Adhesive-Containing Wound Closure Device and Method

(19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0255610 A1 Jonn et al. US 20080255610A1 (43) Pub. Date: Oct. 16, 2008 (54) ADHESIVE-CONTAINING WOUND CLOSURE DEVICE AND METHOD (75) Inventors: Jerry Jonn, Raleigh, NC (US); Julian Quintero, Raleigh, NC (US); Glenn Hoskin, Apex, NC (US); Susan L. Roweton, Raleigh, NC (US) Correspondence Address: BRINKS, HOFER, GILSON & LIONE 2801 SLATER ROAD, SUITE 120 MORRISVILLE, NC 27560 (US) (73) Assignee: (21) Appl. No.: Closure Medical Corporation, Raleigh, NC (US) 12/163,021 (22) Filed: Jun. 27, 2008 Related U.S. Application Data (62) Division of application No. 10/887,884, filed on Jul. 12, 2004. Publication Classification (51) Int. Cl. A61B 17/04 (2006.01) (52) U.S. Cl. ...................................................... .. 606/214 (57) ABSTRACT An article, such as a tissue bonding article, includes a flexible material, a polymerization initiator or rate modifier disposed in or on the flexible material, and a polymerizable adhesive composition permeated throughout at least a portion of the flexible material, where the polymerization initiator or rate modifier is a polymerization initiator or rate modifier for the polymerizable adhesive composition. US 2008/0255610 A1 ADHESIVE-CONTAINING WOUND CLOSURE DEVICE AND METHOD BACKGROUND OF THE INVENTION [0001] 1. Field of Invention [0002] The present invention relates to medical and surgi- cal wound closure and management, and methods for making and using such devices. In particular, the present invention relates to medical and surgical wound closure and manage- ment, and related methods, where the tissue bonding article or wound closure device incorporates a polymerizable adhesive material applied to an initiator-loaded textile material. The materials and methods of the present invention provide an improvement over, and a substitute for, conventional ban- dages, sutures and staples, and provide improved methods for both approximating and covering and/or closing wounds, thus providing improved wound management. [0003] 2. Description of RelatedArt [0004] There are currently in primary use at least four basic ways for closing wounds resulting from surgical incisions or accidental lacerations. These are sutures, surgical staples, surgical skin tapes, and adhesive compositions. Sutures are generally recognized as providing adequate wound support for the duration of wound healing. However, suturing involves additional trauma to the wound, as the needle and suture material must be passed through the tissue at the mar- gins of the wound. In addition, suturing can cause cosmeti- cally unattractive wound closure marks, can be time consum- ing, and, depending on techniques and types of sutures used, may require removal. Such removal entails further medical attention and can involve additional pain and trauma to the patient particularly if the sutures become embedded in the wound. In some cases, suture removal can require anesthetic, and can result in a railroad track appearance at the wound site. [0005] Surgical staples have disadvantages similar to sutures in terms of cosmetic result. However, staples are generally believed to be even worse then sutures, at least in terms of the pain and trauma inflicted on the patient, and the resultant cosmetic appearance of the staple and wound marks. Further, removal of the staples can be painful and, depending on location and patient pain threshold, may require topical anesthetics. [0006] Skin closure strips, such as conventional adhesive bandages, are utilized for closure of relatively superficial skin wounds, but their use is limited to only certain types and degrees of wounds. However, the contact adhesives that are used with such strips typically retain holding power for no more than a day or two and can lose holding power quickly in the presence of moisture, for example, perspiration. [0007] Direct application of adhesives has also been pro- posed and used for wound closure purposes, especially involving cyanoacrylate adhesives. Such materials are achieving more widespread use for wound closure. [0008] For example, monomer and polymer adhesives are used in both industrial (including household) and medical applications. Included among these adhesives are the 1,1- disubstituted ethylene monomers and polymers, such as the ot-cyanoacrylates. Since the discovery of the adhesive prop- erties of such monomers and polymers, they have found wide use due to the speed with which they cure, the strength of the resulting bond formed, and their relative ease of use. These characteristics have made ot-cyanoacrylate adhesives the pri- Oct. 16, 2008 mary choice for numerous applications such as bonding plas- tics, rubbers, glass, metals, wood, and, more recently, bio- logical tissues. [0009] It is known that monomeric forms of 0t-cyanoacry- lates are extremely reactive, polymerizing rapidly in the pres- ence of even minute amounts of an initiator, including mois- ture present in the air or on moist surfaces such as animal tissue. Monomers of 01-cyanoacrylates are anionically poly- merizable or free radical polymerizable, or polymerizable by zwitterions or ion pairs to form polymers. Once polymeriza- tion has been initiated, the cure rate can be very rapid. [0010] Medical applications of 1,1-disubstituted ethylene adhesive compositions include use as an altemate or an adjunct to surgical sutures and staples in wound closure as well as for covering and protecting surface wounds such as lacerations, abrasions, burns, stomatitis, sores, and other sur- face wounds. When an adhesive is applied, it is usually applied in its monomeric form, and the resultant polymeriza- tion gives rise to the desired adhesive bond. [0011] For example, polymerizable 1,1-disubstituted eth- ylene monomers, and adhesive compositions comprising such monomers, are disclosed in U.S. Pat. No. 5,328,687 to Leung et al. Suitable methods for applying such compositions to substrates, and particularly in medical applications, are described in, for example, U.S. Pat. Nos. 5,582,834, 5,575, 997, and 5,624,669, all to Leung et al. [0012] Combinations of the above approaches have also been used in the art. For example, attempts have been made to combine the use of sutures or staples and adhesive composi- tions. See, for example, U.S. Pat. No. 5,254,132. Likewise, attempts have been made to combine the use of conventional bandages or tapes and adhesive compositions. See, for example, U.S. Pat. Nos. 5,259,835 and 5,445,597. However, these approaches have typically met the same issues as described above for the individual approaches, namely difli- culties arising from the use of the sutures, staples and/or bandages or tapes. [0013] Current approaches for combining the above wound closure approaches also include combining the use of adhe- sive compositions and bandage-like dressings. For example, U.S. Patent Publications Nos. 2002-0049503 and 2004- 0106888 each disclose the combined use of adhesive compo- sitions and mesh bandage-like materials. In each case, a mesh-like structure is applied to a wound, and an adhesive composition is applied to the mesh-like structure. When the adhesive composition sets, it bonds the mesh-like structure to the wound. In U.S. Patent Publication No. 2004-0106888, the wound dressing includes removable ends that adhere the mesh-like structure to the wound, but which can be removed after the adhesive composition sets, leaving the adherent dressing in place. [0014] Commonly assigned U.S. patent application Ser. No. 10/779,721, filed Feb. 18, 2004, also discloses a com- bined adhesive composition and bandage-like dressing. The application discloses a tissue bonding article, comprising: a flexible material; an adhesive substance applied over at least a portion of a bottom side of said flexible material, for at least temporarily adhering the flexible material to a wound surface; and a polymerizable adhesive composition permeated throughout at least a portion of said flexible material. When the polymerizable adhesive polymerizes, the flexible material is adhered to the wound surface to provide an adherent com- posite dressing. The entire disclosure of this application is incorporated herein by reference. US 2008/0255610 A1 [0015] A difficulty with these combined adhesive/flexible substrate approaches is in the application and polymerization of the adhesive composition. For example, where a polymer- izable adhesive composition is applied to the substrate, the adhesive is either applied from an applicator device that includes a polymerization initiator, or the adhesive composi- tion (which contains no initiator) is applied to the flexible substrate and wound site where polymerization is initiated by moisture or other fluids present at the wound site. In the first instance, polymerization of the adhesive composition is rapid, but the presence of the polymerization initiator in the applicator device creates a short working time, requiring that the adhesive composition be applied rather quickly. In the second instance, the working time of the adhesive composi- tion is longer because the applicator device does not include a polymerization initiator. However, polymerization of the adhesive composition on the wound site is typically much longer and less consistent because polymerization relies upon weaker species (such as moisture or other natural substances present on the skin and not added specifically for polymer- ization initiation) that may be present in differing amounts. [0016] Accordingly, a need continues to exist for improved materials and methods for wound approximation. A need also continues to exist for improved materials and methods that have a wider range of applications, from extemal to internal use, and from essentially non-biodegradable (where the mate- rials are removed from the application site) to biodegradable (where the materials are not directly removed from the appli- cation site, but instead degrade over time). SUMMARY OF THE INVENTION [0017] The present invention addresses the above needs in the art, and others, by providing improved materials and methods for wound management, bonding, and approxima- tion. [0018] In embodiments, the materials and methods of the present invention provide significant advantages over the cur- rent materials and methods for wound closure. The materials and methods of the present invention can fully replace the use of bandages, sutures, and/or staples on a variety of wounds and tissue surfaces. These advantages include, among others, improved wound closure, improved wound approximation, provision of an improved durable microbial barrier, reduced procedure time, improved working time, improved cosmesis, less pain (during staple/ suture removal) resulting in increased patient satisfaction, and improved financial/economic out- comes by eliminating follow-up visits for staple/suture removal. [0019] In embodiments, the materials and methods of the present invention also provide significant advantages in terms of application of the wound closure device. In particular, because the flexible material is loaded with initiator for the subsequently applied polymerizable adhesive material, the polymerizable adhesive material rapidly and uniformly poly- merizes on and in the flexible material to form an adherent device, but without unacceptably high heat generation. This faster set time (the time between application and substantial polymerization of the polymerizable adhesive material) means that wound closure can be quickly effected. Further- more, because the flexible material is loaded with initiator for the subsequently applied polymerizable adhesive material, the polymerizable adhesive material does not need to be applied in a mixed state including initiator or through an applicator device that provides an initiator. As such, the work- Oct. 16, 2008 ing time (the time during which the polymerizable adhesive material can be applied before becoming polymerized in the applicator) is unlimited. [0020] In an embodiment, the present invention provides an article, comprising: a flexible material; a polymerization ini- tiator or rate modifier disposed in or on said flexible material; and a polymerizable adhesive composition permeated throughout at least a portion of said flexible material, wherein said polymerization initiator or rate modifier is a polymeriza- tion initiator or rate modifier for said polymerizable adhesive composition. The article can be a tissue bonding article for bonding tissue surfaces, or can be used in other applications. [0021] In another embodiment, the present invention pro- vides a method of bonding tissue, comprising: placing a flex- ible material over a substrate, wherein a polymerization ini- tiator or rate modifier disposed in or on said flexible material; applying a polymerizable adhesive composition over and substantially covering at least a portion of the flexible mate- rial; and allowing the polymerizable adhesive composition to permeate into and under the flexible material and polymerize to form a composite structure bonded to said substrate. [0022] The composite structures of the present invention, when used as tissue bonding articles, can be used to bond a variety of tissue ranging from hard tissue (such as bone) to soft tissue (such as skin, organs, mucous membranes, and the like). The tissue can be either intemal or extemal. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS [0023] In embodiments, the present invention provides wound closure devices and methods, that provide some or all of the above advantages. The present invention provides such benefits by providing, as a wound closure device, a flexible material that can be applied to a surface, and impregnated with a polymerizable monomeric adhesive composition, which upon setting or curing provides an adherent structure over the surface. Polymerization (setting or curing) of the polymerizable monomeric adhesive composition is assisted by the flexible material being loaded, coated, or the like with a polymerization initiator or rate modifier for the polymeriz- able monomeric adhesive composition. [0024] In embodiments, the flexible or compliant material can be formed of any suitable flexible or compliant material, providing that the aims of the present invention are obtained. Preferably, the flexible or compliant material is a material that is flexible, porous, and non-toxic. As used herein, the term “flexible” is used to refer to the flexible or compliant material. However, unless stated differently in context, the term “flex- ible” is meant to cover a range of materials, which exhibit one or more properties such as being flexible, compliant, elastic, or memory retentive. For example, “flexible” is also meant to refer to materials that exhibit elastic or memory properties, i.e., the ability for the material to retum to its original shape when stresses applied thereto are reduced or eliminated. [0025] The flexible material is preferably flexible or com- pliant, to allow the flexible substrate to be placed on the desired surface (such as skin, organ, tissue, or the like) in a manner that allows the flexible substrate to conform to the topology of the desired surface. Likewise, the flexible mate- rial is preferably porous, to allow the subsequently applied polymerizable adhesive material to pass through or permeate through the flexible material and to polymerize as a layer beneath the flexible material, while adhering the flexible material to the desired substrate. By “porous” is meant herein US 2008/0255610 Al either that the bulk of the flexible material has pores, such that the subsequently applied polymerizable adhesive material is soaked up or absorbed by the bulk material, or that the bulk of the flexible material has voids (like a net or screen), such that the subsequently applied polymerizable adhesive material passes directly through the bulk material, with or without being soaked up or absorbed by the bulk material. For example, in the case of textile materials, “porous” is generally used to mean that the applied adhesive composition perme- ates and passes through interstices between the fibers, but does not necessarily pass into and through the fibers them- selves. [0026] Such porosity (or other properties such as hydro- phobicity or hydrophilicity) will also allow a polymerization initiator or rate modifier to be loaded on the flexible material prior to use, to initiate the subsequently applied polymeriz- able adhesive material. Such porosity will also preferably allow air and water to pass through the flexible material (either through pores per se, or through voids in the bulk material). Depending upon the degree of porosity (and/ or the size of the openings in the textile), such porosity of the flex- ible material or ability of air and water to permeate through the flexible material may be tailored to either remain after the final composite material is formed, or to be absent therefrom. The flexible material is also preferably non-toxic, as it is intended to be used as a wound covering, such as on biologi- cal tissues. As such, the flexible material should be biologi- cally compatible with the desired substrate (such as tissue, skin, organ, or the like), and is preferably a material that is govemmentally approved or generally regarded as safe for the desired purpose. [0027] In other embodiments, the flexible material may be selected to be elastic or have some memory effect. In such embodiments, the elastic properties of the flexible material may desirably provide a degree of pressure or stress at the application site, for example, to maintain wound edge approximation. Likewise, in embodiments where such addi- tional degree of pressure or stress at the application site is not desired, the flexible material may be selected to have less or no elasticity. [0028] In embodiments of the present invention, the flex- ible material can be either biodegradable, or not biodegrad- able. “Biodegradable” in this invention is meant that the flex- ible substrate biodegrades over time in vivo, such that it does not require physical removal (such as by peeling) of the composite structure after a set period of time. Thus, for example, a biodegradable flexible material is one that, in the in vivo environment, will biodegrade over a period of from about one week to about five years. A non biodegradable material is one that does not biodegrade in an in vivo envi- ronment within about five years. Such a non biodegradable material thus would require physical removal of the compos- ite structure at a desired time, rather than slowly deteriorating over time. Likewise, in some embodiments, it is preferred that the combination of materials forming the composite structure (i.e., the flexible material and the polymerizable adhesive composition) together be biodegradable, while in other embodiments, it is preferred that the combination of materials forming the composite structure (i.e., the flexible material and the polymerizable adhesive composition) together be not bio- degradable. Biodegradable and non-biodegradable polymer- izable adhesive compositions are known in the art and are described below. Altematively, combination of two or more Oct. 16, 2008 biodegradable and/or non-biodegradable materials can be used, to provide tailored results in terms of properties such as biodegradation and the like. [0029] For biodegradable materials, a range of materials can be selected as the flexible material, preferably to provide a desired target biodegradation time. Thus, for example, suit- able materials can be selected to provide either a short bio- degradation period (such as between about one week and about two months) or a longer biodegradation period (such as between about two months and about five years). Suitable selection of the flexible material will thus allow tailoring of the flexible substrate to the particular application. For example, in embodiments where the flexible substrate is used to form a composite structure on the surface of a patient’s skin (such as in the conventional context of a bandage), it is desir- able that the flexible substrate is not biodegradable. Rather, after a set period of time, the composite structure is physically removed (such as by peeling, by the use of a chemical removal substance to break the adhesive bond, or by natural sloughing off of the composite structure with the surface skin), either to permit completion of healing or to reapply a new composite structure. Such removal of the composite structure from the tissue surface is easier than removal of a layer of polymeriz- able adhesive composition alone. In other embodiments, however, it may be desirable that the composite structure biodegrade over a set period of time, for example when the composite structure is used intemally where subsequent removal would otherwise require further trauma to the tissue. [0030] In embodiments, it is preferred that the flexible material is a textile or mesh/web material. Suitable textile materials can be formed of either synthetic or natural mate- rials. Such textile material can be formed of either woven or non-woven fabrics or materials. The flexible material may be, for example, any suitable polymeric film, plastic foam (in- cluding open celled foam), a woven fabric, knitted fabric, a non-woven fabric, mixture thereof, or the like. In particular, suitable flexible materials may thus be prepared, for example, from nylon, a polyolefin film, such as polyethylene, polypro- pylene, ethylene propylene copolymers, and ethylene buty- lene copolymers, polyurethanes, polyurethane foams, poly- styrenes, plasticized polyvinylchlorides, polyesters, polyamides, and cotton. Suitable specific examples include, for example, nylon, polyethylene, polypropylene, ethylene propylene copolymers, ethylene butylene copolymers, poly- urethane, polystyrene, plasticized polyvinylchloride, polyes- ter, polyarnide, cotton, polytetrafluoroethylene (PTFE), bio- vascular material, collagen, Gore-Tex®, DACRON®, etc. [0031] In some embodiments, it is preferred that the textile material not be formed of elastin, or elastin-based materials. Although elastin may be suitable for some uses, synthetic materials are preferred in embodiments in view of their avail- ability, ease of manufacture, physical properties such as strength and durability, and biological compatibility. Thus, in such embodiments, it is preferred that the textile material is substantially or completely free of elastin or elastin-based materials. Further, in such embodiments, it is preferred that the entire flexible substrate (i.e., the combination of the flex- ible material and the adhesive substance) is substantially or completely free of elastin or elastin-based materials. [0032] In other embodiments, it is preferred that the flexible material be formed of a synthetic, semi-synthetic, or natural organic material. Thus, for example, it is preferred that the flexible material be formed of a synthetic or natural polymer US 2008/0255610 Al material, but not from a material such as metal (such as silver, steel or the like) or glass or ceramic. [0033] The flexible material is preferably flexible, as described above, yet resistant to tearing. In one embodiment, the thickness of the flexible material of the present invention is from about 0.1 mil to about 50 mils. In another embodi- ment, the thickness of the flexible material is from about 0.5 mil to about 20 mils, preferably from about 0.7 mil to about 10 mils, or from about 1 mil to about 5 mils. [0034] The flexible material may be opaque or translucent. In some embodiments of the present invention, the flexible material is provided to have a skin color, such that the flexible material masks the appearance of the underlying surface (such as a wound). However, in other embodiments, the flex- ible material can be provided with “designer” colors and/or pattems, or even cartoon character designs. In other embodi- ments, the flexible material may be clear, thus not masking the underlying surface. [0035] In some embodiments, the flexible material can include a pressure sensitive adhesive on at least one face, to assist in initial placement of the flexible material on the desired surface. However, in other embodiments, the flexible material preferably does not include such pressure sensitive adhesive on one or both sides, as such pressure sensitive adhesive can hinder subsequent attachment of the flexible material to the surface by the polymerizable adhesive com- position. [0036] In embodiments where the flexible material includes a pressure sensitive adhesive applied to portions of the flexible material, the pressure sensitive adhesive can be applied to an entire surface of the flexible material, or only to portions (such as peripheral edges) of the surface of the flex- ible material. The exposed pressure sensitive adhesive can be covered by a suitable release layer or liner, if desired, to preserve the adhesiveness of the flexible material until time of use. The pressure sensitive adhesive, if present, canbe applied in the various manners shown in U.S. patent application Ser. No. 10/ 779,72 1, the entire disclosure of which is incorporated herein by reference. [0037] The size of the flexible material can be tailored for specific intended uses, or it can be provided in a sheet or roll form. Thus, for example, when forming a rectangular com- posite for use in the present invention, any suitable dimen- sions of the flexible material can be provided. For example, in the conventional bandage configuration, the flexible material can range in width from about 1/: inch to about 2 or 3 inches or more, although preferred widths in embodiments may be from about 1/2 to about 1 or l1/2 inches, and can range in length from about 1/2 inch to about 4 or 5 inches or more, although preferred lengths in embodiments may be from about 1 to about 2 or 3 inches. Likewise, in the configuration of being a lengthwise bandage or rolled tape, such as to be used to cover lengthwise wounds or surfaces, the flexible material can range in width from about 1/2 inch to about 4 or 5 inches or more, although preferred widths in embodiments may be from about 1 to about 2 or 3 inches, and can range in length from about 1 inch to about 6 or 8 inches or more, although preferred lengths in embodiments may be from about 2 to about 4 or 5 inches. However, a particular advantage of this embodiment is that the flexible material may be used to form a composite structure over a longer wound, such as a long laceration on incision. As such, embodiments of the present invention can provide a flexible material having a length exceeding 8 or even 12 inches, such as ranging in lengths up Oct. 16, 2008 to 18 inches, 24 inches, 30 inches, or more. When provided in the configuration of a roll, the flexible material can have virtually any practical length, such as 5, 6, 8, 10, or 12 feet or more, which can be cut to desired length at the time of use. Of course, it will be apparent that the materials of the present invention are not limited to any particular dimensions, and that the dimensions (length, width, thickness, etc.) of the flexible material can be varied and tailored, as desired. [0038] As such, various sized flexible materials can be pre- pared and packaged for use. For example, shorter length materials (for example, in lengths up to about 2, 3 or 4 inches) can be prepared and packaged for use in “short laceration” applications, while longer length materials (for example, in lengths up to about 10, 15, 20 or 30 inches) can be prepared and packaged for use in “long laceration” applications. In other embodiments, a variety of length materials can be pro- vided, with the intention that the materials are single use materials, where any leftover length of the flexible material is discarded. Such single-use embodiments are particularly desirable where the flexible material is sterilized, and sterility is desired to be maintained until the time of use. In other embodiments, such as where sterility is not a requirement, a longer length of flexible material can be provided where any unused portion can be saved for later use. [0039] Still other configurations for the flexible material will be apparent to those skilled in the art. For example, although described above as being in rectangular or square configurations, the flexible substrate can take any number of other shapes, which can be designed for particular applica- tions. For example, circular or round (disc-shaped) flexible materials can be used, such as to cover blister bases, sores, or the like; arc-shaped (curved rectangular shaped) flexible materials can be used, such as to cover curved lacerations or incisions; and the like. Other shapes, such as oval, triangular, polygonal, semi-circular, and the like, can also be used, in embodiments. [0040] Preferably, the flexible material does not include additional structures for attaching the flexible material to the desired application or treatment site. Thus, for example, the flexible material does not further include other physical attachment means such as hooks, barbs, pins, projections, or the like, which operate to physically latch or otherwise attach the flexible substrate to the desired application or treatment site. Such attachment means are not desired, for example, because they introduce additional trauma to the underlying surface. Thus, it is preferred that the flexible material not include features that penetrate even surface layers of the underlying substrate, such as dermal layers of the skin. [0041] According to the present invention, the flexible material includes one or more chemical materials located within the flexible material. For example, one or more chemi- cal substances can be dispersed in the flexible material, such as being chemically bound, physically bound, absorbed, or adsorbed to the flexible material. Thus, for example, the flex- ible material includes at least a polymerization initiator or rate modifier, and can optionally include one or more bioac- tive materials. As desired, the one or more chemical sub- stances can be either immobilized on the flexible material, for example so that it has a desired effect but is not detached from the flexible material during use, or it can be attached to the flexible material in a manner such that it becomes detached during use. [0042] For example, according to the present invention, a polymerization initiator or rate modifier is loaded on the US 2008/0255610 Al flexible material, so that the initiator or rate modifier provides the desired initiation or rate modification effect to a subse- quently applied polymerizable adhesive composition. The polymerization initiator or rate modifier can be immobilized on the flexible material, so that the initiator or rate modifier does not become detached from the flexible material and its residues dispersed in the resultant polymeric material. Alter- natively, for example, the polymerization initiator or rate modifier may be initially attached to the flexible material, but only in such a manner that it becomes mobilized or solubi- lized by a subsequently applied polymerizable adhesive com- position and dispersed in the resultant polymeric material. [0043] If desired, a combination of chemical substances can also be provided on the flexible material, to provide multiple effects. For example, as described above, a first chemical species (such as a polymerization initiator or rate modifier) can be immobilized on the flexible material, while a second, different chemical species (such as a bioactive material) can be detachably attached to the flexible material. Other combinations of chemical species and resultant effects are also envisioned by the present invention. [0044] When present in or on the flexible material, the chemical substances (i.e., polymerization initiator, rate modi- fier, and/or bioactive materials, or other additives), can be incorporated in or on the flexible material in any suitable manner. For example, the chemical substance can be added to the flexible material by contacting the flexible material with a solution, mixture, or the like including the chemical sub- stances. The chemical substance can be added to the flexible material, for example, by dipping, spraying, roll coating, gravure coating, brushing, vapor deposition, or the like. Alter- natively, the chemical substance can be incorporated into or onto the flexible material during manufacture of the flexible material, such as during molding or the like of the flexible material. [0045] The chemical substance can be present in or on the flexible material in any suitable concentration and manner. For example, the chemical substance can be applied in a uniform manner to the flexible material, such that there is a substantially uniform concentration of the chemical sub- stance across the flexible material. Altematively, the chemical substance can be applied such that a concentration gradient exists across or through the flexible material. For example, a greater or smaller concentration of the chemical substance could exist at the center or edges of the flexible material, or a greater or smaller concentration of the chemical substance could be applied on one side of the flexible material as com- pared to an opposite side. Further, the chemical substance can be applied in a uniform manner to the flexible substrate, or it can be applied in a non-uniform random or pattemed manner (such as lines, dots, concentric circles, or the like). [0046] Other chemical substances that can be present in or on the flexible material include, but are not limited to, any suitable and preferably compatible additive that enhances performance of the composite structure. Such additional chemical substances can be bioactive or non-bioactive. Suit- able other chemical substances thus include, but are not lim- ited to, colorants (such as inks, dyes and pigments), scents, protective coatings that do not chemically detach, tempera- ture sensitive agents, drugs, and the like. [0047] The present invention, by virtue of the polymeriza- tion initiator or rate modifier being loaded on the flexible material, provides a number of advantages over the prior art. For example, the structure of the present invention, in Oct. 16, 2008 embodiments, allows for tailoring of the setting or polymer- ization time of the applied polymerizable adhesive composi- tion. For example, as is well known in the art, the type and/or concentration of initiator that is applied to the flexible mate- rial can be selected so as to provide faster or slower polymer- ization time. For example, the concentration of polymeriza- tion initiator or rate modifier can be increased to provide a faster polymerization time, or can be decreased to provide a slower polymerization time. [0048] Other properties of the polymerization can also be adjusted, in embodiments. For example, the polymerization can be made more uniform than previously possible, at least because the polymerization initiator or rate modifier is gen- erally more uniformly applied to the flexible material. The cure temperature of the polymerizable adhesive composition can also be more easily tailored. For example, the initiator type and/or concentration can be selected to provide a desired polymerization or set time, while not generating excessive heat that could damage the underlying application surface. [0049] These embodiments are preferred over at least some embodiments of the prior art. In the prior art, one method of applying a polymerizable adhesive composition was to apply the polymerizable adhesive composition to a substrate, and allow polymerization to be initiated by moisture of other species that may naturally be present. This often created long polymerization or set times, and led to undesirable results. For example, if tissue surfaces were being joined, the tissue surfaces would need to be physically held in place longer while the slow polymerization progressed, to avoid the wound from being opened. In such methods, polymerization time often varied from use to use, and thus was less reliable. [0050] The present invention also provides, in embodi- ments, a longer working time for the polymerizable adhesive composition that is being used. Because the polymerization initiator or rate modifier is loaded directly on the flexible material, it is not necessary to mix the polymerizable adhesive composition with a polymerization initiator or rate modifier in an applicator prior to application. Thus, the applicator of the polymerizable adhesive composition does not suffer from the drawback of becoming plugged and unusable as polymer- izable adhesive composition polymerizes in an applicator tip. This can allow a longer working time, where the polymeriz- able monomer composition can be more precisely and care- fully applied over a longer period of time. [0051] These embodiments are thus likewise preferred over at least some other embodiments of the prior art. In the prior art, another method of applying a polymerizable adhesive composition was to apply the polymerizable adhesive com- position through a porous applicator tip. The porous applica- tor tip is loaded with polymerization initiator or rate modifier, such that the polymerizable adhesive composition and poly- merization initiator or rate modifier mix in the applicator tip. A drawback is that because the materials mix in the applicator tip, polymerization starts in the applicator tip. Accordingly, material within the applicator tip begins to polymerize, and can rapidly plug or clog the applicator tip, rendering the applicator and any further polymerizable adhesive composi- tion contained therein unusable. Such embodiments accord- ingly required faster use of the adhesive composition, and higher waste of adhesive composition. [0052] In other embodiments, the present invention also provides still further operational advantages. For example, because the textile material tends to trap or act as a barrier to flow of the polymerizable adhesive composition, there is less US 2008/0255610 Al running of the adhesive composition away from the applica- tion site. In addition, where one or more chemical substances are present in or on the textile, such chemical substances can be more specifically or precisely applied to the textile. For example, the chemical substances can be applied to the textile material only at specific locations, or in a gradient pattern, if desired. In these and other embodiments, the present inven- tion provides a stronger composite structure than is provided by a polymerizable adhesive composition alone. [0053] The above advantages, alone or in combination, can be provided by various embodiments of the present invention. [0054] A method for using the flexible substrate and result- ant composite structure will now be described. [0055] The materials of the present invention are advanta- geously used as wound dressings. For example, the materials of the present invention are advantageously used as replace- ments for conventional bandages, or as replacements for con- ventional use of sutures and staples for closing wounds. As compared to conventional bandages, the flexible material of the present invention generally provides the same wound approximation and pressure benefits. However, because the flexible material is used to provide a composite structure by the addition of a polymerizable adhesive composition, the resultant composite structure provides significant benefits over the conventional bandage in terms of improved wound management, stronger adhesion to the underlying application site, microbial barrier properties, improved patient satisfac- tion, and the like. According to embodiments of the present invention, a polymerizable adhesive material is applied to the upper surface of the flexible material, which subsequently permeates through the flexible material (or at least through openings such as voids or pores in the flexible material) as the adhesive polymerizes, to form a flexible, adherent wound dressing. If desired, a first amount of a polymerizable adhe- sive material can be applied to the application site prior to applying the flexible material. The result is a unitary compos- ite structure over the wound. Furthermore, as compared to conventional sutures and staples, the composite structure of the present invention also generally provides the same wound approximation and pressure benefits. However, because the composite structure uses a polymerizable adhesive composi- tion rather than punctures for adhesion to the underlying application site, the resultant composite structure provides significant benefits over the conventional sutures and staples in terms of improved wound management, stronger adhesion to the underlying application site, microbial barrier proper- ties, improved patient satisfaction, less tissue trauma (since additional punctures are not made), lessened scarring, and the like. [0056] The materials of the present invention can also be advantageously used in non-medical or non-healthcare set- tings. For example, the materials of the present invention can also advantageously be used in commercial or household settings, where the flexible material/polymerizable adhesive composition composite structure can be used to provide stronger adhesion. [0057] One method according to the present invention is described below. The method is described with reference to closing and covering a wound on a tissue surface. However, the invention is not limited to this embodiment. [0058] In a first step, the application site, such as a wound or the like, is preferably cleaned by removing excess exudates (blood or the like) to provide as dry a wound as possible to assist in wound closure. Oct. 16, 2008 [0059] In a second step, a portion of flexible material is provided. Preferably, the length and width of the flexible material is longer and wider than the wound to be closed, and extend beyond opposite ends of the wound a sufficient dis- tance to permit suflicient bonding. Thus, for example, the length of flexible material is preferably suflicient to extend at least 1/4 inch, more preferably at least 1/2 inch or at least 3/: inch, and even more preferably at least one inch beyond each end of the wound. Furthermore, the flexible material is pref- erably wide enough to extend beyond each lateral edge of the wound throughout the length of the wound. The width of the flexible material is preferably wide enough that the entire wound is covered, with excess coverage, by the flexible mate- rial. That is, the flexible material preferably covers the full width of the wound, and extends beyond opposite lateral edges of the wound a suflicient distance to permit sufficient bonding. Thus, for example, the width of flexible material is preferably suflicient to extend at least 1/4 inch, more prefer- ably at least 1/2 inch or at least 3/: inch, and even more pref- erably at least one inch beyond each lateral edge of the wound. [0060] In the second step, the flexible material is applied over the wound or desired surface. For ease of application, the surface is preferably horizontal, to help avoid slipping of the flexible material from the application site prior to complete polymerization of the subsequently applied polymerizable adhesive composition. However, where horizontal applica- tion is not possible or practical, the flexible material can be held in place by any suitable means including, but not limited to, by hand, forceps, tape, pressure sensitive adhesive, pres- sure, vacuum, or the like. [0061] In a modification of this application method, a por- tion of a polymerizable adhesive material is applied to the application site prior to applying the flexible material. When so applied, the polymerizable adhesive material is preferably not allowed to fully polymerize prior to application of the flexible material and subsequent application of further amounts of polymerizable adhesive material. The polymeriz- able adhesive material applied prior to application of the flexible material can be the same as or different from the polymerizable adhesive material subsequently applied to the flexible material. [0062] In a third step, a polymerizable adhesive composi- tion, such as a polymerizable monomeric adhesive composi- tion, is applied over at least a portion of the surface of the flexible material. Preferably, the polymerizable adhesive composition is applied to fully cover the surface of the flex- ible material. However, if desired, a lesser amount of the polymerizable adhesive composition can be used to conserve materials and assist in subsequent removal. For example, if a portion of the flexible material is not covered by the polymer- izable adhesive composition, that portion can be used either to maintain control over the flexible material during placement and polymerization, and then subsequently trimmed off, or it can be maintained and used as a tab to assist in subsequent removal (such as by sloughing off or peeling off of the com- posite structure, or by the use of a remover substance). In this instance, the polymerizable adhesive composition is prefer- ably applied to the flexible material at least in an area sufli- cient to cover the underlying wound or substrate. [0063] In this step of applying the polymerizable adhesive composition, a suflicient amount of polymerizable adhesive composition should be applied to form the desired composite structure once the polymerizable adhesive composition has US 2008/0255610 A1 polymerized (or cured). Thus, for example, the amount of polymerizable adhesive composition should be suflicient to preferably allow the composition to penetrate through the flexible material to form a continuous coating between the flexible material and substrate, which continuous coating subsequently polymerizes or cures to form a continuous poly- meric coating between the flexible substrate and the underly- ing surface. The quantity of polymerizable adhesive compo- sition should preferably further allow for a quantity of the composition to remain in, and preferably over, the flexible material. This further amount of polymerizable adhesive composition polymerizes or cures with the remaining poly- merizable adhesive composition to provide a unitary compos- ite structure that is bonded to the underlying surface. [0064] If necessary or desired, the step of applying poly- merizable adhesive composition to the flexible material can be repeated one or more times. Thus, for example, a second or subsequent coating of the polymerizable adhesive composi- tion can be applied, either prior or subsequent to complete curing of the underlying layer of polymerizable adhesive composition. Preferably, where multiple layers are to be applied, it is preferred that sub sequent layers be applied after curing of the underlying layer has begun, but before curing is complete. If desired or necessary, subsequent layers of poly- merizable adhesive material can be applied with an added polymerization initiator or rate modifier, to assist in polymer- ization of the adhesive composition. [0065] As appropriate, the polymerizable adhesive compo- sition can be applied to the flexible material either in the form of a continuous coating, or as discrete dots or dabs. For example, the discrete dots or dabs can be used either where the polymerizable adhesive composition is of high viscosity, and it is desired that the composite structure retain such discrete areas of adhesion, or where the polymerizable adhe- sive composition is of low viscosity such that the discrete dots or dabs will readily flow to form a continuous coating. A continuous coating can be assisted, for example, by spreading the applied polymerizable adhesive composition to any extent necessary. [0066] However, if a continuous coating is desired when applying the polymerizable adhesive composition to the flex- ible material, the polymerizable adhesive composition is preferably applied over an entire surface of the flexible mate- rial. That is, while the flexible material may provide some wicking, flowing, or capillary movement of the polymeriz- able adhesive composition within the bulk material of the flexible substrate, such wicking or capillary movement is minimal, and is not intended to provide complete coverage of the polymerizable adhesive composition over the flexible material. Thus, for example, it will generally not be possible to apply one or two drops of the polymerizable adhesive composition to the flexible material, and expect the polymer- izable adhesive composition to completely cover the flexible material (unless, of course, the flexible material is such a small size that the drops substantially cover the surface). Rather, in embodiments of the present invention, the poly- merizable adhesive composition is applied by dabbing, brushing, rolling, painting, swabbing or the like, the polymer- izable adhesive composition onto the flexible material. If necessary, the applied polymerizable adhesive composition can be spread around on the surface of the flexible material to provide improved coverage. [0067] Once the polymerizable adhesive composition is cured, it forms a composite structure with the flexible mate- Oct. 16, 2008 rial, covering the desired surface. The composite structure is adherent to the underlying surface, and provides the benefits described above. [0068] Of course, although the invention is described with respect to the above application method, other methods will be readily apparent to those skilled in the art. The application methods are in no way limited to the methods described above. [0069] As described above, one or more additives may be applied to the flexible substrate, which can subsequently chemically or physically interact with an applied polymeriz- able adhesive composition. Such chemical substances can include, for example, one or more polymerization initiators or rate modifiers, one or more additive materials, combinations thereof, and the like. According to the present invention, in embodiments, the flexible material is at least loaded or impregnated with one or more polymerization initiators or rate modifiers, as described above, to provide polymerization initiation to the subsequently applied polymerizable adhesive composition. [0070] Suitable polymerization and/ or cross-linking initia- tors and rate modifiers, and methods for applying them to substrates, are described in, for example, U.S. Pat. Nos. 5,928,611, 6,352,704, 6,455,064, 6,579,469 and 6,595,940 and U.S. patent applications Ser. Nos. 09/430,177, filed Oct. 29, 1999, 09/430,289; 09/385,030 filed Aug. 30, 1999; and 09/176,889 filed Oct. 22, 1998, the entire disclosures of which are incorporated herein by reference. Preferred initia- tors for some medical uses include benzalkonium chloride, benzyldimethylhexa-decylamrnonium chloride, and for some industrial uses include dimethyl toluidine. [0071] Particular initiators and rate modifiers for particular monomers may be readily selected by one of skill in the art without undue experimentation. Control of the molecular weight distribution of the applied adhesive can be enhanced by selection of the concentration and functionality of the initiator or rate modifier vis-a-vis the selected monomer. Suit- able polymerization initiators and rate modifiers for cyanoacrylate compositions include, but are not limited to, detergent compositions; surfactants, including nonionic sur- factants such as polysorbate 20 product (e.g., Tween 20TM product; ICI Americas), polysorbate 80 product (e.g., Tween 80TM product; ICI Americas), and poloxamers; cationic sur- factants such as tetrabutylamrnonium bromide; anionic sur- factants, including quaternary ammonium halides such as benzalkonium chloride or its pure components, and benze- thonium chloride; stannous octoate (tin (H) 2-ethylhex- anoate), and sodium tetradecyl sulfate; and amphoteric or zwitterionic surfactants such as dodecyldimethyl(3-sulfopro- pyl) ammonium hydroxide, inner salt; amines, imines, and amides, such as imidazole, tryptamine, urea, arginine and povidine; phosphines, phosphites and phosphonium salts, such as triphenylphosphine and triethyl phosphite; alcohols such as ethylene glycol; methyl gallate; ascorbic acid; tannins and tarmic acid; inorganic bases and salts, such as sodium bisulfite, magnesium hydroxide, calcium sulfate and sodium silicate; sulfur compounds such as thiourea and polysulfides; polymeric cyclic ethers such as monensin, nonactin, crown ethers, calixarenes and polymeric epoxides; cyclic and acy- clic carbonates, such as diethyl carbonate; phase transfer catalysts such as AliquatTM 336 (General Mills, lnc., Minne- apolis, Minn.); organometallics; manganese acetylacetonate; radical initiators and radicals, such as di-t-butyl peroxide and azobisisobutyronitrile; and bioactive compounds or agents. US 2008/0255610 A1 [0072] In preferred embodiments, the initiator may be a bioactive material (i.e., a material that affects a surrounding biological environment in addition to acting as a polymeriza- tion initiator), including quatemary ammonium halides such as alkylbenzyldimethylamrnonium chloride (benzalkonium chloride; BAC) its pure components, or mixtures thereof, especially those with an alkyl containing 6-18 carbon atoms; benzethonium chloride; and salts of sulfadiazine. Cobalt napthenate can be used as an accelerator for peroxide. [0073] In preferred embodiments, the initiator may also be a bioactive material that possesses antiviral, antimicrobial, antifungal and/or wound healing properties. An example of such a material that possesses polymerization initiation and antiviral, antimicrobial, and/or antifungal properties is Gen- tian Violet, also known as crystal violet or methylrosaniline chloride. Examples of materials that possess polymerization initiation and wound healing properties also include various zinc complexes and zinc salts, antioxidants such as vitamin E and other vitamins and the like, and copper compounds such as copper chloride, copper sulfate and copper peptides. Such materials are particularly preferredbecause they can serve not only as the polymerization initiator or rate modifier for the cyanoacrylate monomer, they can also provide additional benefits to the wound site, such as antiviral effects, antimi- crobial effects and/or antifungal effects or help to promote wound healing. [0074] When zinc compounds are present, the zinc com- pound can be present in various forms, such as zinc salts. For example, suitable zinc compounds include, but are not limited to, zinc salts of cyanoacrylic acid, zinc salts of cyanoacetic acid, zinc salts of dicyanoglutaric acid, zinc salts of rosin, zinc oxide, zinc salts of polycyanoacrylic acid, zinc salts of poly- acrylic acid, zinc bacitracin, zinc salicylate, zinc stearate, zinc citrate, zinc lactate, mixtures thereof, and the like. Pref- erably, the zinc compounds are ofZn2+. Incorporation of such zinc compounds into the polymerizable adhesive composi- tion is particularly effective in promoting wound healing of leg ulcers, thermal bums, and the like. [0075] The polymerizable adhesive composition and/ or the flexible material may also contain an initiator and/or a rate modifier which is inactive until activated by a catalyst or accelerator (included within the scope of the term “initiator” as used herein). Initiators activated by stimulation such as heat and/or light (e.g., ultraviolet or visible light) are also suitable if the flexible material is appropriately subjected to such stimulation. [0076] In addition to the polymerization and/ or cross-link- ing initiator and/ or rate modifier, the flexible material can also include various other materials that may or may not act as a polymerization initiator and/or rate modifier. For example, the flexible material can include a bioactive material, which may or may not also be a polymerization and/or cross-linking initiator and/or rate modifier. Thus, in embodiments, the ini- tiator and/or the rate modifier can be, but does not have to be, bioactive. In embodiments where the initiator and/ or the rate modifier is bioactive, the method of the invention can be used to close, cover, or protect tissue and wounds while simulta- neously providing a bioactive material to the tissue or wound. [0077] Suitable bioactive materials include, but are not lim- ited to, medicaments such as antibiotics, antimicrobials, anti- septics, bacteriocins, bacteriostats, disinfectants, steroids, anesthetics, antifungal agents, anti-inflammatory agents, antibacterial agents, antiviral agents, antitumor agents, growth promoting substances, antioxidants, or mixtures Oct. 16, 2008 thereof. Such compounds include, but are not limited to, acetic acid, aluminum acetate, bacitracin, bacitracin zinc, benzalkomum chloride, benzethonium chloride, betadine, calcium chloroplatinate, certrimide, cloramine T, chlorhexi- dine phosphanilate, chlorhexidine, chlorhexidine sulfate, chloropenidine, chloroplatinatic acid, ciprofloxacin, clinda- mycin, clioquinol, cysostaphin, gentamicin sulfate, hydrogen peroxide, iodinated polyvinylidone, iodine, iodophor, minocycline, mupirocin, neomycin, neomycin sulfate, nitro- furazone, non-onynol 9, potassium permanganate, penicillin, polymycin, polymycin B, polymyxin, polymyxin B sulfate, polyvinylpyrrolidone iodine, povidone iodine, 8-hydrox- yquinoline, quinolone thioureas, rifampin, rifamycin, copper chloride, copper sulfate, copperpeptides, silver acetate, silver benzoate, silver carbonate, silver chloride, silver citrate, sil- ver iodide, silver nitrate, silver oxide, silver sulfate, sodium chloroplatinate, sodium hypochlorite, sphingolipids, tetracy- cline, zinc oxide, salts of sulfadiazine (such as silver, sodium, and zinc), antioxidants such as vitamins such as vitamin E, other agents mentioned above, and mixtures thereof. Prefer- able bioactive materials are USP approved, more preferably USP monographed. [0078] As described above, the polymerization and/or cross-linking initiator and/or rate modifier, and/ or the bioac- tive material, may be applied to the flexible material by any suitable means, including, but not limited to, spraying, dip- ping, injecting, or brushing the flexible material with a liquid medium containing the material to be applied. [0079] As also described above, the composite structure is formed by applying a polymerizable adhesive composition to the flexible material, and allowing the polymerizable adhe- sive composition to polymerize. Polymerization of the poly- merizable adhesive composition is initiated, or assisted, by the polymerization initiator or rate modifier that was previ- ously loaded on the flexible material. [0080] The polymerizable (i.e., monomer and/or prepoly- meric) adhesive composition may include one or more poly- merizable monomers, which preferably are synthetic or semi- synthetic monomers. Preferred monomers that may be used in this invention are readily polymerizable, e.g. amonically polymerizable or free radical polymerizable, or polymeriz- able by zwitterions or ion pairs to formpolymers. Such mono- mers include those that forrn polymers, that may, but do not need to, biodegrade. Such monomers are disclosed in, for example, U.S. Pat. Nos. 5,328,687, 5,928,611 and 6,183,593, U.S. patent application Ser. No. 09/430,177, filed on Oct. 29, 1999, and U.S. Pat. No. 6,183,593, which are hereby incor- porated in their entirety by reference herein. [0081] Preferred monomers include 1,1-disubstituted eth- ylene monomers, such as 01-cyanoacrylates including, but not limited to, alkyl ot-cyanoacrylates having an alkyl chain length of from about 1 to about 20 carbon atoms or more, preferably from about 3 to about 8 carbon atoms. [0082] The 01-cyanoacrylates of the present invention can be prepared according to several methods known in the art. U.S. Pat. Nos. 2,721,858, 3,254,111, 3,995,641, and 4,364, 876, each of which is hereby incorporated in its entirety by reference herein, disclose methods for preparing 0t-cy- anoacrylates. [0083] Preferred ot-cyanoacrylate monomers used in this invention include methyl cyanoacrylate, ethyl cyanoacrylate, n-butyl cyanoacrylate, 2-octyl cyanoacrylate, methoxyethyl cyanoacrylate, ethoxyethyl cyanoacrylate, dodecyl cyanoacrylate, 2-ethylhexyl cyanoacrylate, butyl cyanoacry- US 2008/0255610 A1 late, 3-methoxybutyl cyanoacrylate, 2-butoxyethyl cyanoacrylate, 2-isopropoxyethyl cyanoacrylate, 1-meth- oxy-2-propyl cyanoacrylate, hexyl cyanoacrylate, or dode- cylcyanoacrylate. [0084] Other suitable cyanoacrylates for use in the present invention also include, but are not limited to, alkyl ester cyanoacrylate monomers such as those having the formula CN HZC o 0 R1 0 1. wherein R1 and R2 are, independently H, a straight, branched or cyclic alkyl, or are combined together in a cyclic alkyl group, and R3 is a straight, branched or cyclic alkyl group. Preferably, R1 is H or a C1, C2 or C3 alkyl group, such as methyl or ethyl; R2 is H or a C1, C2 or C3 alkyl group, such as methyl or ethyl; and R3 is a C1 -C1 6 alkyl group, more prefer- ably a C1-C10 alkyl group, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl or decyl, and even more preferably a C2, C3 or C4 alkyl group. Such alkyl ester cyanoacrylates and other suitable monomers are disclosed in, for example, U.S. patent application Ser. No. 09/919,877, filed Aug. 2, 2001, and U.S. Pat. No. 6,620,846, the entire disclosures of which are incorporated herein by reference. [0085] Examples of preferred alkyl ester cyanoacrylates include, but are not limited to, butyl lactoyl cyanoacrylate (BLCA), butyl glycoloyl cyanoacrylate (BGCA), ethyl lac- toyl cyanoacrylate (ELCA), and ethyl glycoloyl cyanoacry- late (EGCA). BLCA may be represented by the above for- mula, wherein R1 is H, R2 is methyl and R3 is butyl. BGCA may be represented by the above formula, wherein R1 is H, R2 is H and R3 is butyl. ELCA may be represented by the above formula, wherein R1 is H, R2 is methyl and R3 is ethyl. EGCA may be represented by the above formula, wherein R1 is H, R2 is H and R3 is ethyl. [0086] The composition may optionally also include at least one other plasticizing agent that assists in imparting flexibility to the polymer formed from the monomer. The plasticizing agent preferably contains little or no moisture and should not significantly affect the stability or polymer- ization of the monomer. Examples of suitable plasticizers include but are not limited to tributyl citrate, acetyl tri -n-butyl citrate (ATBC), polymethylmethacrylate, polydimethylsilox- ane, hexadimethylsilazane and others as listed in U.S. Pat. No. 6,183,593, the disclosure of which is incorporated in its entirety by reference herein. [0087] The composition may also optionally include at least one thixotropic agent. Suitable thixotropic agents are known to the skilled artisan and include, but are not limited to, silica gels such as those treated with a silyl isocyanate, and optionally surface treated titanium dioxide. Examples of suit- able thixotropic agents and thickeners are disclosed in, for example, U.S. Pat. No. 4,720,513, and U.S. Pat. No. 6,310, 166, the disclosures of which are hereby incorporated in their entireties by reference herein. Oct. 16, 2008 [0088] The composition may optionally also include thick- eners. Suitable thickeners may include poly(2-ethylhexyl methacrylate), poly(2-ethylhexyl acrylate) and others as listed in U.S. Pat. No. 6,183,593, the disclosure of which is incorporated by reference herein in its entirety. [0089] The composition may also optionally include at least one natural or synthetic rubber to impart impact resis- tance. Suitable rubbers are known to the skilled artisan. Such rubbers include, but are not limited to, dienes, styrenes, acry- lonitriles, and mixtures thereof. Examples of suitable rubbers are disclosed in, for example, U.S. Pat. Nos. 4,313,865 and 4,560,723, the disclosures of which are hereby incorporated in their entireties by reference herein. [0090] The composition may optionally also include one or more stabilizers, preferably both at least one anionic vapor phase stabilizer and at least one anionic liquid phase stabi- lizer. These stabilizing agents may inhibit premature poly- merization. Suitable stabilizers may include those listed in U.S. Pat. No. 6,183,593, the disclosure of which is incorpo- rated by reference herein in its entirety. Furthermore, certain stabilizers may also function as anti-microbial agents, such as, for example, various acidic anti-microbials, as identified above. [0091] The compositions may also include pH modifiers to control the rate of degradation of the resulting polymer, as disclosed in U.S. Pat. No. 6,143,352, the entire disclosure of which is hereby incorporated by reference herein in its entirety. [0092] To improve the cohesive strength of adhesives formed from the compositions of this invention, difunctional monomeric cross-linking agents may be added to the mono- mer compositions of this invention. Such crosslinking agents are known. U.S. Pat. No. 3,940,362 to Overhults, which is hereby incorporated herein in its entirety by reference, dis- closes exemplary cross-linking agents. [0093] The compositions of this invention may further con- tain colorants such as dyes, pigments, and pigment dyes. [0094] The polymerizable compositions useful in the present invention may also further contain one or more pre- servatives, for prolonging the storage life of the composition. Suitable preservatives, and methods for selecting them and incorporating them into adhesive compositions, are disclosed in U.S. patent application Ser. No. 09/430,180, the entire disclosure of which is incorporated herein by reference. Such preservatives can be in addition to any anti-microbial agent that may or may not be added to the composition. Such preservatives can be included irrespective of whether the composition and containers are sterilized. [0095] In embodiments, the materials and processes of the present invention provide significant advantages over the cur- rent materials and methods for wound closure. These advan- tages include, among others, improved wound closure, improved wound approximation, improved strength, ability to use on longer wounds, less run-off of adhesive, longer working time, provision of an improved durable microbial barrier, reduced procedure time, improved cosmesis, less pain (during staple/ suture removal) resulting in increased patient satisfaction, and improved financial/economic outcomes by eliminating follow-up visits for staple/ suture removal. [0096] The materials and processes of the present invention provide improved wound closure. Because the composite structure provides a flexible polymeric covering over the wound site, it provides a degree of tension to assist in closing the wound and maintain the wound closed. By a combination US 2008/0255610 A1 of the flexible material within the composite structure, and the rigidity and adhesion provided by polymerization of the poly- merizable adhesive composition, the composite structure pro- vides improved strength, decreases wound dehiscence, and assists healing. [0097] The materials and processes of the present invention also provide an improved microbial barrier. Because the com- posite structure fully covers the wound, microbial transport into and out of the wound are decreased. This in tum helps battle or prevent infection, in tum resulting in faster wound healing. [0098] The materials and processes of the present invention also provide improved cosmesis. Such cosmesis benefits includes improved cosmetic appearances both during and after the wound healing process. For example, during wound healing, the composite structures of the present invention provide decreased dressing bulk and thickness and improved appearance. Furthermore, because the composite structures permit more precise and sustained wound approximation, the composite structures can provide decreased scar appearance, such as in terms of scar width, scar tissue height, scar colora- tion, and the like. [0099] Related to the above advantages, the materials and processes of the present invention provide increased patient satisfaction. Increased satisfaction is provided, for example, due to the improved cosmetic results, and improved assurance of wound closure and dressing strength, and the like. In addi- tion, because of the strong bond provided, the composite structure of the present invention is expected to remain in place over an external wound for about 10 to 14 days, although shorter or longer times may be provided. During that time, the patient can bathe without worrying about water and contaminants entering the wound through the dressing. Fur- thermore, because staple or suture removal is not required, the patient experiences less pain and anticipation, improving the healing experience. [0100] The present invention is thus applicable to a wide range of treatments, including wound treatment and other medical procedures. For example, the present invention can be used as a replacement for, or in addition to, sutures or staples to join together two surfaces. The invention can also be used to coat, protect, or otherwise cover surface, superfi- cial, intemal, or topical wounds including, but not limited to, minor cuts, scrapes, irritations, compromised skin, superfi- cial lacerations, abrasions, burns, sores, and stomatitis. The methods of the invention can also be used on tissues that do not show any signs of tissue damage. For example, the meth- ods can be used to deliver medicaments to a patient through healthy tissue. They can also be used, for example, to locally deliver medicaments to tissues such as tumors or organs. [0101] Specific embodiments of the invention will now be described in detail. These Examples are intended to be illus- trative, and the invention is not limited to the materials, con- ditions, or process parameters set forth in these embodiments. All parts and percentages are by weight unless otherwise indicated. EXAMPLES Example 1 [0102] The working and setting times of the inventive com- posite device, using a flexible textile material and a cyanoacrylate polymerizable adhesive formulation, are com- pared to the working and setting times of conventional avail- Oct. 16, 2008 able cyanoacrylate devices. The conventional available cyanoacrylate devices used are the DERMABOND® topical skin adhesive products comprising a polymerizable monomer dispersed from an applicator having a porous tip containing polymerization initiator. Two DERMABOND® adhesive formulations are tested namely, a low viscosity adhesive for- mulation, referred to here as DERMABOND LV and a high viscosity adhesive formulation, referred to here as DERMA- BOND HV (both manufactured by Closure Medical Corpo- ration and available from Ethicon). The composite devices of the present invention are also prepared using the cyanoacry- late polymerizable adhesive compositions of the DERMA- BOND LV and DERMABOND HV formulations, with the cyanoacrylate polymerizable adhesive compositions being extracted from the commercial applicators so that the com- position does not contact polymerization initiator that is present in the applicator tips. These extracted cyanoacrylate polymerizable adhesive compositions are referred to here as “composite adhesive formulations”. [0103] Working time is a measurement of the time during which the polymerizable adhesive composition can be expressed as a liquid from the application device. Once the working time has expired, the adhesive has polymerized within the applicator, clogging or plugging the applicator tip. Setting time is the time required for the adhesive to polymer- ize on a substrate once it has been applied. [0104] Synthetic SPECTRA MESH® filtration material (available from Spectrum Laboratories, Inc .), a textile with 70 um pores (openings) and an open area of 36%, is cut into strips 1.0 cm>8 hours 49.6 2 10.2 50.1 2 5.9 Composite Control >8 hours >5400 ND (non-detectable) [0109] Evaluation of the data presented in the table reveals the effects of the initiation method used in the cyanoacrylate textile (mesh) composite on both working and setting times, and the resulting composite structure. Initiation of the adhe- sive polymerization using initiator immobilized within the mesh, instead of initiator contained within a porous applicator tip, dramatically increases the working time of the adhesive. Commercially-available DERMABOND® adhesive applica- tors have a working time that is determined by the polymer- ization time of the adhesive within the initiated applicator. The inventive composite formulation does not require an initiated application tip. The initiator is present within the mesh, and initiation of the adhesive occurs only on the sub- DERMABOND LV DERMABOND LV DERMABOND HV DERMABOND LV without increasing setting temperatures, something that would not be possible using conventional application devices that include initiator in the applicator tip. To decrease setting time using current applicator technology, the amount of im- tiator in the porous applicator tip would have to be signifi- cantly increased, which would be accompanied by a con- comitant increase in the associated setting temperature. Having initiator evenly distributed throughout the textile alters initiation and polymerization kinetics, facilitating more efiicient initiator-adhesive mixing. This improved mixing configuration serves to lower setting times while maintaining low setting temperatures. In addition, this mixing configura- tion enables improved control of setting time and temperature through controlled distribution of initiator within the com- posite. As a result, the composite structure can be formed as a wound covering and closure device in a manner that is quick (i.e., that has a fast setting time) and easier to apply (longer working time), but which remain comfortable to the patient (i.e., as not having a significantly high setting temperature). [0111] The above improvements provided by the present invention also provide valuable benefits to medical profes- sionals or other using the methods and devices of the inven- tion. For example, the faster setting time enables medical professionals to apply the composite structure as a wound closure device much faster than previously possible, freeing up the medical professional to proceed to other tasks and to speed the treatment process, providing faster and more effi- cient procedures. This in tum could result in lower operating room and treatment costs, and reduced patient and insurance charges. Example 2 [0112] The tensile strength of film samples of DERMA- BOND LV adhesive are compared to the tensile strength of Composite A, described in Example 1 above. US 2008/0255610 A1 [0113] Thin films of DERMABOND LV adhesive are pre- pared by expressing the adhesive from a DERMABOND LV applicator onto a glass plate. Subsequently, a second glass plate of the same size is placed on top of the adhesive such that the adhesive is pressed between the two plates. Once the adhesive polymerizes, the glass plates are separated and the film of adhesive is removed. This film was then cut into strips with dimensions 4.0 inch>X< * >X< *