Patent Publication Number: US-11654250-B2

Title: Resorbable, drug-eluting submucosal turbinate implant device and method

Description:
RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 14/836,594, filed Aug. 26, 2015, the contents of which is incorporated by reference herein. 
    
    
     TECHNICAL FIELD 
     This invention relates to the treatment of sinus conditions including inflammation of the turbinates. 
     BACKGROUND 
     The turbinates are soft mucosal tissue ridges which are supported by bony understructure, project into the nasal passages, and help warm and moisturize air flowing through the nose. Swollen or otherwise enlarged turbinates can inhibit or obstruct breathing. Treatment therapies include topical or oral administration of nasal decongestants, steroids, anti-inflammatories or other medicaments, and in some instances the use of surgery to remove, reduce or resection the swollen mucosal or supporting bone tissue. 
     A variety of drug-eluting biodegradable or non-biodegradable devices have been proposed for insertion into nasal passages and sinus cavities. Typically these devices are exposed to air within the nasal or sinus cavity, and in some instances a suture or other fastener is used to retain the device in place. 
     SUMMARY OF THE INVENTION 
     The turbinates are exposed to air and fluids, may vibrate or otherwise move during normal breathing, sneezing or nose blowing, and employ cilia and other natural defenses to remove foreign matter and other debris. These factors may dislodge or help dislodge a drug eluting device. Although drug eluting devices may be placed and retained using sutures, doing so represents an extra step and may cause added trauma. 
     The invention provides in one aspect a surgical device comprising:
         (a) a proximal grip portion configured to be grasped outside a patient;   (b) a distal hollow sharp needle portion configured to be manipulated using the grip portion and inserted submucosally into mucosal turbinate tissue in the patient;   (c) one or more biodegradable, drug-eluting solid implants disposed within the hollow needle portion, the implants having a length along the hollow needle portion, and one or more implant withdrawal-discouraging, mucosal tissue-engaging surface features along such length; and   (d) an actuator disposed within the device and configured to deliver one or more of the implants from the hollow needle portion into such mucosal turbinate tissue and submucosally bury at least one such tissue-engaging feature therein.       

     The invention provides, in another aspect, a method for sinus treatment, the method comprising providing a surgical device comprising:
         (a) a proximal grip portion configured to be grasped outside a patient;   (b) a distal hollow sharp needle portion configured to be manipulated using the grip portion and inserted submucosally into mucosal turbinate tissue in the patient;   (c) one or more biodegradable, drug-eluting solid implants disposed within the hollow needle portion, the implants having a length along the hollow needle portion, and one or more implant withdrawal-discouraging, mucosal tissue-engaging surface features along such length; and   (d) an actuator disposed within the device and configured to deliver one or more of the implants from the hollow needle portion into such mucosal turbinate tissue and submucosally bury at least one such tissue-engaging feature therein;
 
manipulating the grip portion to pierce such mucosal turbinate tissue and submucosally insert the hollow needle portion therein, and activating the actuator to deliver one or more of the implants from the hollow needle portion into such soft tissue and submucosally bury at least one such tissue-engaging feature within such tissue.
       

    
    
     
       BRIEF DESCRIPTION OF THE DRAWING 
         FIG.  1    is a schematic view of the turbinates; 
         FIG.  2    is an exploded view of a surgical device for implanting the disclosed drug-eluting implants into mucosal turbinate tissue; 
         FIG.  3    is a cross-sectional view of the distal needle end of the  FIG.  2    device inserted into turbinate tissue and with a plurality of the disclosed drug-eluting implants disposed therein; and 
         FIGS.  4 A through  4 K  are side sectional views of exemplary drug-eluting implants with a variety of implant withdrawal-discouraging, mucosal tissue-engaging surface features. 
     
    
    
     Like reference symbols in the various figures of the drawing indicate like elements. The elements in the drawing are not to scale. 
     DETAILED DESCRIPTION 
     The following detailed description discusses certain embodiments and is not to be taken in a limiting sense. All weights, amounts and ratios herein are by weight, unless otherwise specifically noted. 
       FIG.  1    shows a schematic view of the nasal and sinus passages in human patient  1 . Eyes  4  and nostrils  6  are included in the view to assist in visualizing the location and size of maxillary sinuses  8  and nearby turbinates  10 ,  20 ,  30 ,  40 ,  50  and  60 . Superior turbinate  10 , middle turbinate  20  and inferior turbinate  30  are located on the left side of  FIG.  1   , and right of the patient midline from the perspective of patient  1 , and are in a normal, unswollen condition. Superior turbinate  40 , middle turbinate  50  and inferior turbinate  60  are located on the right side of  FIG.  1   , and left of the midline from the perspective of patient  1 , and are each in an abnormal, swollen condition such as may interfere with normal breathing. In an adult human patient with chronic rhinosinusitis (CRS), the turbinates may for example be swollen sufficiently so as to have a thickness of about 1 cm and a length of 3-4 cm. In pediatric human patients with CRS the corresponding dimensions may for example be a thickness of about 0.5 cm and a length of about 2-3 cm. The disclosed surgical devices may for example be sized to fit submucosally within such swollen tissue. 
     Referring to  FIG.  2    and  FIG.  3   , exemplary surgical device  100  may conveniently be made from an injection-molded sterilization-resistant thermoplastic co-molded with a metal needle portion discussed in more detail below. Exemplary thermoplastics include ABS, nylon, polycarbonate, polystyrene and other materials that will be familiar to persons having ordinary skill in the art. Device  100  includes a proximal pistol-grip portion  202  shaped and sized to be received within the gloved palm of a physician. A plurality of optional ribs  204  in handle  202  facilitate uniform distribution of plastic in the molding process and provide an improved gripping surface. Handle  202  is also shaped and sized so that the physician&#39;s thumb can readily apply force towards bore opening  208  in barrel  210 . Barrel  210  extends from handle  202  and connects with a needle retention and alignment portion  212  which terminates at a distal end  214 . Portion  212  may be curved or otherwise bent as shown in  FIG.  1    or may have other shapes (e.g., straight) to facilitate manipulation of distal end  214  into position near a target site on a turbinate. Hollow needle  216  projects from distal end  214  and includes a sharp distal tip  218  that can be used to pierce mucosal turbinate tissue. Needle  216  may be straight as shown in  FIG.  1    or may have other shapes (e.g., curved or otherwise bent) to facilitate insertion of tip  218  into mucosal turbinate tissue. Optional depth of insertion marks  220 ,  222  and  224  provide an indicator for judging the extent to which needle  216  has been inserted into tissue. 
     The length and shape of needle retention and alignment portion  212  and needle  216  may be selected so that device  100  is optimally used to access only one turbinate (e.g., a superior, middle or inferior turbinate) or so that device  100  may be used to access more than one turbinate (e.g., a superior and middle turbinate, a middle and inferior turbinate, or each of a superior, middle and inferior turbinate). Device  100  may also be made in a variety of shapes and sizes, e.g., for human adult, human pediatric or veterinary (e.g., bovine, equine, ovine, porcine, canine or feline) use. Exemplary lengths for needle  216  (including both the visible or exposed portion or needle  216  as well as portion  216   a  extending into portion  212 ) may for example be about 5 to about 10 cm for human adult use, about 3 to about 8 cm for human pediatric use, and shorter, similar or longer lengths for veterinary use depending on the chosen animal. The exposed portion of needle  216  may for example have a length of about 2 to about 5 cm or about 2 to about 4 cm for human adult use, about 1 to about 3 cm or about 1 to about 2 cm for human pediatric use, and shorter, similar or longer lengths for veterinary use. Needle  216  may for example have an outer diameter of about 0.23 mm to about 4.6 mm or about 0.23 mm to about 1.7 mm, and an inner diameter of about 0.1 mm to about 3.8 mm or about 0.1 mm to about 1.2 mm, corresponding approximately to Needle Wire Gauge values of 32 gauge to 7 gauge or 32 gauge to 16 gauge. 
     In the embodiment shown in  FIG.  2   , barrel  210  includes three openings  226 ,  228  and  230  along the left side of barrel  210  as viewed by the physician and spaced along its axial dimension, and three optional similar opposing openings (not shown in  FIG.  2   ) on the right side of barrel  210  as viewed by the physician. The  FIG.  2    device may be supplied with one or two similar or different implants  232   a  and  232   b  shown outside needle  216  in the  FIG.  2    exploded view, and shown axially stacked end-to-end inside needle  216  in the  FIG.  3    cross-sectional view. Implants  232   a  and  232   b  have one or more implant withdrawal-discouraging, mucosal tissue-engaging surface features along their length as is discussed in more detail below. A protective cap  234  may be included with device  100  to cover tip  218 . 
     As will be appreciated by persons having ordinary skill in the art, the embodiment shown in  FIG.  2    and  FIG.  3    may be modified so as to be supplied to a physician with any desired number of implants, e.g., with three or more implants located axially inside needle  216 . The spacing between openings  226  and  228  desirably corresponds to the axial length of implant  232   a , and the spacing between openings  228  and  230  desirably corresponds to the axial length of implant  232   b . For the embodiment shown in  FIG.  2    and  FIG.  3   , the axial lengths of implants  232   a  and  232   b , the space between openings  226  and  228 , and the space between openings  228  and  230  are all the same, but need not be so. Openings  226 ,  228  and  230  cooperate with slider mechanism  300  to provide one or more and preferably each of visual, audible and tactile feedback to a physician of the progress of an implant or implants through needle  216  as is discussed in more detail below. 
     Slider mechanism  300  has a generally cylindrical body  302  sized to be slidably received within bore  208 . Body  302  includes a proximal thumb tab  304  positioned to be engaged by the thumb of the physician gripping handle  202 . Flexible pin  306  extends axially and distally from the distal end of body  302  and is sized to pass through a corresponding bore opening  308  in portion  212 , shown in phantom in  FIG.  2   . One or more flexible lever arms  310  (two are shown in the  FIG.  2    embodiment) project laterally and rearwardly from pin  306  and terminate at a latch or latches  312 . Locating tab  314 , and an optional further locating tab (not shown in  FIG.  2   ) that may be located for example on the right side of slider mechanism  300 , project laterally and outwardly from body  302 . Latch or latches  312  and tab or tabs  314  are sized to be slidably received by interior recessed slot or slots  316  axially located along the sides of barrel  210 . Latch or latches  312  are also sized to expand into and engage openings  226 ,  228  and  230  and the optional similar openings on the right side of barrel  210  as body  302  travels through bore  208  of barrel  210 . Latch or latches  312  are shaped and sized to permit insertion of body  302  into bore  208  and distal advancement of body  302  via thumb pressure on thumb tab  304 . When so advanced, body  302  can move from a position in which a latch  312  is engaged in opening  226  to a position in which such latch  312  becomes engaged in opening  228 , or from a position in which a latch  312  is engaged in opening  228  to a position in which such latch  312  becomes engaged opening  230 . Latch or latches  312  are also shaped and sized so that once a latched position has been reached at openings  226 ,  228  or  230 , body  302  cannot be proximally withdrawn from bore  208  unless latch or latches  312  are pressed inwardly before pulling body  302  from bore  208 . 
     As supplied to the physician, body  302  desirably is already inserted into bore  208  so that latch or latches  312  and tab or tabs  314  ride within recess or recesses  316 . Body  302  also desirably is advanced sufficiently far into bore  208  so that the distal end of pin  306  contacts the proximal end of the nearest implant. For example, when only one implant like implant  232   a  will be provided in device  100 , then the distal end of pin  306  may contact the proximal end of such implant. When as is shown in  FIG.  3    two implants like implants  232   a  and  232   b  are provided in device  100 , then the proximal end  307  of pin  306  may contact the proximal end  233  of the most rearwardly-located implant  232   b . Latch  312  desirably engages opening  228  when only one implant is provided in device  100  as supplied to the physician, and desirably engages opening  226  when two implants are provided in device  100  as supplied to the physician. Similar engagement desirably is present if the above-mentioned optional right side latches and openings are employed. A removable lockplate  320  may also be provided in device  100  to block or otherwise prevent or limit accidental advancement of body  302  into barrel  210  until such time as the physician is ready to use device  100 . 
     Device  100  normally will be provided to the physician in sterile packaging such as a sealed and suitably irradiated vial, pouch, bag, box or tray. When the time comes for a physician to use device  100  in a surgical procedure, device  100  is removed from such packaging, cover  234  and lock  320  are removed if present, needle  216  and portion  212  are inserted into one of the nares and grip  202  is manipulated so that needle  216  pierces the desired turbinate mucosal tissue target area. For example,  FIG.  3    shows needle  216  partially inserted into turbinate tissue  330 , at an insertion depth of about one-half the length of implant  232   a . Insertion guides  220 ,  222  and  224  may be employed to judge how deeply tip  218  should be inserted submucosally so as to provide a desired depth of implant insertion. When the desired depth is reached, the physician may press thumb tab  304  towards the distal end of device  100 , causing latch  312  to vacate its current opening  226  or  228  and travel axially towards the next opening  228  or  230 , and causing the distal end of pin  306  to force implant  232   a  or  232   b  through needle  216  and out of needle tip  218  so as to bury submucosally at least a portion containing a tissue-engaging feature, and more preferably a majority and most preferably all of the length such implant, into the target turbinate mucosal tissue. Upon departure of latch  312  from its current opening  226  or  228 , the physician will receive visual, audible or tactile indication that implantation of the distal end of the implant into the tissue has commenced. Partial submucosal burying of the implant may be carried out by inserting enough of the implant into the target tissue to submucosally bury at least one tissue-engaging feature therein while holding needle  216  at a desired insertion depth less than the length of the implant (e.g., at depth indicator  220  or  222 ), halting pressure upon thumb tab  304  before latch  312  reaches the next opening  228  or  230 , and then withdrawing needle  216  from the target tissue so that the implant remains behind and partially projects from the target site into the surrounding air-filled cavity. Complete submucosal burying of an implant, or submucosal burying of more than one implant in a single insertion site, may be carried out for example by inserting needle  216  to a desired insertion depth (which may be but need not be a depth greater than the implant length), pressing thumb tab  304  until latch  312  arrives at the next opening  228  or  230  while holding needle  216  at the desired insertion depth, and then withdrawing needle  216  from the tissue so that the implant or implants remain behind, completely buried, and entirely in contact with the surrounding turbinate tissue. The physician may be aided in doing so by the visual, audible or tactile indication provided by arrival of a latch or latches  312  at the next opening  228  or  230 , which indication will also signal that the proximal end of the implant has exited needle  216  via tip  218  and that pressure upon thumb tab  304  may be halted. If desired, such pressure may be continued to further advance body  302  and cause another implant to exit needle  216  and become wholly or partly buried in the target tissue site. 
     If only one or less than all the implants in the disclosed surgical device have been used, device  100  may if desired be removed from the patient and discarded. Alternatively, needle  216  may be moved to a new target site (e.g., from a superior turbinate to the middle turbinate or to another site on the initial target turbinate) so that any remaining implant or implants may be submucosally buried at the new target site. Desirably however this is done while taking appropriate care to avoid microbial cross-contamination between target sites. Consequently the disclosed device preferably is used to bury multiple implants within only a single turbinate. 
     The disclosed surgical device may be modified in a variety of ways. In place of the disclosed pistol grip device, other configurations such as a finger grip device or a power-assisted device may be employed. Endoscopic, luminescent, electromagnetic, magnetic, radiographic or other navigation aids may be added to the device to aid in positioning the device and its needle tip. For example, a miniature light-emitting diode may be added to distal end  214  and employed as an endoscopic illumination or external transillumination aid to help position needle tip  218  near the desired target area. Lumens to provide features such as irrigation, suction, administration of local anesthetic or the removal of biopsy samples may also be added to the device. A larger-diameter trocar may be used in place of a smaller-diameter needle such as needle  216 . Magazines to facilitate loading additional implants may also be employed if desired. Persons having ordinary skill in the art will appreciate that other modifications may be made if desired. 
     A variety of implants may be employed in the disclosed surgical device. Preferably, the implant includes a biodegradable matrix (for example, a polymeric matrix) with the drug dispersed therein or coated thereon. The biodegradation characteristics of the implant preferably are such that it remains at the implantation site for at least three days, for at least one week, or for at least two weeks. The biodegradation characteristics of the implant also preferably are such that the implant substantially disappears from the implantation site in less than about two months, in less than about one month, or in less than about three weeks. The drug elution characteristics of the implant preferably are such that the drug elutes from the implant for at least three days, for at least one week or for at least two weeks after implantation. 
     Exemplary matrix polymers include synthetic polymers such as polyesters (for example, polylactides such as polylactic acid or “PLA”, poly(lactide-co-glycolide) or “PLGA” copolymers, and cyclic esters such as ε-caprolactone), polyanhydrides, polyorthoesters, polyalkylene glycols (for example, polyethylene glycol or “PEG”), polycarbonates, polyamides, polyphosphoesters, polyphosphazenes and polycyanoacrylates, and natural polymers such as polysaccharides, proteins and nucleic acids. Polyalkylene glycols and PLGA copolymers represent a preferred form of synthetic polymer, and polysaccharides represent a preferred class of natural polymer. Exemplary polysaccharides include agars, alginates, carrageenans, celluloses, chitins, chitosans, chondroitin sulfates, dextrans, galactomannans, glycogens, hyaluronic acids, starches, derivatives (including oxidized polysaccharides and salts) of any of the foregoing, and mixtures of any of the foregoing. The matrix polymer may be uncrosslinked or crosslinked. Additional matrix materials are described in U.S. Patent Application Publication Nos. US 2007/0014830 A1 (Tijsma et al.) and US 2007/0110788 A1 (Hissong et al.). The matrix may include colorants, radiopaque fillers or other additives to aid in visualization or navigation. 
     A variety of drugs may be used in the disclosed implant. Preferred drugs are useful for the treatment of nasal and sinus conditions and include angiotensin convertin enzyme (ACE) inhibitors; angiotensin receptor blockers (ARBS); antihistamines; steroidal or non-steroidal anti-inflammatory agents; chymase inhibitors; cyclooxygenase-2 (COX-2) inhibitors; decongestants; matrix metalloproteinase (MMP) inhibitors (e.g., doxycycline, TIMP metallopeptidase inhibitor  1  and dexamethasone); mucolytics; therapeutic polymers and combinations thereof. Additional examples of these and other drug classes and drugs are listed in the above-mentioned Tijsma et al. and Hissong et al. applications. If desired, other therapeutic agents for the treatment or prevention of various conditions may be employed, including analgesics, anti-cholinergics, anti-fungal agents, anti-parasitic agents, antiviral agents, biostatic compositions, chemotherapeutic/antineoplastic agents, cytokines, hemostatic agents (e.g., thrombin), immunosuppressors, nucleic acids, peptides, proteins, vasoconstrictors, vitamins, mixtures thereof, and additional other therapeutic agents that will be familiar to persons having ordinary skill in the art. A useful list of such other therapeutic agents may be found, for example, in U.S. Patent Application Publication No. US 2007/0264310 A1 (Hissong et al.). The implant may consist of or consist essentially of the drug, or the drug and other therapeutic agent, or may consist of or consist essentially of the above-mentioned matrix and drug, or the matrix, drug and other therapeutic agent. When a matrix is employed, the drug or drug and other therapeutic agent may be impregnated into or dispersed within the matrix, or the surface of the matrix may be dip coated, spray coated, conjugated with or otherwise covered with or bound to the drug or the drug and other therapeutic agent. 
     Exemplary lengths for the disclosed implants may for example be about 1 mm to about 2 cm or about 1 mm to about 1 cm for human adult use, about 1 mm to about 1 cm or about 1 mm to about 7 mm for human pediatric use, and about 1 mm to about 4 cm or about 1 mm to about 3 cm for veterinary use. Exemplary outer diameters for the disclosed implants may for example be about 0.1 mm to about 3.8 mm or about 0.1 mm to about 1.2 mm for human adult, human pediatric use or veterinary use. 
       FIG.  4 A  through  FIG.  4 K  show several exemplary implants with withdrawal-discouraging, mucosal tissue-engaging surface features. Such features may include projections (e.g., bumps, ribs, hooks or a ratchet rack), recesses (e.g., dimples, grooves or porosity), changes in cross-sectional shape or changes in cross-sectional area along the length of the implant. The implant may be symmetrical or asymmetrical about a central longitudinal axis, they have a generally cylindrical or non-cylindrical e.g. prismatic) shape with respect to such axis, and may have a blunt (e.g., flat), rounded (e.g., domed), sharpened (e.g., pointed) or chiseled (e.g., wedge-shaped) proximal (insertion) end, and a similar or different distal end. The implant may be rigid, or may be compressible with no, slow or rapid recovery of the shape prior to compression. In one embodiment, the withdrawal-discouraging, mucosal tissue-engaging surface features have a configuration such that the work (expressed as a product of force times distance) required to bury the implant submucosally in turbinate tissue is less than the work required to remove the buried implant from such tissue. In another embodiment, the withdrawal-discouraging, mucosal tissue-engaging surface features have a configuration such that the maximum force required to bury the implant submucosally in turbinate tissue is less than the maximum force required to remove the buried implant from such tissue. Preferably at least a majority of implant volume and more preferably all of the implant volume is buried in and contacts turbinate tissue after implantation. In one embodiment, the implant is not tensioned after implantation. In another embodiment, the implant does not draw tissue together after implantation. In yet another embodiment, the implant is not injected into or through and does not contact bone. 
       FIG.  4 A  is a cross-sectional view of implant  402  whose central constricted region  403  has a withdrawal-discouraging stop surface  404  near domed distal (insertion) end surface  406  and a gradual tapered surface  408  near proximal (trailing) end surface  409 . Implant  402  preferably is made from a relatively stiff biodegradable matrix that will penetrate and laterally displace turbinate tissue when injected therein. After implant  402  has been submucosally buried, nearby displaced tissue preferably returns to the constricted region  403  to provide a tissue-engagement surface adjacent stop surface  404 . 
       FIG.  4 B  is a cross-sectional view of implant  410  having a plurality of outwardly-projecting bumps  412  arrayed around the otherwise generally cylindrical surface  414  of implant  410 . Bumps  412  provide a withdrawal-discouraging, mucosal tissue-engaging surface feature. Implant  410  may if desired employ a less stiff biodegradable matrix than the matrix used for implant  402 , as the design of implant  410  has a substantial minimum diameter and consequently may have better inherent resistance to bending than will be the case for implant  402 . The end surfaces of implant  410  may if desired be symmetrical so that either end may serve as the distal (insertion) end surface. 
       FIG.  4 C  is a side sectional view of implant  420  having a plurality of outwardly-projecting circumferential ribs  422  arrayed around and along the length of the otherwise generally cylindrical surface  424  of implant  420 .  FIG.  4 D  is a cross-sectional view of implant  430  having a plurality of inwardly-directed grooves  432  arrayed around and along the length of the otherwise generally cylindrical surface  434  of implant  430 . Both the ribs  422  and grooves  432  provide withdrawal-discouraging, mucosal tissue-engaging surface features. 
       FIG.  4 D  is a cross-sectional view of implant  440  having a row of outwardly-projecting asymmetric latches formed by stops  442  and ramps  444  arrayed along the side of implant  440  between distal end surface  446  and proximal end surface  448 . The stops  442  and ramps  444  provide withdrawal-discouraging, mucosal tissue-engaging surface features, and are analogous to the ratchet rack in a so-called “zip tie” fastener. 
       FIG.  4 F  is a side sectional view of implant  450  having a braided structure formed by fibers such as fibers  452  and  454 . Both the exposed outer portion of the fibers and the small depressions such as depression  456  formed where fibers overlap provide withdrawal-discouraging, mucosal tissue-engaging surface features. 
       FIG.  4 G  and  FIG.  411    show cross-sectional views of a swellable implant  460  which may as shown in  FIG.  4 G  be generally cylindrical or prismatic prior to injection. As shown in  FIG.  411   , after implant  460  has been injected below the surface of turbinate tissue  468 , contact with fluids (e.g., water, mucus or blood) present in or near tissue  468  causes implant  460  to become swollen. The resulting increase in implant diameter provides a withdrawal-discouraging, mucosal tissue-engaging surface feature. 
       FIG.  4 I  is a cross-sectional view of a resilient, compressible implant  470  having a reduced diameter when constrained inside needle  216 . When injected into turbinate tissue  478 , implant  470  expands while in contact with such tissue and assumes its normal unrestrained shape with an expanded diameter. The resulting expanded diameter provides a withdrawal-discouraging, mucosal tissue-engaging surface feature. 
       FIG.  4 J  is a side sectional view of a helical implant  480  that with the aid of a suitable rotating insertion device can be screwed into turbinate tissue. Implant  480  preferably is made from a very stiff biodegradable matrix that can withstand the associated insertion forces. 
       FIG.  4 K  is a cross-sectional view of a generally curved implant  490  lodged in turbinate tissue  498 . Implant  490  may be inserted into such tissue with the aid of a suitably curved insertion needle. If implant  490  has sufficient resiliency and shape memory, it may also be inserted using a straight insertion needle and allowed to assume a curved shape after it exits the needle tip. The curved shape provides a withdrawal-discouraging, mucosal tissue-engaging surface feature. 
     The complete disclosure of all cited patents, patent applications, technical bulletins and other publications are incorporated herein by reference as if individually incorporated. 
     Although specific and in some cases preferred embodiments have been illustrated and described, it will be appreciated by those of ordinary skill in the art that a variety of alternate or equivalent embodiments calculated to achieve the same purposes may be substituted for the specific embodiments shown and described above. This application is intended to cover any such adaptations or variations of the embodiments discussed herein. Therefore, it is manifestly intended that this invention be limited only by the claims and the equivalents thereof.