EP1494597A1 - Materiau composite favorisant la cicatrisation d'une plaie - Google Patents

Materiau composite favorisant la cicatrisation d'une plaie

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Publication number
EP1494597A1
EP1494597A1 EP03746135A EP03746135A EP1494597A1 EP 1494597 A1 EP1494597 A1 EP 1494597A1 EP 03746135 A EP03746135 A EP 03746135A EP 03746135 A EP03746135 A EP 03746135A EP 1494597 A1 EP1494597 A1 EP 1494597A1
Authority
EP
European Patent Office
Prior art keywords
composition
tissue
wound
group
agents
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP03746135A
Other languages
German (de)
English (en)
Other versions
EP1494597A4 (fr
Inventor
Charles E. Butler
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Texas System
Original Assignee
University of Texas System
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of Texas System filed Critical University of Texas System
Publication of EP1494597A1 publication Critical patent/EP1494597A1/fr
Publication of EP1494597A4 publication Critical patent/EP1494597A4/fr
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/0059—Cosmetic or alloplastic implants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/362—Skin, e.g. dermal papillae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A61L27/3813—Epithelial cells, e.g. keratinocytes, urothelial cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/48—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers

Definitions

  • the present invention relates to compositions and methods for wound and tissue repair. More specifically, the present invention provides a composition including a support material and a barrier material, as well as methods for using the composition to facilitate wound and tissue repair.
  • a wide variety of implantable biomaterials has been used to repair tissue defects and tissue loss in mammals.
  • tissue repairs can only be done with prosthetic material or use of a section of autologous tissue from another location with similar functional characteristics, often from a different organ system.
  • the use of prosthetic material is limited by its non- viability, lack of specialized function, immunologic reaction or rejection and increased risk of infection.
  • Autologous tissue from a separate location is often used to replace tissue defects.
  • intestine can be used for esophageal replacement and bladder reconstruction, and urinary conduit can be used for ureter loss or bile duct replacement.
  • donor veins are used to replace arteries.
  • Using autologous tissue for replacement requires a surgical procedure and tissue loss from an uninjured organ.
  • the donor tissue often does not have the identical structural or function characteristics of the native tissue and suffers from lack of specific anatomic and physiologic function.
  • Prosthetic mesh such as polypropylene
  • adhesions form between intraperitoneal structures, such as bowel and omentum, and the repair site.
  • the repair site often exhibits irregular or inadequate cellular infiltration and neovascularization, resulting in excessive scarring and a thin tissue layer that is more susceptible to infection or other additional damage.
  • wound cavities are often created by raising soft tissue flaps which, after closure, lie directly adjacent to the support material. These wound cavities leak serous fluid and ooze blood which leads to seroma and hematoma formation.
  • Absorbable meshes made of polygalactin 910 (VicrylTM (Ethicon Inc., Somerville, NJ)) and polyglycolic acid (DexonTM) can provide an intact structural repair, but lose tensile strength as they degrade (Yannas et al., J. Biomed. Mater. Res. 14:107-132 (1980); Kateusz et al., PomeryW Medycynie 24:3-39 (1994)). Once degraded, the fibrous tissue response that results does not have the strength to provide ongoing support of the repair and eventually breaks down.
  • the Yannas patent refers to a multilayer membrane consisting of a CG matrix layer that is insoluble by body fluids and nonbiodegradable in the presence of body enzymes (col. 3, lines 40-45), in conjunction with a separate, non-integrated moisture transmission control layer necessary to control moisture flux with the external environment.
  • Yannas further refers to the use of an optional third material to provide mechanical reinforcement of the epidermis.
  • the mechanical reinforcement material of Yannas is a separate cotton or other textile mesh that is placed over the CG matrix, covered with the moisture transmission control layer by knife coating and then cured to create the final composition, resulting in a stiffer composite, (col. 13, line 61-col. 14, line 4).
  • the cotton layer of Yannas is used to reinforce the CG matrix to allow easier handling during use.
  • cotton is not a suitable support material for bridging gaps in wounds or tissues.
  • the elasticity and low tensile strength of cotton results in increased scarring and stretching of the wound repair.
  • the multifilament structure of cotton leads to increased inflammation, infection and formation of undesirable fibrotic tissue at the wound site.
  • the compositions of Yannas et al. are specifically referred to as skin replacements for epidermal use.
  • Nonabsorbable structural meshes composed of polypropylene (PP) (e. g., MarlexTM (C.R.
  • PP mesh is the most commonly used prosthetic mesh for tissue defects, and it is ultimately the standard to which materials are compared due to its favorable mechanical properties and biocompatibility.
  • This macroporous mesh is inert, strong, and rapidly traversed by fibrous tissue. Scar tissue that forms around and through the mesh strengthens the repair zone. This tissue infiltration, however, is not well organized and the resulting scar tissue can contract and distort the mesh.
  • the outer ends of the mesh contain rigid monofilaments that are sharp and abrasive; these sharp edges have been reported to injure underlying viscera and erode through overlying skin and soft tissue, leading to visceral perforation, fistulization, and infection.
  • PP mesh also causes dense adhesions when it is placed adjacent to the abdominal viscera (Deguzman et al., Endoscopy 27:257-461 (1995)). Complications with the use of PP mesh include wound infection, scarring (Elliot et al., Am. J. Surg. 137:342-344 (1979)), seromas (Gilbert, South Med. J. 80:191-195 (1987)), sinus formation (Molloy et al., Br. J. Surg. 78:242-244 (1991); Boyd, Surg. Gynecol. Obstet. 144:251-252 (1977)), mesh extrusion (Noyles et al, Ann. Surg.
  • DacronTM has been reported to elicit an inadequate fibrous response; several investigators have indicated that the fibrous tissue which grows into DacronTM mesh becomes only loosely associated with the fibers of the mesh (Johnson-Nurse and Jenkins, Biomaterials 10(6):425- 428 (1989)). DacronTM also causes bowel adhesions and can cause visceral perforation and fistula formation. In addition, DacronTM has a multifilament construction and has been associated with increased infection rates, as multifilament fibers provide an environment for bacteria to colonize which is relatively inaccessible to macrophages.
  • Expanded polytetrafluoroethylene is the least reactive of prosthetic materials and produces the least inflammatory response.
  • the microporous structure is smooth, and, unlike PP and DacronTM, does not adhere well to abdominal viscera. This mesh does not optimally integrate into host tissue, however, and investigators have attributed a higher rate of recurrent hernias to this fact.
  • the strength of repairs using expanded polytetrafluoroethylene are ultimately dependent on the strength of suture fixation between the edge of the tissue defect and the prosthetic component. (Amid, et al., J Biomed Mater Res 28: 373-375, (1994), Nairn, et al., J Laparoendosc Surg 3: 187-190, (1993))
  • a well vascularized mesenchymal tissue layer is rapidly formed which completely surrounds the support material.
  • Many of the complications encountered using materials known in the prior art may be reduced by the formation of a vascularized tissue layer between the support material and the subcutaneous tissue. As newly formed tissue surrounds the support material, it protects the adjacent tissue from perforations, erosion of the support material through the skin and soft tissue, scar and adhesion formation, and trauma leading to bleeding or fluid accumulation.
  • Structural materials used to reconstruct abdominal wall defects restore abdominal wall integrity but may cause adhesions to the underlying abdominal viscera as well as additional problems associated with incomplete or irregular cellular infiltration and neovascularization of new tissue.
  • the present invention demonstrates that integrating nondegradable structural support materials with biodegradable barrier materials reduces adhesions and increases well organized, cellular infiltration and neovascularization, resulting in thicker, healthier tissue development at the repair site.
  • the composite materials described herein provide wound or tissue closing and healing properties superior to those in the prior art.
  • the present invention pertains to compositions comprising at least one support material integrated with at least one biodegradable barrier material.
  • the composition can comprise two or more different biodegradable barrier materials, one of which can function as a support material.
  • the support material provides a structural bridge or reinforcement for the wound or defect being repaired.
  • the support material can be an absorbable or nonabsorbable material.
  • the support material can be polypropylene mesh such as ProleneTM (Ethicon Inc., Somerville, NJ) and MarlexTM (C.R.
  • polyester such as DacronTM and MersileneTM (Ethicon Inc., Somerville, NJ), silicone, polyethylene, polyamide, titanium, stainless steel, polymethylmethacrylate, silk, cotton, polyglactic acid such as NicrylTM mesh (Ethicon Inc., Somerville, ⁇ J), polyglycolic acid such as DexonTM mesh, poliglecaprone, collagen, gelatin, polydioxone and expanded polytetrafluoroethylene such as DualMeshTM, MycromeshTM or other expanded PTFE (W.L. Gore and Associates).
  • the barrier materials described below may function as support materials.
  • One of skill in the art can identify barrier materials with the necessary characteristics to function as a support material.
  • Biodegradable barrier material of the present invention serves as a temporary tissue substitute and template for new tissue formation.
  • the biodegradable barrier material can be, for example, collagen glycosaminoglycan matrix (e.g., a crosslinked collagen glycosaminoglycan matrix), GelfoamTM (Pharmacia and Upjohn, Inc., Kalamazoo, MI), SurgicelTM (Johnson & Johnson), carboxymethylcellulose or carboxymethylcellulose/sodium hyaluronate such as SeprafilmTM, oxidized regenerated cellulose such as Interceed TC7 and Surgicel ® , acellular cadaveric dermal matrix such as Alloderm 8 or a particulate form of acellular cadaveric dermal matrix such as CymetraTM.
  • collagen glycosaminoglycan matrix e.g., a crosslinked collagen glycosaminoglycan matrix
  • GelfoamTM Pharmacia and Upjohn, Inc., Kalamazoo, MI
  • the support material of the disclosed composition is made of combinations of biological and non- biological materials. Examples include dermis, fascia, tendon, or any other material described herein or recognized by a skilled artisan to be a useful material for support and reinforcement of the tissue repair, in combination with polymeric or other materials as listed above or as would be recognized by a person skilled in the art to be useful [0020]
  • the barrier material aids the formation of mesenchymal tissue adjacent to and incorporated in the support material. This orderly, well vascularized tissue grows around and through the support material, providing strength, vascularity, and a healthy barrier layer of tissue to separate the support material from surrounding tissue and organs while fixing the support material in place.
  • This healthy tissue such as new tissue including new mesenchymal tissue, is distinct from the thin, scar tissue normally associated with wound and tissue repair using materials and methods of the prior art.
  • Suitable barrier material comprises materials including but not limited to, cellular materials, biologically-derived or synthetically-produced acellular materials or cellular components, or combinations of these.
  • materials that can be used include, without limitation, dermal, epidermal, epithelial, muscosal or submucosal tissue or cells, or cellular or non-cellular components of the dermis, epidermis, epithelium, muscosa, or submucosa, including the extracellular matrix, basement membranes, or their analogs, or combinations of any of these.
  • the dermis, epidermis, epithelial, mucosa or submucosa can be decellularized, thus decreasing viral transfer from the graft to the host.
  • Dermal cells epidermal cells, epithelial cells, mucosal cells or submucosal cells, intact extracellular matrices, intact basement membranes and other acellular structures including analogs, contain a scaffold for cellular infiltration and promote wound healing and tissue repair. Additional barrier materials include pleura, fascia, tendon, dura, peritoneal cells, pericardium, mesothelium, blood vessels, synovial surfaces, joint tissues, fat, and amnionic membrane.
  • Processed or synthetic materials that may be used as a barrier material include decellularized tissue that may or may not include the basement membrane, such as decellularized cadaveric dermis, such as Alloderm ® or CymetraTM, soft tissue grafts, such as SurgisisTM; bioresorbable hyaluronic-based material such as SeprafilmTM, SeprameshTM and SepracoatTM; carboxymethylcellulose; oxidized regenerated cellulose; gelatin foam such as Gelfoam or Gelfilm ® "
  • Example barrier materials include collagen, particularly coUagen- glucosaminoglycan matrices (CG); and decellularized cadaveric dermis such as AllodermTM or CymetraTM (LifeCell Corp., Branchburg, NJ).
  • the composition can also comprise a temporary optional moisture barrier to prevent evaporation and provide protection from the environment until sufficient epithelial coverage is obtained.
  • the present invention also relates to synthetic tissue comprising a composition according to the invention. Also disclosed are methods for using the composite materials of the invention.
  • FIG. 1 This figure is a schematic representation of a composition 1, including a barrier material of the composition 2, and a support material of the composition 3.
  • FIG. 2 This figure is a cross-sectional view of the composition 1 of FIG. 1 along axis A, including a barrier material of the composition 2, and a support material of the composition 3.
  • FIG. 3 This figure is a schematic representation of one method of making a composition according to the invention.
  • the composition formed by this method is the collagen-glucosaminoglycan/polypropylene mesh composite used in Example 1.
  • Mammals suffer tissue loss from a variety of mechanisms including trauma, tumor removal, vascular disease, genetic defects, cosmetic surgery and infections. Replacement of lost tissue or organs is often essential for either survival or function of the mammal.
  • Many mammalian tissues can be thought of as bi-layer constructs. The surface layer contacts the environment or one or more body fluids, and the stromal layer provides mechanical support and a vascular supply to the surface layer(s). These bilayer tissue types include skin, trachea, bronchi, vermillion, oral lining, nasal lining, stomach, intestines, biliary ducts, ureters, bladder and blood vessels.
  • abdominal hernia repair will be described in detail as an example of a tissue repair.
  • This invention is not construed to be limited to abdominal or intestinal tissue as the appropriate tissue; the invention is intended to encompass any and all of the tissue constructions known in the art, including but not limited to bi-layer tissues.
  • compositions of the invention comprising at least one support material integrated with at least one biodegradable barrier material have been developed and tested in a guinea pig model.
  • a method of repairing or regenerating tissue has been developed which optimizes functional repair, isolates or separates the support material from the underlying tissue or organs to minimize adhesion to surrounding tissue, enhances formation of a pronounced fibrovascular infiltration into the composition, and provides a vascularized tissue bed which rapidly and completely surrounds the st uctural material and readily supports grafted tissue, such as split thickness skin grafts.
  • Also disclosed are methods for employing the disclosed composition to repair wounds and tissue defects.
  • the barrier material of the disclosed compositions is a material that can be substantially organic or biodegradable, that minimizes formation of adhesions between the internal structures being protected through closure of the wound, and the support material. Once installed, the barrier material is infiltrated with, and in some cases degraded and replaced with, vascularized host tissue, while dense fibrovascular ingrowth incorporates the support material to the edges of the wound or tissue. This provides a solid, reliable repair with limited complications of adhesions and minimization of fluid or air leakage.
  • compositions and methods presently disclosed provide structural support for wound or tissue closure and allow dense fibrovascular ingrowth and scarring localized to the synthetic supporting material, minimizing adhesions to organs or structures of the host, without significantly sacrificing the strength or reliability of the wound or tissue repair.
  • the support material of the present invention can be comprised of any materials possessing the strength and structural integrity to promote the integrity of the wound or tissue closure.
  • the composition and structure of the material must be such that it does not provoke a substantial immune response from the mammal in whom it is implanted.
  • the material is preferably permanent and non-biodegradable, particularly for load-bearing tissue, as absorbable materials lose tensile strength as they degrade and the resultant fibrous tissue does not have the strength to provide ongoing support of the repair.
  • the material can be biodegradable but should preferably persist for a period of time sufficient for the formation of new tissue sufficient to support surrounding tissue associated with wound location and tissue function.
  • Characteristics such as pore size, strength, permeability and flexibility can be used to select an optimal material for specific tissue repair or reconstruction. Such optimization is routine and is dependent upon the desired properties of the material and the tissue to be repaired. Desirable characteristics are easily recognized by one of skill in the art and can be determined, for .example, with reference to Scales, Proc. Roy. Soc. Med. 26:647 (1953).
  • the support material can be made of the host's tissue (in other words, tissue obtained from the subject that has the wound or tissue defect being repaired) or other tissue from an allogenic, homogenic, autologous, xenogenic or synthetic source.
  • the support material comprises a processed material. Examples of such polymeric or other materials commonly used as support materials include, but are not limited to, polypropylene mesh such as ProleneTM (Ethicon Inc., Somerville, NJ) and MarlexTM (C.R.
  • polyester such as DacronTM and MersileneTM (Ethicon Inc., Somerville, NJ)
  • silicone polyethylene, polyamide, titanium, stainless steel, polymethylmethacrylate, silk, cotton
  • polyglactic acid such as VicrylTM mesh (Ethicon Inc., Somerville, NJ)
  • polyglycolic acid such as DexonTM mesh, poliglecaprone, collagen, polydioxone and expanded polytetrafluoroethylene such as DualMeshTM, MycromeshTM or other expanded PTFE (W.L. Gore and Associates).
  • the support material of the disclosed composition is made of combinations of biological and non-biological materials. Examples include dermis, fascia, tendon, intestinal submucosal tissue, decellularized cadaveric dermis or any other material described herein or recognized by a skilled artisan to be a useful material, in combination with polymeric or other materials as listed above or as would be recognized by a person skilled in the art to be useful.
  • the barrier materials described below may function as support materials. One of skill in the art can identify barrier materials with the necessary characteristics to function as a support material. II. The Barrier Material
  • the biodegradable barrier material can be a highly porous, fibrous lattice.
  • the lattice serves as a temporary tissue substitute and template for new tissue formation and, when combined with support materials, it directs the formation of mesenchymal tissue adjacent to and incorporated in the support material.
  • the adjacent tissue which is formed from cellular infiltration, neovascularization and/or collagen deposition, is incorporated into the support material by surrounding individual fibers. This orderly, well vascularized tissue grows around and through the support material, providing strength, vascularity and a barrier layer of tissue (unlike scar tissue) to separate the support material from surrounding tissue and organs.
  • the tissue formation also fixes the support material securely to the surrounding tissue.
  • the composition and structure of the barrier material should be such that it does not provoke a substantial immune response from the graft recipient.
  • the barrier material should be sufficiently porous to permit blood vessels and cells such as inflammatory cells, mesenchymal cells, fibroblasts and other cells from healthy tissue surrounding the wound to migrate into the barrier material. As discussed herein, this migration is referred to as "infiltration” and is responsible for the generation of the new tissue.
  • Appropriate barrier materials can also be selected on the basis of properties such as degradation rate, hemostatic ability, degree of neovascularization, cellular infiltration and scar formation attributed to a particular barrier material. This optimization is routine in the art.
  • the barrier material should be biodegradable. This biodegradation must not proceed so rapidly that the barrier material disappears before sufficient healing occurs, i.e. before sufficient infiltration and neovascularization occurs. Barrier materials that degrade too slowly often result in excessive scarring and increased adhesion formation.
  • One skilled in the art can determine the appropriate degradation according to the wound or tissue damage being repaired. Determination of optimal biodegradation periods according to individual circumstances is routine in the art.
  • Barrier materials of the present invention may be allogenic, homogenic, autologous, xenographic or synthetic in origin. Alternatively, the barrier materials can be made from a combination of these or other sources known to the skilled artisan, or can be synthesized.
  • Allogenic sources include living or deceased humans, so the materials can be cadaveric or living.
  • Barrier materials comprise cellular materials such as dermal, epidermal, or epithelial cells or tissue such as peritoneal tissue; mucosal or submucosal cells or tissue; acellular materials, such as an intact basement membrane or an acellular mucosal, submucosal, epithelial, epidermal or dermal layer; or any combinations or equivalents thereof.
  • Dermal tissue, dermal layer cells, epidermal tissue, epidermal layer cells, epithelial tissue including peritoneal tissue, or epithelial cells including peritoneal cells can be used to form all or part of the barrier material of the present invention, alone or in combination with any other suitable barrier material as will be recognized by one of skill in the art.
  • Dermal, epidermal or epithelial cells that are useful include glands, vascular cells or networks, fibroblasts, and keratinocytes. Additional dermal, epidermal, or epithelial cells that are useful will be apparent to the skilled artisan.
  • the dermal, epidermal, or epithelial tissues or cells that can be used can be derived from a wide variety of sources such as human or animal sources.
  • mucosal or submucosal tissue or cells can be used as barrier material, alone or in combination with any other suitable barrier material as will be recognized by one of skill in the art.
  • Mucosal or submucosal cells that can be used to form all or part of the barrier material include any connective tissue cells, such as those, which when obtained from naturally occurring source, are found in the intestinal tract, such as the esophagus, stomach, large intestine or small intestine; the urogenital tract, such as the bladder; the reproductive tract, such as the uterus; or from other organs such as the pericardium.
  • mucosal or submucosal cells that are useful include glands, fibroblasts, smooth muscle cells, gastric cells, uro-epithelial cells, respiratory epithelial cells, or oral or vascular endothelial cells. Additional mucosal or submucosal cells that are useful will be apparent to the skilled artisan.
  • the mucosal or submucosal tissues or cells that can be used can be derived from a wide variety of sources, or combinations of sources, such as the intestine, bladder, stomach, blood vessels, and the like, and may be obtained from humans or other animals.
  • tissue or cells can be used as barrier material, alone or in combination with any of the other suitable barrier materials as will be recognized by one of skill in the art.
  • tissue or cells that can be used include pleura, fascia, tendon, dura, pericardium, mesothelium, blood vessels, synovial surfaces, joint tissues, fat, and amnionic membrane.
  • acellular structures can be used as all or part of the barrier material of the present invention, alone or in combination with any of the other barrier materials.
  • acellular structures that are useful as the barrier material include, but are not limited to, the extracellular matrix, or ground substance, or any other matrix, including those matrices composed of polysaccharides and proteins.
  • the proteins included in useful matrices will be fibrous or adhesive or elastic, or some combination of these, so that the barrier material naturally forms a membrane or connective structure, or can be engineered or formulated to form a membrane or connective structure.
  • acellular structures that can be used to form all or part of the barrier material include, but are not limited to the following, either alone, or in combination with other acellular structures, dermal tissues or cells, or submucosal tissue or cells: basement membrane, fibrin, laminin, hyaluronic acid, bamacan, heparin sulfate proteoglycan, perlecan, agrin, collagen, or intactin.
  • decellularized tissue that may or may not include the basement membrane, such as decellularized cadaveric dermis, such as Alloderm ® ; soft tissue grafts, such as SurgisisTM; bioresorbable hyaluronic-based material such as SeprafilmTM, SeprameshTM and SepracoatTM; carboxymethylcellulose; oxidized regenerated cellulose such as Interceed TC7 ® and Surgicel ® ; gelatin foam such as Gelfoam ® or Gelfilm ® ; peritoneal cells; fascia; pleura; dura; pericardium; tendon; or blood vessels.
  • decellularized tissue that may or may not include the basement membrane, such as decellularized cadaveric dermis, such as Alloderm ® ; soft tissue grafts, such as SurgisisTM; bioresorbable hyaluronic-based material such as SeprafilmTM, SeprameshTM and SepracoatTM; carboxymethylcellulose; oxidized regenerated
  • a preferred barrier material is acellular dermal matrix such as decellularized cadaveric dermis marketed under the tradename AllodermTM by LifeCell Corp., Branchburg, NJ.
  • Cadaveric donor tissue is collected and epidermal material is removed while preserving the underlying dermis.
  • This dermal tissue is then treated to denature and remove dermal cells while retaining the structural integrity of the dermal scaffold such as channels for vascularization, collagens, proteoglycans and elastin structures necessary for proper cellular infiltration and neovascularization.
  • basement membrane components, including laminin and collagen types IN and Nil remain intact and attached to the surface, enhancing the infiltration, proliferation and attachment of epithelial cells during healing.
  • Decellularized cadaveric dermis may be in sheet form such as AllodermTM or it may be in particulate form such as CymetraTM.
  • a second preferred barrier material is coUagen-glucosaminoglycan matrix ("CG matrix").
  • CG matrix is a highly porous lattice made of collagen and glycosaminoglycan.
  • the CG matrix serves as a supporting or scaffolding structure into which blood vessels and mesenchymal cells infiltrate, creating new mesenchymal tissue which replaces the CG matrix as it biodegrades. CeUs from undamaged tissue surrounding the edges of the wound migrate into the CG matrix to create a new, vascularized tissue bed.
  • GAG glycosaminoglycan
  • concentration of GAG the concentration of GAG
  • collagen density the ability of collagen to activate platelets.
  • GAG glycosaminoglycan
  • Various forms of GAG which may be suitable for use in this material include chondroitin 6-sulfate, chondroitin 4-sulfate, heparin, heparin sulfate, keratin sulfate, dermatan sulfate, chitin and chitosan.
  • More than one layer of barrier material can be used to make up the composite. This allows for varying thickness of the barrier depending on the type of wound or tissue closure desired. For example, two, three, four, five or even more layers of barrier material can be used. AdditionaUy, when multiple layers of barrier material are used, the layers can be made from the same material or combinations of materials, or the layers can be made from different suitable barrier materials. For example, each layer can be the same barrier material or combination of materials as the other layers, two or more can be the same, or they can all be different, according to the needs of the individual, or the wound or tissue being repaired.
  • compositions of the invention can comprise two or more layers in accordance with the teachings herein.
  • the composition comprises one layer of biodegradable barrier material and one layer of support material.
  • the composition can also comprise three layers, wherein the support material is disposed between and completely integrated with two layers of biodegradable barrier material.
  • One benefit to the completely integrated composition is that the outer barrier material provides the ability to separate the support material from surrounding tissue, and the inner barrier material provides a vascularized bed which will support grafted tissue, help fill dead space or contour irregularities. Grafting of tissue can be performed using any of several methods known in the art. Additional layers of biodegradable barrier material and support material can also be incorporated as desired to improve the properties of the compositions.
  • biodegradable barrier materials used can be the same or different.
  • one or both of the biodegradable barrier material layers is larger than the support material to allow the barrier material to surround the support material and prevent it from contacting the surrounding tissue.
  • Compositions comprising support materials and biodegradable barrier materials can be constructed by methods described herein or by other methods known in the art.
  • the present invention provides a composition that has been specifically constructed to have various characteristics useful in different applications, according to the needs of the artisan employing the compositions or methods disclosed herein, or the wound or tissue being repaired.
  • the composition can be designed so that either or both materials have one or more of the following properties: anti-adhesive; antibiotic; anti-viral; anti-fungal; anti-thrombotic; pro- thrombotic (hemostatic); immunosuppressive; anti-inflammatory; wound-healing-promoting or suppressing; angiogenic or anti-angiogenic.
  • antibiotic anti-viral
  • anti-fungal anti-thrombotic
  • pro- thrombotic pro- thrombotic (hemostatic)
  • immunosuppressive anti-inflammatory
  • wound-healing-promoting or suppressing angiogenic or anti-angiogenic.
  • anti-adhesive substances that could be added to the materials of the disclosed compositions include, but are not limited to, heparin or anti-thrombolytics, which include streptokinase, urokinase, tissue plasminogen activator, or other defibrinogenating enzymes such as ancrod (marketed under the tradename ViprinexTM by Knoll Pharmaceuticals).
  • Anti-inflammatory agents that could be used include steroids, non-steroidal anti-inflammatory agents, and chemotherapeutic agents.
  • Enhanced wound-healing properties can be achieved through the use of any of the known growth factors such as, without limitation, vascular endothelial growth factors, platelet-derived growth factors, epidermal growth factors, insulin-like growth factors, tiansforming growth- factor beta, or fibroblast growth factor.
  • Suppressed wound-healing can be achieved through use of any of the known growth factor suppressors.
  • compositions of the invention can also comprise an optional moisture barrier, such as an impermeable silicone surface layer, which can provide a temporaiy border or cutaneous reconstruction to prevent evaporation and provide protection from the environment while the epithelial layer is forming and becoming confluent.
  • the optional moisture barrier is any material which can serve as an outer surface to the composition and should be capable of being absorbed after a suitable period of time or manually removed at will from the composition. Materials suitable for use as a moisture barrier must also have the property of being semipermeable to the passage through the wound of fluids from inside the body and impermeable to microorganisms such as bacteria and viruses from outside the body.
  • the moisture barrier layer may not be necessary for internal uses or other applications such as, for example, those in which the tissue or organ is not exposed to the external environment, and thus it is optional in such applications.
  • Silicone elastomers are suitable for use in the moisture barrier of the present invention.
  • the barrier material may be attached to, integrated around, or placed onto the support material by a wide variety of means. Examples of such means are simply placing the barrier material over the supporting material or physically attaching the barrier material to the supporting material by means such as but not limited to, bonding, including by using adhesives such as cyanoacrylate or other types of adhesives or glue, fibrin glue, fibrin, thrombin, plasma, or ceUular derived hemostatic/adhesive agents; mechanic agents such as suturing or stapling; or laminating.
  • the support material may be encased by barrier material such that the support material is substantially surrounded by and integrated with the barrier material. Other means of attaching the supporting material to the barrier material or layers will be readily apparent to those skiUed in the art.
  • compositions according to the present invention can be used to repair any type or size of wound or tissue defect. Examples include but are not limited to repairing pelvic defects, joint defects, abdominal defects, chest wall defects, cranial defects, hernias, congenital abnormalities, skin lesions, burns, surgical incisions or traumatic wounds. [0055]
  • the present invention has application to massively burned patients as well as to patients undergoing reconstructive surgery, tissue trauma, surgical resection, infection, chronic skin diseases and chronic wounds.
  • the present invention will also be useful in the replacement of other specialized epithelial tissues in a variety of organ systems, including but not limited to, bone, cartilage, oral mucosa, uroepithelial, gastrointestinal, respiratory and vascular.
  • Tissue loss from malignancy, congenital or acquired disease and surgical removal can be replaced with tissue composed of the same specialized native cells.
  • Specialized epithelial tissue such as bladder, ureter, oral mucosa, esophagus, trachea, blood vessel and intestine often requires replacement or reconstruction after surgical excision.
  • Compositions described herein can be used by the oncologic, trauma or reconstructive surgeon to replace tissue defects with a tissue composed of organ-specific cells identical to the native tissue, without the need to violate uninjured organs for donor tissue. Such tissue can be replaced after surgical resection for malignancy, disease or trauma.
  • This method allows for replacement of various commonly lost tissues such as oropharyngeal, nasal and bronchial mucosa, lip vermillion, blood vessels, trachea, esophagus, stomach, small and large bowel, biliary ducts, ureter, bladder, urethra, periosteum, synovium, areolar tissue, chest wall, abdominal wall and vaginal mucosa.
  • Structural defects such as ventral, inguinal and diaphragmatic hernias, replacement or augmentation of tendons, ligaments and bone and abdominal and thoracic wall reconstruction can also be repaired as described herein.
  • composition is flexible enough to be molded into the appropriate shape or form and then secured to adjacent or contiguous uninjured tissue while tissue regeneration progresses.
  • tissue regeneration progresses.
  • the wound or tissue is readied for application of the composite. Areas of tissue that have been destroyed or damaged are surgicaUy removed to prevent them from interfering with the healing process. The entire area of dead and damaged tissue is excised, so that intact epithelial cells are present at the perimeter of the wound or tissue.
  • the composition, with the optional moisture barrier, if present, away from the wound or tissue, is draped across the wound to avoid the entrapment of air pockets between the wound or tissue and the composition.
  • the composite is sutured or stapled to the wound or tissue using conventional techniques and the wound or tissue is then covered or closed, as appropriate.
  • abnormal tissue can be intentionally (e.g., surgically) removed from an individual and new tissue can be elicited in its place using this method.
  • the method of the present invention can be used to produce new tissue in place of tissue which has been lost due to accident or disease.
  • the present invention provides a method for repairing wounds or tissue defects by employing the disclosed composition to promote strength of a wound or tissue closure.
  • the present invention provides methods for preventing adhesion of a composite to undesired organs or other structures (or both) of the host.
  • the present invention provides a method for promoting the formation of a tissue layer at the site of a wound or tissue repair, by using the compositions disclosed herein.
  • the tissue layer will generally form between the barrier material, which can be dissolved over time, and the support material.
  • the composition can be stapled, sutured, glued, or otherwise placed in the patient to repair the wound or tissue defect.
  • Other alternative forms of placement of the composite for wound or tissue repair are also available and will be readily appreciated by one of skill in the art.
  • Example 1 Polypropylene Mesh Supporting Material Integrated with and Encased by Collagen-Glucosaminoglycan Barrier Material
  • Bovine hide collagen (Sigma Chemical Co., St. Louis, MO) 0.5% by weight was dispersed in 0.05M acetic acid and co-precipitated with chondroitin-6-sulfate (Sigma Chemical Co., St. Louis, MO). The co-precipitate was concentrated by centrifugation and excess acetic acid was decanted. Concentrated co-precipitate, 3 ml, was poured into 3 x 5 cm wells on a flat stainless steel freezing pan placed on a cooled (-30°C) shelf of a freeze-drier.
  • polypropylene (PP) mesh (Prolene® , Ethicon Inc., Somerville, NJ) (2 x 4 cm) was placed over the coUagen-glucosaminoglycan (CG) mesh and 3 additional ml of the CG co-precipitate was poured over the mesh.
  • PP polypropylene
  • CG coUagen-glucosaminoglycan
  • the frozen composite was then sublimated at 200 milliTorr to produce a highly porous composite completely surrounding the PP mesh.
  • the collagen fibers of the matrix were cross-linked using a 24 hour dehydrothermal treatment at 105°C and 30 miUiTorr.
  • a PP or CG/PP mesh was placed within the peritoneal cavity dorsal to the abdominal wall and peritoneum. Twelve animals were used for PP mesh implantation. Additionally, 14 animals were implanted with CG/PP composites which had been GA crosslinked, and 14 animals were implanted with CG/PP composites without GA cross-linking.
  • the edge of the abdominal wall defect was sutured directly to the edges of the implants with a rurming 5/0 nylon suture. This repair resulted in an elliptical fascial defect (3 x 1 cm) bridged by the implant with a 0.5 cm overlap at all edges.
  • a running 5/0 nylon suture was used to close the skin and the incision was dressed with petroleum impregnated gauze and an elastic bandage. Dressings were removed at 7 to 14 days and wounds left open to air.
  • a transverse section of fuU-thickness abdominal wall including attached viscera was fixed in 10% formalin, embedded in paraffin and sectioned for staining with hematoxylin and eosin. Results were expressed as mean ⁇ standard deviation. Comparisons were made using an unpaired Student's t-test. 4. Results
  • Thickness of tissue 0.05 ⁇ 0.02 0.34 ⁇ 0.30 8.0 x 10 "3 below mesh (mm)
  • Thickness of tissue 0.05 ⁇ 0.02 0.68 ⁇ 0.14 8 x 10 "3 below mesh (mm)
  • Hartley guinea pigs underwent ventral hernia repair with one of three meshes: PP mesh alone (control), AllodermTM/PP composite mesh with the dermal basement membrane oriented toward the peritoneal cavity, and AllodermTM/PP composite mesh with the basement membrane oriented away from the peritoneal cavity (i.e., toward the mesh). Gross and histologic observations were made at 4 weeks. Strength, surface area involvement by adhesions, and histologic appearance of the repair sites are compared.
  • the animal was placed in a supine position, prepared with providone-iodine solution, and sterilely draped. Three-centimeter long midline ventral hernia defects centered between the xiphoid and pubis were created, with incision through the ventral midline skin, subcutaneous fat, linea alba, and peritoneum. Composite mesh implants or control implants were inserted into the peritoneal cavity with the AllodermTM material facing the peritoneal cavity. The linea alba was sutured to the mesh implants using a running 5/0 Prolene ® suture, resulting in an elliptical, 3 x 1 cm defect in the abdominal wall bridged by the implant alone. The implant was positioned completely intraperitoneally to facilitate adhesions. The skin was closed with stainless steel clips. Animals were monitored until fully recovered from anesthesia and then individually housed. Skin clips were removed 1 week postoperatively.
  • the density of cellular infiltration within the AllodermTM/PP graft was quantified and compared between groups.
  • the thickness of the tissue layer beneath the mesh and that of the neoperitoneum as well as that of the neoperitoneum itself was determined and compared.
  • FIG. 1 illustrates the synthetic mesh 1 and a composition 10.
  • the composition 10 comprises a barrier membrane of AllodermTM 12 and a supporting membrane that, in this embodiment, comprises a synthetic material 14.
  • the barrier membrane 12 covers the edges
  • the composition 10 has the advantage of having a strong closure with decreased adhesions as compared to the prior art 1.
  • FIG. 3 illustrates an intra-abdominal wound four weeks after composition 34 implantation. As compared to the adhesions 26 in FIG. 2, the adhesions 30 in FIG. 3 are substantially decreased. The barrier membrane 32 is partially degraded and replaced with host tissue and is vascularized.
  • Example 3 Alloderm Barrier Material with PP Mesh Supporting Material Composition Reduced Adhesions in Larger Studies
  • the average surface area of adhesions for the two Alloderm ® /PP groups were 9.5 ⁇ 12.1% for the PP/AlloOut group and 12.4 ⁇ 8.3% for the PP/AUoIn group.
  • the adhesion strengths for the control group had an average of 2.9 ⁇ 0.20 on the grading scale.
  • the adhesion strengths for the two Alloderm ® /PP groups were 0.5 ⁇ 0.45 for the PP/AlloOut group and 1.0 ⁇ 0.41 for the PP/AUoIn group. There was, however, no statistically significant difference in either adhesion surface area or grade between the PP/AUoIn and PP/AlloOut groups. All repair sites in each group involved the greater omentum. The incidence of bowel adherence to the repair site was significantly greater with PP repairs (72%) than the PP/AlloOut (0%) or the PP/AUoIn (0%) repairs.
  • All implants were rigidly incorporated into the musculofascial edges of the repair sites with dense fibrovascular infiltration around the PP fibers and through the interstices.
  • the vascularized tissue layer that formed beneath the polypropylene mesh at the repair site was significantly thicker in both the PP/AUoIn (634 ⁇ 175 ⁇ m) and PP/AlloOut (541 ⁇ 161 ⁇ m) than the PP (52 ⁇ 6 ⁇ m) group.
  • the Alloderm ® /PP composites were further characterized by highly vascularized host tissue incorporating and replacing the Alloderm ® over the 4 weak healing period.

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Abstract

L'invention concerne un composite (1) comprenant un matériau barrière (2) et un matériau support (3), ce composite étant utilisé pour favoriser la cicatrisation d'une plaie ou d'un tissu. Ce composite présente les avantages suivants : adhérence réduite aux organes, ou autres structures, adjacents au site de cicatrisation, flux de fluides limité, vascularisation et infiltration cellulaire accrues, inflammation réduite et formation limitée de tissu cicatriciel.
EP03746135A 2002-04-01 2003-04-01 Materiau composite favorisant la cicatrisation d'une plaie Ceased EP1494597A4 (fr)

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US36906302P 2002-04-01 2002-04-01
US369063P 2002-04-01
PCT/US2003/010289 WO2003084410A1 (fr) 2002-04-01 2003-04-01 Materiau composite favorisant la cicatrisation d'une plaie

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Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4638562B2 (ja) 1996-12-10 2011-02-23 パーデュー・リサーチ・ファウンデーション 脊椎動物肝臓組織由来の生物材料
WO2003059061A1 (fr) 2002-01-11 2003-07-24 Purdue Research Foundation Biomateriau tire du tissu hepatique de vertebres
US7655047B2 (en) 2003-04-16 2010-02-02 Porex Surgical, Inc. Craniofacial implant
US8298292B2 (en) 2003-04-16 2012-10-30 Howmedica Osteonics Corp. Craniofacial implant
ES2546393T3 (es) 2004-04-20 2015-09-23 Genzyme Corporation Implante quirúrgico tipo malla
AU2006244393B2 (en) * 2005-05-05 2012-06-21 Cook Biotech Incorporated Implantable materials and methods for inhibiting tissue adhesion formation
AU2008223798A1 (en) * 2007-03-07 2008-09-12 Coloplast A/S Mesh comprising ECM
WO2009009620A2 (fr) 2007-07-10 2009-01-15 Lifecell Corporation Compositions de matrices tissulaires acellulaires destinées à la réparation de tissus
US8808314B2 (en) 2008-02-18 2014-08-19 Covidien Lp Device and method for deploying and attaching an implant to a biological tissue
US9034002B2 (en) 2008-02-18 2015-05-19 Covidien Lp Lock bar spring and clip for implant deployment device
US9833240B2 (en) 2008-02-18 2017-12-05 Covidien Lp Lock bar spring and clip for implant deployment device
EP2247245B1 (fr) 2008-02-18 2017-06-28 Covidien LP Dispositif pour déployer et faire tenir un patch sur un tissu biologique
US8758373B2 (en) 2008-02-18 2014-06-24 Covidien Lp Means and method for reversibly connecting a patch to a patch deployment device
US9393093B2 (en) 2008-02-18 2016-07-19 Covidien Lp Clip for implant deployment device
US8317808B2 (en) 2008-02-18 2012-11-27 Covidien Lp Device and method for rolling and inserting a prosthetic patch into a body cavity
US9044235B2 (en) 2008-02-18 2015-06-02 Covidien Lp Magnetic clip for implant deployment device
US9301826B2 (en) 2008-02-18 2016-04-05 Covidien Lp Lock bar spring and clip for implant deployment device
US9393002B2 (en) 2008-02-18 2016-07-19 Covidien Lp Clip for implant deployment device
US9398944B2 (en) 2008-02-18 2016-07-26 Covidien Lp Lock bar spring and clip for implant deployment device
US9480549B2 (en) 2008-04-25 2016-11-01 Allosource Multi-layer tissue patches
AU2009240564A1 (en) * 2008-04-25 2009-10-29 Allosource Anti-adhesion barrier wound dressing comprising processed amniotic tissue and method of use
US9358320B2 (en) 2008-04-25 2016-06-07 Allosource Multi-layer tissue patches
JP2011526811A (ja) 2008-07-01 2011-10-20 クック・バイオテック・インコーポレイテッド 漿膜下筋膜を含む分離された細胞外マトリクス材料
EP2337502B1 (fr) 2008-10-20 2014-08-06 Covidien LP Dispositif pour fixer un pansement sur un tissu biologique
WO2011021082A1 (fr) 2009-08-17 2011-02-24 PolyTouch Medical, Inc. Moyen et procédé pour relier de manière réversible un implant à un dispositif de déploiement
EP2467093B1 (fr) 2009-08-17 2019-08-28 Covidien LP Dispositif de déploiement de pièce articulée
US9549812B2 (en) * 2012-01-13 2017-01-24 Lifecell Corporation Breast prostheses, methods of manufacturing breast prostheses, and methods of treatment using breast prostheses
EP3281607B1 (fr) 2012-06-21 2019-03-06 LifeCell Corporation Prothèse implantable pourvue d'attaches tissulaires acellulaires
ES2523458B1 (es) * 2013-05-23 2015-07-15 José Manuel GALEANO SALVADOR Composición farmacéutica o cosmética para la regeneración y cicatrización de la piel
WO2016143746A1 (fr) * 2015-03-12 2016-09-15 一般財団法人化学及血清療法研究所 Matériau anti-adhérence et membrane biologique artificielle comprenant chacun un tissu décellularisé
CA2985537A1 (fr) 2015-05-15 2016-11-24 Lifecell Corporation Matrices de tissu pour chirurgie plastique
CN110923193A (zh) * 2015-07-29 2020-03-27 广东博与再生医学有限公司 皮肤溃疡修复基质用培养基的配制方法
US10850008B2 (en) 2015-12-11 2020-12-01 Lifecell Corporation Methods and systems for stiffening of tissue for improved processing
WO2018112480A1 (fr) * 2016-12-16 2018-06-21 Iviva Medical, Inc. Interposition de film mince pour échafaudages de membrane basale
CN107261116A (zh) * 2017-06-17 2017-10-20 河南艾尔恩生物技术有限公司 一种促进组织再生修复剂
JP7042730B2 (ja) * 2018-10-31 2022-03-28 株式会社ハイレックスコーポレーション 生体内非分解性癒着阻止材
US11298220B2 (en) 2019-05-03 2022-04-12 Lifecell Corporation Breast treatment device
EP4008368A4 (fr) * 2019-08-01 2023-06-07 KM Biologics Co., Ltd. Inhibiteur de fibrose tissulaire dans lequel un polymère biocompatible est utilisé
CN114984323B (zh) * 2022-06-15 2023-09-12 上海交通大学医学院附属第九人民医院 一种腹壁缺损修复材料及制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4060081A (en) * 1975-07-15 1977-11-29 Massachusetts Institute Of Technology Multilayer membrane useful as synthetic skin
WO2000016822A1 (fr) * 1998-09-21 2000-03-30 The Brigham And Women's Hospital, Inc. Reparations tissulaires et compositions a cet effet
EP1177800A1 (fr) * 2000-08-04 2002-02-06 Depuy Orthopaedics, Inc. Sous-muqueuse de l'intestin grêle renforcée

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2678945B2 (ja) * 1989-04-17 1997-11-19 有限会社ナイセム 人工血管とその製造方法及び人工血管用基質
US6087552A (en) * 1994-11-15 2000-07-11 Sisters Of Providence Of Oregon Method of producing fused biomaterials and tissue
US5733337A (en) * 1995-04-07 1998-03-31 Organogenesis, Inc. Tissue repair fabric
TW510803B (en) * 1996-11-20 2002-11-21 Yasuhiko Shimizu Man-made esophagus and its manufacturing method

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4060081A (en) * 1975-07-15 1977-11-29 Massachusetts Institute Of Technology Multilayer membrane useful as synthetic skin
WO2000016822A1 (fr) * 1998-09-21 2000-03-30 The Brigham And Women's Hospital, Inc. Reparations tissulaires et compositions a cet effet
EP1177800A1 (fr) * 2000-08-04 2002-02-06 Depuy Orthopaedics, Inc. Sous-muqueuse de l'intestin grêle renforcée

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
BUTLER CHARLES E ET AL: "Reduction of adhesions with composite AlloDerm/polypropylene mesh implants for abdominal wall reconstruction." PLASTIC AND RECONSTRUCTIVE SURGERY. AUG 2004, vol. 114, no. 2, August 2004 (2004-08), pages 464-473, XP008059049 ISSN: 0032-1052 *
BUTLER, CHARLES E. ET AL: "Reduction of abdominal adhesions using composite collagen-GAG implants for ventral hernia repair" JOURNAL OF BIOMEDICAL MATERIALS RESEARCH , VOLUME DATE 2001, 58(1), 75-80 CODEN: JBMRBG; ISSN: 0021-9304, 2000, XP002364584 *
DATABASE MEDLINE [Online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; March 1996 (1996-03), WAINWRIGHT D ET AL: "Clinical evaluation of an acellular allograft dermal matrix in full-thickness burns." XP002364725 Database accession no. NLM8675502 & THE JOURNAL OF BURN CARE & REHABILITATION. 1996 MAR-APR, vol. 17, no. 2, March 1996 (1996-03), pages 124-136, ISSN: 0273-8481 *
DATABASE MEDLINE [Online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; November 1998 (1998-11), ACHAUER B M ET AL: "Augmentation of facial soft-tissue defects with Alloderm dermal graft." XP002364726 Database accession no. NLM9827953 & ANNALS OF PLASTIC SURGERY. NOV 1998, vol. 41, no. 5, November 1998 (1998-11), pages 503-507, ISSN: 0148-7043 *
DINSMORE R C ET AL: "Prevention of adhesions to polypropylene mesh in a traumatized bowel model." August 2000 (2000-08), JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS. AUG 2000, VOL. 191, NR. 2, PAGE(S) 131 - 136 , XP002364722 ISSN: 1072-7515 * abstract * *
GREENAWALT, KEITH E. ET AL: "Evaluation of Sepramesh Biosurgical Composite in a Rabbit Hernia Repair Model" JOURNAL OF SURGICAL RESEARCH , 94(2), 92-98 CODEN: JSGRA2; ISSN: 0022-4804, 2000, XP002364583 *
LIVESEY S A ET AL: "TRANSPLANTED ACELLULAR ALLOGRAFT DERMAL MATRIX" TRANSPLANTATION, WILLIAMS AND WILKINS, BALTIMORE, MD, US, vol. 60, no. 1, 15 July 1995 (1995-07-15), pages 1-9, XP000196602 ISSN: 0041-1337 *
See also references of WO03084410A1 *

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AU2003260086A1 (en) 2003-10-20
AU2009202536A1 (en) 2009-07-16
WO2003084410A1 (fr) 2003-10-16
CA2480875A1 (fr) 2003-10-16

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