Patent Publication Number: US-10315005-B2

Title: Methods and systems for treatment of a bladder

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application is a continuation application of U.S. patent application Ser. No. 14/212,247, filed Mar. 14, 2014, which claims the benefit of U.S. Provisional Application No. 61/799,260, filed Mar. 15, 2013, the disclosures of each are incorporated herein by reference in their entirety. 
    
    
     BRIEF DESCRIPTION 
     Field 
     Embodiments of this disclosure relate generally to methods and systems for treating a bladder within a patient. In particular, embodiments of the present disclosure relate to methods and systems for treating bladder overactivity. 
     Background 
     Overactive Bladder (OAB) is a urological condition that affects approximately 50 million patients worldwide. A patient suffering from OAB typically experiences sudden yet frequent and unstoppable urges to urinate, even though the bladder may contain only a small amount of urine. This condition is usually associated with frequent and spontaneous contractions of the detrusor muscle, which is located in the bladder wall and surrounds the bladder. 
     The etiology of OAB is unclear, and indeed there may be multiple possible causes. OAB, however, is most often associated with detrusor muscle overactivity (i.e., frequent and spontaneous contractions of the detrusor muscle). These frequent contractions may fuse into a global and sustained contraction resulting in an urge to urinate. A malfunctioning detrusor muscle may cause overactive bladder. Indeed, there is a body of evidence suggesting that, in comparison with healthy bladders, overactive bladders exhibit localized changes in detrusor muscle morphology. These changes likely originate from defects on cellular and multi-cellular levels and changes in the nervous system. Such nervous system changes have been correlated to the observed local pathological changes in the muscle (e.g., patchy denervation, increased amount of connective tissue between muscle bundles) which may contribute to the abnormal function of the detrusor muscle. 
     Identifiable underlying causes include the following: nerve damage caused by abdominal or pelvic trauma or surgery, bladder stones, drug side effects, and neurological disease (e.g., multiple sclerosis, Parkinson&#39;s disease, stroke, and spinal cord lesions). 
     Recent evidence suggests that the detrusor muscle may be triggered by chemicals released from the bladder wall when the wall experiences stimulation, including, but not limited to, stretching of the bladder wall or the presence of potassium or a composite/fluid having a specific pH level, all of which may be associated with increasing accumulation of urine. The released chemicals may include adenosine triphosphate, prostaglandins, nitric oxide, and acetylcholine. The release of these chemicals has been linked to over expression of multiple receptors (muscarinic and cholinergic receptors, TRPV, etc.). 
     Current therapies for OAB include a variety of approaches. Non-invasive procedures include first-line behavioral and medical therapies employing a class of systemic drugs called anticholinergics. For patients who do not react well to drugs, invasive procedures such as neural stimulation or surgery can be more effective. Both invasive and non-invasive treatments target overall bladder function and do not address local or anatomical abnormalities. Recent studies, however, suggest that abnormal activity may originate from one or more distinct anatomical areas of the bladder such as the dome, internal sphincter, or trigone. Therefore, there exists a need for medical devices and methods of treatment capable of identifying and providing therapy to specific areas of the bladder. 
     SUMMARY 
     Embodiments of the disclosure provide methods and systems for treatment of a bladder. 
     One embodiment of the invention is directed to a medical device. The medical device may include an elongate member having a proximal end and a distal end. The medical device may further include an expandable end effector assembly extending distally from the distal end of the elongate member. The end effector assembly may include a plurality of end effector units each having an injector for simultaneously delivering material into tissue. 
     In various embodiments, the medical device may include one or more of the following additional features; wherein the injector induces a distal portion that penetrates the tissue to inject material at a predetermined depth; wherein the end effector assembly further includes a dispenser coupled to the injector, the fluid dispenser being an elastomeric fluid container configured to retain the material and rupture upon application of pressure to the fluid container; wherein each end effector unit includes an injection mechanism configured to exert a force on the dispenser to collapse the dispenser and deliver the material into the injector; wherein the expandable end effector assembly includes a first expandable member configured to expand to an expanded configuration, and wherein the injection mechanism includes a second expandable member configured to expand from a partially collapsed configuration to an expanded configuration when the first expandable member is in the expanded configuration within the first expandable member, when the first expandable member is in the expanded configuration so as to exert force on the dispensers; wherein each end effector unit includes an injector positioning mechanism configured to drive the injector into tissue; wherein the injector positioning mechanism includes a first arm and a second arm connected to the first arm via a pivot, wherein the injector is provided on the first arm; wherein the injector positioning mechanism includes: a housing having a closed top, an open bottom, and a space therebetween, at least one magnetic structure disposed within the space configured to move relative to the housing between the closed top and the open bottom, wherein an electromagnetic force is applied to the at least one magnetic structure to move the at least one magnetic structure towards the open bottom of the housing and drive the injector into tissue. 
     Another embodiment of the invention is directed to a device for treating a bladder. The device may include an elongate member having a proximal end, a distal end, and one or more lumens. The device may further include an end effector assembly extending distally from the distal end of the elongate member. The end effector assembly may define a plurality of apertures. Each aperture may be in communication with a corresponding lumen of the elongate member. An injection unit may be fixed in each aperture of the end effector assembly to direct delivery of material from the end effector assembly. 
     In various embodiments, the device may include one or more of the following additional features: wherein each injection unit includes a catheter having a distal facing surface defining an aperture and a lumen extending proximally of the aperture, wherein the lumen is configured to receive an injector; wherein the injector is movable relative to the aperture between a retracted position and a deployed position, the injector being configured to deliver material between a first tissue layer and a second tissue layer of the bladder in the deployed position; wherein the injector is movable between a first position and a second position in the deployed position to position the injector between the first tissue layer and the second tissue layer; wherein the distal facing surface includes a ramp adjacent tie aperture for driving the injector between the first position and the second position; wherein the ramp is disposed in a plane that is not perpendicular to a longitudinal axis of the catheter; wherein the injector includes an aligning member configured to orient the injector relative to the catheter. 
     Another embodiment of the invention is directed a method of treating an organ of a patient. The method may include inserting a medical device within the organ. The medical device may include an elongate member having a proximal end and a distal end, and an end effector assembly extending distally from the distal end of the elongate member. The end effector assembly may include a plurality of end effectors each having an injector for delivering material between two tissue layers of an organ wall. The method may further include expanding the end effector assembly and injecting a material to separate a first layer of tissue from a second layer of tissue. 
     In various embodiments, the device may include one or more of the following additional features: wherein the first layer of tissue is the mucosal layer, and wherein the second layer of tissue is the detrusor layer; wherein the step of injection a material includes injecting the material through the injectors of all the end effector units; further including inserting the injector into the bladder wall to inject material at a predetermined depth; and further including detecting a location of abnormal function and injecting the material at the location. 
     Additional objects and advantages of the disclosure will be set forth in part in the description, which follows, and in part will be evident from the description, or may be learned by practice of the disclosed subject matter. The objects and advantages of the disclosed subject matter will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. 
     It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. 
    
    
     
       BRIEF DESCRIPTION Of THE DRAWINGS 
       The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the disclosure and together with the description, serve to explain the principles of the disclosure. Wherever-possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts. 
         FIG. 1  illustrates a system for treatment of a bladder having a medical device, according to an embodiment of the disclosure; 
         FIG. 2  is a cross-section of the medical device along line  2 - 2  of  FIG. 1 ; 
         FIG. 3A  is a side view of an end effector assembly of the medical device of  FIG. 1 , the end effector assembly including a first expandable member in a partially collapsed configuration, according to an embodiment of the disclosure; 
         FIG. 3B  is a side view of the end effector assembly of  FIG. 3A , with the first expandable member in the expanded configuration; 
         FIG. 4  is a cross-section of the end effector assembly along line  4 - 4  of  FIG. 3B ; 
         FIG. 5A  is a side view of the end effector assembly of  FIG. 3B , the end effector assembly including a second expandable member in a collapsed configuration; 
         FIG. 5B  is a side view of the end effector assembly of  FIG. 5A  with the second expandable member in the expanded configuration; 
         FIG. 6  is a cross-section of the end-effector assembly along line  6 - 6  of  FIG. 5B ; 
         FIG. 7A  illustrates a medical device being inserted into a bladder through an outer sheath, according to an embodiment of the disclosure; 
         FIG. 7B  illustrates an end effector assembly of the medical device being positioned in the bladder and a first expandable member of the end effector assembly being in a partially collapsed configuration; 
         FIG. 7C  illustrates the first expandable member of the end effector assembly being in an expanded configuration; 
         FIG. 7D  illustrates a second expandable member of the end effector assembly being inflated in the first expandable member; 
         FIG. 7E  illustrates an injection of material between two tissue layers of the bladder wall; 
         FIG. 8  illustrates a system for treatment of a bladder including a medical device, according to a second embodiment of the disclosure; 
         FIG. 9  is a cross-section of the medical device along line  9 - 9  of  FIG. 8 ; 
         FIG. 10  is a side view of an end effector assembly of the medical device of  FIG. 8 , according to a second embodiment of the disclosure: 
         FIG. 11  is an exploded view of a portion of a leg of the end effector assembly of  FIG. 10 ; 
         FIG. 12  is an end view of a catheter of an infection unit feed in an exit aperture on the leg shown in  FIG. 11 ; 
         FIG. 13A  is a partial side view of the injection unit with an injector in a retracted configuration; 
         FIG. 13B  is a partial side view of the injection unit with the injector in a first position in the deployed configuration; 
         FIG. 13C  is a partial side view of the injection unit with the injector in a second position in the deployed configuration; 
         FIG. 14A  illustrates an end effector assembly of the medical device being positioned in the bladder, according to another embodiment of the disclosure; 
         FIG. 14B  illustrates the end effector assembly in an expanded configuration; 
         FIG. 15A  illustrates an individual injection unit contacting the bladder wall; 
         FIG. 15B  illustrates an injector being deployed from a catheter of the injection unit with the injector in a first position; 
         FIG. 15C  illustrates the injector in a second position; 
         FIG. 15A-E  illustrate alternative configurations of the end effector assembly of the medical device of  FIG. 8 , according to embodiments of the disclosure; 
         FIG. 17A  is a partial side view of a catheter of an injection unit, in accordance with another embodiment of the disclosure; 
         FIG. 17B  is a perspective view of a distal facing surface of the catheter; 
         FIG. 17C  is a partial side view of the catheter and an injector disposed in the catheter; 
         FIG. 18A  is schematic view of an injection unit, in accordance with another embodiment of the disclosure; 
         FIG. 18B  is a schematic view of the injection unit of  FIG. 18A , with an injector inserted into tissue of the bladder wall; 
         FIG. 18C  is a schematic view of the injection unit of  FIG. 18A , with a collapsed dispenser; 
         FIG. 18D  is a schematic view of the injection unit of  FIG. 18A , with the injector retracted from the tissue; 
         FIG. 19A  is a schematic view of an injection unit with an injector in a refracted position, in accordance with another embodiment of the disclosure; and 
         FIG. 19B  is a schematic view of the injection unit of  FIG. 19B , with the injector in a deployed position. 
     
    
    
     DESCRIPTION 
     Reference will now be made in detail to embodiments of the disclosure, examples of which are illustrated in the accompanying drawings. 
     Embodiments of the disclosure relate generally to systems and methods for treating a bladder within a patient. More particularly, embodiments of the disclosure relate to systems and methods for treating bladder overactivity. Bladder overactivity is characterized by involuntary contractions of the detrusor muscle during bladder filling, which result in a sudden urge to urinate. The disclosed embodiments include systems and methods for treating bladder overactivity by a hydro-dissection procedure, which separates the muscarinic and cholinergic receptors located in the mucosa (e.g., the urothelial and mucosal layers) from the detrusor muscle by injecting a compound into certain areas of the urinary bladder wall. The injected compound may be saline or a similar inert compound, in the form of a fluid or get other applications that disclose methods for treating bladder overactivity by hydro-dissection include U.S. Provisional Patent Application No. 61/535,710, filed Sep. 16, 2011, and U.S. Provisional Patent Application No. 61/677,590, filed Jul. 31, 2012, all of which are incorporated herein by reference in their entirety. 
     Those skilled in the art will understand that systems and methods described herein may be used to treat conditions of the bladder other than bladder overactivity such as, for example, bladder sphincter dyssynergia, stress incontinence, or painful bladder syndrome (interstitial cystitis). In addition, the same systems and methods may be employed in treating other organs such as, for example, the esophagus, stomach, intestines, colon, or the oral cavity, without departing from the scope of the present disclosure. 
     FIG. illustrates an exemplary system  5  according to an embodiment of the present disclosure. System  5  includes a medical device  10 , at least one fluid source  12  connected to medical device  10  by way of at least one fluid conduit  14 , and an outer sheath  18  surrounding at least a portion of medical device  10 . For purposes of this disclosure, outer sheath  18  may he constructed from an insulating polymer material such as polyamide, polyurethane, or any other suitable material. 
     Medical device  10  includes an elongate member  20 , a handle portion  18 , and an end effector assembly  22 . Elongate member  20  has a proximal end  20   a  and a distal end  20   b . For purposes of this disclosure, “proximal” refers to the end closer to the device operator during use, and “distal” refers to the end further from the device operator during use. Handle portion  18  is disposed at proximal end  20   a  of elongate member  20  and end effector assembly  22  is disposed at distal end  20   b  of elongate member  20 . End effector assembly  22  includes one or more injection units  28  for delivering material to tissue layers of a bladder. 
       FIG. 2  is a cross-section of elongate member  20  along lines  2 - 2  in  FIG. 1 . Elongate member  20  is a solid rod or tube, made from any suitable biocompatible material known to one of ordinary skill in the art having sufficient flexibility to traverse an anatomical lumen such as a urethra. Such materials may include, but are not limited to, rubbers silicon, synthetic plastics, stainless steel, metal-polymer composites, and metal alloys of nickel, titanium, copper cobalt, vanadium, chromium, and iron. In one embodiment, the material forming elongate member  20  may be a superelastic material such as nitinol, which is a nickel-titanium alloy. Elongate member  20  may have any cross-sectional shape and/or configuration and may be any desired dimension that can be received in the urethra and/or other portions of the urinary tract. Elongate member  20  includes at least one lumen  28  extending from proximal end  20   a  of the elongate member  20  to distal end  20   b  of the elongate member  20  for passage of fluid and/or tools to end effector assembly  22 . 
     Referring to  FIGS. 3A and 3B , end effector assembly  22  includes a first expandable member  24 . The phrase “expandable member” generally relates to any expandable structure, such as a balloon or other inflatable structure, regardless of the elasticity of the material comprising the structure. For example, the phrase “expandable member” may denote a thin-walled structure made of material of low elasticity (which does not stretch significantly during inflation) or highly elastic material (which does stretch significantly during inflation). For example, first expandable member  34  may be made from polyethylene terephthalate (PET), polyurethanes, polyethylenes and ionomers, copolyesters, rubbers, polyamides, silicone, latex, or any other suitable materials known in the art. 
     First expandable member  24  may be made integral with elongate member  20  through connection of a proximal end  22   a  of the end effector assembly  22  to a region of elongate member  20 , such as distal end  20   b  of elongate member  20 . The connection at proximal end  22   a  of end effector assembly  22  may be accomplished through any suitable means of fixedly connecting end effector assembly  22  to elongate member  12 . For example, possible connections may include, but are not limited to, welding, soldering, and/or crimping. 
     First expandable member  24  may be in fluid communication with lumen  28  of elongate member  20 . Lumen  28  may provide a fluid pathway through which a fluid, such as a liquid or gas, may pass to expand (inflate) and contract or collapse (deflate) first expandable member  24 . The inflation fluid may be air, water, carbon dioxide, saline solution, or a contrast agent. In alternative embodiments; first expandable member  24  may be mechanically, electrically, or pneumatically expanded and collapsed without departing from the scope of the disclosure. 
       FIG. 3A  shows first expandable member  24  in a partially collapsed configuration, and  FIG. 3B  shows first expandable member  24  in an expanded configuration. The particular expanded exterior configuration of first expandable member  24 , such as the volume, width, radius, length, or other dimension, may be selected so that first expandable member  24  substantially fills the interior of a bladder in the expanded configuration to position the one or more injection units  28  adjacent a bladder wall. For example, in the embodiment shown in  FIG. 3B , first expandable member  24  in its expanded configuration may be substantially spherical in shape. It is understood that the outer profile of first expandable member  24  may have an oval, elliptical, square, rectangular or any other shape known to one skilled in the art. 
     The one or more injection units  26  may be uniformly distributed on first expandable member  24  in the partially collapsed configuration and the expanded configuration. First expandable member  24  may act as a positioning mechanism to position the one or more injection units  28  adjacent the bladder wall. Although the depicted embodiment includes twelve injection units  28 , end effector assembly  22  may include a greater or lesser number of infection units  28 . Referring to  FIG. 4 , each individual injection unit  28  may be fixed in an exit aperture  27  on first expandable member  24  and extend outwardly of an exterior surface  24   a  of first expandable member  24 . 
     Each individual injection unit  28  includes an injector  30 . Injector  30  may be a conventional needle, including, for example, a micro-needle, having a proximal end  30   a , a sharpened distal point  30   c , and a hollow interior. Injector  30  may be provided within exit aperture  27  with proximal end  30   a  of injector  30  positioned within an interior space  24   b  of first expandable member  24 , and distal point  30   c  extending outwardly of exterior surface  24   a  of first expandable member  24 . The portion of injector  30  within exit aperture  27  may be fixed to exit aperture  27  by welding, soldering, and/or crimping. First expandable member  24  may be a positioning mechanism configured to position each individual injector unit  26  adjacent the bladder wall as first expandable member  24  expands from the partially collapsed configuration to the expanded configuration. 
     Injector  30  may have any size, shape, and/or configuration, in the exemplary embodiment, injector  30  may have a generally cylindrical shape. The particular dimensions of injector  30 , such as the length and/or diameter, may be selected to penetrate tissue and deliver materials at a predetermined depth. In particular, injector  30  may be dimensioned to enter a bladder wall as deep as the mucosa-detrusor junction without penetrating the detrusor muscle. It is contemplated that injector  30  may have any other shape and/or configuration that may accommodate the desired depth. 
     A dispenser  32  may be a part of injector  30  and may be positioned adjacent proximal end  30   a  of injector  30  within interior space  24   b  of first expandable member  24 . Dispenser  32  may be a fluid container configured to retain material for injection between tissue layers of a bladder. The material may be saline or a similar inert compound, or in the form of a fluid, gas, gel, or composite fluid. In some embodiments, the material may be a hydrogel. 
     In the exemplary embodiment, dispenser  32  may be a fluid bulb having an impermeable membrane. In other embodiments, dispenser  32  may be an elastomeric container. In alternative embodiments, dispenser  32  may have a housing, and at least a portion of the housing may have a collapsible wall. In each of these embodiments, dispenser  32  may be positioned adjacent proximal end  30   a  of injector  30  so that, as the dispenser collapses and/or ruptures, the material may he delivered into an opening at proximal end  30   a  of injector  30  for delivery to tissue via an opening at distal point  30   c.    
     Referring now to  FIGS. 5A-5B , an injection mechanism  34  may be positioned within first expandable member  24  adjacent to distal end  20   b  of elongate member  20 . The phrase “injection mechanism” generally relates to any known structure or mechanism configured to exert a force on dispenser  32  or a like fluid reservoir so as to deliver the material from dispenser  32  into injector  30  for delivery into the tissue. In this embodiment, injection mechanism  34  includes a second expandable member  38 . Second expandable member  36  is connected to a tube  38  which extends proximally through lumen  28  of elongate member  20 . In some embodiments, tube  39  may be operably connected to an actuator (not shown) on handle portion  18  and may be movable relative to elongate member  20  in order to advance second expandable member  38  from a refracted position within lumen  28  of elongate member  20  to a deployed position distally of distal end  20   b  of elongate member  20 . In other embodiments, injection mechanism  34  may be inserted into lumen  28  of elongate member  20  via a port  19  ( FIG. 1 ) on handle portion  18 , and may be manually deployed and/or retracted. 
     Tube  38  includes a lumen  39  in fluid communication with the same and/or different fluid source  12 . Lumen  39  provides a fluid pathway for a fluid, such as a liquid or gas, to pass to expand (inflate) and contract or collapse (deflate) second expandable member  36 .  FIG. 5A  shows second expandable member  38  in a partially collapsed configuration, and  FIG. 5B  shows second expandable member  24  in an expanded configuration. The particular expanded, exterior configuration of second expandable member  36 , such as the volume, width, radius, length, or other dimension, may be selected so that second expandable member  38  substantially fills the volume within interior space  24   b  of first expandable member  24 . 
       FIG. 6  is a cross-section of end effector assembly  22  along lines  6 - 6  in  FIG. 5B . As shown in  FIG. 6 , when second expandable member  38  is expanded to the expanded configuration, second expandable member  36  may exert a force on dispenser  32 . Upon further expansion of second expandable member  36 , pressure may rise on dispenser  32  and rupture impermeable membrane  32   a . The material may then be introduced into injector  30  for delivery through distal point  30   c.    
       FIGS. 7A-7E  illustrate a method for treating a bladder in accordance with an embodiment of the present disclosure. In particular,  FIGS. 7A-7C  illustrate a method for treating bladder overactivity by separating two tissue layers within the bladder wall. Those of skill in the art will readily recognize that the principles of the disclosed embodiments may have utility relative to any organ within a patient&#39;s body, such as the uterus, stomach, lung, etc. 
     Referring to  FIGS. 7A and 7B , medical device  10  is inserted into the urethra of a patient after bladder emptying, and may be advanced to bladder  50  through outer sheath  16  ( FIG. 7A ). Once a distal end of outer sheath  18  is positioned in bladder  50 , end effector assembly  22  is advanced distally out of outer sheath  18  ( FIG. 7B ). This may be achieved by, for example, pushing elongate member  20  distally relative to outer sheath  16 , or polling outer sheath  18  proximally relative to elongate member  20 . Any suitable actuator on handle portion  18  may be used to effect deployment of end effector assembly  22 . 
     Once end effector assembly  22  has been removed from outer sheath  16 , inflation fluid is delivered through lumen  28  to first expandable member  24  to inflate first expandable member  24  from a partially collapsed configuration ( FIG. 7B ) to an expanded configuration ( FIG. 7C ). When fully expanded, expandable member  24  may have a substantially spherical shape, positioning each injection unit  26  adjacent an interior surface of bladder wall  40  ( FIG. 7C ). It is understood that the expandable member may have alternative shapes, such as shapes mimicking the shape of the organ the medical device  10  is being inserted into. Further expansion of first expandable member  24  causes injector  30  of each injection unit  28  to pierce bladder wall  40 . In some embodiments, injector  30  may be configured to pierce the bladder wall  40  as deep as the mucosa-detrusor junction without penetrating the detrusor muscle. The penetration depth may be monitored in a number of ways. For example, injector  30  may be dimensioned to penetrate bladder wall  40  and deliver material at a predetermined depth (i.e., injector  30  may be a single predetermined length). Additionally and/or alternatively, injector  30  may be provided with radiopaque markers that can be visualized as injector  30  is penetrating tissue. In further embodiments, the device may include an actuator that may enable operator to simultaneously advance injectors  30  in known increments. Alternatively, the injector  30  may include a flange, stop, or shoulder to press up against tissue to control the depth of penetration of the injector  30 . 
     The procedure continues with the physician advancing injection mechanism  34  within lumen  28  of elongate member  20 . In particular, the physician may move tube  38  of actuation mechanism  34  relative to elongate member  20  in order to advance second expandable member  36  from a retracted position within lumen  28  of elongate member  20  to a deployed position within interior space  24   b  of first expandable member  24 . The mechanisms for extending second expandable member  38  into interior space  24   b  of first expandable member  24  are well known in the art and need not be discussed here. 
     Once second expandable member  38  is in the deployed position, inflation fluid may be delivered through lumen  39  of tube  38  to inflate second expandable member  36  from a collapsed configuration to an expanded configuration ( FIGS. 7D and 7E ). As second expandable member  36  expands, second expandable member  38  may come into contact with the one or more dispensers  32  associated with the one or more injection units  28 . Further expansion of second expandable member  38  may exert a force on dispensers  32 . Upon application of sufficient force, the impermeable membrane  32   a  of each dispenser  32  may rupture injecting material from dispensers  32  into injectors  30  for delivery between tissue layers of the bladder. It is understood that dispensers  32  may take any number of shapes other than that disclosed in the figures, such as, for example, a bellows shape. 
     The injected material or compound may be a liquid (e.g., saline), a gel, or a liquid/gel that cures into a solid or fluid. For example, the material may include a hydrogel (e.g., PEG, hyaluronic acid, polyacrylamide gel, chitosan, sodium alginate, PLA or hydrogel mixture) which, after injection, may be cured by cross-linking as is known in the art. The injected material may have any desired composition, viscosity, and/or biodegradability characteristics so as to permit the injected material such as a cured hydrogel, to carry and deliver a drug over an extended period of time, such as, for example, several months or years. Further, the injected material, such as a hydrogel, may include high expansion properties (e.g. expanding between approximately five to approximately ten times its original volumetric size). As such, a large physical barrier may be achieved while using a small volume/amount of the injected material. Additionally, such a hydrogel may be absorbable into bladder wall  40 . 
     The material may be injected into a space between two tissue layers  40   a ,  40   b  in bladder wall  40  to separate and maintain the two layers. For example, the material may be injected between the mucosal layer  40   b  and the detrusor layer  40   a  to create a semi-permanent barrier between the layers that may prevent the detrusor muscle contraction and expansion. The injections may be performed at sites spaced equidistantly from one another along bladder wall  40  so as to uniformly treat bladder  50 . It is contemplated, however, that first expandable member  24  may be partially expanded, and end effector assembly  22  may be positioned adjacent a site of abnormal activity, to selectively treat that portion of bladder  50 . 
       FIG. 8  illustrates an exemplary system  105  according to another embodiment of the present disclosure. System  105  has similar components as the embodiment discussed above. In this embodiment, however, at least one external dispenser  113  may be connected to medical device  110  via injector  130 . Dispenser  113  maybe a syringe, vial, or other known container configured to retain the material to be injected between tissue layers of the bladder. 
     In the exemplary embodiment illustrated in  FIG. 8 , medical device  110  include an elongate member  120 , a handle portion  118 , and an end effector assembly  122 . Elongate member  120  has a proximal end  120   a  and a distal end  120   b . Handle portion  118  is disposed at proximal end  120   a  of elongate member  120  and includes at least one actuator  117 . End effector assembly  122  is disposed at distal end  120   b  of elongate member  120 . End effector assembly  122  includes one or more injection units  126 . 
       FIG. 9  is a cross-section of elongate member  120  along lines  9 - 9  in  FIG. 8 . As discussed above, elongate member  120  may be a solid rod or tube, made from any suitable biocompatible material known to one of ordinary skill in the art having sufficient flexibility to traverse an anatomical lumen such as a urethra. In this embodiment, elongate member  120  includes one- or more lumens  128  extending from proximal end  120   a  of the elongate member  120  to distal end  120   b  of the elongate member  120 . It is to be understood that lumens  128  may have any size, cross-sectional area, shape, and/or configuration. Although the depicted embodiment includes sixteen lumens, elongate member  120  may include a greater or lesser number of lumens  128 . It is to be understood that the number of lumens  128  may depend on the number of injection units  126  on end effector assembly  122 . 
       FIG. 10  depicts a side view of end effector assembly  122 . As shown in  FIG. 10 , end effector assembly  122  extends distally from distal end  120   b  of elongate member  120 , and includes a plurality of legs  124   a  extending from a proximal end  122   a  of end effector assembly  122  to a distal end  122   b  of end effector assembly  122  in some embodiments, end effector assembly  122  may also include one or more circumferentially extending legs, such as legs  124   b . In this disclosure, descriptions of legs  124   a  also pertain to legs  124   b , and vice versa. 
     End effector assembly  122  may he made out of the same piece of material as elongate member  120 . Alternatively, end elector assembly  122  may be fabricated independently by any known means and may be made integral with elongate member  120  through connection of a proximal end  122   a  of the end effector assembly  122  to a region of elongate member  120 , such as the distal end  120   b  of elongate member  120 . The connection of proximal end  122   a  of end effector assembly  120  may be accomplished through any suitable means of fixedly connecting end effector assembly  122  to elongate member  120 . For example, possible connections may include, but are not limited to welding, soldering, and/or crimping. 
     End effector assembly  122  may have any shape and/or configuration and may be any desired dimension that can be received in a bladder. In the exemplary embodiment shown in  FIG. 10 , legs  124   a  are configured so that end effector assembly  122  forms a three-dimensional sphere in an expanded state. Legs  124   a  may be constructed from a material such as, for example, elastic, a shape memory, or super elastic material so that legs  124   a  may collapse to have a smaller cross-section in a collapsed state. 
     Although  FIG. 10 , shows that that end effector assembly  122  comprises six legs  124   a  extending from proximal end  122   a  of end effector assembly  122  to distal end  122   b  of end effector assembly  122  (and four circumferential legs  124   b ), end effector assembly  122  may include any number of legs  124   a  (or  124   b ) having any desired pattern and/or configuration. For example, legs  124   a  may form a cylinder, square, semi-circle, rectangle, or any other suitable shape. In addition, legs  124   a  may be any cross-sectional shape known in the art including, but not limited to, circular, square, or ovular. 
     Referring to  FIG. 11 , each leg  124   a  of end effector assembly  122  includes one or more lumens  125  located longitudinally therein. Lumens  125  may have any size, cross-sectional area, shape, and/or configuration. Each lumen  125  is in communication with a corresponding lumen  128  of elongate member  120 , and extends from proximal end  122   a  of end effector assembly  122  to an exit aperture  127  on leg  124   a.    
     An individual injection unit  128  is fixed in each exit aperture  127 . In the exemplary embodiment, injection unit  128  includes a catheter  132  and an injector  130  disposed therein. Catheter  132  may include a proximal end (not shown) terminating proximally of exit aperture  127  in lumen  125 , and a distal facing surface  132   b  flush with, or protruding from, exit aperture  127 . Distal facing surface  132   b  may be configured to contact tissue. It is contemplated that in some embodiments, catheter  132  may move relative to exit aperture  127 . In these embodiments, catheter  132  may extend proximally through lumen  125  of legs  124   a  and a corresponding lumen  128 , and may be connected to a push and/or pulling mechanism in handle portion  118 . 
     Referring to  FIG. 12 , catheter  132  includes a lumen  133  extending longitudinally therein. Lumen  133  may have any size, cross-sectional area, shape, and/or configuration, and may extend from the proximal end (not shown) to an aperture  133   b  on distal facing surface  132   b . In the exemplary embodiment, aperture  133  may have a substantially ovular shape to permit lateral movement of injector  130 . It will be understood, however, that aperture  133  may have any other size, shape, and/or configuration. 
     Injector  130  may be positioned in lumen  133  of catheter  132 . In particular, injector  130  may extend proximally from catheter  132  through lumen  125  of leg  124   a , a corresponding lumen  128  of elongate member  120 , and handle portion  118  ( FIG. 8 ), injector  130  may be a conventional needle, including, for example, a micro-needle, having a proximal end  130   a , a sharpened distal point  130   c , and a hollow interior. Referring back to  FIG. 8 , proximal end  130   a  may extend proximally of handle portion  118  for coupling to dispenser  113 . In some embodiments, proximal end  130   a  may include a luer fitting or any other fitting to facilitate coupling between proximal end  130   a  and dispenser  113 . 
     Referring to  FIGS. 13A-13C , injector  130  may include a distal portion  130   b . The particular shape, configuration, and/or dimensions of distal portion  130   b  of injector  130  may be selected to penetrate issue and deliver material at a predetermined depth. In the exemplary embodiment, distal portion  130   b  of injector  130  may have a right angle bend and terminate at distal point  130   c , it will be understood that the bend of distal portion  130   b  may be abrupt or curved and may have an angle greater or lesser than 90°. Distal portion  130   b  may have any other shape and/or configuration that may penetrate tissue at the desired depth. 
     Injector  130  may be operatively connected to the at least one actuator  117  on handle portion  118  to move distal portion  130   b  of injector  130  longitudinally relative to lumen  133  from the retracted configuration in  FIG. 13A  to the deployed configuration in  FIG. 13B . In the deployed configuration, distal portion  130   b  of injector  130  may extend beyond distal facing surface  132   b  of catheter  132  ( FIG. 13B ). The same actuator  117  or a different actuator  117  may be configured to move injector  130  laterally within lumen  133  and aperture  133   b  between a first position ( FIG. 13B ) and a second position ( FIG. 13C ) to facilitate placement of distal point  130   c  between tissue layers of the bladder. In some embodiments, distal portion  130   b  of injector  130  and/or aperture  133   b  may include one or mere retaining mechanisms to retain distal portion  130   b  in the second position during the injection procedure. 
     A method of treating a bladder in a patient will now be described. Referring to  FIGS. 14A and 14B , medical device  110  may be inserted into the urethra of a patient after bladder emptying, and may be advanced to bladder  60  through outer sheath  118  ( FIG. 14A ). Once a distal end of outer sheath  116  is positioned in bladder  50 , end effector assembly  122  may be advanced distally out of outer sheath  118 . This may be achieved by, for example, pushing elongate member  120  distally relative to outer sheath  118 , or pulling outer sheath  118  proximally relative to elongate member  120 . 
     Once end-effector assembly  122  has been removed from outer sheath  118 , end effector assembly  122  may be expanded to an expanded configuration ( FIG. 14B ). In some embodiments, end effector assembly  122  may self-expand. In other embodiments, an expansion mechanism such as, for example, a balloon may be used to facilitate expansion of end effector assembly  122 . When fully expanded, end effector assembly  122  may have a substantially spherical shape, positioning each injection unit  128  adjacent an interior surface of bladder wall  40 . 
     The procedure continues with the physician inserting distal portion  130   a  of each injector  130  into bladder wall  40 . In particular, the physician may engage the at least one actuator  117  on handle portion  118  to move injectors  130  relative to lumens  128  in elongate member  120 , lumens  125  in legs  124   a  (or legs  124   b ), and lumens  133  in catheters  132  in order to advance distal portion  130   b  of injectors  130  from a retracted position within lumen  133  of catheter  132  to a deployed position distal to a distal facing surface  132   b  of catheter  132  ( FIGS. 15A and 15B ). 
     As distal portion  130   b  extends out of aperture  133   b , distal point  130   c  may be configured to penetrate tissue. As discussed in the embodiment described above, it may be desirable to penetrate tissue and inject material at a predetermined depth. For example, injector  130  may be configured to penetrate the bladder wall  40  as deep as the mucosa-detrusor junction without penetrating the detrusor muscle. The penetration depth may be monitored in a number of ways. For example, distal portion  130   b  of injector  130  may be shaped and/or dimensioned to piece bladder wall  40  to a desired depth so that material may be delivered at the predetermined depth (i.e., between the detrusor layer and the mucosal layer). Additionally and/or alternatively, injector  130  may be provided with radiopaque markers that can be visualized as distal portion  130   b  is penetrating tissue. In further embodiments, actuator  117  may enable operator to advance injectors  130  simultaneously or individually in known increments. 
     Once injectors  130  are in the deployed position, the same actuator  117  or a different actuator  117  may be configured to drive distal portion  130   b  of each injector  130  laterally in apertures  133   b . Lateral movement of injector  130  between a first position shown in  FIG. 15B  and a second position shown in  FIG. 15C  may facilitate positioning of distal point  130   c  between mucosal layer  40   b  and the detrusor layer  40   a  of bladder wall  40 . Material may then be injected from dispenser  113  through the proximal end  130   a  of each injector  130  to deliver the material between the two tissue layers. 
     In some embodiments, the physician may uniformly treat bladder  50  by simultaneously delivering material through all of the injection units  126 . In other embodiments, the physician may selectively deliver material through one or more specific injection units  128  to treat areas of abnormalities within bladder  50 . In these embodiments, medical device  110  may include a sensing element to detect an area of abnormal function in the bladder and transmit the data via a cable or wirelessly to the physician. 
     As in the prior embodiment, the material may be delivered between the mucosal layer  40   b  and the detrusor layer  40   a  to separate and maintain the two layers. In additional and/or alternative embodiments, the medical device may include a suction lumen positioned at a distal end  120   b  of elongate member  120 , a distal end  122   b  of end effector assembly  122 , and/or in each catheter  132  to assist in the lifting of tissue layers through suction to separate the two tissue layers. The suction procedure is followed with fluid/material insertion between the layers. 
     Alternative non-limiting examples of end effector assemblies having various shapes and/or distal configurations are shown in  FIGS. 16A-16E ,  FIGS. 16A and 16D  depict end effector assemblies having wire configurations. In particular, end effector assembly  522   a , as shown in  FIG. 16A , may have a substantially linear configuration. A single end effector unit  126  may be disposed at a distal end of end effector assembly  522   a . In another embodiment, end effector assembly  522   d , as shown in  FIG. 16D , may have a helical configuration preferably tapering from a larger diameter at a distalmost end thereof to a smaller diameter proximally of the distalmost end thereof. A kink may be disposed adjacent a proximal end of end effector assembly  522   d .  FIG. 16C  depicts an end effector assembly  522   c  having a plurality of legs curving away from a longitudinal axis of end effector assembly  522   c .  FIGS. 16B and 16E  depict end effector assemblies having a mesh configuration. In particular, end effector assembly  522   b , as shown in  FIG. 16B , may have a circular shape. And in yet another embodiment, end effector assembly  522   e , as shown in  FIG. 16E , may have a semi-circular shape. End effector assemblies  522   c  and  522   e  may be additionally planar, concave, or convex. 
     Alternative embodiments of injection units will now be described, it will be noted that at least certain aspects of the embodiments discussed below may be combined with other aspects of the embodiments discussed above. For example, one or more of the following injection units may be provided on one of the end effector assemblies discussed above to position the injection units within the bladder. 
       FIGS. 17A-17C  illustrate an injection unit  228 . Injection unit  228  includes a catheter  232  and an injector  230 . Catheter  232  may have a proximal end (not shown), a distal end  232   b , and a lumen  233  extending therethrough. In the exemplary embodiment, distal end  232   b  of catheter  232  may be wedge shaped. It is contemplated that distal end  232   b  may be sharpened to facilitate insertion into tissue. 
     Lumen  233  may terminate at an aperture  233   b  on a distal facing surface  232   c  of catheter  232 . Distal facing surface  232   c  may include one or more features to drive injector  230  to a desired position and orient injector  230  relative to catheter  232 . For example, distal facing surface  232   c  may include a ramp  232   d  adjacent aperture  233   b . Ramp  232   d  may be shaped to drive injector  230  from a first position on one end (side) of distal end  232   b  of catheter  232  to a second position on an opposing end (side) of distal end  232   b  of catheter  232 , in particular, ramp  232  may be disposed in a plane that is not perpendicular to a longitudinal axis of catheter  232  ( FIGS. 17A ). Furthermore, ramp  232   d  may be sized and shaped to interact with one or more aligning members  235  on injector  230  to orient injector  230  relative to catheter  232 . For example, the width of ramp  232   d  may be sized to receive an aligning member  235  and to prevent rotation of the aligning member  235  and injector  230 . 
       FIGS. 18A-18C  illustrate an injection unit  326 . In accordance with another embodiment of the disclosure, injection unit  326  may include a frame  340  having a first arm  340   a  and a second arm  340   b  pivotably connected to the first arm  340   a  via a pivot  340   c . An injector  330  may be provided on first arm  340   a . In particular, injector  330  may be fixed to a surface of first arm  340   a  and may extend in a direction generally perpendicular to first arm  340 . Frame  340  may be a positioning mechanism configured to position injector  330  adjacent tissue and facilitate insertion of injector  330  into tissue. 
     In this embodiment, injector  330  may be a curved needle, including, for example, a micro-needle, having a sharpened distal point  330   c  and a hollow interior, injector  330  may be sized to penetrate tissue and inject material at a predetermined depth. It is understood that injector  330  may have any other size and/or configuration to penetrate tissue at the predetermined depth. 
     A dispenser  332  may be mounted be first and  340   a  opposite to injector  330 . Dispenser  332  may be in fluid communication with injector  330  via an aperture (not shown) in first arm  340   a . In this embodiment, dispenser  332  may be an elastomeric fluid container retaining material to be injected between two tissue layers of the bladder. Dispenser  232  may have an impermeable membrane or a collapsible wall configured to collapse on application of sufficient force by an injection mechanism such as, for example, second arm  340   b . As dispenser collapses, the material may be introduced into injector  330 . 
     Injection unit  328  may be introduced into the bladder and positioned adjacent bladder wall  40  using the procedures discussed above. Injection unit  326  may be placed adjacent the bladder wall  40  with second arm  340   b  parallel to the detrusor layer  40   a  and mucosal layer  40   b  of bladder wail  40 , in order to insert injector  330  into tissue, frame  340  may be rotated, so that second arm  340   b  is generally perpendicular to the tissue. Any known actuation mechanism, such as an electrical actuator or linear actuator, may be attached to frame  340  and may be configured to apply sufficient force to rotate frame  340 . As frame  340  rotates, distal point  330   c  of injector  330  may be inserted into the tissue. 
     The procedure may continue by collapsing dispenser  332 . For example, the same actuation mechanism or a different actuation mechanism may apply a force to second arm  340   b  to pivot second arm  340   b  relative to first arm  340   a  about pivot  340   c . As second arm  340   b  pivots towards the first arm  340   a , second arm  340   b  may apply sufficient force to collapse dispenser  332 . In this manner, material  42  may be injected into injector  330  for delivery between tissue layers of the bladder. Injector  330  may be removed by rotating first arm  340   a , so that first arm  340   a  and second arm  340   b  are generally perpendicular to the tissue. 
       FIGS. 19A-19B  illustrate an injection unit  428  in accordance with another embodiment of the disclosure. In this embodiment, injection unit  426  includes a housing  440  having a closed top  450 , an open bottom  480 , and a space  470  extending therebetween. The closed top  450  may be closed by, for example, a cap. In some embodiments, the cap may include a breathable membrane. The open bottom  460  may be configured to be oriented towards tissue and contact tissue. 
     A first magnetic disk  444  may be disposed in space  470 , and may be configured to move relative to housing  440  between the closed top  450  and open bottom  480 . The first magnetic disk  444  may sealingly engage the inner walls of housing  440 . For example, first magnetic disk  444  may have radial seals, such as, for example an O-ring or a lip seal, to engage housing  440 . A second magnetic disk  442  may be disposed between the first magnetic disk  444  and the open bottom  460 . Second magnetic disk  442  may have similar seals. 
     An injector  430  may be fixed to second magnetic disk  442 . In particular, a proximal end  430   a  of injector  430  may extend through an aperture (not shown) in second magnetic disk  442  and may be fixed to the aperture. In this embodiment, injector  430  may be a cylindrical needle, such as, for example, a micro-needle, having a sharpened distal point  430   c  and a hollow interior, injector  430  may be sized to penetrate tissue and inject material at a predetermined depth. It is understood that injector  430  may have any other size and/or configuration to penetrate tissue. 
     A dispenser  432  may be disposed between the first magnetic disk  444  and the second magnetic disk  442 . In this embodiment, dispenser  432  may be a collapsible dispenser retaining fluid in, for example, a collapsible, impermeable membrane. The membrane may be configured to collapse and rupture on application of sufficient force to inject the material into proximal end  430   a  of injector  430 . 
     Housing  440  may further include coil windings  446  disposed on an outer surface of housing  440 . Coil windings  446  may attach to an electrical wire (not shown) that may extend proximally through a medical device to a source of electricity, in operation, housing  440 , first magnetic disk  444 , second magnetic disk  442 , and coil windings  446 , together, may be a positioning mechanism configured to position injector  430  adjacent tissue and facilitate insertion of injector  330  into tissue. In particular, current may pass through the coil windings  446  inducing an electrical field whose electromotive force may be used to drive first magnetic disk  444  and second magnetic disk  442  downward. The force may be sufficient to insert injector  430  into the adjacent tissue. 
     After injector  430  has been inserted into tissue, the electromotive force may continue to drive the first magnetic disk  444  downward. First magnetic disk  444  may act as an injection mechanism by applying sufficient pressure on dispenser  432  to rupture dispenser  432  disposed between the first magnetic disk  444  and the second magnetic disk  442 . In this manner, material may be injected into injector  430  for delivery between two tissue layers of the bladder. 
     The same deployment may be accomplished with an electrical coil and a spring recoil. In particular, current may be applied to the coil windings of the injection unit in/only one direction to insert injector into tissue and inject material between the two tissue layers. The recoil spring (placed between second magnetic disk  442  and open bottom  460 ) may then retract injector  430 . In another embodiment, deployment may be accomplished with a compressed fluid end a spring recoil. In this embodiment, the compassed fluid, applied to first magnetic disk  444 , may be configured to apply sufficient force to deploy injector  430  and inject the material. As in the embodiment described above, the recoil spring may retract injector  430  once the fluid pressure is relieved. 
     Other injection units are contemplated. For example, in other embodiments, each of the one or more injection units may have a micro-needle array in place of a single injector. In this manner, the injection unit may target a wider area of tissue within the bladder. In additional and/or alternative embodiments, the material may be dispersed through the injector (or needle array device) onto tissue adjacent the injection units without perforating the bladder wall. This procedure may be performed for a set duration at varying amplitudes to increase the permeability of the mucosal layer (e.g., the urothelium). 
     Other embodiments of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein, it is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims. 
     In some embodiments, the fluid dispenser  32  does not rupture, but rather fluid is releasable upon application of pressure which forces fluid through pores in the wall of the dispenser. The pores may be elastic or nonelastic, and may be holes, slots, or slits. Alternatively, the fluid dispenser  32  may remain sealed and the needle includes pores, slots, holes, or slits that open with increased pressure and convey fluid from the dispenser to the tissue.