nerve conduit

Abstract

The present invention relates to a nerve conduit for connecting the end of a damaged nerve to a target site. In particular, the present invention relates to a nerve conduit that assists in the repair of nerve damage and the restoration of motor control, and / or reduces the risk of neuroma formation at the end of the damaged nerve. Accordingly, a nerve conduit (10) for connecting the end of a damaged nerve (26) to a target site (28) is proposed. The nerve conduit (10) includes an elongate body (12) formed by a wall (22). The elongate body (12) includes a central portion (14) defining an internal cavity (16) and a plurality of end portions (18, 19) disposed adjacent the central portion (14) and at longitudinally opposed ends of the elongate body (12) that define respective openings (20, 20') to the internal cavity (16). One of the end portions (18) is configured as an insertion portion configured to receive a respective nerve end (26). According to the invention, the other end portion is configured as an exit portion (19) for the nerve end, and the outer diameter of the wall defining the exit portion (19) is greater than the outer diameter of the wall defining the central portion (14).

Description

Detailed Description of the Invention

[0001] [Technical Field] The present invention relates to nerve conduits for connecting the ends of damaged nerves to target tissue. In particular, the present invention relates to nerve conduits that assist in the repair of nerve damage and the restoration of motor control or sensory function (e.g., skin sensitivity) and / or reduce the risk of neuroma formation at the ends of damaged nerves. [Technical background]

[0002] When a person is injured, tissue damage may be accompanied by one or more nerve damage in the peripheral nervous system. As a result, partial sensory loss and / or deterioration of motor skills may occur. Such trauma accompanied by nerve damage occurs particularly in the lower and upper limbs (e.g., the human hand or fingers). If the nerve damage is not properly treated, the person may suffer, for example, from a loss of tactile or haptic feedback and / or have difficulty controlling fine motor skills in the injured area.

[0003] Current treatments for nerve injuries include joining the nerve ends using various suturing techniques to create a substantially tension-free connection between the respective nerve ends. In more severe cases where the nerve ends are not directly adjacent to each other, reconstruction may be required to overcome the corresponding gap. For example, reconstruction can be performed using autologous or allogenic nerve grafts. Alternatively, reconstruction can be performed by providing a tubular structure to provide a nerve guide in the form of a lumen that provides a directional pathway for neurogenesis. For example, autologous or allogenic venous structures or artificial nerve conduits made from biocompatible materials can provide such tubular structures to accommodate the respective nerve ends. The use of tubular structures can further facilitate injury repair, regardless of the presence of a gap, by, for example, providing additional mechanical support and structural stability, providing tension-free repair, reducing inflammatory responses to the injury site, and / or limiting the spread of fibrous tissue growth.

[0004] However, in clinical situations where distal nerve ends have been lost, for example, due to amputation or tissue resection, such connections between nerve ends are not possible. This not only complicates treatment to at least partially restore motor control or sensory function, but also increases the risk of neuromas forming at the end of the severed nerve. Such neuromas can arise from disorganized axons growing at the end of a transected nerve, for example, after severe trauma or surgery, attempting to cross the severed epineurial sheath and reinnervate distal muscles or skin. Axonal sprouting can result in the formation of a disorganized, hyperexcitable bundle of nerve tissue (called a neuroma) that lacks a native nerve structure. Neuromas are usually accompanied by neuropathic pain, numbness, and tingling, and can interfere with rehabilitation, functional recovery, and even sensory impairment. Attempts to treat or prevent neuromas can be based on suturing the proximal end of the injured nerve to a different motor nerve in a newly denervated, intact muscle. This suturing technique may at least partially restore muscle control while reducing the risk of neuroma formation.

[0005] Other surgical alternatives have been proposed for repair of peripheral nerve injuries when a proximal nerve stump is unavailable or when a significant nerve gap exists, or when the nerve is transected and too far from the target organ, muscle, or skin, such as end-to-side (ETS) nerve repair, in which the distal stump of the injured nerve is attached to the side of the uninjured nerve (Lykissas, 2011, World Journal of Orthopaedics, vol. 2, no. 11, 102-106).

[0006] Another method, called targeted muscle reinnervation (TMR), is surgical nerve transfer. In TMR, remaining nerves from the amputated limb are transferred to a new muscle target. As part of the nerve transfer procedure, the target muscle is separated from its natural motor nerve input so that the newly transferred nerve can reinnervate the target muscle (Bergmeister et al., 2021, Hand Clin, 37(3):415-424; Janes et al., 2021, Hand Clin, 37(3):345-359). Summary of the Invention

[0007] Departing from the known prior art, there is a need to further facilitate the repair of nerve damage, more particularly repair of nerve damage following amputation, which results in nerve endings that can form neuromas or cause phantom limb pain.

[0008] According to the present invention, it is recognized that connecting the proximal or distal nerve end of a nerve (preferably an injured nerve) to a target muscle tissue or a target organ or a side of the target nerve can be difficult and / or may not produce satisfactory results, for example, to restore (partial) motor control and / or sensory function, and / or to avoid neuroma formation, and / or to cause regeneration of the injured nerve. Suturing the nerve end can cause undesirable tissue damage and / or complicate proper orientation of the distal end of the proximal nerve end, thereby compromising the intended restoration of motor control or nerve coaptation. Furthermore, when connecting to a target muscle tissue, suturing techniques within the muscle tissue can complicate efficient fixation of the nerve end. Alternative fixation methods, for example, using the application of medical adhesives, have proven to have limited success due to the small surface area available for application. Furthermore, the required curing time can result in loss of proper placement of each nerve end and / or loss of proper attachment altogether.

[0009] Thus, one object of the present invention is to further facilitate the repair of nerve injuries, particularly by facilitating the proper fixation and placement of nerve ends to target tissue (e.g., muscle, bone, or skin) or to the side of a target organ or nerve (collectively referred to as a target site). A particular object of the present invention may be to facilitate the effective and efficient connection of proximal nerve ends to target muscles or skin for the restoration of motor control and / or sensory feedback and / or the prevention of neuroma formation. Another object of the present invention may be to facilitate the connection of proximal nerve ends to the side of a targeted (uninjured) donor nerve in an effective and efficient end-to-side (ETS) nerve repair procedure. Another object of the present invention may be to facilitate the connection of nerve ends to organs, such as transplanted organs (e.g., heart, liver, and kidney).

[0010] This object is achieved by the independent claims. Preferred embodiments are set forth in the dependent claims, the description and the drawings.

[0011] Thus, a nerve conduit for connecting a nerve end, e.g., the end of a damaged nerve, to a target site (e.g., a target tissue, a target organ, or a side of a target nerve) is proposed. The nerve conduit includes an elongated body formed by a wall. The elongated body includes a central portion defining an internal cavity and a plurality of end portions defining respective openings to the internal cavity and disposed adjacent to the central portion at longitudinally opposite ends of the elongated body. One of the end portions is configured as an insertion portion for a nerve end portion, into which a respective nerve end portion is inserted. According to the present invention, the other end portion is configured as an exit portion for a nerve end portion. The outer diameter of the wall defining the exit portion is larger than the outer diameter of the wall defining the central portion.

[0012] The increased diameter facilitates connection to the target site due to the correspondingly increased surface area. This may not only increase the potential fixation force between the exit section and the target site, but may also facilitate accurate application of the medical adhesive, for example, by displaying and / or defining a more prominent target application surface for the medical adhesive. Furthermore, the increased diameter of the exit section facilitates proper placement and orientation of the nerve conduit and the nerve ends contained therein relative to the target site (e.g., a denervated muscle or muscle section (e.g., a muscle flap), a nerve side, a bone, or an organ) while improving stability during placement of the nerve conduit. The exit section and / or its material may also be resilient to provide a level of conformance to the anatomical structure of the target site. According to a preferred embodiment, the term "target site" according to the present invention generally refers to tissue, for example, muscle (preferably a denervated muscle or muscle section (e.g., a muscle flap)), or bone, a nerve side, or an organ.

[0013] The increased diameter of the exit section may make it easier to identify each end section so that the surgeon can easily understand which end section to use to insert the nerve end and accommodate the nerve end within the insertion section and internal cavity. In this regard, the nerve end of each nerve injury may be secured to the nerve conduit after proper insertion of the nerve end into the corresponding insertion section. It may be ensured that the medical adhesive or other means used to secure each nerve end to the nerve conduit has been properly applied. Thus, the nerve end may be secured or attached to the nerve conduit prior to connecting the nerve conduit to the target site.

[0014] Providing an internal cavity and an enlarged exit portion further has the advantage that nerve ends can be observed or inspected after insertion into the insertion portion and internal cavity. In particular, each nerve end may be received into the internal cavity via the corresponding insertion portion, extend through the internal cavity toward the corresponding exit portion, or extend through the internal cavity to the corresponding exit portion. In other words, the nerve end may be inserted to terminate at or within the exit portion, or may be inserted to terminate at the junction between the opening 20′ and the internal cavity, so that the nerve end can be observed through the exit portion. Thus, proper insertion of the nerve end may be monitored prior to connection to the target site and possible application of a medical adhesive.

[0015] The nerve conduit may generally have a tubular shape. A lumen or internal cavity is defined by the walls, with opposing openings so as to provide a continuous channel or through-hole. In other words, the walls form an elongated body extending in the longitudinal direction. Prior to insertion of the nerve ends and connection of the nerve conduit to the target site, a fluid connection or communication between the exterior and the internal cavity is provided through the respective openings in the end portions.

[0016] The cross section of the internal cavity and opening preferably has a circular or ellipsoidal shape. A tubular or cylindrical shape can provide sufficient structural stability and can prevent sharp (abrupt) bending or twisting during tissue movement, i.e., contraction or extension. A tubular shape can provide a homogeneous structure that reacts in a predetermined manner along the entire central portion when a force is applied to the central portion (e.g., during an impact).

[0017] Preferably, the maximum outer diameter of the wall defining the exit section is 1 mm to 10 mm larger, more preferably 2 mm to 6 mm larger, than the outer diameter of the wall defining the central section. This larger diameter, at a predetermined dimension, can provide a predetermined contact or retention surface for connection to a target site. The radial extension of the exit section can depend on the diameter of the nerve end to be accommodated within the nerve conduit and the corresponding diameter of the internal cavity. For example, a nerve conduit having an internal cavity of 1.5 mm to 4 mm can have an exit section with a diameter, e.g., 2 mm or 3 mm larger, than the outer diameter of the wall defining the central section. On the other hand, a nerve conduit having an internal cavity of approximately 8 mm to 10 mm can require a larger radial extension of the exit section, e.g., 6 mm to 10 mm larger than the outer diameter of the wall defining the central section, to ensure adequate and stable connection to the target tissue. Furthermore, the predetermined dimension can provide a corresponding surface for applying, for example, a medical adhesive, thereby ensuring a predetermined fixation or securing force.

[0018] Furthermore, the ratio between the maximum outer diameter of the wall defining the exit section and the outer diameter of the wall defining the central section may be 1.1:1.0 to 8.0:1.0, preferably 1.3:1.0 to 5.5:1.0, or 1.1:1.0 to 3.0:1.0, preferably 1.4:1.0 to 2.0:1.0. In this manner, an enlarged exit section is provided that is easily identifiable and facilitates connection to the target site. This increased size of the exit section further ensures that axonal growth can be directed to the target site even in the event of unintended misalignment or placement of the nerve conduit. For larger nerve ends, e.g., having a diameter greater than 6 mm, the corresponding ratio may be limited by absolute dimensions to avoid potential mismatch of nerve conduit dimensions to the target site and surrounding tissue and / or surgical procedure.

[0019] The diameter of the inner cavity is preferably 1 mm to 12 mm, more preferably 1.5 mm to 6.5 mm, so as to accommodate the corresponding diameter of the nerve endings, making the nerve conduit particularly advantageous for accommodating nerve endings, for example in the upper or lower limbs of a patient, and for restoring fine motor control and / or restoring sensory feedback and / or preventing the formation of neuromas.

[0020] To increase the structural stability of the connection surface and limit the overall dimensions of the nerve conduit, the ratio between the longitudinal extension of the outlet section and the longitudinal extension of the central section is preferably 0.1:1.0 to 0.6:1.0. This reduced longitudinal extension compared to the internal cavity can result in the outlet section being formed essentially as a radial flange. This can facilitate proper orientation of the nerve conduit, for example, during application of a medical adhesive, and can also provide an improved retention and / or fixation surface for the medical adhesive or other attachment means.

[0021] The radial extension of the outlet section preferably exceeds the longitudinal extension of the central section, since nerve ends may be directly connected to the target site, i.e., the longitudinal extension of the central section as a nerve guide may be smaller, since bridging of a large gap between each nerve end and the target site is preferably not required.

[0022] Therefore, the ratio between the maximum outer diameter of the exit section (19) and the longitudinal extension of the central section (14) is preferably 0.5:1.0 to 2.5:1.0. This allows the exit section, which forms the connection to the target site, to be provided as a more prominent functional portion and also reduces the overall longitudinal dimension of the nerve conduit. However, it will be understood that the inner cavity of the nerve conduit may be sized to bridge a predetermined gap, in which case the nerve end may be accommodated within the inner cavity at an appropriate location.

[0023] Preferably, the maximum outer diameter of the wall defining the exit section is greater than the outer diameter of the wall defining the insertion section. This creates asymmetry in the nerve conduit, with the larger diameter of the exit section unambiguously indicating the section to be connected to the target site. This also reduces the prominence of the radial dimension of the insertion section, which may be advantageous for the surrounding tissue at the implantation site and for handling during surgery.

[0024] The wall of the elongate body is preferably a single tubular wall having a substantially continuous thickness circumferentially and longitudinally along the elongate body. This may provide improved structural stability and integrity throughout the elongate body. This may also provide similar material properties (e.g., flexibility or stiffness levels) along the longitudinal extent of the elongate body, which may facilitate handling during nerve conduit implantation. Furthermore, a continuous thickness may facilitate manufacturing and reduce the total amount of material required for the nerve conduit.

[0025] Furthermore, the continuous wall thickness may result in a corresponding opening or cross-sectional area of ​​the opening in the exit section enlarged relative to the internal cavity, which may further improve visual feedback for the surgeon as they insert the respective nerve ends into the insertion section and internal cavity to ensure that the nerve ends are properly seated within the internal cavity and that the distal ends are positioned in the correct longitudinal location.

[0026] Preferably, the inner and outer diameters of the central portion are substantially continuous along the length of the elongate body. Thus, a constant inner diameter may be provided between the end portions. This may improve containment and support of the nerve end, particularly when the diameter of the inner cavity is matched to the corresponding diameter of the nerve end to be connected to the target site. Furthermore, a constant inner diameter may provide an improved guide surface for axonal growth during nerve regeneration.

[0027] As mentioned above, the cross-sectional area of ​​the opening in the outlet portion is preferably greater than the cross-sectional area of ​​the inner cavity in the central portion.

[0028] More preferably, the cross-sectional area of ​​the opening of the outlet portion and / or the outer diameter of the wall of the outlet portion may increase longitudinally away from the central portion, such an increase may provide improved conformance to the anatomy of the target site.

[0029] The outlet portion and the corresponding opening may be formed, in particular, as a rotationally symmetrical shape. Preferably, the shape is a cone, a concave, a funnel, a trumpet, or a paraboloid. Rotational symmetry may facilitate orientation of the nerve conduit during placement and connection to the target site. Furthermore, the mechanical properties of the outlet portion may be substantially the same along its circumference. This preferred shape of the outlet portion ensures that a gradual extension may be provided, which may further facilitate connection to the target site, for example, by facilitating the application of a medical adhesive. According to a particular embodiment, the outlet portion and the corresponding opening may be formed, in particular, as a rotationally symmetrical shape along (or across) the longitudinal axis defined by the elongate body.

[0030] In particular, a horn shape is preferred, which may include a substantially conical shape with an increased radial extension at the end face. Such a shape further improves application of the medical adhesive and provides an increased contact and / or retention surface with the target site beyond the wall thickness of the outlet section. This shape may also provide an optimal balance between the required connection or attachment, on the one hand, and ease of insertion into or over the target site, on the other hand.

[0031] Thus, the wall defining the outlet portion may extend radially from the wall defining the central portion at an angle of preferably from 40 degrees to less than 180 degrees relative to the longitudinal axis defined by the elongate body, more preferably from 40 degrees to 150 degrees, even more preferably from 40 degrees to 120 degrees, and even more preferably from 40 degrees to 90 degrees.

[0032] An angle between 80 and 90 degrees can result in the outlet portion being substantially perpendicular to the central portion. As used herein, the term "substantially perpendicular" includes a slight deviation from perpendicular (90°). This deviation is shown as angle (α) in the exemplary embodiment of FIG. 6. Preferably, angle (α) does not exceed 10°, more preferably does not exceed 7°, more preferably does not exceed 5°, and even more preferably does not exceed 3°. In some embodiments, angle (α) is in the range of 0.5° to 10°, preferably in the range of 1° to 5°, and more preferably in the range of 1.5° to 3°. If the opening or its cross-sectional area is correspondingly enlarged, a corresponding steepness of the opening can be provided. In other words, a radial flare can be provided, in which case the longitudinal extension of the outlet portion is minimized.

[0033] Lower angles (e.g., 40 to 70 degrees, or 45 to 65 degrees) may result in a more gradual increase in the outer diameter of the outlet portion. As such, a variety of angles (including angles greater than 90 degrees) may be provided, and the angle may depend on the predetermined or desired longitudinal and maximum radial extent of the outlet portion relative to the central portion or its internal cavity. Such longitudinal and radial extent may depend on the target site and surrounding tissue, and in particular, on the contact or retention surface required for proper connection to the target site.

[0034] The wall of the outlet portion is preferably continuous with the wall defining the central portion and may be rounded at its interface with the wall of the central portion, in other words, the wall portions may be aligned or flush, and preferably have corresponding outer surfaces without steps or edges.

[0035] According to one embodiment, the wall defining the exit section may be continuous in the circumferential direction, thus eliminating any gaps along the circumference. Such a configuration may be advantageous for handling purposes and for increased structural stability. Furthermore, such a configuration may improve the sealing function of the exit section against the exterior with respect to axonal growth of the nerve ends housed within the internal cavity. Furthermore, such a configuration substantially prevents axonal growth and / or neuromuscular junction development at the exit section from being impaired by surrounding tissue.

[0036] In an alternative embodiment, the wall defining the outlet portion may be formed as a plurality of arms extending radially outward and spaced apart from one another in the circumferential direction. Accordingly, a plurality of gaps may be provided circumferentially so that each arm can form an individual contact surface with the target tissue. This may provide an improved level of flexibility and conformance to the anatomical structure of the target tissue, while allowing the medical adhesive to be applied in a manner that increases both the amount of rim and the contact surface of the target site covered by the medical adhesive. Furthermore, the provision of individual arms may facilitate insertion of the end face of the outlet portion into a slit or recess in the target site if such a connection is desirable for the respective treatment and / or anatomical structure of the target site.

[0037] Preferably, each of the plurality of arms has a circumferential extension of 10 to 150 degrees. Such a circumferential extension may provide sufficient structural stability and connection force while providing an advantageous level of flexibility and conformance to the target site. The circumferential extension may be tailored to the number of arms and / or the predetermined gap extension.

[0038] The arms are preferably equally circumferentially spaced apart to ensure rotational symmetry, which is advantageous for accurate orientation of the nerve conduit relative to the target site, and to ensure uniformity of connection to the target site.

[0039] However, other configurations of arms may be provided, such as multiple pairs of adjacent arms or multiple adjacent arms arranged along respective radial axes. In this case, two or more radial axes may be provided at predetermined angles to one another. Such configurations may be advantageous with respect to the corresponding extension of the target tissue anatomy, for example, when the target site has a more pronounced extension in a particular direction and / or when connection to a particular portion of the target site is desired.

[0040] Depending on the maximum outer diameter of the outlet section and the anatomical structure of the target site, an appropriate number of arms may be provided to ensure proper connection to the target site and structural stability of the arms. Preferably, the wall is formed with 2 to 16 arms, more preferably 6 to 12 arms. For example, it may be particularly advantageous in this regard if the outlet section is formed with 10 arms, preferably equally spaced apart from one another, each arm preferably having a circumferential extension of about 20 degrees.

[0041] To improve the flexibility and adaptability of each arm, the arms may include radially tapered sections. In other words, each arm may have a smaller circumferential extension, for example, at its intermediate radial section, i.e., between the end of the arm connected to the central section and the opposite free end. The tapered shape, for example, defining an hourglass-shaped arm, allows the arm to bend or flex around the tapered section. The position of such tapered section can thus be adapted to the required surface of the end of the arm required for connection to the target site and / or the optional insertion depth into the target site.

[0042] To facilitate application and adhesive strength of a medical adhesive or to increase retention when the exit portion is inserted into a target site, the exit portion may have a greater surface roughness at the outer surface of its wall compared to the outer surface of the wall defining the central portion. Alternatively, or in addition, such increased surface roughness may be provided with respect to (or on) the outer surface of the wall defining the insertion portion. Thus, both the exit portion and the central portion may exhibit increased surface roughness relative to the insertion portion, or only the exit portion may exhibit such increased surface roughness. This may depend on the handling requirements of the nerve conduit during surgery and implantation of the nerve conduit at the target site.

[0043] The exit portion is preferably configured to be connected to muscle tissue to facilitate at least partial restoration of motor control and / or restoration of sensory feedback and / or prevention of neuroma formation. The muscle tissue may be, for example, a denervated target muscle adjacent to or near the end of each damaged nerve, facilitating motor control of the damaged anatomical structure (e.g., a finger). Muscle tissue may also be effective in reducing the incidence of neuroma formation, and embedding the ends of each nerve within the muscle may be particularly advantageous.

[0044] Thus, the exit portion may be configured to be mounted on the muscle tissue or within an internal recess or slit within the muscle tissue. As described above, the exit portion may, for example, exhibit flexibility. This flexibility may be advantageous for (partial) insertion of the exit portion into the slit in the muscle tissue and / or may provide a level of conformance to the outer surface of the target site and corresponding anatomical structure. The slit in the muscle tissue may, for example, extend substantially perpendicular to the longitudinal axis defined by the elongate body such that the exit portion can extend at least partially into the slit. As such, the exit portion may be configured to be received within the slit and at least partially covered by the muscle tissue, resulting in an interference fit or positive lock. In some embodiments, the target muscle tissue is used for centrifugal signal amplification for prosthesis control.

[0045] Alternatively, the exit section may be configured to connect to the side of the nerve. This alternative is known in the art as end-to-side (ETS) nerve repair. In ETS nerve repair, the distal stump of the transected nerve is attached to the side of an uninjured donor nerve. ETS nerve repair provides a technique for repairing peripheral nerve injuries when a proximal nerve stump is unavailable or a significant nerve gap exists.

[0046] The maximum outer diameter (and / or inner diameter) of the exit section is preferably larger than the maximum outer diameter of the insertion section, but the cross-sectional area of ​​the opening of the insertion section may also increase with increasing longitudinal distance from the internal cavity or the central section. Thus, the insertion section may have an enlarged opening relative to the internal cavity, facilitating insertion of the corresponding nerve end into the nerve conduit. As described above with respect to the exit section, the insertion section and its opening may be formed as a rotationally symmetric shape along the longitudinal axis defined by the elongate body, preferably a conical, concave, funnel-shaped, trumpet-shaped, or parabolic shape. The increase in the opening is preferably gradual and uniform over the entire radial extension. For example, the opening may have a circular cross-section along the entire longitudinal length of each end section, with the diameter of the circular shape gradually increasing. Such a shape has the additional advantage that the placement of the nerve conduit during implantation is rotationally independent. However, other shapes may also be provided, such as an ellipsoid, in which case the (progressive) increase in opening is effected by an increase in at least one radial extension.

[0047] For example, the elongate body, either as a whole or as a central portion and / or exit portion and / or insertion portion, may contain a drug within its lumen or internal cavity, e.g., by a coating or by being incorporated into the material (e.g., wall) of the respective portion. The drug may be released over time and may, for example, promote nerve growth. Similarly, the lumen or internal cavity may have holes, pores, grooves, or particular geometric shapes or irregular surfaces, and / or may contain a filler material (e.g., hydrogel) to facilitate the insertion, retention, and / or growth of nerve ends.

[0048] In some embodiments, the outer surfaces of a plurality of the end portions (e.g., outlet portion and / or insertion portion) may further support or comprise an exterior structure having a particular geometric shape or an irregular surface shaped to form a retention surface, such as holes, grooves, or striations.

[0049] In particular, such an external structure may advantageously (i) increase contact between the surface of the end portion and the adhesive and / or (ii) form anchoring points for the adhesive. Such external structures are disclosed, for example, in patent application PCT / EP2022 / 061084, the contents of which are incorporated herein by reference in their entirety.

[0050] In some embodiments, the retention surface may be formed as at least one groove extending helically along a longitudinal axis defined by the elongate body, and the helical shape may define striations extending along the outer surfaces of a plurality of the end portions.

[0051] In some embodiments, the walls defining the elongate body may be generally discontinuous in the circumferential direction, allowing the elongate body to be opened and used to wrap around the nerve end. Such a configuration may be advantageous for handling and for facilitating nerve insertion at the insertion portion.

[0052] According to a particular embodiment, the nerve conduit is free of a central portion 14 and an internal cavity 16 .

[0053] The nerve conduit is preferably formed from a biocompatible, inert, bioimplantable, and / or biodegradable material. The material may be selected to provide a desired structural stability while substantially avoiding, or at least reducing, an inflammatory response in the patient being treated. For example, a biocompatible material may be selected that gradually degrades over time after implantation, but may initially provide sufficient structural support to properly repair nerve damage, ensuring that the nerve ends are properly and sufficiently stably connected, for example, during tissue movement.

[0054] Additionally, certain materials may be selected to promote or support nerve growth, for example, by providing, incorporating, or including a corresponding coating with one or more biologically active agents, including neurotrophic factors. Other examples of such biologically active surface functionalities include, but are not limited to, anti-inflammatory agents, immunosuppressants, and neuroprotective agents. The bioactive agent may be surface bound to and / or entrapped within the structure defining the elongate body (e.g., the wall described above). Alternatively, the bioactive agent(s) may be cross-linked to a gel matrix within the nerve conduit of the present invention or injected directly into the lumen of the nerve conduit.

[0055] Examples of such bioactive agents are cytokines, nerve growth factors, hyaluronic acid, tacrolimus, cyclosporin A, melatonin, vitamin B12, methylprednisolone, riluzole, taxol, cetuximab, brain-derived neurotrophic factor (BDNF), laminin, nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), glial growth factor (GGF), alpha fibroblast growth factor (α-FGF), and a preferred example is a bioactive agent with nerve regenerative properties (e.g., tacrolimus).

[0056] Preferably, the nerve conduit is made of a polymer-based material, preferably an elastomer, which has the advantage that multiple manufacturing methods can be applied and / or specific material properties can be obtained, for example, based on the polymer unit. In particular, the polymer-based material may be a biocompatible material that further has elastic properties so that the nerve conduit can adapt to the movements of the tissue surrounding the repaired nerve injury when implanted.

[0057] The nerve conduit may be formed from polymerized and / or crosslinked polymer units comprising an ester group component and an acidic ester group component, the ester group component preferably being a polyol and the acidic ester group component preferably being a polyacid.

[0058] The materials used for each section may be the same, which may facilitate easier manufacturing and may result in substantially uniform structural properties of the nerve conduit along its length. In this regard, when the nerve conduit system is constructed accordingly, biodegradation (and / or bioresorption) may occur in a predetermined or desired manner.

[0059] Preferably, the sections are integrally formed or formed from a single piece, for example by material bonding and corresponding structural integration. By providing the nerve conduit as a single piece, the robustness of the nerve conduit may be further improved, as separate connections between the sections are effectively avoided.

[0060] The nerve conduit is preferably formed by a 3D printing process. This is particularly advantageous when the nerve conduit material is polymeric. In this case, the material can be cured virtually instantly, for example, using (UV) light. This also allows for a level of precision that cannot be easily achieved by extrusion and / or dipping processes. In particular, the 3D printing process allows for the specific shape of each nerve conduit to be obtained. In this case, for example, the printing process can incorporate specific bioactive agents into the 3D structure according to a predetermined pattern, for example, into the mesh structure, and / or especially into the pockets or cavities formed by the 3D structure. This can result in further improved orchestration and support of nerve repair and / or more controllable material biodegradation.

[0061] The above objects are further achieved by the use of the nerve conduit described above for repairing, supporting and / or guiding nerve tissue, particularly for repairing peripheral nerve injuries. Furthermore, the nerve conduit may be used in combination with a medical adhesive.

[0062] According to another aspect of the present invention, there is provided a method for treating peripheral nerve injury, the method comprising: providing a nerve conduit as described above; inserting a nerve end of the injured nerve into the insertion portion of the nerve conduit and securing the nerve end to the nerve conduit; connecting the nerve conduit to a target site; Includes.

[0063] The step of fixing the end of the damaged nerve is preferably performed by applying a medical adhesive to the outside of the insertion section and / or by applying a medical adhesive through a corresponding opening into the opening. Furthermore, the connection to the target site is preferably performed on the exterior of the target site or by inserting at least a portion of the exit section into a slit in the target site. The target site is preferably a (denervated) muscle. The connection of the nerve conduit to the target site preferably includes applying a medical adhesive around the circumference of the exit section, at least at the interface with the target site (e.g., target tissue).

[0064] The medical adhesive according to the present invention may be any medical adhesive in the art. In some embodiments, the medical adhesive is capable of polymerizing when exposed to light. Prior to such polymerization, the medical adhesive may be fluid or viscous. Preferably, the medical adhesive is a light-curable compound. In some embodiments, the photoinitiator is sensitive to ultraviolet (UV) radiation. Preferably, the medical adhesive is or includes polyglycerol sebacate acrylate (PGSA) or PGSAA (e.g., as described in WO2021 / 078962).

[0065] According to another aspect of the present invention, a method for treating peripheral nerve injury comprises target muscle reinnervation (TMR). In some embodiments, the method maximizes the number of motor axons innervating the target muscle. In some embodiments, the method improves signal transmission from the target muscle. In some embodiments, the target muscle is used for efferent signal amplification for prosthesis control.

[0066] It should be understood that the nerve conduit of the present invention could also be used in similar applications, such as connecting the end of a tendon or ligament to a target bone or bone section, etc. In this embodiment, the end of the tendon or ligament would replace the nerve end in all of the above descriptions, the target site would include the bone or bone section, and the nerve conduit would be referred to as a tendon or ligament conduit.

[0067] More broadly, therefore, the present invention relates to a conduit (10) for connecting a tubular structure end (26) to a target site (28), the conduit (10) comprising an elongate body (12) formed by a wall (22), the elongate body (12) including a central portion (14) defining an internal cavity (16), and a plurality of end portions (18, 19) defining respective openings (20, 20') to the internal cavity (16) and disposed adjacent the central portion (14) at longitudinally opposed ends of the elongate body (12), one end portion (18) being an insertion portion configured for insertion of a respective tubular structure end (26) and the other end portion (19) being an exit end portion, the outer diameter of the wall defining the exit portion (19) being greater than the outer diameter of the wall defining the central portion (14). The tubular structure is selected from the group consisting of a nerve, a tendon, and a ligament. BRIEF DESCRIPTION OF THE DRAWINGS

[0068] The present disclosure will be more readily understood by reference to the following detailed description considered in conjunction with the accompanying drawings, in which: FIG. 1 shows a schematic diagram of a nerve conduit according to the present invention in a perspective side view. FIG. 2 shows a schematic representation of the nerve conduit according to FIG. 1 in longitudinal section. FIG. 3 shows a schematic diagram of a nerve conduit according to the present invention having an alternative exit portion in perspective side view. FIG. 4 shows a schematic side view of the nerve conduit according to FIG. FIG. 5 shows a schematic bottom view of the nerve conduit according to FIG. 3 looking towards the outlet portion. FIG. 6 shows a schematic representation of the nerve conduit according to FIG. 3 in longitudinal section. FIG. 7 shows a schematic cross-sectional view of a nerve conduit according to the invention in connection with a target tissue. FIG. 8 shows a schematic cross-sectional view of a nerve conduit according to the present invention in an alternative connection with the target tissue. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0069] The present invention will now be described in more detail with reference to the accompanying drawings, in which like elements are designated by the same reference numerals and repeated descriptions may be omitted to avoid redundancy.

[0070] FIG. 1 shows a schematic perspective side view of a nerve conduit 10 according to the present invention. The nerve conduit 10 includes an elongate body 12, which includes an insertion portion 18 and an exit portion 19. The insertion portion 18 and the exit portion 19 are located at opposite ends of the elongate body 12 in a longitudinal direction defined by the main extension of the elongate body 12. The insertion portion 18 is configured to receive a respective nerve end (not shown) (e.g., the proximal nerve end of an injured nerve). The nerve end is to be connected to a target site, e.g., target tissue, particularly a (denervated) muscle, via the exit portion 19. A central portion 14 is located directly adjacent to or contiguous with the insertion portion 18 and the exit portion 19. The central portion 14 defines an internal cavity 16, which is adapted to accommodate the nerve end received via the insertion portion 18.

[0071] As such, a continuous lumen or channel of the nerve conduit 10 is provided from the opening 20 in the insertion portion 18 to the opening 20' in the exit portion 19. As shown, the elongate body 12 is substantially formed by a tubular wall 22 that defines the lumen or channel of the nerve conduit 10. The wall 22 preferably has a substantially constant thickness (t) along the longitudinal extension of the elongate body 12.

[0072] The central portion 14 and its internal cavity 16 are formed as a substantially cylindrical portion having a constant inner diameter (Dc) (see FIG. 2) and outer diameter. This cylindrical portion is adapted to accommodate a received nerve end having a corresponding diameter. However, the outlet portion 19 extends radially in the longitudinal direction away from the central portion 14. That is, the outer diameter and corresponding cross-sectional area of ​​the opening 20' gradually increase toward the longitudinal end face of the outlet portion 19. As shown, the outlet portion 19 in this embodiment is formed as a conical or horn-like portion. This is advantageous for connection to the target site, for example, by increasing the connection surface and / or the surface for applying the medical adhesive. Furthermore, the conical shape can provide a conformal connection after the medical adhesive cures, which can provide improved retention or adhesion, at least in the longitudinal direction.

[0073] The insertion portion 18 also includes a radially extending opening 20 and its cross-sectional area, which is advantageous for the insertion of the nerve end portion into the nerve conduit and its accommodation within the internal cavity 16. However, the maximum radial extension (Df) of the insertion portion 18 does not exceed the maximum radial extension (Dt) of the exit portion 19, so that the functionality of each of the multiple end portions can be unambiguously determined by a medical professional or surgeon during implantation and surgery.

[0074] In Figure 2, the nerve conduit 10 according to Figure 1 is depicted in a cross-sectional side view. From this cross-section, it can be seen that the thickness (t) of the wall 22 is substantially the same throughout the elongate body 12. Furthermore, this view more clearly illustrates the radial increase of the openings 20, 20' in the insertion and exit sections 18 and 19, respectively. Thus, the maximum outer diameter (Dt) of the exit section 19 and the corresponding cross-sectional area of ​​the opening 20' are shown to exceed the outer diameters of the inner cavity 16 and central section 14 by a ratio of approximately 1.5:1 to 2.5:1.

[0075] However, compared to the longitudinal extent of the central portion 14, the exit portion 19 has a smaller longitudinal dimension, thereby providing a significant exit portion 19 that may function as a connection to the target site. However, its longitudinal extent is limited to maintain the overall dimensions within a physiologically acceptable range and provide improved structural stability of the nerve conduit 10 as a whole.

[0076] FIGS. 3-6 illustrate various views of an alternative embodiment of a nerve conduit 10 according to the present invention. Similar to the embodiment shown in FIGS. 1 and 2, this embodiment modifies the outlet section 19. Instead of a circumferentially continuous surface, the wall 22 defining the outlet section 19 is formed of radially extending arms 24. These arms 24 are preferably equally spaced apart circumferentially. At their junctions with the central section 14, the arms 24 extend radially at approximately 80-90 degrees relative to the longitudinal axis. As a result, the arms 24 form a substantially perpendicular radial flare relative to the wall of the central section 14. This is best seen in FIGS. 4 and 6. As can be seen from FIG. 6, the term "substantially perpendicular" includes a slight deviation, designated as angle (α). The angle (α) typically does not exceed 10°, preferably does not exceed 7°, more preferably does not exceed 5°, and even more preferably does not exceed 3°. As shown, the arms 24 extend without any steps or edges between the central portion 14 and the outlet portion 19 and form rounded connecting ends at the central portion 14 .

[0077] According to this embodiment, the outlet portion 19 is formed with ten arms 24. As best shown in FIG. 5, the arms 24 have a circumferential extension of approximately 20 degrees (β). While the number and circumferential extension of the arms can vary, the illustrated configuration has been found to allow particularly advantageous flexibility and connection to the target tissue while maintaining sufficient structural stability. The flexibility of the arms 24 may be further improved by optional tapered sections of the arms 24, as shown in FIG. 5 as intermediate sections between the free and connection ends of each arm 24.

[0078] The opening 20′ of the outlet portion 19, and thus its cross-sectional area, gradually increases in the embodiment according to FIGS. 1 and 2. On the other hand, the opening 20′ of the outlet portion 19 in the embodiment shown in FIGS. 3-6 substantially corresponds to the diameter of the inner cavity 16 of the adjacent central portion 14. This may improve the mechanical stability of the outlet portion 19 with respect to each arm 24, as shown, for example, in FIGS. 3, 5, and 6. However, it will be appreciated that the opening 20′ of the outlet portion 19 may gradually extend radially while maintaining sufficient structural stability, for example, by increasing the thickness of the wall 22 at least at the junction between the central portion 14 and the outlet portion 19. Alternatively, it is even possible to reduce this thickness of the wall 22 so as to provide flexibility in the orientation of the outlet portion 19.

[0079] 7 and 8 depict two alternative approaches to connecting a nerve conduit 10 according to the present invention to a target site (preferably target tissue 28).

[0080] According to the embodiment shown in Figure 7, the (proximal) nerve end 26 may be introduced into the nerve conduit 10 via a corresponding insertion portion 18 at the apical end and received by the central portion 14. The nerve end 26 may be secured to the nerve conduit 10 by medical adhesive or other means (e.g., suturing techniques). The exit portion 19 may then be connected to the target tissue 28 (e.g., a denervated muscle section) by applying medical adhesive 30 to the interface between the exit portion 19 and the target tissue 28. After connection and implantation, the nerve conduit 10 may promote axonal growth toward and into the target tissue 28, as shown.

[0081] In the embodiment according to FIG. 8, the nerve end portion 26 may be secured to the nerve conduit 10 in a similar manner. However, a slit, recess, or flap in the target tissue 28 may be provided instead of a local connection, i.e., at the outer surface of the target tissue 28. The slit, recess, or flap is configured to at least partially receive the exit portion 19 of the nerve conduit 10, as shown. The flap or slit provides initial fixation of the nerve conduit 10 to the target tissue 28. Further fixation may be provided by applying a medical adhesive 30 to the exit portion 19 and at its interface with the outer surface of the target tissue 28. However, in this embodiment, this application may be provided closer to the junction with the central portion compared to the embodiment provided in FIG. 7. Due to the conical or flared shape of the exit portion 19, the medical adhesive 30 may still provide sufficient retention or adhesion force, such that the nerve conduit 10 may be securely connected to the target tissue.

[0082] It will be apparent to those skilled in the art that these embodiments and items merely illustrate examples of multiple possibilities. Therefore, the embodiments illustrated herein should not be understood as limiting these features and configurations. Any possible combination and configuration of the described features can be selected in accordance with the scope of the present invention.

[0083] [List of reference numbers] 10 Nerve conduit 12 Long and slender body 14 Central part 16 Inner cavity 18 Insertion 19 Exit part 20, 20´ opening 22 Wall 24 Arm 26 Nerve Endings 28 Target tissue 30 Medical Adhesives [Brief explanation of the drawings]

[0084] [Figure 1]1 shows a schematic diagram of a nerve conduit according to the present invention in perspective side view. [Figure 2] FIG. 2 shows a schematic representation of a nerve conduit according to FIG. 1 in longitudinal section. [Figure 3] 1 shows a schematic diagram of a nerve conduit according to the present invention having an alternative exit portion in a perspective side view. [Figure 4] FIG. 4 shows a schematic side view of a nerve conduit according to FIG. [Figure 5] FIG. 4 shows a schematic bottom view of the nerve conduit according to FIG. 3, looking towards the outlet portion. [Figure 6] FIG. 4 shows a schematic representation of a nerve conduit according to FIG. 3 in longitudinal section. [Figure 7] 1 shows a schematic cross-sectional view of a nerve conduit according to the present invention in connection with a target tissue. [Figure 8] 1A and 1B show schematic cross-sectional views of a nerve conduit according to the present invention in alternative connection states with target tissue.

Claims

1. A nerve conduit (10) for connecting a nerve end (26) to a target site (28), comprising: an elongated body (12) formed by a wall (22); The elongated body (12) a central portion (14) defining an internal cavity (16); a plurality of end portions (18, 19) defining respective openings (20, 20') to the internal cavity (16) and disposed adjacent the central portion (14) at longitudinally opposite ends of the elongated body (12); Including, one of said end portions (18) being an insertion portion adapted to receive a respective nerve end portion (26); The other end portion (19) is the exit portion of the nerve end, A nerve conduit (10) wherein the outer diameter of the wall defining the outlet portion (19) is greater than the outer diameter of the wall defining the central portion (14).

2. 2. The nerve conduit (10) of claim 1, wherein the maximum outer diameter of the wall defining the outlet portion (19) is 1 mm to 10 mm greater, preferably 2 mm to 6 mm greater, than the outer diameter of the wall defining the central portion (14).

3. 3. The nerve conduit (10) of claim 1 or 2, wherein the ratio between the maximum outer diameter of the wall (22) defining the outlet portion (19) and the outer diameter of the wall (22) defining the central portion (14) is 1.1:1.0 to 8.0:1.

0.

4. The nerve conduit (10) according to any one of claims 1 to 3, wherein the diameter of the inner cavity (16) is between 1 mm and 12 mm, preferably between 1.5 mm and 6.5 mm.

5. The nerve conduit (10) according to any one of claims 1 to 4, wherein the ratio between the longitudinal extension of the outlet portion (19) and the longitudinal extension of the central portion (14) is between 0.1:1.0 and 0.6:1.

0.

6. The nerve conduit (10) according to any one of claims 1 to 5, wherein the ratio between the maximum outer diameter of the outlet portion (19) and the longitudinal extension of the central portion (14) is between 1.5:1.0 and 2.5:1.

0.

7. A nerve conduit (10) according to any one of claims 1 to 6, wherein the maximum outer diameter of the wall (22) defining the outlet portion (19) is greater than the outer diameter of the wall (22) defining the insertion portion (18).

8. A nerve conduit (10) according to any one of claims 1 to 7, wherein the wall (22) of the elongate body (12) is a single tubular wall having a substantially continuous thickness along the circumferential and longitudinal directions of the elongate body (12).

9. The nerve conduit (10) of any one of claims 1 to 8, wherein the inner and outer diameters of the central portion (14) are substantially continuous along the length of the elongate body (12).

10. A nerve conduit (10) according to any one of claims 1 to 9, wherein the cross-sectional area of ​​the opening (20') of the outlet portion (19) is greater than the cross-sectional area of ​​the inner cavity (16) of the central portion (14).

11. A nerve conduit (10) according to any one of claims 1 to 10, wherein the cross-sectional area of ​​the opening (20') of the outlet portion (19) and / or the outer diameter of the wall (22) of the outlet portion (19) increases longitudinally away from the central portion (14).

12. the outlet portion (19) and the corresponding opening (20') are rotationally symmetrical about a longitudinal axis defined by the elongate body (12); 12. The nerve conduit (10) of claim 11, wherein the shape is preferably selected from the group consisting of a cone shape, a concave shape, a funnel shape, a trumpet shape, or a paraboloid shape.

13. 13. The nerve conduit (10) of claim 11 or 12, wherein the wall (22) defining the outlet portion (19) extends radially from the wall (22) defining the central portion (14) at an angle of from 40 degrees to less than 180 degrees relative to a longitudinal axis defined by the elongate body (12), more preferably at an angle of from 40 degrees to 150 degrees, even more preferably at an angle of from 40 degrees to 120 degrees, and even more preferably at an angle of from 40 degrees to 90 degrees.

14. The nerve conduit (10) of any one of claims 1 to 13, wherein the wall (22) defining the outlet portion (19) is circumferentially continuous.

15. A nerve conduit (10) according to any one of claims 1 to 13, wherein the wall (22) defining the outlet portion (19) is formed as a plurality of arms (24) extending radially outward and spaced apart from one another in the circumferential direction.

16. 16. The nerve conduit (10) of claim 15, wherein each of the plurality of arms (24) has a circumferential extension of from 10 to 150 degrees, preferably from 10 to 30 degrees.

17. 17. The nerve conduit (10) of claim 15 or 16, wherein the arms (24) are equally spaced apart circumferentially.

18. A nerve conduit (10) according to any one of claims 15 to 17, wherein the wall (22) is formed of 2 to 16 arms (24), preferably 6 to 12 arms (24).

19. The nerve conduit (10) of any one of claims 15 to 18, wherein the plurality of arms (24) include radially tapered portions.

20. The nerve conduit (10) according to any one of the preceding claims, wherein the outlet section (19) is adapted to be attached to / connected to muscle tissue.

21. 21. The nerve conduit (10) of claim 20, wherein the outlet portion (19) is configured to be mounted on the muscle tissue or within an internal recess or slit in the muscle tissue.

22. A nerve conduit (10) according to any one of claims 1 to 21, wherein the outlet portion (19) has a greater surface roughness at the outer surface of the wall (22) compared to the outer surface of the wall (22) defining the central portion (14).

23. The nerve conduit (10) of any one of claims 1 to 22, wherein the cross-sectional area of ​​the opening (20) of the insertion portion (18) increases with increasing longitudinal distance from the internal cavity (16).

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