This invention relates to the field of ultrasonics and the application of ultrasonic energy in medicine, particularly as it relates to the “harvesting” of adipose tissue from an animal, e.g., a human patient, through the application of ultrasonic energy and aspiration of the disassociated adipose tissue from the patient.
In the past few years, the use of lipoaspirate material, that is, the material removed from a patient during liposuction, has expanded. Traditionally, the goal of the liposuction treatment was the removal of adipose tissue, including the “fat cells” (adipocytes) in the adipose tissue, in order to achieve some level of body contouring, and the lipoaspirate, composed of adipose tissue and tumescent fluid, was disposed of as a biological waste material.
Now, however, there is another distinct use for the lipoaspirate. It has been found that in addition to mature adipocytes, the lipoaspirate also contains pre-adipocytes (also known as Adipose Derived Stem Cells or “ADSCs”) and other cellular material such as leukocytes, neutrophils, etc. (the other cellular material being cumulatively referred to as the Stromal Vascular Fraction or “SVF”). The lipoaspirate can be separated into components, including “ADSCs.” The ADSCs can be processed to have a therapeutic purpose within the body, since, like other induced pluripotent stem cells, they can be used to regenerate nearly any other type of cell. See, for example, U.S. patent application entitled “Selective Lysing of Cells using Ultrasound,” Ser. No. 12/941,868 filed on Nov. 8, 2010, which is incorporated by reference herein. This is an area of great interest within the regenerative medicine community.
Typically, ADSCs are harvested during a cosmetic medical procedure employing liposuction, and then used primarily as an adjunct to a re-implantation of the patient's fat into his/her body. For example, fat may be extracted from the hips or stomach region and re-injected into the buttocks, breast, or face for an improved cosmetic appearance. The ADSCs are used to improve the percentage of injected material which remains viable and thrives in its new location within the body. Thus, currently, the aesthetic needs of the patient drives the overall procedure.
Soon, however, the therapeutic benefits of ADSC treatment will be shown to be sufficient to justify lipoaspiration independent of any cosmetic or aesthetic need of the patient. For example, a heart attack victim may be treated with ADSCs to stimulate the regeneration of heart muscle. In this case, the removal of fat will not be driven by cosmetic or aesthetic reasons.
Nevertheless, the current approach to fat removal is still grounded in the cosmetic and plastic surgery markets, in that the equipment and personnel operating the equipment are all of a sophistication and skill level commensurate with an aesthetic result. In other words, only plastic surgeons, dermatologists or other medical specialists with specific training in cosmetic procedures are able to operate the multifaceted ultrasonic equipment. The equipment is designed to facilitate the removal of cosmetically significant volumes of fat, in a way that provides the operator with the ability to “sculpt” the body for the desired (i.e., cosmetic) goal. The surgeon is therefore in control of infiltration amounts, ultrasound amounts, and aspiration.
What is needed is a system designed specifically to remove a small volume of lipoaspirate, suitable for processing into ADSCs, in a way that would be easily operated by clinical personnel who do not have specific training in cosmetic procedures. This would eliminate the need for plastic surgeons, etc. to be involved in therapeutic procedures (which may eventually occur in the Emergency Room or Interventional Radiology setting, at odd hours).
It has been shown that ultrasonic energy aids in the removal of fat through the action of cavitation and acoustic streaming. Ultrasound assisted liposuction equipment, specifically the VASER® from Sound Surgical Technologies (Louisville, Colo.), has been found to be uniquely suited for ADSC harvesting. It produces a smooth aspirate with small cell packets, with high cell viability. Also, it is more selective for harvesting adipose tissue as opposed to muscle, nerve or other cells.
Previous efforts have simply used the existing equipment for ADSC harvesting, either through manual means (Suction Assisted Liposuction, SAL) or using Ultrasound (UAL), or Water Jet (WAL, commercially available as the BodyJet system). The prior solutions comprise various devices and components effecting separate process steps which make for a difficult and cumbersome approach when the objective is to harvest ADSCs with minimal necrosis. Even when the VASER® is used for tissue fragmentation followed by aspiration of the fragmented tissue via the VentX® system (both available from Sound Surgical Technologies LLC of Louisville, Colo.), the optimum result is not achieved. The VASER® and VentX® systems are designed for a wide range of possible cosmetic potentials, with a wide range of output settings, multiple cannulae, an infiltration system capable of large dosages, an aspiration system concomitantly designed to handle liters of lipoaspirate. Even with proper instructions, it would require operation by a trained surgeon to produce the desired result. And the result may not be easily replicated on a repeated basis with confidence in the results for further processing of the harvested cells. In addition, the expense of the VASER® and VentX® prevents its widespread adoption to this focused, non-cosmetic application.
Even where fragmentation and aspiration are incorporated in a single device such as the Lysonix® system available from Mentor Corporation, Santa Barbara, Calif. there are significant issues with multiple components and process variables, expense and a high level of skill required for successful, reliable recovery of ASCSs for successful post processing into therapeutic stem cells. Of particular note, the Lysonix® system has been designed to operate at ultrasound frequencies which are not as appropriate for cell survival.
Thus, there is a need for an inexpensive, integrated system that can be operated by one of lesser medical skill than a surgeon to reliably extract ADSCs from a patient with minimal cell necrosis for the purpose of subsequently processing the cells into therapeutic stem cells for re-insertion into the same patient. The system should be designed to minimize the trauma that can be caused to a patient, and remove only the necessary amount of tissue from a patient. Such a system can be operated effectively with minimal removal of lipoaspirate, e.g., about 250 cc of lipoaspirate (exclusive of the injected infiltration material, which is also partially removed during the procedure).
Embodiments of the present invention are directed to extracting lipoaspirate with ADSCs for regenerative medicine. The embodiments of the present invention are therefore different from systems and methods used in conventional liposuction procedures used for cosmetic purposes.
The present invention includes, in embodiments, therapeutic systems and methods that are self contained, and separate from any cosmetic liposuction equipment and methods. Systems embodying the invention combine the lipoaspiration processes of infiltration, energy deposition, and aspiration. Further, since the current standard approach to processing lipoaspirate down to ADSCs components uses a 250 cc container, embodiments provide for extracting this amount. This puts an upper bound on the amount of infiltration fluid (which is in proportion to the amount expected to be withdrawn), as well as the size of the container(s) used during the aspiration portion of the procedure.
The current invention includes the use of a cannula for infiltration, ultrasound exposure, and aspiration. Embodiments also provide for using a fixed amount of infiltration fluid, in specific ratio with the amount of lipoaspirate to be removed. The amount of ultrasonic energy is a fixed amount of ultrasonic energy, both in amplitude and time, commensurate with the amount of infiltration and aspiration is applied. The ultrasonic cannula used in embodiments of the present invention can also include holes that are positioned so as not to interfere with the ultrasonic action. The cannula is also designed to withstand the stresses of ultrasonic vibrations and deliver infiltration of fluid to an anatomical site and remove lipoaspirate, which includes adipocytes. Embodiment also provide for limiting the extent to which the cannula can be positioned within the patient, enhancing safety while naturally limiting the cosmetic utility of the device.
Embodiments of the present inventions include a method for the ultrasonic harvesting of adipose tissue from a medical patient utilizing a medical device for that purpose. The method includes providing an ultrasonic device capable of delivering ultrasonic energy to a surgical site in a patient and providing a cannula to be used for the application of infiltration fluid to the surgical site. The method includes application of ultrasonic energy to the surgical site, and aspiration of adipose tissue from the surgical site. The cannula in embodiments includes at least one hole for delivery of the infiltration fluid and for removal of the lipoaspirate. The hole is positioned so as not to interfere with the delivery of ultrasonic energy. The method further provides for delivering a fixed amount of infiltration fluid to the surgical site, in specific ratio with the amount of lipoaspirate to be removed and delivering a fixed amount of ultrasonic energy, both in amplitude and time, commensurate with the amount of infiltration and aspiration. Finally, the method involves removing the lipoaspirate using the cannula.
Some embodiments of the present invention have as a main, intended purpose the harvesting/removal of adipose tissue and adipose derived stem cells (ADSCs) in the adipose tissue for purposes other than any cosmetic benefits achieved by that removal. Those embodiments include devices dedicated and/or optimized for the harvesting of adipose tissue and ADSCs. This permits embodiments, including devices and methods, to be presented that can be optimized to achieve this result, can be utilized by someone who is skilled but not at the same level as a cosmetic, i.e., “plastic,” surgeon, and therefore can be manufactured and employed less expensively than a full, multipurpose UAL device designed for and used in cosmetic surgery. As described in greater detail below, the device is optimized for removal of a predetermined amount of lipoaspirate containing sufficiently viable tissue suitable for post-processing and/or re-injection by delivering a preset amount of infiltration fluid to a surgical site, applying a predetermined amount of ultrasonic energy to the surgical site, and removing the predetermined amount of lipoaspirate using a single cannula. Additionally, the device includes features that limit the depth to which the cannula can be inserted into a patient. These features allow the removal of adipose tissue and ADSCs safely and efficiently even by a user with less medical skill than typical of cosmetic surgeons.
Shown in
The device 10 is used for infiltration, delivery of ultrasonic energy, and aspiration of the surgical site. Device 10 includes cannula 100 which serves to provide infiltration, conduct ultrasonic energy from the ultrasound generating handpiece 200, and also provide a conduit for aspiration to the fluid system 400 used for infiltration and collection. Cannula 100 includes a channel 102 that provides the fluid path to fluid system 400 that includes components for both delivery of infiltration fluid to a surgical location and collection of lipoasiprate from the surgical location.
Referring again to
As shown in
The piezoelectric stack 204 may be in some embodiments rings, wherein the back end of cannula 100 fits within the stack of rings. The ultrasonic driver assembly 202 is acoustically coupled to cannula 100 so that the vibrations are conducted through cannula 100 which is placed in contact with a patient for delivering ultrasonic energy to a surgical site.
Fluid system 400 shown in
In embodiments, the infiltration fluid is delivered at rates between about 50 ml/min to about 200 ml/min. As can be appreciated, delivering the fluid more quickly reduces the amount of time it takes to perform the procedure. However, delivering the fluid too quickly may be uncomfortable to a patient who may be conscious during delivery of the fluid. In one embodiment, pump 404 is configured to deliver infiltration fluid at about 150 ml/min. The amount of fluid delivered to the surgical site may range from about 250 cc to about 500 cc depending on the predetermined ratio of infiltration fluid to lipoaspirate. As indicated above, one preferred end result is to obtain about 250 cc of lipoaspirate. Accordingly, the ratios of infiltration fluid to lipoaspirate may range from about 1:1 to about 2:1.
Fluid system 400 also includes a reservoir 406 for storing lipoaspirate removed from the surgical site after infiltration fluid has been delivered to the surgical site and after ultrasonic energy has been applied to the surgical site. The lipoaspirate includes a portion of the infiltration fluid delivered to the surgical site as well as adipose tissue that may include adipocytes, stem cells, and other fluids. Pump 408 is connected to reservoir 406 and is used to create suction that removes the lipoaspirate from the surgical site and to the reservoir 406. In the embodiment shown in
As those with skill in the art will appreciate, reservoirs 402 and 406 can be any suitable sterile container for storing fluids including plastic fluid bags, plastic bottles, or glass bottles. Pumps 404 and 408 can be any suitable pump for delivering fluids to, and removing fluids from, surgical sites. In one embodiment, pumps 404 and 408 are peristaltic pumps.
In embodiments, system 400 may also include a filter 412. The use of the filter can aid in filtering out larger adipocytes thereby creating a more useful lipoaspirate for use in generating stem cells. Any suitable filter can be used as filter 410 including one or more screens or other mechanisms that remove larger adipocytes and other material from the lipoaspirate. For example, the filter 412 may include a number of filters of different sizes that are used in sequence to remove larger tissues first. The filters used to filter the lipoaspirate may range from about 200 μm to about 800 μm. In one specific embodiment, the filters for filtering lipoaspirate range from about 400 μm to about 500 μm. After the larger material has been removed from the lipoaspirate it can be processed to obtain the ADSC's.
System 400 illustrated in
System 400 and 400A are merely two embodiments of a fluid system (for infiltration and aspiration) that may be used, and the present invention is not limited thereto. In other embodiments, a fluid system may combine aspects of both system 400 and 400A such as: use of one or more compressors, use of one or more peristaltic pumps, use of one or more side port(s), use of a back port, use of one or more reservoirs, etc. Embodiments may also combine different aspects of the overall systems shown in
The embodiment shown in
The use of a kit as shown in
Referring again to
It should be understood that although
In embodiments, the distance between at least a portion of the guide 500 and the cannula 100 may be more than about 1 cm, and less than about 3 cm, such as about 1.5 cm, about 2.0 cm, or about 2.5 cm. This would help to assure that the cannula 100 is neither too shallow nor too deep. As can be seen in
In one embodiment, the probe head 700 is used to set the distance between guide 500 and cannula 100. A user can use the probe head 700 to scan the surgical site and determine the depth to the muscle layer. The distance between the guide 500 and the cannula 100 can then be set by the user to prevent the cannula 100 from puncturing the muscle layer. In other embodiments, the use of ultrasound to locate the muscle layer and set the distance between the guide 500 and the cannula 100 may be performed using a separate ultrasound imaging system instead of the probe head 700.
As noted above, guide 500 is designed to prevent cannula 100 from being too shallow or too deep within a patient. The length of guide 500 will therefore depend on the length of cannula 100. In embodiments, cannula 100, and therefore guide 500, is designed to have a length that is optimal in removing adipose tissue from a surgical location on a patient. As those with skill in the art will appreciate, different locations in a human body have different characteristics that may be considered when designing cannula 100 and guide 500. For example, some locations may have relatively thick layers of fat while others have thinner areas. These characteristics can be considered for example to optimize the features (e.g., length, width, construction material) of cannula 100 and guide 500 for removal of tissue from specific locations in a patient.
Referring again to operation of the device 10, once the tissue is infiltrated through cannula 100 with tumescent fluid, which may contain a number of different components such as saline and anesthetic, the ultrasound handpiece 200 is energized, causing ultrasonic vibrations at the end of the cannula 100. As can be appreciated, the infiltration fluid may include some anesthetic that requires some time to properly numb the surgical site. As a result, in some embodiments, the ultrasonic driver assembly within handpiece 200 is programmed to be inoperable for a preset period of time, e.g., about 15 minutes, after the delivery of the infiltration fluid. This programming provides a level of safety that ensures that the user cannot prematurely apply the ultrasonic energy before the anesthetic has time to take effect.
When the ultrasonic energy is applied, the vibrations act to selectively dislodge the fat at the surgical site, through means described in literature and patents and otherwise known to one of ordinary skill in the art. Embodiments of the present invention operate at frequencies that are preset, which eliminates the need of a user to select a frequency. The frequencies can range from about 35 kHz to about 45 kHz. In some embodiments, the frequency may be from about 36 kHz to about 42 kHz or alternatively from about 36 kHz to about 40 kHz. In one embodiment, the frequency may be from about 36 kHz to about 38 kHz. In embodiments, the system operates at frequencies typical of the VASER® system manufactured by Sound Surgical Technologies of Louisville, Colo. These systems in embodiments operate at frequencies at or about 36 kHz. Once the fat cells have been put into suspension, the same cannula 100 is used to withdraw the fat out of the body and into a collection system, e.g., 400 (
The device 10 may be configured in some embodiments to allow a second infiltration step, followed by subsequent ultrasonic energy application and aspiration steps. These second series of steps may be allowed if the amount of lipoaspirate initially obtained is below the amount necessary to process into ADSC's, e.g., less than 250 cc.
The ultrasonic vibration and aspiration process can be controlled so that it is done simultaneously if desired. In contrast to other systems which may do this simultaneous action automatically, the present system can in embodiments be controlled to only energize the handpiece for a fixed time and amplitude, corresponding to the amount of infiltration fluid introduced into the patient. The predetermined time and the predetermined amplitude of the applied ultrasonic energy may be based on the amount of infiltration fluid and/or the anticipated amount of lipoaspirate to be removed from the patient. Applying a fixed amount of ultrasonic energy provides a level of safety that is not found in other systems. Devices embodying the present invention can be configured to provide ultrasonic energy with amplitudes ranging from about 30 μm to about 80 μm. More specifically, the ultrasonic energy may have amplitudes from about 50 μm to about 60 μm. The ultrasonic energy may be applied for about 2 to about 4 minutes, such as about 2.5 minutes, about 3 minutes, or about 3.5 minutes.
The cannula 100 can be made such that it passes through the entire length of the ultrasound handpiece with the connection to the rest of the system (infiltration, aspiration) at the end opposite that put into the patient (see
If the cannula passes through the length of the handpiece, the connection point of the ultrasonic energy must be controlled, again, as would be understood by those skilled in the art. Since the cannula is used for all three portions of the procedure, it must be designed to accommodate all the various requirements. In other words, the holes at the end of the cannula must be designed taking into account the ultrasound vibrations. In order to be used safely for infiltration, the tip of the cannula must be closed (blunt), which again, must be incorporated into the ultrasound design problem, as stress concentrations can occur near the tip.
As one example,
Shown in
In other embodiments, probe 662 does not extend beyond sheath 660. In these embodiments, sheath 660 is used to transmit ultrasonic energy to the surgical site. In addition, probe 662 can be vibrated during aspiration to break up groups of adipocytes in the lipoaspirate as it travels through channel 664.
As can be appreciated, the cannula designs shown in
A device that includes a cannula is used to remove lipoaspirate from a surgical location in a patient. The device also includes a guide that prevents the cannula from being inserted too deeply into the patient. The guide includes a shaft that extends substantially parallel to the cannula. The distance between the guide and the cannula is set to about 2.5 cm.
The cannula is in fluid communication with a fluid delivery system that is used to deliver 300 cc of an infiltration fluid through the cannula to the surgical location in a patient at a rate of 150 ml/min. The infiltration fluid includes saline as well as other components such as a local anesthetic (e.g., lidocaine) and a vascular constrictor (e.g. epinephrine). The fluid system includes a pump that delivers the fluid at the rate of 150 ml/min.
The cannula is acoustically connected to an ultrasonic driver assembly that is preset to a frequency of 36 kHz to apply ultrasonic energy with amplitude of 55 μm for 3 minutes to the surgical location. The cannula conducts the ultrasonic energy from the driver assembly to its tip where it is applied to the surgical location.
After the ultrasonic energy is applied to the surgical location, the fluid system is used to remove lipoaspirate from the patient through the cannula by applying a vacuum. The fluid system applies a vacuum of 15 inHg for removing the lipoaspirate from the surgical site. 250 cc of lipoaspirate are removed from the surgical location.
As those with skill in the art will appreciate, different locations in a human body have different characteristics that may be considered when designing aspects of embodiments of the present invention for use in harvesting adipose cells from a patient. As noted above, some surgical locations in a patient may have relatively thick layers of fat while others have thinner areas. These characteristics can be considered for example to optimize various features of embodiments of the present invention (some of which are described herein and illustrated in the drawings). These features include but are not limited to: length, width, and spacing of the cannula and the guide; amount of infiltration fluid used; composition of infiltration fluid; the amount of pressure or vacuum used in infiltration or aspiration steps; and the amount of ultrasound delivered to the surgical location. These features, and others, can be modified to optimize the harvesting of adipose tissue from different surgical locations in a patient.
As will be appreciated by those of skill in the art, the embodiments described herein are distinct from conventional ultrasonic assisted lipoplasty. Among other things, the apparatus and method of the present invention differ from the ultrasonic assisted lipoplasty equipment and procedures commonly employed in that: (1) a cannula is used for infiltration, ultrasound exposure, and aspiration; (2) a fixed amount of infiltration fluid is injected into the surgical site in specific ratio with the amount of lipoaspirate to be removed; (3) a fixed amount of ultrasound energy, both in amplitude and time, is delivered to the surgical site commensurate with the amount of infiltration and aspiration; (4) an ultrasonic cannula is employed with holes positioned to not interfere with the ultrasonic action; and (5) the device includes a guide that limits the depth to which the cannula can be inserted into a patient. The features can be combined in various embodiments to provide safe and efficient systems and methods for removing adipose tissue from a patient by medical personnel that are less skilled than a typical cosmetic surgeon.
As a result, the apparatus and method of the present invention provide a simple device and technique that can be operated efficiently and successfully by non-cosmetic surgeons, for the purpose of harvesting ADSC's and processing for regenerative medicine. A disposable cannula can be used to improve sterility and reduce processing costs.
Reference has been made throughout this specification to “embodiment,” “one embodiment,” “an embodiment,” “another embodiment,” and “some embodiment” meaning that a particular described feature, structure, or characteristic is included in at least one embodiment of the present invention. Thus, usage of such phrases may refer to more than just one embodiment. Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
One skilled in the relevant art may recognize, however, that the invention may be practiced without one or more of the specific details, or with other methods, resources, materials, etc. In other instances, well known structures, resources, or operations have not been shown or described in detail merely to avoid obscuring aspects of the invention.
While example embodiments and applications of the present invention have been illustrated and described, it is to be understood that the invention is not limited to the precise configuration and resources described above. Various modifications, changes, and variations apparent to those skilled in the art may be made in the arrangement, operation, and details of the methods and systems of the present invention disclosed herein without departing from the scope of the claimed invention.
This application claims priority to U.S. Provisional Patent Application Ser. No. 61/347,378 filed May 21, 2010 entitled, “ULTRASONIC DEVICE DEDICATED TO HARVESTING OF ADIPOCYTES” and to U.S. Provisional Patent Application Ser. No. 61/411,423, filed Nov. 8, 2010 entitled, “ULTRASONIC DEVICE FOR HARVESTING ADIPOCYTES,” both provisional applications are hereby incorporated by reference in their entirety as if set forth herein in full.
Number | Date | Country | |
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61347378 | May 2010 | US | |
61411423 | Nov 2010 | US |