Adhesive-Containing Wound Closure Device and Method

US20090076542

By:

Jerry Jonn

Glenn Hoskin

Folder:

Year:

Abstract:

A tissue bonding article includes a flexible material, an adhesive substance applied over at least a portion of a bottom side of the flexible material, and a polymerizable adhesive composition permeated throughout at least a portion of the flexible material.

Language:

English

url:

http://www.google.com/patents/US20090076542

US 20090076542A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0076542 A1 Jonn et al. (43) Pub. Date: Mar. 19, 2009 (54) ADHESIVE-CONTAINING WOUND CLOSURE Related U.S. Application Data DEVICE AND METHOD (63) Continuation of application No. 10/779,721, ﬁled on Feb. 18, 2004, now abandoned. (76) Inventors: Jerry J onn, Raleigh, NC (U S); Glenn H05ki11sAPeXs NC (US); Publication Classiﬁcation Julian Quintero, Raleigh, NC (U S) (51) Int. Cl. Correspondence Address: A613 I 7/03 (200601) PHILIP s_ JOHNSON (52) U.S. Cl. ...................................................... .. 606/215 JOHNSON & JOHNSON ONE JOHNSON & JOHNSON PLAZA (57) ABSTRACT NEW BRUNSWICK, NJ 08933-7003 (US) A tissue bonding article includes a ﬂexible material, an adhe- sive substance applied over at least a portion of a bottom side (21) Appl. No.: 12/207,984 of the ﬂexible material, and a polymerizable adhesive com- position permeated throughout at least a portion of the ﬂex- (22) Filed: Sep. 10, 2008 ible material. Patent Application Publication Mar. 19, 2009 Sheet 1 of 7 US 2009/0076542 A1 FIG. 1 FIG. 221 10 lI'.IA’ll&’Il"_l_l_, 20 FIG. 2b 10 l.VI IIlI'ﬂ 20 Patent Application Publication Mar. 19, 2009 Sheet 2 of 7 US 2009/0076542 A1 FIG. 3 1 —\ 10 FIG. 4 10 20 Patent Application Publication Mar. 19, 2009 Sheet 3 of 7 US 2009/0076542 A1 FIG. 5 Patent Application Publication Mar. 19, 2009 Sheet 4 of 7 US 2009/0076542 A1 FIG. 6a 30 40 FIG. 6d FIG. 6e Patent Application Publication Mar. 19, 2009 Sheet 6 of 7 US 2009/0076542 A1 FIG. 7a FIG. 7b Patent Application Publication Mar. 19, 2009 Sheet 7 of 7 US 2009/0076542 A1 FIG. 70 US 2009/0076542 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 device incorporates a polymerizable adhesive material. The materials and methods of the present invention provide an improvement over, and a substitute for, conventional bandages, sutures and staples, and provide improved methods for both approximating and covering wounds, thus providing improved wound manage- ment. [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. [0005] Surgical staples have disadvantages similar to sutures in terms of cosmetic result. 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. 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- 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 Mar. 19, 2009 zwitterions or ion pairs to form polymers. Once polymeriza- tion has been initiated, the cure rate can be very rapid. [0010] Medical applications of l,l-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 l,l-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 stapes 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] 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 external to intemal 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 [0014] The present invention addresses the above needs in the art, and others, by providing improved materials and methods for wound approximation. [0015] 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, thereby providing not only improved wound approximation, but also improved wound closure. These advantages include, among others, improved wound closure, provision of an improved durable microbial barrier, reduced procedure time, improved cosmesis, less pain (dur- ing staple/ suture removal) resulting in increased patient sat- isfaction, and improved ﬁnancial/economic outcomes by eliminating follow-up visits for staple/ suture removal. [0016] In an embodiment, the present invention provides a tissue bonding article, comprising: [0017] a ﬂexible or compliant material; [0018] an adhesive substance applied over at least a portion of a bottom side of said ﬂexible or compliant material; and [0019] a polymerizable adhesive composition permeated throughout said ﬂexible or compliant material. [0020] In a modiﬁcation of the above embodiment, the tissue bonding article can further include a polymerization initiator or rate modiﬁer, a bioactive material, or combina- US 2009/0076542 A1 tions thereof. Such additive can be included, for example, as part of the ﬂexible or compliant material, or mixed with the polymerizable adhesive composition. [0021] In another embodiment, the present invention pro- vides a method of bonding tissue, comprising: [0022] placing a ﬂexible or compliant substrate over a sec- tion of tissue; [0023] applying a polymerizable adhesive composition over and substantially covering the ﬂexible or compliant sub- strate; and [0024] allowing the polymerizable adhesive composition to permeate into and under the ﬂexible or compliant substrate and polymerize to form a composite structure bonded to said tissue. [0025] As with the tissue bonding article described above, the method of bonding tissue according to the present inven- tion can also incorporate a polymerization initiator or rate modiﬁer, a bioactive material, or combinations thereof. Such additive can be included, for example, as part of the ﬂexible or compliant material, or mixed with the polymerizable adhe- sive composition. [0026] In other embodiments of the present invention, the ﬂexible substrate can include one or more adhesive strips, which carry the adhesive substance and thereby adhere the ﬂexible substrate to the desired application site. BRIEF DESCRIPTION OF THE DRAWINGS [0027] These and other advantages and features of this invention will be apparent. from the following, especially when considered with the accompanying drawings, in which: [0028] FIG. 1 is a schematic view of a ﬁrst embodiment of the present invention. [0029] FIGS. 2a and 2b are cross-sectional views of the embodiment of FIG. 1. [0030] FIG. 3 is a schematic view of another embodiment of the present invention. [0031] FIG. 4 is a schematic view of another embodiment of the present invention. [0032] FIG. 5 is a schematic view of another embodiment of the present invention. [0033] FIGS. 6a-6e illustrate a method ofusing a compos- ite structure according to an embodiment of the present inven- tion. [0034] FIG. 7a is a perspective view of another embodi- ment of the present invention. [0035] FIG. 7b is a perspective view of a different embodi- ment of the present invention shown in FIG. 7a. [0036] FIG. 7c is a perspective view of a further embodi- ment of the present invention shown in FIG. 7b. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS [0037] An embodiment of the present invention is shown schematically in FIG. 1. In FIG. 1, a ﬂexible substrate 1 is shown as including a ﬂexible material 10 coated on several portions with an adhesive substance 2. FIGS. 2a and 2b are cross-sectional views of the ﬂexible substrate 1 of FIG. 1, taken along lines 211-211 and 2b-2b, respectively. FIGS. 1 and 211-219 show that, in embodiments, the adhesive substance does not cover an entire portion of the ﬂexible substrate, but only portions thereof. [0038] In the embodiment of FIG. 1, the ﬂexible or com- pliant material 10 can be formed of any suitable ﬂexible or Mar. 19, 2009 compliant material, providing that the aims of the present invention are obtained. Preferably, the ﬂexible or compliant material 10 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 10. However, unless stated differently in context, the term “ﬂexible” 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 exhibits 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. [0039] 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. Such porosity will also preferably allow air and water to pass through the ﬂexible material. Depending upon the degree of porosity (and/or the size of the openings in the mesh), such porosity of the ﬂexible 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. [0040] 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. [0041] In embodiments of the present invention, the ﬂex- ible material can be either biodegradable, or not biodegrad- able. By “biodegradable” in this invention is meant that the ﬂexible substrate biodegrades over time in vivo, such that it does not require physical removal 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 environment within about ﬁve years. Such a non biodegradable material thus would require physi- cal removal of the composite 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 biode- gradable, 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 biodegradable. Biodegradable US 2009/0076542 A1 and non-biodegradable polymerizable adhesive composi- tions are known in the art and are described below. Alterna- tively, combination of two or more biodegradable and/or non- biodegradable materials can be used, to provide tailored results in terms of properties such as biodegradation and the like. [0042] 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, either to permit completion of healing or to reapply a new composite structure. 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 internally where subsequent removal would otherwise require further trauma to the tissue. [0043] In embodiments, it is preferred that the ﬂexible material is a mesh material. Suitable mesh materials can be formed of either synthetic or natural materials. Such mesh 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 (including 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, polypropylene, ethyl- ene propylene copolymers, and ethylene butylene copoly- mers, polyurethanes, polyurethane foams, polystyrenes, plas- ticized polyvinylchlorides, polyesters, polyamides, and cotton. Suitable speciﬁc examples include, for example, nylon, polyethylene, polypropylene, ethylene propylene copolymers, ethylene butylene copolymers, polyurethane, polystyrene, plasticized polyvinylchloride, polyester, polya- mide, cotton, polytetraﬂuoroethylene (PTFE), biovascular material, collagen, Gore-Tex®, Dacron, etc. [0044] In some embodiments, it is preferred that the mesh 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 mesh 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. [0045] 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 material, but not from a material such as metal (such as silver, steel or the like) or glass or ceramic. The ﬂexible material is preferably ﬂexible, as described above, yet resistant to tear- Mar. 19, 2009 ing. 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 embodiment, the thickness of the ﬂexible material is from about 0.5 mil to about 20, preferably from about 0.7 mil to about 10 mils, or from about 1 mil to about 5 mils. [0046] 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. [0047] As shown in FIGS. 1-3, the ﬂexible substrate 1 includes an adhesive substance 20 applied to portions of the ﬂexible material 10. Preferably, as shown in FIG. 1, the adhe- sive substance 20 is applied to the ﬂexible material 10 on opposite ends of the ﬂexible material 10. In this manner, the ﬂexible substrate 1 can be applied over a wound or other desired substrate such that the portion of the ﬂexible material not coated with the adhesive substance straddles the wound. (This use of the composite structure will be described in more detail below.) Accordingly, the adhesive substance is applied to the same side of the ﬂexible material, and the exposed adhesive substance can be covered by a suitable release layer or liner (not shown) to preserve the adhesiveness of the ﬂex- ible substrate until time of use. [0048] Although not limited to any particular orientation, the adhesive substance can be applied either on a short or a long edge of the ﬂexible material 10. Thus, for example, FIG. 1 shows the adhesive substance 20 applied on opposite short (substantially parallel) ends of a rectangular ﬂexible material 10. This embodiment roughly corresponds to a conventional bandage, where the adhesive portions are applied on opposite sides of a wound and the central (uncoated) portion of the ﬂexible material covers the wound. Altematively, FIG. 3 shows an embodiment where the adhesive substance 20 is applied on opposite long (substantially parallel) ends of a rectangular ﬂexible material 10. This embodiment roughly corresponds to a tape design, where the edges of the tape are applied on opposite sides of a lengthwise wound and the central (uncoated) portion of the ﬂexible material covers the lengthwise wound. Of course, the invention is not limited to such embodiments, and other orientations of the invention will be readily apparent to those skilled in the art based on the present disclosure. For example, FIG. 4 shows an embodi- ment where the adhesive substance 20 is applied on all four ends or edges of a square ﬂexible material 10, and FIG. 5 shows an embodiment where the ﬂexible substrate is in a form of a roll of material 5, and the adhesive substance 20 is applied on the long lengthwise edges of the ﬂexible material 10. [0049] Preferably, the adhesive substance is thus applied to the ﬂexible material so as to form distinct ﬁrst, second and third regions across a width or length dimension of the ﬂex- ible material. In the ﬁrst region, the ﬂexible substrate is not covered with the adhesive substance. This region is intended to be placed over an underlying wound or tissue trauma, such that the wound is not contacted (or is substantially not con- tacted) by the adhesive substance. The second and third regions, which adjoin the ﬁrst region on opposing edges thereof, are the regions where the adhesive substance is applied. These second and third regions are intended to be placed on opposite sides of an underlying wound or tissue US 2009/0076542 A1 trauma, to temporarily secure the ﬂexible substrate to the desired application site, such that the wound per se is not contacted (or is substantially not contacted) by the adhesive substance. [0050] Although not speciﬁcally shown in the ﬁgures, a suitable backing or release material may also be used to cover the adhesive substances applied to the bottom side of the ﬂexible material. Such backing materials are well known in the art for covering pressure sensitive adhesives and can include, for example, paper, plastic, or the like. [0051] When forming rectangular ﬂexible substrates for use in the present invention, any suitable dimensions of the material can be provided. For example, in the conventional bandage conﬁguration, where the adhesive substance is pro- vided on the short parallel ends of the ﬂexible material, the ﬂexible material can range in width from about M: inch to about 2 or 3 inches or more, although preferred widths in embodiments may be from about 1/2 to about 1 or 11/2 inches, and can range in length from about 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 conﬁgu- ration of being a lengthwise bandage or rolled tape, where the adhesive substance is provided on the long parallel ends of the ﬂexible material, the ﬂexible material can range in width from about 1/2 inch to about 4 or 5 inches or more, although pre- ferred 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 substrate may be used to form a composite struc- ture over a longer wound, such as a long laceration on inci- sion. As such, embodiments of the present invention can provide a ﬂexible substrate having length exceeding 8 or even 12 inches, such as ranging in lengths up to 18 inches, 24 inches, 30 inches, or more. When provided in the conﬁgura- tion of a roll, the ﬂexible substrate 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 substrate can be varied and tailored, as desired. [0052] As such, various sized ﬂexible materials can be pre- pared and packaged for use. For example, shorter length materials (for example, 15-inch) can be prepared and pack- aged for use in “short laceration” applications, while longer length materials (for example, 30-inch) can be prepared and packaged for use in “long laceration” applications. In other embodiments, a variety of length materials can be provided, 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. [0053] Still other conﬁgurations for the ﬂexible substrate 1 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 ﬂexible materials can be Mar. 19, 2009 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. [0054] Although shown in the ﬁgures as dotted areas, the adhesive substance, preferably with a release layer or backing when the material is not to be immediately used, may be applied to the desired portions of the ﬂexible material in either a continuous or discontinuous manner. Thus, for example, the adhesive substance can be applied as a solid layer over the desired area, or in a set or random pattem. Preferably, the adhesive substance is applied to form a pattem on the ﬂexible material. The adhesive may be applied in any number of pattems, including, for example, in a sine wave using either a smooth pattem (rounded waves) or a sharp pattem (triangle shaped waves) closely packed together. In a preferred embodiment, the adhesive forms a continuous network so that the adhesive-free areas are not interconnected. The adhesive substance is typically present in coat weight from about 10 to about 200, or from about 20 to 150 grams per square meter (gsm). Of course, other coat weights of the adhesive sub- stance can be used, as desired. [0055] The adhesive substance used in the ﬂexible substrate of the present invention may, for example, be any suitable adhesive substance. Preferably, the adhesive substance is a medical grade adhesive, such as acrylic based pressure sen- sitive adhesives (PSAs), rubber based pressure sensitive adhesives, silicone pressure sensitive adhesives, mixtures thereof, or the like. In embodiments, it is preferred that the adhesive sub stance be different from the polymerizable adhe- sive composition. Thus, for example, it is preferred that while the polymerizable adhesive composition can be, for example, a polymerizable monomeric adhesive composition, the adhe- sive substances is an adhesive material that is not a polymer- izable adhesive composition, such as a pressure sensitive adhesive. [0056] Suitable rubber based PSAs include, but are not limited to, those taught in U.S. Pat. No. 5,705,551 and in U.S. Pat. No. 4,080,348, the disclosures of which are hereby incor- porated by reference. Examples of polymeric rubber bases include one or more of styrene-isoprene-styrene polymers, styrene-oleﬁn-styrene polymers including styrene-ethylene/ propylene-styrene polymers, polyisobutylene, styrene-buta- diene-styrene polymers, polyisoprene, polybutadiene, natu- ral rubber, silicone rubber, acrylonitrile rubber, nitrile rubber, polyurethane rubber, polyisobutylene rubber, butyl rubber, halobutyl rubber including bromobutyl rubber, butadiene- acrylonitrile rubber, polychloroprene, and styrene-butadiene rubber. [0057] A particularly useful rubber based adhesive is that which has a thermoplastic elastomeric component and a resin component. The thermoplastic elastomeric component con- tains about 55-85 parts of a simple A-B block copolymer wherein the A-blocks are derived from styrene homolo gs and the B-blocks are derived from isoprene, and about 15-45 parts of a linear or radical A-B-A block copolymer wherein the A-blocks are derived from styrene or styrene homologs and the B-blocks are derived from conjugated dienes or lower alkenes, the A-blocks in the A-B block copolymer constitut- ing about 10-18 percent by weight of the A-B copolymer and the total A-B and A-B-A copolymers containing about 20 percent or less styrene. The resin component consists of essentially of tackiﬁer resins for the elastomeric component. US 2009/0076542 A1 In general any compatible conventional tackiﬁer resin or mix- ture of such resins may be used. These include hydrocarbon resins, rosin and rosin derivatives, polyterpenes and other tackiﬁers. The adhesive composition contains about 20-300 parts of the resin component per one hundred parts by weight of the thermoplastic elastomeric component. One such rubber based adhesive is commercially available from Ato Findley under the trade name HM3210. [0058] Useful acrylic based PSAs include, but are not lim- ited to, those taught in U.S. Pat. No. 5,947,917 and U.S. Pat. No. 5,164,444 (acrylic emulsion), U.S. Pat. No. 5,623,011 (tackiﬁed acrylic emulsion). It can also be radiation curable mixture of monomers with initiators and other ingredients such as those taught in U.S. Pat. No. 5,232,958 (UV cured acrylic) and U.S. Pat. No. 5,232,958 (EB cured). The disclo- sures of these patents are hereby incorporated by reference. [0059] It is contemplated that any acrylic based polymer capable of forming an adhesive layer with suﬂicient tack to adhere to the ﬂexible material, the release liner or to a sub- strate, and with acceptable adhesion to skin, may function in the present invention. In certain embodiments, the acrylic polymers for the pressure-sensitive adhesive layers include those formed from polymerization of at least one alkyl acry- late monomer or methacrylate, an unsaturated carboxylic acid and optionally a vinyl lactam. Examples of suitable alkyl acrylate or methacrylate esters include, but are not limited to, butyl acrylate, ethyl acrylate, 2-ethylhexyl acrylate, isooctyl acrylate, isononyl acrylate, isodecyl acrylate, methyl acry- late, methylbutyl acrylate, 4-methyl-2-pentyl acrylate, sec- butyl acrylate, ethyl methacrylate, isodecyl methacrylate, methyl methacrylate, and the like, and mixtures thereof. Examples of suitable ethylenically unsaturated carboxylic acids include, but are not limited to, acrylic acid, methacrylic acid, fumaric acid, itaconic acid, and the like, and mixtures thereof. A preferred ethylenically unsaturated carboxylic acid monomer is acrylic acid. Examples of suitable vinyl lactams include, but are not limited to, N-vinyl caprolactam, 1-vinyl- 2-piperidone, 1 -vinyl-5 -methyl-2 -pyrrolidone, vinyl pyrroli- done, and the like, and mixtures thereof. [0060] The adhesive substance may also include a tackiﬁer. Tackiﬁers, are generally hydrocarbon resins, wood resins, rosins, rosin derivatives, and the like. It is contemplated that any tackiﬁer known by those of skill in the art to be compat- ible with elastomeric polymer compositions may be used with the present embodiment of the invention. One such tackiﬁer, found to be useful is Wingtak 10, a synthetic poly- terpene resin that is liquid at room temperature, and sold by the Goodyear Tire and Rubber Company of Akron, Ohio. Wingtak 95 is a synthetic tackiﬁer resin also available from Goodyear that comprises predominantly a polymer derived from piperylene and isoprene. Other suitable tackifying addi- tives may include Escorez 1310, an aliphatic hydrocarbon resin, and Escorez 2596, a C5-C8 (aromatic modiﬁed ali- phatic) resin, both manufactured by Exxon of Irving, Tex. Of course, as can be appreciated by those of skill in the art, a variety of different tackifying additives may be used to prac- tice the present invention. [0061] In addition to the tackiﬁers other additions may be included in the adhesive substances to impart desired prop- erties. For example, plasticizers may be included and they are known to decrease the glass transition temperature of an adhesive composition containing elastomeric polymers. Shellﬂex 371 plasticizer is an example of a useful naphthenic processing oil available from Shell Oil Company of Houston, Mar. 19, 2009 Tex. Antioxidants also may be included on the adhesive sub- stance. Also included as suitable are Irgafos 168 antioxidant and Irganox 565 antioxidant available from Ciba-Geigy, Hawthome, N.Y. Cutting agents such as waxes and surfac- tants also may be included in the adhesive substance. Other optional materials that may be added to the adhesive sub- stance layer in minor amounts (typically less than about 25% by weight of the elastomeric phase) include pH controllers, medicaments, bactericides, growth factors, wound healing components such as collagen, antioxidants, deodorants, per- fumes, antimicrobials and fungicides. [0062] Useful silicone pressure sensitive adhesives include those commercially available from Dow Coming Corp., Medical Products and those available from General Electric. Examples of silicone adhesives available from Dow Cormng include those sold under the trademarks BIO-PSA X7-3027, BIO-PSA X7-4919, BIO-PSA X7-2685, BIO-PSA X7-3122 and BIO-PSA X7-4502. Additional examples of silicone pressure sensitive adhesives useful in the present invention are described in U.S. Pat. Nos. 4,591,622, 4,584,355, 4,585, 836 and 4,655,767, the entire disclosures of which are incor- porated herein by reference. [0063] In another embodiment of the present invention, the ﬂexible substrate can be coated on one side with an adhesive substance. In this embodiment, the adhesive substance can be located on substantially an entire surface of the ﬂexible sub- strate, rather than only on opposing edges of the ﬂexible substrate as described above. When prepared in this manner, the adhesive substance can be coated to cover the entire surface in a continuous coating or layer. Altematively, or preferably in some embodiments, the coating is discontinu- ous to provide areas that are not covered by the adhesive substance, such as by the adhesive substance being provided in a form of regular or random spots, lines, or the like. Where the adhesive sub stance does not cover the entire surface of the ﬂexible substrate to form a continuous layer, it is preferred that the adhesive is coated on at least 25% but no more than 75% of the surface area, and more preferably between about 40 and about 60% of the surface area. [0064] In this embodiment, the ﬂexible substrate can be applied to the desired surface much in the same marmer as a piece of tape, where substantially the entire surface of the ﬂexible substrate adheres to the desired surface. The poly- merizable adhesive composition can then be applied to the exposed surface of the ﬂexible substrate, in the marmer as described above. A beneﬁt of this embodiment is that the entire applied ﬂexible substrate can be retained on the desired surface, without trimming off the adhered portions in the manner described above. [0065] When the ﬂexible substrate is provided according to this embodiment, it is preferred that the adhesive substance applied to the surface of the ﬂexible substrate be a pressure sensitive adhesive, which preferably exhibits a low degree of adhesiveness. The adhesive substance to be applied can be, if desired, the same as the adhesive substance described above, which is applied to only portions of the ﬂexible substrate. Or, the adhesive substance used in this embodiment can be a weaker or different adhesive substance. That is, the purpose of the adhesive substance is only to maintain the ﬂexible substrate in position on the desired surface, and optionally provide a minimal adhesion force to approximate or appose the wound surfaces, until the polymerizable adhesive com- position is applied and allowed to set to fully adhere the ﬂexible substrate to the desired surface. The adhesive sub- US 2009/0076542 A1 stance is thus weak enough to allow the applied polymeriz- able adhesive material to penetrate through the ﬂexible sub- strate and the applied adhesive substance, to form a polymerized bond between the ﬂexible substrate (and applied adhesive substance) and the underlying desired substrate. [0066] In this embodiment, any suitable adhesive substance can be used, as desired. Preferably, the adhesive substance should be non-toxic, and capable and/ or approved for use on biological surfaces. Suitable adhesive substances thus include, for example, those adhesive substances commonly used in production of conventional adhesive bandages. Fur- thermore, in this embodiment where the adhesive substances covers substantially an entire face of the ﬂexible material, and thus remains in the ﬁnal composite structure, it is preferred that the polymerizable adhesive composition (described in more detail below) be able to interact with and/or solubilize the adhesive sub stances. That is, it is preferred that the poly- merizable adhesive composition be able to in essence replace the adhesive substance as the primary means of attaching the composite structure to the underlying substrate (application site, such as tissue or wound). This can occur, for example, either by the polymerizable adhesive composition solubiliz- ing the adhesive substance, or by the polymerizable adhesive composition being able to bond the ﬂexible material to the underlying substrate through gaps or voids either pre-existing or created in the adhesive substance layer. [0067] Preferably, the adhesive substances is the only attachment means present on the ﬂexible substrate for attach- ing the ﬂexible material to the desired application or treat- ment site. Thus, for example, the ﬂexible substrate 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 pre- ferred that the ﬂexible substrate not include features that penetrate even surface layers of the underlying substrate, such as dermal layers of the skin. [0068] In addition to including the ﬂexible material and an amount of adhesive substance, as described above, the ﬂex- ible substrate can, if desired, include one or more chemical materials located within the ﬂexible material. For example, one or more chemical 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 ﬂexible substrate can include a polymeriza- tion initiator or rate modiﬁer, or can include one or more bioactive materials. As desired, the one or more chemical substances 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. [0069] For example, it may be desirable to immobilize a polymerization initiator or rate modiﬁer on the ﬂexible mate- rial, so that the initiator or rate modiﬁer provides the desired initiation or rate modiﬁcation effect to a subsequently applied polymerizable adhesive composition, but without the initiator or rate modiﬁer becoming detached from the ﬂexible material and its residues dispersed in the resultant polymeric material. Altematively, for example, a bioactive material may be ini- tially attached to the ﬂexible material, but only in such a manner that it becomes mobilized or solubilized by a subse- Mar. 19, 2009 quently applied polymerizable adhesive composition and dis- persed in the resultant polymeric material. If desired, a com- bination 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 polymer- ization 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 inven- tion. [0070] 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. Altematively, the chemical substance can be incor- porated into or onto the ﬂexible material during manufacture of the ﬂexible material, such as during molding or the like of the ﬂexible material. [0071] A method for using the ﬂexible substrate and result- ant composite structure will now be described. [0072] 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 substrate of the present invention generally provides the same wound approximation and pressure beneﬁts. However, because the ﬂexible substrate 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. Thus, for example, the materials of the present invention, by means of the applied adhesive substance on the bottom side of the ﬂexible material, provide wound approximation prior to application of a polymerizable adhe- sive material to the upper surface of the ﬂexible material, which subsequently permeates through the ﬂexible material as the adhesive polymerizes, to form a ﬂexible, adherent wound dressing. The portions of the ﬂexible material previ- ously coated with the adhesive substance can then, if desired, be trimmed away to provide a unitary composite 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 approxi- mation and pressure beneﬁts. However, because the compos- ite structure uses a polymerizable adhesive composition rather than punctures for adhesion to the underlying applica- tion site, the resultant composite structure provides signiﬁ- cant beneﬁts over the conventional sutures and staples in terms of improved wound management, stronger adhesion to the underlying application site, microbial barrier properties, improved patient satisfaction, less tissue trauma (since addi- tional punctures are not made), lessened scarring, and the like. [0073] One method according to the present invention is shown successively in FIGS. 6a-6e. Although the method is shown using a ﬂexible substrate such as that shown in FIG. 3 US 2009/0076542 A1 or FIG. 5, the invention is not limited to this embodiment. In FIGS. 6a-6e, a surface is shown having a lengthwise wound. Thus, for example, the ﬁgures show a skin surface (arm or leg 30) having a jagged, lengthwise wound or laceration 40. The wound is closed using the composite structure according to the present invention. [0074] In a ﬁrst step as shown in FIG. 6a, the arm or leg 30 is shown having an open wound 40. Preferably, the wound is ﬁrst cleaned by removing excess exudates (blood or the like) to provide as dry a wound as possible to assist in wound closure. [0075] In a second step as shown in FIG. 6b, a length of ﬂexible substrate is provided. Preferably, the length of ﬂex- ible substrate is longer than the wound to be closed, and extends 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 IA inch, more preferably at least 1/2 inch or at least 3A: inch, and even more preferably at least one inch beyond each end of the wound. Furthermore, the ﬂexible substrate 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 substrate is preferably wide enough that the entire wound is covered, with excess coverage, by the portion of the ﬂexible substrate that is not previously coated with an adhe- sive substance for temporary bonding to the desired surface. That is, the uncoated portions of the ﬂexible substrate pref- erably cover the ﬁll width of the wound, and extend beyond opposite lateral edges of the wound a suﬂicient distance to permit sufﬁcient bonding. Thus, for example, the width of ﬂexible substrate is preferably sufﬁcient to extend at least M: inch, more preferably at least 1/2 inch or at least 3A: inch, and even more preferably at least one inch beyond each lateral edge of the wound. [0076] In the second step, the previously applied adhesive substance on one edge of the ﬂexible substrate is exposed. For example, the adhesive substance can be exposed either by applying the adhesive substance to the edge of the ﬂexible substrate (or to the area of application adjacent the wound), or by removing a release layer covering the adhesive substance on the ﬂexible substrate. The ﬂexible substrate 1 is then applied to the arm or leg 30 at an area adjacent the wound 40, by applying the exposed adhesive substance to the arm or leg surface. If necessary, pressure can be applied to the ﬂexible substrate 1 to help adhere the ﬂexible substrate to the arm or leg 30. [0077] In a third step as shown by FIG. 6c, the opposite end of the ﬂexible substrate is applied to the wound. Preferably, slight to moderate pressure is applied to opposite edges of the wound (such as by forceps, ﬁngers, clamps, or the like) to approximate or appose the wound edges. Preferably, such approximation is conducted in a medically accepted manner, such as to as precisely as possible position the wound edges to help reduce subsequent scarring. With the wound edges approximated, the previously applied adhesive substance on the second edge of the ﬂexible substrate is exposed. The remaining edge of the ﬂexible substrate 1 is then applied to the arm or leg 30 at an area adjacent the wound 40, but opposite the wound 40 from the previously applied ﬁrst edge of the ﬂexible substrate 1, by applying the exposed adhesive substance to the arm or leg surface. If necessary, pressure can be applied to the ﬂexible substrate 1 to help adhere the ﬂexible substrate to the arm or leg 30. Mar. 19, 2009 [0078] In a fourth step as shown by FIG. 6d, a polymeriz- able adhesive composition, such as a polymerizable mono- meric adhesive composition 50, is applied over at least a portion of the surface of the ﬂexible substrate 1. Preferably, the polymerizable adhesive composition 50 is applied to fully cover the surface of the ﬂexible substrate 1. However, if desired, a lesser amount of the polymerizable adhesive com- position can be used to conserve materials and assist in sub- sequent steps. In this instance, the polymerizable adhesive composition is preferably applied to the ﬂexible substrate 1 at least in an area suﬂicient to cover the portion of the ﬂexible substrate that will remain on the surface following comple- tion of the application process. Thus, for example, where portions of the ﬂexible substrate are to be removed as described in the following step 5, the polymerizable adhesive composition is applied to the ﬂexible substrate to fully cover the non-removed portions. Alternatively, the polymerizable adhesive composition can be applied to only portions of the ﬂexible substrate, such as only to portions overlying an under- lying wound, or to portions overlying part, but not all, of the underlying wound. [0079] 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 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 arm or leg 30 and wound 40, and the ﬂexible material of the ﬂexible substrate 1, which continuous coating subsequently polymerizes or cures to form a continuous polymeric coating between the ﬂexible substrate and the underlying surface. The quantity of polymerizable adhesive composition should pref- erably further allow for a quantity of the composition to remain in, and preferably over, the ﬂexible substrate. This further amount of polymerizable adhesive composition poly- merizes or cures with the remaining polymerizable adhesive composition to provide a unitary composite structure that is bonded to the underlying surface, such as the underlying surface of the arm or leg 30 and wound 40. [0080] If necessary or desired, the step of applying poly- merizable adhesive composition to the ﬂexible substrate 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 subsequent layers be applied after curing of the underlying layer has begin, but before curing is complete. [0081] When applying the polymerizable adhesive compo- sition to the ﬂexible substrate, the polymerizable adhesive composition is preferably applied over an entire surface of the ﬂexible substrate. That is, while the ﬂexible substrate may provide some wicking, ﬂowing, or capillary movement of the polymerizable 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 substrate. Thus, for example, it will generally not be possible to apply one or two drops of the polymerizable adhesive composition to the ﬂexible substrate, and expect the polymer- izable adhesive composition to completely cover the ﬂexible US 2009/0076542 A1 substrate (unless, of course, the ﬂexible substrate 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 substrate. If necessary, the applied polymerizable adhesive composition can be spread around on the surface of the ﬂexible substrate to provide improved coverage. [0082] In a ﬁfth step as shown in FIG. 6e, portions of the thus-formed composite structure are trimmed off, to provide a ﬁnal composite structure covering the underlying wound. In this embodiment, the portions of the composite structure 1 corresponding to the portions of the ﬂexible substrate 10 coated with the adhesive substance 20, are trimmed off. Such trimming may be preferred and/or required, for example, because the adhesive properties of the adhesive substance differ from the adhesive properties provided by the polymer- izable adhesive composition. Where the adhesive substance 20 provides less adhesion than the polymerizable adhesive composition 50, it is likely that the portions adhered only by the adhesive substance 20 will prematurely separate from the underlying tissue. To prevent such premature separation, and resulting problems of lessened appearance and the like, these portions can be trimmed off after the polymerizable adhesive composition has cured. [0083] Where the portions are to be trimmed off, such trim- ming can be conducted by any desired and suitable means. For example, the portions can be peeled back from the under- lying surface, and trimmed using scissors, a knife, a scalpel, or the like. Altematively, the ﬂexible material used in forming the ﬂexible substrate can be provided with one or more per- forations or tear lines, to assist in the subsequent trimming operation. [0084] To assist in the subsequent trimming operation, it is preferred that the adhesive substance applied to the underside of the ﬂexible material be provided in such a marmer that the polymerizable adhesive composition applied to the topside of the ﬂexible substrate does not penetrate into or under the adhesive substance. That is, it is preferred that the relatively weaker adhesiveness provided by the adhesive substance, is not strengthened by interaction with the relatively stronger polymerizable adhesive composition. Preventing such inter- action will assist in being able to peel back the ﬂexible sub- strate in the areas of the adhesive substance to permit trim- ming of those portions. This interaction between the adhesive materials can be prevented, for example, by using adhesive materials that are not soluble in each other, by providing a substantially continuous coating of the adhesive substance on the desired portions of the ﬂexible material, or the like. How- ever, even if some interaction between the adhesive sub stance and the polymerizable adhesive composition does occur, the adhesive bond provided by the resultant combined adhesive may still be weak enough to permit trimming of the desired portions of the ﬂexible substrate. Alternatively, if a bond is provided that is too strong to permit convenient trimming, then the portions of the ﬂexible substrate having the adhesive substance can be retained on the application site, as the bond will tend not to prematurely separate and thus trimming of the portions may not be necessary. [0085] A modiﬁcation of the above-described process involves “rolling” or “taping” the ﬂexible substrate onto the desired application site. In this embodiment, the ﬂexible material is applied to the application site starting at one Mar. 19, 2009 lengthwise end of the site, and straddling the width direction of the site, and progresses along the application site to the opposite lengthwise end of the site. This application is par- ticularly useful, for example, when the application site is long and the ﬂexible material is, for example, a length or roll of ﬂexible material. [0086] In a ﬁrst step, the application site (e.g., arm or leg 30 having an open wound 40), is preferably ﬁrst cleaned by removing excess exudates (blood or the like) to provide as dry a wound as possible to assist in wound closure. [0087] In a second step, a length of ﬂexible substrate is provided. Preferably, the length of ﬂexible substrate is longer than the wound to be closed, and extends beyond opposite ends of the wound a sufﬁcient distance to permit sufﬁcient bonding. Thus, for example, the length of ﬂexible material is preferably suﬂicient to extend at least 1/4 inch, more prefer- ably at least 72 inch or at least 3/: inch, and even more pref- erably at least one inch beyond each end of the wound. Fur- thermore, the ﬂexible substrate is preferably wide enough to extend beyond each lateral edge of the wound throughout the length of the wound. The width of the ﬂexible substrate is preferably wide enough that the entire wound is covered, with excess coverage, by the portion of the ﬂexible substrate that is not previously coated with an adhesive substance for tempo- rary bonding to the desired surface. That is, the uncoated portions of the ﬂexible substrate preferably cover the full width of the wound, and extend beyond opposite lateral edges of the wound a sufﬁcient distance to permit suﬂicient bond- ing. Thus, for example, the width of ﬂexible substrate 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. [0088] In the second step, the previously applied adhesive substances on the edges of one lengthwise end of the ﬂexible substrate are exposed. For example, the adhesive substances can be exposed either by applying the adhesive substance to the edges of the ﬂexible substrate (or to the areas of applica- tion adjacent the wound), or by removing release layers cov- ing the adhesive substance on the ﬂexible substrate. The ﬂex- ible substrate is then applied to the application site at areas adjacent the wound, by applying one of the exposed adhesive substances to the arm or leg surface on one side of the wound and the other of the exposed adhesive substances to the arm or leg surface on opposite lateral side of the wound. If necessary, pressure can be applied to the ﬂexible substrate to help adhere the ﬂexible substrate to the application site. [0089] In this second step, prior to applying the second edge or second adhesive substance, however, the wound edges are preferably approximated. Thus, for example, one hand can be used to approximate the wound edges, as the other hand is used to apply the ﬂexible material. For example, slight to moderate pressure can be applied to opposite edges of the wound (such as by forceps, ﬁngers, clamps, or the like) to approximate or appose the wound edges. As above, such approximation is preferably conducted in a medically accepted marmer, such as to as precisely as possible position the wound edges to help reduce subsequent scarring. [0090] In a third step, application of the ﬂexible substrate continues along the length of the application site. For example, application can continue by “rolling” or “taping” the ﬂexible material onto the application site, progressing from one lengthwise end of the site to the other lengthwise end. Preferably, or if necessary, lateral edges of the wound at US 2009/0076542 Al the application site can be approximated in the manner described above as the ﬂexible material is applied in the lengthwise direction. [0091] In a fourth step, a polymerizable adhesive compo- sition, such as a polymerizable monomeric adhesive compo- sition, is applied over the surface of the ﬂexible substrate. The polymerizable adhesive composition can be applied in the same manner as described above, and thus the details are not repeated here. [0092] In a ﬁfth step, portions of the thus-formed composite structure can be trimmed off, if desired, to provide a ﬁnal composite structure covering the underlying wound. The trimming likewise can be conducted in the same manner as described above, and thus the details are not repeated here. [0093] A particular advantage of this application method, as compared to the ﬁrst application method described above, is that the method is particularly well suited for longer wounds or longer application sites. Once a ﬁrst end of the ﬂexible substrate is applied to the wound, the remaining length of the ﬂexible substrate is applied by rolling or taping the ﬂexible substrate in place, with gradual approximation of wound edges as necessary. Where wounds or application sites are long, this method is well suited for use by a single indi- vidual, as assistance in applying the ﬂexible substrate may not be required. [0094] Of course, although two application methods are described above, 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. [0095] A still further embodiment of the present invention is shown in FIGS. 7a and 7b. In this embodiment, the ﬂexible substrate 1 includes a ﬂexible material 10, as described above. However, instead of applying the adhesive substance 20 directly to the bottom side of the ﬂexible material 10, the adhesive substance 20 is applied to bottom sides of one or more adhesive strips, such as pressure sensitive adhesive strips 25. The adhesive strips 25 can then be suitably located either on the bottom (application site contacting) side of the ﬂexible material 10 (as shown in FIG. 7a), or on the top (exposed) side of the ﬂexible material 10 (as shown in FIG. 7b). [0096] In these embodiments, the adhesive substance 20 applied to the adhesive strips 25 can extend across the entire length of the adhesive strip, such as shown in FIG. 7b, or only across one or more portions of the adhesive strip, such as shown in FIG. 7a. Applying the adhesive substance 20 across the entire length of the adhesive strip 25 is useful, for example, when the adhesive strip is being applied to the top (exposed) side of the ﬂexible material 10. In this embodiment, the adhesive substance serves two purposes—adhering the adhesive strip to the ﬂexible material, and adhering the ﬂex- ible substrate (composite ﬂexible material and adhesive sub- stance) to the application site prior to application of the poly- merizable adhesive composition. Alternatively, the adhesive substance can be provided on only one or more portions of the adhesive strip, for example, where it is desired to provide as much surface area as possible for application and setting of the polymerizable adhesive composition. It will be under- stood that where the adhesive strips 25 are provided on the bottom side of the ﬂexible material 10, the adhesive substance can be provided on both sides of the adhesive strip, so that one side can be adhered to the ﬂexible material while the other side provides adhesion to the application site. Mar. 19, 2009 [0097] An alternative to this embodiment is shown in FIG. 7c. FIG. 7c represents a modiﬁcation of the embodiment of FIG. 7b, but where the adhesive strips 25 do not extend completely across the ﬂexible material 10. In this embodi- ment, the adhesive strips are attached to sides of the ﬂexible material 10, but do not traverse the ﬂexible material 10. As described above, the adhesive strips could be located either on the top or bottom sides of the ﬂexible material 10, as desired. [0098] When these latter embodiments of the ﬂexible sub- strate are used, the 4 ﬂexible substrate can be applied sub- stantially by the methods described above. That is, the ﬂex- ible substrate can be applied by exposing the adhesive substance and applying the ﬂexible substrate to the applica- tion site. Once the polymerizable adhesive composition is applied and set, the adhesive strips can be trimmed off or retained, as desired. Other modiﬁcation of these embodi- ments will also be apparent to those skilled in the art. [0099] As described above, one or more chemical sub- stances may be applied to the ﬂexible substrate, which can subsequently chemically or physically interact with an applied polymerizable adhesive composition. Such chemical substances can include, for example, one or more polymer- ization initiators or rate modiﬁers, one or more bioactive materials, and combinations thereof. [0100] 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 application Ser. Nos. 09/430,177, ﬁled Oct. 29, 1999, 09/430,289 09/430,180 ﬁled Oct. 29, 1999; 09/385, 030 ﬁledAug. 30, 1999; and 09/176,889 ﬁled Oct. 22, 1998, the entire disclosures of which are incorporated herein by reference. Preferred initiators for some medical uses include benzalkomum chloride, and for some industrial uses include dimethyl toluidine. [0101] 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 benzalkomum chloride or its pure components, and benze- thonium chloride; starmous octoate (tin(II) 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 US 2009/0076542 A1 catalysts such as AliquatTM 336 (General Mills, Inc., Minne- apolis, Minn.); organometallics; manganese acetylacetonate; radical initiators and radicals, such as di-t-butyl peroxide and azobisisobutyronitrile; and bioactive compounds or agents. [0102] In preferred embodiments, the initiator may be a bioactive material, including quatemary ammonium halides such as alkylbenzyldimethylammonium chloride (benzalko- nium 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. [0103] In preferred embodiments, the initiator may 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. [0104] 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 applied cyanoacrylate composition, either prior to or concurrent with application and/ or initiation, is particularly effective in promoting wound healing of leg ulcers, thermal burns, and the like. [0105] The polymerizable and/or cross-linkable 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). Ini- tiators activated by stimulation such as heat and/ or light (e.g., ultraviolet or visible light) are also suitable if the ﬂexible substrate is appropriately subjected to such stimulation. In addition to the polymerization and/or cross-linking initiator and/or rate modiﬁer, the ﬂexible substrate can also include various other materials that may or may not act as a polymer- ization initiator and/ or rate modiﬁer. For example, the ﬂexible substrate can include a bioactive material, which may or may not also be a polymerization and/or cross-linking initiator and/ or rate modiﬁer. Examples of suitable bioactive materials include, but are not limited to, medicaments such as antibi- otics, antimicrobials, antiseptics, bacteriocins, bacteriostats, disinfectants, steroids, anesthetics, antifungal agents, anti- inﬂammatory agents, antibacterial agents, antiviral agents, antitumor agents, growth promoting substances, antioxi- dants, or mixtures thereof. Thus, in embodiments, the initia- tor 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 Mar. 19, 2009 to close, cover, or protect tissue and wounds while simulta- neously providing a bioactive material to the tissue or wound. [0106] 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 thereof. Such compounds include, but are not limited to, acetic acid, aluminum acetate, bacitracin, bacitracin zinc, benzalkonium chloride, benzethonium chloride, betadine, calcium chloroplatinate, certrimide, cloramine T, chlorhexi- dine phosphanilate, chlorhexidine, ehlorhexidine sulfate, chloropenidine, chloroplatinatic acid, ciproﬂoxacin, clinda- mycin, clioquinol, cysostaphin, gentamicin sulfate, hydrogen peroxide, iodinatedpolyvinylidone, iodine, iodophor, minoy- cline, mupirocin, neomycin, neomycin sulfate, nitrofurazone, non-onynol 9, potassium permanganate, penicillin, polymy- cin, polymycin B, polymyxin, polymyxin B sulfate, polyvi- nylpyrrolidone iodine, povidone iodine, 8-hydroxyquinoline, quinolone thioureas, rifampin, rifamycin, copper chloride, copper sulfate, copper peptides, silver acetate, silver ben- zoate, silver carbonate, silver chloride, silver citrate, silver iodide, silver nitrate, silver oxide, silver sulfate, sodium chlo- roplatinate, sodium hypochlorite, sphingolipids, tetracycline, 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. Preferable bioactive materials are USP approved, more preferably USP mono graphed. [0107] The polymerization and/or cross-linking initiator and/or rate modiﬁer, and/or the bioactive material, may be applied to the ﬂexible substrate by any suitable means, including, but not limited to, spraying, dipping, injecting, or brushing the ﬂexible substrate with a liquid medium contain- ing the material to be applied. [0108] As mentioned above, the composite structure is formed by applying a polymerizable adhesive composition to the ﬂexible substrate, and allowing the polymerizable adhe- sive composition to polymerize. [0109] 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. anionically polymerizable or free radical polymerizable, or polymeriz- able by zwitterions or ion pairs to form polymers. Such mono- mers include those that form 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. [0110] 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. [0111] 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. US 2009/0076542 A1 [0112] 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- late, 3-methoxybutyl cyanoacrylate, 2-butoxyethyl cyanoacrylate, 2-isopropoxyethyl cyanoacrylate, l-meth- oxy-2-propyl cyanoacrylate, hexyl cyanoacrylate, or dode- cylcyanoacrylate. [0113] 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 O R1 R O 2 1 R3 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 -C36 alkyl group, more prefer- ably a C1-C10 alkyl group, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, ocrty, 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. [0114] 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. [0115] 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. [0116] In embodiments, the composition may also include one or more polymerization initiators or rate modiﬁers. Although the polymerization initiator or rate modiﬁer is Mar. 19, 2009 described above as being incorporated into or onto the ﬂex- ible material, it is also possible for the polymerization initia- tor or rate modiﬁer to be incorporated directly into the poly- merizable adhesive composition. In such embodiments, the polymerization initiator or rate modiﬁer is mixed with the polymerizable adhesive composition preferably immediately prior to or concurrent with application of the polymerizable adhesive composition to the ﬂexible substrate. For example, the polymerization initiator or rate modiﬁer and polymeriz- able adhesive composition can be mixed prior to application by suitable mixing devices in an applicator itself or in a separate container, or they can be mixed concurrent with application by mixing as the polymerizable adhesive material is expressed form an applicator. Any suitable polymerization initiators or rate modiﬁers, including those described above, can be used in these embodiments. [0117] 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, 1 66, the disclosures of which are hereby incorporated in their entireties by reference herein. [0118] The composition may optionally also include thick- eners. Suitable thickeners may include poly (2-ethylhexy 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. [0119] 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. [0120] 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. [0121] 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. [0122] 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. [0123] The compositions of this invention may further con- tain ﬁbrous reinforcement and colorants such as dyes, pig- ments, and pigment dyes. Examples of suitable ﬁbrous rein- forcement include PGA microﬁbrils, collagen microﬁbrils, US 2009/0076542 A1 and others as described in U.S. Pat. No. 6,183,593, the dis- closure of which is incorporated by reference herein in its entirety. [0124] 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. [0125] 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, pro- vision 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. [0126] 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 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. [0127] 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. [0128] 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. [0129] 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 “feel” of the wound dressing, the improved cosmetic results, and improved assurance of wound closure and dressing strength, and the like. In addition, because of the strong bond provided, the composite structure of the present invention is expected to remain in place over an extemal 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. Furthermore, Mar. 19, 2009 because staple or suture removal is not required, the patient experiences less pain and anticipation, improving the healing experience. [0130] 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, internal, 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. [0131] 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 Preparation of Flexible Substrate Material [0132] A length of polypropylene mesh material is obtained having a length of about four feet and a width of about 1% inches. The polypropylene mesh is dipped into a solution of benzalkonium chloride and acetone, to adsorb the benzalkonium chloride on the polypropylene mesh. The mesh is subsequently dried to volatilize and remove the acetone solvent. To a backside of the mesh, a conventional pressure sensitive adhesive is applied as a continuous layer along the 4-foot length of the mesh, and extending about % inch from each edge, thus leaving a 1 inch strip along the center of the length of the mesh that is not covered by the adhesive sub- stance. The applied pressure sensitive adhesive is subse- quently covered by respective 4-foot by 3/8 inch strips of release paper. The thus-produced ﬂexible substrate is used in the following Examples. Example 1 [0133] A patient is presented having a one inch cut on the arm. The cut does not extend fully through the dermal layers of the skin. [0134] Following suitable washing, disinfecting and drying of the area around the cut, a 2-inch length of the prepared ﬂexible substrate is applied to the wound site. The ﬂexible substrate is applied by ﬁrst removing one of the two release strip papers and aﬂixing the pressure sensitive adhesive edge to one side of the cut, about 7/8 inch from the edge of the cut. The second release strip paper is then removed from the ﬂexible substrate. After approximating the wound edges using slight pressure applied by two ﬁngers, the remaining pressure sensitive adhesive edge of the ﬂexible substrate is applied to the other side of the cut, about % inch from the edge of the cut. The ﬂexible substrate extends about 1/2 inchbeyond each end of the wound. [0135] A quantity of a stabilized 2-octyl cyanoacrylate adhesive is applied to the exposed surface of the ﬂexible substrate, and is spread to permeate into and fully cover the ﬂexible substrate. Polymerization of the composition pro- US 2009/0076542 A1 ceeds in about 1 minute. After complete polymerization, the edges of the ﬂexible substrate adhered to the tissue using pressure sensitive adhesive are peeled back, and those por- tions of the ﬂexible substrate are removed by trimming with surgical scissors. The result is a ﬁrmly bonded composite structure, bonded to the skin over the full area of the cut. [0136] The composite structure remains in place for about 10 to 14 days, during which time the wound heals. Example 2 [0137] A patient is presented having a four inch cut on the leg. The cut extends fully through the dermal layers of the skin. [0138] Following suitable washing, disinfecting and drying of the area around the cut, subcutaneous dissolvable sutures are used to approximate and close the subcutaneous layers in the wound. Next, a 5-inch length of the prepared ﬂexible substrate is applied to the wound site. The ﬂexible substrate is applied by ﬁrst removing one of the two release strip papers and afﬁxing the pressure sensitive adhesive edge to one side of the cut, about % inch from the edge of the cut. The second release strip paper is then removed from the ﬂexible substrate. After approximating the wound edges using slight pressure applied by the hands, the remaining pressure sensitive adhe- sive edge of the ﬂexible substrate is applied to the other side of the cut, about % inch from the edge of the cut. The ﬂexible substrate extends about 1/2 inch beyond each end of the wound. [0139] A quantity of a stabilized 2-octyl cyanoacrylate adhesive is applied to the exposed surface of the ﬂexible substrate, and is spread to permeate into and fully cover the ﬂexible substrate. Polymerization of the composition pro- ceeds in about 1 minute. After complete polymerization, the edges of the ﬂexible substrate adhered to the tissue using pressure sensitive adhesive are peeled back, and those por- tions of the ﬂexible substrate are removed by trimming with surgical scissors. The result is a ﬁrmly bonded composite structure, bonded to the skin over the full area of the lacera- tion. [0140] The composite structure remains in place for about 10 to 14 days, during which time the cut heals. Comparative Example 1 [0141] A patient is presented having a four inch cut on the leg, substantially similar to the laceration of the patient in Example 2. The cut extends fully through the dermal layers of the skin. [0142] Following suitable washing, disinfecting and drying of the area around the cut, subcutaneous dissolvable sutures are used to approximate and close the subcutaneous layers in the wound, in a similar manner to Example 2. Next, conven- tional sutures and staples are used to close the surface layers of the wound. The wound is subsequently covered by gauze pads and an ace bandage to control residual bleeding. [0143] The wound dressing is maintained in place for about 10 to 14 days, being changed several times over that period to provide clean gauze. After the dressing is removed, the sutures and staples on the surface of the skin are removed. [0144] A comparison of the results of Example 2 and Com- parative Example 1 indicate that healing of the wounds is substantially identical. However, the results of Example 2 indicate an improvement in wound appearance, with less evident skin trauma. The patient in Example 2 also reports Mar. 19, 2009 increased comfort in initial dressing application, in appear- ance and feeling over the intervening 10-14 days, and in removal of the dressing. [0145] While the invention has been described with refer- ence to preferred embodiments, the invention is not limited to the speciﬁc examples given, and other embodiments and modiﬁcations can be made by those skilled in the art without departing from the spirit and scope of the invention. 1-55. (canceled) 56. A method of bonding tissue, comprising: placing a ﬂexible material over a section of tissue, wherein said ﬂexible material comprises a polymerization initia- tor or rate modiﬁer disposed in or on said ﬂexible mate- rial, and an adhesive substance applied over at least a portion of a bottom side of said ﬂexible material; applying a polymerizable adhesive composition to at least a portion of a top surface of the ﬂexible material; and allowing the polymerizable adhesive composition to per- meate into and under the ﬂexible material and polymer- ize to form a composite structure bonded to said tissue. 57. The method of claim 56, wherein the ﬂexible material is biodegradable or nonbiodegradable. 58. The method of claim 57, wherein the ﬂexible material is a mesh. 59. The method of claim 58, wherein the mesh is formed of either woven or non-woven fabrics or materials. 60. The method of claim 56, wherein the polymerization initiator or rate modiﬁer is selected from the group consisting of detergent compositions, nonionic surfactants, cationic sur- factants, anionic surfactants, stannous octoate (tin(ll) 2-eth- ylhexanoate), sodium tetradecyl sulfate, arnphoteric or zwit- terionic surfactants, amines, imines, amides, phosphines, phosphates, phosphonium salts, alcohols, methyl gallate, ascorbic acid, tannins, tannic acid, inorganic bases and salts, sulfur compounds, polymeric cyclic ethers, cyclic and acyclic carbonates, phase transfer catalysts, organometallics, manga- nese acetylacetonate, radical initiators and radicals, and bio- active compounds or agents. 61. The method of claim 60, wherein the polymerization initiator is one or more quaternary ammonium halide. 62. The method of claim 61, wherein the polymerization initiator is one or more alkylbenzyldimethylammonium chlo- ride having an alkyl ranging from 6-18 carbon atoms. 63. The method of claim 56, wherein the adhesive sub- stance is a pressure sensitive adhesive. 64. The method of claim 56, wherein the polymerizable adhesive composition is a monomeric composition. 65. The method of claim 64, wherein polymerizable adhe- sive composition comprises one or more 1,1-disubstituted ethylene monomers. 66. The method of claim 65, wherein polymerizable adhe- sive composition comprises one or more monomer selected from the group consisting of methyl cyanoacrylate, ethyl cyanoacrylate, n-butyl cyanoacrylate, 2-octyl cyanoacrylate, methoxyethyl cyanoacrylate, ethoxyethyl cyanoacrylate, dodecyl cyanoacrylate, 2-ethylhexyl cyanoacrylate, butyl cyanoacrylate, 3-methoxybutyl cyanoacrylate, 2-butoxyethyl cyanoacrylate, 2-isopropoxyethyl cyanoacrylate, 1-meth- oxy-2-propyl cyanoacrylate, hexyl cyanoacrylate, butyl lac- toyl cyanoacrylate, butyl glycolcyl cyanoacrylate, ethyl lac- toyl cyanoacrylate, and ethyl glycoloyl cyanoacrylate. US 2009/0076542 A1 67. The method of claim 61, wherein the polymerizable adhesive composition a monomeric composition. 68. The method of claim 67, wherein polymerizable adhe- sive composition comprises one or more l,l-disubstituted ethylene monomers. 69. The method of claim 68, wherein polymerizable adhe- sive composition comprises one or more monomer selected from the group consisting of methyl cyanoacrylate, ethyl cyanoacrylate, n-butyl cyanoacrylate, 2-octyl cyanoacrylate, methoxyethyl cyanoacrylate, ethoxyethyl cyanoacrylate, dodecyl cyanoacrylate, 2-ethylhexyl cyanoacrylate, butyl cyanoacrylate, 3-methoxybutyl cyanoacrylate, 2-butoxyethyl cyanoacrylate, 2-isopropoxyethyl cyanoacrylate, l-meth- oxy-2-propyl cyanoacrylate, hexyl cyanoacrylate, butyl lac- toyl cyanoacrylate, butyl glycolcyl cyanoacrylate, ethyl lac- toyl cyanoacrylate, and ethyl glycoloyl cyanoacrylate. 70. The method of claim 56, wherein the ﬂexible material is a polypropylene mesh, the polymerization initiator is ben- zalkonium chloride, the adhesive substance is a pressure sen- sitive adhesive, and the polymerizable adhesive composition comprises 2-octyl cyanoacrylate monomer. Mar. 19, 2009 71. A method of bonding tissue, comprising: placing a biodegradable ﬂexible material over a section of tissue, wherein said ﬂexible material comprises a poly- merization initiator or rate modiﬁer disposed in or on said ﬂexible material; applying a polymerizable adhesive composition compris- ing at least one alkyl ester cyanoacrylate monomer to at least a portion of a top surface of the biodegradable ﬂexible material; and allowing the polymerizable adhesive composition to per- meate into and under the biodegradable ﬂexible material and polymerize to form a composite structure bonded to said tissue. 72. A wound closure kit, comprising: a ﬂexible material, wherein said ﬂexible material com- prises a polymerization initiator or rate modiﬁer dis- posed in or on said ﬂexible material, an adhesive sub- stance applied over at least a portion of a bottom side of said ﬂexible material, and a release liner to preserve the adhesiveness of the ﬂexible material until time of use; and a polymerizable adhesive composition in an applicator. * >X< * >X< *

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Adhesive-Containing Wound Closure Device and Method

Adhesive-Containing Wound Closure Device and Method

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method 2