WO2010026429A2

WO2010026429A2 - Sutureless connector

Info

Publication number: WO2010026429A2
Application number: PCT/GB2009/051125
Authority: WO
Inventors: Stephen Ralph Large; Samer Abdel-Malik Nashef
Original assignee: Papworth Hospital Nhs Foundation Trust
Priority date: 2008-09-05
Filing date: 2009-09-04
Publication date: 2010-03-11
Also published as: WO2010026429A3; EP2352443A2

Abstract

A sutureless connector device (1) for joining together two ends of natural and/or artificial vessels, said device comprising a hollow cylindrical member (2) with a single, central annular groove (3) characterised in that the central groove (3) has a friction-enhancing surface whereby, in use, the device is inserted into the lumen of the vessels to be joined.

Description

SUTURELESS CONNECTOR

The invention relates to a sutureless connector device for joining together two portions of natural and/or artificial hollow tubular biological structures. The invention also relates to a method of joining together two portions of said structures and to kits comprising said connector device.

Anastomoses are surgical procedures where two separate ends of a hollow tubular organ are joined together. They are most commonly used in the vasculature where part of an artery that is damaged through aneurysm or sclerotic disease is removed and replaced with a graft vessel. The most commonly used method is a direct suture to achieve the join. A range of devices has been described to allow the joining together of a native vessel to either a natural or artificial graft vessel, but all of these have certain disadvantages. The key difficulties faced in such procedures are damaging the already weakened vessel, bleeding from the wall of the vessel and the amount of time required to complete the procedure.

Previously disclosed devices have the drawback of requiring penetration of the wall of the vessel to be joined. This can take the form either of suture holes where the tissue is stitched to a connector device or of holes caused by securing the vessel wall to spike-like protrusions on the connector device. The inevitable consequence of such penetration of the vessel wall is bleeding which results in undesirable loss of blood and complicates the grafting procedure, both of which increase the risk to the patient. The suturing process is also technically demanding and time- consuming, resulting in a lengthy procedure which adversely affects the health of a vessel that is already diseased. Moreover, the longer a surgical procedure is, the greater the overall risk to the patient, so reducing the duration is generally desirable. Another disadvantage of existing devices is that many require a significant length of healthy vessel in order to attach the connector device in preparation for joining to the vessel graft. Particularly in the case of diseased vessels, there is often little viable tissue available for the grafting procedure and limiting the requirement for such tissue would be a clear advantage. One example of a known device is disclosed in US 2002/0170535.

According to one aspect of the invention there is provided a sutureless connector device for joining together two ends of natural and/or artificial vessels, said device comprising a hollow cylindrical member with a single, central annular groove characterised in that the central groove has a friction-enhancing surface.

Generally, in use, the device is inserted into the lumen of the vessels to be joined. Such an arrangement is convenient as it can simplify procedures in which the device is used as expanded upon below.

Embodiments of the invention are designed to simplify anastomoses procedures such as grafting an artificial or biological tube graft onto a native vessel. The presence of a single groove allows the device to be short in length thus requiring only a short portion of healthy vessel for a successful graft. The friction-enhancing surface of the groove allows the device to be more securely located inside the lumen of the first vessel or graft. As a result, it will be prevented from sliding further inside the lumen while the second vessel is brought into position over the edge of the first. The single groove provides the advantage of allowing both vessels to be secured to the device by the application of a single securing means . The connector also avoids the requirement for suturing of the vessels . On the one hand, this reduces the risk of bleeding and minimises damage to the vessel while on the other hand, it allows the procedure to be completed quickly and reduces the overall risk to the patient. As a result, the process of replacing damaged vessels is faster and more straightforward.

A further advantage of the device is that is consists of a single unit rather than multiple units which must be fitted together in order to secure the vessels to each other. Embodiments of the present invention therefore benefits from greater simplicity, ensuring that a reliable anastomosis can be completed quickly, helping to minimise the risk to the patient. In addition, the device should require the simple insertion of one vessel into another. Other manipulations such as everting the wall of the vessel by folding it back onto itself are avoided thus reducing the physical strain placed on the vessel and maximising its structural integrity. Moreover, the device does not require a long length of healthy vessel to allow the successful joining of two vessels as would be required by the above- mentioned procedure.

In one embodiment, the central annular groove is flanked by two terminal flanges . These serve to assist in effectively securing the device in position within the lumen of the tissue preventing unwanted movement.

References to "friction-enhancing surface" include references to a surface which is able to resist the natural forces causing movement of the device relative to the inner wall of the tissue when inserted into a natural or artificial vessel. The friction-enhancing surfaces are generally arranged not to penetrate into the wall of the vessel into which the connector device is inserted. Such penetration may lead to the vessel being damaged, possibly weakening it and leading to undesirable bleeding from the vessel wall. Thus, the friction-enhancing surface of the present connector device are generally arranged not to penetrate into the wall of the vessel and therefore does not cause any gross physiological damage to the vessel.

In one embodiment, the friction-enhancing surface comprises one or more ribs or grooves, a roughened surface, a non-slip polymer coating, a quartz coating, a silica glass coating, a grit coating or a powder coating such as a metal powder coating, a fabric covering or any combination thereof.

In a further embodiment, the friction-enhancing surface comprises a metal powder coating, a silica glass coating or a fabric covering.

In a yet further embodiment, the friction-enhancing surface comprises a fabric covering.

In another embodiment, the sutureless connector comprises a fabric covering over at least a portion of and may be over substantially all of its surface. This feature has the additional advantage of potentially increasing the bio-compatibility of the device. Some embodiments, may cover the connector substantially only on an inner or an outer surface.

It will be appreciated by the skilled person that a suitable material for covering the device may be a woven material that is used to make artificial vascular grafts. The material used to construct such grafts is chosen to create an environment that is as physiological compatible as possible which helps to maximise the graft's ability to allow unimpeded blood flow. Covering the device in such a material should therefore help to ensure that the parts of the device in contact with the circulation would provide an equally favourable environment for blood flow. The skilled person will appreciate that it is desirable for any material in direct contact with the circulation to minimises the risk of clot formation. Thus, coating the inside of the connector, may be with a fabric, may help to provide such advantages.

Possible materials that may be used as any of the fabrics discussed herein are polyester which may be in the form of woven Dacron, ePTFE, low density polyethylene or polydimethylsiloxane. These may or may not be coated or impregnated with collagen to improve bio-compatibility. The material covering the device can also be coated or impregnated with therapeutic agents that are suitable for local delivery within the blood vessel. Possible examples of such agents are anti-biotics for minimising the risk of infection or anti-coagulants for minimising the risk of clot- formation.

According to a second aspect of the invention there is provided a sutureless connector device for joining together two ends of natural and/or artificial vessels, said device comprising a hollow cylindrical member with a single, central annular groove characterised in that one edge of the member comprises a plurality of radially projecting protrusions.

Generally, the radially projecting protrusions are non-penetrating into the wall of the vessel into which the connector is, in use, inserted.

Embodiments of the invention are designed to simplify anastomoses procedures such as grafting an artificial vessel onto a native vessel. The presence of a single groove allows the device to be short in length thus requiring only a short portion of healthy vessel for a successful graft.

Bending the radially projecting protrusions towards the wall of the vessel, serves to clamp the device into position at the edge of the first vessel, preventing it from sliding any further into the lumen. The second vessel can then be brought into position over the first and both vessels secured to the device. The single groove provides the advantage of allowing both vessels to be secured to the device by the application of a single securing means. The connector also avoids the requirement for suturing of the vessels. On the one hand, this reduces the risk of bleeding and minimises damage to the vessel while on the other hand, it allows the procedure to be completed quickly and reduces the overall risk to the patient. As a result, the process of replacing damaged vessels is faster and more straightforward.

References to 'radially projecting protrusion' include references to features which extend outwardly from the cylinder beyond the surface of the cylinder member.

In one embodiment, the protrusions are constructed of a deformable material. The presence of the deformable material provides the advantage of allowing the protrusions to be subjected to plastic deformation towards the wall of the vessel. The protrusions are designed to be non-penetrating and are not intended to pierce through the wall of the vessel but rather to grip the edge of the vessel. Damage to the structure of the vessel and any resulting bleeding or weakening of the wall will therefore be minimised.

In a further embodiment, the deformable material comprises metal or plastic.

In another embodiment, the connector device comprises between 2 and 6 protrusions . It will be appreciated that the number of protrusions will depend on the size of the vessels to be joined. For example, the larger the vessel, the greater the number of protrusions required.

In yet another embodiment, the protrusions are equally spaced around the circumference of the device. This embodiment ensures that the device is secured as well as possible to the vessel, being clamped into position at regular intervals around its circumference. It also ensures that the protrusions apply pressure in a largely uniform manner around the wall of the tissue.

In a further embodiment, the protrusions have a length equating to between 10 and 50 % of the length of the cylindrical member. This embodiment ensures that they are long enough to securely hold the device in position. For example a connector that is 10mm in length will have protrusions that are roughly 3mm long. This length is sufficient to effectively hold the device in place and prevent it being moved when the second vessel is placed over the first.

It will be appreciated that both aspects of the invention hereinbefore described can be combined in one connector device. The result would be a connector device for joining together two ends of natural or artificial vessels comprising a single, central annular groove having a friction- enhancing surface, additionally comprising a plurality of radially projecting protrusions on one edge of the device.

In one embodiment, the sutureless connector device additionally comprises a coating composition comprising a therapeutic agent. This embodiment provides the advantage of providing localised delivery of therapeutic agents to the lumen of a natural vessel. It will be appreciated that the sutureless connector device may be coated with the therapeutic agent or the therapeutic agent may be incorporated within the sutureless connector device.

References herein to "therapeutic agent" include references to drugs, genetic materials, and biological materials and can be used interchangeably with "biologically active material" . References herein to "genetic materials" include DNA or RNA, including, without limitation, DNA/RNA encoding a useful protein stated below, intended to be inserted into a human body including viral vectors and non-viral vectors.

References herein to "biological materials" include cells, yeasts, bacteria, proteins, peptides, cytokines and hormones . Examples of peptides and proteins include: vascular endothelial growth factor (VEGF) , transforming growth factor (TGF) , fibroblast growth factor (FGF) , epidermal growth factor (EGF) , cartilage growth factor (CGF) , nerve growth factor (NGF) , keratinocyte growth factor (KGF) , skeletal growth factor (SGF) , osteoblast-derived growth factor (BDGF) , hepatocyte growth factor (HGF) , insulin-like growth factor (IGF) , cytokine growth factors (CGF) , platelet-derived growth factor (PDGF) , hypoxia inducible factor-1 (HIF-I) , stem cell derived factor (SDF) , stem cell factor (SCF) , endothelial cell growth supplement (ECGS) , granulocyte macrophage colony stimulating factor (GM-CSF) , growth differentiation factor (GDF) , integrin modulating factor (IMF) , calmodulin (CaM) , thymidine kinase (TK) , tumour necrosis factor (TNF) , growth hormone (GH) , bone morphogenic protein (BMP) (e.g. BMP-2, BMP-3 , BMP-4, BMP-5 , BMP- 6 (Vgr-1) , BMP-7 (PO-I) , BMP-8, BMP-9, BMP-IO, BMP-I l , BMP-12, BMP-14, BMP-15, BMP-16, etc.) , matrix metalloproteinase (MMP) , tissue inhibitor of matrix metalloproteinase (TIMP) , cytokines, interleukin (e.g. , IL-I, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL- 10, IL-I l , IL- 12, IL- 15, etc.) , lymphokines, interferon, integrin, collagen (all types) , elastin, fibrillins, fibronectin, vitronectin, laminin, glycosaminoglycans, proteoglycans, transferrin, cytotactin, cell binding domains (e.g. RGD) , and tenascin. Cells can be of human origin (autologous or allogeneic) or from an animal source (xenogeneic) , genetically engineered, if desired, to deliver proteins of interest at the transplant site. The delivery media can be formulated as needed to maintain cell function and viability. Cells include progenitor cells (e.g. endothelial progenitor cells) , stem cells (e.g. mesenchymal, hematopoietic, neuronal) , stromal cells, parenchymal cells, undifferentiated cells, fibroblasts, macrophage, and satellite cells. In one embodiment, the therapeutic agent is selected from: anti- thrombogenic agents such as heparin, heparin derivatives, urokinase, and PPack (dextrophenylalanine proline arginine chloromethylketone) ; antiproliferative agents such as enoxaprin, angiopeptin, or monoclonal antibodies capable of blocking smooth muscle cell proliferation, hirudin, acetylsalicylic acid, tacrolimus, everolimus, pimecrolimus, sirolimus, zotarolimus, amlodipine and doxazosin; anti-inflammatory agents such as glucocorticoids, betamethasone, dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, rosiglitazone, mycophenolic acid and mesalamine; anti-neoplastic/anti-proliferative/anti- miotic agents such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, methotrexate, azathioprine, adriamycin and mutamycin; endostatin, angiostatin and thymidine kinase inhibitors, cladribine, taxol and its analogs or derivatives, paclitaxel as well as its derivatives, analogs or paclitaxel bound to proteins, e.g. Abraxane^1M; anesthetic agents such as lidocaine, bupivacaine, and ropivacaine; anticoagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide- containing compound, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, aspirin, dipyridamole, protamine, hirudin, prostaglandin inhibitors, platelet inhibitors, antiplatelet agents such as trapidil or liprostin and tick antiplatelet peptides; DNA demethylating drugs such as 5-azacytidine, which is also categorized as a RNA or DNA metabolite that inhibit cell growth and induce apoptosis in certain cancer cells; vascular cell growth promoters such as growth factors, vascular endothelial growth factors (VEGF, all types including VEGF-2) , growth factor receptors, transcriptional activators, and translational promoters; vascular cell growth inhibitors such as antiproliferative agents, growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; cholesterol-lowering agents, vasodilating agents, and agents which interfere with endogenous vasoactive mechanisms; anti-oxidants, such as probucol; antibiotic agents, such as penicillin, cefoxitin, oxacillin, tobranycin, rapamycin (sirolimus) ; angiogenic substances, such as acidic and basic fibroblast growth factors, estrogen including estradiol (E2) , estriol (E3) and 17-beta estradiol; drugs for heart failure, such as digoxin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors including captopril and enalopril, statins and related compounds; and macrolides such as sirolimus or everolimus.

In an alternative embodiment, the therapeutic agent is selected from: nitroglycerin, nitrous oxides, nitric oxides, antibiotics, aspirins, digitalis, estrogen, estradiol and glycosides.

In an alternative embodiment, the therapeutic agent is an antiproliferative drug such as a steroid, vitamin, and a restenosis-inhibiting agent. In one embodiment, the restenosis-inhibiting agent includes microtubule stabilizing agents such as Taxol^®, paclitaxel (i.e. , paclitaxel, paclitaxel analogs, or paclitaxel derivatives, and mixtures thereof) . In a further embodiment, the therapeutic agent is selected from 2' -succinyl-taxol, 2'- succinyl-taxol triethanolamine, 2 '-glutaryl-taxol, 2 '-glutaryl-taxol triethanolamine salt, 2'-O-ester with N-(dimethylaminoethyl) glutamine, and 2 ' -O-ester with N-(dimethylaminoethyl) glutamide hydrochloride salt. In an alternative embodiment, the therapeutic agent is selected from: tacrolimus; halofuginone; inhibitors of HSP90 heat shock proteins such as geldanamycin; microtubule stabilizing agents such as epothilone D; phosphodiesterase inhibitors such as cliostazole; Barkct inhibitors; phospholamban inhibitors; and Serca 2 gene/proteins.

In an alternative embodiment, the therapeutic agent is selected from an antibiotic such as erythromycin, amphotericin, rapamycin, adriamycin, etc. In one embodiment, the therapeutic agent is capable of altering the cellular metabolism or inhibiting a cell activity, such as protein synthesis , DNA synthesis, spindle fibre formation, cellular proliferation, cell migration, microtubule formation, microfilament formation, extracellular matrix synthesis, extracellular matrix secretion, or increase in cell volume. In another embodiment, the therapeutic agent is capable of inhibiting cell proliferation and/or migration.

In one embodiment, the therapeutic agent comprises at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 97%, at least 99% or more by weight of the coating composition. In a further embodiment, the therapeutic agent is about 0.01% to about 50 % by weight of the coating composition.

In one embodiment, the coating composition additionally comprises a polymer. It is possible, however, to deploy a drug without a carrier polymer, so that the coating composition is 100% therapeutic agent.

It will be appreciated that the polymers useful for forming the coating compositions of the present invention should be ones that are biocompatible, particularly during insertion or implantation of the device into the body and avoids irritation to body tissue. Examples of such polymers include, but are not limited to, polyurethanes, polyisobutylene and its copolymers, silicones, and polyesters. Other suitable polymers include polyolefins, polyisobutylene, ethylene-alphaolefin copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers such as polyvinyl chloride, polyvinyl ethers such as polyvinyl methyl ether, polyvinylidene halides such as polyvinylidene fluoride and polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics such as polystyrene, polyvinyl esters such as polyvinyl acetate; copolymers of vinyl monomers, copolymers of vinyl monomers and olefins such as ethylene-methyl methacrylate copolymers, acrylonitrile- styrene copolymers, ABS resins, ethylene-vinyl acetate copolymers, polyamides such as Nylon 66 and polycaprolactone, alkyd resins, polycarbonates, polyoxyethylenes, polyimides, polyethers, epoxy resins, polyurethanes, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, collagens, chitins, polylactic acid, polyglycolic acid, and polylactic acid- polyethylene oxide copolymers.

In one embodiment the polymer comprises a hydrophobic polymer. Examples of suitable hydrophobic polymers or monomers include, but are not limited to, polyolefins, such as polyethylene, polypropylene, poly(l- butene) , poly(2-butene) , poly(l-pentene) , poly(2-pentene) , poly(3-methyl- 1-pentene) , poly(4-methyl-l-pentene) , poly(isoprene) , poly(4-methyl-l- pentene) , ethylene-propylene copolymers, ethylene-propylene-hexadiene copolymers, ethylene-vinyl acetate copolymers, blends of two or more polyolefins and random and block copolymers prepared from two or more different unsaturated monomers; styrene polymers, such as poly(styrene) , styrene-isobutylene copolymers, poly (2- methylstyrene) , styrene- acrylonitrile copolymers having less than about 20 mole-percent acrylonitrile, and styrene-2,2,3,3,-tetrafluoropropyl methacrylate copolymers; halogenated hydrocarbon polymers, such as poly(chlorotrifluoroethylene) , chlorotrifluoroethylene- tetrafluoroethylene copolymers, poly(hexafluoropropylene) , poly (tetrafluoroethylene) , tetrafluoroethylene, tetrafluoroethylene-ethylene copolymers, poly(trifluoroethylene) , poly (vinyl fluoride) , and poly(vinylidene fluoride) ; vinyl polymers, such as poly(vinyl butyrate) , poly( vinyl decanoate) , poly(vinyl dodecanoate) , poly(vinyl hexadecanoate) , poly(vinyl hexanoate) , poly(vinyl propionate) , poly (vinyl octanoate) , poly(heptafluoroisopropoxyethylene) , poly(heptafluoroisopropoxypropylene) , and poly (methacrylonitrile) ; acrylic polymers, such as poly(n-butyl acetate) , poly(ethyl acrylate) , poly(l-chlorodifluoromethyl)tetrafluoroethyl acrylate, poly di(chlorofluoromethyl)fluorornethyl acrylate, poly(l , l- dihydroheptafluorobutyl acrylate) , poly(l , l-dihydropentafluoroisopropyl acrylate) , poly(l , l-dihydropentadecafluorooctyl acrylate) , poly(heptafluoroisopropyl acrylate) , poly 5-(heptafluoroisoρropoxy)pentyl acrylate, poly ll-(heptafluoroisopropoxy)undecyl acrylate, poly 2- (heptafluoropropoxy) ethyl acrylate, and poly(nonafluoroisobutyl acrylate) ; methacrylic polymers, such as poly(benzyl methacrylate) , poly(n-butyl methacrylate) , poly(isobutyl methacrylate) , poly(t-butyl methacrylate) , poly(t-butylaminoethyl methacrylate) , poly(dodecyl methacrylate) , poly (ethyl methacrylate) , poly(2-ethylhexyl methacrylate) , poly(n-hexyl methacrylate) , poly (phenyl methacrylate) , poly(n-propyl methacrylate) , poly(octadecyl methacrylate) , poly (1 ,1- dihydropentadecafluorooctyl methacrylate) , poly(heρtafluoroisopropyl methacrylate) , poly(heptadecafluorooctyl methacrylate) , poly(l- hydrotetrafluoroethyl methacrylate) , poly(l,l-dihydrotetrafluoropropyl methacrylate) , poly(l-hydrohexafluoroisopropyl methacrylate) , and poly(t- nonafluorobutyl methacrylate) ; polyesters, such as poly (ethylene terephthalate) and poly(butylene terephthalate) ; condensation type polymers such as polyurethanes and siloxane-urethane copolymers; polyorganosiloxanes, i.e. polymers characterized by repeating siloxane groups, represented by Ra SiO 4-a/2, where R is a monovalent substituted or unsubstituted hydrocarbon radical and the value of a is 1 or 2; and naturally occurring hydrophobic polymers such as rubber.

In an alternative embodiment, the polymer comprises a hydrophilic polymer. Examples of suitable hydrophilic polymers or monomers include, but are not limited to; (meth) acrylic acid, or alkaline metal or ammonium salts thereof; (meth)acrylamide; methylenebisacrylamide; (meth)acrylonitrile; polylactic acid; polyglycolic acid; polylactic-glycolic acid; those polymers to which unsaturated dibasic, such as maleic acid and fumaric acid or half esters of these unsaturated dibasic acids, or alkaline metal or ammonium salts of these dibasic acids or half esters, is added; those polymers to which unsaturated sulfonic, such as 2- acrylamido-2-methylpropanesulfonic, 2-(meth)acryloylethanesulfonic acid, or alkaline metal or ammonium salts thereof, is added; and 2- hydroxyethyl (meth)acrylate and 2- hydroxypropyl (meth)acrylate.

In one embodiment, the hydrophilic polymer is polyvinyl alcohol. Polyvinyl alcohol may contain a plurality of hydrophilic groups such as hydroxyl, amido, carboxyl, amino, ammonium or sulfonyl (-SO,) . Hydrophilic polymers also include, but are not limited to, starch, polysaccharides and related cellulosic polymers; polyalkylene glycols and oxides such as the polyethylene oxides; polymerized ethylenically unsaturated carboxylic acids such as acrylic, methacrylic and maleic acids and partial esters derived from these acids and polyhydric alcohols such as the alkylene glycols; homopolymers and copolymers derived from acrylamide; and homopolymers and copolymers of vinylpyrrolidone. In an alternative embodiment, the polymer is selected from thermoplastic elastomers in general, polyolefins, polyisobutylene, ethylene-alphaolefin copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers such as polyvinyl chloride, polyvinyl ethers such as polyvinyl methyl ether, polyvinylidene halides such as polyvinylidene fluoride and polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics such as polystyrene, polyvinyl esters such as polyvinyl acetate, copolymers of vinyl monomers, copolymers of vinyl monomers and olefins such as ethylene-methyl methacrylate copolymers, acrylonitrile- styrene copolymers, ABS (acrylonitrile-butadiene-styrene) resins, ethylene-vinyl acetate copolymers, polyamides such as Nylon 66 and polycaprolactone, alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, polyether block amides, epoxy resins, rayon- triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, collagens, chitins, polylactic acid, polyglycolic acid, polylactic acid-polyethylene oxide copolymers, EPDM (ethylene-propylene-diene) rubbers, fluoropolymers, fluorosilicones, polyethylene glycol, polysaccharides, phospholipids, and combinations thereof. In a further embodiment the polymer is selected from SIBS triblock polymers comprising styrene and isobutylene, or PVDF.

The coating compositions comprising the therapeutic agent and/or polymer can be formed using a solvent. Solvents that may be used to prepare coating compositions include ones which can dissolve or suspend the polymer and/or therapeutic agent in solution. Examples of suitable solvents include, but are not limited to, tetrahydrofuran, methylethylketone, chloroform, toluene, acetone, isooctane, 1 , 1 , 1 , trichloroethane, dichloromethane, isopropanol, IPA, and mixtures thereof.

The coating compositions can be applied to the sutureless connector device by any method. Examples of suitable methods include, but are not limited to, spraying such as by conventional nozzle or ultrasonic nozzle, dipping, rolling, electrostatic deposition, and a batch process such as air suspension, pan coating or ultrasonic mist spraying. Also, more than one coating method can be used.

According to a further aspect of the invention there is provided a use of a device as hereinbefore defined for joining together two ends of natural and/or artificial vessels.

It will be apparent to a person skilled in the art that the connector device would find use in a wide range of surgical procedures for joining vessels. In one embodiment, the natural vessels comprise blood vessels such as arteries or veins, lymphatic vessels, ducts or other tubular muscular organs within the body of a human or animal. It will be appreciated that this list is not intended to be exhaustive.

According to a further aspect of the invention, there is provided a method for joining together two ends of a natural and/or artificial vessel comprising the following steps: a) insertion of a sutureless connector device comprising a hollow cylindrical member with a single central annular groove into a first vessel; b) insertion of an end of the first vessel containing the device into a second vessel; and c) securing both vessels to the device by application of a securing means to the exterior of the second vessel at the position of the central annular groove.

This aspect provides the advantage of requiring only a single securing means, which significantly reduces the duration of the procedure. According to a yet further aspect of the invention, a method is provided for joining together two ends of a natural and/or artificial vessel comprising the following steps: a) insertion of a sutureless connector device comprising a hollow cylindrical member with a single central annular groove into a first vessel; b) securing the first vessel to the device by application of a first securing means to the exterior of the vessel at the position of the central annular groove; c) insertion of an end of the first vessel containing the device into a second vessel; and d) securing a second vessel to the device by application of a second securing means to the exterior of the second vessel at the position of the central annular groove.

In one embodiment the securing means comprise suture material, tape, plastic ties such as cable ties or other tightening member.

In another embodiment, one of the vessels consists of a natural vessel and the other consists of an artificial vessel.

It will also be appreciated by the skilled person that whatever the embodiment of the connector device or the securing means, they will each be constructed of a biocompatible material, given their use within the body of a human or animal.

In a further aspect of the invention, there is provided a kit for performing anastomoses comprising a sutureless connector device as hereinbefore defined and securing means as hereinbefore defined. Embodiments of the invention will now be described, by way of example only, with reference to the accompanying figures, in which:

Figures 1 - 4 show perspective and side views of the sutureless connector aspect of the invention comprising a friction-enhancing surface;

Figures 5 - 8 show perspective and side views of the sutureless connector aspect of the invention comprising radially projecting protrusions;

Figure 9 shows a side elevation of an embodiment of the sutureless connector device comprising a fabric covering;

Figure 10 shows, in cross-section, an embodiment of the sutureless connector device comprising a fabric covering;

Figure 11 demonstrates the use of the sutureless connector device in conjunction with a single securing means in perspective view;

Figure 12 demonstrates the use of the sutureless connector device in conjunction with a single securing means in cross-section;

Figure 13 demonstrates the use of the sutureless connector device in conjunction with two securing means in perspective view;

Figure 14 demonstrates the use of the sutureless connector device in conjunction with two securing means in cross-section; Figure 15 shows a cut-away perspective view of a sutureless connector device joining a natural vessel to and artificial graft vessel; and

Figure 16 shows an example of the use of sutureless connector devices in situ in an artificial aortic graft vessel.

Referring first to the upper panel in Figure 1 , a sutureless connector device shown generally as 1 , comprises a hollow cylindrical member 2 and a single, central annular groove having a friction-enhancing surface 3, flanked by two terminal flanges 4. The lower panel of Figure 1 shows the same connector device in side view, demonstrating the central annular groove which in this embodiment is trapezoid in cross-section 5.

Alternative embodiments of the device are shown in Figures 2 - 4 which share the same essential characteristics of the device in Figure 1. The embodiments of Figures 2 - 4 are distinguished from the embodiment in Figure 1 by a central groove having a different shape when seen in cross- section. Figure 2 shows a device with a groove that is semi-circular in cross-section 6, Figure 3 shows a device with a groove that is rectangular in cross-section 7, and Figure 4 shows a device with a groove that is triangular in cross-section 8.

Figure 5 shows a second aspect of the sutureless connector device shown generally as 101 in the upper panel, comprising a hollow cylindrical member 102 and a single central annular groove 103 flanked by two terminal flanges 104. One side of the device comprises four protrusions made of a deformable material 105 (one of which is not visible) . The lower panel of Figure 5 shows the same connector device in side view, demonstrating the central annular groove which in this embodiment is trapezoid in cross-section 106. It will be seen that the four protrusions 105 have a blunt end such that they do not penetrate a vessel in which the connector is used. In the embodiment shown, the end regions of the protrusions 105 have a shape but other shapes may be equally possible. For example, the end regions of the protrusions 105 may be semi-circular, curved or otherwise rounded.

Alternative embodiments of the device are shown in Figures 6 - 8 which share the same essential characteristics of the device in Figure 5. The embodiments of Figures 6 - 8 are distinguished from the embodiment in Figure 5 by a central groove having a different shape when seen in cross- section. Figure 6 shows a device with a groove that is semi-circular in cross-section 107, Figure 7 shows a device with a groove that is rectangular in cross-section 108, and Figure 8 shows a device with a groove that is triangular in cross-section 109.

Representations of an embodiment of the device that comprises a fabric covering are shown in Figures 9 and 10. A side view of a device comprising a fabric covering is shown generally as 110 in Figure 9. The embodiment shown is equivalent to the device of Figure 1 but which has been wrapped in a fabric cover 111. A cross-section of the same embodiment is shown in Figure 10. In this view, the trapezoid central annular groove 112 which this embodiment shares with the device of Figure 1 can clearly been seen. It is also evident from this cross-sectional view that in this embodiment the fabric 113 covers every external surface of the device 114. This need not be the case in all embodiments.

Figure 11 demonstrates a means of connecting an artificial graft vessel 11 to a natural vessel 10 according to one aspect of the invention. The perspective view shows all components required for an anastomosis procedure prior to joining the two vessels 10, 11 together: the sutureless connector device 1, the natural vessel 10, the artificial graft vessel 11 and the securing means which in this example is shown as a cable tie fastener 12, although it will be appreciated that other securing means could be envisaged. In use, the connector device 1 is inserted a short distance into the end of the natural vessel 10 where it is held in position by the friction-enhancing surface of the central groove 3. The end of the vessel containing the connector device 1 is then inserted a short distance into one end of the artificial graft vessel 11 and both vessels 10, 11 are secured to the connector device 1 by application of a cable tie fastener 12 to the exterior of the artificial graft 11 at the position of the central groove 3. The fastener 12 firmly binds both vessels 10, 11 to the connector 1.

Figure 12 demonstrates a cross sectional view of two vessels 10, 11 joined together using the device 1 as shown in Figure 10. The connector device 1 is positioned within the lumen of the natural vessel 10, which in turn is within the lumen of the artificial vessel 11. Binding the two vessels to the device 1 is a single cable tie fastener 12 on the exterior wall of the artificial graft vessel 11.

Figure 13 is analogous to Figure 11 differing only in that two cable tie fasteners 12, 13 are used to secure the vessels 10, 11 rather than a single one. All components highlighted for Figure 11 are also present in Figure 10 as well as the additional second fastener 13. Similarly to the aforementioned method, the connector device 1 is inserted a short distance into the natural vessel 10. However in this embodiment, the natural vessel 10 is itself secured to the device 1 by application of a first cable tie fastener 13 to its exterior wall at the position of the central groove 3. The end of the natural vessel 10 secured to the connector device 1 is then inserted a short distance into the artificial graft vessel 11 and the artificial vessel 11 in turn is secured to the connector device 1 by application of a second cable tie fastener 12 to its exterior wall, also at the position of the central groove 3.

This arrangement is once again demonstrated in a cross-sectional view of the two vessels joined together in Figure 14. The connector device 1 is located within the lumen of the natural vessel 10 which is itself within the lumen of the artificial graft vessel 11. In this embodiment however, the natural vessel 10 is secured to the device 1 by a first fastener 13 and the artificial graft vessel 11 is also secured to the device 1 by a second fastener 12. Both fasteners 12, 13 are located in the position of the central groove 3 of the device 1.

Figure 15 shows a perspective cut-away view of a natural vessel joined to an artificial graft vessel 11 using the connector device 1. It can be seen that in this embodiment, both the natural 10 and the artificial vessel 11 are secured to the connector device 1 with separate cable tie fasteners 12 and 13.

Figure 16 shows an example of an aortic graft where sutureless connector devices (not shown) can be used. The artificial graft vessel replaces the ascending aorta 20 and the aortic arch 21 as well as the initial segments of the brachiocephalic artery 22, the left common carotid artery 23 and the left subclavian artery 24. In each case, a cable tie fastener 12 can be seen joining the open ends of the graft vessel assembly and a remaining, healthy portion of the corresponding natural vessel to a connector device

(obscured by vessels) .

Claims

1. A sutureless connector device for joining together two ends of natural and/or artificial vessels, said device comprising a hollow cylindrical member with a single, central annular groove characterised in that the central groove has a friction-enhancing surface whereby, in use, the device is inserted into the lumen of the vessels to be joined.

2. A device according to claim 1 in which the friction-enhancing surface is arranged not to penetrate the wall of a vessel into which it is inserted.

3. A device according to claim 1 or 2 which comprises a single component.

4. A device as defined in any preceding claim wherein the central annular groove is flanked by two terminal flanges.

5. A device as defined in any preceding claim wherein the friction- enhancing surface comprises one or more ribs or grooves, a roughened surface, a non-slip polymer coating, a quartz coating, a silica glass coating, a grit coating or a powder coating such as a metal powder coating, a fabric covering or any combination thereof.

6. A device as defined in claim 5 wherein the friction-enhancing surface comprises a metal powder coating, a silica glass coating or a fabric covering.

7. A sutureless connector device arranged to join together two ends of natural and/or artificial vessels, said device comprising a hollow cylindrical member with a single, central annular groove characterised in that one edge of the member comprises a plurality of radially projecting, non-penetrating protrusions.

8. A device as defined in claims 7 wherein the protrusions are constructed of a deformable material.

9. A device as defined in claim 8 wherein the deformable material comprises metal or plastic.

10. A device as defined in claims 7 to 9 comprising between 2 and 6 protrusions.

11. A device as defined in claims 7 to 10 wherein the protrusions are equally spaced around the circumference of the device.

12. A device as defined in claims 7 to 11 wherein the protrusions have a length equating to between 10 and 50 % of the length of the cylindrical member.

13. A device as defined in claims 1 to 6 additionally comprising a plurality of radially projecting protrusions as defined in claims 7 to 12.

14. A device as defined in claims 7 to 12 wherein the central groove has a friction-enhancing surface as defined in claims 1 to 6.

15. A device as defined in any preceding claims which additionally comprises a coating composition comprising a therapeutic agent.

16. A device as defined in claim 15 wherein the therapeutic agent comprises 0.01% to about 50 % by weight of the coating composition.

17. A device as defined in claim 15 or claim 16 wherein the coating composition additionally comprises a polymer.

18. A device as defined in any preceding claim, comprising a fabric covering over all or part of its surface.

19 A device as defined in claim 18 wherein the fabric is coated or impregnated with collagen.

20. A device as defined in claims 18 and/or 19 wherein the fabric is coated or impregnated with a therapeutic agent.

21. Use of a device as defined in claims 1 to 20, for joining together two ends of natural and/or artificial vessels .

22. A device or use as defined in any preceding claims wherein the natural vessels comprise blood vessels such as arteries or veins, lymphatic vessels, ducts or other tubular muscular organs within the body of a human or animal.

23. A method for joining together two ends of natural and/or artificial vessels comprising the following steps: a) insertion of a sutureless connector device comprising a hollow cylindrical member with a single central annular groove into a first vessel; b) insertion of an end of the first vessel containing the device into a second vessel; and c) securing both tissues to the device by application of a securing means to the exterior of the second vessel at the position of the central annular groove.

24. A method for joining together two ends of natural and/or artificial vessels comprising the following steps: a) insertion of a sutureless connector device comprising a hollow cylindrical member with a single central annular groove into a first vessel; b) securing the first vessel to the device by application of a first securing means to the exterior of the vessel at the position of the central annular groove; c) insertion of an end of the first vessel containing the device into a second vessel; and d) securing a second vessel to the device by application of a second securing means to the exterior of the second vessel at the position of the central annular groove.

25. A method as defined in claims 23 or 24 wherein the securing means comprise suture material, tape, plastic ties such as cable ties or other tightening member.

26. A use or method as defined in claims 21 to 25 wherein one of the vessels consists of a natural vessel and the other consists of an artificial vessel.

27. A kit for performing anastomoses comprising a device as defined in claims 1 to 20 and securing means as defined in claim 25.