CA2133028A1 - Absorbable structures for ligament and tendon repair - Google Patents
Absorbable structures for ligament and tendon repairInfo
- Publication number
- CA2133028A1 CA2133028A1 CA002133028A CA2133028A CA2133028A1 CA 2133028 A1 CA2133028 A1 CA 2133028A1 CA 002133028 A CA002133028 A CA 002133028A CA 2133028 A CA2133028 A CA 2133028A CA 2133028 A1 CA2133028 A1 CA 2133028A1
- Authority
- CA
- Canada
- Prior art keywords
- bioabsorbable
- layer
- prosthesis according
- gel
- sponge
- 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.)
- Abandoned
Links
Classifications
-
- 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
- A61F2/02—Prostheses implantable into the body
- A61F2/08—Muscles; Tendons; Ligaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/11—Surgical instruments, devices or methods, e.g. tourniquets for performing anastomosis; Buttons for anastomosis
- A61B17/1146—Surgical instruments, devices or methods, e.g. tourniquets for performing anastomosis; Buttons for anastomosis of tendons
-
- 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
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B2017/00004—(bio)absorbable, (bio)resorbable, resorptive
-
- 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
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
- A61F2002/3006—Properties of materials and coating materials
- A61F2002/30062—(bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
-
- 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
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
- A61F2002/3006—Properties of materials and coating materials
- A61F2002/30062—(bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
- A61F2002/30064—Coating or prosthesis-covering structure made of biodegradable material
-
- 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
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30108—Shapes
- A61F2002/30199—Three-dimensional shapes
- A61F2002/30224—Three-dimensional shapes cylindrical
-
- 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
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30108—Shapes
- A61F2002/30199—Three-dimensional shapes
- A61F2002/30291—Three-dimensional shapes spirally-coiled, i.e. having a 2D spiral cross-section
-
- 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
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30108—Shapes
- A61F2002/30199—Three-dimensional shapes
- A61F2002/30291—Three-dimensional shapes spirally-coiled, i.e. having a 2D spiral cross-section
- A61F2002/30293—Cylindrical body made by spirally rolling up a sheet or a strip around itself
-
- 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
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/3094—Designing or manufacturing processes
- A61F2002/30971—Laminates, i.e. layered products
-
- 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
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
-
- 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
- A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2230/0063—Three-dimensional shapes
- A61F2230/0069—Three-dimensional shapes cylindrical
-
- 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
- A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2230/0063—Three-dimensional shapes
- A61F2230/0091—Three-dimensional shapes helically-coiled or spirally-coiled, i.e. having a 2-D spiral cross-section
-
- 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
- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2240/001—Designing or manufacturing processes
-
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/10—Materials or treatment for tissue regeneration for reconstruction of tendons or ligaments
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S623/00—Prosthesis, i.e. artificial body members, parts thereof, or aids and accessories therefor
- Y10S623/901—Method of manufacturing prosthetic device
Abstract
ABSTRACT
ABSORBABLE STRUCTURE FOR LIGAMENT AND TENDON REPAIR
A fully absorbable prosthesis (1) for the repair of damaged ligaments and/or tendons in the form of a multilayer spiral roll comprising the following spiral layers: a foraminous layer (2) of a synthetic bioabsorbable material;
a bioabsorbable film (3); and a layer (4) of a bioabsorbable biopolymer sponge. The invention also provides a method of making such a prosthesis, comprising the steps of: providing a laminate of a foraminous layer of bioabsorbable material and a bioabsorbable film; coating the laminate with a layer of an aqueous gel comprising a bioabsorbable polymer;
rolling up the laminate and the gel layer into a spiral roll, followed by drying the gel to form a layer of bioabsorbable sponge. The foraminous layer (2) preferably comprises a synthetic bioabsorbable polymer having high tensile strength. The bioabsorbable film (3) and sponge layer (4) preferably comprise a chemotactic biopolymer such as collagen.
(Figure 1)
ABSORBABLE STRUCTURE FOR LIGAMENT AND TENDON REPAIR
A fully absorbable prosthesis (1) for the repair of damaged ligaments and/or tendons in the form of a multilayer spiral roll comprising the following spiral layers: a foraminous layer (2) of a synthetic bioabsorbable material;
a bioabsorbable film (3); and a layer (4) of a bioabsorbable biopolymer sponge. The invention also provides a method of making such a prosthesis, comprising the steps of: providing a laminate of a foraminous layer of bioabsorbable material and a bioabsorbable film; coating the laminate with a layer of an aqueous gel comprising a bioabsorbable polymer;
rolling up the laminate and the gel layer into a spiral roll, followed by drying the gel to form a layer of bioabsorbable sponge. The foraminous layer (2) preferably comprises a synthetic bioabsorbable polymer having high tensile strength. The bioabsorbable film (3) and sponge layer (4) preferably comprise a chemotactic biopolymer such as collagen.
(Figure 1)
Description
~1 3 ~ 0 2 ~ JJM-88 ABSORBABLE STRUCTURES FOR LIGAMENT AND TENDON REPAIR
The present invention relates to absorbable structures for use as ~emporary prostheses in the repair of damaged ligaments and/or tendons.
Damage to ligaments and~or tendons is a frequent occurrence, particularly as a consequence of violent exercise or contact sports. An especially common and difficult to treat sports injury is tearing o~ tha anterior cruciate ligament (ACL) of the kneeO
Various approaches have been tried to restore the ~unction of torn tendons or ligaments. The simplest approach is simply to suture together the torn ends of the ligament or tendon. However, the healing rate of ligaments or tendons sutured in this way is extremely slow, and even after healing is complete the strength of the ligament or tendon is substantially reduced. Moreover, the scar tissue tends to propagate into surrounding tissues causing discomfort and loss of mobility.
In another approach, the ligament or tendon is replaced by a permanent prosthesis o~ biocompatible but non-resorbable material, such as Dacron~, PTFE or polypropylene.
A favoured permanent prosthesis consists of bundles of carbon fibers, optionally coated with a biocompatible polymer. However, none of the permanent prostheses has proved to be sufficiently durable to replace a ligament or tendon for the life of a user. In particular, it has been found that the carbon-fiber based prostheses tend to crack after 12-18 months of use, thereby releasing carbon 3~ particles that can cause ssvere inflammatory reactions and even arthritis. ~-A further approach to the repair of damaged tendons or ligaments has been to implant a temporary, biodegradable prosthesis that can stabilize the tendon or ligament and provide a framework for healing of the tendon or ligament while gradually being absorbed into the body. Accordingly, the re~uirements for such a temporary prosthesis include~
high t~nsile strenyth to restore tendon or ligament '.`~'".'~, ,~
3 3 ~ ~ 8 function, slow but complete bioabsorption in situ, low antigenicity, and a directional (uniaxial) structure that promotes formation of strong, well-oriented sc~r tissue by directional i~growth of fibroblasts from the undamayed ends of the ligament or tendon.
W085/00511 describes a collagen~based material for regeneration of ligaments andlor tendons. The material is ~ormed from strands of eollagen that have been cross-linked with glutaraldehyde to increase their tensile strength. The collagen strands are provided in the form of a suitable weav~ with sufficient space betwe~n the stra~ds to function a~ a "scaffold" through which ligament fibroblasts can propagate. A sheet of the collagen weave may be rolled up to form a cylinder of spiral cross-section which is positioned between ends of e.g. a torn anterior cruciate ligament~ the ends of the cylinder being sutured to the undamaged ends of the ligament. The joint is immobilized, and healing of the ligament is said to be completed in as little as three weeks.
Similarly, US-A-5171273 describes absorbable ligament or tendon prostheses formed fro~n high-strength collagen ~ibexs. The high-strength collagen ~ibers are formed by the steps of: dissolving typ~ I collagen in dilute HCl, extruding the solution into a special buff'er bath to reconstitute the collagen fibers, and cross-linking the reconstituted fibers using glutaraldehyde or a combination of severe dehydration and treatment with cyanamide. The ~ibers are woven, twisted or braid~d together to form the absorbable ligament and/or tendon prostheses.
A drawback of tendon and/or ligament prostheses that are formed solely from collagen is that the collagen loses its tensile strength rapidly in vivo, eYen when cross-linked as de~cribed above. This characteristic of collagen is incompatible with the relatively long healing times required for repa.ir of ligaments or tendons.
W088/06872 dPscribes an implantable prosthesi~ for the repair of tendon~ or liyaments, characterized by a structure of a bioabsorbable material other than proteins or ~ \ ~133~2~ JJM-88 polypeptides or derivatives thereof. The structure exhibits longitudinal grooves or channels intended to serve as initial propagation guides for new fibrous tissue. For example, the prosthesis may consist of a plurality of 5 concentric tubes of a synthetic bioabsorbable polymer, such as a copolymer of lactic and glycolic acids, polyhydroxy butyric acid or the like. The interstices between the tubes provide the longitudinal channels for tissue ingrowth.
EP-A-0241252 describes an absorbable ligament or tendon prosthesis formed from melt spun filaments of a special end capped lactide polymer having exceptionally high tensile strength. The filaments are plied, twisted or braided to form the ligament or tendon prosthesis. The twist or braid provides a relatively open structure which is geometrically capable o~ allowing natural tissue to be deposited along the filaments and develop natural tendon or ligamentous tissue.
A drawback o~` the above absorbable prostheses based solely on synthetic, non-collagenous polymers is that the prostheses cannot exhibit the beneficial wound-healing properties of biopolymers such as collagen. It is well known that wound-healing cells such as fibroblasts have a special affinity for collagen and certain other biopolymers.
This property is termed the chemotactic effect of collagen A further drawback of all previous absorbable tendon and/or ligament prostheses is that the porosity of the prostheses to cellular invasion by fibroblasts is not optimised. It has been de~ermined that a pore or channel size in the range 50-2~0 ~m is preferred for promoting c~llular invasion, but hitherto the implant materials have not provided a controlled porosity in this range.
Accordingly, it is an object of the present invention to provide fully bioabsorbable ligament and/or tendon prostheses that combine high tensile strength, chemotactic properties and optimised porosity for directional cellular invasion and healing.
The present invention provides a bioabsorbable ligament or tendon prosthesis in the form of a multilayered spiral roll comprising the following spiral layers: a foraminous : ''.`' 3 0 ~ 8 JJM--88 4 . ~ ::
layer of a synthetic bioabsorbablP material; a bioabsorbable film, and a layer of a bioabsorbable spongeO
The prostheses ~ccording to the present invention are in the form o~ a multilayered spiral roll, also known as a r' ~'Swiss roll" structure. That iS to say, the prostheses ar~
formed by rolling up a plurality of overlapping layeris into a cylindrical roll~ Each of the layers is thsreby rolled into a spiral roll that is coaxial with and radially alternating with the othar layers.
The spiral roll preferably has a diameter in the range of from 1.2 to 21 mm, more preferably 300 to 10.0 mm. The length of the spiral roll is preferably 5 to 80 mm. The spiral roll preferably contains from 2 to 6 complete 360 turns of the spiral.
The chief function of the foraminouis layer of a synthetic bioabsorbable material is to provide tensile strength to the prosthesis. The foraminous nature of this layer enhances the ~lexibility of the prosthesis and allows easy suturiny of the prosthesis. Preferably the foraminous layer is a woven, non-woven or knitted mesh.
Preferably, the foraminous layer comprises a pol~mer or copolymer o~ lactic acid or glycolic acid, oxidized regenerated cellulose, polydioxanone tPDS), a copolymer of lactic acid and ~-~aprolactam, polyhydroxybutyric acid or a 25 copolymer of hydroxybutyric acid and hydroxyvaleric acid. ~ -~
More preferably, the foraminous layer comprises one of the copolymers of lactic acid and glycolic acid sold under the Registered Trad~ Mark VICRYh, or the oxidized regenerated ~ ~
cellulose sold under the Registered Trade Mark SURGICEL. ~ ~ -Most preferably, the foraminous layer comprises the melt~
spun polylactide or polylactide/polyglycolide copolymer ~ r descri~ed in EP-A-0241252.
The foraminous layer does not need to be bonded to either the continuous film or to the sponge layers.
However, pxeferably, the foraminous layer is bonded to one or both of the film or the sponge layer,iand more prefarably the foraminous layer is actually embedded in one or oth~r of ~ ;
the film or the sponge layer, as described further below.
~,, ,;~ " ~ ,- "
~3302~ JJM--88 The maximum thickness of the foraminous layer is preferably in the range 0.02 to 0.3 mm, more preferably 0.04 to o.l mm.
The bioabsorbable film is a continuous or substantially continuous layer of bioabsorbable material that serves to block cellular migration in radial directions inside the prosthesis. That is to say, the barriar layer of bioabsorbable film serves to guide cellular migration axially along the prosthesis, resulting in the formation of well orientad and strong replacement tissue. The bioabsorbable film is preferably formed by drying an aqueous solution or suspension comprising a biopolymer such as collagen, a glycosaminoglycan such as hyaluronic acid, or tha like. Preferably, the bioabsorbable film contains a bioabsorbable plasticiser. Preferably the plasticiser is a polyhydric alcohol such as glycerol, and preferably it is present in an amount of 5% to 50% w/w.
The biopolymer is preferably cross-linked to reduce the rate at which it is bioabsorbed. Preferred cross-linking agents include aldehydes such as glutaraldehyde, isocyanates and carbodiimides. The biopol~er film preferably also contains oil microdroplets di~persed therein in order further to reduce the rate of bioabsorption. The oil microdroplets may comprise any biocompatible and bioabsorbable oil, such as sunflower seed oil, sesame seed oil or fish oil. Preferably, the oil is present in an amount of 1 to 90% by weight, more preferably 10 to 75% by weight based on the weight of the biopol~mer film.
Preferably, the foraminous layer is actually coated with th~ bioabsorbable ilm or embedded therein, so that the interstices in the foraminous layer are substantially all filled by the material of the bioabsorbable film.
Particularly preferred composite materials comprising a reinforcing mesh embedded in a ollagen film are described 35 and claimed in EP-A-0194192. ~ -The thickness of the bioabsorbable film (except when it forms a composite with the foraminous layer) is preferably in the range 0.01-0.1 mm, and more preferably 0.0~5-0O03 mm.
;~1 33028 JJM--8a The layer of a bioabsorbable biopolymer sponge serves as a spacer between the coils of the reinforcing layer and the bioabsorbable film, defining a uniform and directional interstitial channel for cellular in~asion. Th~ porosity of the sponge and the chemstactic effect of the biopolymer combine to promote rapid invasion by fibroblasts, resulting in rapid tissue regeneration. Preferably~ the sponge comprises collagen, a glycosaminoglycan such as chondroitin sul~ate or hyaluronic acid or a mixture of such biopolymers.
Preferably, the porosity of the sponge is optimised for maximum cellular ingrowth, implying that at least 80% of the pores have an average pore diameter in the range 50 ~m - 250 ~m. Such relatively small pore sizes can be obtained, for example, by flash freezing of a collayen solution or suspension (resulting in very small ice crystals) followed by freeze drying, as described in WO90/00060. Alternatively or additionally, small pore siæes may be obtained by including a volatile anti-fre~eze such as ethanol or isopropanol in the gel, preferably in an amount o~ 5 -25% w/v. The presence of the anti-freeze results in the formation of smaller ice crystals on freezing, and hence smaller pores on freeze-drying. :~
Preferably, the sponge compri~3es chemotherapeutic agents in addition to the structural biopolym r. For example, the sponge may contain an antis~ptic or an antibiotic.
Preferably, the sponge contains a wound healing factor such as a growth factor, a cytokine, an alginate, a -~:~
glycosaminoglycan or an active derivative thereof. The bioabsorbable film may alternakively or additionally contain the same or a di~ferent therapeutic agent ox agents.
Preferably, the structural biopolymer of the sponge is cross~linked to reduce the rate of bio-absorption of the sponge. Preferably, the structural biopolymer is collagen and the cross-linking agent is one of those described above :
for the bioabsorbable filmD Also pre~erably, the biopolymer sponge contains preferably 1 to 90% by weight, more ::
preferably 10 to 75% by weight based on the weight of the :~
sponge, of oil microdroplets dispersed therein. The oil may ~:~
~. r ..~
33~28 be any biocompatible and biodegradable oil such as sunflower seed oil, sesame seed oil or fish oil. The presence of the oil microdroplets substantially reduces the rate of bioabsorption of the sponge. Furthermore, the oil microdropl~ts can be used as vehicles for hydrophobic, oleophilic therapeutic agents.
Preferably, the thickness of the sponge layer is in the range O.5 to 2.5 mm, more preferably 1.~ to 1.5 mm.
Preferably, the sponge layer has embedded therein one or more solid bioabsorbable rods extending longitudinally through part or all of the prosthesis. The rods may be sections of bioabsorbable stuture, prPferably collagen suture. The rods enhance the uniaxial directionality of the sponge layer and reduce thP rate at which the layer is absorbed in ViYo.
The present invention also provides the use of a bioabsorbable prosthesis as described above for the preparation of a surgical implant for the repair of a damaged tendon or ligament.
The present invention furthler pxovides a m~thod of making a bioabsorbable prosthesis for use in surgical repair of a damaged ligamenk or tendon, the method comprising the steps of: providing a laminate of a foraminous ~ayer of bioa~sorbable material and a bioabsorbable film; coating the laminate with a layer of an aqueous gel comprising a bioab~orbable polymer; rolling up the laminate and the gel layer into a ~piral roll, followed by drying the gel to form a layer of bioabsorbable sponge.
Preferably, the gel is dried to form the bioabsorbable sponge by freezing (preferably flash freezing), followed by fr~eze-drying by evaporation o~ water from the gel under reduced pressure. In alternative preferred methods, the gel is frozen or fl~sh~frozen and the frozen gel is then solvent dried by treatment with a hygroscopic solvent such as isopropyl alcohol~
The laminate comprises overlapping layers of the foraminous layer of bioabsorbable material and the bioabsorbable ~ilm. Preferably, the laminate comprises a 8 JJ~-88 high ten~ile strength foraminous mesh embedded in a ~ilm of a biopolym~r such as collagen, a~ described in EP-A-01941920 The compositions of the foraminous layer and the bioabsorbable film may be the same or different, and are preferably as defined above for preferred embodiments of the tendon or ligament prostheses of the present invention.
Preferably, the aqueous gel comprises acid-swollen collagen ~ibers, pre~erably at a concentration of 0.1%-5% w/v. In preferred methods, fibrous collagen is extracted from bovine corium or tendon and pre-washed to remove the majority of non-collagenous components as described in US-A-4614794 or US-A-4320201. The collagen is then suspended in clean deionised pyro~en-free water and homogenised to a fine fibrous suspension by passage through a homogenising system. Suitable homoqenising systems are described in US~
A-4320201.
Homogenization is continued until a desired degree of fiber division is achieved. Th:is results in a preferred fiber size in the range 0.01 to lOmm.
The homogenized collagen is acidi~ied to cause it to swell and form a gel suitable for freeze drying. The acidifying step may use an organic acid such as formic, acetic, propionic, lactic or malonic, or dilute inorganic acids such as hydrochloric acid. Preferably the homogenized colla~en suspension is acidified to pH 2 to 6, more preferably pH 300 to 4.5.
rhemotherapeutic agents, preferably as described above, may be dispersed in the aqueous g~l of the bioabsorbakle polymer, preferably in an amount of 0.1% to 50% w/w, based on the dry weight of the sponge. Also preferably, microdroplets of a bioabsorbable oil may be dispersed in the aqueous gel by emulsification at high shear ~collagen i5 an effective emulsifier). Preferably, the oil microdroplets are present in an amount of from 1% to 90% by weight, more preferably 10% to 75%, based on the dry weight of the sponge.
Preferably, the aqueous gel is dried by flash ~reezing at temperatures below -20C, followed by freeze drying, V ~
~''`':'''`''`'''."`"`",'"','.
~` ~13302~ JJM-88 preferably as described in W090/00060. The flash freezing results in smaller ice crystals, and thus provides smaller pores in the freeze-dried sponge. The pore size of the freeze-dried sponge may also be reduced by adding volatile anti-freeze substances such as ethanol or isopropanol to the aqueous gel before it is frozen, since these also will tend to reduce the size of the ice crystals ~ormed on freezing.
Preferably, the anti-freeze substance is added in an amount of 5% - 25% w/v, based on the volume of the gel.
Preferably, the freeze-drying step is carried out either by evaporating the water (a~d other volatile components) from the frozen gel under reduced pressure, or by solvent drying, which involves treating the frozen gel with a hygroscopic solvent, such as isopropyl alcohol, to extract th~ water from the frozen gel. Surprisingly, it has been found that the presence of volatile antifree~e agents such as ethanol or isopropyl alcohol in the ~rozen gel results in accelerated solvent dxying.
Preferably, the laminate with the layer of aqueous gel thereon is rolled up through 2 to 6 complete 360 revolutions prior to drying. The aqueous gel may be prechilled to 0-5~C prior to the rolling-up step in order to increase the rigidity of the gel ii~nd reduce the gel lost by squeezing out of the ends of the roll. Preferably, the rolling-up step is initiated by rolling up about a small diameter bobbin, e.g. a hypodermic needle, which is removed after the rolling up is complete. A small excess of the aqueous gel (up to 50~ excess~ may be used to compensate for gel lost in the rolling up step.
In other preferred methods according to the invention, one or more bioabsorbable rods is laid atop the laminate and extending substantially parallel to the axis about which the laminate is to be rolled up. The bioabsorbable rods are preferably sections of bioabsorbable suture, and preferably comprise collaqen. The rods help to ensure a uniform thickness for the spong~i layer in the dried prosthe~is.
In yet other priPferred embodiments, the method according to the present invention may further comprise the step of incubating the dried prosthesis in vitro with host cells such as host synovial cells or host fibrobla~t cells prior to implan~ation. The cells may even b8 injected into the body of the prosthesis. After a suitable time to achieve required cellular growth and proliferation in the prosthesis, the structure can be implanted in the body~
A specific embodiment of the tendon or ligament prosthesis of the invention will now be described ~urthar, by way of example with reference to the accompanying drawings, in which:
Fiqure 1 shows a transverse cross-section through a bioabsorbable prosthesis according to the present invention;
Fiqure 2 shows stages in the method of making the bioabsorbable prosthesis of Figure l; and Fi~ure 3 shows the bioabsorbable prosthesis of Figure 1 in use to repair a severed ligament.
Referring to Figure 1, the prosthesis 1 comprises a multilayered spiral roll consisting of a foraminous layer 2 of a synthetic bioabsorbable matexial, a bioabsorbable ~ilm 2 and a layer 3 of bioabsorbable sponge. The foraminous layer 2 is composed of a polylacticle/polyglycolide mesh sold under the Re~istered Trade Mark VICRYL. The bioabsorbable film 3 is composed of Type I colLagen fibers cross-linked with hexamethylene diisocyanate. The sponge layer 4 is also ~ormed from Type I collagen fibers cross-linked with hexamethylene diisocyanate.
In use, the prosthesis 1 is used to r~place part or all of a damaged ligament or tendon, as shown in Figure 3. The ends 5, 6 of the prosthesis are sutured to the undamaged ends 7, 8 of the ligament or tendon. Alternatively, one of the ends 5, 6 of the prosthesis may be attached directly onto a bone or into a socXet provided in a bone.
Figure 3 also shows schematically, by means of arrows, the dirPction of cellular migration and tissue ingrowth into the prosthesis 1 from the undamaged ends 7, 8 of the ligament or tendon. The cells, especially ~ibroblasts, migrate rapidly into the collagen sponge on account o~ its porosity and the chemotactic e~fect of collagen. Howevex, the cell migration is highly directional, since the collage~
sponge spiral layer 4 de~ines a longitudinal channel for cellular migration. Radial cellular migration is blocked by the bioabsorbable film layer 3. The VICRYL mesh layer 2 provides the necessary tensilP strength to the prosthesis while retaining sutureabilityO
Specific embodiments of method of manufacture of prosthesis according to the present invention will now be described further, by way of the following examples~
Example 1 A prosthesis for a ligament or tendon according to the present invention comprising separate layers of foraminous synthetic bioabsorbable polymer, bioabsorbable film, and bioabsorbable sponge is prepared as follows~
A. Preparation of collaqen slurry Fibrous collagen, obtained ~rom bovine corium and pre~
washed to remove the majority of non-collagenous components as described in US-A-4614794 or US-A-4320201 is suspended in clean deionised pyrogen-free water at 0.45% w/v concentration and homogenised to a fine ~ibrous suspension by passag~ through a homogenizing system similar to that described in US-A 4320201. Homlogenisation is continued until the collagen fiber size is in the range 0.1-l.Omm.
The suspension is acidified to pH 4.5 with acetic acid to swell the collagen.
B. Preparation of collaqen film layPr To the collagen gel pr~pared in Step A above glycerol is added as a plasticiser to a final weight of 0.5% w/w and the gel is then spread in a flat tray having a non-stick surface (e.g. PTFE) to a depth of about 2mm. The gel is then dried in warm air to leave a continuous, flexible ~ilm of collagen about 0.02mm thick.
C. Preparation of Laminate A piace of VICRYL~ polylactide/polyglycolide mesh of rectangular shape and dimensions approximately 20mm x 40mm x 0.lmm is placed in a flat-bottomed tray. A piece of the csllagen film prepared in Step B of identical size and shape is placed atop the VICRYL mesh.
~`,,',';,'1'','`'''".'''.'''''''"",..'''.''.',.''',"' ' '` ' ' ~ ~ 3~
D. _Preparation o~_the prosthesis A layer of the collagen gel pr~pared as in Step A but containing 0.5% w/v collagen solids and 10~ w/v isopropanol, and with a final pH of 4~5 is spread approximately 1~2mm deep across the top surface o~ the laminate prepared in Step C. The gel is quickly degassed and the laminate with the gel layer thereon is quickly but gently rolled up around one long edge of the rectangular piece. The resulting helical coil is flash ~rozen as described in W030/00060 followed by 1~ freeze drying to produce the prosthesis. In the resulting collagen sponge layer, at least 80% of the pores have average por~ sizes in the range 35 to 250~m, which is near-optimum for cellular invasion.
Example 2 A pro~thesis for the repair of a ligament ox ten~on according to the present invention, in which the foraminous synthetic bioabsorbable layer is embedded in the bioabsorbable film is prepared a~; ~ollows:
First, a collagen slurry is prepared as in Step A of Example 1, and a glycerol plasticiser is added to the slurry as in Step B. A layer of VICRYL mesh is placed in the bottom of a flak tray having a non-stick (e.g. PTFE~
surface, and the slurry is then poured over the VICRYL mesh to a depth of about 2mm, thereby immersing the VICRY~ mesh in the collagen slurry. The slurry is then dried in warm air to produce a composite layer of material comprising the VICRYL mesh embedded in a collagen film. The preparation of such composite layers is described in detail in EP-A
Olg4192 ~
A rectangular piece of the composite material of dimensions 20mm x 40mm i5 then used as khe laminate in Step D above to produce the desired prosthesis.
Example 3 A bioabsorbable prosthesis for the repair o~ a ligament or tendon having oil microdroplets dispersed in the bioaksorbable film and in the bioabsorbable sponge is prepared as follows:
A collagen slurry is prepared as in step A of Example 1. To this slurry is added ~esame seed oil at 50% (as ~ of the collagen content w/w), and the mixture is homogenized at high shear to emulsify the sesame seed oil. The collagen serves as an e~fective emulsifier. The remaining steps of the method are carried out as described above for Example 2.
The resulting prosthesis undergoes substantially slower bioabsorption and loss of tensile strength in vivo than the prosthesis produced in Example 2.
The above specific embodiment and example~ ar~ intended for the purpose o~ illustration only. Many other embodiments and methods according to the present invention as defined in the accompanying claims will be apparent to the skilled reader.
The present invention relates to absorbable structures for use as ~emporary prostheses in the repair of damaged ligaments and/or tendons.
Damage to ligaments and~or tendons is a frequent occurrence, particularly as a consequence of violent exercise or contact sports. An especially common and difficult to treat sports injury is tearing o~ tha anterior cruciate ligament (ACL) of the kneeO
Various approaches have been tried to restore the ~unction of torn tendons or ligaments. The simplest approach is simply to suture together the torn ends of the ligament or tendon. However, the healing rate of ligaments or tendons sutured in this way is extremely slow, and even after healing is complete the strength of the ligament or tendon is substantially reduced. Moreover, the scar tissue tends to propagate into surrounding tissues causing discomfort and loss of mobility.
In another approach, the ligament or tendon is replaced by a permanent prosthesis o~ biocompatible but non-resorbable material, such as Dacron~, PTFE or polypropylene.
A favoured permanent prosthesis consists of bundles of carbon fibers, optionally coated with a biocompatible polymer. However, none of the permanent prostheses has proved to be sufficiently durable to replace a ligament or tendon for the life of a user. In particular, it has been found that the carbon-fiber based prostheses tend to crack after 12-18 months of use, thereby releasing carbon 3~ particles that can cause ssvere inflammatory reactions and even arthritis. ~-A further approach to the repair of damaged tendons or ligaments has been to implant a temporary, biodegradable prosthesis that can stabilize the tendon or ligament and provide a framework for healing of the tendon or ligament while gradually being absorbed into the body. Accordingly, the re~uirements for such a temporary prosthesis include~
high t~nsile strenyth to restore tendon or ligament '.`~'".'~, ,~
3 3 ~ ~ 8 function, slow but complete bioabsorption in situ, low antigenicity, and a directional (uniaxial) structure that promotes formation of strong, well-oriented sc~r tissue by directional i~growth of fibroblasts from the undamayed ends of the ligament or tendon.
W085/00511 describes a collagen~based material for regeneration of ligaments andlor tendons. The material is ~ormed from strands of eollagen that have been cross-linked with glutaraldehyde to increase their tensile strength. The collagen strands are provided in the form of a suitable weav~ with sufficient space betwe~n the stra~ds to function a~ a "scaffold" through which ligament fibroblasts can propagate. A sheet of the collagen weave may be rolled up to form a cylinder of spiral cross-section which is positioned between ends of e.g. a torn anterior cruciate ligament~ the ends of the cylinder being sutured to the undamaged ends of the ligament. The joint is immobilized, and healing of the ligament is said to be completed in as little as three weeks.
Similarly, US-A-5171273 describes absorbable ligament or tendon prostheses formed fro~n high-strength collagen ~ibexs. The high-strength collagen ~ibers are formed by the steps of: dissolving typ~ I collagen in dilute HCl, extruding the solution into a special buff'er bath to reconstitute the collagen fibers, and cross-linking the reconstituted fibers using glutaraldehyde or a combination of severe dehydration and treatment with cyanamide. The ~ibers are woven, twisted or braid~d together to form the absorbable ligament and/or tendon prostheses.
A drawback of tendon and/or ligament prostheses that are formed solely from collagen is that the collagen loses its tensile strength rapidly in vivo, eYen when cross-linked as de~cribed above. This characteristic of collagen is incompatible with the relatively long healing times required for repa.ir of ligaments or tendons.
W088/06872 dPscribes an implantable prosthesi~ for the repair of tendon~ or liyaments, characterized by a structure of a bioabsorbable material other than proteins or ~ \ ~133~2~ JJM-88 polypeptides or derivatives thereof. The structure exhibits longitudinal grooves or channels intended to serve as initial propagation guides for new fibrous tissue. For example, the prosthesis may consist of a plurality of 5 concentric tubes of a synthetic bioabsorbable polymer, such as a copolymer of lactic and glycolic acids, polyhydroxy butyric acid or the like. The interstices between the tubes provide the longitudinal channels for tissue ingrowth.
EP-A-0241252 describes an absorbable ligament or tendon prosthesis formed from melt spun filaments of a special end capped lactide polymer having exceptionally high tensile strength. The filaments are plied, twisted or braided to form the ligament or tendon prosthesis. The twist or braid provides a relatively open structure which is geometrically capable o~ allowing natural tissue to be deposited along the filaments and develop natural tendon or ligamentous tissue.
A drawback o~` the above absorbable prostheses based solely on synthetic, non-collagenous polymers is that the prostheses cannot exhibit the beneficial wound-healing properties of biopolymers such as collagen. It is well known that wound-healing cells such as fibroblasts have a special affinity for collagen and certain other biopolymers.
This property is termed the chemotactic effect of collagen A further drawback of all previous absorbable tendon and/or ligament prostheses is that the porosity of the prostheses to cellular invasion by fibroblasts is not optimised. It has been de~ermined that a pore or channel size in the range 50-2~0 ~m is preferred for promoting c~llular invasion, but hitherto the implant materials have not provided a controlled porosity in this range.
Accordingly, it is an object of the present invention to provide fully bioabsorbable ligament and/or tendon prostheses that combine high tensile strength, chemotactic properties and optimised porosity for directional cellular invasion and healing.
The present invention provides a bioabsorbable ligament or tendon prosthesis in the form of a multilayered spiral roll comprising the following spiral layers: a foraminous : ''.`' 3 0 ~ 8 JJM--88 4 . ~ ::
layer of a synthetic bioabsorbablP material; a bioabsorbable film, and a layer of a bioabsorbable spongeO
The prostheses ~ccording to the present invention are in the form o~ a multilayered spiral roll, also known as a r' ~'Swiss roll" structure. That iS to say, the prostheses ar~
formed by rolling up a plurality of overlapping layeris into a cylindrical roll~ Each of the layers is thsreby rolled into a spiral roll that is coaxial with and radially alternating with the othar layers.
The spiral roll preferably has a diameter in the range of from 1.2 to 21 mm, more preferably 300 to 10.0 mm. The length of the spiral roll is preferably 5 to 80 mm. The spiral roll preferably contains from 2 to 6 complete 360 turns of the spiral.
The chief function of the foraminouis layer of a synthetic bioabsorbable material is to provide tensile strength to the prosthesis. The foraminous nature of this layer enhances the ~lexibility of the prosthesis and allows easy suturiny of the prosthesis. Preferably the foraminous layer is a woven, non-woven or knitted mesh.
Preferably, the foraminous layer comprises a pol~mer or copolymer o~ lactic acid or glycolic acid, oxidized regenerated cellulose, polydioxanone tPDS), a copolymer of lactic acid and ~-~aprolactam, polyhydroxybutyric acid or a 25 copolymer of hydroxybutyric acid and hydroxyvaleric acid. ~ -~
More preferably, the foraminous layer comprises one of the copolymers of lactic acid and glycolic acid sold under the Registered Trad~ Mark VICRYh, or the oxidized regenerated ~ ~
cellulose sold under the Registered Trade Mark SURGICEL. ~ ~ -Most preferably, the foraminous layer comprises the melt~
spun polylactide or polylactide/polyglycolide copolymer ~ r descri~ed in EP-A-0241252.
The foraminous layer does not need to be bonded to either the continuous film or to the sponge layers.
However, pxeferably, the foraminous layer is bonded to one or both of the film or the sponge layer,iand more prefarably the foraminous layer is actually embedded in one or oth~r of ~ ;
the film or the sponge layer, as described further below.
~,, ,;~ " ~ ,- "
~3302~ JJM--88 The maximum thickness of the foraminous layer is preferably in the range 0.02 to 0.3 mm, more preferably 0.04 to o.l mm.
The bioabsorbable film is a continuous or substantially continuous layer of bioabsorbable material that serves to block cellular migration in radial directions inside the prosthesis. That is to say, the barriar layer of bioabsorbable film serves to guide cellular migration axially along the prosthesis, resulting in the formation of well orientad and strong replacement tissue. The bioabsorbable film is preferably formed by drying an aqueous solution or suspension comprising a biopolymer such as collagen, a glycosaminoglycan such as hyaluronic acid, or tha like. Preferably, the bioabsorbable film contains a bioabsorbable plasticiser. Preferably the plasticiser is a polyhydric alcohol such as glycerol, and preferably it is present in an amount of 5% to 50% w/w.
The biopolymer is preferably cross-linked to reduce the rate at which it is bioabsorbed. Preferred cross-linking agents include aldehydes such as glutaraldehyde, isocyanates and carbodiimides. The biopol~er film preferably also contains oil microdroplets di~persed therein in order further to reduce the rate of bioabsorption. The oil microdroplets may comprise any biocompatible and bioabsorbable oil, such as sunflower seed oil, sesame seed oil or fish oil. Preferably, the oil is present in an amount of 1 to 90% by weight, more preferably 10 to 75% by weight based on the weight of the biopol~mer film.
Preferably, the foraminous layer is actually coated with th~ bioabsorbable ilm or embedded therein, so that the interstices in the foraminous layer are substantially all filled by the material of the bioabsorbable film.
Particularly preferred composite materials comprising a reinforcing mesh embedded in a ollagen film are described 35 and claimed in EP-A-0194192. ~ -The thickness of the bioabsorbable film (except when it forms a composite with the foraminous layer) is preferably in the range 0.01-0.1 mm, and more preferably 0.0~5-0O03 mm.
;~1 33028 JJM--8a The layer of a bioabsorbable biopolymer sponge serves as a spacer between the coils of the reinforcing layer and the bioabsorbable film, defining a uniform and directional interstitial channel for cellular in~asion. Th~ porosity of the sponge and the chemstactic effect of the biopolymer combine to promote rapid invasion by fibroblasts, resulting in rapid tissue regeneration. Preferably~ the sponge comprises collagen, a glycosaminoglycan such as chondroitin sul~ate or hyaluronic acid or a mixture of such biopolymers.
Preferably, the porosity of the sponge is optimised for maximum cellular ingrowth, implying that at least 80% of the pores have an average pore diameter in the range 50 ~m - 250 ~m. Such relatively small pore sizes can be obtained, for example, by flash freezing of a collayen solution or suspension (resulting in very small ice crystals) followed by freeze drying, as described in WO90/00060. Alternatively or additionally, small pore siæes may be obtained by including a volatile anti-fre~eze such as ethanol or isopropanol in the gel, preferably in an amount o~ 5 -25% w/v. The presence of the anti-freeze results in the formation of smaller ice crystals on freezing, and hence smaller pores on freeze-drying. :~
Preferably, the sponge compri~3es chemotherapeutic agents in addition to the structural biopolym r. For example, the sponge may contain an antis~ptic or an antibiotic.
Preferably, the sponge contains a wound healing factor such as a growth factor, a cytokine, an alginate, a -~:~
glycosaminoglycan or an active derivative thereof. The bioabsorbable film may alternakively or additionally contain the same or a di~ferent therapeutic agent ox agents.
Preferably, the structural biopolymer of the sponge is cross~linked to reduce the rate of bio-absorption of the sponge. Preferably, the structural biopolymer is collagen and the cross-linking agent is one of those described above :
for the bioabsorbable filmD Also pre~erably, the biopolymer sponge contains preferably 1 to 90% by weight, more ::
preferably 10 to 75% by weight based on the weight of the :~
sponge, of oil microdroplets dispersed therein. The oil may ~:~
~. r ..~
33~28 be any biocompatible and biodegradable oil such as sunflower seed oil, sesame seed oil or fish oil. The presence of the oil microdroplets substantially reduces the rate of bioabsorption of the sponge. Furthermore, the oil microdropl~ts can be used as vehicles for hydrophobic, oleophilic therapeutic agents.
Preferably, the thickness of the sponge layer is in the range O.5 to 2.5 mm, more preferably 1.~ to 1.5 mm.
Preferably, the sponge layer has embedded therein one or more solid bioabsorbable rods extending longitudinally through part or all of the prosthesis. The rods may be sections of bioabsorbable stuture, prPferably collagen suture. The rods enhance the uniaxial directionality of the sponge layer and reduce thP rate at which the layer is absorbed in ViYo.
The present invention also provides the use of a bioabsorbable prosthesis as described above for the preparation of a surgical implant for the repair of a damaged tendon or ligament.
The present invention furthler pxovides a m~thod of making a bioabsorbable prosthesis for use in surgical repair of a damaged ligamenk or tendon, the method comprising the steps of: providing a laminate of a foraminous ~ayer of bioa~sorbable material and a bioabsorbable film; coating the laminate with a layer of an aqueous gel comprising a bioab~orbable polymer; rolling up the laminate and the gel layer into a ~piral roll, followed by drying the gel to form a layer of bioabsorbable sponge.
Preferably, the gel is dried to form the bioabsorbable sponge by freezing (preferably flash freezing), followed by fr~eze-drying by evaporation o~ water from the gel under reduced pressure. In alternative preferred methods, the gel is frozen or fl~sh~frozen and the frozen gel is then solvent dried by treatment with a hygroscopic solvent such as isopropyl alcohol~
The laminate comprises overlapping layers of the foraminous layer of bioabsorbable material and the bioabsorbable ~ilm. Preferably, the laminate comprises a 8 JJ~-88 high ten~ile strength foraminous mesh embedded in a ~ilm of a biopolym~r such as collagen, a~ described in EP-A-01941920 The compositions of the foraminous layer and the bioabsorbable film may be the same or different, and are preferably as defined above for preferred embodiments of the tendon or ligament prostheses of the present invention.
Preferably, the aqueous gel comprises acid-swollen collagen ~ibers, pre~erably at a concentration of 0.1%-5% w/v. In preferred methods, fibrous collagen is extracted from bovine corium or tendon and pre-washed to remove the majority of non-collagenous components as described in US-A-4614794 or US-A-4320201. The collagen is then suspended in clean deionised pyro~en-free water and homogenised to a fine fibrous suspension by passage through a homogenising system. Suitable homoqenising systems are described in US~
A-4320201.
Homogenization is continued until a desired degree of fiber division is achieved. Th:is results in a preferred fiber size in the range 0.01 to lOmm.
The homogenized collagen is acidi~ied to cause it to swell and form a gel suitable for freeze drying. The acidifying step may use an organic acid such as formic, acetic, propionic, lactic or malonic, or dilute inorganic acids such as hydrochloric acid. Preferably the homogenized colla~en suspension is acidified to pH 2 to 6, more preferably pH 300 to 4.5.
rhemotherapeutic agents, preferably as described above, may be dispersed in the aqueous g~l of the bioabsorbakle polymer, preferably in an amount of 0.1% to 50% w/w, based on the dry weight of the sponge. Also preferably, microdroplets of a bioabsorbable oil may be dispersed in the aqueous gel by emulsification at high shear ~collagen i5 an effective emulsifier). Preferably, the oil microdroplets are present in an amount of from 1% to 90% by weight, more preferably 10% to 75%, based on the dry weight of the sponge.
Preferably, the aqueous gel is dried by flash ~reezing at temperatures below -20C, followed by freeze drying, V ~
~''`':'''`''`'''."`"`",'"','.
~` ~13302~ JJM-88 preferably as described in W090/00060. The flash freezing results in smaller ice crystals, and thus provides smaller pores in the freeze-dried sponge. The pore size of the freeze-dried sponge may also be reduced by adding volatile anti-freeze substances such as ethanol or isopropanol to the aqueous gel before it is frozen, since these also will tend to reduce the size of the ice crystals ~ormed on freezing.
Preferably, the anti-freeze substance is added in an amount of 5% - 25% w/v, based on the volume of the gel.
Preferably, the freeze-drying step is carried out either by evaporating the water (a~d other volatile components) from the frozen gel under reduced pressure, or by solvent drying, which involves treating the frozen gel with a hygroscopic solvent, such as isopropyl alcohol, to extract th~ water from the frozen gel. Surprisingly, it has been found that the presence of volatile antifree~e agents such as ethanol or isopropyl alcohol in the ~rozen gel results in accelerated solvent dxying.
Preferably, the laminate with the layer of aqueous gel thereon is rolled up through 2 to 6 complete 360 revolutions prior to drying. The aqueous gel may be prechilled to 0-5~C prior to the rolling-up step in order to increase the rigidity of the gel ii~nd reduce the gel lost by squeezing out of the ends of the roll. Preferably, the rolling-up step is initiated by rolling up about a small diameter bobbin, e.g. a hypodermic needle, which is removed after the rolling up is complete. A small excess of the aqueous gel (up to 50~ excess~ may be used to compensate for gel lost in the rolling up step.
In other preferred methods according to the invention, one or more bioabsorbable rods is laid atop the laminate and extending substantially parallel to the axis about which the laminate is to be rolled up. The bioabsorbable rods are preferably sections of bioabsorbable suture, and preferably comprise collaqen. The rods help to ensure a uniform thickness for the spong~i layer in the dried prosthe~is.
In yet other priPferred embodiments, the method according to the present invention may further comprise the step of incubating the dried prosthesis in vitro with host cells such as host synovial cells or host fibrobla~t cells prior to implan~ation. The cells may even b8 injected into the body of the prosthesis. After a suitable time to achieve required cellular growth and proliferation in the prosthesis, the structure can be implanted in the body~
A specific embodiment of the tendon or ligament prosthesis of the invention will now be described ~urthar, by way of example with reference to the accompanying drawings, in which:
Fiqure 1 shows a transverse cross-section through a bioabsorbable prosthesis according to the present invention;
Fiqure 2 shows stages in the method of making the bioabsorbable prosthesis of Figure l; and Fi~ure 3 shows the bioabsorbable prosthesis of Figure 1 in use to repair a severed ligament.
Referring to Figure 1, the prosthesis 1 comprises a multilayered spiral roll consisting of a foraminous layer 2 of a synthetic bioabsorbable matexial, a bioabsorbable ~ilm 2 and a layer 3 of bioabsorbable sponge. The foraminous layer 2 is composed of a polylacticle/polyglycolide mesh sold under the Re~istered Trade Mark VICRYL. The bioabsorbable film 3 is composed of Type I colLagen fibers cross-linked with hexamethylene diisocyanate. The sponge layer 4 is also ~ormed from Type I collagen fibers cross-linked with hexamethylene diisocyanate.
In use, the prosthesis 1 is used to r~place part or all of a damaged ligament or tendon, as shown in Figure 3. The ends 5, 6 of the prosthesis are sutured to the undamaged ends 7, 8 of the ligament or tendon. Alternatively, one of the ends 5, 6 of the prosthesis may be attached directly onto a bone or into a socXet provided in a bone.
Figure 3 also shows schematically, by means of arrows, the dirPction of cellular migration and tissue ingrowth into the prosthesis 1 from the undamaged ends 7, 8 of the ligament or tendon. The cells, especially ~ibroblasts, migrate rapidly into the collagen sponge on account o~ its porosity and the chemotactic e~fect of collagen. Howevex, the cell migration is highly directional, since the collage~
sponge spiral layer 4 de~ines a longitudinal channel for cellular migration. Radial cellular migration is blocked by the bioabsorbable film layer 3. The VICRYL mesh layer 2 provides the necessary tensilP strength to the prosthesis while retaining sutureabilityO
Specific embodiments of method of manufacture of prosthesis according to the present invention will now be described further, by way of the following examples~
Example 1 A prosthesis for a ligament or tendon according to the present invention comprising separate layers of foraminous synthetic bioabsorbable polymer, bioabsorbable film, and bioabsorbable sponge is prepared as follows~
A. Preparation of collaqen slurry Fibrous collagen, obtained ~rom bovine corium and pre~
washed to remove the majority of non-collagenous components as described in US-A-4614794 or US-A-4320201 is suspended in clean deionised pyrogen-free water at 0.45% w/v concentration and homogenised to a fine ~ibrous suspension by passag~ through a homogenizing system similar to that described in US-A 4320201. Homlogenisation is continued until the collagen fiber size is in the range 0.1-l.Omm.
The suspension is acidified to pH 4.5 with acetic acid to swell the collagen.
B. Preparation of collaqen film layPr To the collagen gel pr~pared in Step A above glycerol is added as a plasticiser to a final weight of 0.5% w/w and the gel is then spread in a flat tray having a non-stick surface (e.g. PTFE) to a depth of about 2mm. The gel is then dried in warm air to leave a continuous, flexible ~ilm of collagen about 0.02mm thick.
C. Preparation of Laminate A piace of VICRYL~ polylactide/polyglycolide mesh of rectangular shape and dimensions approximately 20mm x 40mm x 0.lmm is placed in a flat-bottomed tray. A piece of the csllagen film prepared in Step B of identical size and shape is placed atop the VICRYL mesh.
~`,,',';,'1'','`'''".'''.'''''''"",..'''.''.',.''',"' ' '` ' ' ~ ~ 3~
D. _Preparation o~_the prosthesis A layer of the collagen gel pr~pared as in Step A but containing 0.5% w/v collagen solids and 10~ w/v isopropanol, and with a final pH of 4~5 is spread approximately 1~2mm deep across the top surface o~ the laminate prepared in Step C. The gel is quickly degassed and the laminate with the gel layer thereon is quickly but gently rolled up around one long edge of the rectangular piece. The resulting helical coil is flash ~rozen as described in W030/00060 followed by 1~ freeze drying to produce the prosthesis. In the resulting collagen sponge layer, at least 80% of the pores have average por~ sizes in the range 35 to 250~m, which is near-optimum for cellular invasion.
Example 2 A pro~thesis for the repair of a ligament ox ten~on according to the present invention, in which the foraminous synthetic bioabsorbable layer is embedded in the bioabsorbable film is prepared a~; ~ollows:
First, a collagen slurry is prepared as in Step A of Example 1, and a glycerol plasticiser is added to the slurry as in Step B. A layer of VICRYL mesh is placed in the bottom of a flak tray having a non-stick (e.g. PTFE~
surface, and the slurry is then poured over the VICRYL mesh to a depth of about 2mm, thereby immersing the VICRY~ mesh in the collagen slurry. The slurry is then dried in warm air to produce a composite layer of material comprising the VICRYL mesh embedded in a collagen film. The preparation of such composite layers is described in detail in EP-A
Olg4192 ~
A rectangular piece of the composite material of dimensions 20mm x 40mm i5 then used as khe laminate in Step D above to produce the desired prosthesis.
Example 3 A bioabsorbable prosthesis for the repair o~ a ligament or tendon having oil microdroplets dispersed in the bioaksorbable film and in the bioabsorbable sponge is prepared as follows:
A collagen slurry is prepared as in step A of Example 1. To this slurry is added ~esame seed oil at 50% (as ~ of the collagen content w/w), and the mixture is homogenized at high shear to emulsify the sesame seed oil. The collagen serves as an e~fective emulsifier. The remaining steps of the method are carried out as described above for Example 2.
The resulting prosthesis undergoes substantially slower bioabsorption and loss of tensile strength in vivo than the prosthesis produced in Example 2.
The above specific embodiment and example~ ar~ intended for the purpose o~ illustration only. Many other embodiments and methods according to the present invention as defined in the accompanying claims will be apparent to the skilled reader.
Claims (27)
1. A bioabsorbable ligament or tendon prosthesis in the form of a multilayered spiral roll comprising the following spiral layers:
a foraminous layer of a synthetic bioabsorbable material;
a bioabsorbable film, and a layer of a bioabsorbable sponge.
a foraminous layer of a synthetic bioabsorbable material;
a bioabsorbable film, and a layer of a bioabsorbable sponge.
2. A bioabsorbable prosthesis according to claim 1, wherein the diameter of the multilayered spiral roll is from 1.2 to 21 mm.
3. A bioabsorbable prosthesis according to claim 1 or 2, wherein the foraminous layer comprises a polymer or copolymer of lactic acid and/or glycolic acid, oxidised regenerated cellulose, polydioxanone (PDS), a copolymer of lactic acid and .epsilon.-caprolactam, polyhydroxybutyric acid or a copolymer of hydroxybutyric acid and hydroxyvaleric acid.
4. A bioabsorbable prosthesis according to claim 1, 2 or 3, wherein the foraminous layer is embedded in the bioabsorbable film or in the sponge layer.
5. A bioabsorbable prosthesis according to any preceding claim wherein the maximum thickness of the foraminous layer is in the range 0.02 to 0.3 mm.
6. A bioabsorbable prosthesis according to any preceding claim, wherein the bioabsorbable film comprises a biopolymer or a chemically cross-linked biopolymer derivative.
7. A bioabsorbable prosthesis according to claim 6, wherein the biopolymer comprises collagen or a glycosaminoglycan.
8. A bioabsorbable prosthesis according to any preceding claim, wherein oil microdroplets are dispersed in the bioabsorbable film.
9. A bioabsorbable prosthesis according to claim 8, wherein the oil is present in an amount of from 1% to 90% by weight, based on the weight of the bioabsorbable film.
10. A bioabsorbable prosthesis according to any preceding claim, wherein the thickness of the bioabsorbable film is in the range 0.01 to 0.1 mm.
11. A bioabsorbable prosthesis according to any preceding claim, wherein the bioabsorbable sponge comprises a biopolymer or a chemically cross-linked biopolymer derivative.
12. A bioabsorbable prosthesis according to claim 11, wherein the bioabsorbable sponge comprises collagen or a glycosaminoglycan.
13. A bioabsorbable prosthesis according to any preceding claim, further comprising microdroplets of a bioabsorbable oil dispersed in the bioabsorbable sponge.
14. A bioabsorbable pro thesis according to claim 13, wherein the bioabsorbable oil which is present in the amount of from 1% to 90% by weight, based on the weight of the bioabsorbable sponge.
15. A bioabsorbable prosthesis according to any preceding claim, wherein the thickness of the bioabsorbable sponge layer is in the range 0.5 to 2.5 mm.
16. A bioabsorbable prosthesis substantially as hereinbefore described with reference to the Figure 1.
17. Use of a bioabsorbable prosthesis according to any preceding claim for the preparation of a surgical implant for the repair of a damaged tendon or ligament.
18. A method of making a bioabsorbable prosthesis for use in surgical repair of a damaged ligament or tendon, the method comprising the steps of:
providing a laminate of a foraminous layer of bioabsorbable material and a bioabsorbable film; coating the laminate with a layer of an aqueous gel comprising a bioabsorbable polymer; rolling up the laminate and the gel layer into a spiral roll, followed by drying the gel to form a layer of bioabsorbable sponge.
providing a laminate of a foraminous layer of bioabsorbable material and a bioabsorbable film; coating the laminate with a layer of an aqueous gel comprising a bioabsorbable polymer; rolling up the laminate and the gel layer into a spiral roll, followed by drying the gel to form a layer of bioabsorbable sponge.
19. A method of making a bioabsorbable prosthesis according to claim 18, wherein the said step of rolling up comprises rolling up through between 2 and 6 complete 360°
revolutions.
revolutions.
20. A method of making a bioabsorbable prosthesis according to claim 18 or 19, wherein the step of providing a bioabsorbable film comprises the steps of:
providing a layer of an aqueous solution or suspension of bioabsorbable material, and drying the said layer.
providing a layer of an aqueous solution or suspension of bioabsorbable material, and drying the said layer.
21, A method of making a bioabsorbable prosthesis according to claim 20, wherein the said layer of an aqueous solution or suspension of the bioabsorbable material is coated onto the foraminous layer of a synthetic bioabsorbable material, or wherein the layer of a synthetic bioabsorbable material is immersed in the layer of an aqueous solution or suspension of bioabsorbable material.
22. A method of making a bioabsorbable prosthesis according to claim 20 or 21, further comprising the steps of emulsifying a bioabsorbable oil in said aqueous solution or suspension of bioabsorbable material.
23. A method of making a bioabsorbable prosthesis according to any of claims 18 to 22, wherein the aqueous gel comprises acid-swollen collagen.
24. A method of making a bioabsorbable prosthesis according to any of claims 18 to 23, further comprising the step of emulsifying a bioabsorbable oil in the aqueous gel.
25. A method of making a bioabsorbable prosthesis according to any of claims 18 to 24, wherein the step of drying the gel to form a bioabsorbable sponge comprises the steps of freezing the gel, followed by freeze-drying the gel by evaporation of water under reduced pressure.
26. A method of making a bioabsorbable prosthesis according to any of claims 18 to 25, wherein the step of drying the gel to form a bioabsorbable sponge comprises the steps of freezing the gel, followed by solvent drying the frozen gel.
27. A method of making a bioabsorbable prosthesis substantially as hereinbefore described with reference to the Examples.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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GB9320100.2 | 1993-09-29 | ||
GB9320100A GB2282328B (en) | 1993-09-29 | 1993-09-29 | Absorbable structures for ligament and tendon repair |
Publications (1)
Publication Number | Publication Date |
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CA2133028A1 true CA2133028A1 (en) | 1995-03-30 |
Family
ID=10742718
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CA002133028A Abandoned CA2133028A1 (en) | 1993-09-29 | 1994-09-27 | Absorbable structures for ligament and tendon repair |
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US (2) | US5514181A (en) |
EP (1) | EP0645149B1 (en) |
JP (1) | JP2963015B2 (en) |
KR (1) | KR950007805A (en) |
AT (1) | ATE180977T1 (en) |
AU (1) | AU673769B2 (en) |
CA (1) | CA2133028A1 (en) |
ES (1) | ES2134907T3 (en) |
GB (1) | GB2282328B (en) |
HK (1) | HK1002251A1 (en) |
IN (1) | IN182132B (en) |
MY (1) | MY114130A (en) |
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ZA (1) | ZA947263B (en) |
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- 1993-09-29 GB GB9320100A patent/GB2282328B/en not_active Expired - Fee Related
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1994
- 1994-09-19 ZA ZA947263A patent/ZA947263B/en unknown
- 1994-09-19 IN IN752CA1994 patent/IN182132B/en unknown
- 1994-09-27 CA CA002133028A patent/CA2133028A1/en not_active Abandoned
- 1994-09-28 ES ES94307076T patent/ES2134907T3/en not_active Expired - Lifetime
- 1994-09-28 EP EP94307076A patent/EP0645149B1/en not_active Expired - Lifetime
- 1994-09-28 MY MYPI94002577A patent/MY114130A/en unknown
- 1994-09-28 AT AT94307076T patent/ATE180977T1/en not_active IP Right Cessation
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- 1994-09-28 JP JP6257351A patent/JP2963015B2/en not_active Expired - Fee Related
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- 1994-10-14 TW TW083109525A patent/TW298565B/zh active
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1995
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1998
- 1998-02-16 HK HK98101185A patent/HK1002251A1/en not_active IP Right Cessation
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MY114130A (en) | 2002-08-30 |
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ZA947263B (en) | 1996-03-19 |
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IN182132B (en) | 1999-01-09 |
ES2134907T3 (en) | 1999-10-16 |
EP0645149B1 (en) | 1999-06-09 |
EP0645149A1 (en) | 1995-03-29 |
AU673769B2 (en) | 1996-11-21 |
GB2282328B (en) | 1997-10-08 |
AU7430694A (en) | 1995-04-13 |
KR950007805A (en) | 1995-04-15 |
GB9320100D0 (en) | 1993-11-17 |
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