Abstract:
A mechanical system for sequentially securing skin tissue preferably utilizes a tissue manipulator apparatus to approximate a portion of an interior surface of each of two pieces of living dermis tissue along a vertical interface below an exterior surface such that discrete target tissue zones are defined within the two pieces of living dermis tissue. An applicator apparatus includes a driving head portion positioned in the vertical interface and at least partially below the exterior surface and a handle portion positioned at least partially above the exterior surface. The applicator apparatus unilaterally drives a fastener through a first side of the living dermis tissue and then sequentially drives the fastener through a second side of the living dermis such that the fastener is positioned below the exterior surface and a portion of the fastener is positioned generally transverse to the vertical interface. The manipulator apparatus and the applicator apparatus can be arranged to be integral components operably connected together as part of a hand-held instrument capable of carrying and deploying fasteners.

Description:
RELATED APPLICATIONS AND PRIORITY CLAIM 
     The present application is a continuation application of U.S. patent application Ser. No. 10/448,838, filed May 30, 2003, entitled “Mechanical Method and Apparatus for Bilateral Tissue Fastening”, which is a divisional of U.S. patent application Ser. No. 10/179,628, filed Jun. 25, 2002, now issued as U.S. Pat. No. 6,726,705, and is also a continuation-in-part application of U.S. Continuation-In-Part application Ser. No. 10/607,497, entitled “Mechanical Method and Apparatus for Bilateral Tissue Fastening”, filed Jun. 25, 2003 and U.S. Continuation-In-Part application Ser. No. 10/603,397, entitled “Dynamic Bioabsorbable Fastener for Use in Wound Closure”, filed Jun. 25, 2003 now U.S. Pat. No. 7,112,214, all of which are herein incorporated by reference in their entirety. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates generally to the field of surgical instruments such as surgical staplers, clip applicators and sutureless closure devices. More particularly, the present invention relates to a mechanical method and apparatus for fastening tissue, such as skin tissue, with a fastener positioned below the tissue surface that secures opposed pieces of tissue. 
     BACKGROUND OF THE INVENTION 
     When an opening in tissue is created either through an intentional incision or an accidental wound or laceration, biological healing of the opening commences through the proximity of the opposed living tissue surfaces. If the opening is very large or if its location subjects the wound to continual movement, a physician will seek to forcibly hold the sides of the opening in close proximity so as to promote the healing process. 
     In the case of skin tissue, for example, healing occurs best when the opposing dermal layers of the skin tissue are held in proximity with each other. Human skin tissue is comprised of three distinct layers of tissue. The epidermal layer, also known as the epidermis, is the outermost layer and includes non-living tissue cells. The dermal layer, or dermis, is the middle layer directly below the epidermal layer and comprises the living tissue of the skin that is the strongest of the three layers. The subcutaneous, or hypodermis layer is the bottom layer of skin tissue and includes less connective tissue making this the weakest layer of skin tissue. 
     The most prevalent method for forcibly closing a tissue opening is through the use of a suture or “stitches.” As early as the second century, the Greeks were using sutures to physically close skin openings. In its simplest form, a suture is simply a length of material that is attached to a tissue-piercing device, such as a needle, and looped through the opposing sides of an opening. The suture is then pulled tight and the loop closes causing the opposing sides of the tissue to come into close physical proximity. The suture loop is held tight by the tying of a knot or some other locking mechanism. The first sutures were made of animal gut. Eventually other natural suture materials including leather, horsehair, flax, cotton and silk came into use. 
     As the sciences of medical and materials technology have advanced over the course of the past century, new bioabsorbable materials have been developed to further improve upon the basic suturing concept. Examples of modem improvements to the suturing process include enhancements to the suturing apparatus as shown, for example, in U.S. Pat. Nos. 755,921, 2,439,383, 2,959,172, 3,344,790 and 3,633,582, as well as advances in sutures and suture materials as shown, for example, in U.S. Pat. Nos. 3,123,077, 3,297,033, 3,636,956, 3,792,010 4,027,676 and 4,047,533. More recently, the suturing apparatus has been improved in the way of developing surgical “sewing machines” as shown, for example, in U.S. Pat. Nos. 5,496,334, 5,728,112, 5,735,862, 5,876,412, and 6,332,889, as well as in U.S. Publication Ser. Nos. 20030171761A1 and 20030216755A1. In addition, the suturing apparatus has been improved and tailored for specialty applications, for example endoscopic applications as shown, for example, in U.S. Pat. Nos. 5,080,663, 5,389,103, 5,522,820, 5,578,044, 5,674,230, 5,797,927, 5,817,110, 5,871,488, 5,938,668, 5,976,161, and 6,641,592, as well as in U.S. Publication Ser. Nos. 20020049453A1, 20020065526A1, 0020128666A1, 20030105475A1, 20030105476A1, and 20030114863A1. Finally, suturing applications have been developed in which a secondary tissue fixation method is used in conjunction with a suture as shown, for example, in U.S. Pat. Nos. 6,264,675 and 6,478,809. 
     While suturing remains a popular method of effectuating closure of skin openings, the use of staples and staplers as a skin closure technique has become increasingly popular, especially in surgical settings where the opening is created through a purposeful incision. In these settings, the incision tends to make a clean, straight cut with the opposing sides of the incision having consistent and non-jagged surfaces. Typically, stapling of a skin opening, for example, is accomplished by manually approximating the opposing sides of the skin opening and then positioning the stapler so that a staple will span the opening. The stapler is then manipulated such that the staple is driven into the skin with one leg being driven into each side of the skin and the cross-member of the staple extending across the opening external to the skin surface. Generally, the legs of the staple are driven into an anvil causing the staple to deform so as to retain the skin tissue in a compressed manner within the staple. This process can be repeated along the length of the opening such that the entire incision is held closed during the healing process. 
     Much work has been devoted to improving upon the basic stapling process. Developments have gone in a variety of directions and include work devoted to the stapling apparatus as shown, for example, in U.S. Pat. Nos. 3,082,426, 3,643,851, 4,410,125, 4,493,322, 4,592,498, 4,618,086, 4,776,506, 4,915,100, 5,044,540, 5,129,570, 5,285,944, 5,392,979, 5,489,058, 5,551,622, 5,662,258, 5,794,834, 5,816,471, 5,893,855, 6,131,789, 6,250,532 and 6,283,984. In addition to the stapling apparatus, developments have also been made in the staple design as shown, for example, in U.S. Pat. Nos. 2,351,608, 2,526,902, 2,881,762, 3,757,629, 4,014,492, 4,261,244, 4,317,451, 4,407,286, 4,428,376, 4,485,816, 4,505,273, 4,526,174, 4,570,623, 4,719,917, 4,741,337, 5,007,921, 5,158,567, 5,258,009, 5,297,714, 5,324,307, 5,413,584, 5,505,363 and 5,571,285. 
     In some instances, work has been devoted to combining the advantages of sutures and staples into a single medical fastener for purposes of wound closure. Various different styles and techniques of combining sutures and staples have evolved as shown, for example, in U.S. Pat. Nos. 5,342,376, 5,425,747, 5,584,859, 5,931,855, 6,106,544, 6,270,517, and 6,599,310. 
     While modern suturing and stapling techniques continue to provide an effective manner of effectuating skin closure, there remains a series of inherent disadvantages in using either of these techniques. The standard technique for both suturing and stapling includes puncturing both the epidermis and dermis. This can result in a wound closure having an unaesthetically pleasing appearance on the surface of the skin. The presence of the fastener exposed through the skin surface provides an opportunity for infection and for accidentally catching the fastener and tearing the wound open. In the case of non-absorbable fasteners, further action by a medical professional is necessary in order to remove the fastener once biological healing is complete. 
     In order to overcome these limitations, practitioners have developed a number of specialized suturing techniques where the suture is passed only through the dermis effectively positioning the suture below the skin surface, or in a subcuticular fashion. A surgeon has the choice of placing individual or interrupted sutures along the length of an opening. Another suturing option is for the surgeon to use a single strand of suture material to place a plurality of continuing suture loops or running sutures along the length of an opening. While the presence of the suture below the surface can improve the aesthetic nature of the closure, it requires greater skill and technique to accomplish effectively and takes longer than conventional external suturing. 
     While there has been active development of dermal layer suturing techniques, little has been done in the area of staples and staplers for use in connection with the dermal layer. In a series of patents issued to Green et al., including U.S. Pat. Nos. 5,292,326, 5,389,102, 5,489,287 and 5,573,541, a subcuticular stapling method and apparatus are disclosed that were ultimately commercialized as the U.S. Surgical SQS Subcuticular Stapling Apparatus. The Green et al. patents describe a stapling technique employing a handheld apparatus with jaws to proximate, interdigitate and overlap opposing sides of dermal layer tissue along the length of a skin opening. The apparatus then drives a single spike through the interdigitated and overlapped dermal layers of the opposing skin surfaces in order to secure both sides of the dermal tissue on the single spike. Although this technique reduced the time required to effectuate a subcuticular skin closure, the SQS device was not commercially successful in part because the resulting closure produced an undesirable wave-like scar that sometimes did not heal effectively. 
     Another alternative bioabsorbable approach is disclosed and described in a series of patents issued to Brotz, including U.S. Pat. Nos. 5,425,747, 5,584,859, 6,270,517 and 6,478,809. The Brotz patents describe a suturing technique using a bioabsorbable suture structure having a plurality of lateral members extending perpendicularly from a central body member. Lateral members on opposed sides of the central body extend into tissue on opposing sides of an incision whereby the lateral members hold the incision closed. 
     Another bioabsorbable approach for wound closure is disclosed and described in U.S. Pat. No. 6,645,226 that comprises a series of attachment points projecting from a common supportive backing. The backing is then placed below the wound, generally in the sub-dermal layer, such that the backing extends across the wound. Next, the tissue is pressed over the attachment points such that the wound stress is distributed by the backing. 
     In yet another bioabsorbable approach for wound closure, U.S. Pat. No. 6,599,310 to Leung et al., describes a barbed suture that can be used for approximating and retaining subcuticlar tissue during the healing process. The barbed suture can be looped by a surgeon through opposing sides of a tissue wound, along the length of the wound, whereby the suture is pulled tight and the wound is held closed. 
     Unfortunately, none of these bioabsorbable fasteners designed for use in the dermal layer have achieved significant commercial or medical success. 
     A novel bilateral approach to fastening dermal tissue using bioabsorbable fasteners is disclosed and described in U.S. Pat. No. 6,726,705, as well as in U.S. patent application Ser. Nos. 10/448,838, 10/607,497 and 10/603,397, to Peterson et al, all of which are commonly assigned to the assignee of the present application and all of which are incorporated by reference in their entirety. This bilateral approach to tissue fastening first manipulates opposed sides of tissue to form target tissue zones followed by a bilateral insertion of a tissue fastener to retain opposed dermal layers across an incision or wound in close approximation to facilitate healing. By maintaining contact of the dermal layers through the healing process, the healing process is enhanced which results in less chance of infection, faster recovery and improved aesthetic appearance. In addition, no subsequent medical follow-up is necessary to remove fasteners as is typically necessary with nonabsorbable fasteners. 
     While the bilateral tissue fastening methods and apparatus taught by Peterson et al. provide many advantages, it would be advantageous to extend the principles taught by Peterson et al. to other suitable tissue fastening applications. 
     SUMMARY OF THE INVENTION 
     The present invention is a mechanical system for unilaterally securing opposing sides of skin tissue in a sequential or alternating manner. A tissue manipulator is used to retain a portion of an interior surface of each of two pieces of living dermis tissue along a vertical interface below an exterior surface in order to present a target tissue zone for each piece of tissue. An applicator apparatus includes a driving head portion and a handle portion positioned at least partially above the exterior surface. The applicator apparatus unilaterally drives at least one portion of a fastener first through one target tissue zone and then through the target tissue zone of the other piece of dermis tissue. The two pieces of dermis tissue can be brought together before, during or after the insertion of the fastener. 
     In one embodiment, a fastener is driven sequentially through a pair of target tissue zones defined on opposing sides of a tissue interface. The pair of target tissue zones may be located directly across the tissue interface from one another or may be displaced such that one target tissue zone is forward of the other target tissue zone relative to the tissue interface. The fastener can have has flexible body portion with a barb at a distal end. The fastener can further comprise an attachment flap at a proximal end. The attachment flap can include a slot formed therethrough, which is adapted to receive the barb. The applicator assembly can include an anvil portion with a concave deflector. The concave deflector causes the flexible body portion to bend and advance from one target tissue zone, across the tissue interface and into the other target tissue zone. Once the barb emerges from the second target tissue zone, the attachment flap may be bent so that barb can be captured such that the secured fastener forms a loop capturing both sides of the skin opening. In an alternative embodiment, the application assembly can make use of a single U-shaped needle in place of a pair of generally parallel pilot needles. Numerous other combinations of sequential, unilateral fastener insertion and tissue capture are contemplated by the scope of the present invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows a typical opening in skin tissue such as may be closed by the present invention. 
         FIG. 2  shows a cross-sectional view of the skin tissue and opening of  FIG. 1 . 
         FIG. 3  shows an enlarged view of a target tissue zone. 
         FIG. 4  shows a cross-section view of unilaterally everted skin tissue. 
         FIG. 5  shows a cross-section view of unilaterally everted skin tissue including a unilaterally inserted fastener. 
         FIG. 6  shows a cross-section view of a wound having a fastener sequentially inserted through opposed target tissue zones. 
         FIG. 7  is a pictorial representation of a skin opening closed with conventional subcutaneous sutures. 
         FIG. 8  is a pictorial representation of a skin opening closed by conventional surgical stapling. 
         FIG. 9  is a pictorial representation of an opening closed with the prior art interdigitated subcuticular stapler. 
         FIG. 10  is a pictorial representation of an opening closed using the bilateral fastening technique of the present invention. 
         FIG. 11  is a perspective view of an embodiment of an applicator apparatus of the present invention. 
         FIG. 12  is a side view of an insertion head of the present invention. 
         FIG. 13  is a plan view of the insertion head of  FIG. 12 . 
         FIG. 14  is a perspective view of the insertion head of  FIG. 12 . 
         FIG. 15  is a perspective view of an embodiment of a tissue manipulator assembly. 
         FIG. 16  is a perspective view of a pair of tissue forms on the tissue manipulator assembly of  FIG. 15 . 
         FIG. 17  is a side view of a sequential fastener of the present invention. 
         FIG. 18  is a plan view of the sequential fastener of  FIG. 17 . 
         FIG. 19  is a perspective view of the sequential fastener of  FIG. 17 . 
         FIG. 20  is a perspective view of the insertion head of  FIG. 12  inserting the sequential fastener of  FIG. 17 . 
         FIG. 21  is a perspective view of the insertion head of  FIG. 12  inserting the sequential fastener of  FIG. 17 . 
         FIG. 22  is a perspective view of an embodiment of an applicator including a tissue manipulator assembly. 
         FIG. 23  is a perspective view of an embodiment of an applicator including a tissue manipulator assembly. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     In  FIGS. 1-3  there is shown a depiction of a typical opening  50  in the surface of skin  52 , such as may be made, for example, by a surgical incision or a wound. As illustrated in  FIG. 1 , for purposes of describing the present invention, opening  50  may be described as having a length or longitudinal orientation parallel to the y-y axis, a width orientation parallel to the x-x axis, and a depth orientation parallel to the z-z axis. The x-y-z axis for purposes of the present invention is defined with respect to an external tissue surface, which in the case of skin  52  is the outer surface. References to a vertical and horizontal planar orientation in connection with the present invention are made with respect to the external tissue surface at the site of the opening in question. The vertical inner surfaces  60  formed by each side of the opening  50  can be visualized as meeting along a generally vertical interface  51 . It will be understood that in the case of an opening that extends over a curved tissue surface, the corresponding horizontal and vertical surfaces associated with the opening will be defined with respect to such curved tissue surface. It also will be understood that the vertical interface  51  may be vertical in only one orientation with respect to the tissue surface, such as in the case when an angled incision has formed the opening  50 . 
     As is best illustrated in the sectional views of  FIGS. 2 and 3 , human skin  52  generally has three discrete layers. These layers comprise an epidermal layer  54  of mostly non-living tissue having an exterior surface  55 , a dermal layer  56  of mostly living tissue, and a subcutaneous tissue layer  58 . Although the preferred embodiment of the present invention will be described with respect to human skin tissue  52 , it will be understood that the present invention is applicable to closure of openings in other types of tissue having generally defined surfaces, such as fascia, membranes organs, vessels, vasculature, vascular pedicles, skin grafts, bladder and other biocompatible materials with generally defined surfaces such as artificial skin, artificial membranes and synthetic mesh. 
     It has long been known that the most rapid healing of a skin opening with a minimum of scarring occurs when the inner surfaces  60  of the living dermal layer  56  at each side of the vertical interface  51  of skin opening  50  are brought together and held in close contact as illustrated in  FIG. 6 . One method of approximating the inner surfaces  60  is by everting the dermal layers  56 . One method of everting the dermal layers  56  is through simultaneous bilateral capture of the dermal layers  56  as disclosed and describe in the related U.S. Pat. No. 6,726,705 and U.S. patent application Ser. Nos. 10/179,628, 10/607,497, and 10/603,397. Alternatively, the dermal layers  56  can be unilaterally and sequentially everted, for example, as shown in  FIGS. 4 and 5 . 
     The ability of the present invention to provide a more effective and efficacious tissue closure can be seen with reference to  FIGS. 7 ,  8 ,  9  and  10 , which show skin openings closed by various prior art methods as compared with an opening closed using the bilateral fastening techniques of the present invention. In  FIG. 7 , there is shown a skin opening closed with subcutaneous sutures. The generally everted condition of the closed opening can produce unattractive scarring and less than optimal healing if the eversion is excessive or inadequate. As can be seen from  FIG. 7 , obtaining consistency from suture to suture is difficult and the quality of the closure is highly dependent upon the skill of the surgeon.  FIG. 8  shows a skin opening closed by conventional surgical stapling. In addition to the generally unattractive appearance of the closed opening, staple openings and the excessive everted condition of the opening may lead to undesirable scarring. In addition, if non-resorbable staples are used, the staples must be removed before complete healing can occur.  FIG. 9  shows a depiction of an opening closed with the interdigitated subcuticular stapler known as the SQS device that is described, for example, in U.S. Pat. Nos. 5,292,326, 5,389,102, 5,489,287 and 5,573,541. The characteristic undulating appearance caused by the overlapping interdigitation of the skin may lead to an unusual appearing scar in the healed opening. The overlapping and interdigitation of the skin can also cause epidermis tissue to be interposed between dermal layers, thereby leading to incomplete healing or excessive scarring. 
     By comparison, an opening that has been partially closed by the method and using the apparatus of the present invention is shown in  FIG. 10 . As shown, the closed portion of the opening is tightly closed, yet lies flat without undue eversion of the opening leading to better healing performance with minimal scarring. There is consistency in the closure from fastener to fastener. Because the fasteners are positioned below the skin surface (i.e., subcuticular), the fasteners are not exposed and there is no puncturing or button holing of the epidermis that can lead to the increased possibility of infection or interference with the normal healing process. In addition, if fasteners made of a bioresorbable, bioabsorbable or even a bioerodible material are used, there is no need to later remove the fasteners. 
     The advantages of the present invention are accomplished by an apparatus and method that unilaterally engages target tissue zones  70 , shown in  FIGS. 3 ,  5  and  6 , on each side of a skin opening  50  with a fastener that is preferably made of a bioresorbable material. As used in connection with the present invention, the term unilaterally refers to a single axis of insertion for a fastener on one side of the vertical interface  51  of an opening  50 . The unilateral engagement is then made on an opposed side of the vertical interface  51  such that a fastener is inserted sequentially through both target tissue zones  70 . The fastener used may have a variety of configurations and be oriented in a variety of ways as will be further described herein. The location, geometry and orientation of the fastener and the dermal layers in relation to the mechanical apparatus of the present invention are all important considerations to obtaining the most optimal contact and compression of the dermal layer for efficacious closing of the opening. While the skin opening  50  will be described in connection with an opening in a single piece of tissue, it will be understood that the opening  50  could also be between two separate and otherwise unconnected pieces of tissue, or even between a piece of tissue and a piece of biocompatible material to be secured to that piece of tissue. 
     As is shown in  FIGS. 3 ,  5  and  6 , there exists an optimal target tissue zone  70  on each side of vertical interface  51  that may be bilaterally engaged by a fastener in order to achieve optimal dermal contact for healing. This target tissue zone  70  lies within the dermal layer  56 , and can be visualized as a rectangular cross-sectional area when the tissue is in a relaxed condition as shown best in  FIG. 3 . In addition, within target tissue zone  70 , there exists a most preferred area  72  for tissue engagement. In the depth orientation, target tissue zone  70  lays between a distance L 3  of about 0.1 mm below the surface  55  of epidermal layer  54 , and a distance L 4  up to 2.0 mm below the surface  55 . The most preferred area  72  lies between a distance L 5  of about 0.2 mm and a distance L 6  of about 0.8 mm below the surface. In the width orientation, target tissue zone  70  lies between a distance L 7  of about 1.0 mm and a distance L 8  of about 20.0 mm from vertical interface  51 . Most preferred area  72  lies between a distance L 9  of about 2.0 mm and a distance L 10  of about 8.0 mm from vertical interface  51 . Because the target tissue zone  70  is not visible to an operator, the manipulator assembly  400  and applicator assembly  100  are preferably designed to consistently and repeatedly enable the operator to position the target tissue zone  70  for deployment of a fastener  400 . 
     As illustrated in  FIG. 5 , due to the inherent flexibility and resilience of skin tissue, it is most desirable that a fastener  400  be deployed into the target tissue zone  70  while the skin opening is everted. A first dermal layer  56   a  is everted, as shown in  FIG. 4 , followed by the insertion of fastener  400  into a first target tissue zone  72   a  as shown in  FIG. 5 . The process is then repeated such that a second dermal layer  56   b  is everted followed by the sequential insertion of the fastener  400  into a second target tissue zone  72   b . Once the eversion and insertion is accomplished on both sides of opening  50 , fastener  400  retains the first dermal layer  56   a  and second dermal layer  56   b  in proximity during the healing process as illustrated in  FIG. 6 . To the extent that the primarily non-living material of epidermal layer  54  can be excluded from the healing opening, the rapidity and level of scar tissue formed during the healing process will be improved. The dermal layers  56  are retained in close contact with each other by the fastener  400  after the everting pressure is removed and the skin relaxes into a flat condition as shown in  FIG. 6 . 
     An embodiment of an applicator assembly  100  of the present invention is shown in  FIG. 11 . The application assembly  100  generally comprises upper handle portion  110  and lower handle portion  120 , to which is attached driving head  140 . Trigger  200 , which pivots about pivot  202  is provided to allow user actuation of the mechanism. Although a manual pivoting trigger arrangement  200  is shown, it will be understood that a variety of other user-actuated manual triggers, buttons or actuator mechanisms may be utilized with the applicator assembly  100 , such as a push button, slide mechanism, cam mechanism, spring actuated apparatus, cable actuated pull mechanism, rotating mechanism or tab actuated trigger. Alternatively, an automatic actuator in the form of an electronic, pneumatic, motion controlled, remote controlled or computer-activated trigger may be used to operate the applicator  100 . 
     In  FIGS. 12-14 , there are shown detailed views of an embodiment of a driving head  140  and lower handle portion  120 . Driving head  140  is preferably U-shaped and has an anvil portion  142  separated from backing portion  144  by a cross-member  146 , thereby forming a gap  148 . Cross-member  146  preferably has concave areas  150  allowing the dermal layer  56  of skin to be compressed into gap  148  such that target tissue zones  70  are presented for capture on either side of vertical interface  51  as will be further explained hereinbelow. Although driving head  140  is shown in a fixed orientation relative to lower handle portion  120  and upper handle portion  110 , it will be understood that driving head  140  may be articulated, either in the plane of the vertical interface  51  or perpendicular to the plane of the vertical interface  51 , to allow for increased maneuverability and orientation of driving head  140 . Alternatively, lower handle portion  120  may be articulated relative to upper handle portion  110 , or both lower handle portion  120  and driving head  140  may be articulated. 
     Preferably, anvil portion  144  of driving head  140  has apertures  152 . Apertures  152  are appropriately sized so as to slidingly receive penetrators or pilot needles  154 ,  156  and may be bored directly into the material of anvil portion  144  or may be lined with a metal guide tube or the like inserted into a bore in anvil portion  144 . Pilot needles  154 ,  156  have a generally arcuate shaped cross-section throughout distal portions  155 ,  157 , and a solid cylindrical cross-section in proximal portions  159 ,  161 . Each distal portion  155 ,  157  has an inner concave surface  158 ,  160  for accommodating and retaining a fastener  400 , and proximal portion  159 ,  161  can engage the back surface of the fastener  400 , allowing the fastener to be advanced distally with the needles. The distal ends  162 ,  164  of pilot needles  154 ,  156  can have a sharp point for penetrating skin. Alternatively, the distal ends  162 ,  164  can be configured merely for directing fastener  400  when the fastener  400  includes its own penetrating tip. Pilot needles  154 ,  156  are vertically disposed at a distance d 1  below top surface  166  of anvil portion  142 . It is preferably that top surface  166  be usable as a reference datum for visually gauging whether pilot needles  154 ,  156  are located within target tissue zone  70 . Accordingly, it is preferable that distance d 1  be between 0.1 mm and 2.0 mm, and most preferably between 0.2 mm and 0.8 mm, so that when top surface  166  is aligned with the outer skin surface, pilot needles  154 ,  156  are located within target tissue zone  70  and most preferably within most preferred area  72 . 
     Delivery mechanism  128  serves to eject a fastener from driving head  140 . Preferably, slide block  122  is slidably mounted on guides  124 ,  126 , within lower handle portion  120 . Slide block  122  is engaged with trigger  200  so that actuation of the trigger causes sliding movement of slide block  122 . Pilot needles  154 ,  156  are fixedly attached to slide block  122 , and extend outwardly through backing portion  144  of driving head  140  through slot  168 . Thus, back and forth sliding motion of slide block  122  causes pilot needles  154 ,  156  to be extended and retracted from slot  168 , gap  148  and apertures  152 . It will be understood that any number of mechanical driving arrangements can be used to impart the necessary force to pilot needles  154 ,  156 , or alternatively to the fastener  400  directly. Examples include sliding mechanisms, cam mechanisms, spring-operated mechanisms, screw drives, pneumatic drives, automated motion control drives, or the like. 
     Pilot needles  154 ,  156  are preferably spaced apart by an interneedle distance of between about 2.0 mm and 20 mm and most preferably between about 4.0 mm and 16.0 mm, so that when the driving head in placed within a skin opening to be fastened, and with the skin opening aligned with the approximate midpoint between the pilot needles, the pilot needles will be located within the width orientation of the target tissue zone  70 . 
     In  FIGS. 17 and 18 , there is shown an embodiment of a tissue manipulator assembly  300  for use in approximating and everting tissue with respect to applicator assembly  100 . The proximal ends  307  of arms  302 ,  304  are joined together at fulcrum  306 , forming the tweezer-like structure of the overall assembly. Gripping areas  312  are provided on each arm to allow gripping of the assembly with the fingers. Any suitable fastening method may be used at fulcrum  306 , including rivets  316  as shown, or the arms  302 ,  304  may be welded, cast, or molded together or may otherwise be integrally formed together. The material and overall dimensions for arms  302 ,  304  are selected so as to allow the arms to be resiliently compressed inwardly with the fingers, and with a memory characteristic for returning to the original position upon the removal of pressure. In addition, the material used for the arms and other portions of the assembly are preferably thermally and chemically stable so as to allow sterilization with either heat or chemical means. The preferred material for arms  302 ,  304  is stainless steel. 
     At the distal ends  309  of each arm  302 ,  304  are formed tissue manipulator surfaces  318 . Manipulator surfaces  318  are preferably semi-cylindrically shaped as shown, with the diametrical dimension of each semi-cylinder selected so as to conform to the diameter and shape of the concave areas  150  of applicator assembly  100 . Skin gripping jaw members  314  are preferably attached to the exterior surfaces  326  of each arm member  302 ,  304 . Each jaw member  314  has a backing portion  324  for attaching to the arms, and a pair of inwardly directed projections  320  disposed on both sides of manipulator surfaces  318 . Directly opposed serrations  322  are preferably provided on the inward-most edge of each projection  320  for better skin purchase. Backing member  324  may be attached to each arm  302 ,  304  using any suitable attachment method, including mechanical fasteners such as the rivets  316  as shown. For reasons that will be further explained, it is preferable that each jaw member  314  is of sufficient resilience and is attached so that inwardly directed projections  320  may deflect separately from skin manipulator surfaces  318  under moderate finger pressure applied to arms  302 ,  304 . This may be achieved through concerted selection of the material used for jaw member  314 , the thickness dimension of backing member  324 , and the free length L 1  of each backing member  324  between the inwardly directed projections  320  and the fastener  316  closest to the distal end  309  of the arm. The objective of the design of the backing member  324  is to have the jaw members  314  engage tissue with a first force and have the manipulator surfaces  318  engage tissue between the jaw members  314  with a second force that is greater than the first force. In addition, the use of a pair of directed projections  320  on each side of the vertical interface  51  serves to stabilize the tissue laterally between the pair of projections  320 . 
     Mechanical stops  330  are provided to prevent pressure beyond that necessary to ensure optimal approximation of tissue into gap  148  and concave portions  150  of applicator assembly  100  from being transmitted through manipulator surfaces  318 . Preferably, mechanical stops  330  are set so that manipulator surfaces  318  close to a distance that is spaced apart from the interneedle distance of pilot needles  154 ,  156  by a range of 0.2-0.8 millimeters, such that the total distance between mechanical stops  330  is 0.4-1.6 millimeters greater than the interneedle distance between pilot needles  154 ,  156 . In a preferred embodiment in which the interneedle distance is set at 3.25 millimeter, the mechanical stops  330  would allow the surfaces  318  to close to within a range of 3.65-4.85 millimeters when approximating tissue into gap  148 . Although jaw members  314  may be formed from any suitable material, the preferable material is stainless steel. 
     An embodiment of the fastener  500  for use in unilateral tissue capture and sequential fastener insertion is shown in  FIGS. 17 ,  18  and  19 . Fastener  500  has flexible body portion  502  with a barb  506  at distal end  505  and an attachment flap  504  at proximal end  503 . Flexible body portion  502  is dimensioned so as to be received within either concave inner surface  158 ,  160  of pilot needles  154 ,  156 . Attachment flap  504  has slot  508  formed therethrough, which is adapted to receive barb  506 . 
     Fastener  500  can be applied using applicator assembly  100 . In applicator assembly  100 , anvil portion  142  has concave deflector  153  formed between apertures  152  and extending into a portion of each aperture  152  so that only an area of each aperture is open sufficient to allow the arcuate cross-section of pilot needles  154 ,  156  to pass. In operation, and with reference to  FIGS. 1-6  and  11 - 19 , fastener  500  is axially aligned with pilot needle  154 , and is inserted within the corresponding concave inner surface of the needle with barb  506  oriented toward the point of the needle. Applicator assembly  100  is then introduced into the interface portion  51  of the skin opening  50  as described above. Tissue manipulator assembly  300  is then applied as before to bring the dermal layer  56  into contact within gap  148 , and thereby properly positioning target tissue zone  70 . As slide block  122  and the attached pilot needles  154 ,  156  are moved distally through actuation of trigger  280 , fastener  500  is advanced through the skin tissue on one side of skin opening  50  along with pilot needle  154  in which it is disposed. Once the tip of barb  506  reaches aperture  152 , however, it is engaged by, and begins to slide laterally along, concave deflector  163 , causing flexible body portion  502  to bend. As pilot needles  154 ,  156  are further advanced, barb  506  is turned in direction 180 degrees by deflector  163 . It will be appreciated that the barb  506  may either be positioned in front of pilot needle  154  by an amount sufficient to redirect barb  506  into the opposite direction or pilot needle  154  may advance into the corresponding aperture  152  to a depth at which the redirection of barb  506  upon the entry to aperture  152  will be sufficient to redirect barb  506  into the opposite direction. Once redirected and positioned in line with the second skive, barb  506  is advanced in the opposite direction by pilot needle  156  and through the skin tissue on the opposite side of the vertical interface  51  as pilot needle  156  is withdrawn. Once barb  506  emerges from the dermal tissue, attachment flap  504  may be bent so that barb  506  may be pushed through slot  508 , thus securing fastener  500  in a loop and bilaterally capturing both sides of the skin opening  50 . It will also be appreciated that attachment flap  504  may be replaced by suitable structure on flexible body  502  for engaging a suture. The suture lock of co-pending application entitled “Suture Lock Having Non-Through Bore Capture Zone,” U.S. patent application Ser. No. 10/166,161, filed Jun. 10, 2002, which is commonly owned by the assignee of the present invention and the disclosure of which is hereby incorporated by reference, may then be used to secure the suture to barb  506 , completing the bilateral capture. In this embodiment described herein, the skives are created simultaneously and the fastener  400  is inserted sequentially into each corresponding skive from an opposite direction. Alternatively, a single U-shaped needle could be utilized in place of pilot needles  154 ,  156  and both the skives and fastener could be created and inserted sequentially. Numerous other combinations of bilateral creation of skives and insertion of fasteners are contemplated by scope of the present invention. 
     As described herein, the fastener is oriented so that a working plane defined by the flexible body  502  of fastener  500  is substantially parallel to a plane generally defined by exterior surface  55  of epidermal layer  54 , and transverse to vertical interface  51 . Those of skill in the art will appreciate, however, that the working plane of fastener  500  could also be oriented substantially orthogonal, or oblique, with the plane generally defined by exterior surface  55  while remaining in a transverse orientation with respect to vertical interface  51 . Those of skill in the art will also appreciate that other bilateral capture mechanical fastening systems wherein the target tissue zones are penetrated by a fastener in sequential fashion are possible within the scope of the present invention. For instance, a semi-circular, oval, or spiral fastener may be advanced sequentially through target tissue zones  70  on each side of vertical interface  51  using a mechanism that imparts a rotational motion to the fastener, but without causing interdigitation or overlapping of skin across vertical interface  51 . The mechanism may have means for creating a semi-circular, oval or spiral skive through which the fastener may be advanced, or the fastener itself may be formed from sufficiently rigid material and have a sharpened point so as to be capable of creating a skive as it passes through the skin. In another alternative embodiment providing a sequential bilateral capture motion, a fastener is provided having a cross-member connecting two legs wherein the legs are staggered so that when the fastener is advanced into the skin in a linear fashion, one of the legs precedes the other. In still another embodiment, two straight fasteners comprising a shaft portion with skin-engaging barbs are provided. These fasteners are oriented in opposite directions on either side of the vertical interface  51 , and are sequentially advanced through respective skives by an applicator assembly allowing a reversible motion. 
     In alternative embodiments of an applicator apparatus, an applicator assembly can incorporate an integral tissue manipulator assembly, for example applicator assembly  700  as shown in  FIG. 22  or applicator assembly  800  as shown in  FIG. 23 . 
     Although the present invention has been described with respect to the various embodiments, it will be understood that numerous insubstantial changes in configuration, arrangement or appearance of the elements of the present invention can be made without departing from the intended scope of the present invention. Accordingly, it is intended that the scope of the present invention be determined by the claims as set forth.