(19)
(11)EP 2 900 292 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
22.07.2020 Bulletin 2020/30

(21)Application number: 13771745.0

(22)Date of filing:  25.09.2013
(51)International Patent Classification (IPC): 
A61L 31/04(2006.01)
(86)International application number:
PCT/US2013/061586
(87)International publication number:
WO 2014/052392 (03.04.2014 Gazette  2014/14)

(54)

MATERIALS AND METHODS FOR PROTECTING AGAINST NEUROMAS

MATERIALIEN UND VERFAHREN ZUM SCHUTZ GEGEN NEUROME

MATÉRIAUX ET PROCÉDÉS POUR LA PROTECTION CONTRE LES NÉVROMES


(84)Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

(30)Priority: 25.09.2012 US 201261705251 P

(43)Date of publication of application:
05.08.2015 Bulletin 2015/32

(73)Proprietor: AxoGen Corporation
Alachua, Florida 32615 (US)

(72)Inventors:
  • DEISTER, Curt
    Alachua, FL 32615 (US)
  • SIMON, Crystal
    Alachua, FL 32615 (US)

(74)Representative: Cozens, Paul Dennis et al
Mathys & Squire LLP
The Shard 32 London Bridge Street London SE1 9SG
The Shard 32 London Bridge Street London SE1 9SG (GB)


(56)References cited: : 
WO-A2-2012/097297
US-A- 5 705 178
US-A- 4 778 467
US-A1- 2010 055 149
  
      
    Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


    Description

    CROSS-REFERENCE TO A RELATED APPLICATION



    [0001] This application claims the benefit of U.S. provisional application Serial No. 61/705,251, filed September 25, 2012.

    BACKGROUND OF INVENTION



    [0002] Neuromas develop as a part of a normal reparative process following peripheral nerve injury. They are formed when nerve recovery towards the distal nerve end or target organ fails and nerve fibers improperly and irregularly regenerate into the surrounding scar tissue. Neuromas consist of a deranged architecture of tangled axons, Schwann cells, endoneurial cells, and perineurial cells in a dense collagenous matrix with surrounding fibroblasts (Mackinnon SE et al. 1985. Alteration of neuroma formation by manipulation of its microenvironment. Plast Reconstr Surg. 76:345-53). The up-regulation of certain channels and receptors during neuroma development can also cause abnormal sensitivity and spontaneous activity of injured axons (Curtin C and Carroll I. 2009. Cutaneous neuroma physiology and its relationship to chronic pain. J. Hand Surg Am. 34:1334-6). Haphazardly arranged nerve fibers are known to produce abnormal activity that stimulates central neurons (Wall PD and Gutnick M. 1974. Ongoing activity in peripheral nerves; physiology and pharmacology of impulses originating from neuroma. Exp Neurol. 43:580-593). This ongoing activity can be enhanced by mechanical stimulation, for example, from the constantly rebuilt scar at the injury site (Nordin M et al. 1984. Ectopic sensory discharges and paresthesiae in patients with disorders of peripheral nerves, dorsal roots and dorsal columns. Pain. 20:231-245; Scadding JW. 1981. Development of ongoing activity, mechanosensitivity, and adrenaline sensitivity in severed peripheral nerve axons. Exp Neurol. 73:345-364).

    [0003] Neuromas of the nerve stump are unavoidable consequences of nerve injury when the nerve is not, or cannot be, repaired and can result in debilitating pain. This is particularly likely if the neuroma is present at or near the surface as physical stimulation induces signaling in the nerve resulting in a sensation of pain.

    [0004] Neuroma prevention and attenuation strategies have used various methods to limit the size of the neuroma and protect the neuroma from external stimuli. Current prevention methods, see Fig 1, attempt to limit the size of the neuroma and so reduce or limit possible communications between axons within the injured nerve site by limiting the number of other axons and axons contacts in the disorganized structure that characterizes neuromas. Due to a variety of factors, current methods of neuroma mitigation/prevention have an unacceptable level of efficacy.

    [0005] While various methods to prevent, minimize, or shield neuromas have been attempted, the current clinical "gold standard" for treating neuromas is to bury the nerve end (that will form the neuroma) into muscle or a hole drilled in bone. The surrounding tissue cushions and isolates the neuroma so that it is not stimulated (so it does not cause painful sensations). However this procedure can greatly complicate the surgery as significant additional dissection of otherwise healthy tissue is required to place the nerve stump. For these reasons, placement of the nerve stump is often not performed in amputations (and many other nerve procedures) despite the fact that -30% of neuromas become painful and problematic.

    [0006] Another method used is to dissect the nerve stump back to leave a segment of epineurium overhanging and then ligate the overhanging epineurium, or covering the face of the nerve stump with the freed epineurium (or use a segment of the epineurium from the distal nerve). Yet another method that is commonly used today is a suture ligation. Basically, a loop of suture is placed around the end of the nerve and tightened. This pressure is then believed to mechanically block the exit of axons and eventually form scar tissue at the site. However clinical and pre-clinical evidence has shown that a painful neuroma can form behind a ligation. The ligated nerve is generally not positioned to minimize mechanical stimulation of the neuroma, though studies have shown that positioning the nerve in a protected area can resolve chronic stump pain.

    [0007] Covering the nerve stump with a silicone rubber tube, a vein, or a silicone rubber plug (i.e. a tube with a sealed end) has also been used.

    [0008] US 4778467 A describes prosthesis and methods for promoting nerve regeneration. The proximal and distal ends of a severed nerve are brought into close proximity and are enclosed by a tubular prosthesis. In one example, an epineurial or endoneurial monosuture is used to hold the nerve ends in close proximity. A tight seal is formed between the prosthesis and the injured nerve so as to isolate the injured nerve within the prosthesis from the rest of the body of the host. Additionally, in one example, nerve grafts may be incorporated into the prosthesis and nerve regeneration promoting substances may be incorporated within the nerve graft to further enhance nerve regeneration. In another example, a prosthesis is coated with a material which is slippery with relation to the surrounding body tissue and the prosthesis is formed of or coated with a material around the inside of the prosthesis which will substantially adhere to the severed nerve ends so as to prevent substantial movement of the severed nerve ends within the prosthesis. In yet another example, such an outside coating around the prosthesis terminates in two longitudinal flaps which serve to form a fluid-tight seal along the tubular prosthesis. In still another example, the ends of the prosthesis overlap and are formed so as to bias against each other in a spiral tube configuration, thereby providing for firm closure of the prosthesis around a variety of sizes of injured nerves. Also described are various devices and methods for inhibiting the formation of neuromas, such as an open-ended tube or a neuroma-inhibition device formed as a cap member having a reservoir formed therein.

    [0009] Current methods for addressing neuromas have not been generally successful and therefore not generally adopted.

    BRIEF SUMMARY



    [0010] The invention is defined by the claims.

    [0011] The subject invention provides devices and methods for manufacturing these, wherein these devices are for alleviating discomfort associated with neuroma formation. Specifically, the subject invention provides biomedical devices and methods for manufacturing these, wherein these devices are for neuroma size limitation and neuroma protection.

    [0012] In preferred embodiments, the subject device is a cylindrical cap to be applied to nerves within a subject's body (e.g., sterile), wherein the internal chamber of the cylindrical cap physically partitions the nerve to enable an arrangement of nerve fibers (as opposed to haphazardly arranged nerve fibers often produced in neuromas). Preferably the device is sterile. In addition, the cap's material remodels into a tissue cushion after implantation, which protects the neuroma from being stimulated and inducing pain. Preferably, the dimensions of the body of the device are: about 1 mm to 25 mm in diameter and 1 mm to 100 mm in length.

    [0013] In a specific embodiment, the internal partitioning of the cap is in the form of a spiral channel. The material of the cap is a biomaterial that can remodel to generate a volume of protective connective tissue around a neuroma (rather than the current use of a biomaterial to contain a neuroma volumetrically). In a preferred embodiment, the material of the cap is a membrane biomaterial such as small intestine submucosa (SIS), amnion, dermis, or decellularized fascia.

    [0014] A device is provided that contains a hollow indentation at one end to allow insertion of the nerve stump and a dense layer of biomaterial on the exterior surface to mechanically isolate the neuroma and prevent axons from escaping the device. The hollow indentation contains partitions to subdivide the neuroma that will form from the nerve stump. The nerve stump is secured in the hollow indentation. After the device is implanted, it is remodeled into the body's own tissue to provide a cushion for the neuroma.

    [0015] The combination of limiting the growth of the neuroma through physical partitioning along with the creation of a connective tissue capsule is unique. This novel combination of features and design effectively uses the body's natural response of reconstructing implanted biomaterials to minimize the size of, isolate, and protect the neuroma.

    BRIEF DESCRIPTION OF THE DRAWINGS



    [0016] 

    Figure 1 shows schematic presentation of consecutive steps of various current nerve stump capping methods: 1 - nerve transection; 2 - nerve stump preparation (A and B, nerve sheath must be slid off, then a piece of the nerve is removed to prepare a sleeve-like fragment of epineurium; C, cap can be formed of any autologous tissue, sutured to the epineurium); 3 - the end of epineurium can be tied up (A) or sutured (B and C). Lewin-Kowalik J. et al. (2006) Prevention and Management of Painful Neuroma. Neurol Med Chir (Tokyo), 46:62-68.

    Figure 2 shows perspective views (2A and 2C) of two embodiments of the invention and a side view (2B) of an embodiment of the device of the subject invention.

    Figure 3 shows a side cut-away view of and top view of the proximal end of the embodiment shown in Figure 2.

    Figure 4A is a schematic drawing showing an untreated neuroma.

    Figure 4B is a schematic drawing showing a neuroma treated using an embodiment of a device of the subject invention.

    Figure 5A is a schematic drawing showing a perspective view of another embodiment of the device of the invention.

    Figure 5B is a view illustrating a press-forming process executed by the press-forming apparatus to manufacture an embodiment of the device shown in Figure 5A.


    DETAILED DISCLOSURE



    [0017] The subject invention provides devices for alleviating discomfort associated with neuromas, and methods of manufacturing these devices. More specifically, the subject invention pertains to devices for limiting neuroma size and physically surrounding the neuroma to prevent stimulation that elicits neuropathic pain, and to methods of manufacturing these devices. In certain embodiments, the subject invention is directed to a tissue-engineered scaffold that provides: a barrier limiting the size of a neuroma, subdivision of neuroma volume to reduce axonal cross-talk, and mechanical isolation of the neuroma.

    [0018] A device of the subject invention is designed to become a protective, connective tissue capsule surrounding the neuroma. Within the volume created by the barrier, subdividing the injured nerve limits the amount of interaction between axons thereby limiting signaling cascades inside the neuroma that can be interpreted as pain when sensory neurons signaling occurs. By providing mechanical isolation, the subject device limits stimulation of the neuroma, which is a prominent cause of signaling cascades, which in turn are the direct cause of pain. The ability of the material of the subject device to bio-remodel into a native tissue cushion is another advantageous feature when combined with the physical partitioning of the axon stump.

    [0019] This subject invention provides the benefits of epineural flap (or ligation) to limit neuroma size and bury the nerve in a mechanically isolated location in a single off-the-shelf device. This device isolates and protects the neuroma thereby preventing painful sensations without the need for any repositioning of the nerve. Instead, the device is secured to the stump of the nerve and then integrated into the host tissues.

    [0020] A schematic of an embodiment of the subject invention is shown in Figures 2-4. In one embodiment illustrated in Figure 2, the device 10 of the subject invention has a body 15 that comprises a proximal end 20 and a distal end 25.

    [0021] It can be seen in Figure 2 that one embodiment of the body 15 of the device 10 is cylindrical in shape. However, the shape of the body 15 of the device 10 can vary depending upon the type, diameter and location of a nerve stump, as well as other factors known to those with skill in the art. For example, the circumferential shape of the body can be variable and be, by way of non-limiting examples, an ovoid, circular, square, rectangular, triangular, or any other polygonal shape. In an exemplified embodiment, the circumferential shape of the body is generally circular.

    [0022] The dimensions of the body can vary depending on the type, diameter and location of a nerve stump, as well as other factors known to those skilled in the art. The body of the device can have dimensions of approximately 1mm to 25mm in diameter and 1 mm to 100mm length. The body of the device will typically be less than 100 mm in diameter and less than 500 mm in length.

    [0023] In one embodiment, the diameter of the distal end 25 of the body 15 can be narrower than the diameter of the proximal end 20, as seen, for example, in Figures 2 and 3. In one embodiment, for example, as shown in Figure 3, the proximal end 20 is open and the distal end 25 of the body 15 is closed off entirely 30 to form a cap. Figure 3 also illustrates an embodiment in which a hollow indentation 35 is provided in the body 15. In certain embodiments, the interior surface of the closed off 30 portion of body 15 can be in the form of a bevel 40; alternatively, a closed off portion can be a flat surface.

    [0024] According to one embodiment of the invention, the body 15 can include spiral partitions 45. Advantageously, the spiral partitions enable subdivision and arrangement of axons from the nerve stump. In certain related embodiments, the body comprises a tightly packed spiral of a solid sheet of biomaterial. Preferably, where the body comprises a tightly packed spiral of a solid sheet of biomaterial, there are no voids present that could lead to axonal escape from the device.

    [0025] In one embodiment, as illustrated in Figure 4B, an unchambered layer of biomaterial 50 is provided on the exterior surface of the chambered body 15 of the device. The biomaterial preferably isolates the neuroma and prevents axons from escaping the body 15 of the device. Figure 4A is a schematic drawing showing an untreated neuroma.

    [0026] Both natural and synthetic biomaterials can be used to manufacture the device of the subject invention. In certain embodiments, the biomaterial is a homogenous material. Examples of biomaterials for use in manufacturing the subject invention include, but are not limited to, high density polyethylene (HDPE), polyethylene glycol (PEG) hydrogel, purified proteins from human or animal sources (e.g., membrane of purified collagen or fibrin), and decellularized tissue constructs (e.g., demineralized bone, amnion, SIS, dermis, or fascia). An HDPE or PEG device can comprise or consist of a cylinder of porous HDPE or PEG surrounded by a layer of non-porous HDPE or PEG. Biomaterials which can form a fluid material, such as soluble purified collagen or particulate SIS and dermis, can be directly cast to form the device without a membrane as an intermediate.

    [0027] In certain embodiments, the body of the device can be made by rolling a sheet of biomaterial to form spiral partitions. Where the body of the device is a "roll" of spiral partitions, the layers of the roll separate slightly to allow nerve regeneration to proceed a short distance into the device before encountering, and being stopped by, infiltrating non-nerve tissue (i.e. the rolled version has longitudinal pores or characteristics). In specific related embodiments, layers of the rolled biomaterial are situated such that a spiral channel is present on the face of the device facing the nerve stump but the device face external to the nerve sump is solid.

    [0028] In other embodiments, the body of the device can be made of a porous biomaterial. In yet other embodiments, the body includes a hollow central cavity to facilitate insertion of a nerve stump. In certain other embodiments, a body is provided with a hollow cavity wherein layers of biomaterial scaffolding fill a portion of the hollow cavity to create a laminar or multi-laminar construct 60 (see Figure 2C).

    [0029] In an alternate embodiment as illustrated in Figure 5A, the body 15 of the device resembles a test tube, where the body is made of a thin layer of biomaterial (either a single layer or a small number of layers) and there is a hollow central cavity 55 to facilitate insertion of a nerve stump.

    [0030] Illustrated in Figure 5B is a method for producing the embodiment of the device of Figure 5A. Figure 5B illustrates a press formation apparatus 100 for manufacturing the device of Figure 5A. As shown in Figure 5A, a thin layer of biomaterial 105 (either a single layer or a small number of layers of biomaterial) is mounted on a receiving portion 115 of the press formation apparatus 100. The receiving portion 115 has an opening 120 for receiving a punch 125, where the shape of the opening 120 corresponds with that of the punch 125. The receiving portion 115 and the punch 125 can be manufactured by die molding. Preferably, the punch 125 is rod shaped; however, other shapes known to the skilled artisan can be used for the opening of the receiving portion and the punch.

    [0031] The thin layer of biomaterial 105 is arranged over the opening 120 of the receiving portion 115. Once the biomaterial 105 is positioned, the punch 125 is then driven downward and received in the opening 120. In this way, the body 15 of the device is formed.

    [0032] In further embodiments, a cylindrical body having a hollow interior with open ends is provided. The distal end of the body may be "crimped" during the manufacturing process to present a more solid biomaterial as a barrier to axonal escape from the device. An example is the use of a crimped mold during vacuum pressing of a rolled cylinder, such that one end is of a smaller diameter.

    [0033] In a preferred embodiment, the body of the subject device comprises a cylinder of SIS. A hollow cavity is provided at the proximal end to allow insertion of a nerve stump. A deep spiral partition is present in the body to subdivide the neuroma that will form from the nerve stump, and a dense layer of biomaterial is provided on the entire exterior surface to mechanically isolate the neuroma and prevents axons from escaping the device.

    [0034] In using the device, a nerve stump is secured in the hollow indentation by means of a suture, staple, clip, or surgical adhesive or sealant. After implantation, the cap is remodeled into the body's own tissue and provides a cushion for the neuroma. As host cells infiltrate the biomaterial, it is converted into a form of connective tissue. Axons and Schwann cells will also infiltrate from the stump. As fibroblasts (and other cells supporting remodeling into a connective tissue) 1) migrate and proliferate faster than Schwann cells/axons and 2) infiltrate from multiple sides and 3) axonal regeneration stops when it encounters other tissues (such as muscle, connective tissue layers, etc); the device will result in a layer of connective tissue surrounding a small neuroma in a vascularized tissue capsule. This capsule provides the desired isolation and protection.


    Claims

    1. A sterile device for protecting against neuromas comprising a cap having a body with a proximal end and a distal end, wherein the proximal end is open and the distal end is closed off, wherein the body of the device is less than 100 mm in diameter and less than 500 mm in length, wherein the body is chambered such that it has an internal chamber and the internal chamber comprises partitions, and wherein the cap comprises an unchambered layer of biomaterial provided on the exterior surface of the chambered body of the device to prevent axons from escaping the body of the device, wherein the unchambered layer of biomaterial remodels into a tissue cushion after insertion, thereby protecting against a neuroma.
     
    2. The device according to claim 1, wherein the partitions are in the form of a spiral channel.
     
    3. The device according to claim 1, wherein the partitions are in the form of a laminar or multi-laminar scaffold.
     
    4. The device according to claim 1, wherein the biomaterial is selected from the group consisting of: polyethylene glycol (PEG) hydrogel, purified proteins from human or animal sources, and decellularized tissue constructs.
     
    5. The device according to claim 4, wherein the biomaterial is small intestine submucosa (SIS), amnion, dermis, collagen or decellularized fascia.
     
    6. The device according to claim 4, wherein the cap is composed of porous PEG surrounded by a layer of non-porous PEG.
     
    7. The device according to claim 1, wherein the body is cylindrical in shape, preferably wherein the diameter of the distal end of the body is narrower than the diameter of the proximal end.
     
    8. The device according to claim 1 wherein the unchambered layer of biomaterial is provided as a dense layer on the exterior surface of the chambered body of the device.
     
    9. The device according to claim 1 wherein the unchambered layer of biomaterial is further provided on the exterior surface of the chambered body of the device to isolate a neuroma.
     
    10. A method for making the device according to claim 1, comprising rolling a sheet of biomaterial to form a cylindrical body with spiral partitions.
     
    11. The method according to claim 10, further comprising the step of crimping one end of the cylindrical body of the rolled spiral sheet of biomaterial.
     
    12. The method according to claim 10, wherein the sheet of biomaterial is selected from the group consisting of: small intestine submucosa (SIS), amnion, dermis, collagen and decellularized fascia.
     
    13. The method according to claim 10, further comprising the steps of: press forming a thin layer of biomaterial into a rod shape; and inserting the rolled spiral sheet of biomaterial into the rod shaped biomaterial, preferably wherein the sheet of biomaterial and the thin layer of biomaterial are individually composed of a material selected from the group consisting of: small intestine submucosa (SIS), amnion, dermis, collagen and decellularized fascia.
     


    Ansprüche

    1. Sterile Vorrichtung zum Schutz vor Neuromen, die eine Kappe mit einem Körper mit einem proximalen Ende und einem distalen Ende umfasst, wobei das proximale Ende offen und das distale Ende verschlossen ist, wobei der Körper der Vorrichtung einen Durchmesser von weniger als 100 mm und eine Länge von weniger als 500 mm hat, wobei der Körper so gekammert ist, dass er eine innere Kammer hat und die innere Kammer Trennwände umfasst, und wobei die Kappe eine nicht gekammerte Schicht aus Biomaterial umfasst, die auf der Außenfläche des gekammerten Körpers der Vorrichtung vorgesehen ist, um zu verhindern, dass Axone aus dem Körper der Vorrichtung austreten, wobei sich die ungekammerte Schicht aus Biomaterial nach dem Einsetzen zu einem Gewebekissen umgestaltet, wodurch sie vor einem Neurom schützt.
     
    2. Vorrichtung nach Anspruch 1, wobei die Trennwände die Form eines spiralförmigen Kanals haben.
     
    3. Vorrichtung nach Anspruch 1, wobei die Trennwände in Form eines laminaren oder multilaminaren Gerüsts vorliegen.
     
    4. Vorrichtung nach Anspruch 1, wobei das Biomaterial ausgewählt ist aus der Gruppe bestehend aus: Polyethylenglykol-(PEG)-Hydrogel, gereinigten Proteinen menschlichen oder tierischen Ursprungs und dezellularisierten Gewebekonstrukten.
     
    5. Vorrichtung nach Anspruch 4, wobei das Biomaterial Dünndarm-Submukosa (SIS), Amnion, Dermis, Kollagen oder dezellularisiertes Bindegewebe ist.
     
    6. Vorrichtung nach Anspruch 4, wobei die Kappe aus porösem PEG besteht, das von einer Schicht aus nicht porösem PEG umgeben ist.
     
    7. Vorrichtung nach Anspruch 1, wobei der Körper eine zylindrische Gestalt hat, wobei der Durchmesser des distalen Endes des Körpers vorzugsweise schmaler ist als der Durchmesser des proximalen Endes.
     
    8. Vorrichtung nach Anspruch 1, wobei die ungekammerte Schicht aus Biomaterial als dichte Schicht auf der Außenfläche des gekammerten Körpers der Vorrichtung vorgesehen ist.
     
    9. Vorrichtung nach Anspruch 1, wobei die ungekammerte Schicht aus Biomaterial ferner auf der Außenfläche des gekammerten Körpers der Vorrichtung vorgesehen ist, um ein Neurom zu isolieren.
     
    10. Verfahren zur Herstellung der Vorrichtung nach Anspruch 1, das das Wickeln eines Stücks Biomaterial zur Bildung eines zylindrischen Körpers mit spiralförmigen Trennwänden beinhaltet.
     
    11. Verfahren nach Anspruch 10, das ferner den Schritt des Zusammendrückens eines Endes des zylindrischen Körpers des gewickelten spiralförmigen Stücks Biomaterial beinhaltet.
     
    12. Verfahren nach Anspruch 10, wobei das Stück Biomaterial ausgewählt ist aus der Gruppe bestehend aus: Dünndarm-Submukosa (SIS), Amnion, Dermis, Kollagen oder dezellularisiertem Bindegewebe.
     
    13. Verfahren nach Anspruch 10, das ferner die folgenden Schritte beinhaltet: Pressformen einer dünnen Schicht aus Biomaterial zu einer Stabform; und Einsetzen des gewickelten spiralförmigen Stücks Biomaterial in das stabförmige Biomaterial, wobei das Stück Biomaterial und die dünne Schicht aus Biomaterial vorzugsweise individuell aus einem Material bestehen, das ausgewählt ist aus der Gruppe bestehend aus: Dünndarm-Submukosa (SIS), Amnion, Dermis, Kollagen und dezellularisiertem Bindegewebe.
     


    Revendications

    1. Dispositif stérile de protection contre les névromes, comprenant un capuchon comportant un corps ayant une extrémité proximale et une extrémité distale, dans lequel l'extrémité proximale est ouverte et l'extrémité distale est fermée, dans lequel le corps du dispositif mesure moins de 100 mm de diamètre et moins de 500 mm de long, dans lequel le corps est agencé en chambres de telle sorte qu'il comporte une chambre interne et la chambre interne comprend des cloisons, et dans lequel le capuchon comprend une couche non agencée en chambres de biomatériau disposée sur la surface extérieure du corps agencé en chambres du dispositif pour empêcher les axones de s'échapper au corps du dispositif, dans lequel la couche non agencée en chambres de biomatériau se transforme en un coussin de tissu après l'insertion, en assurant ainsi une protection contre un névrome.
     
    2. Dispositif selon la revendication 1, dans lequel les cloisons sont sous la forme d'un canal en spirale.
     
    3. Dispositif selon la revendication 1, dans lequel les cloisons sont sous la forme d'un échafaudage laminaire ou multilaminaire.
     
    4. Dispositif selon la revendication 1, dans lequel le biomatériau est sélectionné dans le groupe constitué d'un hydrogel de polyéthylène glycol (PEG), de protéines purifiées provenant de sources humaines ou animales, et de constructions de tissus décellularisés.
     
    5. Dispositif selon la revendication 4, dans lequel le biomatériau est une sous-muqueuse d'intestin grêle (SIG), une membrane amniotique, un derme, un collagène ou un fascia décellularisé.
     
    6. Dispositif selon la revendication 4, dans lequel le capuchon se compose de PEG poreux entouré d'une couche de PEG non poreux.
     
    7. Dispositif selon la revendication 1, dans lequel le corps est de forme cylindrique, préférablement dans lequel le diamètre de l'extrémité distale du corps est plus étroit que le diamètre de l'extrémité proximale.
     
    8. Dispositif selon la revendication 1, dans lequel la couche non agencée en chambres de biomatériau est présente sous la forme d'une couche dense sur la surface extérieure du corps agencé en chambres du dispositif.
     
    9. Dispositif selon la revendication 1, dans lequel la couche non agencée en chambres de biomatériau est présente en outre sur la surface extérieure du corps agencé en chambres du dispositif pour isoler un névrome.
     
    10. Procédé de fabrication du dispositif selon la revendication 1, comprenant le laminage d'une feuille de biomatériau pour former un corps cylindrique comportant des cloisons en spirale.
     
    11. Procédé selon la revendication 10, comprenant en outre l'étape de sertissage d'une extrémité du corps cylindrique de la feuille de biomatériau laminée en spirale.
     
    12. Procédé selon la revendication 10, dans lequel la feuille de biomatériau est sélectionnée dans le groupe constitué d'une sous-muqueuse d'intestin grêle (SIG), d'une membrane amniotique, d'un derme, d'un collagène ou d'un fascia décellularisé.
     
    13. Procédé selon la revendication 10, comprenant en outre les étapes de formage sous pression d'une fine couche de biomatériau pour lui donner la forme d'une tige, et d'insertion de la feuille de biomatériau laminée en spirale dans le biomatériau en forme de tige, préférablement dans lequel la feuille de biomatériau et la fine couche de biomatériau se composent individuellement d'un matériau sélectionné dans le groupe constitué d'une sous-muqueuse d'intestin grêle (SIG), d'une membrane amniotique, d'un derme, d'un collagène ou d'un fascia décellularisé.
     




    Drawing














    Cited references

    REFERENCES CITED IN THE DESCRIPTION



    This list of references cited by the applicant is for the reader's convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.

    Patent documents cited in the description




    Non-patent literature cited in the description