HK1134008B - Porous bioresorbable dressing conformable to a wound and methods of making same - Google Patents

Abstract

A method of making a porous bioresorbable dressing is provided for use in applying reduced pressure therapy to a wound site. The process includes manufacture of a dressing by use of one or more bioresorbable polymers and a porogen system. The malleability of the dressing allows the dressing to be placed into the wound site such that it fills the shape and size of the wound. Embodiments include use of hand molding and formation of a rope dressing. The porogen system may be activated external to the wound site or formed in situ within the wound site, thus creating a porous dressing. A reduced pressure delivery tube is fluidly connected to the wound site to delivery a reduced pressure to the wound site.

Description

Porous bioresorbable dressing suitable for wounds and method of making same

Technical Field

The present invention relates generally to methods, systems, and compositions for making and using porous bioresorbable dressings (porous bioresorbable dressing) of various configurations.

Description of the related Art

Wound healing can be broadly divided into three overlapping basic phases: inflammation, proliferation and suppuration (metastasis). The inflammatory phase is characterized by hemostasis and inflammation. The next stage consists mainly of epithelialization, angiogenesis, granulation tissue formation and collagen deposition. The final stage involves maturation and remodeling. The effects of local factors such as ischemia, edema, and infection, and systemic factors such as diabetes, age, hypothyroidism, malnutrition, and obesity add to the complexity of the three-step wound healing process. However, the rate-limiting step in wound healing is usually angiogenesis. The hallmarks of wound angiogenesis are the migration of endothelial cells and the formation of capillaries, with sprouting (sprouting) of capillaries into the wound bed being the key to supporting regenerative tissue. The granulation phase and tissue deposition require nutrients provided by the capillaries. Thus, injury to wound angiogenesis can lead to chronically problematic wounds.

The expression of the angiogenic phenotype is a complex process that requires many cellular and molecular events to occur in successive steps. Some of these activities include endothelial cell proliferation, degradation of the surrounding basement membrane, migration of endothelial cells through the connective tissue matrix, formation of tubular structures, and maturation of endothelial-lined (endotelial-lined) tubes into new blood vessels. Angiogenesis is controlled by positive and low (reduced) regulators. In addition to endothelial cells, cells associated with tissue repair, such as platelets, monocytes, and macrophages, release angiogenic growth factors, such as Vascular Endothelial Growth Factor (VEGF), to the site of injury that initiates angiogenesis.

There are several methods currently used to promote wound healing, including irrigation of wounds to remove toxins and bacteria, topical and systemic antibiotics and anesthetics, and topical application of growth factors. One of the most successful ways to promote wound healing of slow or non-healing soft tissue wounds is reduced pressure therapy. Reduced pressure therapy generally refers to the application of a pressure below ambient pressure at a wound site, where the magnitude and duration of reduced pressure therapy is sufficient to promote healing. Examples of devices for administering reduced pressure include the Kinetic Concepts, inc. by San Antonio, Texas, by which VACUUMASSISTED is commercially availableOrThose devices that are deployed in production lines. Reduced pressure to induce the healing process has been described in U.S. patent nos. 5,636,643 and 5,645,081, the disclosures of which are incorporated by reference in their entirety.

Reduced pressure is used to promote migration of epithelial and subcutaneous tissue from healthy tissue to the wound site. Typical reduced pressure treatment includes applying reduced pressure to a wound site through a dressing that serves as a manifold to distribute the reduced pressure. The dressing is made to fit the existing wound, placed in contact with the wound, and then periodically replaced with smaller pieces of dressing as the wound begins to heal and become smaller. Although the use of reduced pressure therapy with dressings has been very successful, there are a number of difficulties with this approach. For example, it may be difficult to obtain a dressing of the appropriate width, length, or depth that fits entirely across the wound. In addition, when the dressing is removed, it may also remove healthy tissue, thus causing further trauma to the wound site.

It has been suggested to use biodegradable materials to make dressings, thus creating dressings that do not require removal from the wound site. However, for many of these dressings, the biodegradable polymer is preformed into a particular shape. However, each wound has a constant shape and size.

Accordingly, there is a need for a dressing that is easily manufactured and formed to a shape and size that fits the wound of an individual patient. There is also a need for a dressing that does not require removal from the wound site. In addition, there is a need for a dressing containing pores such that the dressing can promote healing and healthy tissue growth at a wound site.

All references cited herein are incorporated by reference to the maximum extent allowed by law. For background purposes and to the extent that they are not fully incorporated herein, references can be incorporated by reference for all purposes and to the extent that they are not fully incorporated by reference.

Brief description of the invention

These and other needs are met by the use of a bioresorbable dressing containing open cell holes, wherein the dressing is designed to readily fit the size and shape of the wound site. In its broadest sense, the present invention therefore proposes methods, systems and compositions for making and using porous bioresorbable dressings in a variety of configurations.

One embodiment in accordance with the present invention is a method and apparatus for making a porous bioresorbable dressing to be used at a wound site undergoing reduced pressure therapy, whereby pore formation occurs in situ. In this embodiment, the bioabsorbable polymer is dissolved in a suitable solvent and mixed with a stoichiometric amount of a pore forming agent (porogen). The residual solvent was removed. The resulting dressing is then placed into the wound by being hand molded (hand mold) to fill the shape and size of the wound. Alternatively, the resulting dressing may be shaped into a rope, which is then rolled into or over the wound site to fit the shape and size of the wound. The wound fluid reacts with the pore-forming agent in the dressing to create pores in situ within the dressing. A drape (drapee) for sealing the dressing is placed over the dressing at the wound site. A reduced pressure delivery tube is fluidly connected to the dressing to deliver reduced pressure to the wound site.

Another embodiment in accordance with the present invention is a method and apparatus for making a porous bioresorbable dressing to be used at a wound site undergoing reduced pressure therapy. In this embodiment, the bioabsorbable polymer is dissolved in a suitable solvent and mixed with a stoichiometric amount of porogen. The residual solvent was removed. The dressing is then placed in a fluid whereby the fluid reacts with the porogen in the dressing to create pores within the dressing. The resulting dressing is then dried and placed into the wound site by hand molding the dressing to the shape and size of the wound site. Alternatively, the resulting dressing may be shaped into a rope, which is then rolled into the wound to fit the shape and size of the wound. A drape for sealing the dressing is placed over the dressing at the wound site. A reduced pressure delivery tube is fluidly connected to the dressing to deliver reduced pressure to the wound site.

Another embodiment in accordance with the present invention is a method and apparatus for making a porous bioresorbable dressing to be used at a wound site undergoing reduced pressure therapy whereby pore formation occurs in situ. In this embodiment, the bioabsorbable polymer and plasticizer are dissolved in a suitable solvent and mixed with the porogen. The resulting mixture is then contacted with a non-solvent, such that the entire mixture will precipitate out of solution as a dressing. The remaining non-solvent is removed. The resulting dressing is placed into the wound site by being hand molded into the shape and size of the wound. Alternatively, the resulting dressing may be shaped into a rope, which is then rolled into the wound to fit the shape and size of the wound. Wound fluid (wind fluid) reacts with the pore-forming agent in the dressing, creating pores in situ within the dressing. A drape for sealing the dressing is placed over the dressing at the wound site. A reduced pressure delivery tube is fluidly connected to the dressing to deliver reduced pressure to the wound site.

Another embodiment in accordance with the present invention is a method and apparatus for making a porous bioresorbable dressing to be used at a wound site undergoing reduced pressure therapy. In this embodiment, the bioabsorbable polymer and plasticizer are dissolved in a suitable solvent and mixed with the porogen. Then, the resulting mixture is put into a non-solvent. The non-solvent should be one that allows the polymer, plasticizer, and porogen to precipitate out of solution. The remaining non-solvent is removed. The resulting precipitate, i.e. the dressing, is placed in a fluid, whereby the fluid reacts with the pore-forming agent in the dressing, creating pores within the dressing. The resulting dressing is then dried and placed into the wound site by hand molding the dressing to the shape and size of the wound site. Alternatively, the resulting dressing may be shaped into a rope, which is then rolled into or over the wound to fit the shape and size of the wound site. A drape for sealing the dressing is placed over the dressing at the wound site. A reduced pressure delivery tube is fluidly connected to the dressing to deliver reduced pressure to the wound site.

One embodiment in accordance with the present invention is a method and apparatus for making a porous bioresorbable dressing to be used at a wound site undergoing reduced pressure therapy, wherein the dressing further contains factors (factors) that promote tissue growth and/or healing. In this embodiment, the bioabsorbable polymer is dissolved in a suitable solvent and mixed with a stoichiometric amount of porogen. The residual solvent was removed. The resulting dressing is then placed in a fluid whereby the fluid reacts with the pore-forming agent in the dressing to create pores within the dressing. Once the reaction is complete, the dressing is removed from the fluid and allowed to dry. At this point, the resulting porous dressing may be coated with various substances including, but not limited to, cells, growth factors, or other nutrients that promote cell growth and/or healing. The porous dressing is then placed into the wound site by being hand molded into the shape and size of the wound. Alternatively, the resulting dressing may be shaped into a rope, which is then rolled into or over the wound to fit the shape and size of the wound site. A drape for sealing the dressing is placed over the dressing at the wound site. A reduced pressure delivery tube is fluidly connected to the dressing to deliver reduced pressure to the wound site.

One aspect of the invention provides a method for promoting neogenetic tissue growth and/or wound healing at a wound site, comprising: forming a dressing by dissolving one or more bioresorbable polymers and a porogen system in a solvent and removing the solvent; placing the dressing in the wound site such that the dressing fills the size and shape of the wound site; placing a manifold in contact with the dressing; covering the manifold with a cloth; securing the drape to a skin surface surrounding the wound; applying reduced pressure to the wound site through the dressing and the manifold; and forming pores in situ within the dressing by contacting wound fluid with a porogen system within the dressing.

In the method of the present invention for promoting neogenetic tissue growth and/or wound healing at a wound site, the porogen system may be sodium bicarbonate and at least one acid. The acid may be citric acid.

The porogen system may be a salt.

Forming the dressing may further comprise adding one or more plasticizers to the solvent.

The size of the pores may be between 100 microns and 500 microns.

Placement of the dressing into the wound site may occur by hand molding the dressing.

One aspect of the invention provides another method for promoting neogenetic tissue growth and/or wound healing at a wound site, comprising: forming a dressing by dissolving one or more bioresorbable polymers in a solvent, mixing a porogen system with the polymers in the solvent, and removing the solvent; contacting the dressing with a fluid such that the porogen system forms pores; placing the dressing in the wound site such that the dressing is in contact with the wound site; placing a manifold in contact with the dressing; covering the manifold with a cloth; securing the drape to a skin surface surrounding the wound; applying reduced pressure to the wound site through the dressing and the manifold.

In another method of the invention for promoting neogenetic tissue growth and/or wound healing at a wound site, the porogen system may be sodium bicarbonate and at least one acid. The acid may be citric acid.

The porogen system may be a salt.

Forming the dressing may further comprise adding one or more plasticizers to the solvent.

Placement of the dressing into the wound site may occur by hand molding the dressing.

One aspect of the invention provides a method for forming a dressing to be used to support neonatal tissue growth and/or wound healing at a wound site, the method comprising: dissolving one or more bioabsorbable polymers in a solvent; adding porogen system particles to the solvent; removing the solvent to form a solid dressing; heat pressing the dressing; the formation of the pores is facilitated by contacting the dressing with a fluid.

In the method of the invention for forming a dressing to be used to support new tissue growth and/or wound healing at a wound site, the method may further comprise: coating the dressing with porogen system particles prior to thermo-compression of the dressing.

The method may further comprise: the wafer is pressed onto the top and/or bottom of the dressing by using a heated platen.

The method may further comprise: the dressing is coated with one or more substances that promote healing.

One aspect of the present invention provides a method of promoting the growth and/or healing of new tissue at a wound site, comprising:

forming a dressing by:

i) dissolving one or more bioabsorbable polymers and a porogen system in a solvent to form a mixture;

ii) placing the mixture in a non-solvent such that the one or more bioabsorbable polymers and the porogen system precipitate out of the ii) solution; and

removing excess non-solvent;

placing the dressing in the wound site such that the dressing is in contact with the wound site;

placing a manifold in contact with the dressing;

covering the manifold with a cloth;

securing the drape to a skin surface surrounding the wound;

applying reduced pressure to the wound site through the dressing and the manifold.

In yet another method of the present invention for promoting the growth and/or healing of new tissue at a wound site, the dressing may further comprise at least one plasticizer.

The porogen system may be sodium bicarbonate and at least one acid.

The acid may be citric acid.

The porogen system may be a salt.

Placement of the dressing into the wound site may occur by hand molding the dressing.

Yet another method of the present invention for promoting the growth and/or healing of new tissue at a wound site may further comprise: forming the dressing into a rope configuration prior to placing the dressing in the wound site.

One aspect of the invention provides a method of promoting the growth of new tissue at a wound site, comprising:

forming a dressing by:

i) forming a mixture by dissolving one or more bioabsorbable polymers in a solvent and adding a porogen system to the solvent;

ii) precipitating the mixture in the shape of a rope having a desired diameter by extruding the mixture into a non-solvent using a device having the desired tip diameter; and

iii) removing excess non-solvent;

placing the dressing in the wound site such that the dressing is in contact with the wound site;

placing a manifold in contact with the dressing;

covering the manifold with a cloth;

securing the drape to a skin surface surrounding the wound;

applying reduced pressure to the wound site through the dressing and the manifold.

Other objects, features and advantages of the present invention will become apparent from the accompanying drawings and the detailed description that follows.

Brief Description of Drawings

Figure 1 illustrates a flow diagram according to some embodiments of the present invention illustrating a method of making a bioabsorbable polymer with a sodium bicarbonate (sodium bicarbonate) and acid porogen system and its use in reduced pressure therapy.

Figure 2 illustrates a flow diagram according to some embodiments of the present invention that illustrates a method of making a bioresorbable polymer with a salt porogen system and its use in reduced pressure therapy.

Figure 3 illustrates a flow diagram according to some embodiments of the invention illustrating a method of making a porous dressing by using a bioresorbable polymer and porogen system and the use of the porous dressing in reduced pressure therapy.

Figure 4 illustrates a flow diagram according to some embodiments of the invention illustrating a method of making a porous dressing by using a bioresorbable polymer and porogen system and the use of the porous dressing in reduced pressure therapy.

Figure 5 illustrates a flow diagram according to some embodiments of the invention illustrating a method of making a porous dressing in the shape of a rope and the use of the porous dressing in reduced pressure treatment. Detailed description of the preferred embodiments

In the following detailed description of the preferred embodiments, reference is made to the accompanying drawings, which form a part hereof, and in which is shown by way of illustration specific preferred embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that other embodiments may be utilized and that logical structural, mechanical, electrical, and chemical changes may be made without departing from the spirit or scope of the present invention. To avoid detail not necessary to enable those skilled in the art to practice the invention, the description may omit certain information known to those skilled in the art. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present invention is defined only by the appended claims.

All embodiments of the present invention include the use of a bioresorbable dressing to be used in conjunction with reduced pressure therapy to treat a wound site. The present invention is not necessarily limited by the specific location of the wound site, nor by the type of tissue that is the target of reduced pressure therapy. Thus, a wound site treated by the present invention may be a location on or within the body where it is desired to promote the growth and/or healing of tissue.

A first embodiment according to the present invention is a method and apparatus for making a bioresorbable porous polymer dressing and the use of the dressing in reduced pressure therapy, as shown in figure 1.

First, one or more bioabsorbable polymers are dissolved in a suitable solvent (101). The type of solvent used will depend on the bioabsorbable polymer selected. Bioabsorbable polymers are biocompatible materials whose degradation byproducts can be bioassimilated or excreted via natural pathways in the body. Bioabsorbable polymers may include, but are not limited to, lactide, Polylactide (PLA), glycolide polymers, polyglycolic acid (PGA), poly (lactide-co-glycolide) (poly (lactide-co-glycolide), PLGA), ethylene glycol/lactide copolymers, polycaprolactone, polyhydroxybutyrate, polyurethane, polymers containing phosphorus-nitrogen chains, poly (ethylene glycol-co-glycolide) copolymers (poly (lactide-co-glycolide) co-polymers), polyhydroxy acids, polycarbonates, polyamides, polyanhydrides, polyamino acids, polyorthoesters, polyacetals, degradable polycyanoacrylates, polycarbonates, polyfumarates, degradable polyurethanes, proteins (e.g., albumin, collagen, fibrin, synthetic and natural polyamino acids), Polysaccharides (e.g., polymers of alginate, heparin, and other naturally occurring biodegradable saccharide units). Further, in a preferred embodiment, the polymer is a PLA: PCL copolymer, wherein the ratio of PLA to PCL can range from 100: 0 to 0: 100. In some preferred embodiments, the ratio of PLA: PCL copolymer is about 90: 10. In other embodiments, the ratio of PLA: PCL copolymer is about 80: 20. In yet another embodiment, the ratio of PLA: PCL copolymer is about 70: 30.

A porogen system of sodium bicarbonate and acid is also added to the mixture of bioabsorbable polymers (102). The acid may be any acid which is not in liquid or gaseous form and is therefore in a solid or crystalline state. Examples of suitable acids for use therein include, but are not limited to, citric acid. The amounts of sodium bicarbonate and acid used may be used in stoichiometric amounts. It is also contemplated that sodium bicarbonate can be used in non-stoichiometric amounts. In addition, the amount of porogen used should be an amount that creates a sufficient number of openings or channels so that wound fluid can be drained and reduced pressure can continue unabated.

The solvent is then removed from the resulting dressing (103). Examples of methods of removing the solvent include, but are not limited to, evaporation, oven drying (oven drying), vacuum drying, hand kneading (hand kneading), and the like. In one embodiment, the solvent is evaporated over a period of about 48 hours.

In one embodiment, the dressing may be heat pressed to compress it and remove any residual air bubbles that may be present. The plates of the heated press are preferably covered or coated with a material that inhibits the adherence of the dressing to the plates. Examples of suitable materials include, for example, teflon. To increase the porosity of the dressing, the practitioner (practioner) may cover the top and/or bottom plates of the heated press with additional sodium bicarbonate and acid. In a preferred embodiment, the bottom surface of the dressing is coated with particles of sodium bicarbonate and acid having a size greater than about 500 μm, and/or the top surface of the dressing is coated with particles of sodium bicarbonate and acid having a size of about 90 μm to about 250 μm. Alternatively, one may use an embossed wafer as the top and/or bottom plate to imprint holes, lines or other designs onto the top and bottom of the dressing. The dressing is hot pressed at a given temperature and pressure and then cooled.

At this stage, the dressing should be malleable. Thus, the dressing may be placed in the wound site (104) by using, for example, hand molding the dressing to fit the shape and size of the wound site.

The reduced pressure treatment device is then fluidly connected to the wound site (105). Here, the wound site and dressing are covered by a cloth made of a flexible substance. Preferably, the cloth is impermeable, thus hindering or slowing down the transfer of liquid or gas. Preferably, the cloth is made of a material that allows water vapor to diffuse when reduced pressure therapy is applied, but provides an airtight seal over the wound site. The drape will extend over the wound site and surface of the dressing and extend beyond the edges of the wound. The cloth is secured to the skin surface in the vicinity around the wound by, for example, an adhesive material. At least one reduced pressure conduit is positioned beneath and extends from the underside of the cloth. The reduced pressure conduit may be made from any medical grade tubing material including, but not limited to, parylene-coated silicone or urethane. In addition, the tube may be coated with an agent that prevents the tube from adhering to the wound. For example, the tube may be coated with heparin, an anticoagulant, anti-fibrinogen (anti-fibrinogen), an anti-adhesion agent, antithrombin, or a hydrophilic substance. A reduced pressure conduit is placed in fluid communication with a reduced pressure source, which preferably includes a canister (canister) that is safely placed under vacuum by being in fluid communication with the reduced pressure source. Thus, in this embodiment, the dressing acts as a manifold to distribute reduced pressure, aid in the application of reduced pressure to the wound site, the delivery of fluids to the wound site, or the removal of fluids from the wound site.

In an alternative embodiment, a bioresorbable dressing is placed in the wound site and a manifold is placed over the dressing. The manifold promotes uniform distribution of reduced pressure across the wound site. The wound site, dressing and manifold are then covered by a drape made of a flexible impermeable substance. The drape will extend over the surface of the wound site, dressing and manifold, and extend beyond the edges of the wound and is preferably secured to the skin surface. At least one reduced pressure delivery tube is fluidly connected to the manifold. The reduced-pressure conduit is also placed in fluid communication with a reduced-pressure source, which preferably includes a canister that is safely placed under vacuum by being in fluid communication with the reduced-pressure source.

Wound fluid from the wound site then initiates an acid-base reaction between the sodium bicarbonate and the acid, producing carbon dioxide gas (106). The generation of carbon dioxide gas will thus convert the dressing in situ into a three-dimensional structure with interconnected pores or "scaffold". In addition, a fluid such as water may be added to the wound site to assist the porogen system reaction. In an alternative embodiment, step (106) may occur before step (105).

Typically, the pores resulting from the generation of carbon dioxide gas have a size of about 50 microns to about 1500 microns. In one embodiment, the size of the pores is between about 100 microns and about 500 microns. In another embodiment, the size of the pores is between about 100 microns and about 250 microns. It will be appreciated that the size of the resulting pores will depend on the size of the sodium bicarbonate and acid particles and the amount of gas produced. Thus, one can use any method to control the size of the sodium bicarbonate and acid particles, including but not limited to sieving and centrifugation. In one embodiment, the sodium bicarbonate and acid are sieved through one or more sieves to produce particles of a certain size. Thus, the size of the pores will be at least the size of the particles produced by sieving. If the dressing is sufficiently malleable, the carbon dioxide gas generated will further increase the pore size.

In addition, the amount of porogen system used and the particle size of the porogen system will control the percent porosity of the resulting porous dressing. It will be appreciated that the percentage of porosity preferred by the practitioner may depend on the following factors: such as the mechanical properties of the materials used in the dressing (e.g., bioabsorbable polymers), the desired pore penetration (cell infiltration), the presence or absence of wound healing or tissue treatment substances, and the like. In a preferred embodiment, the percent porosity is at least about 50%. In another preferred embodiment, the percent porosity is about 70%.

Reduced pressure therapy is then applied to the wound (107). It will be appreciated that the frequency of reduced pressure treatment will depend on the site of the body, the size and shape of the wound site, the particular dressing or dressings used, and the type (if any) of various agents applied to the site. Further, reduced pressure treatment may be substantially continuous administration or cyclical administration, such that the pressure fluctuates over time, depending on the treatment regimen (regimen). As the wound heals, the porous dressing is consumed by the body and replaced by granulation tissue.

In an alternative embodiment, one or more plasticizers are added to the bioabsorbable polymer in a solvent (102). The plasticizer may be any material that increases the deformability of the polymeric compound, which increases the softening and flexibility of the compound. Plasticizers may include, but are not limited to, cetyl esters, glycerin, glycerides, acetylated glycerides, glyceryl monostearate, glyceryl triacetate, glyceryl tributyrate, phthalate, dibutyl phthalate, diethyl phthalate, dimethyl phthalate, dioctyl phthalate, citrate esters, acetyl tributyl citrate, acetyl triethyl citrate, tributyl citrate, triethyl citrate, sebacate, diethyl sebacate, dibutyl sebacate, adipate, azelate, benzoate, vegetable oil, fumarate, diethyl fumarate, malate, diethyl malate, oxalate, diethyl oxalate, succinate, dibutyl succinate, butyrate, cetyl alcohol ester, salicylic acid, triacetin, malonate, diethyl malonate, castor oil, triethylene glycol, and poloxamer. If one or more plasticizers are included in the polymer, the residual solvent (103) may be removed by any method, such as oven drying or vacuum drying, as long as the conditions used do not promote evaporation of the plasticizer.

A second embodiment according to the present invention is a method and apparatus for making a bioresorbable porous polymer dressing and the use of a porous dressing in reduced pressure therapy, as shown in figure 2.

The bioabsorbable polymer is dissolved in a suitable solvent (201). The bioabsorbable polymer can be made of one or more bioabsorbable polymers. Suitable polymers include those disclosed in other embodiments of the present invention. In an alternative embodiment, one or more plasticizers are also added to the bioabsorbable polymer.

The bioabsorbable polymer is then mixed with a crystalline or solid salt that acts as a porogen system (202). The invention is not limited by the type of salt as long as the salt has a suitable particle size and is soluble in fluids, i.e., gases, liquids, or flowable materials, including but not limited to colloids, dressings, liquids, slurries, suspensions, viscous gels, pastes, putties (putty), and particulate solids. Examples of suitable salts for use herein include, but are not limited to, sodium chloride and potassium chloride. The amount of salt used can be used in stoichiometric amounts. It is also contemplated that the salt may be in non-stoichiometric amounts.

The solvent is then removed (203). Examples of methods of removing the solvent include, but are not limited to, evaporation, oven drying, vacuum drying, hand kneading, and the like. In one embodiment, the solvent is evaporated over a period of about 48 hours.

In an alternative embodiment, the resulting dressing may be heat pressed to compress the dressing and remove any residual air bubbles that may be present. The plates of the heated press are preferably covered or coated with a material that inhibits the adherence of the dressing to the plates. Examples of suitable materials include, for example, teflon. In order to allow the dressing to later develop into a more porous dressing, the practitioner may cover the top and/or bottom plates of the heated press with additional salt particles, i.e., a porogen system. In a preferred embodiment, the bottom surface of the dressing is coated with salt particles having a size greater than about 500 μm and the top surface of the dressing is coated with salt particles having a size of about 90 μm to about 250 μm. Alternatively, one may use an embossed wafer as the top and/or bottom plate to imprint holes, lines or other designs onto the top and bottom of the dressing. The dressing is pressed at a given temperature and pressure and then cooled.

At this stage, the dressing should be malleable. Accordingly, one may place the dressing in the wound site by using, for example, hand molding the dressing to fill the shape and size of the wound (204).

The reduced pressure device is then fluidly connected to the wound site (205). In this step, the wound site and dressing are covered by a cloth made of a flexible impermeable substance. Preferably, the cloth is made of a material that allows diffusion of water vapour but provides an airtight enclosure. The drape will extend over the wound site and surface of the dressing and extend beyond the edges of the wound. The cloth is secured to the skin surface in the vicinity around the wound by, for example, an adhesive material. At least one reduced pressure conduit is positioned beneath and extends from the underside of the cloth. The reduced pressure conduit may be made from any medical grade tubing material including, but not limited to, parylene-coated silicone or urethane. In addition, the tube may be coated with an agent that prevents the tube from adhering to the wound. For example, the tube may be coated with heparin, an anticoagulant, an anti-fibrinogen, an anti-adherent, an antithrombin, or a hydrophilic substance. Thus, in this embodiment, the dressing acts as a manifold to distribute the reduced pressure.

In an alternative embodiment, a bioresorbable dressing is placed in the wound site and a manifold is placed over the dressing. The manifold promotes uniform distribution of reduced pressure across the wound site. The wound site, dressing and manifold are then covered by a drape made of a flexible impermeable substance. The drape will extend over the surface of the wound site, dressing and manifold, and extend beyond the edges of the wound and is preferably secured to the skin surface. At least one reduced pressure delivery tube is fluidly connected to the manifold. The reduced-pressure conduit is also placed in fluid communication with a reduced-pressure source, which preferably includes a canister that is safely placed under vacuum by being in fluid communication with the reduced-pressure source.

The wound fluid, which may include interstitial fluid or fluid exuded from the tissue of the wound site or capillaries thereof, will then react with the porogen system, dissolving the salt particles and thus creating pores in situ within the dressing (206). In addition, a fluid such as water may be added to the wound site to assist the porogen system reaction. The resulting spaces left by the dissolved salts produce a dressing with interconnected pores. The size of the resulting pores depends on the size of the salt particles used. Thus, one can use various methods to control the size of the salt particles. For example, salt particles may be sieved through one or more screens to produce particles of a certain size. When the salt particles dissolve, the pores left are about the size of the salt particles. The size of the pores resulting from the dissolved salt may be from about 50 microns to about 500 microns. In another embodiment, the size of the pores is between about 100 microns and about 400 microns. In another embodiment, the size of the pores is between about 100 microns and about 250 microns.

In addition, the amount of porogen system used and the particle size of the porogen system will control the percent porosity. It will be appreciated that the preferred percent porosity may depend on the following factors: such as the mechanical properties of the materials used to make the dressing, the desired pore penetration, the presence or absence of wound healing or tissue treatment substances encapsulated within or incorporated into the dressing, and the like. Wound healing or tissue treatment substances may be covalently or non-covalently bound to the dressing by, for example, the use of cross-linking agents, the inclusion of specific reactive groups on a solid carrier or on a single molecule or on two molecules, electrostatic interactions, hydrophilic interactions, hydrophobic interactions, adhesion by the use of molecules such as streptavidin, and the use of a combination of covalent and non-covalent interactions.

In a preferred embodiment, the percent porosity is at least about 50%. In another preferred embodiment, the percent porosity is about 70%.

In an alternative embodiment, step (206) may occur before step (205).

Reduced pressure therapy is then applied to the wound (207). As the wound heals, the dressing is consumed by the body and replaced by granulation tissue.

In an alternative embodiment, one or more plasticizers are added to the bioabsorbable polymer in a solvent (202). If one or more plasticizers are included in the polymer, the residual solvent (203) may be removed by any method, such as oven drying or vacuum drying, as long as the conditions used do not promote evaporation of the plasticizer.

A third embodiment according to the present invention is a method and apparatus for making a bioresorbable porous polymer dressing and the use of the dressing in reduced pressure therapy, as shown in figure 3.

One or more bioabsorbable polymers are dissolved in a suitable solvent (301). Suitable bioabsorbable polymers may include any of the polymers discussed in other embodiments of the invention. In an alternative embodiment, at least one plasticizer is also added to the bioabsorbable polymer.

The bioresorbable polymer is then mixed with a porogen system, which may include one or more compounds that cause pores to be created within the dressing (302). The type of porogen system is not limited and may include compounds that dissolve when placed in contact with a fluid. Such porogen systems include inorganic salts such as sodium chloride, sucrose crystals or gelatin spheres dissolved in a fluid such as water. Another type of porogen system is a mixture of sodium bicarbonate and an acid. When placed in contact with a fluid, the sodium bicarbonate and acid cause the bicarbonate and acid to react to form carbon dioxide gas. The gas may then increase the size of the pores.

The solvent is then removed, leaving the dressing (303). Examples of methods of removing the solvent include, but are not limited to, evaporation, oven drying, vacuum drying, hand kneading, and the like.

In an alternative embodiment, the dressing may be heat pressed to compress the dressing and remove any residual air bubbles that may be present. The plates of the heated press are preferably covered or coated with a material that inhibits the adherence of the dressing to the plates, such as teflon. To allow the dressing to later develop into a more porous dressing, the practitioner may cover the top and/or bottom plates of the heated press with additional porogen system particles. In a preferred embodiment, the bottom surface of the dressing is coated with porogen system particles having a size greater than about 500 μm and the top surface of the dressing is coated with porogen system particles having a size of about 90 μm to about 250 μm. Alternatively, one may use an embossed wafer as the top and/or bottom plate to imprint holes, lines or other designs onto the top and bottom of the dressing. The dressing is pressed at a given temperature and pressure and then cooled.

The dressing is then placed in warm water to increase its extensibility and react with the porogen system, thereby promoting the creation of pores (304). The resulting space left by the porogen system makes the dressing a dressing with interconnected pores. The size of the resulting pores depends on the size of the porogen particles used. Thus, one can use various methods to control the size of the pore former particles, such as by using a screen to screen the particles. In addition, the amount of porogen system used and the particle size of the porogen system will control the percent porosity. In a preferred embodiment, the percent porosity is at least about 50%. In another preferred embodiment, the percent porosity is about 70%.

In an alternative embodiment, one or more substances may be used to coat or may be bound to the porous dressing. For example, the dressing may be coated with collagen, hyaluronic acid, gelatin chitosan, antibacterial agents, therapeutic agents, antiviral agents, growth factors, bioactive substances, and other agents that may further promote healing and/or tissue growth. In addition, the dressing may be coated with a substance that renders the dressing radiopaque.

In one embodiment, the dressing is soaked in a solution containing collagen. The dressing is then drained of excess solution and lyophilization of the dressing is performed.

In an alternative embodiment, the dressing is soaked in a solution containing collagen, excess solution is drained, and the collagen is then cross-linked to the dressing.

The dressing is then placed in the wound site by using hand to shape the dressing at the wound site to fill the shape and size of the wound (305). In another embodiment, the dressing is cut to fit the size and shape of the wound. Any wound fluid from the wound site may also act on any remaining porogen system to create more pores.

The reduced pressure device is then fluidly connected to the wound site (306). The wound site and dressing are covered by a drape made of a flexible impermeable substance. Preferably, the cloth is made of a material that allows diffusion of water vapour but provides an airtight enclosure. The drape will extend over the wound site and surface of the dressing and extend beyond the edges of the wound. The cloth is secured to the skin surface of the periwound enclosure by, for example, an adhesive material. At least one reduced pressure conduit is positioned beneath and extends from the underside of the cloth. The reduced pressure conduit may be made from any medical grade tubing material including, but not limited to, parylene-coated silicone or urethane. In addition, the tube may be coated with an agent that prevents the tube from adhering to the wound. The reduced-pressure conduit is also placed in fluid communication with a reduced-pressure source, which preferably includes a canister that is safely placed under vacuum by being in fluid communication with the reduced-pressure source. Thus, in this embodiment, the dressing acts as a manifold to distribute the reduced pressure.

In one embodiment, the manifold is placed on a bioresorbable dressing. The manifold promotes uniform distribution of reduced pressure across the wound site. The reduced-pressure delivery tube is then fluidly connected to the manifold.

Reduced pressure therapy is then applied to the wound (307). As the wound heals, the dressing is consumed by the body and replaced by granulation tissue.

A fourth embodiment according to the present invention is a method and apparatus for making a bioresorbable porous polymer and the use of the polymer as a dressing in reduced pressure therapy, as shown in figure 4.

The bioabsorbable polymer is dissolved in a suitable solvent (401). Suitable bioabsorbable polymers may include, but are not limited to, the polymers disclosed in other embodiments of the invention.

The bioresorbable polymer is then mixed with one or more plasticizers and a porogen system to form a non-solid mixture such as a fluid or slurry (402). The porogen system may include, but is not limited to, a soluble salt or a combination of sodium bicarbonate and acid. The amount of porogen system used may be used in stoichiometric amounts. It is also contemplated that the porogen system may be in non-stoichiometric amounts.

The resulting mixture is then added to a non-solvent for the polymer, plasticizer, and porogen such that when the mixture contacts the non-solvent, the mixture precipitates out of solution (403). Excess non-solvent is then removed from the resulting precipitate (404). Examples of methods for removing the non-solvent include, but are not limited to, evaporation, hand kneading, and the like. Residual solvent may be removed by any method, such as oven drying or vacuum drying, provided that the conditions used do not promote evaporation of the plasticizer. The resulting dressing may also be heat pressed to remove any residual air bubbles that may be present.

The resulting dressing should be malleable. Thus, one may place the dressing in the wound site by using, for example, hand molding the dressing at the wound site to fill the shape and size of the wound (405). Alternatively, the dressing may be shaped to fill the shape and size of the wound. In another embodiment, the dressing is shaped by rolling the dressing into a sheet of the desired thickness and cutting the dressing to the desired shape and size of the wound.

The reduced pressure device is then fluidly connected to the wound site (406). In this step, the wound site and dressing are covered by a cloth made of a flexible impermeable substance. Preferably, the cloth is made of a material that allows diffusion of water vapour but provides an airtight enclosure. The drape will extend over the surface of the wound site and dressing and extend beyond the edges of the wound, where the drape is secured to the skin surface by, for example, an adhesive material. At least one reduced pressure conduit is positioned beneath and extends from the underside of the cloth. The reduced pressure conduit may be made of any medical grade tubing material and may be coated with an agent that prevents the tubing from adhering to the wound. The reduced-pressure conduit is also placed in fluid communication with a reduced-pressure source, which preferably includes a canister that is safely placed under vacuum by being in fluid communication with the reduced-pressure source. Thus, in this embodiment, the dressing is used to distribute reduced pressure.

In an alternative embodiment, a bioresorbable dressing is placed in the wound site and a manifold is placed over the dressing. The manifold promotes uniform distribution of reduced pressure across the wound site. The wound site, dressing and manifold are then covered by a drape made of a flexible impermeable substance. The drape will extend over the surface of the wound site, dressing and manifold, extending beyond the edges of the wound and preferably secured to the skin surface. At least one reduced pressure delivery tube is fluidly connected to the manifold. The reduced-pressure conduit is also placed in fluid communication with a reduced-pressure source, which preferably includes a canister that is safely placed under vacuum by being in fluid communication with the reduced-pressure source.

Wound fluid from the wound site will then react with the porogen system, forming pores in situ (407). The resulting space left by the porogen system creates a scaffold, i.e., a dressing with interconnected pores. The size of the resulting pores depends on the size of the porogen particles used. Thus, one can use various methods to control the size of the pore former particles, such as by using a screen to screen the particles. In addition, the amount of porogen system used and the particle size of the porogen system will control the percent porosity. In a preferred embodiment, the percent porosity is at least about 50%. In another preferred embodiment, the percent porosity is about 70%.

In an alternative embodiment, the porogen system is contacted with a fluid prior to step (406) such that the porogen system reacts with the fluid and forms interconnected pores before the dressing, i.e., scaffold, is placed into the wound site.

Reduced pressure therapy is then applied to the wound (408). As the wound heals, the dressing is consumed by the body and replaced by granulation tissue.

In a fifth embodiment, as shown in fig. 5, a porous bioresorbable rope dressing or dressing is prepared that, due to its rope configuration and flexibility, can be placed into a wound of any size, shape or depth and is capable of completely filling the wound. The shape of the cord may be non-woven, knitted, twisted polymer fibers, and the like. These different shapes introduce additional channels or pockets of air and are based on the shape of the polymer fibers and the degree of their interlacing properties.

The bioabsorbable polymer is dissolved in a suitable solvent (501). Suitable polymers include, but are not limited to, the polymers disclosed in other embodiments of the present invention. The bioresorbable polymer is then mixed with one or more plasticizers and a porogen system to form a non-solid mixture such as a fluid or slurry (502). The porogen system may include, but is not limited to, a soluble salt or a combination of sodium bicarbonate and acid. The amount of porogen system used may be used in stoichiometric or non-stoichiometric amounts.

The resulting mixture is then extruded into a non-solvent for the polymer, plasticizer, and porogen by a syringe or other device having the desired tip diameter, causing the mixture to precipitate out of solution in the form of a string or rope (503). In an alternative embodiment, the strands may be formed by rolling the resulting mixture into a sheet of the desired thickness and cutting the dressing into the shape of a strand.

The rope dressing is then transferred to an aqueous medium, such as water, to react with the porogen system and thereby form a porous dressing (504). The resulting space left by the porogen system results in a dressing with interconnected pores. The size of the resulting pores depends on the size of the porogen particles used. Thus, one can use various methods to control the size of the pore former particles, such as by using a screen to screen the particles. In addition, the amount of porogen system used and the particle size of the porogen system will control the percent porosity. In a preferred embodiment, the percent porosity is at least about 50%. In another preferred embodiment, the percent porosity is about 70%.

Excess media (505) may then be removed by methods including, but not limited to: evaporation, hand kneading and the like. In addition, oven drying or vacuum drying may also be used, provided that the conditions used do not promote evaporation of the plasticizer. The rope dressing may also be heat pressed to remove any residual air bubbles that may be present, if desired.

The resulting dressing should be malleable. Thus, the rope dressing may be rolled into the wound site to fill the shape or size of the wound (506). In another embodiment, two or more ropes are braided or twisted together to form a rope of thicker diameter, which is then wound into the wound site.

The reduced pressure device is then fluidly connected to the wound site (507). In this step, the wound site and dressing are covered by a cloth made of a flexible impermeable substance. Preferably, the cloth is made of a material that allows diffusion of water vapour but provides an airtight enclosure. The drape will extend over the wound site and surface of the dressing and extend beyond the edges of the wound. The cloth is secured to the skin surface in the vicinity around the wound by, for example, an adhesive material. At least one reduced pressure conduit is positioned beneath and extends from the underside of the cloth. The reduced pressure conduit may be made of any medical grade tubing material and may be coated with an agent that prevents the tubing from adhering to the wound. The reduced-pressure conduit is also placed in fluid communication with a reduced-pressure source, which preferably includes a canister that is safely placed under vacuum by being in fluid communication with the reduced-pressure source. Thus, in this embodiment, the dressing serves to distribute the reduced pressure.

In an alternative embodiment, a bioresorbable dressing is placed in the wound site and a manifold is placed over the dressing. The manifold promotes uniform distribution of reduced pressure across the wound site. The wound site, dressing and manifold are then covered by a drape made of a flexible impermeable substance. The drape will extend over the surface of the wound site, dressing and manifold, and extend beyond the edges of the wound and is preferably secured to the skin surface. At least one reduced pressure delivery tube is fluidly connected to the manifold. The reduced-pressure conduit is also placed in fluid communication with a reduced-pressure source, which preferably includes a canister that is safely placed under vacuum by being in fluid communication with the reduced-pressure source.

Wound fluid from the wound site reacts with any residual porogen system and forms additional pores in situ (508). Reduced pressure therapy is then applied to the wound (509). As the wound heals, the dressing is consumed by the body and replaced by granulation tissue. The diameter of the cord may vary, but preferably will be between about 2mm and about 7 mm.

It is also understood that the bioresorbable dressing may be formed by any method suitable for a practitioner. For example, in a sixth embodiment, a porous bioresorbable dressing is prepared by heating one or more bioresorbable polymers above its glass transition temperature so that the polymers are flowable. Suitable polymers include, but are not limited to, the polymers disclosed in other embodiments of the present invention. The bioresorbable polymer is then mixed with the porogen system. In another embodiment, one or more plasticizers are also added to the bioabsorbable polymer. The resulting mixture is stirred, with or without additional heating, until the biodegradable polymer is mixed with the porogen system. The mixture may then be formed into a sheet or mold and cooled. The resulting mixture may be formed into the desired dressing to the shape and size of the wound site by any method, including but not limited to hand molding, laser cutting, and the like.

A porous bioabsorbable interfacial layer was prepared by mixing a solution of 2.36g 90: 10 PLA: PCL and 0.26g triethyl citrate in 12mL methylene chloride with a mixture of 1.65g citric acid and 2.73g sodium bicarbonate that had been sieved to a particle size of 90-250. The suspension was cast onto a teflon coated mold and dried. The resulting sheet was then hot pressed, soaked in water for 12 hours to remove the pore former and dried. Using a grid provided with fluid ports and pressure sensors, a 500 mL/day saline infusion rate and an applied pressure of 50, 125 or 200mmHg, simulations were performedAnd (6) treating. The test (n-3) was performed on a 4 x 6 inch piece of porous bioabsorbable interfacial layer for 48 hours. The fluid was collected at a predetermined time point and the pressure was monitored. A 5-cm diameter, full-thickness resected porcine wound model was used to evaluate tissue ingrowth into the dressing. A reticulated open-cell dressing was applied to the control wound (n-3), while the test wound (n-3) was covered with a porous bioabsorbable interface layer with a reticulated open-cell dressing. Then start the continuation of-125 mmHgAnd (6) treating. At each pressure setting, there was little difference (0.5-1.6mmHg) between the reticulated open-cell dressing and the porous bioresorbable interface layer with the reticulated open-cell dressing. After 7 days, the tissue with the dressing is excised en bloc, fixed and H&And E, dyeing.

The results indicate that the presence of the porous bioresorbable interface layer under the reticulated open-cell dressing does not impede fluid flow through the dressing. Ingrowth into the reticulated open-cell dressing is extensive when the reticulated open-cell dressing is placed directly over the wound. When a porous bioresorbable interface layer was placed between the wound beds, no ingrowth into the reticulated open-cell dressing was observed. The ingrowth is only seen in the interfacial layer. Thus, if a bioabsorbable interface layer is used, removal of only the reticulated open-cell dressing will not disrupt new tissue growth.

It will be apparent from the foregoing that an invention having significant advantages has been provided. Although the present invention has been described in only some of its forms, it is not just limited but is susceptible to various changes and modifications without departing from the spirit thereof.

Claims (23)

1. A dressing for promoting neonatal tissue growth and/or wound healing at a wound site, the dressing being formed by dissolving one or more bioresorbable polymers and a porogen system in a solvent and removing the solvent;

wherein the porogen system within the dressing forms pores in situ within the dressing by contact with wound fluid;

thus, when the dressing is placed into the wound site such that the dressing fills the size and shape of the wound site, and a manifold is placed in contact with the dressing and covered with a drape to secure the drape to the skin surface surrounding the wound, reduced pressure may be applied to the wound site through the dressing and the manifold.

2. The dressing of claim 1, wherein the porogen system is sodium bicarbonate and at least one acid.

3. The dressing of claim 2 wherein the acid is citric acid.

4. The dressing of claim 1, wherein the porogen system is a salt.

5. The dressing of claim 1, wherein the formation of the dressing further comprises adding one or more plasticizers to the solvent.

6. The dressing of claim 1, wherein the pores are between 100 and 500 microns in size.

7. A dressing for promoting neonatal tissue growth and/or wound healing at a wound site, the dressing being formed by dissolving one or more bioresorbable polymers in a solvent, mixing a porogen system with the polymers in the solvent and removing the solvent,

wherein the porogen system can form pores by contacting the porogen system with a fluid;

thus, when the dressing is placed into the wound site such that the dressing is in contact with the wound site, and a manifold is placed in contact with the dressing and covered with a drape to secure the drape to the skin surface surrounding the wound, reduced pressure may be applied to the wound site through the dressing and the manifold.

8. The dressing of claim 7, wherein the porogen system is sodium bicarbonate and at least one acid.

9. The dressing of claim 8, wherein the acid is citric acid.

10. The dressing of claim 7, wherein the porogen system is a salt.

11. The dressing of claim 7, wherein the formation of the dressing further comprises adding one or more plasticizers to the solvent.

12. A method for forming a dressing to be used to support neonatal tissue growth at a tissue site, the method comprising:

dissolving one or more bioabsorbable polymers in a solvent;

adding porogen system particles to the solvent;

removing the solvent to form a solid dressing;

heat pressing the dressing; and is

The formation of the pores is facilitated by contacting the dressing with a fluid.

13. The method of claim 12, wherein the method further comprises:

coating the dressing with porogen system particles prior to thermo-compression of the dressing.

14. The method of claim 12, wherein the method further comprises:

the wafer is pressed onto the top and/or bottom of the dressing by using a heated platen.

15. The method of claim 12, wherein the method further comprises:

the dressing is coated with one or more substances that promote tissue growth.

16. A dressing formed by the steps of: i) dissolving one or more bioabsorbable polymers and a porogen system in a solvent to form a mixture; ii) placing the mixture in a non-solvent such that the one or more bioabsorbable polymers and the porogen system precipitate out of solution; and iii) removing excess non-solvent,

thus, when the dressing is placed into the wound site such that the dressing is in contact with the wound site, and a manifold is placed in contact with the dressing and covered with a drape to secure the drape to the skin surface surrounding the wound, reduced pressure may be applied to the wound site through the dressing and the manifold.

17. The dressing of claim 16, wherein the dressing further comprises at least one plasticizer.

18. The dressing of claim 16 wherein the porogen system is sodium bicarbonate and at least one acid.

19. The dressing of claim 18, wherein the acid is citric acid.

20. The dressing of claim 16 wherein the porogen system is a salt.

21. The dressing of claim 16, wherein placing the dressing into the wound site occurs by hand molding the dressing.

22. The dressing of claim 16, wherein the dressing is formed into a rope configuration prior to placement of the dressing in the wound site.

23. A dressing formed by the steps of: i) forming a mixture by dissolving one or more bioabsorbable polymers in a solvent and adding a porogen system to the solvent; ii) extruding the mixture into a non-solvent through a device having a desired tip diameter such that the mixture precipitates in the shape of a rope having the desired diameter; and iii) removing excess non-solvent,

thus, when the dressing is placed into the wound site such that the dressing is in contact with the wound site, and a manifold is placed in contact with the dressing and covered with a drape to secure the drape to the skin surface surrounding the wound, reduced pressure may be applied to the wound site through the dressing and the manifold.