Conductive mesh for neurostimulation

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CONDUCTIVE MESH FOR NEUROSTIMULATION

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to devices and methods for simultaneously treating different medical conditions of a patient, and more particularly, to implantable meshes having conductive elements incorporated therein, that may be used in conjunction with neurostimulation devices or other devices for electrically stimulating selected body parts.

2. Background Discussion

Implantable surgical meshes have been widely used for a variety of different surgical procedures such as hernia repair, pelvic floor repair, urethral slings for treating incontinence, and many others. In hernia repair, meshes are placed surgically to repair the protrusion or defect. Various mesh materials and configurations have been proposed to reinforce the abdominal wall and to close abdominal wall defects by different methods well known in the art. In pelvic floor repair, mesh is used to repair the prolapse of organs within the pelvic cavity. These conditions typically involve organs, namely the bladder, bowel and uterus, that are normally supported by the pelvic floor, but have herniated or protruded into the vagina. The most common cause of pelvic floor prolapse is vaginal childbirth.

Implantable meshes have also been used to treat incontinence. The relatively thin piece of mesh, known as a “urethral sling”, is passed using a needle, without open surgery, via a suitable path that leaves the sling positioned beneath the urethra so that it provides support to the urethra under circumstances where pressure is being exerted on the urethra from the abdomen (i.e., during coughing). One such method is described in detail in U.S. Patent No. 5,899,909. According to this method, the tape

CA 02659634 2014-10-31 or sling is implanted by passing an elongated, curved needle that is attached to one end of the tape through an incision in the vaginal wall, to one lateral side of the urethra, through the pelvic tissue behind the pelvic bone, and exiting out through an incision made in the abdominal wall. The procedure is then repeated passing the other end of the tape on the other lateral side of the urethra. After the tape is properly positioned, the free ends that extend outside of the abdominal wall are trimmed. Over time, fibroblasts grow into the tape to anchor the tape in the surrounding tissue. Thus, the tape is left as an implant in the body to form an artificial ligament supporting the urethra.

Sub-urethral slings have also been placed by a different approach, wherein a needle is passed first through the abdominal wall, along the same path as described above, and eventually exiting through the vaginal incision. The tape is then coupled to the needle in some manner, and pulled back through the body from the vaginal incision and out through the abdominal incision. The chosen approach, vaginal or abdominal, will often depend on the preferences of the surgeon. Yet another approach for implanting a sub-urethral sling has been recently developed, wherein the sling is placed via a pathway extending from a vaginal incision out through the obturator foramen. In still another known method, the sling is similarly placed beneath the urethra, yet is anchored within the pelvic cavity in some fashion (bone or tissue anchors) rather than extending out of the body through an incision in the abdomen or obturator foramen.

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As indicated above, urethral slings, of whatever type and placed by whatever means, are used to treat stress incontinence. While stress incontinence is typically a result of an anatomical defect, another form of incontinence, urge incontinence, appears to be neurologically based and generally revealed as detrusor muscle instability or “bladder spasms.” As such it is usually not conducive to surgical correction. In some cases, women can have both stress and urge incontinence, a condition known as mixed incontinence. In many of these cases, the woman is treated for stress incontinence only to be disappointed when incontinence due to bladder spasms does not resolve itself. The urge component of mixed incontinence would then need to be treated on its own, involving additional intervention. Urge incontinence may or may not result in urine leakage, but both conditions otherwise have similar symptoms and similar forms of treatment, which generally include a combination of behavioral modification (learned strategies for reducing the urge sensation, scheduled voiding, avoidance of bladder-stimulating substances such as caffeine, and pelvic muscle exercises, with or without biofeedback) and drug therapy (typically anticholinergeic agents such as oxybutynin or tolterodine). These treatments require life-long therapy. Unfortunately, behavioral modification requires continuous effort to maintain results and the available drugs have significant side effects for many patients, causing 80% to discontinue therapy within a year. The alternative therapy is to modify lifestyle to accommodate the condition - frequent urination to avoid “accidents” and wearing protective pads or undergarments, depending on the severity of the condition.

Another approach for treating urge incontinence is the stimulation of nerves that innervate the pelvis or lower urinary tract. The sacral spinal nerve roots separate in pairs to exit laterally through the nerve root foramina. The main destinations for these roots are the sacral plexus. Nerves from this plexus provide the motor and sensory innervation of the lower limbs and pelvic organs. Specifically, the sacral plexus splits into five sacral nerve pairs, sacral spinal nerves S1 to S5. These nerves supply the thighs and lower parts of the legs, the

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GYN5022WOPCT4 feet, most of the external genital organs, and the area around the anus. The pudendal nerve is the largest branch of the pudendal plexus and is composed of somatosensory, somatomotor and autonomic elements derived from the anterior primary divisions of the second, third and fourth sacral nerves. The pudendal nerve affects the function of the bladder, urethral sphincter and genitals. Lower branches of the pudendal nerve contribute to peristalsis of the colon and anal sphincter contraction force. The pudendal nerve is closer to the bladder, and its stimulation innervates the bladder, thus eliminating or lessening its contractions. At least one known commercial device sold by Medtronic, Inc. of Minneapolis, MN stimulates the sacral nerve through a needle extended into the sacral nerve bundle. This device, however, supplies a continuous signal to provide constant stimulation of the nerve. Various drawbacks of this device include its invasive nature, and unwanted stimulation effects on other areas of the body, since the sacral nerve as a whole is being stimulated and multiple other areas of the body are innervated by such stimulation (i.e., resulting in leg twitches or the like).

A company called Advanced Bionics has an implantable stimulation device that targets the pudendal nerve specifically rather than the sacral nerve. This device is implanted in the vicinity of the pudendal nerve, but also is invasive and supplies a constant signal as described above and therefore, has the same drawbacks.

In addition to incontinence, women can suffer from other diseases as well, often simultaneously with incontinence. Interstitial cystitis is a chronic bladder condition involving an inflamed or irritated bladder wall. Patients with this condition may experience mild discomfort, pressure, tenderness, or intense pain in the bladder and surrounding pelvic area. Other symptoms may include an urgent need to urinate (urgency), frequent need to urinate (frequency), or a combination of these symptoms. The inflammation can lead to scarring and stiffening of the bladder, less bladder capacity (the bladder is able to hold less urine), and pinpoint bleeding in the bladder lining. In rare cases, ulcers form in the

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GYN5022WOPCT4 bladder lining. Of the more than 700,000 Americans estimated to have interstitial cystitis, about 90 percent are women.

Treatments for interstitial cystitis include oral medicines, such as aspirin, ibuprofen, other painkillers, antidepressants and antihistamines. Another treatment is bladder instillation (a bladder wash or bath) in which the bladder is filled with a solution that is held for varying periods of time before being emptied. These treatments require life-long therapy. Sacral nerve stimulation implants are also used for the treatment of interstitial cystitis, but, as stated previously, its invasive nature and unwanted stimulation effects on other areas of the body make this treatment undesirable. Surgery, considered a treatment of last resort, does not necessarily improve symptoms.

Other diseases that may occur simultaneously with urinary incontinence include fecal and anal incontinence. Fecal incontinence is the inability to control the bowels, and can have several causes with constipation being the most common. Fecal incontinence can also be caused by injury to one or both of the ring-like muscles at the end of the rectum called the anal internal and/or external sphincters. In women, the damage often happens when giving birth. Hemorrhoid surgery can damage the sphincters as well. Fecal incontinence can also be caused by damage to the nerves that control the anal sphincters or to the nerves that sense stool in the rectum. Nerve damage can also be caused by childbirth, a long-term habit of straining to pass stool, stroke, and diseases that affect the nerves, such as diabetes and multiple sclerosis. In addition, rectal surgery, radiation treatment, and inflammatory bowel disease can cause scarring that makes the walls of the rectum stiff and less elastic. Abnormalities of the pelvic floor, which is typically caused by childbirth, can also lead to fecal incontinence. Examples of some abnormalities are decreased perception of rectal sensation, decreased anal canal pressures, decreased squeeze pressure of the anal canal, impaired anal sensation, a dropping down of the rectum (rectal prolapse), protrusion of the rectum through the vagina (rectocele), and/or generalized weakness and sagging of the pelvic floor. Treatment depends on the cause and 5

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GYN5022WOPCT4 severity of fecal incontinence, and may include dietary changes, medication, bowel training, or surgery. A last resort is a colostomy, which is the surgical creation of an opening between the large intestine and the abdominal wall. More than one treatment may be necessary for successful control since continence is a complicated chain of events.

One type of treatment typically cannot be used to treat the different conditions described above, and, as indicated above, many of the known treatments are invasive or have other negative side effects. Accordingly, what is needed is an improved device and method for simultaneously treating different diseases or conditions.

SUMMARY OF THE INVENTION

The present invention provides a medial treatment device for treating at least first and second medical conditions of a patient. The device includes a neurostimulation device for treating a first neurologically based condition of the patient, which further includes a first waveform generator adapted to generate a first waveform having a frequency capable of stimulating a predetermined nerve of the patient, a second waveform generator adapted to generate a carrier waveform having a frequency capable of passing through tissue of the patient, a modulation device electrically coupled to the first and second waveform generators and adapted to modulate the first and carrier waveforms to create a modulated waveform, and an electrode electrically coupled to the modulation device and positioned substantially adjacent to skin of the patient, and adapted to apply the modulated waveform thereto. The device also includes an implantable mesh adapted for implantation within the patient to treat a second medical condition of the patient, wherein the implantable mesh has a plurality of incorporated electrically conductive elements adapted to conduct the applied modulated waveform to a position closer to the predetermined nerve than the electrode when the mesh is implanted.

Also provided is a method for treating at least first and second medical conditions of a patient, the method including generating a first waveform having a

CA 02659634 2009-01-30 frequency capable of stimulating a predetermined nerve of the patient to treat a first neurologically based condition of the patient, generating a carrier waveform having a frequency capable of passing through tissue of the patient, modulating the first waveform with the carrier waveform to produce a modulated signal, applying the modulated signal to the patient’s skin, and using an implanted mesh having a plurality of incorporated conductive elements to conduct the applied modulated signal to a location closer to the predetermined nerve than the electrode.

Also provided is an implant for treating female urinary incontinence in a patient including a substantially flat, flexible mesh or netting adapted to be implanted into a female patient’s body as a supportive loop beneath the patient’s urethra, wherein the mesh or netting is further comprised of interwoven fibers, at least one of which is electrically conductive.

The present invention also provides a medial treatment device for treating at least first and second medical conditions of a patient, including a stimulation device for treating a first medical condition of the patient with electrical stimulation, and an implantable mesh adapted for implantation within the patient to treat a second medical condition of the patient, wherein the implantable mesh has a plurality of incorporated electrically conductive elements adapted to conduct electrical stimulation from the stimulation device to a position closer to a predetermined body part the stimulation of which at least partially treats the first medical condition.

There is also provided a use of the device or implant described above for treating at least first and second medical conditions of a patient, or for treating female urinary incontinence in a patient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGURES 1 and 1a are schematic illustrations of transdermal transmission devices according to selected embodiments of the present invention;

FIGURES 2a and 2b illustrates exemplary waveforms generated by the devices of Figs. 1 and 1a;

FIGURE 3 is a schematic illustration of the device of Fig. 1 further incorporating a biofeedback mechanism;

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FIGURE 4 illustrates an exemplary implantable sensor device that can be used in conjunction with the device of Fig. 3;

FIGURE 5a illustrates the sensor device of Fig. 4 within an expandable cage in its non-expanded state;

FIGURE 5b illustrates the sensor device of Fig. 4 within an expandable cage in the expanded state;

FIGURE 6 illustrates an alternate embodiment of an implantable sensor device;

FIGURES 7a-7c illustrate various steps of deployment of the implantable sensor device of Figs. 5a and 5b;

FIGURE 8 illustrates the implantable sensor device of Figs. 5a and 5b deployed within the bladder and having a tail extending into the urethra;

FIGURE 9 illustrates first and second implantable sensor devices that can be used in conjunction with the system of Fig. 3;

FIGURE 10 illustrates an alternate embodiment of an implantable sensor device;

FIGURE 10a illustrates yet another embodiment of an implantable sensor device;

FIGURE 11 illustrates one embodiment of a patch within which the devices of the present invention may be incorporated;

FIGURES 12a-c illustrate use of the transdermal transmission device in connection with a conductive gel tract; and

FIGURES 13a-13f illustrate use of the transdermal transmission devices described herein in connection with a conductive, implantable mesh.

DETAILED DESCRIPTION OF THE INVENTION

Before explaining the present invention in detail, it should be noted that the invention is not limited in its application or use to the details of construction and arrangement of parts illustrated in the accompanying drawings and description. The illustrative embodiments of the invention may be implemented or incorporated

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GYN5022WOPCT4 in other embodiments, variations and modifications, and may be practiced or carried out in various ways. For example, although the present invention is described in detail as it relates to sub-urethral slings for females, it is to be understood that it can be readily adapted for use with other types of implantable meshes, and for use in treating various conditions in males, and children as well as adults.

As will be described more fully below, the present invention provides a conductive mesh capable of conducting electrical energy deeper into the body.

The present invention also provides a neuro-stimulation device for treating a selected nerve-based physiological condition or other physical condition treatable with electrical stimulation, in conjunction with a such a surgical mesh implant for treating a second, different condition. The mesh implant itself is uniquely designed to improve the effectiveness of the neuro-stimulation.

A preferred embodiment of a stimulation device will be described below in detail, although it is to be understood that other stimulation devices may be used as well. Referring first to a preferred embodiment of a neuro-stimulation device, a unique aspect of this device is the manner in which the nerve(s) or other body parts are stimulated, which is transdermally rather than via a needle or other invasive element inserted within the body in close proximity to the nerve. This has obvious advantages in comfort for the patient, but also eliminates the surgical risk of mistakenly injuring other nerves or vessels. The system provides direct, but preferably selective stimulation to a nerve or the like that may be, if desired, controlled in part based on biofeedback data corresponding to physiological conditions sensed in the body, such as bladder contractions.

With regard to its application for stimulating nerves, an underlying principal of its operation is the fact that nerves within the body can be selectively targeted for stimulation without affecting adjacent neurons. As is well known to those skilled in the art, bioelectric potentials are produced as a result of electrochemical activity of excitable cells found within nervous system tissue. These excitable cells exist in two electrical states, resting potential or action potential. Cells

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GYN5022WOPCT4 remain in the resting potential state until adequate stimulus is provided to cause the cell to reach the action or threshold potential, at which time the nerve “fires,” and the action potential travels at a constant conduction velocity unattenuated along the cell membranes. This all-or-nothing response of the action potential causes the cell’s membrane potential to go through a characteristic repeatable cycle, where the potential first goes from the negative resting potential, to a positive action potential, and then back down to the negative resting potential again all within approximately 1ms. The response remains the same regardless of the magnitude of the stimulus, so long as it exceeds the threshold potential.

As is also well known, when an excitable cell membrane has an action potential response (from an adequate stimulus), its ability to respond to a second stimulus is significantly altered. During the initial, depolarizing portion of the action potential, the cell membrane cannot respond to additional stimulus regardless of its intensity. This period is referred to as the absolute refractory period. Immediately following the absolute refractory period is the relative refractory period where the cell membrane can respond only to intense stimulation. The existence of the absolute and relative refractory periods results in an upper frequency limit at which a cell can be repeatedly discharged. Thus, neurons can be seen as frequency dependent devices. The frequency dependent component of the neuron depends on its total capacitance, which will vary from neuron to neuron and will be a function of its length, diameter, coating (myelination) and the permeativity of the dielectric medium. In other words, for any given dielectric medium, varying either the length or diameter of the neuron, or its myelination, will vary its total capacitance.

Since neurons in the human body do vary greatly in diameter, length and myelination, the capacitance and conduction velocity (operating frequency) for these neurons vary as well. Using these differences in physical characteristics of adjacent neurons, selected nerves can be targeted for stimulation without affecting adjacent neurons. That is, selective neural stimulation can be achieved by characterizing the frequency response (capacitance) of adjacent neurons, and 10

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GYN5022WOPCT4 tuning the stimulation frequency to an area of no-overlap. For example, consider two adjacent neurons, where neuron A has a frequency band of operation from 020 Hz, and neuron B has a frequency band of operation from 20-30 Hz. Thus, within the frequency band of 20-30 Hz, neuron B can be selectively stimulated with no effect on neuron A. Further, neuron A can be selectively stimulated even in an overlapping frequency range if stimulation is applied during neuron B’s absolute refractory period, during which no amount of stimulation will cause neuron B to fire as discussed above, or if the stimulation is less than the magnitude required to cause stimulation during the relative refractory period. As described further below, these principles can be applied to achieve selective stimulation of two or more nerves within the body.

As indicated above, it is known that surface electrodes can be used to stimulate both nerves and muscles within the body. One problem that is encountered, however, is that the applied electrical signals tend to spread widely, affecting untargeted muscles and nerves as well as targeted ones, which is often undesirable. Further, to account for this signal dissipation, the applied current levels must be significantly increased to ensure adequate current densities at the targeted site. Another challenge associated with transdermal application of electrical signals is the fact that some nerves are stimulated by a low frequency signal, such as the pudendal nerve which is stimulated by a frequency on the order of 10-40 Hz. Such a low frequency signal cannot itself pass through body tissue, and therefore is not conducive to direct transdermal application. Many of these challenges have been overcome by the devices described in detail below.

Fig. 1 illustrates schematically an exemplary transdermal signal transmission device 100 in accordance with the present invention. The signal transmitter is preferably contained within a transdermal patch 101 or the like that can be removably secured to the surface of the skin, preferably in the lower abdominal region or lower sacrum of the patient. The patch may be any suitable adhesive bandage or the like, such as the exemplary embodiment shown in Fig.

that will be described further below.

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The signal transmitter 100 includes a suitable power source 102 such as a lithium ion film battery by CYMBET™ Corp, of Elk River, Minnesota, model number CPF141490L, and at least first 104, second 106 and third 107 waveform generators that are electrically coupled to and powered by the battery. These waveform generators may be of any suitable type, such as those sold by Texas Instruments of Dallas, Texas under model number NE555. The first waveform generator 104 generates a first waveform 202 (see Fig. 2a) or signal having a frequency known to stimulate a first selected body part, such as the pudendal nerve, which is known to be stimulated by a frequency approximately within the range of 10-30Hz. As indicated above, such a low frequency signal applied to the skin, in and of itself, cannot pass through body tissue to reach the pudendal nerve with sufficient current density to stimulate the nerve. Thus, the second waveform generator 106 is provided to generate a higher frequency carrier waveform 204, which is applied along with the first waveform to an amplitude modulator 108, such as an On-Semi MC1496 modulator by Texas Instruments. The first waveform is preferably a square wave having a frequency of approximately 10-30 Hz, and the second waveform is preferably a sinusoidal signal having a frequency in the range of 10-400 KHz. As those skilled in the art will readily recognize, modulation of this first waveform 202 with the second waveform (carrier waveform) 204 results in a modulated waveform or signal 206 having generally the configuration shown in Fig. 2a. The signals shown in Figs. 2a and 2b are for illustrative purposes only, and are not intended as true representations of the exemplary signals described herein.

As described in detail in co-pending U.S. Patent Application Ser. No. 11/146,522, this modulated signal 206 can be provided to an appropriate surface electrode 110, such as DURA-STICK Self Adhesive Electrodes from Chattanooga Group, Inc. of Hixson, TN, that applies the modulated waveform directly to the skin. As is readily understood by those skilled in the art, the use of the modulated signal enables transmission of the waveform through tissue due to the high frequency nature of

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GYN5022WOPCT4 the carrier waveform, yet allows it to be detected (and responded to) by the pudendal nerve due to the low frequency envelope of the modulated signal.

Although a simple modulated signal 206 can be applied to selectively affect one nerve, the modulated signal 206 has periodic periods of inactivity 209 that can further be taken advantage of to generate a signal package capable of transdermally and selectively stimulating two or more nerves or other body parts. To accomplish this, a third waveform generator 107 generates a third waveform having a frequency different from the first waveform and that is specifically selected to stimulate a second nerve or body part. An exemplary third waveform

210 is shown in Fig. 2. This third waveform must be out of phase with the first waveform 202 to avoid interfering with modulated signal 206. Further, if the frequency ranges that simulate first and second nerves overlap, the third waveform can be generated or applied during the refractory period of the first nerve to ensure the first nerves inability to respond to this subsequent stimulus.

The first 202, second 204 and third 210 waveforms are all applied to amplitude modulator 108, which modulates the three waveforms into a modulated signal package 212. The term “signal package” is used herein to describe a single output signal consisting or three or more individual signals modulated together in any way.

As indicated above, the first and third waveform generators generate their respective waveforms 202, 210 out of phase with each other so that when combined with the carrier waveform 204 they appear along separate and discrete portions of the signal package 212, and each of the first and third waveforms have a frequency selected to specifically target different nerves or body portions. For example, the first waveform 202 may have a frequency of 20 Hz, which is known to have an effect on the autonomic element branches of the pudendal nerve which is known to affect overactive bladder, and the third waveform may have a frequency of 10 Hz, which is known to have an effect on the somatomotor branch of the pudendal nerve that is useful in treating intersticial cystitis. To the extent

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GYN5022WOPCT4 there is an overlap in frequency ranges, the third waveform can be applied during the refractory period of the first nerve as previously stated.

By the system and method described above, individual components of the modulated signal package can be used to selectively target different nerves, different nerve branches, or selected other body parts. That is, a single patch could provide stimulation signals designed to relieve multiple different symptoms such as those associated with overactive bladder, fecal incontinence, interstitial cystitis and any other pelvic floor disorder.

Although one specific embodiment has been described thus far, those skilled in the art will recognize that the appropriate signals may be manipulated in many different ways to achieve suitable modulated signals and/or signal packages. For example, a fourth waveform generator 109 may also be included that generates a fourth carrier waveform 214 having a frequency different from the second carrier waveform. This may be desirable if stimulation of the first and second nerve or body part will require the signal(s) to pass through different types or amounts of tissue. As illustrated, using a single amplitude modulator 108 the fourth carrier waveform 214 must be applied only during periods of inactivity of the first waveform to avoid affecting what would be modulated signal 206. In the alternative, as shown in Fig. 1a, the first waveform 202 and second carrier wave 204 may be provided to a first amplitude modulator 108a to result in a first modulated waveform as shown as 206 in Fig. 2b. Similarly, the third waveform 210 and fourth carrier waveform 214 may be provided to a second amplitude modulator 108b to result in a second modulated waveform 216 as shown in Fig. 2b. These first and second modulated waveforms may be further modulated by a third modulator 108c to create a signal package (i.e., 210) that can be transdermally applied by electrode 110. First and second modulated signals, of course, could also be applied separately via first and second electrodes.

As can be seen from signal package 212, there are still periods of the waveform that are not active. Additional signals can be inserted into these periods to target other frequency independent pudendal nerves or other body parts.

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Referring now back to Fig. 11, the transdermal stimulation devices described herein may be incorporated into a transdermal patch 101. This patch may include a first layer 1110 having any suitable adhesive on its underside, with the active and return electrodes 1112, 1114 being secured to the top side 1111 of the first layer. The adhesive layer may further include holes therein (not shown) to accommodate the shape of the electrodes and allow direct contact of the electrodes with the surface of the patient’s skin. The electrodes may be secured directly to the first layer, or may be held in place by a second layer 1116 comprised of any suitable material such as a plastic. A third layer 1118 consists of a flexible electronics board or flex board that contains all of the electronic elements described above and that is electrically coupled to the electrodes. A fourth layer 1120 is a thin film battery of any suitable size and shape, and the fifth layer 1122 is any suitable covering such as the plastic coverings commonly used in bandages.

Although capable of being applied transdermally only, the conductance of the stimulation energy from the surface electrode to the target nerve can be increased by the placement of a conductive pathway or “tract” that may extend either fully or partially from the surface electrode to the target nerve as illustrated by Figs. 12a-12c. The conductive tract may be a cross-linked polyacrylamide gel such as the Aquamid® injectable gel from Contura of Denmark. This bio-inert gel, injected or otherwise inserted, is highly conductive and may or may not be an aqueous solution. The implanted gel provides benefits over rigid implants like wire or steel electrodes. Some of those advantages include ease of delivery, a less invasive nature, and increased patient comfort as the gel is not rigid and can conform to the patient’s body. As stated above, the injected gel tract is a highly conductive path from the surface electrode to the target nerve that will further reduce energy dispersion and increase the efficiency of the energy transfer between the surface electrode and the target nerve. The conductive gel pathway may provide a conductive pathway from an electrode positioned exterior of the

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GYN5022WOPCT4 body (i.e., on the skin) or an electrode positioned under the surface of the skin, both of which are considered to be “in proximity” to the skin.

Fig. 12a illustrates an instance where the conductive gel tract 1201 extends from the transdermal stimulation device positioned on the skin 1200 of a patient to a location closer to the targeted nerve 1202 or nerve bundle. Another advantage of using such a gel material, however, is that unlike rigid conductors (wire), the gel can be pushed into foramina and other recessed areas. Wire or needle electrodes can only come in proximity to one plane of the target nerve, whereas the deformable and flowable gel material can envelope the target nerve as shown in Fig. 12b. That is, the gel tract can be in electrical and physical contact with the full 360 degrees of the target nerve, thereby eliminating conventional electrode alignment issues. Although described above as extending substantially from the transdermal stimulation device to a position closer to the target nerve, the conductive gel tract could also extend from a location substantially in contact with the target nerve, to a location closer to (but not substantially in contact with) the transdermal stimulation device. This type of configuration is illustrated in Fig. 12c. Multiple gel pockets or tracts in any configuration could be used.

Although one suitable conductive gel has been described above, various others are also suitable. Many thermoset hydrogels and thermoplastic hydrogels could be used as well. Examples of thermoset hydrogels include cross-linked varieties of polyHEMA and copolymers, N-substituted acrylamides, polyvinylpyrrolidone (PVP), poly(glyceryl methacrylate), polyethylene oxide), poly(vinyl alcohol), poly(acrylic acid), poly(methacrylic acid), poly(N, Ndimethylaminopropyl-N’-acrylamide), and combinations thereof with hydrophilic and hydrophobic comonomers, cross-linkers and other modifiers. Examples of thermoplastic hydrogels include acrylic derivatives such as HYPAN, vinyl alcohol derivatives, hydrophilic polyurethanes (HPU) and Styrene/PVP block copolymers.

In accordance with the present invention, the conductance of stimulation energy from the surface electrode to the target nerve can also be increased by the placement of a mesh with conductive element, or fibers or wires integrated therein

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GYN5022WOPCT4 as illustrated by Figs. 13a-13g. This can be a highly advantageous way to enhance conductance, particularly if such a mesh can be used to simultaneously treat a separate conditions of the patient. For example, as was discussed briefly above, often times female patients will have both stress incontinence that can be treated with a sub-urethral sling, and a neurologically based urge incontinence condition. A mesh constructed in accordance with the present invention will both treat stress incontinence, and also enhance the effectiveness of the neurostimulation device described herein that can be used to treat the urge incontinence. The conductive fibers of the mesh conduct the electricity deeper into the tissue and closer to the targeted nerve, thereby providing more efficient stimulation. Further, meshes constructed as described herein may also be used in various other surgical procedures such as hernia repair and pelvic floor repair. Even absent a separate neurologically based or other condition that will benefit from electrical stimulation, the meshes described herein are advantageous in that they can be used to stimulate surrounding tissue to, in some instances, accelerate the healing process.

As described above, in the case of urinary incontinence, a mesh or tape having such conductive elements incorporated therein as described further below, is passed through pelvic tissue and positioned between the urethra and vaginal wall, creating a supportive sling. The mesh provides a structure for tissue ingrowth and thereby provides newly created body tissue for supporting the urethra. When pressure is exerted upon the nerves within the lower abdomen, such as during a cough or sneeze, the mesh provides support to the urethra, allowing it to keep its seal and prevent the unwanted discharge of urine.

Referring now to Figs. 13a-13f, the mesh 1300 comprises any suitable biocompatible natural and/or synthetic material having a pore size sufficient for tissue in-growth. In a preferred embodiment, the mesh is a non-absorbable knitted polypropylene mesh, such as PROLENE® and PROLENE® Soft, manufactured by Ethicon, Inc. of Somerville, N.J. In an alternate embodiment, the

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GYN5022WOPCT4 mesh is a partially absorbable polypropylene and polyglactin mesh such as Vypro™, which is also manufactured by Ethicon, Inc.

The mesh may be of any convenient shape that suits the intended purpose. The mesh may be single or double ply, generally planar in structure, or, if appropriate, tubular to provide additional supporting strength and more surface area on which tissue fibers may attach. Moreover, the mesh may consist of different types of material, such as bioabsorbable and non-bio-absorbable material. The mesh may also be coated with an antimicrobial additive to prevent or minimize infection and a lubricious coating, for example, a bioabsorbable hydrogel, to facilitate the mesh passing through the tissue as discussed below.

The mesh may also be made radio-opaque and/or of a contrasting color to the body tissue to allow for future diagnostic visualization.

According to one embodiment shown in Fig. 13a, incorporated into the mesh construction (i.e., mesh fibers 1301) are one or more conductive fibers, strands, wires or the like 1302 (collectively referred to as “fibers”). By “incorporated” what is meant is interwoven, partially interwoven (including woven without attaching the ends to allow for movement for optimal placement of the fibers once the mesh is implanted), or coupled thereto by any suitable means such as thermal bonding, ultrasonic welding, adhesive or mechanical coupling. These conductive fibers preferably have a thread-like structure and are capable of conducting and channeling electrical or thermal energy through the mesh. The fibers may be round, flat, rectangular, or any other suitable shape or configuration. The length of the fibers may be a portion or the entire length of the mesh. Alternatively, rather than fiber strands, conductive elements 1303 of any suitable shape or form (i.e., spherical, helical, rectangular etc.) may be attached to the mesh structure at specific locations along the length and/or width of the mesh as shown in Fig. 13b.

Conductive fibers 1301 may be made of metal such as Nitonol, or any other biocompatible conductive metal. The fibers may also be a non-conductive material such as a polypropylene coated with a conductive metal or polymer. The 18

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GYN5022WOPCT4 conductive portion 1305 of the fiber may extend the entire length of the fiber as shown in Fig. 13c, or may only be a portion of the fiber as shown in Fig. 13d. A predetermined pattern of dispersion of the coating may create unique, electroresistive properties. Coating the mesh with broken or disrupted conductive material as shown in Fig. 13d will affect the impedance of the overall construct. Further, multiple coated or uncoated wires could be used to create electromagnetic fields at specific points along the mesh. For instance, one wire 1306 could be a positive pole, while the adjacent wire 1307 could be the negative pole, as shown in Fig. 13e. Together they induce an electro-magnetic field that spans the tissue. When implanted, the resultant electromagnetic field could stimulate a specific nerve, muscle group or any physiological function. Although individual coated fibers are shown in Figs. 13c and 13d, a conductive coating may also be applied to predetermined portions of the mesh after it has fully constructed to achieve similar results.

Referring now to Fig. 13f, multiple different lengths of conductive wires could also be used to incite a specific response from stimulation across the mesh. For example, in the case of urinary incontinence, the mesh could be placed below and around the urethra 1315, with the conductive elements 1306, 1307 positioned with lead ends 1306a, 1307a in proximity to the pudendal nerve 1316. The ends of these elements are then offset within the mesh construct, to create an electrical pathway for energy to flow and create variability in the pathway. Then, combinations of positive and negative stimulation are applied to stimulate the tissues and nerves in the vicinity of those controlled by the pudendal nerve. In this way, select areas on the length of the nerve could then be targeted. Also, by utilizing different placements of endpoints of the wires along the length of the mesh, the best combination for pudendal nerve stimulation can be achieved.

As stated previously, mesh constructed as described herein can conduct stimulation energy from the surface electrode to the target nerve, reducing energy dispersion and increasing the efficiency of the energy transfer between the surface electrode and the target nerve.

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The mesh can be implanted by any accepted surgical method of placing meshes in the body. Once the mesh is properly positioned, the conductive fibers, if movable, may then be optimally positioned in order to perform their intended function. If also used for neurostimulation, the transdermal patch is then placed on the appropriate region of the skin (i.e, the sacral region if used to stimulate the pudendal nerve), and the energy is transmitted from the patch through the skin and conductive fibers in the mesh, to the desired nerve.

The above-described devices may also be used in conjunction with biofeedback mechanisms that are used to control application of the electrical stimulation. For example, bio-feedback can be used to create a closed-loop system for treating urge incontinence in which pudendal nerve stimulation is selective and applied only when necessary as opposed to constantly as has been the case with known attempts at pudendal nerve stimulation. Such a system further includes one or more sensor devices 115 that are preferably implanted within the body. The sensor devices preferably include at least one sensor 120 (Fig. 3) that will sense a selected bio-physiological property, and a data transmission device 122 that transmits data or information gathered by the sensor back outside the body to be further processed as described more fully below.

Referring now to Fig. 3, signal transmitter 100 is part of a larger signal control device 300 that further includes a receiving device 310 such as a MAX1472 from Maxim Semiconductors of Sunnyvale, CA, that is electrically coupled to and powered by the battery 102. The receiving device receives data from the one or more sensors 115 and provides this data to a microcontroller 312 or the like. The microcontroller is programmed to receive and analyze the data, and based on this data to provide input to the first and second waveform generators 104, 106 to thereby control signal transmission by the signal transmitter 100. For example, the biofeedback sensor 115 may be a pressure sensor that is implanted within the bladder as described in detail below. As pressure measured within the bladder overtime is indicative of the existence and magnitude of bladder contractions, when such measurements indicate spastic 20

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GYN5022WOPCT4 bladder muscle activity (as compared to normal bladder contractions which will result in a slow and steady rise of pressure within the bladder), a feedback signal can be transmitted to the receiving device and subsequently to the microcontroller. Based on receipt of this signal, the microcontroller will, via control of the waveform generators, cause the electrode to transmit the modulated signal. Receipt of the signal by the pudendal nerve will innervate the bladder muscles to substantially eliminate the spastic muscle contractions.

Referring now to Figs. 4, 5a and 5b, exemplary biofeedback devices 115 will now be described in greater detail. In a preferred embodiment, the implantable biofeedback device 115 consists of multiple electronic components including a power source 402, one or more sensor components 404, and an electronic interface 406, each of which are electrically coupled to one another and mechanically mounted on a printed circuit board 407 in a manner well known in the art. The one or more sensor components 404 sense predetermined physiological properties within the body, and transmit signals or data representing such properties to the electrical interface 406. The system may include a data storage element for storing data correlating to the sensed physiological properties, but may also include a transmitter 409 for transmitting the data external of the patient’s body so that it can be used to control generation of the modulated signal as described above. As shown in both Figs. 5a and 5b, in one embodiment the biofeedback device 115 is substantially surrounded by a collapsible housing 510 or cage.

Preferably, the biofeedback system (exclusive of the housing) has an overall size of about 0.65-10mm in diameter d, and about 0.65-10mm in length I.

In a preferred embodiment, the sensor component is a micro-miniature piezoresistive pressure transducer for measuring pressure within a patient’s bladder. A suitable transducer is an MPX series pressure sensor from Motorola of Schaumburg, III. Other suitable components may include the MSP430F149 microcontroller from Texas Instruments, Inc. of Dallas, TX that can be used to acquire, filter and store data from the pressure sensor, and power source such as 21

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GYN5022WOPCT4 any suitable biocompatible lithium battery. Although particular suitable electronic components have been named above, many others also exist and could be incorporated into the present invention. As indicated, the electronic components are preferably mounted on printed circuit board. Subsequently, the components and circuit board can be covered or encapsulated in silicone or other suitable covering to protect them from the environment, such as the fluid environment in the bladder

Referring now again to the housing 510 as illustrated in greater detail in Figs. 5a and 5b, in a preferred embodiment the housing is a collapsible cage made of a suitable metal such as Nitonol, stainless steel, or a titanium alloy, or a suitable biocompatible polymer such as polypropylene or polyethylene terapthalate. The collapsible cage is advantageous in that it can exist in a collapsed state shown in Fig. 5a that is sufficiently small to allow insertion through the patient’s urethra. Once inserted into the bladder as will be described further below, however, the cage can assume the expanded state shown in Fig. 5b, which has a size sufficiently large so that it cannot pass back into the urethra, and thus will remain in the bladder until physical removal is desired. The housing or cage returns to its expanded state (Fig. 5b) when not compressed by an external force. The electrical components and printed circuit board can be mechanically affixed to the cage in any suitable manner, such as by using a biocompatible adhesive. The housing may further include a tail element 512 extending outwardly therefrom. This tail element 512 may operate as the transmitter for the device in place of the transmitter configuration shown in Fig. 4. As will be further described below, this tail element 512 may also incorporate additional sensor elements if desired.

In another embodiment, the expandable cage may be made of an absorbable material such as Ethisorb® (an absorbable synthetic composite made from polyglactin and polydioxanon) from Ethicon, Inc. of Somerville, N.J., ora combination of absorbable and non-absorbable materials. The absorbable material would preferably dissolve after a predetermined period of time, such as at

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GYN5022WOPCT4 least 2-3 days, so that the implantable device could be used for temporary data acquisition and subsequently expelled from the body in a non-invasive manner after sufficient data has been gathered.

As an alternative to the collapsible cage described above, the housing could have a stable structure rather than a collapsible structure that itself has an outer diameter D that is smaller than the diameter of the urethra to allow insertion therethrough into the bladder (see Fig. 6). The housing may further have one or more projections 602, such as screw threads, barbs or the like, extending outwardly therefrom that can be attached to the sidewall of the bladder by being pushed or driven therein. In yet other alternate embodiments, the implantable device could be sutured to the bladder wall, or adhered thereto using a suitable biocompatible adhesive.

In order to implant the device 115, the housing 510 is compressed and loaded into a single or multi-lumen catheter 700 as shown in Fig. 7a, which is inserted through the urethra 702 until the tip or distal end 703 is positioned within the bladder 704. The catheter may be any catheter suitable for intra-urethral applications, such as a Foley catheter. Fluoroscopy, ultrasound or other similar technology known to those skilled in the art may be used to aid in delivery and placement of the implantable system within the bladder. If a multi-lumen catheter is used, other lumens may be used to fill or drain the bladder, deliver drugs, provide an access for visualization, or monitor pressure while placing the implantable system. An expulsion element 706, such as a push rod or the like is inserted into the primary lumen behind the device and housing, and once the distal end of the catheter is properly positioned within the bladder, the expulsion element is moved toward the distal end of the catheter in the direction of the arrow as shown in Figs. 7b and 7c to thereby expel the device and housing from the distal end of the catheter and into the bladder. As the implantable system exits the catheter, the collapsible cage 510 is no longer being held in its collapsed state, and proceeds to expand to its fully expanded state. Although use of a catheter is described, other suitable implantation methods may also be used, such

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GYN5022WOPCT4 as placement via the working channel in a cystoscope or similar surgical tool, or placement via laparoscopic or open surgical methods. Once deployed within the bladder, the expandable cage is dimensioned to prevent the device from being lodged in the bladder neck or otherwise passing into the urethra, but further allows urine to freely flow through it. Fig. 8 illustrates the device fully deployed within the bladder 704.

As mentioned above, alternate embodiments that do not employ expandable cages may also be suitable, such as that shown in Fig. 6. The method of implantation of such devices would be similar to that described above, with the expulsion element within the catheter being used to drive the projecting element 602 into the wall of the bladder to thereby anchor the device to the bladder.

For purposes of the present invention, the device 115 would preferably remain within the bladder for an extended period of time to provide constant feedback used to control operation of the electrode. Where constant feedback is not used (i.e., Fig. 1), the implantable sensors described herein may nevertheless be used to obtain data useful in rendering an accurate diagnosis and/or appropriate treatment. For example, the device could remain within the bladder for 1-2 days, with bladder pressure measurements being taken every % second.

The type and frequency of bladder pressure changes can be subsequently analyzed to provide feedback to assess urinary function. For example, vesicle pressure measured over time can reveal voiding times and frequency, can provide an indication of an overactive bladder, or of bladder overfilling. In one embodiment, the sensor element(s) are designed to operate in an extended sleep mode, “waking up” at fixed intervals of time to measure pressure or the like. Once sufficient data has been gathered, the device can subsequently be removed from the bladder by inserting a catheter into the bladder to retrieve the implantable device, or using the operating channel of a cystoscope or other suitable instrument to retrieve the device. The catheter or cystoscope would be inserted

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GYN5022WOPCT4 into the bladder, and the device grasped and pulled back into the catheter or cystoscope channel and subsequently removed from the body.

Under these circumstances, the biofeedback device may further incorporate a data storage device 408 (Fig. 4) in addition to or in place of the transmitter for storing rather than transmitting the data. The data can be subsequently retrieved and manipulated, preferably by uploading the data to a PC based software application in any suitable manner, such as wirelessly, for example, via an infrared data acquisition unit such as ENDEC HSDL-7001 and an IrDA transceiver HSDL-3202 interfaced to the microprocessor, via radiofrequency acquisition, or via a hard wire connection such as through an RS232 interface.

Referring again to Fig. 3, where biofeedback data is utilized, receiver 310 may receive feedback data from more than one biofeedback device 115. In one embodiment shown in Fig. 9, a second implantable sensor device 902 similar to that shown and described in conjunction with Fig. 4 is designed for insertion into the vaginal canal of a patient, and thus is preferably encapsulated in a “tamponlike” device or casing as shown. This casing 912 is preferably simply rolled up or bound cotton, similar to a tampon. With the second implantable device sensing abdominal pressure, and the first implantable device sensing bladder pressure, the detrusor pressure (pressure of the muscle lining of the wall of the bladder tissue) can be determined by subtracting the bladder pressure from the abdominal pressure. Rises in detrusor pressure will occur if the patient strains, coughs, sneezes, laughs, etc., and detection of these pressures are clinically significant in the diagnosis of various bladder and lower urinary tract disease states. For example, the frequency of detrusor pressure increases provides meaningful data for assessing urge incontinence.

In an alternate embodiment, one of the two implantable devices transmits data to the other, which then wirelessly transmits both sets of data to receiver 310.

In yet another embodiment, the first implantable device within the bladder further includes one or more additional sensors 950 that are incorporated into one or more tail elements, as shown in Figs. 10 and 10a. In one particular

CA 02659634 2015-05-27 implementation, the sensor(s) are leak detection sensors incorporated into a tail that is designed to extend from the device within the bladder, through the sphincter and into the urethral canal 702 as shown in Fig. 8. This sensor(s) detect the presence of fluid, and thus will detect leakage of urine such as occurs in a stress incontinent patient, while at the same time the pressure sensor within the bladder measures bladder pressure. Thus, stress incontinence episodes can be recorded by correlating time at which a rise in bladder pressure occurs concurrently with detection of fluid leakage through the urethra.

Further, multiple tail elements 950a, 950b, 950c may incorporate multiple sensor elements 952a, 952b, 952c as shown in Fig. 10a to record the pressure at different points in the bladder, and thus provide more accurate readings.

It will be apparent from the foregoing that, while particular forms of the invention have been illustrated and described, various modifications can be made.