HK1193331B - Devices and bandages for the treatment or prevention of scars and/or keloids and methods and kits therefor - Google Patents

Description

Device and bandage for treating or preventing scars and/or scars, and method and kit therefor

This application is a divisional application of patent application No. 200780036288.6 (PCT/US 2007/017320) entitled "apparatus and bandage for treating or preventing scars and/or scars and method and kit thereof", filed on chinese patent office on 3/8/2007.

Cross Reference to Related Applications

This application claims priority to U.S. provisional patent application No. 60/835,654 filed on 3.8.2006, and is incorporated herein by reference in its entirety.

Technical Field

The devices, kits, and methods described herein relate to the field of wound healing, and in particular, to scar treatment and amelioration of scar formation. For example, the devices, kits, and methods described herein may be used for the treatment, amelioration, or prevention of scars and/or scars.

Background

As part of the natural wound healing process, scars form as a result of skin trauma. Wound healing is a long and continuous process, although it is generally considered to be staged. The process begins with an inflammatory phase immediately after the wound. During this phase, which typically lasts from two days to one week (depending on the wound), damaged tissue and foreign bodies are removed from the wound. The inflammatory phase is followed by a proliferative phase characterized by proliferation of fibroblasts and production of collagen and proteoglycans. The intercellular matrix is synthesized during the proliferation phase to provide structural integrity to the wound. The proliferative phase usually lasts about four days to several weeks, depending on the nature of the wound, and hypertrophic scars are usually formed during this phase. The final phase is called the remodeling phase. During the remodeling stage, the previously formed and randomly organized interstitium is remodeled into a highly cross-linked and organized structure to increase mechanical strength.

Although the histological features that describe hypertrophic scars are well documented, their pathophysiology is not well known. Hypertrophic scars are a by-product of excessive wound healing and often result in an excessive production of cells, collagen and proteoglycans. Often, these scars result from and are characterized by a random distribution of tissue bundles. The appearance (i.e., size, shape, and color) of these scars varies depending on the body part in which they are formed, as well as the ethnic nature of the affected person. Hypertrophic scars are very common and can occur after any full-thickness trauma to the skin. Recently, it has been shown in U.S. patent application publication No. 2006/0037091 (U.S. patent application No. 11/135,592, entitled "method for producing hypertrophic scar screening for identifying an agent for preventing and treating hypertrophic scars of the human body", filed 24/5/2005), that mechanical stress can increase hypertrophic scars in murine models, the entire contents of which are incorporated herein by reference.

Scars are often characterized by tumors formed by highly proliferative substances, which appear in the dermis and nearby subcutaneous tissue of sensitive individuals, most commonly after trauma. Scars are generally more severe than hypertrophic scars, as they tend to invade normal nearby tissue, while hypertrophic scars tend to remain confined within the confines of the initial scar.

Previous approaches to treating scars and scars have included surgery, silicone dressings, steroids, x-ray radiation, and cryotherapy. Each of these techniques has drawbacks. Perhaps the greatest disadvantage is that none of these methods is effective in preventing or ameliorating scar or scar formation at the first time. That is, these techniques are mainly used to treat scars after they have been sufficiently formed.

There is therefore a need for devices and methods for preventing or ameliorating scarring and/or scarring.

Disclosure of Invention

Described herein are devices, bandages, kits, and methods for improving scarring and/or scarring at a wound site. Typically, the device is removably secured to the skin surface in the vicinity of the wound site. The apparatus is configured to protect the wound from endogenous (i.e., dermal) or exogenous (i.e., physiological) stresses, and in some variations, the apparatus is configured to protect the wound from endogenous and exogenous stresses.

The device may comprise or be made of a polymer such as a shape memory polymer (e.g. acrylic-, styrene-and epoxy-based) or a biocompatible silicone. At least a portion of the device may be made of a transparent material or at least a portion of the device may be perforated. The device may or may not be closed, in some variations. Similarly, the device may or may not include an aperture, and in some variations, the device includes at least one aperture.

The device may be removably secured to the skin surface in various ways. The device is removably secured to the skin surface, for example by adhesive material, by a skin puncturing device, or the like. Suitable bonding materials include pressure sensitive adhesives such as polyacrylic based, polyisobutylene based, and silicone based pressure sensitive adhesives. Suitable skin puncturing devices include microneedles, sutures, anchors, spikes, prongs, and the like.

The device may have any suitable or desired shape or size. For example, the shape of the device may be selected from the group consisting of rectangular, circular, square, trapezoidal, annular, oval, and fan-shaped, and combinations thereof. For example, some devices may be substantially circular, others may be substantially annular, and still others may be substantially rectangular.

In some variations, the apparatus is configured to actively protect the wound from endogenous and/or exogenous stress. In other variations, the apparatus is configured to passively protect the wound from endogenous and/or exogenous stress. The apparatus may be configured to protect the wound from endogenous and/or exogenous stresses in a dynamic or static manner.

The device may also include an active agent. The active agent may be any suitable active agent capable of contributing to certain aspects of the wound healing process. For example, the active agent can be a pharmaceutical ingredient, a protein (e.g., a growth factor), a vitamin (e.g., vitamin E), and combinations thereof. Of course, the device may include more than one active agent, and the device may release one or more active agents.

In some variations, the device may desirably include a mechanism for changing the temperature at the skin surface. The mechanism may be electronic, chemical, mechanical, or a combination thereof. In a similar manner, the device may include a mechanism that causes a color change of at least a portion of the device. For example, the color change can correspond to a change in device stiffness, device efficacy, and the like.

Also disclosed are bandages for improving scarring and/or scarring at a wound site. Typically, the bandage is configured to be removably secured to a skin surface and has a first, tensioned configuration and a second, relaxed configuration. In some variations, the first configuration is tensioned about 5% relative to its relaxed configuration. In other variations, the first configuration is tensioned about 10%, 15%, or 20% relative to its relaxed configuration. In still other variations, the first configuration is tensioned about 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% relative to its relaxed configuration. It should be understood that the term "about" is used for each of these percentages.

The bandage may comprise a polymer, such as a biocompatible silicone polymer or a shape memory polymer. Suitable shape memory polymers are described above. As with the devices described above, the bandage may be removably secured to the skin surface by any desired means, may include one or more active agents, may include a mechanism for changing the temperature at the skin surface, or may include a mechanism that causes a color change of at least a portion of the bandage. Similarly, the bandage may have any suitable shape or size. At least a portion of the bandage may be made of a transparent material, and the bandage may or may not be closed.

Also described herein are bandages for improving scarring and/or scarring at a wound site, wherein the bandages comprise at least a first, second, and third configuration. The second configuration is tensioned relative to the first configuration. The bandage is removably secured to the skin surface in the second configuration, and is actuatable to assume a third configuration in the second configuration. In some variations, the second configuration is thermally actuated (e.g., thermally actuated by body heat, a heating pad, a blower, a heat gun, etc.) to assume the third configuration.

In some variations, the second configuration is tensioned about 5% relative to the first configuration. In other variations, the second configuration is tensioned about 10%, about 15%, or about 20% relative to the first configuration. In still other variations, the second configuration is strained by about 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% relative to the first configuration. Again, the term "about" is used for each of these percentages.

The third configuration may be the same as or different from the first configuration, and in some variations the third configuration is substantially the same as the first configuration. In other variations, the third configuration differs from the second configuration in at least one direction. In still other variations, the third configuration differs from the second configuration in at least two directions. In some variations, the third configuration differs from the first configuration by less than about 10% in at least one direction. In other variations, the third configuration differs from the first configuration by less than about 10% in at least two directions. In some variations, the third configuration is determined, at least in part, by a constraint placed on the bandage, which may or may not be affected by skin compliance.

Also described herein are kits for ameliorating scar or scar formation. The kit includes at least two devices in a packaged combination. Each apparatus is configured to be removably secured to a skin surface proximate a wound site to protect the wound from endogenous and/or exogenous stress. In some variations of the kit, the devices have different colors or shapes. The devices may also have different sizes and thicknesses. The at least two apparatuses are configured to protect the wound from endogenous and/or exogenous stress in different amounts. The kit may also include instructions for indicating how to use the device, a blower, a heat gun, a heating pad, a wound dressing, at least one wound cleaner, and other suitable or useful materials.

Methods for ameliorating scar or scar formation are also described. In general, the method includes applying to skin in the vicinity of a wound an apparatus configured to protect the wound from endogenous and/or exogenous stress. The device may be applied at any suitable time during the wound healing process, in some variations, the device is applied during the proliferative phase of wound healing. Similarly, the device may be applied to the wound for any suitable length of time. For example, the device may be applied to the wound for at least about 10 days, at least about 20 days, at least about 30 days, at least about 40 days, at least about 50 days, at least about 60 days, at least about 70 days, at least about 80 days, at least about 90 days, or at least about 100 days. In some variations, the device may be applied to the wound for a longer period of time, such as about 6 months, about 9 months, about 12 months, or about 15 months. In some variations, the method includes removing the device after a period of time, where the period of time may or may not be predetermined.

The method may further comprise applying a second device to the skin in the vicinity of the wound. The second apparatus may be configured to protect the wound from endogenous and/or exogenous stress, or may be configured to be removably secured to a skin surface and configured to reduce wound stress in at least one direction.

Drawings

Fig. 1 is a schematic view of an exemplary apparatus applied to a skin surface near a wound site.

Fig. 2A is a cross-sectional view of an exemplary device having an adhesive layer. Fig. 2B is a cross-sectional view of an apparatus having an adhesive layer and a wound dressing. Fig. 2C is a bottom view of the apparatus shown in fig. 2B.

Fig. 3A is a cross-sectional view of an exemplary apparatus having an adhesive layer and a wound dressing. Fig. 3B is a top view of the apparatus shown in fig. 3A.

Fig. 4A is a cross-sectional view of a device having an orifice. Fig. 4B is a top view of the apparatus shown in fig. 4A.

Fig. 5 is a top view of an apparatus having a plurality of orifices.

Fig. 6 is a cross-sectional view of a device or bandage secured to the skin surface near the wound site.

Fig. 7A is a cross-sectional view of a device or bandage having a first tensioned configuration secured to a skin surface near a wound site. Fig. 7B is a cross-sectional view of the device shown in fig. 7A in a relaxed configuration.

Fig. 8A-B are top views of a device or bandage having a first tensioning configuration that is tensioned primarily in one direction.

Fig. 9A-B are top views of a device or bandage having a first tensioning configuration that is tensioned in two directions.

Fig. 10A provides a top view of a variation of an apparatus or bandage having a first configuration and a second configuration, wherein the second configuration is taut relative to the first configuration. Fig. 10B illustrates the recovery of the tensioned configuration of the device or bandage shown in fig. 10A without significant restraint. Fig. 10C illustrates the recovery of the tensioned configuration of the device or bandage shown in fig. 10A in the presence of a constraint in one direction.

Fig. 11 shows a device comprising a wire or a fiber.

Fig. 12A-D illustrate a device or bandage having a first configuration, a tensioned second configuration attached to the skin, and a third configuration attached to the skin. The third configuration differs from the second configuration in one direction.

Fig. 13A-D illustrate a device or bandage having a first configuration, a tensioned second configuration attached to the skin, and a third configuration attached to the skin. The third configuration differs from the second configuration in two directions.

Fig. 14A-D illustrate other variations of devices or bandages in which the third configuration differs from the second configuration in two directions.

Fig. 15A-B illustrate an apparatus or bandage capable of preferentially protecting a wound from endogenous and/or exogenous stress in one direction.

Fig. 16A-B illustrate other variations of devices or bandages that are capable of preferentially protecting a wound from endogenous and/or exogenous stress in one direction.

Fig. 17 shows a top view of a mechanical tensioning device used in example 1 described below.

Fig. 18 shows wound stress applied in the murine model of example 1, where the wound is stressed in a direction generally orthogonal to the incision direction.

Fig. 19 shows wound stress applied in the murine model of example 1, where the wound is stressed in a direction substantially parallel to the incision direction.

Fig. 20 shows the qualitative effect of mechanical loading on scar volume.

Fig. 21 is an optical micrograph showing strain applied to the skin of a human forearm either before or after (respectively) application of the apparatus described herein.

Fig. 22 shows the strain applied to the skin as a function of the initial strain in the device backing.

Fig. 23 shows the stress applied to the skin as a function of time as a function of the pressure sensitive adhesive formulation.

Fig. 24 illustrates the extent of viscoelastic recovery and subsequent stress during the initial phase after device attachment.

Fig. 25 is an optical micrograph showing a device attached to skin under stress, with an area at its center that is free of pressure sensitive adhesive.

Detailed Description

The mechanical environment of the wound may be an important factor in the tissue's response to the wound. The mechanical environment includes both exogenous stress (i.e., physiological stress, which includes stress transmitted to the wound by muscle action or body movement) and endogenous stress (i.e., dermal stress resulting from the physical properties of the skin itself, including stress at the wound site due to swelling or contraction of the skin). The skin includes the outer stratum corneum, epidermis and dermis. The devices, bandages, kits, and methods described herein can control or regulate the mechanical environment of a wound to improve scar and/or scar formation. The mechanical environment of the wound includes stress, strain, and any combination of stress and strain. The control of the mechanical environment of the wound can be active or passive, dynamic (e.g., by applying oscillating stress), or static. The devices and methods described herein are capable of protecting a wound from its mechanical environment. The term "protection" means promoting the unloading of the stress to which the wound is subjected as well as providing a physical barrier against contact, infection, and the like. The devices and methods described herein are capable of protecting a wound by unloading endogenous and/or exogenous stress to the wound and surrounding tissue. In this way, the devices and methods described herein are able to reduce the stress experienced by the wound and surrounding tissue to a lower degree than that experienced by normal skin and tissue. Unloading endogenous and/or exogenous stress in the vicinity of the wound can improve the formation of scars, hypertrophic scars, or scars.

The external mechanical environment of a cell can trigger biological responses within the cell and alter cell behavior. Cells are able to sense and respond to changes in their mechanical environment through integrins (integrins in the plasma membrane of cells) and intracellular pathways. Intracellular pathways begin with receptors attached to the cell membrane and the cell membrane capable of sensing mechanical forces. For example, mechanical forces can result in the secretion of cytokines, chemokines, growth factors, and other bioactive compounds that can increase or elicit an inflammatory response. Such secretion can act in the cells that secrete them (endocrine), on the cells that secrete them (autocrine), on the surrounding cells of the cells that secrete them (paracrine), or at a distance from the point of secretion (endocrine). Intracellular endocrine intervention can alter cellular signals, which in turn can alter cellular behavior and physiology-including wound cell recruitment, wound cell proliferation, and cell death in the wound. In addition, the intercellular substance is affected.

Wound healing and scar formation

As mentioned above, the healing process of a wound is divided into three phases: early inflammatory phase, proliferative phase, and remodeling. The inflammatory phase occurs immediately after the wound and usually lasts for about two days to one week. Blood clots to stop blood loss and factors are released to attract cells that can remove dead cells, bacteria and damaged tissue from the wound. In addition, factors are released to initiate the proliferative phase of wound healing. In the proliferative phase, which lasts about four days to weeks, fibroblasts grow and form new intercellular substances by secreting collagen and proteoglycans. At the end of the proliferation phase, fibroblasts can be used to further contract the wound. In the remodeling stage, randomly oriented collagen is organized along the skin tension lines and cross-linked. Cells that are no longer needed may be apoptotic. The remodeling stage can last for many weeks or months, or can be performed indefinitely after an injury. After 6-8 weeks of trauma, scars typically achieve approximately 75-80% of the normal skin breaking strength. Generally, scars typically have a triangular cross-section. That is, scars generally have a minimal volume near the skin surface (i.e., stratum corneum and epidermis) and increase in volume as they enter deeper dermal layers.

There are generally three possible outcomes to the wound healing process. First, normal scarring can result. Second, it can lead to increased morbidity in scar formation, such as the formation of hypertrophic scars or scars. Third, the wound may not heal completely and become a long-term wound or ulcer. The devices, kits, and methods described herein can improve the formation of any type of scar. Furthermore, the devices, kits, and methods described herein can be adapted for use with a variety of wound sizes and for different skin thicknesses, e.g., the devices can be configured for use with different areas of the body. Furthermore, the devices, kits, and methods described herein can be adapted to improve scar formation for any type of skin, such as any body part, age, race, or condition.

Without wishing to be bound by any particular theory, it is believed that the mechanical strain generated early in the proliferative phase of the wound healing process inhibits apoptosis, resulting in significant accumulation of cells and interstitium, leading to increased scarring or the formation of hypertrophic scars. Due to the potential similarity between hypertrophic scars and scars in the formation of excess interstitium, we believe that the devices and methods described herein can also be used to prevent and treat scars.

Device

Devices for improving scarring and/or scarring at a wound site are described herein. The scar may be any type of scar, such as a general scar, a hypertrophic scar, and the like. Typically, the apparatus is configured to be removably secured to a skin surface in the vicinity of a wound. The device is capable of protecting the wound from endogenous stresses from the skin itself (e.g., stresses transmitted to the wound through the stratum corneum, epidermal or dermal tissue), and/or exogenous stresses (e.g., stresses transmitted to the wound through body movement or muscle action). In some variations, the device protects the wound from endogenous stresses, while having no effect on exogenous stresses on the wound, such as devices that modulate the elastic properties of the skin, etc. In other variations, the apparatus protects the wound from exogenous stress without affecting endogenous stress on the wound. Such variations may include the following: muscles and tissue surrounding wounds have been paralyzed, for example, due to botulinum toxin and the like. In still other variations, the apparatus protects the wound from both endogenous and exogenous stresses.

The devices and bandages described herein may improve the formation of scarring at the wound site by applying stress and strain to deeper layers of epidermal and dermal tissue surrounding the wound in a controlled manner, thereby reducing the tension and pressure at the wound site itself. The stress at the wound site can be reduced to a level below that to which normal skin and tissue is subjected. Stress or strain can be applied to the surrounding tissue in one, two, or three directions to reduce endogenous or exogenous stress at the wound site in one, two, or three directions.

Referring to fig. 1, the device or bandage 100 includes a body 112, the body 112 being removably secured to a skin surface 135 surrounding a wound site 120, as indicated by arrow 116. The device 100 can be removably secured to a skin surface (e.g., stratum corneum and epidermis) 135 by an adhesive or by using one or more skin piercing devices (e.g., sutures, anchors, microneedles, spikes, etc.). In certain variations, the device is removably secured to tissue below the skin surface, e.g., sutures, anchors, staples, etc., can be used to removably secure the device to the deepest layer of the dermis all the way to the sarcolemma. In the variation shown in fig. 1, wound 120 extends below epidermis 135 through dermis 130 to hypodermis or subcutaneous tissue 140. Although device 100 is shown as a single layer in fig. 1 for simplicity, the devices described herein can include multiple layers and have any number of different configurations. In some variations, the device includes multiple layers that remain independent. In other variations, the device includes multiple layers in a stacked configuration. In still other variations, the apparatus includes multiple layers bonded or welded together, for example, in a laminated structure.

As shown in fig. 2A, device 200 may include an adhesive layer 214 for removably securing device 200 to the skin. The adhesive layer can be applied to the surface 213 of the body 212 to be in contact with the skin in any suitable manner. For example, the adhesive layer 214 can be a continuous layer around the periphery of the surface 213. In other variations, the adhesive layer 214 can be a continuous layer that substantially covers the surface 213. The adhesive layer 214 may be a continuous or discontinuous layer on the surface 213. In some variations, the adhesive layer 214 includes a pressure sensitive adhesive, such as a polyacrylic-based, polyisobutylene-based, and silicone-based pressure sensitive adhesives, among others. As shown in fig. 2B, in some variations, the apparatus 200 can include an optional wound dressing 218 applied to a wound (not shown). The surface 213 of the device 200 that will contact the skin is shown in fig. 2C. In this variation, the combination of adhesive layer 214 and wound dressing 218 substantially covers surface 213. In some variations (not shown), a wound dressing may be disposed on at least a portion of the adhesive layer. Alternatively, as shown in fig. 3A-B, the adhesive layer 314 of the device 300 may partially cover the surface 313 of the body 312, for example, by forming a frame around the periphery of the surface 313. An optional wound dressing 318 can be centrally disposed within the frame formed by the adhesive 314.

The body of the device need not be solid. For example, as shown in each of the side and top views of fig. 4A-B, the apparatus 400 can include a body 412 including at least one orifice 422. As indicated by arrow 416, an aperture 422 may be provided around the wound 120. As shown in fig. 5, the apparatus 500 can include a body 512 including a plurality of apertures 524. Although fig. 5 shows the apertures 524 arranged in a grid, the apertures can be arranged randomly or in any suitable manner, for example, in rows, columns, or in circles, ovals, or diagonal arrangements. The apertures (e.g., apertures 422, 524 in fig. 4 and 5) may also have any suitable shape, such as square, rectangular, quadrilateral, oval, circular, and the like. The apertures may also be of any suitable size. In addition, the contour of the orifice can be cut into the device according to the shape of the wound. For example, for an elongated wound, an aperture, such as aperture 422 in fig. 4, can have an elongated shape with the long axis of the aperture being substantially parallel to the long axis of the wound. In other variations involving elongated wounds, the aperture, such as aperture 422 in fig. 4, can have an elongated shape with the long axis of the aperture being substantially orthogonal to the long axis of the wound. In these variations, the opening may be cut by the user or an associated medical professional prior to use.

As noted above, the devices and bandages described herein protect a wound from endogenous and/or exogenous stress. Referring to fig. 6, the device 600 is removably secured to the stratum corneum (not shown) and epidermis 135 by a securing mechanism 626. As described above, the securing mechanism 626 may be any mechanism suitable for removably securing the device 600 to a skin surface proximate a wound site, such as an adhesive, a spike, a suture, a microneedle, an anchor, and the like. If an adhesive is used as the securing mechanism, the adhesive may be selected to have minimal creep over time. For example, the rheological properties of the adhesive may be adjusted. One method of adjusting the rheological properties of an adhesive includes adding a crosslinking agent to increase the crosslink density of the adhesive, such as a pressure sensitive adhesive. Suitable cross-linking agents may comprise highly functionalized molecules such as aluminum acetylacetonate (aluminum acetylacetonate). The crosslink density of the adhesive can be adjusted to achieve the desired viscosity value while minimizing creep of the adhesive over time. When the device is sutured, riveted, or stapled to the skin, the device may be attached to the dermis 130 or subcutaneous tissue 140 and epidermis 135. This may help to improve isolation and unloading of the wound from exogenous and/or endogenous stresses.

The device may be applied to the wound site at any suitable time. For example, in some variations, it may be desirable to apply the device to the wound site from about one to about three days after the wound, i.e., during initiation such as the early part of the proliferative phase. It should be understood that the device may or may not be applied to the wound site if the wound has been initially closed (e.g., by sutures, adhesives, bandages, etc.). Similarly, the device may be applied to a new wound resulting from the scar removal process. In some instances, the device is not applied until seven days after the wound, i.e., at a later stage of the proliferation stage. For example, swelling and wound secretions may indicate that the device is applied later than three days after being injured. In some applications, the first bandage can be applied at an initial stage after the wound, for example within the first three days, and then removed, after which the second bandage can be applied. The second bandage is able to adapt to changes in the skin and tissue surrounding the wound that occur after the initial phase-such as swelling and reduction of secretions.

Referring again to fig. 6, after the device 600 is attached to the skin near the wound site, the device 600 contracts as the body 612 contracts in at least one direction. As the device 600 contracts, the stress is transferred to the skin at or beyond the securing mechanism 626, as indicated by arrows 642, thereby reducing the stress at the wound site. By adjusting the amount and direction of contraction of the device 600, the wound 120 can be effectively isolated from exogenous and/or endogenous stresses in many cases. That is, the apparatus 600 is operable to unload the wound 120 and surrounding tissue from endogenous stresses from skin tension and exogenous stresses from muscle action and body movement. In this way, scar formation at the wound 120 may be reduced.

The devices and bandages described herein may have any suitable shape. For example, the device or bandage may be rectangular, square, circular, oval, annular, or fan-shaped, or a combination thereof. In many variations, the device may be flexible and flat to allow shape-retaining placement on the skin. Of course, the device and bandage may also be of any suitable size to cope with a variety of wounds. In some variations, the device and bandage may be cut from a roll or sheet of bandage just prior to use to ensure proper coverage of the wound site. In some cases, the device and bandage can extend about 20cm (about 8 inches) from the wound, in other cases, the device and bandage can extend about 2, 4, 6, 8, 10, 12, 14, 16, or 18cm from the wound, where "about" is used for each distance. In still other variations, the bandage can extend about 22cm, about 24cm, about 26cm, or more from the wound. In some variations, the device is made of a polymer, such as a shape memory polymer. Any suitable shape memory polymer may be used, for example styrene-based, epoxy-based or acrylic-based shape memory polymers.

The device and bandage may or may not be closed, and in some variations, the device and bandage are closed. At least a portion of the device and bandage may also be made of a transparent material. A transparent material may be disposed over the wound to allow monitoring of the wound (e.g., monitoring infection or healing processes). In some variations, the devices or bandages described herein can be perforated, partially perforated, or at least partially perforated. For example, some variations of devices and bandages allow for the exchange of oxygen and/or moisture with the environment.

The device and bandage may also contain a mechanism for increasing the temperature at the skin surface to which the device or bandage is applied. This may be advantageous, for example, to assist the healing process. The mechanism may be electronic, such as a resistive heating element, chemical, such as an exothermic chemical reaction, or mechanical, such as forming a frictional element against the skin.

The devices and bandages described herein may also include a mechanism that causes a color change in at least a portion of the bandage. This may help, for example, to alert the user that the efficacy, stiffness, etc. of the device is poor. In some variations, the color change of the device or bandage may correspond to a change in the stiffness of the bandage. For example, if the device or bandage is tightened or tensioned, at least a portion of the device or bandage may have a different color than when it is relaxed. Similarly, a color change of the device or bandage may correspond to an efficacy change of the bandage. For example, at least a portion of the device or bandage may change color as its moisture content changes. In other variations, the device or bandage may change color after a predetermined period of time.

The devices or bandages described herein may also include or release one or more active agents. The active agent is capable of assisting wound healing, and thus may comprise any suitable component. For example, the active agent may be a pharmaceutical ingredient, a protein, a vitamin, or the like. Exemplary active agents that may be suitable for use in the devices and bandages described herein include, but are not limited to: a growth factor; enzymes such as elastase to degrade additional intercellular substance; proteases such as aspartate, serine and metalloproteases, which are capable of digesting and remodeling tissue; inhibitors of enzymes such as tissue inhibitors of metalloproteinases, antibiotics, antimicrobials, vitamin E and combinations thereof. In some variations, the release of the active agent can be controlled by sustained release, for example by encapsulating or placing the active agent in a sustained release formulation, such as a drug release polymer or sustained release agent (depot).

In some variations, a bandage for improving scarring and/or scarring at a wound site has a first tensioned configuration (e.g., as shown in fig. 7A) and a second relaxed configuration (e.g., as shown in fig. 7B). For example, as shown in fig. 7A, a device or bandage 700 having a body 712 can be removably secured to a skin surface or epidermis 135 near a wound 120 by a securing mechanism 726 while in a first configuration 706'. As shown in fig. 7A, the configuration 706' is stretched in at least one direction. In some variations, the device 700 is removably secured to the dermis 130 and epidermis 135 by a securing mechanism 726, such as using sutures, anchors, spikes, microneedles, and the like. In still other variations, device 700 is removably secured to tissue deeper than dermis 130. As mentioned above, if an adhesive is used as the securing mechanism, the adhesive may be selected to have minimal creep over time, for example by adjusting the cross-link density of the adhesive. The crosslink density of the adhesive can be adjusted to achieve the desired viscosity value while minimizing creep exhibited by the adhesive. When the tensile stress is removed from the device 700, the device 700 will assume the relaxed configuration 706 shown in FIG. 7B, tightening tissue at or beyond the securing mechanism 726 as indicated by arrow 707. In this manner, wound tissue beneath the device 700 is pulled inward to reduce stress at the wound, as indicated by arrows 708. The first tensioned configuration 706' may be tensioned about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% relative to the relaxed configuration 706. It should be understood that the term "about" is used for each of these percentages. By adjusting the amount and direction of stress of the tensioning configuration 706', stress at the wound site 120 may be minimized. That is, the device is capable of protecting wounds and tissues from endogenous and/or exogenous stress. In some cases, the device can reduce stress at the wound site such that it is below the stress experienced by normal unbacked skin. Further, the stress in the tensioning configuration 706' may be adjusted for different skin types and thicknesses to protect, i.e., unload, the wound from endogenous stresses. In addition, the stress in the tensioning configuration 706' may be adjusted to accommodate different ranges of motion to protect, e.g., unload, the wound from exogenous stress.

In the variation shown in fig. 8A-B, the bandage 800 has a (width) X in the X-direction in its relaxed configuration 806₈And (length) Y in the Y-direction₈. As shown in fig. 8B, the bandage 800 can be tensioned, i.e., stretched, in at least one direction to form a tensioned configuration 806'. In this variation, bandage 800 is stretched in the Y-direction to a length Y₈', but remain substantially untensioned in the X-direction to substantially maintain the width X₈. Bandage 800 in its tensioned configuration 806' can then be placed over wound 120 and removably secured to the skin surface by securing mechanism 826. In this variation, securing mechanism 826 is disposed adjacent to bandage edge 802. The tension on bandage 800 may isolate and protect wound 120 from endogenous and/or exogenous stress in the Y-direction.

In the variation shown in fig. 9A-B, bandage 900 has a width X in its relaxed configuration 906₉And length Y₉. As shown in fig. 9B, bandage 900 with body 912 and optional aperture 922 can be tensioned in at least two directions to form a bandage having a width X₉' and length Y₉'tensioning configuration 906'. The tensioning configuration 906' can then be applied to the wound 120, for example, by framing the wound 120 in tensionIn tight aperture 922' and is removably secured to the skin surface by securing mechanism 926. Bandages such as bandage 900 are tensioned in at least two directions and may protect, i.e., isolate, the wound from endogenous and/or exogenous stress in at least two directions.

In certain variations, the first tensioning configuration may be mechanically induced. For example, the device or bandage may comprise at least one spring element. The spring element is extendable to form a tensioned configuration and the spring element is releasable to form a relaxed configuration. Alternatively, the device or bandage may comprise an elastic material, such as a biocompatible polymer, for example silicone. The elastic material may be stretched to form a tensioned configuration. In other variations, the first tensioned configuration may be at least partially induced by at least one piezoelectric element. In still other variations, the first tensioning configuration may be electrostatically induced. In some variations, the bandage is made of a shape memory polymer and therefore can be easily made to have a first, tensioned configuration and a second, relaxed configuration. The device or bandage may be tensioned in a dynamic manner, for example, by applying an oscillating force to the device or bandage. For example, if the bandage comprises a piezoelectric element, an alternating electrical potential can be applied to the piezoelectric element such that the device alternately elongates and contracts in at least one direction. Similarly, if the bandage comprises an electrostatic element, an alternating electrical potential can be applied to the electrostatic element to cause the bandage to alternatingly elongate and contract in at least one direction.

Some bandages include at least a first, second, and third configuration. In these variations, typically, the second configuration is tensioned relative to the first configuration. The bandage is configured to be removably secured to a skin surface when in a second configuration, and is actuatable to achieve a third configuration when in the second configuration. In some variations, the second configuration can be thermally actuated to achieve the third configuration. For example, body heat, a heating pad, a blower, a heat gun, etc. may be used to actuate the second configuration to achieve the third configuration.

The first configuration may be "stored" in the bandage. For example, when using raw materialsA compatible, non-shape memory polymer (e.g., such as a silicone polymer sheet), the first configuration may be stored in the following manner: the polymeric sheet is stretched and then clamped along its edges to a stiffer polymeric sheet using any suitable attachment device. The bandage may be relaxed for a period of time (e.g., about 5 minutes, about 10 minutes, about 20 minutes, etc.) or not prior to application to the skin. If the bandage comprises a shape memory polymer, the first configuration may be stored by cross-linking the polymer sheet to form a flexible first configuration. At the glass transition temperature T of the polymer_gAbove, the polymer is capable of deforming or straining to achieve the second configuration. By cooling the polymer to well below the T of the polymer while maintaining the strain_gThe second strained configuration can be stabilized or "locked in". In a number of variations, the shape memory polymer can be cooled to at least below T_gAbout 10 ℃, about 20 ℃, about 30 ℃ or about 50 ℃ to stabilize the strained configuration. In some cases, the shape memory polymer can be cooled below T_gAbove about 50 ℃. If stored in ratio T_gAt sufficiently low temperatures, the second strain configuration can be stabilized indefinitely. For example, in many variations, the ratio T can be_gThe strain state of the shape memory polymer bandage is preserved indefinitely at temperatures above about 20 ℃. In some variations, at ratio T_gThe strain state of the polymeric bandage can be preserved indefinitely at a temperature about 15 c or about 10c lower. If the polymer is heated to above T_gAnd is no longer significantly loaded or constrained, the polymer may return to substantially its original first configuration. Thus, in certain variations, the third configuration may be substantially the same as the first configuration. If the polymer is loaded or constrained, it may assume a third configuration between the first configuration and the second configuration. That is, the shape memory polymer bandage in the second configuration is heated to above T_gIt is possible to return at least partially to its first configuration, subject to the constraints to which the bandage is subjected. For example, recovery of the strained configuration of a shape memory polymer bandage attached to the skin may be affected by skin compliance. Shape memoryThe memristive polymer may be selected to have a T compatible with use on human skin_gFor example from about 35 ℃ to about 55 ℃. In certain variations, the device may include one or more thermal barriers that allow for the use of T_gA shape memory polymer above about 55 ℃. Higher T_gMay have a higher modulus of elasticity and less creep deformation over time.

In certain variations, the third configuration of the bandage can differ from the second strain configuration in at least one dimension or direction. In other variations, the third configuration can differ from the second strained configuration in at least two directions. In some variations, the third configuration differs from the initial first configuration by less than about 10%, about 20%, about 30%, about 40%, about 50%, or about 60% in at least one direction. In other variations, the third configuration differs from the initial configuration by less than about 10%, about 20%, about 30%, about 40%, about 50%, or about 60% in at least two directions. In some variations, the second configuration is deformed by about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% relative to the first configuration. It should be understood that the term "about" is used for each of these percentages. By adjusting the amount and direction of strain of the strain configuration, stress at the wound site may be minimized. That is, the amount and direction of strain in the pre-straining device or bandage can be adjusted for different skin types, thicknesses, and conditions to protect, i.e., unload, the wound from endogenous stresses. In addition, the amount and direction of strain in the pre-strain device or bandage can be adjusted to accommodate different ranges of motion or muscle action to protect the wound from exogenous stress.

Figures 10A-C illustrate a variation of a bandage or device for improving scarring and/or scarring. As shown in fig. 10A, device or bandage 1000 includes a polymeric backing layer 1048, backing layer 1048 having a first configuration 1006, first configuration 1006 being generally shaped to have a width X₁₀And lengthY₁₀A flat rectangular sheet of (a). The first configuration 1006 has been stored in the polymer layer 1048, e.g. by cross-linking or by pre-stretching. The polymer layer 1048 can be heated to exceed the T of the polymer_gAnd deformed to assume a second configuration 1006', such as by applying forces in the X-direction and the Y-direction. Strain configuration 1006' can also have a generally flat rectangular sheet configuration, but with a width X₁₀' and length Y₁₀'. Can be made, for example, by subsequently cooling the polymer layer 1048 to below T while still under tension_gTo stabilize the second configuration 1006'. The tension can then be removed if it remains at T relative to the polymer_gThe strain configuration 1006' may be stable at sufficiently low temperatures, e.g., about 10 deg.C, about 15 deg.C, about 20 deg.C, or more. Once the device or bandage 1000 is reheated above T without significant restraint_gCan generally recover its stable strain configuration 1006' to have a general X₁₀Width and approximately Y₁₀As shown in fig. 10B, as an initial configuration 1006 of the length of (a).

The devices or bandages described herein are typically removably secured to a skin surface in a strained configuration. If the bandage or device is reheated to above T in its stable strained configuration_gSubject to a load or constraint, the ability to return to the original configuration may be limited by the constraint. Referring to fig. 10C, the strain configuration 1006' is removably secured to the skin (not shown) by a securing mechanism 1026 and is thus constrained. The strained configuration 1006' reverts to the third configuration 1006 "rather than the initial configuration 1006. In the variation shown in FIG. 10C, the device 1000 is constrained primarily only in the X-direction. The apparatus 1000 is capable of achieving a third configuration 1006 "-which has recovered to a considerable extent the initial length Y₁₀But only partially restoring its width along the X-direction, resulting in a restored X-direction X₁₀"falls in X₁₀' and X₁₀In the meantime.

When the device or bandage is made of a polymer, the polymer may have any suitable thickness. For example, the polymer thickness may be from about 100 or 200 microns to several millimeters. The thickness of the polymer sheet, e.g., a silicone polymer sheet or a shape memory polymer sheet, can be selected to provide sufficient load bearing capacity for the device or bandage to achieve a desired recoverable strain, as well as to prevent undesirable amounts of creep deformation of the bandage or device over time. In some variations, the thickness on the device or bandage is not uniform, e.g., the thickness on the device can be varied to change stiffness, load carrying capacity, or recovery strain in a selected direction and/or location. In some variations, the device or bandage is tapered near the edges to reduce thickness. Devices or bandages having tapered edges may increase the flexibility of the device or reduce the likelihood of the device or bandage debonding over time. Furthermore, a device with tapered edges may increase wearer comfort.

In some variations, the bandage or device comprises a mesh or wire frame. As shown in fig. 11, the elements 1160, 1162 forming at least a portion of the mesh or frame 1130 can be integrated into a bandage or device 1100. In some variations, the elements 1160, 1162 comprise a shape memory metal. That is, in some variations, the bandage or device includes a shape memory metal formed as a mesh or wire frame. In other variations, elements 1160, 1162 comprise a shape memory polymer. In still other variations, element 1160 or 1162 may be an elastic fiber having a first tensioned configuration (not shown). The device 1100 can be removably secured to the skin adjacent the wound site with the element 1160 or 1162 in its tensioned configuration. Although fig. 11 shows mesh or frame 1130 having a grid configuration with elements 1160 oriented generally perpendicular to elements 1162, elements 1160, 1162 may be any suitable configuration, such as linear strips, diagonal, circular, oval, or various three-dimensional configurations, such as a three-dimensional mesh. When the elements 1160, 1162 are shape memory metals, any suitable shape memory metal may be used, such as nitinol or the like. In addition to the shape memory metal, the elements 1160, 1162 of the device or bandage may also include a polymer.

If shape memory gold is usedAnd the first unstrained configuration may be formed by shaping the metal in the high strength austenite phase into the desired configuration. Storing the second strain configuration in the following manner: first, the metal is heated to a temperature above M_f(at this temperature, the metal is completely in its soft martensite phase) plastically deforming the shape memory metal; then, the metal is cooled to below A under the strain_f(at this temperature, the metal reverts to its high strength austenite phase). If the second strain configuration of the shape memory metal is heated above M without restraint_fThe shape memory metal is then able to return substantially to the dimensions of the first configuration. If the second strain configuration of the shape memory metal is heated above M under constraint_fIt may only partially return to the dimensions of the first configuration, i.e. it will return to the third configuration. In some variations, the shape memory metal may be a metal wire, mesh, or foil, such as a thin metal wire, mesh, or thin foil. Any combination of metal wires, mesh or foil shape memory metals may also be used. Of course, combinations of different shape memory materials may be used in the device or bandage, such as a combination of shape memory metals or a combination of shape memory metals and shape memory polymers. In still other variations, the shape memory metal is at least partially covered by plastic or fiber in the first unstrained configuration or the second strained configuration. The phase transition temperature of the shape memory metal used in the devices or bandages described herein may be selected to be compatible with use on the skin, for example between about 35 ℃ and about 55 ℃. In certain variations, the device may include one or more thermal barriers that may allow the use of shape memory metals with phase transition temperatures in excess of about 55 ℃. In some variations, the body heat may be sufficient to raise the temperature of a shape memory metal used in the device above M_f。

Variations of the first unstrained configuration, the second strained configuration, and the third recovered configuration are also shown in fig. 12A-D, 13A-D, and 14A-D, in addition to those variations described above in connection with fig. 10A-C. FIG. 12A shows a first configuration 1206 of the apparatus 1200, the first configuration 1206 having a width X₁₂And lengthDegree Y₁₂Is rectangular. The device 1200 is heated above a transition temperature, e.g., T>T_gOr T>M_fTo assume a second strain configuration 1206'. The second strain configuration 1206' is stabilized by cooling the device 1200 below its transition temperature. In this variation, the strain of the strained configuration 1206' relative to the initial configuration 1206 is primarily elongation in the Y-direction, and substantially unstrained in the X-direction, having a width X₁₂And length Y₁₂' (FIG. 12B). At a temperature below the transition temperature, the strained configuration 1206 'is applied proximate the wound 120, and the strained configuration 1206' is removably secured to the skin (not shown) by a securing mechanism 1226 adjacent the device edge 1253 (fig. 12C). Heat is applied to the strained configuration 1206' such that its temperature exceeds its transition temperature, and it will attempt to assume its initial first configuration 1206. However, because the configuration 1206' is constrained in the Y-direction by attachment to the skin along both edges 1253 in its deformed state, the device 1200 cannot recover its original Y-direction dimension Y₁₂. Conversely, the device may be restored to have a length Y₁₂"intermediate third configuration 1206" (FIG. 12D), wherein Y₁₂"is the initial length Y falling in the first configuration 1206₁₂And strain length Y of the strained configuration 1206₁₂Length between'. Fixed configuration 1206 "transfers stress in the Y-direction to skin at fixation mechanism 1226 and beyond fixation mechanism 1226, as indicated by arrow 1252. Thus, the device 1200 attached in configuration 1206 "is able to protect, i.e., unload, the wound from endogenous and/or exogenous stress in at least the Y-direction, thereby improving scar formation at the wound 120.

Fig. 13A shows a variation of apparatus 1300 having a first configuration 1306. The first configuration 1306 has a width X₁₃And length Y₁₃And has an aperture 1322. The device is heated to its transition temperature (e.g. T)_gOr M_f) And in the X-direction and Y-direction. As shown in fig. 13B, device 1300 is also approximately rectangular in strain configuration 1306', having a width X₁₃' and length Y₁₃'. In thatIn some variations, the size and/or shape of the aperture 1322 can be varied to form the aperture 1322 'in the strained configuration 1306'. Device 1300 stabilizes in a strained configuration 1306' by cooling below the transition temperature under strain. As shown in fig. 13C, device 1300 in its deformed configuration 1306' is removably secured to the skin surface by securing mechanism 1326 to frame wound 120. Although the securing mechanism 1326 is shown as generally following the shape of the device 1300, other variations may be employed. For example, the device can be removably secured to the skin at spaced apart fixed locations, or around the periphery of the device. After the device 1300 is secured to the skin, heat is applied to raise the temperature of the device above its transition temperature so that the device will attempt to return to its original configuration 1306. If the device 130 in the strained configuration 1306' is subject to constraint, for example by being secured to the skin, the device will not be able to fully return to its original configuration 1306 but may change to a third configuration 1306 ". The third configuration 1306 'can fall between the first configuration 1306 and the second configuration 1306', having a fall X₁₃And X₁₃Width X between₁₃"and fall in Y₁₃And Y₁₃Length Y between `₁₃". As indicated by arrows 1356 and 1358, the apparatus 1300 is capable of protecting, i.e., unloading, the wound 120 from endogenous and/or exogenous stress in at least two directions, thereby improving scar formation at the wound 120.

Another variation of the device or bandage is shown in fig. 14A-D. As shown in fig. 14A, the device has a first configuration 1406 that is generally circular or oval in cross-sectional diameters D1 and D2. The device 1400 is strained while being heated above the transition temperature to form a second configuration 1406' (fig. 14B). In this variation, the device 1400 is strained in both the X-and Y-directions to result in a second configuration 1406 ' that is circular or oval in shape, having cross-sectional diameters D1 ' and D2 '. The temperature of the device 1400 is then lowered below the transition temperature while the device 1400 is still under strain, such that the strained configuration 1406' is stabilized. Removable version of device 1400 using securing mechanism 1426 in deformed configuration 1206' (fig. 14C)Secured to the skin (not shown) over the wound 120. Although the securing mechanism 1426 is shown here as a suture, staple, microneedle, anchor, or the like, as described above, the device 1400 can be secured to the skin surface using any suitable means. Applying heat to increase the temperature of the device 1400 to its transition temperature (e.g., T)_gOr M_f) The above. The deformed state 1406' is then able to achieve its initial configuration 1406 under constraint. As shown in fig. 14D, if the device 1400 is significantly constrained in the X-and Y-directions, the resulting configuration 1406 "may be generally circular or oval with cross-sectional diameters D1" and D2 ", where D1" falls generally between D1 and D1 ', and D2 "falls generally between D2 and D2'. In some variations, the constraint in one or both directions will be sufficiently small that D1 "is substantially equal to D1 and/or D2" is substantially equal to D2. In other variations, the constraints in one direction will be greater than the constraints in the other direction. In some variations, skin compliance constrains the recovery of the strained configuration 1406'. The device 1400 may transmit stress at the wound site to the skin at or beyond the securing mechanism 1426, thereby protecting the wound 120 from endogenous and/or exogenous stress and improving scar formation. If D1 "or D2" is significantly altered relative to D1 'or D2', apparatus 1400 is able to protect wound 120 from endogenous and/or exogenous stress in at least one direction. If both D1 "and D2" are significantly different from D1 'and D2', apparatus 1400 is able to protect wound 120 from endogenous and/or exogenous stress in at least two directions.

In some variations, the device and bandage may include or be made of more than one material, such as more than one polymer or more than one shape memory material. For example, the device can include two different silicone polymers or two different shape memory materials, such as two different shape memory polymers, two different shape memory metals, or one shape memory polymer and one shape memory metal. If more than one material is used in the device, the materials may be selected to have different transition temperatures, different amounts of strain that may be incorporated into the strained configuration, or different ability to return to the original configuration against the constraints-i.e., different load carrying capacity upon heating above the transition temperature.

A variation of a device 1500 including two shape memory polymers is shown in fig. 15A. Device 1500 is formed in its stable strained configuration 1506' having a width X₁₅' and length Y₁₅' is rectangular. The device 1500 in the strained configuration 1506' includes: a strain bandage or fiber 1574' made of a first shape memory material extending in the X-direction; and a strain bandage or fiber 1576' made of a second shape memory material extending in the Y-direction. The initial configuration (1506) is not shown. Although fig. 15A shows the bandages or fibers 1574, 1576' as being interwoven, they may or may not be interwoven. The device 1500 in the second strained configuration 1506' is attached to the skin (not shown). If device 1500 is heated above the transition temperature of the two shape memory materials, then different recovery in the X-and Y-directions may occur due to different relative strains or different compliances of the two materials. As shown in FIG. 15B, the strain bandage or fiber 1576 'relaxes to state 1576 "and the strain bandage or fiber 1574' relaxes to state 1574", resulting in a tape having a width X₁₅"and length Y₁₅"in a third configuration. In this variation, the percent change between the loose bandage 1574 "and the strain bandage 1574 'is less than the percent change between the loose bandage 1576" and the strain bandage 1576'. This asymmetry, in turn, results in the apparatus 1500, in its third configuration 1506 ″ being adopted, advantageously protecting, i.e., unloading, the wound (not shown) from endogenous and or exogenous stress in the X-direction, as indicated by arrows 1570 and 1572.

In some variations, the apparatus may include elements having different dimensions to protect the wound from stress in one or more directions. As shown in fig. 16A, device 1600 in the second strain stabilization configuration 1606' can be removably secured to skin near the wound site. The device in the second configuration 1606 ' has thick bandages or fibers 1686 ' extending in the Y-direction and thin bandages or fibers 1684 ' extending in the X-direction. The bandages or fibers 1686 'and 1684' may be made of the same or different materials and may or may not be interwoven. If device 1600 is heated above the transition temperature of elements 1686 'and 1684', then, third configuration 1606 "can preferentially recover in the Y-direction in certain variations because the ability to recover thicker bandages 1686" in the Y-direction is higher than to recover thinner bandages 1684 "in the X-direction in terms of overcoming the constraint that impedes recovery to the original configuration (not shown). That is, if device 1600 were elongated in both the X-and Y-directions in its second strained configuration 1606 ', the recovered third configuration 1606 "may have characteristics Y16"/Y16 ' < X16 "/X16 '.

External member

Kits for ameliorating scarring and/or scarring are also described herein. Typically, at least two devices are included in the packaged combination of the kit, wherein each device is configured to be removably secured to a skin surface in the vicinity of a wound site. Each device protects, i.e., unloads, the wound from endogenous and/or exogenous stress.

In some variations, the devices in the kit are of different colors. Variations of the kit may include devices that are color coded for different schedules. For example, one color of the device may be specified for an early stage of the proliferative phase of wound healing, while another color of the device may be specified for a later stage of wound healing. In some variations, the devices in the kit have different shapes. For example, the shapes may be independently selected from the group consisting of rectangular, circular, square, trapezoidal, annular, oval, and fan-shaped, and combinations thereof. In some variations, the devices in the kit may have different sizes or different thicknesses. The devices in the kit may also be configured to protect the wound from varying amounts of endogenous and/or exogenous stress. Multiple devices in a kit may be designed to be applied in a parallel fashion, e.g., more than one device secured around a wound at the same time. The parallel application of the devices includes the following cases: the securing of the plurality of devices occurs simultaneously, and the second device is secured while the first device remains secured. Multiple devices may also be applied in a serial fashion, with a first device removed before a second device is secured. For example, some kits may include one device that is applied during the early initiation of a proliferative phase such as wound healing (e.g., three days after wounding) and then removed, and a second device that is applied thereafter. Variations of the kit may include blowers, heat guns, heat pads, etc. to raise the temperature of one or more devices. Some kits may include at least one wound dressing, or at least one wound cleanser, or other components suitable for or desired for wound healing. The kit may further include instructions for use of the device and/or other components therein.

Method of producing a composite material

Also described herein are methods for ameliorating scarring and/or scarring. The methods generally include applying an apparatus configured to protect the wound from endogenous and/or exogenous stress in the vicinity of the wound site. In some variations, the apparatus is configured to protect the wound from both endogenous and exogenous stresses.

The device may be applied during the proliferative phase of wound healing, which has been explained above, or after the old scar has been excised and during the proliferative phase of wound healing. The device may be applied or worn for any suitable length of time. For example, the device may be applied or worn for at least about 10 days, at least about 20 days, at least about 30 days, at least about 40 days, at least about 50 days, at least about 60 days, at least about 70 days, at least about 80 days, at least about 90 days, at least about 100 days, and so forth. In some variations, such as when used on wounds involving burns, the device may be applied for more than 100 days, for example for about 6 months, about 9 months, about 12 months, or about 15 months, or even longer.

The device is typically removed after a period of time, which may or may not be predetermined. For example, the length of time may be predetermined based on the type of wound. In other variations, the length of time may be actively monitored and thus varied according to the progress of the wound healing process.

The method may further comprise applying a second apparatus to the skin adjacent to the wound site, the second apparatus configured to protect the wound from endogenous and/or exogenous stress. In other variations, the method may include applying a second apparatus configured to be removably secured to a skin surface and reduce wound stress in at least one direction to skin proximate the wound site. In some variations, the second apparatus is configured to reduce wound stress in at least two directions. If the second device is applied, it may be applied in parallel with the first device. That is, the second device may be applied before the first device is removed. In some variations of the method, the second device may be applied in a serial manner, i.e. after removal of the first device. For example, the first device may be applied during an initial period such as the early part of the proliferative phase (when the tissue is swollen and the wound is exuding much) and then removed. Thereafter a second device can be applied, wherein the characteristics of the second device are selected to reflect less swelling and/or wound outflow. In some variations of the method, several devices may be applied in parallel or in series to reflect the wound environment as healing progresses.

Examples

Adult wounds can present extensive dermal scarring, while fetal and murine wounds do not usually. Young's modulus, the ratio of stress to strain, is a well established measure of stiffness. Stiff materials, i.e., high young's modulus materials, exhibit small deformations (strains) in response to applied forces (stresses). Soft or flexible materials have a low modulus and exhibit large deformations in response to applied forces. The tension of the dermis layer depends on the resting tension of the skin, which may be affected by factors such as skin thickness, moisture content, and intercellular components. The young's modulus of adult skin is higher than that of mouse or young child skin. Can be applied by placing the mouse on the woundThe mechanical force was increased to a mechanical force close to that on human wounds, thereby forming hypertrophic scars on the dorsal dermis of the rat to establish a murine model system for scarring of human dermal tissue. At rest, typical adult skin is at about 0.4-1N/mm²Under stress of (a). Adult wounds in healing are usually at about 0.6-2N/mm²Under stress of (a).

Example 1 examples of stress that may cause or promote hypertrophic scar formation

Four week old C5/BL6 mice were housed under standard protocols approved by the new york university animal protection and utilization committee (new york university animal care and use mice). A mechanical tensioning device 1700 as schematically shown in fig. 17 was constructed by securing a 22mm expansion bolt 1790 (available from great lakes and architectural products, Tonawanda, NY) to a titanium surgical Luhr plate support 1792 (available from striker-leigningerco, Freiburg, Germany). Expansion bolts 1790 are secured to the plate support 1792 by a plastic interface and clear resin (not shown, available from devcon scientific, rivierbeach, FL, which may be dried overnight). As schematically shown in fig. 18-19, two 2cm linear full thickness incisions (1802, 1802 ', 1902 ') were made spaced 1.25cm apart along the length (1810, 1910) of each rat's back. The incision was closed using 6-0 nylon suture. On the fourth day after the incision, during the proliferative phase of the wound healing process, the suture was removed.

As shown in fig. 18, two mechanical tensioning devices 1800, 1800 'are attached to the rat back 1810 by suturing over wounds 1802, 1802', respectively. The tensioning device 1800, 1800 'does not physically contact the wound 1802 or 1802'. The tensioning device 1800, 1800 'is oriented relative to the incision 1802, 1802' to apply tension to the wound in a direction generally orthogonal to the incision direction. Similarly, as shown in fig. 19, two tensioning devices 1900, 1900 'are attached to the back 1910 of the rat by stitching over wounds 1902, 1902', respectively. In this example, the tensioners 1900, 1900 'are oriented relative to the incisions 1902, 1902' along a direction substantially parallel to the incisionsThe direction of the force is applied to the wound. The tensioning devices 1800, 1900 are adjusted to make the wounds 1802, 1902 free from additional tensioning, respectively. Adjusting the tensioning devices 1800 ', 1900' applies tension to the wounds 1802 ', 1902', respectively. On the fourth day after incision, the substantially uniaxial tension on the wound 1802 ' is increased by increasing the distance between the Luhr plates 1892 ' by 2mm using expansion bolts 1890 ' to produce an estimate of 1.5N/mm²And 4mm every other day for 7 days thereafter to increase the applied stress to about 2.7N/mm². If expansion bolts 1890' are not used to mechanically increase the tension, the natural elongation of the skin results in a continuous reduction of the force on the wound. Range of applied stress (1.5-2.7N/mm)²) Chosen to replicate the stress to which a healing human wound is subjected and below the fracture limit of a murine wound (9.6N/mm)²). Stress is then applied to the wound 1902 ' by increasing the distance between the Luhr plates 1992 ' using expansion bolts 1990 '. After 7 days, all tension was removed from the wound. Scar tissue from stressed and unstressed wounds was collected once a week for one month and again at six months after incision. Three to six mice were used for each experiment.

Tissue collected from unstressed wounds 1802, 1902 after 3 weeks did not exhibit significant fibrosis. However, tissue collected from a wound 1802' stressed in a direction generally normal to the incision, as shown in FIG. 18, is characterized by hypertrophic scar tissue having a cross-sectional area approximately 15 times greater than tissue of an unstressed wound. Further, tissue collected from a wound 1902' stressed in a direction generally parallel to the incision as shown in FIG. 19 has a cross-sectional area that is about 5 times higher than tissue collected from an unstressed scar. Mouse stressed scars exhibit many of the characteristics of human hypertrophic scars. The mouse has a high level of stressed scarring and shows a reduction in epidermal feet (retepegs), appendages and hair follicles. The stressed scar showed cellular proliferation and the fibroblasts were oriented approximately parallel to the collagen fibers and the direction of the tension. Furthermore, the blood vessels in the stressed wound are approximately perpendicular to the wound. Stressed rat scarCollagen wheels (collagenwhorl) are also shown, which are often observed in chronic hypertrophic scars of the human body. It was also shown that scar tissue from stressed murine wounds has at least double the cell density (per mm) by Dapi nuclear staining²Cell number of (d). In addition, stressed rat scars extended a height of approximately 3mm on average above the skin surface, but the unstressed scars remained substantially flat.

After 11 days of tensile stress, all RNA was taken from murine skin tissue and was hybridized to affymetrix43k2.0 gene chips. Displacement-based algorithm-chip Significance Analysis (SAM) showed 347 genes reproducibly recognized in nicking wounds subjected to tensile stress relative to nicking wounds not subjected to tensile stress (false discovery rate < 0.05). The tensile stress on the healing wound results in the expression of genes involved in the formation of additional intercellular stroma (e.g., aposporin, procollagen or collagen of type B, III-VII, lysyl oxidase, etc.). Since it is known that human scars, hypertrophic scars and scars represent an excess of mesenchymal related proteins, these results enable validation of murine models and indicate that mechanical stress promotes or causes hypertrophization of human scars. Furthermore, mechanical stress causes the genes associated with angiogenesis (lysyl oxidase, VCAM-1, angiopoietin-like protein 2, RAMP2, or adrenomedullin receptor), multiple growth factors (IGF 1, Bdnf, Osf2, Raf53, TFPI, Lef1, Csf3 r), signal transducers (signaltranducer) (Vav, c-fes, CK creatine kinase (creatinekinase), Ste20, Neki7, Dcamk1, Macs, Eif2ak 3), and transcription factors (transcription factor) (HIF-1 a, c-maf, Tcf4, MITF4, test 2ip, Mafb) — all of which are associated with cell proliferation and differentiation.

Fig. 20 shows the qualitative effect of mechanical loading on scar volume. The skin of a human fetus is usually almost completely flaccid and is therefore under very little endogenous load. As a measure of skin elasticity of human fetal skin, dynamic resting tension (dynamicrestention) is below the currently available detection limit. Human fetal skin healingWith little or no scar volume, as shown at point 2002. The murine skin was at a higher endogenous load with approximately 0.06N/mm²Dynamic static tension. The baseline scar volume of murine skin is higher than that of human fetal skin, as shown by dots 2004. The data in this example show that for the murine model there is a positive correlation between mechanical load and scar volume, as shown by the solid trend line 1 in figure 20. Adult skin is subjected to higher endogenous stress than murine skin, with 0.132N/mm²Dynamic static tension. The baseline human skin scar volume obtained was higher than in mice, as shown at point 2006. Thus, as shown by dashed trend line 2, increased mechanical loading on adult wounds can increase scar volume. The devices and methods described herein are capable of reducing endogenous and exogenous loads on the wound area, and are expected to reduce the scar volume of the human body, as shown by dashed trend line 3. It should be understood that the dashed trend lines 2 and 3 are predictive, while the real trend line 1 refers to the qualitative correlation between mechanical load and scar volume observed from the murine model in this example.

EXAMPLE 2 preparation of an exemplary device or bandage

T available from MedShapesolutions, Inc.,900Anaconda Coart, CastleRock, CO_gAcrylic acid based shape memory polymer Memori with values of 20 ℃, 30 ℃ and 40 ℃^TMSystem's polymer sheet is cut into rectangular, generally flat, flexible bandages having an in-plane dimension of about 45mm × 20mm, T_gThe thickness of the sheet made of polymer with a value of 20c is about 200 and 500 microns. By T_gThe thickness of the sheet made of polymer having a value of 30 ℃ is about 500 microns; by T_gThe thickness of the sheet made of polymer having a value of 40 c is about 1000 microns. Each of a first set of 8 bandages was individually held between the clamping structures and heated to a temperature greater than the T of the polymer used in the bandage_gA temperature of about 60 ℃ to 90 ℃ higher. Heating the bandage to above T by translating the clamping structure away at a speed of about 1mm/min_gIs longer along the rectangleStretching the bandage to achieve a strain of about 8% to about 12%. By placing the bandages in a strained phase between the clamping structures in a freezer at-10 ℃ while applying strain, each bandage is cooled to a temperature well below the T of the polymer used in the bandage_g. After a cooling time of approximately one hour, each bandage was removed from the freezer and holding structure and stored at a laboratory ambient temperature of approximately 24 ℃, but at T_gExcept for the bandage made of a polymer at 20c, which was kept in a refrigerator at about 5 c.

Next, a pressure sensitive adhesive available from national Standard chemical company, Bridgewater, NJ, Duro-Tak87-4278 was applied to one side of the bandage. The pressure sensitive adhesive is in the form of a layer about 60 microns thick located between two polymeric release layers. One of the release layers is removed and then an adhesive layer pressure is applied to the polymeric bandage using a hand roller to remove air bubbles at the interface between the adhesive and the polymer. Excess adhesive layer is trimmed to the edges of the polymeric bandage. The remaining release layer was then carefully removed. Wound dressings approximately 10mm by 5mm in size obtained from commercially available bandages were adhered to the center of the selected example polymeric bandage. A polymeric release layer is then reapplied to the adhesive and the individual bandages are stored at the storage temperature described previously prior to use.

The polymeric release layer is removed from the selected bandage. Some bandages are heated to a higher T than the polymer used in the respective bandage_gAbout 20 ℃ to about 50 ℃ and is unconstrained. When unconstrained, it is generally observed that the bandage is heated above the polymer T_gIt returns to approximately its original unconstrained size. Using finger pressure will be at T_gOther bandages made of 30 ℃ polymer were attached to human skin at the location of the inner side of the forearm. After attaching the bandage to the skin, the bandage was heated to T using a heat gun_gThe above. It is estimated that a temperature of about 45 c is reached in about 15 seconds. Note that the bandage was partially recovered, achieving approximately 50% of the initial applied strain. These results are summarized in table 1 below.

TABLE 1 recovery of tensioned bandages with and without restraint

EXAMPLE 3 preparation of an exemplary device or bandage

Silicone polymer sheets MED82-5010-05, MED82-5010-10 and CSM82-4032-20 available from NUSILTECHNOLOGYLLLC, 1050CindyLane, Carpinteria, CA93013USA were cut into rectangular, generally flat, flexible bandages having in-plane dimensions of approximately 50mm by 40 mm. The MED82-5010-05 and MED82-5010-10 sheets had a hardness value of 50 and thicknesses of approximately 120 microns and 230 microns, respectively. CSM82-4032-20 sheet has a hardness value of 30 and a thickness of about 490 microns.

An additional silicone polymer sheet available from stockwell elastomers, inc.,4749tolbutst., philiadelphia, PA19136, USA, HT6240 was cut into rectangular, generally flat, flexible bandages having in-plane dimensions of approximately 50mm x 40 mm. The HT6240 sheet had a hardness value of 40 and a thickness of about 500 microns.

Next, MED1356 pressure sensitive adhesive available from NUSILTECHNOLOGYLLLC, 1050CindyLane, Carpinteria, CA93013USA was applied to one side of the bandage. The pressure sensitive adhesive is in the form of a viscous liquid and is applied directly to the silicone bandage by a metal spatula in a layer thickness of about 60 microns. The solvent in the pressure sensitive adhesive layer was allowed to evaporate in a laboratory air environment at a temperature of 25 ℃ for a period of 30 minutes, according to the manufacturer's instructions.

MED1356 pressure sensitive adhesives are manufactured by manufacturers with a range of permissible polymer-to-resin ratios, resin molecular weights, and polymer viscosities. Decisive important properties of these pressure-sensitive adhesives include the release force in the T-peel test and the force in the blunt probe tack test (bluntprobeacktest). The manufacturer has an allowable range for these values (force in the T-peel test is about 125kg/m to 286 kg/m). Our studies revealed that it is important to maintain the release force and blunt probe tack test values high to prevent relaxation of the silicone bandage after application to the skin. For batch 36232 of MED1356, the manufacturer reported values of 285.73kg/m for the release force in the T-peel test and 0.50kg for the blunt probe adhesion test. This batch did not result in relaxation of the silicone after more than three days of application to the skin. On the other hand, for batch 39395 of MED1356, the manufacturer reported values of 125.01kg/m for the release force in the T-peel test and 0.45kg for the blunt probe tack test. This pressure sensitive adhesive exhibits creep relaxation, resulting in complete relaxation of the initial silicone strain after 24 hours of application.

Prior to applying the bandage, the skin was marked where the bandage was to be applied with parallel lines of pen spaced approximately 10mm apart. In some cases, orthogonal line groups are established. All silicone bandages used were light transmissive and the lines could be seen through the bandage after attachment to the skin. This allows direct measurement of the strain of the skin by measuring the displacement of the wire before and after the bandage is applied. Strain in the skin can be continuously monitored by continuous optical microimages acquired over a period of time. An optical microimage showing the initial pen line on the skin (i.e., the image before bandage application) and the image after bandage application is shown in fig. 21. By measuring the change in line spacing, the strain applied to the skin can be directly calculated.

The silicone bandage is initially stretched to predetermined engineering strains of 10%, 20%, 30%, 40%, 50%, and 60% prior to attachment to human skin at a location inboard of the upper arm. In some bandages strain is applied in only one direction, in others it is applied biaxially in two orthogonal directions in the plane of the bandage. The strain is applied by stretching the bandage and clamping the bandage to the elastic, stiffer polymer sheet with rigid paper clips at the edges of the bandage. By varying the dimensions of the stiffer polymer sheets, the initial strain in the bandage can be systematically varied.

After the bandage was stretched to a predetermined strain, the bandage was allowed to relax for a period of about 10 minutes. This results in some stress relaxation in the bandage. The bandage is then attached to the human skin at a position inboard of the upper arm using finger pressure. After attaching the bandage to the skin, the clip is released and the bandage immediately exhibits elastic recovery. The degree of strain recovered depends on the initial strain in the bandage, the durometer value and thickness of the silicone polymer bandage. The final strain in the bandage and the strain applied to the skin are determined by the mechanical balance, which involves a balance of forces and moments between the bandage and the skin beneath it.

The bi-directional strain and related stress state in the skin beneath the attached bandage can be systematically controlled by selecting the thickness, mechanical properties, and initial elastic strain of the silicone bandage. For different silicone polymer bandages with different polymer backing thicknesses, a set of functional curves of initial tensile strain in the device and resulting compressive strain in the skin was developed. Examples of curves obtained from MED82-5010-05 and MED82-5010-10 pieces (with a durometer value of 50 and polymer backing thicknesses of about 120 microns and 230 microns, respectively) are shown in FIG. 22.

FIG. 23 illustrates the effect of pressure sensitive adhesive formulation on the skin strain applied by the apparatus. The type 1 formulation corresponds to batch 36232 of MED1356, which has a higher release force value in the T-peel and blunt probe tack test. The result of this batch was that no relaxation of silicone or skin strain was observed after more than three days of application to the skin at two different levels of strain. On the other hand, the type 2 formulation corresponds to MED1356, 39395 lot, which has a lower release force value in the T-peel and blunt probe tack test. The pressure sensitive adhesive exhibits creep relaxation which results in almost complete relaxation of the initial silicone strain after the first 24 hours after application.

Even for the higher levels of applied strain examined, there were no reports of discomfort or skin irritation during the study. To obtain a controlled strain state, the viscoelastic creep and recovery of the silicone bandage were evaluated. This includes creep relaxation at room temperature associated with initial pre-strain of the bandage, followed by elastic and viscoelastic recovery after attachment of the device to the skin. An example of MED82-5010 silicone (which has a hardness value of 50 and a thickness of 120 microns) is shown in fig. 24. The relaxation of the polymer bandage after initial strain at 25 ℃ at room temperature is very clear. The relaxation began to stabilize after about 10 minutes. Elastic strain recovery occurs immediately upon attachment of the bandage to the skin. As shown in fig. 24, the final equilibrium stress and strain levels were obtained and stabilized over time. No further changes in skin or bandage strain were observed.

We have further demonstrated that: the mechanical strain and stress state of the wound area under the central area of the bandage (which may not adhere to the underlying skin and contain, for example, a wound dressing) can be controlled. This is shown in fig. 25, which shows a polymer device having dimensions of about 35 x 20mm in the central area, which does not contain any adhesive layer for adhering the device to the skin. Analysis of the mark on the underlying skin revealed the same strain as the bonded area (the observed bending of the line was related to refraction through the transparent polymer layer in the presence of an air gap in the unbonded area).

Although the apparatus, bandage, kit and method of the present invention have been described in some detail by way of illustration and example, such illustration and example are for clarity and understanding only. It will be apparent to those skilled in the art that certain modifications and variations can be made in the teachings herein without departing from the spirit or scope of the appended claims.

Claims (18)

1. A bandage for ameliorating scarring or scarring at a wound site, wherein the bandage is configured to be removably secured to a skin surface, the bandage comprising:

a stretchable polymeric layer having a second relaxed configuration and a mechanically induced first tensioned configuration;

an adhesive layer attached to one side of the stretchable polymer layer, the adhesive layer comprising a pressure sensitive adhesive configured to resist relaxation of the stretchable polymer layer from the first tensioned configuration to the second relaxed configuration for at least 24 hours;

a relatively stiff polymeric sheet clamped to the other side of the stretchable polymeric layer; and

an attachment device releasably retaining the stretchable polymer layer in a first tensioned configuration by stretching the stretchable polymer layer to the first tensioned configuration and attaching the stretchable polymer layer to the stiffer sheet at an edge.

2. The bandage of claim 1, wherein the first and second ends of the bandage are,

wherein the stretchable polymer layer has a hardness value of 30.

3. The bandage of claim 1, wherein the first and second ends of the bandage are,

wherein the stretchable polymer layer has a hardness value of 40.

4. The bandage of claim 1, wherein the first and second ends of the bandage are,

wherein the stretchable polymer layer has a hardness value of 50.

5. The bandage of claim 1, wherein the first and second ends of the bandage are,

wherein the stretchable polymer layer has a thickness of 120 microns.

6. The bandage of claim 1, wherein the first and second ends of the bandage are,

wherein the stretchable polymer layer has a thickness of 230 microns.

7. The bandage of claim 1, wherein the first and second ends of the bandage are,

wherein the stretchable polymer layer has a thickness of 490 microns.

8. The bandage of claim 1, wherein the first and second ends of the bandage are,

wherein the stretchable polymer layer has a thickness of 500 microns.

9. The bandage of claim 1, wherein the stretchable polymer layer is capable of transitioning from the first, tensioned configuration to the second, relaxed configuration.

10. The bandage of any one of claims 1-9, wherein the first tensioned configuration is tensioned about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% relative to the second relaxed configuration.

11. The bandage of any one of claims 1-9, wherein the pressure sensitive adhesive has a T-peel release force test value of 286 kg/m.

12. The bandage of any one of claims 1-9, wherein the pressure sensitive adhesive has a T-peel release force test value of 125 kg/m.

13. The bandage of any one of claims 1-9, wherein the pressure sensitive adhesive has a blunt probe tack test value of 0.5 kg.

14. The bandage of any one of claims 1-9, wherein the pressure sensitive adhesive has a blunt probe tack test value of 0.45 kg.

15. The bandage of any one of claims 1-9, wherein the stretchable polymer layer is tapered near an edge to reduce thickness.

16. The bandage of any one of claims 1-9, wherein the pressure sensitive adhesive is configured to resist relaxation of the stretchable polymer layer from the first tensioned configuration to the second relaxed configuration for at least 3 days.

17. The bandage of any one of claims 1-9, wherein the first tensioning configuration is a biaxial tensioning configuration tensioned in two orthogonal directions.

18. The bandage of any one of claims 1-9, wherein the stretchable polymer layer is a biocompatible non-shape memory polymer.