals. The signals can be transmitted continuously or as a series of pulses.
During operation, the positioning module 14 is located in the patient's body and holds it, as shown in Figure 3, so that each transducer assembly 16 is laid on the cartilaginous lesion and / or defect and / or osteocartilaginous. A positioning ring, such as the one described in the US patent application under number 08 / 389.148, can be used to determine the location of the injured bone, if the patient wishes to place one of the transducer mounts on a bone lesion, before putting on the positioner module 14. Once a positioner module 14 is located, the transducer inside the transducer assembly 16 is excited for a predetermined period. An ultrasound conductive gel 38 is placed between the transducer assembly 16 and the injured part of the patient's body, to avoid attenuation of the ultrasonic waves as they travel through the articular cartilage 40, as shown in Figure 3.
It is also contemplated to be able to convert one or more transducers so that they receive the diagnostic data reflected from the place where the treatment is applied. This allows a real-time evaluation of the site of the injury and healing process.
Referring to Figure 4, a block diagram of an embodiment of the ultrasonic transducer mounting circuit system is shown. The transducer mounting circuit system 17 includes an RF receiver / oscillator 50 that receives the signals transferred by a signal generator within the MOU 12, via cable 37. The RF receiver / oscillator 50 is connected to the actuator of the transducer 52 that excites transducer 16. An alternative embodiment of the transducer mounting circuit system 17 is shown in Fig. 4A. In this embodiment, the ultrasonic transducer assembly 16 includes an internal battery 60 that feeds the components that are within the transducer assembly 16. For example , the battery 60 provides power to the signal monitoring circuit 62 and signal booster 66. The signal monitoring circuit 62 preferably provides a digital output signal 68 that represents the waveform characteristics of the output of the transducer actuator 70. These characteristics may be presented on a digital display and may include, for example, the frequency, pulse, repetition frequency, pulse width and average output power of transducer 16. The output signal 68 of the signal monitoring circuit 62 is transferred to the signal generator within MOU 12, by means of actuator 66 and cable 37. The signal generator may include a processor and a switch to regulate the characteristics of the signs. Control signals from MOU 12 are received by receiver 72 via cable 37. The safety interlock or fixation 74, which may include switches on the external surface of the positioning module 14 or of the transducer assembly 16, ensures the proper location of the positioning module 14 before feeding the components of the transducer assembly 16.
A second embodiment of the portable ultrasonic treatment apparatus of the present invention is illustrated by FIG. 5 and is generally designated by reference numeral 200. The treatment apparatus 200 includes MOU 12 and transducer mounts 202 fixed to a positioning module 204, by means of extensions 206 to ultrasonically simulate the generation of cartilage in the elbow region. Each transducer assembly 202 includes a power transducer 212 connected to the MOU 12 via the cable 218. An ultrasonic conductive gel 212 is placed between the transducer assemblies 202 and the osteocartilaginous lesion to prevent attenuation of the ultrasonic waves as it travels articular cartilage In order to adapt them to various patients, extensions 206 can be adjusted to various positions by unscrewing the butterfly screws 220. The circuit system for each transducer assembly 202 may be similar to that described for the first embodiment and is schematically illustrated by Figures 4 and 4A.
It is contemplated to be able to construct the positioning module 204 with a suitable conductive plastic, such as, for example, conductive ABS plastic with either carbon, stainless steel, nickel or aluminum fibers, to support the use of wires to connect the transducer assemblies 202 to the cable 218. In said embodiment, the conductive positioner module 204 would be used to electrically connect the transducer mounts 202 to the MOU 12 via the cable 218.
With reference to Figure 6, a third embodiment of the portable ultrasonic treatment apparatus of the present invention is illustrated. In this embodiment, the treatment apparatus 300 includes an MOU 12, a positioning module 304 and ultrasonic transducer assemblies 306. The positioning module 304 is configured to be placed in the shoulder region and includes a positioning band 310 and a positioning support 312 . Each transducer assembly 306 is connected to MOU 12 via cable 318 to the power transducer mounting circuit system within each assembly 306. The circuit system (not shown) may be similar to that described for first and second embodiments and which is schematically illustrated by Figures 4 and 4A.
During operation, the transducers that are within the transducer mounts 306 are excited for a predetermined period to emit ultrasonic waves towards the articular cartilage within the shoulder region.
A fourth configuration that is not in accordance with the invention and that is basically suitable for the treatment of cartilaginous and / or osteocartilaginous lesions and / or defects is illustrated by Figures 7 and 8. In this configuration, the apparatus 400 includes at least an assembly of ultrasonic transducers 402 located inside pockets 404 on a belt 406. Transducer assemblies 402 can be arranged in a plurality of configurations within pockets 404, to adapt them to the anatomical differences of many patients. The belt 406 fits near a cartilaginous and / or osteocartilaginous lesion and / or defect, as shown in Figure 8, by means of a self-restraining material 405. The belt 406 is connected by wires 407 and the cable 408 to an MOU 12, which contains a circuit system to excite an assembly of ultrasonic transducers 402 - at least one - fixed to the belt 406.
During operation, at least one assembly of transducers 402 is excited to emit ultrasonic waves towards the cartilaginous and / or osteocartilaginous lesion and / or defect, as shown in Figure 8. It is contemplated to place an ultrasonic conductive gel between the treatment between the belt 406 and the patient's body, in order to avoid attenuation of the ultrasonic waves.
It is also contemplated to manufacture the belt 406 with suitable conductive plastics, such as conductive ABS plastic, whether with carbon fibers, stainless steel, nickel or aluminum, to dispense with the use of wires for the electrical connection of the only ultrasonic transducer at least 402 to cable 408.
A fifth configuration of the portable ultrasonic treatment apparatus that is not in accordance with the invention, which is basically suitable for the treatment of defects and / or cartilaginous and / or osteocartilaginous lesions, is illustrated in the figures. 9-10B. In this configuration, the apparatus 500 includes an MOU 12 and three assemblies of ultrasonic transducers 502 located inside the pockets 504 on an internal surface of a concave plate 506, as shown in Figure 10B. The concave plate 506 is located at one end of a vertical bar 508, which has a groove 509 in a lower portion. The apparatus 500 also includes an interlocking fastener module 510, which has a thigh support 512 and a leg support 514.
As shown in the developed view of Figure 10A, the thigh support 512 includes a thigh support plate 516, a fixation band 518, and two horizontal fixation extensions 520, which are secured to the plate 516 thigh support using 522 screws and 524 thumb screws. The leg support 514 includes a leg support plate 526, a fixing band 528 and two vertical fixing extensions 530 that are secured to the leg support plate 526. The vertical bar 508 is configured for mounting within a channel 532, in the leg support 514. The vertical bar 508 is secured to the channel 532 by the screw 534 and the thumb screw 536. The vertical bar 508 can move vertically, through the channel 532 by unscrewing the wing screw 536 so that it adapts to several patients.
The thigh support 512 and the leg support 514 are fixed to each other by securing the horizontal fixing extensions 520 and the vertical fixing extensions 530 by means of the screws 538 and the thumb screws 540, in order to prevent the patient move the thigh with respect to the leg, during the treatment and to ensure that the transducer assemblies 502 remain fixed in their corresponding positions. The transducer assemblies 502 are connected by a cable 542, which plugs into a hole 544 to the MOU 12, which contains a circuit system to excite the assemblies of ultrasonic transducers 502. It is contemplated to place, during treatment, a conductive gel Ultrasonic between the transducers 502 mounted on the concave plate 506 and the patient's body, to avoid attenuation of the ultrasonic waves.
A method of treating a cartilaginous and / or osteocartilaginous lesion and / or defect is described by the flow chart of Figure 11. The method comprises stimulating blood flow, in order to induce a biological reconstructive healing response of the underlying area where the cartilaginous and / or osteocartilaginous lesion is found (stage A) and irradiating the place where the cartilaginous lesion is located and / u osteocartilaginous with ultrasonic waves for a period sufficient to accelerate the healing response (stage B). Stage A involves mechanical drilling, induction of a fracture, laser drilling, administration of chemical or biochemical treatments, scraping the site of the lesion to stimulate the growth of cartilaginous tissue.
Stage B preferably involves propagating a primary directional lobe of acoustic energy in the tissue and / or body fluids, around a central or longitudinal axis, and this primary directional lobe is concentrically surrounded by lobes of primary shear waves of acoustic energy The carrier frequency is high enough to establish a standing wave condition in one or more spaces between opposite surfaces, adjacent to the place where the cartilaginous and / or osteocartilaginous lesion is located or in that place, as long as the space is dimensionally characterized at least for a quarter wavelength in the carrier frequency, thus enabling demodulation of the carrier frequency. In a matter of days, healing takes place at an accelerated rate, in the environment of said demodulation, with the resulting development of cartilage in space reduction; Although the pattern of the propagation of carrier waves in the tissue and / or body fluids surrounding the central axis of the acoustic propagation is rich in therapeutically beneficial acoustic energy shear waves.
It is also contemplated to use the present method in conjunction with the autologous cultured chondrocyte transplantation at the site of the lesion, in order to increase the healing time.
With reference to Figures 12A and 12B, steps A and B, respectively, are illustrated. Figure 12A is a perspective view showing the perforation of channels 600 within the defect, using a drill 608 to stimulate blood flow and induce the biological reconstructive healing response of the underlying area at the location where the cartilaginous lesion is located and / or osteocartilaginous. Figure 12B is a cross-sectional view, showing the ultrasonic waves "bouncing" in the channels 600 within the articular walls 602 of the femur 604 and the tibia 606 for a period sufficient to accelerate the healing response.
Figures 13A-19D are photomicrogafies illustrating the postoperative aspect of cartilaginous and / or osteocartilaginous defects created in the region of the patellar groove of rabbits, according to studies (EXI095-01R and EXI096-01R) carried out to demonstrate that daily ultrasound therapy accelerates the healing of cartilaginous and / or osteocartilaginous defects as early as four weeks, as observed both in the macroscopic study and in the histological analysis. The defects treated with ultrasound showed more properties of hyaline cartilage compared to the untreated places, at four, eight and twelve weeks after the surgery. In addition, greater bone restoration was also observed. The second study, the EXI09601R, confirmed the results of the initial study, the EXI095-01R, and added an analysis for a longer period (12 weeks). The defects treated by ultrasound for four weeks after the operation received higher histological scores and in the macroscopic study, compared to the untreated defects, which indicates an acceleration in tissue regeneration and higher levels of proteoglycan formation and similar morphology. to cartilage, in addition to greater integration of repaired cartilage with surrounding host cartilage. The average rating of the macroscopic study for defects treated with ultrasound was 6.92 / 8 versus 4.83 / 8 for defects not treated at four weeks. The mean histological analysis score for defects treated with ultrasound was 15.11 / 24 versus 9.28 / 24 for defects not treated at four weeks. At eight weeks after surgery, the differences were more subtle, both in the macroscopic study and in the histological analysis between the treated and untreated defects. The average rating of the macroscopic study for defects treated with ultrasound was 7.50 / 8, compared with 6.33 / 8 for defects not treated at eight weeks. The mean histological analysis score for defects treated with ultrasound was 15.83 / 24, compared to 13.60 / 24 for defects not treated at eight weeks. However, at twelve weeks after surgery, drastic differences were observed in the macroscopic study between treated and untreated defects (rating of 7.17 / 8 in the macroscopic study for defects treated with ultrasound versus 5, 50/8 for untreated defects). This may represent the initial degeneration of the inferior cartilage produced in untreated defects. The mean histological analysis score for defects treated with ultrasound was 19.06 / 24. The average score for untreated defects was 15.06 / 24.
In general, sites treated with ultrasound demonstrated higher and earlier amounts of subchondral and cartilage bone regeneration. Over time, ultrasound-treated sites denoted extensive subchondral bone regeneration, reduced degeneration of the adjacent cartilage and greater thickness of the chondral layer, as well as a greater amount of integration of the repaired cartilage with surrounding host cartilage. These characteristics indicate a better quality of the repaired cartilage, able to better tolerate loads and degeneration with the evolution of time.
A total of 18 New Zealand white rabbits, male, weighing between five and nine pounds were used when acquired. Particular attention was given to selecting animals that were uniform in size to limit the variability in the burden of osteocartilaginous defects. Bilateral osteocartilaginous defects, 3 mm in diameter and 5 mm deep, were surgically created in the patellar groove of each femur. 20 minutes of ultrasonic therapy were applied daily on the defects of the right knee only, until the animals were slaughtered. The defects in the left leg were left untreated. In an initial pilot study of six animals (EXI095-01R), three were sacrificed four weeks after the surgery and three were sacrificed eight weeks after the surgery. Each defect was evaluated in a macroscopic study and through histological analysis, to determine the quality and extent of cartilage regeneration. According to the results obtained at four and eight weeks in the macroscopic study and at four weeks in the histological study, a similar second study (the EXI096-01R) was carried out, which included 12 rabbits. A macroscopic pathological examination of all vital organs and systems was performed. A summary of the surgery and the treatment scheme for both studies is presented in Table 1.
Table 1. Treatment scheme (EXI095-01R and EX1096-01R)
<dl><dt>Animal No. </dt><dd>Right knee treatment Left knee treatment Surgery date Duration </dd></dl>
<dl><dt>EXI095-01R: </dt><dd /></dl>
<dl><dt>G200 </dt><dd>20 minutes per day None May 16, 1996 4 weeks </dd></dl>
<dl><dt>G203 </dt><dd>20 minutes per day None May 16, 1996 4 weeks </dd></dl>
<dl><dt>G217 </dt><dd>20 minutes per day None May 16, 1996 4 weeks </dd></dl>
<dl><dt>Animal No. </dt><dd>Right knee treatment Left knee treatment Surgery date Duration </dd></dl>
<dl><dt>G198 </dt><dd>20 minutes per day None May 16, 1996 8 weeks </dd></dl>
<dl><dt>G201 </dt><dd>20 minutes per day None May 16, 1996 8 weeks </dd></dl>
<dl><dt>G202 </dt><dd>20 minutes per day None May 16, 1996 8 weeks </dd></dl>
<dl><dt>EXI096-01R: </dt><dd /></dl>
<dl><dt>H155 </dt><dd>20 minutes per day None July 26, 1996 4 weeks </dd></dl>
<dl><dt>H156 </dt><dd>20 minutes per day None July 26, 1996 4 weeks </dd></dl>
<dl><dt>H160 </dt><dd>20 minutes per day None July 26, 1996 4 weeks </dd></dl>
<dl><dt>H152 </dt><dd>20 minutes per day None July 26, 1996 8 weeks </dd></dl>
<dl><dt>H153 </dt><dd>20 minutes per day None July 26, 1996 8 weeks </dd></dl>
<dl><dt>H162 </dt><dd>20 minutes per day None July 26, 1996 8 weeks </dd></dl>
<dl><dt>H154 </dt><dd>20 minutes per day None July 26, 1996 12 weeks </dd></dl>
<dl><dt>H157 </dt><dd>20 minutes per day None July 26, 1996 12 weeks </dd></dl>
<dl><dt>H161 </dt><dd>20 minutes per day None July 26, 1996 12 weeks </dd></dl>
<dl><dt>H163 </dt><dd>20 minutes per day None July 26, 1996 12 weeks </dd></dl>
<dl><dt>H164 </dt><dd>20 minutes per day None July 26, 1996 12 weeks </dd></dl>
<dl><dt>H165 </dt><dd>20 minutes per day None July 26, 1996 12 weeks </dd></dl>
The right knees received 20 minutes per day of ultrasonic therapy, with the Sonic Accelerated Fracture Healing (SAFHS), six days a week, starting on day four after surgery. The left knees received no treatment. The SAFHS units were chosen 5 each day at random, for treatment. Due to the large number of animals included in the EX1096-01R study, certain devices were used twice a day, in two different animals. The animals were sedated by an intramuscular injection of Ketaset and Rompun (83 mg / ml ketamine and 17 mg / ml xylazine) at a dose of 0.3 mg / kg body weight to administer the therapy. This dosage is approximately half of the anesthetic dose intended to provide sedation only. The ultrasonic transducer was placed in the distal femur, in the lateral condyle,
10 With abundant ultrasound coupling gel. The areas of interest were periodically shaved to ensure contact between the transducer, coupling gel and the skin.
The SAFHS device is a non-invasive external device, approved by the FDA [Food and Drug Administration] indicated to accelerate the healing of recent fractures. The SAFHS sends a low sound pressure wave signal, with an intensity of 30 milliwatts per centimeter
fifteen square (equivalent to the intensity used for diagnostic ultrasound) to the skin, at the site of the fracture, for twenty minutes per day.
Through the use of standard aseptic techniques, surgery was performed under anesthesia with halothane gas and monitored by electrocardiograms and cardiac monitors. The anesthesia was administered by an intramuscular injection of Ketaset and Rompun (83 mg / ml of ketamine and 17 mg / ml of xylazine), at a dose of 0.6-20 mg / kg of body weight. Both hindquarters were prepared for surgery and sterilely wrapped. The defect in the knee joint was made with a medial parapatellar incision. The connective tissue that fixed the patella was partially released, to dislocate the patella and expose the medial femoral condyle and the patellar groove (Figure 13A). Using a drill wick, an osteochondral defect 3 mm in diameter and 5 mm deep in the patellar groove of the femur was created (Figure 13B). After irrigation with exit solution, the joint was closed in
25 layers (figure 13C). Routine anteroposterior radiographs were taken after surgery, to ensure proper location of the defect.
Butorphanol tartrate (0.2 mg / kg body weight) was administered subcutaneously, as required. The animals were given antibiotics intramuscularly, for four days, after surgery. They were kept in recovery cages after surgery, until they fully regained consciousness.
30 and proved to support their weight, after which they were moved to standard cages and allowed unrestricted movement. Elizabethan collars were used according to the needs, to prevent the animal from removing the stitches.
Osteochondral healing was evaluated in the macroscopic study and by histological analysis. X-rays were used as needed to assess scarring. The animals were observed daily by qualified personnel, to determine any signs of illness or adverse reaction to the experimental procedures.
The right and left distal femurs were harvested in block, carefully labeled and kept in fresh saline, until the qualification was completed by macroscopic studies and by photomicrograph. The specimens were placed in fixative with formalin and labeled with all the necessary identifications. The internal veterinarian carried out a macroscopic pathological examination of the vital organs. This macroscopic pathological examination was performed on all tissue that in the macroscopic study had been determined as abnormal.
Each defective knee harvested was rated according to its macroscopic appearance, according to the scheme of Moran et al. (The Journal of Bone and Joint Surgery, 74-B, 659-667, 1992), by an observer who did not know the treatment group. This analysis assigns a score, according to the formation of intra-articular adhesions, restoration of the articular surface, erosion and appearance of the cartilage. A total of eight points is the best possible grade (table 2.)
Table 2. Rating scale according to the macroscopic study Intra-articular adhesions Ratings
None = 2
Minimum / fine and loose fibrous tissue = 1
Large / dense fibrous tissue = 0 Restoration of the articular surface
Complete = 2
Partial = 1
None = 0 Erosion of cartilage
None = 2
Defective site / site edge = 1
Defective site and adjacent normal cartilage = 0 Appearance of cartilage
Translucent = 2
Opaque = 1
Discolored or irregular = 0 TOTAL SCORE 8 possible points All specimens were prepared for histological evaluation. Individual specimens were fixed by immersion, either in 10% formalin solution or in 4% paraformaldehyde solution. After fixation, the specimens were slowly decalcified in EDTA. The defective area was bisected by the diameter of the defect. The resulting halves and surrounding tissue were embedded in paraffin and sectioned by the defective site. Three sections, 5-7 um thick, were cut from the three levels of each block. Level 1 was the closest to the center of the defect. Level 3 was closest to the perimeter of the defect and level 2 was centered between levels 1 and 3. Three sections of each level were stained with hematoxylin and eosin dyes, Goldner trichrome and safranine O and fast green (to indicate glycosaminoglycan content in the matrix).
The decalcified histological sections were evaluated by an observer who did not know the treatment group. Sections were scored according to the Moran et al. Scheme, which assigns points based on the nature of the repaired cartilage, structural characteristics and cellular changes (Table 3).
Table 3. Rating scale according to histological analysis
NATURE OF THE PREDOMINANT FABRIC:
Cellular morphology Hyaline articular cartilage = 4
Differentiated incompletely = 2 Bone or fibrous tissue = 0
Matrix with safranin O of the womb
Normal / almost normal = 3 Moderate = 2 Mild = 1 None = 0
STRUCTURAL CHARACTERISTICS:
Surface regularity Smooth / intact 3 Horizontal horizontal lamination 2 Fissures, 25-100% thick = 1 Severe alteration, fibrillation 0 Structural integrity Normal = 2 Slight alteration, even cysts = 1 Severe Disintegration = 0 Thickness 100% normal cartilage thickness = 2 50-100% = 1 0-50% = 0 Adherence to adjacent cartilage Attached to the two ends of the defect = 2 United at one end or partially attached to both = 1 Unbound = 0
EXEMPT FROM CELLULAR CHANGES OR DEGENERATION
Hypocellularity None = 3 Mild = 2 Moderate = 1 Severe = 0 Chondrocyte Grouping None = 2 <25% of cells = 1 > 25% of cells = 0
Free from degenerative changes in adjacent cartilage
Normal cellularity, without clusters, normal staining = 3 Normal cellularity, slight clusters, moderate normal = 2 Mild or moderate hypocellularity, mild staining = 1 Severe hypocellularity, poor or no staining = 0
Immunohistochemical staining of the cartilage sections of the defects treated with ultrasound for 12 weeks and those not treated was carried out to identify the type I and type II collagen. Goat anti-human polyclonal antibodies obtained from Southern Biotechnology, Inc. Immunohistochemical staining were used
5 Identifies the critical components of articular cartilage necessary to correct the regeneration and maintenance of the tissue phenotype. In addition, the presence of other tissues that reflect inappropriate tissue formation is identified. In hyaline articular cartilage, type II collagen should be located only in the cartilage layer that is above the subchondral bone. Staining for type I collagen should be restricted to the subchondral bone region.
10 All surgeries developed normally and without complications after surgery. The pathological examination of the internal organs did not demonstrate an adverse response to daily ultrasound treatment or experimental procedures.
Table 4 shows a summary of the macroscopic evaluation scores obtained from the EXI09501R and EXI096-01R studies. Figures 2 to 4 demonstrate the overall macroscopic appearance of the treated and untreated sites at four, eight and twelve weeks after surgery.
Table 4. Average rating in macroscopic evaluation ± standard deviation (n = 6)
<dl><dt>WITHOUT TREATING </dt><dd>ULTRASOUND </dd></dl>
<dl><dt>4 WEEKS </dt><dd> 4,83 ± 1,72 6,92 ± 1,02 </dd></dl>
<dl><dt>8 WEEKS </dt><dd> 6,33 ± 0,82 7,50 ± 0,45 </dd></dl>
<dl><dt>12 WEEKS </dt><dd> 5,50 ±1,22 7,17 ± 0,98 </dd></dl>
Four weeks after the surgery, the ultrasound-treated defects denoted a more complete and uniform tissue coverage, although the cartilage usually had an opaque appearance. There were incompletely covered lesions in the center of many untreated sites, and the regenerated tissue was irregular in color (Figure 14). At eight weeks, both ultrasound and untreated defects were uniformly covered with new tissue. The defects treated with ultrasound demonstrated less erosion of the new cartilage and surrounding the intact cartilage (Figure 15). At twelve weeks after surgery, the defect edges in the defects treated with ultrasound were difficult to appreciate, and the new cartilage had the appearance of the adjacent tissue (Figure 16) and was well integrated with the adjacent host cartilage. The new cartilage had a more transparent appearance, compared to untreated defects and clearly showed a significantly less erosion of adjacent and newly formed cartilage.
A summary of the average qualification of the histological analysis is presented, obtained from the EXI095-01R and EXI096-01R studies in table 5. One half of each twelve-week specimen had been submitted for a tissue typing analysis, with the purpose of identifying the type of collagen and the percentage composition of tissue.
Table 5. Mean histological qualifications for the sites where the surgery was performed, at four, eight and twelve weeks after the operation, ± standard deviation (sample size) for the EXI095-01R study and for the EXI096-01R study .
<dl><dt>4 weeks after surgery </dt><dd>8 weeks after surgery 12 weeks after surgery </dd></dl>
<dl><dt>Without treating </dt><dd>Ultrasound treatment Without treating Ultrasound treatment Without treating Ultrasound treatment </dd></dl>
<dl><dt>Nature of the predominant tissue </dt><dd> 1,11 ± 1,02 (18) 4,06 ± 2,44 (18) 3,87 ± 1,77 (15) 3,72 ± 1,81 (18) 3,50 ± 2-09 (18) 5,61 ± 1,20 (18) </dd></dl>
<dl><dt>Structural characteristics </dt><dd> 5,78 ± 1,86 (18) 6,78 ± 1,29 (18) 6,27 ± 1,49 (15) 7,28 ± 1,07 (18) 6,22 ± 1,99 (18) 7,17 ± 1,65 (18) </dd></dl>
<dl><dt>Exempt from cell changes or degeneration </dt><dd> 2,39 ± 1,72 (18) 4,28 ± 1,67 (18) 3,47 ± 1,73 (15) 4,83 ± 1,79 (18) 5,33 ± 2,52 (18) 6,28 ± 1,02 (18) </dd></dl>
<dl><dt>TOTAL (of 24 possible points </dt><dd> 9,28 ± 3,61 (18) 15,11 ± 4,80 (18) 13,60 ± 3,68 (15) 15,83 ± 2,81 (18) 15,06 ± 6,30 (18) 19,06 ± 2,73 (18) </dd></dl>
Figures 17, 18 and 19 demonstrate the typical histological aspect of both defects, treated and untreated, at four, eight and twelve weeks after surgery.
At four weeks after surgery, the differences between defects treated with ultrasound and those not treated were substantial. Intense staining with safranin O of the matrix, the great activity of the chondroblasts and the early formation of subchondral bone in the defects treated with ultrasound contrasted significantly with the lack of activity and phenotype of chondroblasts present in the untreated defects. Premature degenerative changes of untreated defects were also evident.
At eight weeks, the histological results were similar to the macroscopic results. In general, staining with safranin O was not as intense at eight weeks after surgery on both defects: those treated with ultrasound and those not treated. However, subchondral bone regeneration was complete at sites treated with ultrasound and repaired cartilage showed less signs of degenerative changes. Untreated sites showed less subchondral bone regeneration and repair tissue organization.
Once again, at twelve weeks the place treated with ultrasound obtained higher histological scores than
5 Untreated defects In most cases, subchondral bone regeneration was complete. However, the tissue repaired in the chondral layer of the ultrasound-treated sites showed greater characteristics of articular cartilage than the untreated sites. Most of the untreated sites were covered with a superficial layer of fibrous tissue maturing. The intensity of safranin O staining was mild or absent in the superficial repaired layer of untreated defects. The adjacent intact cartilage was hypocellular and in several
10 cases, there were large groups of more than 20 chondrocytes at the junction between the repaired tissue and the host cartilage. The staining of safranin O was more intense in the places treated with ultrasound; however, variations were observed within the repaired cartilage of the individual defects. There were regions of chondrocytes arranged in columns, thickness of chondral layer almost normal and intensity of safranin staining OR in defects treated with ultrasound.
fifteen A marked staining of type II collagen was found in the newly regenerated cartilage layer in the defects treated with ultrasound, which indicated a good repair, while the sections with untreated defects, which had a bad repair, showed a staining less intense or staining deep within the defect, which reflects inappropriate tissue formation.
Positive staining for type I collagen in the regenerated bone indicated a very poor or zero location in
twenty the regenerated cartilage layer of the samples treated with ultrasound. The presence of type I collagen in non-bone areas would be an indication of fibrosis or fibrocartilage formation.
An additional study, EXI097-01R, was carried out in 66 rabbits that received bilateral osteocartilaginous defects in the femurs, according to the design of the study described above. A summary of the qualification results for the macroscopic study of this study is presented, taken in conjunction with those obtained in the EXI095-01R and EXI096-01R studies in the “Qualification results for the macroscopic study”, in the table
6.
Table 6. Qualification results for the macroscopic study
Treatment group Evaluation period TOTAL
Abrasion defects 4 weeks Average 5.7
twenty Ultrasound minutes Standard deviation 1.0
Sample Size 6
Average Control 4.8
Standard deviation 0.8
Sample Size 6
Defects in the middle condyle 4 weeks Average 4.9
Standard Deviation 1.4
twenty ultrasound minutes Sample size 6
Average Control 4.8
0.6 standard deviation
Sample Size 6
Defects in the patellar groove 4 weeks Average 5.5
Standard Deviation 1.0
twenty ultrasound minutes Sample size 6
Average Control 5.8
(in pairs) Standard deviation 0.3
Sample Size 6
<dl><dt>Treatment group </dt><dd>Evaluation period TOTAL </dd></dl>
<dl><dt>Defects in the patellar groove </dt><dd>4 weeks Half 6.7 </dd></dl>
<dl><dt>Standard deviation </dt><dd> 1,0 </dd></dl>
<dl><dt>twenty ultrasound minutes </dt><dd>Sample size 6 </dd></dl>
<dl><dt>5 ultrasound minutes </dt><dd>Half 5.8 </dd></dl>
<dl><dt>Standard deviation </dt><dd> 1,0 </dd></dl>
<dl><dt>Sample size </dt><dd> 6 </dd></dl>
<dl><dt>Defects in the patellar groove </dt><dd>4 weeks </dd></dl>
<dl><dt>IN PROGRESS </dt><dd /></dl>
<dl><dt>twenty ultrasound minutes </dt><dd /></dl>
<dl><dt>5 ultrasound minutes </dt><dd /></dl>
<dl><dt>Defects in the patellar groove </dt><dd>4 weeks </dd></dl>
<dl><dt>IN PROGRESS </dt><dd /></dl>
<dl><dt>twenty ultrasound minutes </dt><dd /></dl>
<dl><dt>10 ultrasound minutes </dt><dd /></dl>
<dl><dt>Defects in the patellar groove </dt><dd>4 weeks </dd></dl>
<dl><dt>IN PROGRESS </dt><dd /></dl>
<dl><dt>twenty ultrasound minutes </dt><dd /></dl>
<dl><dt>40 ultrasound minutes </dt><dd /></dl>
<dl><dt>Defects in the patellar groove </dt><dd>4 weeks Half 6.6 </dd></dl>
<dl><dt>Standard deviation </dt><dd> 1.8 </dd></dl>
<dl><dt>twenty ultrasound minutes (together) </dt><dd>Sample size 18 </dd></dl>
<dl><dt>Control </dt><dd>Half 5.3 </dd></dl>
<dl><dt>(on the whole) </dt><dd>Standard deviation 1.3 </dd></dl>
<dl><dt>Sample size </dt><dd> 18 </dd></dl>
<dl><dt>Defects in the patellar groove </dt><dd>4 weeks Half 6.6 </dd></dl>
<dl><dt>Standard deviation </dt><dd> 1,0 </dd></dl>
<dl><dt>twenty ultrasound minutes </dt><dd>Sample size 12 </dd></dl>
<dl><dt>Control </dt><dd>Half 5.0 </dd></dl>
<dl><dt>(on pairs) </dt><dd>Standard deviation 1.5 </dd></dl>
<dl><dt>Sample size </dt><dd> 12 </dd></dl>
<dl><dt>Defects in the patellar groove </dt><dd>8 weeks Half 7.0 </dd></dl>
<dl><dt>Standard deviation </dt><dd> 1,2 </dd></dl>
<dl><dt>twenty ultrasound minutes (in pairs </dt><dd>Sample size eleven </dd></dl>
<dl><dt>Control </dt><dd>Half 5.8 </dd></dl>
<dl><dt>(on pairs) </dt><dd>Standard deviation 1.4 </dd></dl>
<dl><dt>Sample size </dt><dd> 11 </dd></dl>
<dl><dt>Defects in the patellar groove </dt><dd>12 weeks Half 6.5 </dd></dl>
<dl><dt>Standard deviation </dt><dd> 1,1 </dd></dl>
<dl><dt>twenty ultrasound minutes (in pairs </dt><dd>Sample size eleven </dd></dl>
<dl><dt>Control </dt><dd>Half 5.6 </dd></dl>
<dl><dt>(on pairs) </dt><dd>Standard deviation 1.1 </dd></dl>
<dl><dt>Sample size </dt><dd> 11 </dd></dl>
Treatment group Evaluation period TOTAL
Defects in the patellar groove 24 weeks
IN PROGRESS 20 minutes of ultrasound the first 12 weeks after the operation Control (on pairs)
Defects in the patellar groove 24 weeks
IN PROGRESS 20 minutes of ultrasound the first 18 weeks after the operation Control (on pairs)
It will be understood that it is possible to make several modifications to the various embodiments of the present invention described herein without departing from its spirit and its scope. For example, it is possible to make several modifications to the structural configuration of the positioning modules and the configuration of the components used to drive the ultrasonic transducer. Therefore, the above description should not be construed as limiting the invention but as a mere presentation of the preferred embodiments of the invention. Those skilled in the art will contemplate other modifications within the scope and spirit of the present invention, as defined in the claims presented below.
Contents6
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Priority claims3
| Document | Office | Kind | Date |
|---|---|---|---|
| 37367P | United States of America | – | |
| 3736797 | United States of America | P | |
| 9802447 | United States of America | W |
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| EP0977534A1 | European Patent Office (EPO) | A1 | |
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| CA2369475A1 | Canada | A1 | |
| WO0067846A1 | World Intellectual Property Organization (WIPO) | A1 | |
| AU4831300A | Australia | A | |
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| US6355006B1 | United States of America | B1 | |
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| AU2003223711A1 | Australia | A1 | |
| EP1180056B1 | European Patent Office (EPO) | B1 | |
| AT253957T | Austria | T | |
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| DE60006521D1 | Germany | D1 | |
| DE60006521T2 | Germany | T2 | |
| CA2289191C | Canada | C | |
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| EP1496995A1 | European Patent Office (EPO) | A1 | |
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| AU2003223711B2 | Australia | B2 | |
| EP0977534A4 | European Patent Office (EPO) | A4 | |
| US7789841B2 | United States of America | B2 | |
| US2010318003A1 | United States of America | A1 | |
| US8123707B2 | United States of America | B2 | |
| EP0977534B1 | European Patent Office (EPO) | B1 | |
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| ATE552030T1 | Austria | T1 | |
| ES2385305T3This record | Spain | T3 |
Numbers
- Publication
- 2385305
- Application
- 98909994
Titles2
- Spanish
- Kit para estimular el crecimiento del cartílago
- English
- Kit to stimulate cartilage growth
Classification
- CPC, 4
- A61B17/1677
- A61B17/16
- A61B18/20
- A61N7/00
- IPC, 3
- A61N7 00
- A61B17 16
- A61B18 20