WO2025078007A1

WO2025078007A1 - Nerve conduit

Info

Publication number: WO2025078007A1
Application number: PCT/EP2023/078268
Authority: WO
Inventors: Marie MALAFOSSE; Estelle COLLIN; Elise Devries
Original assignee: Tissium SA
Current assignee: Tissium SA
Priority date: 2023-10-11
Filing date: 2023-10-11
Publication date: 2025-04-17
Anticipated expiration: 2026-04-11
Also published as: WO2025078649A1

Abstract

The invention relates to nerve conduits for connecting a lesioned nerve end to a target site. In particular, the invention relates to nerve conduits supporting repair of a nerve lesion and motor control and/or reducing risk of the development of a neuroma at the lesioned nerve end. Accordingly, a nerve conduit (10) for connecting a nerve end to a target site is suggested, comprising an elongate body (12) formed by a wall (22) defining an inner cavity (16) and comprising a central portion (14), wherein the inner cavity (16) extends through the central portion (14), and two end portions (18, 19) defining respective openings (20, 21) to the inner cavity (16), wherein one end portion (18) is an insertion portion configured for inserting a respective nerve end (26) and the other end portion (19) is a nerve end outlet portion. According to the invention, the end portions (18, 19) are arranged such that the cross-sections of the openings (20, 21) are oriented at an angle to each other.

Description

Nerve conduit

Technical field

The invention relates to a nerve conduit for connecting a lesioned nerve end to a target site. In particular, the invention relates to nerve conduits supporting repair of a nerve lesion and motor control or sensory function and/or reducing risk of the development of a neuroma at the lesioned nerve end.

Technological Background

Upon injury of a person, tissue damage may involve one or more nerve lesions of the peripheral nerve system resulting in a partial sensory loss and/or impaired motor skills. Such injuries involving nerve damage particularly occur in the lower limb and upper extremities, such as a hand of a person, such that a person may experience a loss e.g. in tactile or haptic feedback and/or may have difficulties in controlling fine motor skills in the injured region, if the nerve lesion is not treated properly.

Current treatments of nerve lesions include coaptation of the nerve ends by various suturing techniques so as to provide a connection between the respective nerve ends in an essentially tensionless manner. In case a more severe defect is present, wherein the nerve ends are not directly adjacent to each other, a reconstruction may be required to overcome a corresponding gap. A reconstruction may be provided e.g. by an autologous or allogenic nerve graft. Alternatively, a reconstruction may be performed by providing a tubular structure so as to provide a nerve guide in the form of an inner lumen providing a directional path during neurogenesis. Such tubular structure, which accommodates the respective nerve ends, may be provided e.g. by autologous or allogenic venous structures or by artificially manufactured nerve conduits made of a biocompatible material. The use of a tubular structure may furthermore facilitate the repair of the lesion irrespective of the presence of a gap, e.g., by providing further mechanical support and structural stability, providing a tensionless repair, reducing an inflammatory response to the site of the lesion, and/or limiting the extent of fibrous tissue development.

However, in a clinical situation wherein the distal nerve end is lost, e.g. due to amputation or tissue removal, such connection between nerve ends is not possible. This not only complicates the treatment for at least partially restoring motor control or sensory function, but may also result in an increased risk of a neuroma, which may develop at the terminal end of a sectioned nerve. Such neuromas may develop from disorganized axons growing beyond the severed epineural sheath at the end of a transected nerve in an attempt to reinnervate distal muscle or skin, e.g. following severe trauma or surgery, wherein a sprouting of axons may form a bundle of disorganised and hyperexcitable nerve tissue (called neuroma) that does not have the original nerve structure. Neuromas are typically associated with neuropathic pain, numbness and tingling and may also interfere with the rehabilitation, the functional recovery and a sensory deficit. Treatments or attempts in prevention of neuromas may be based on suturing the proximal end of a lesioned nerve to a distinct motor nerve of an intact newly denervated muscle. The suturing technique may at least partially restore muscle control while reducing the risk of neuroma development.

Other surgical alternatives have been proposed to repair peripheral nerve injuries where the distal nerve stump is unavailable or a significant nerve gap exists, or when a nerve is transected too far from target organ or muscle or skin. For example, the End-to-side (ETS) nerve repair in which the distal stump of a damaged nerve is coapted to the side of an uninjured nerve (Lykissas, 2011, World Journal of Orthopaedics, vol. 2, no. 11, 102-106).

Another procedure called Targeted muscle reinnervation (TMR) is a surgical nerve-transfer procedure. According to TMR, residual nerves from the amputated limb are transferred to new muscle targets. As part of the nerve transfer, the target muscles are separated from their native motor nerve input so that the newly transferred nerve can reinnervate them (Bergmeister et al., 2021, Hand Clin, 37(3) :415- 424; Janes et al., 2021, Hand Clin, 37(3):345-359).

Summary of the invention

Starting from the known prior art there is a need to further facilitate the repair of nerve lesions, more particularly after amputation, resulting in nerve endings that can form neuromas or cause phantom limb pain.

According to the invention it has been recognized that the connection of a proximal or distal nerve end of a nerve, in particular a lesioned nerve, to target muscle tissue or target organ or to a side of a target nerve may be difficult and/or may not provide a satisfying result, for example to restore (partial) motor control and/or sensory function and/or avoid the development of a neuroma and/or to result in regeneration of the injured nerve. Suturing the nerve end may result in undesired tissue damage and/or may complicate appropriate orientation of the terminal end of the proximal nerve end, such that the intended restoration of motor control or nerve coaptation is impaired. Furthermore, in the case of connection to target muscle tissue, suture technique into muscle tissue may complicate efficient securing of the nerve end. Alternative fixation methods using e.g. the application of a medical adhesive have been found to have limited success rates due to the small surface available for the application. Required curing times furthermore may result in a loss of proper positioning of the respective nerve end and/or an overall loss of proper attachment.

It is hence an object of the present invention to further facilitate the repair of nerve lesions and, in particular, to facilitate proper securing and positioning of nerve ends to a target tissue (e.g. muscle, bone or skin) or target organ or side of target nerve (collectively named target site). It may be a particular object of the present invention to facilitate the connection of a proximal nerve end to a target muscle or skin in an effective and efficient manner for the restoration of motor control and/or restoration of sensory feedback and/or preventing of neuroma development. It may be another object of the present invention to facilitate the connection of a proximal nerve end to side of a target (uninjured) donor nerve in effective and efficient End-to-side (ETS) nerve repair method. It may be another object of the present invention to facilitate the connection of nerve ends to organs, for example transplanted organs (e.g. heart, liver and kidney). The nerve conduit according to the invention enables sufficient support of the lesioned nerve end in its natural longitudinal extension.

Said object is achieved by the independent claims. Preferred embodiments are depicted in the dependent claims, the description, and the Figures.

Accordingly, a nerve conduit for connecting a nerve end, e.g. a lesioned nerve end, to a target site (e.g. target tissue or target organ or side of target nerve) is suggested, comprising an elongate body that is formed by a wall defining an inner cavity. The elongate body comprises a central portion, wherein the inner cavity extends through the central portion, and two end portions defining respective openings to the inner cavity, wherein one end portion is an insertion portion configured for inserting a respective nerve end and the other end portion is a nerve end outlet portion. According to the invention, the end portions are arranged such that the cross-sections of the openings are oriented at an angle to each other.

The nerve conduit may generally comprise a tubular shape, wherein the wall defines an inner lumen or inner cavity with openings so as to provide a continuous channel or through-hole. In other words, the wall forms a longitudinally extending elongated body, wherein a (fluid) connection or communication between the exterior and the inner cavity is provided via the respective openings of the end portions prior to the insertion of the nerve end and the connection of the nerve conduit to the target site.

By means of the angle between the cross-sections of the openings, the planes of the end faces of the elongate body are also arranged at an angle to each other, such that they are not arranged in parallel. Thereby, it is advantageously provided that a nerve end being accommodated within the inner cavity, preferably within the central portion via the insertion portion, may be connected to a target site, wherein the angle at the outlet portion provides improved mechanical stability for the attachment of the nerve conduit to the target site. For example, the outlet portion may be provided as a portion of the elongate body extending at an angle relative to the central portion or may be provided as a truncated portion of the elongate body. Thereby, the corresponding end face of the elongate body at the outlet portion may define a supporting surface providing a level of structural support at least partially in a direction essentially perpendicular to a direction defined by the insertion portion and/or central portion.

In order to facilitate at least partial restoration of motor control and/or restoration of sensory feedback and/or preventing of neuroma development, the outlet portion is preferably configured for connection to muscle tissue. The muscle tissue may e.g. be a denervated target muscle, which is adjacent to or in proximity of the respective lesioned nerve end and which facilitates motor control of the injured anatomical structure, e.g. a arm. Accordingly, the outlet portion may be particularly configured for attachment on top of the muscle tissue. Alternatively, the muscle tissue may provide an effective tissue for reducing the occurrence of neuroma development, wherein a burying of a respective nerve end within the muscle may be particularly advantageous. In such arrangement, the outlet portion may e.g. be inserted within an inner recess or slit within the muscle tissue.

Alternatively, the outlet portion may be configured for connection to side of nerve. This alternative is well known in the art as end-to-side (ETS) nerve repair, in which the distal stump of a transected nerve is coapted to the side of an uninjured donor nerve. It offers a technique for repair of peripheral nerve injuries where the proximal nerve stump is unavailable or a significant nerve gap exists.

Accordingly, the angle at the outlet portion may not only provide an improved conformity to the target anatomic portion. In particular, the angle enables that a guiding surface may be provided for directing the nerve end towards the outlet portion via the central portion, wherein the angle enables that the nerve end may be connected to the target site at a corresponding angle. The nerve end may hence be connected e.g. to adjacent target site in essentially a side by side manner without requiring the lesioned nerve end to be bent.

In order to facilitate the connection to the target site, the angle between the cross-sections is preferably between 30 degrees and 90 degrees. In particular, the angle between the cross-sections may be between 50 degrees and 90 degrees, or between 70 degrees and 90 degrees or said angle may be about 90 degrees such that the cross-sections of the openings are oriented essentially perpendicular to each other. As described above, the angle may not only provide an improved conformability to the target site, but may also reduce the load bearing on the nerve conduit and the lesioned nerve end accommodated therein. Furthermore, the preferred angle may facilitate the attachment to the target site without requiring the nerve end to be bent. In this regard the outlet portion may e.g. be provided as a truncated portion of the elongate body, wherein a plane of the end face of the elongate body at the level of the outlet opening may e.g. be between 30 degrees and 70 degrees (e.g. 50 degrees) relative to the plane or cross-section defined by the opening of the insertion portion. While a larger angle may also be provided by a corresponding truncation, an angle between 70 degrees (or less than 70 degrees) and 90 degrees is preferably formed by an extension of the elongate body at an angle relative to the central portion. Such larger angle may furthermore facilitate an End-to-side attachment of the nerve end to the target site, wherein an essentially 90 degrees angle or perpendicular orientation is particularly advantageous.

Preferably, the insertion portion is arranged adjacent to the central portion and the outlet portion is arranged at an opposing side of the central portion. Such arrangement adjacent to the central portion is advantageous for the insertion of the nerve end and particularly facilitates the insertion and/or accommodation of the nerve end in the central portion. The insertion portion and the central portion may e.g. define a common longitudinal axis of the elongate body, such that the nerve end may be accommodated in an extended and in an essentially continuous manner.

The arrangement of the outlet portion at the opposing side of the central portion facilitates the conducting of the nerve end towards the outlet portion via the central portion. However, the outlet portion is not necessarily adjacent to the central portion, but may e.g. be arranged at an intermediate portion of the elongate body connecting the central portion to the outlet portion.

To facilitate the orientation of the cross-sections or planes of the openings at an angle to each other, the elongate body may comprise a transition portion adjacent to the central portion and forming the outlet portion, wherein the transition portion defines a curvature of the elongate body and/or extends at an angle to the central portion. The transition portion may hence form an intermediate portion between the outlet opening and the central portion, wherein the transition portion comprises the outlet portion at the side facing away from the central portion.

Due to the curvature or angle defined by the transition portion, which preferably also defines the angle between the cross-sections or planes of the insertion portion and the outlet portion, the outlet opening and insertion opening are not arranged at longitudinally opposing ends of the elongate body. Such arrangement, however, may be provided in a configuration wherein the outlet portion is formed as a truncated portion of the elongate body.

In order to facilitate growth of the lesioned nerve end towards the target site, the cross-section of a portion of the inner cavity defined by the transition portion may gradually increase in a direction away from the central portion. For example, the wall may be formed and dimensioned such that the crosssection of the inner cavity may gradually increase starting from the central portion towards the outlet portion. Thereby, it is ensured that the cross-section or diameter of the transition portion is always larger than the diameter of the central portion, such that growth of the nerve end is not impaired and is facilitated towards the outlet portion.

Alternatively, it may be provided that the wall defining the transition portion at least partially converges towards the outlet portion. Accordingly, the transition portion may define a gradually reducing cross-section in a direction away from the central portion, which may be configured to direct the nerve end growth towards or beyond the outlet portion, e.g. to reduce the occurrence of neuroma without restoring functionality of the nerve end. For example, a wall portion of the transition portion may extend at an angle relative to the central portion while an opposing wall portion extends essentially linearly. Thereby, it may also be provided that the longitudinal extension of the transition portion, relative to the central portion and/or insertion portion, may be reduced. In particular, the outlet portion and/or the transition portion may comprise a conical or funnel shape.

While the opening of the outlet portion may have a variety of shapes, e.g. being circular, the outlet opening is preferably formed as an ellipsoid. Such ellipsoid shape has been found to be advantageous for the attachment to the target site by providing e.g. an improved conformity to the longitudinal extension of nerve. In other words, the ellipsoid is preferably arranged such that the largest diameter extends in a direction of growth of the nerve end. Moreover, the ellipsoid shape of the opening of the outlet portion may facilitate nerve growth towards the target site.

Preferably, a ratio between the largest diameter and the smallest diameter of the opening of the outlet portion is between 1:1 to 4:1, more preferably between 1.1:1 to 2.5:1. Such ellipsoid extension of the opening has been found to be particularly advantageous to facilitate growth towards the target site. Furthermore, such extension may provide an improved conformity to the extension of the target site, e.g. an uninjured nerve end or muscle tissue.

The smallest diameter of the opening of the outlet portion may essentially correspond to a diameter of the inner cavity defined by the central portion. Since the diameter of the inner cavity may be adapted to the diameter or dimensions of the lesioned nerve end to be accommodated, the opening hence provides no restriction to the growth of the nerve end.

The wall of the elongate body is preferably a single tubular wall comprising an essentially continuous thickness. Accordingly, any variations in cross-sectional area of the inner cavity and/or the openings are preferably defined by the extension and dimensioning of the wall rather than by varying thicknesses. This provides an improved structural stability and integrity for the elongate body as a whole and may also provide similar material properties, such as a level of flexibility or rigidity, along the (longitudinal) extension of the elongate body and may hence also facilitate handling during implantation of the nerve conduit. In addition, the continuous thickness may facilitate manufacturing and may reduce the total amount of material required for the nerve conduit. Although a variety of shapes may be provided for the central portion, the inner cavity defined by the central portion preferably comprises a continuous cross-section. In particular, the central portion may comprise an essentially cylindrical shape. The central portion may hence form an essentially straight portion for the nerve end being accommodated therein, defining a longitudinal axis. Thereby, accommodating and support for the nerve end may be improved, in particular, when the diameter of the inner cavity is adapted for the corresponding diameter of the nerve end to be connected to the target site. The constant inner diameter may furthermore provide an improved guiding surface for axonal growth during nerve regeneration. Preferably, the central portion comprises a continuous wall thickness along the circumference and in the longitudinal direction, such that the inner diameter and outer diameter of the central portion are preferably essentially continuous.

The cross-section of the inner cavity of the central portion and preferably the opening of the insertion portion is preferably of circular or ellipsoid shape. A tubular or cylindrical shape may provide improved structural stability and may prevent sharp bends or kinking during tissue movement, i.e. compression or extension. The tubular shape may accordingly also provide that a homogeneous structure is provided, which reacts in a predefined manner along the entire central portion when forces act upon the central portion, e.g. upon impact.

To accommodate a corresponding diameter of the nerve end, the diameter of the inner cavity defined by the central portion is preferably from 1 mm to 12 mm, more preferably from 1,5 mm to 6,5 mm. Thereby, the nerve conduit is particularly advantageous to accommodate nerve ends e.g. in the upper or lower extremities of a patient and for restoration of fine motor control and/or restoration of sensory feedback and/or preventing of neuroma development.

Hence, the inner cavity may be adapted and dimensioned to accommodate a corresponding diameter of a nerve or nerve end. For example, the diameter of the inner cavity may be between 1 mm and 12 mm, depending on the diameter of the nerve (end). To accommodate smaller nerves, the diameter of the inner cavity may e.g. be between 1,5 mm and 6,5 mm. Such dimensions have been found to be particularly advantageous to provide a required support for the nerve end and/or nerve growth or repair. The extension of the wall and inner cavity is above 2.5mm, preferably between 5 mm and 30 mm, preferably between 5 mm and 25 mm, in the longitudinal direction, which may be defined by the central portion and/or the insertion portion, and/or along an overall pathway defined by the inner cavity. Such dimensions may furthermore be particularly advantageous to bridge nerve defects or lesions. The desirable or predefined dimensions may thereby provide a continuous guiding structure for the internal anatomical structure that is particularly advantageous to direct and/or facilitate neurogenesis and/or prevent neuroma.

According to one embodiment, to facilitate growth of an accommodated nerve end and its connection to the target site, a cross-sectional area of the opening of the outlet portion is preferably larger than the cross-sectional area of the inner cavity of the central portion. As described above in view of the transition portion, such increase may ensure that a diameter of the opening of the outlet portion is larger than, or equal to, the diameter of the central portion, such that inadvertent impairment of growth, e.g. inadvertent blocking or directional biasing of the nerve end, is avoided to the largest possible extent. Accordingly, such increase in cross-sectional area of the outlet opening is preferably provided by a corresponding increase of the cross-sectional area of a transition portion extending from the central portion, i.e. when a portion of the wall defining the transition portion is not converging. By providing the enlarged cross-sectional area of the outlet opening, an outer diameter of the wall defining the outlet portion may be larger than an outer diameter of the wail defining the central portion, preferably also larger than the other portions of the elongate body.

Depending on the configuration of the nerve conduit, e.g. having a curvature or having a truncated elongate body at the outlet portion, the provision of an appropriately enlarged outlet opening may have the advantage that the nerve end may be observed or inspected after insertion into the insertion portion and the inner cavity. In particular, the respective nerve end may be received in the inner cavity via the corresponding insertion portion and may extend through the inner cavity towards the corresponding outlet portion. Although the nerve end preferably terminates at the junction between the outlet opening or transition portion and the inner cavity defined by the central portion, the nerve end may alternatively be inserted up to the outlet portion in such manner that the nerve end terminates at the outlet portion, such that the nerve end may be better observed via the outlet portion. Accordingly, proper insertion of the nerve end may be monitored prior to the connection to the target site, and optional application of a medical adhesive.

More preferably, the cross-sectional area of the opening of the outlet portion may increase in a direction away from the central portion. Such extension may result in an improved adaptability to the anatomy of the target site, in particular when the outlet opening is formed as an ellipsoid.

The largest diameter of the opening of the outlet portion may be between 1 mm and 23 mm, preferably between 1.5 mm and 17 mm, larger than the diameter of the inner cavity defined by the central portion. The largest diameter of the outlet portion may simply correspond to the largest diameter of the opening in case of a circular shape, but may particularly correspond to the largest diameter of the opening having an ellipsoid shape while the inner cavity defined by the central portion preferably comprises a circular cross-section. Thereby, an improved directional growth may be facilitated in the direction corresponding to the extension of the ellipsoid shaped opening.

A cross-sectional area of the opening of the outlet portion is preferably larger than the cross-sectional area of the opening of the insertion portion. Thereby, directional growth of the nerve end towards the outlet portion and opening thereof may be facilitated and handling of the nerve conduit is facilitated by accordingly indicating the insertion portion and the outlet portion based on the respective dimensioning of the cross-sectional areas. To facilitate attachment of the outlet portion of the nerve conduit to the target site, an outer diameter of the wall defining the outlet portion is preferably larger than an outer diameter of the wall defining the central portion, preferably also larger than the other portions of the elongate body. Accordingly, a flange portion may be formed by the wall at the outlet opening, wherein said flange portion extends radially outward from the outlet opening. In particular, the flange portion may extend essentially in a plane defined by a cross-section of the outlet opening.

In other words, the wall may extend radially outward from the outlet opening. Preferably, the wall may extend essentially perpendicular to a central axis defined by the elongate body at the level of the outlet opening or corresponding end face of the elongate body. However, in case of a truncated portion of the elongate body forming the outlet portion, said angle may be accordingly adapted, such that the extension of the radially outward protruding wall portion is essentially in a plane defined by the end face of the wall of the outlet portion.

The flange portion at the outlet opening is essentially perpendicular to the cross-section of the outlet opening. As used herein, the expression "essentially perpendicular" includes a slight deviation from perpendicular (90°), wherein said deviation preferably does not exceed 10°, preferably it does not exceed 7°, more preferably it does not exceed 5°, even more preferably it does not exceed 3°. In some embodiments, the deviation angle is in the range of 0,5° to 10°, preferably in the range of 1° to 5°, more preferably in the range of 1,5° to 3°.

According to another embodiment, the flange portion may extend along a curved surface defined by an angle to a central axis defined by the elongate body at the level of the outlet opening or corresponding end face of the elongate body, which decreases in the radial direction. This embodiment may be particularly adapted to end to side use.

While an essentially perpendicular arrangement of the flange portion is particularly advantageous for the attachment of the nerve conduit to a target site, a lower angle, e.g. between 40 degrees and 70 degrees or 45 degrees and 65 degrees, may also be provided to provide a more gradual increase of the outer diameter at the outlet portion. Accordingly, a variety of angles may be provided (including angles above 90 degrees), wherein the angle may be dependent on a predefined or required longitudinal and maximal radial extension of the outlet portion relative to the central portion or inner cavity thereof. Such longitudinal and radial extension may be dependent on the target site and surrounding tissue and, in particular, the contacting or retention surface required for appropriate connection to the target site.

The wall defining the flange portion is preferably contiguous with the adjacent wail portion defining the outlet portion or transition portion and may be rounded at the corresponding interface. Thereby, the wall portions may be aligned or be in flush arrangement and are preferably free of steps or edges at the corresponding outer surface. By means of the flange portion, connection to the target site is facilitated due to the accordingly enlarged surface area. This may not only increase the potential securing force between the outlet portion and the target site, but also facilitates correct application e.g. of a medical adhesive by indicating and/or delimiting a more prominent target application surface forthe medical adhesive. The enlarged end surface provided by the flange portion furthermore renders it easier to properly position and orientate the nerve conduit and the nerve end accommodated therein with regard to the target site, e.g. a denervated muscle or muscle section (e.g. muscle flap), a nerve side, bone or an organ, while providing increased stability and support upon placement of the nerve conduit.

The provision of the flange portion may further facilitate identification of the respective end portions, such that the surgeon readily understands which end portion is to be used for insertion of the nerve end to accommodate the nerve end within the insertion portion and inner cavity. In this regard, the nerve end of the respective nerve lesion may be secured to the nerve conduit after proper insertion of the nerve end into the corresponding insertion portion, wherein it may be ensured that a medical adhesive or other means used for securing the respective nerve end to the nerve conduit has been properly applied. The nerve end may hence be fixed or attached to the nerve conduit prior to connecting the nerve conduit to the target site.

Furthermore, the wall portion (or material thereof) defining the flange portion and/or the outlet portion may furthermore be flexible so as to provide an improved level of adaptability to the anatomy of the target site. In this regard, according to a preferred embodiment, "target site" according to the present invention usually means a tissue, e.g. muscle, preferably denervated muscle or muscle section (e.g. muscle flap), a nerve side, a bone or an organ. In some aspect, the target muscle tissue is used for efferent signal amplification for prosthesis control. Hence, the flexibility of the flange portion may be particularly advantageous for the application on top of an uninjured nerve or muscle tissue by providing a level of adaptability to the outer surface and corresponding anatomy of the target site.

By the same token, the flexibility may be advantageous for (partial) insertion of the flange portion and/or outlet portion into a slit of muscle tissue, wherein a slit of the muscle tissue may e.g. extend essentially perpendicular to the plane of the outlet opening, such that at least the flange portion may at least partially extend into the slit. The flange portion may hence alternatively be configured to be accommodated within the slit and be at least partially covered by the muscle tissue, such that an interference fit or positive locking may be provided.

The flange portion preferably at least partially surrounds the outlet opening. In particular, the flange portion may entirely surround the outlet opening or, preferably, at least half of the circumference of the outlet opening. A configuration of the flange portion entirely surrounding the outlet opening has the advantage that this provides a continuous support surface in the circumferential direction, wherein no gaps are provided along the circumference. Such configuration may be advantageous for handling purposes and to improve structural stability. Furthermore, such configuration may improve a sealing functionality of the outlet portion towards the exterior with regard to axonal growth of the nerve end accommodated in the inner cavity. By the same token, such configuration essentially avoids that surrounding tissue may impair the nerve growth.

The flange portion may comprise an essentially rectangular portion, preferably having rounded edges. The orientation of the rectangular shape may advantageously correspond to the orientation of the extension of the outlet opening, in particular in case of an outlet opening having an ellipsoid shape. Accordingly, the largest extension of the rectangular shape may correspond to the extension of the largest diameter of the ellipsoid outlet opening. Thereby, the dimensioning of the flange portion may be reduced while ensuring that an essentially continuous flange portion is provided along the circumference of the outlet opening. The rounded edges may furthermore reduce inadvertent friction or engagement with the target site and/or may further reduce the dimensioning of the flange portion and conformity to the ellipsoid shape of the outlet opening.

The flange portion may also comprise a triangular portion being oriented in a direction towards the insertion portion. Such triangular portion may present the advantage that a level of flexibility of the flange portion may be provided, such that an improved adaptability and/orconformability of the flange portion to the target site may be achieved. Furthermore, the arrangement of the triangular portion, which may accordingly extend essentially parallel to a longitudinal axis defined by the central portion and/or insertion portion and in a direction of the insertion portion, enables that the insertion and handling of the nerve end are not impaired by the flange portion, since the triangular portion may be dimensioned such that it does not extend beyond the insertion portion and such that its radial dimensions relative to the insertion portion and central portion are reduced due to the triangular shape. The triangular portion may particularly extend from a rectangular portion of the flange portion.

The flange portion may comprise an essentially circular or ellipsoid portion. The orientation of the shape may advantageously correspond to the orientation of the extension of the outlet opening, in particular in case of an outlet opening having an ellipsoid shape. Accordingly, the largest extension of the ellipsoid shape may correspond to the extension of the largest diameter of the ellipsoid outlet opening.

The flange portion outer surface may comprise one or more retention surfaces, e.g. at least partially external structures with particular geometries or surface irregularities, which are configured for securing a medical adhesive to the flange portion. According to special embodiment, the retention surfaces that may be formed as a plurality of (e.g., ellipsoid or circular) holes, e.g. 2 to 20 holes, wherein the holes may advantageously be (equally) spaced apart on the flange portion.

In an alternative embodiment, the wall defining the flange portion may be formed as a plurality of radially outward extending arms that are spaced apart from each other in the circumferential direction. Accordingly, gaps may be provided in a circumferential direction, such that the respective arms may form individual contacting surfaces with the target tissue. Thereby, an improved level of flexibility and adaptability to the anatomy of the target tissue may be provided while at the same time a medical adhesive may be applied in a manner, wherein both the amount of edges and the connecting surface of the target tissue covered by the medical adhesive may be increased. Furthermore, the provision of individual arms may facilitate insertion of the end surface of the flange portion into a slit or recess of the target tissue, if such connection is preferred for the respective treatment and/or anatomy of the target tissue.

Preferably, each of the arms has a circumferential extension of between 10 degrees and 150 degrees. Such circumferential extension may provide a sufficient structural stability and connective force while providing an advantageous level of flexibility and adaptability to the target tissue. The circumferential extension may be adapted to the number of arms and/or predefined gap extensions.

The arms are preferably equally spaced apart from each other in the circumferential direction. Such spacing also provides that a connection to the target tissue may be provided in a homogeneous manner.

However, other arrangements of the arms may also be provided, wherein pairs or a multiple of adjacent arms are arranged along a respective radial axis, wherein two or more radial axes may be provided at a predefined angle to each other. Such configurations may be advantageous for a corresponding extension of the anatomy of the target tissue, e.g., when the target tissue has a more pronounced extension in a particular direction and/or a connection to a particular portion of the target tissue is desirable.

At the outlet opening an inner rim portion may furthermore be present, which is formed by the wall and extends radially inward into the outlet opening. The inner rim portion may accordingly extend within or parallel to the plane of the outlet opening. The inner rim portion may provide for structural support at the target site, preferably in addition to a flange portion. Alternatively, or in addition, the inner rim portion may also provide an adjustment of the diameter and/or cross-sectional area of the outlet opening. Accordingly, the inner rim portion may enable that the diameter of the outlet opening is smaller than e.g. the diameter of the inner cavity defined by the central portion so as to ensure that the nerve end accommodated in the nerve conduit grows in the right direction i.e. out of the outlet portion.

To improve support and/or to sufficiently delimit the outlet opening, the inner rim portion may extend from between one third and two thirds of the inner circumference of the wall. In particular, the inner rim portion may extend along about half the inner circumference in a semi-circular manner or may alternatively also extend along the entire inner circumference. The inner rim portion may have a reduced thickness compared with the wall thickness of the elongate body, e.g. the wall thickness of the outlet portion, central portion, and/or insertion portion. To facilitate the insertion of a nerve end via the insertion portion, the cross-sectional area of the opening of the insertion portion may increase in a direction away from the central portion. Such configuration of the insertion portion may also be present in embodiments, wherein the cross- sectional area of the outlet opening is larger than the opening of the insertion portion.

The insertion portion and opening thereof may be formed as a rotationally symmetric shape along a longitudinal axis, wherein said shape is preferably a conical shape, concave shape, funnel shape, trumpet shape, or parabolic shape. The longitudinal axis is preferably defined by the central portion or inner cavity thereof. The increase in the opening is preferably gradual and homogeneous in all radial extensions. For example, the opening may have a circular cross-section along the entire longitudinal direction of the respective end portion, wherein the diameter of the circular shape is gradually increased. Such shape furthermore has the advantage that during implantation, the insertion of the nerve end is equally guided from the inner surface of the wall defining the insertion portion. Other shapes, such as ellipsoids, may, however, also be provided, wherein the (gradual) increase in the opening is provided by an increase in at least one radial extension.

The provision of the rotationally symmetric shape of the insertion portion furthermore provides that the mechanical properties of the outlet portion may be essentially the same along the circumference. The preferred shape of the insertion portion and the gradually extending opening furthermore facilitates the fixation of the nerve end to the nerve conduit by providing a corresponding interfacing surface and recess e.g. for the application of a medical adhesive.

The wall forming the elongate body is preferably continuous in a circumferential direction. Accordingly, as described above, the nerve conduit is preferably formed as a single continuous tube-like structure, forming a closed structure.

Alternatively, the wall forming the elongate body may be discontinuous in a circumferential direction, wherein the nerve conduit is formed as a medical tissue wrap. The wall is thereby coiled only in a circumferential direction and is at least partially uncoilable and recoilable in the circumferential direction.

In other words, the wall defining the elongate body as a whole may be non-continuous in the circumferential direction, such that the elongate body can be opened and be used to wrap around a nerve end. Such configuration may be advantageous for handling purposes and to facilitate nerve insertion in the insertion portion.

To ensure that the elongate body forms an essentially closed structure in the coiled state of the wall, a circumferential outer wall portion may at least partially overlap a circumferential inner wall portion. Such circumferential inner and outer wail portions may also have a reduced wall thickness, such that the overlapping portions preferably together constitute a wall thickness corresponding to the remaining portion of the elongate body.

The circumferential extension of the circumferential outer end portion hence preferably essentially corresponds to the circumferential extension of the circumferential inner end portion of the wall, such that said outer portion (fully) overlaps the inner portion. Thereby, a circumferential gap of the coiled wall is avoided, ensuring that the nerve end being accommodated within the inner cavity is retained within the nerve conduit and is essentially fully covered and/or surrounded along its circumference.

The circumferential outer end portion is preferably formed by a single wall layer overlapping the circumferential inner end portion. Thereby, application of the nerve conduit may be significantly facilitated compared with configurations having a plurality of adjacent layers overlapping each other in the radial direction. According to preferred embodiment, the circumferential outer end portion is not in any direct contact with the circumferential inner end portion.

Preferably, the wall may be fully uncoilable, such that the wall may define a sheet-like structure extending only in a longitudinal direction in the uncoiled state. By ensuring that the wall is uncoilable, the wall may be wrapped around the internal nerve end to be treated, e.g. a lesioned nerve, and may be recoiled after proper positioning of the wall.

The wall may be at least partially formed of a resilient or elastic material, preferably of a three- dimensional printable material. Such resilience may not only be advantageous to provide a desired support and/or level of flexibility adapted to surrounding tissue movements, but may also facilitate an uncoiling and recoiling of the wall to apply the nerve conduit wrap around the nerve to be treated. Such resilience may e.g. be provided by means of three-dimensional printing, wherein local stresses in the material may provide corresponding biasing forces.

For secure attachment of the nerve end to the nerve conduit and of the nerve conduit to the target site, a medical adhesive or similar means may be required at the corresponding insertion portion and outlet portion. In order to facilitate the attachment, the outlet portion and/or the insertion portion preferably comprises a larger surface roughness at the outer surface of the wall compared with the outer surface of the wall defining the central portion. Alternatively, or in addition, the outer surface of the wall defining the insertion portion may comprise a structural outer surface modification.

The structural outer surface modification and/or the increased surface roughness has the advantage that a bonding strength of an optionally applicable medical adhesive at the corresponding outer surface may be improved, such that a securing and/or anchoring of the medical adhesive to the respective surface may be strengthened. For example, the outer wall surface may provide an increased surface area and/or a form-fitting for the applied medical adhesive and/or may improve the adherence due to a modified surface tension. Thereby, the medical adhesive, which is applied to the outer wall surface and the adjacent tissue, i.e. the nerve end and the target site, may ensure that the nerve end and/or nerve conduit are held in place and maintained secured in the appropriate position.

The structural outer surface modifications may be formed on a thickened wall portion of the respective end portion compared with the wall thickness of the central portion. For example, the thickness of the thickened wall portion may be between 1,1 and 5,0 fold the thickness of the central portion and/or outlet portion, preferably between 1,5 and 2,5 fold. The thickened wall portion may be between 100 pm and 600 pm, preferably between 300 pm and 500 pm, while the wall portion that is not locally modified may e.g. comprise a thickness between 50 pm and 400 pm, preferably between 150 pm and 250 pm.

The wall portion of the flange may e.g. comprise a thickness between 50 pm and 400 pm, preferably between 150 pm and 250 pm.

Alternatively, it may also be provided that a continuous and essentially homogeneous thickness of the wall is provided, wherein the structural outer surface modifications are embedded in the wall. In such case, the overall wall thickness may be adapted to the structural outer surface modifications to ensure structural stability at the portion that has been modified, e.g. having a minimum wall thickness of about 50 pm, preferably (at least) between 50 pm and 200 pm.

The structural outer surface modifications are preferably formed as one or more retention surfaces, e.g. at least partially external structures with particular geometries or surface irregularities, which are configured for securing a medical adhesive to the insertion portion. Thereby, the medical adhesive that has been applied to the insertion portion and/or an adjacent tissue portion of the accommodated lesioned nerve end may remain in situ without any significant movement, even after curing of the medical adhesive. In other words, by means of the retention surfaces, the medical adhesive may be held in place, preferably in a form fitting manner with the one or more retention surfaces. The retention surfaces may provide that a contact surface with the medical adhesive is increased. Furthermore, it may provide that a predefined surface roughness is provided, thereby improving the efficacy of the medical adhesive to bond with the insertion portion. Accordingly, a loosening or slipping of the medical adhesive may be effectively prevented by means of the shape and/or surface of the retention surface.

In other words, such external structures may advantageously (i) increase the contact between the surface of the insertion portion and the adhesive; and/or (ii) create anchor points for the adhesive. Such external structures are disclosed, for example, in patent application PCT/EP2022/061084, the content of which is incorporated herein by reference in its entirety. Preferably, the one or more retention surfaces are formed as at least one groove extending in a helical direction along a longitudinal axis defined by the wall. The helical shape may define a thread extending along the outer surface of the insertion portion.

Although the one or more grooves may define sharp edges, the at least one groove preferably comprises rounded edges. The rounded edges are to be understood such that at the interface with the top outer surface of the insertion portion and at an opposing bottom surface of the groove with the wall no straight (angled) edges or steps are present, but instead a gradual transition is provided at corner surfaces of the groove. By means of the rounded edges, stresses within the material of the wall may be reduced, resulting in a reduced occurrence of rupture or breakage. Accordingly, the provision of rounded edges may also reduce the required thickness of the wall at least at the insertion portion to support the groove.

Alternatively, or (preferably) additionally to the round edges, the at least one groove may define at least one undercut. The provision of an undercut may improve the anchoring of the medical adhesive to the insertion portion. The undercut may be formed such that a bottom portion of the groove is at least partially covered by the outer surface of the wall. That is, the outer wall surface may at least partially extend over the groove in a longitudinal direction. Preferably, such extension forms an angle (between the bottom and the sidewall of the groove) of between 45 degrees and 90 degrees, preferably between 60 and 85 degrees, more preferably between 70 degrees and 80 degrees, even more preferably about 75 degrees. Thereby, a form-fitting or positive locking between an applied medical adhesive and the insertion portion may be improved.

In order to reduce the radial extension of the elongate body and the nerve conduit as a whole, the at least one groove may define an outermost edge of the insertion portion in a longitudinal direction of the wall. The groove may hence end at the longitudinal end surface of the wall and extend along the circumference at said end surface such that the radial extension may be reduced at said end. Thereby, the overall dimensioning of the nerve conduit may be reduced. Alternatively, the groove may also end at a longitudinal offset to said longitudinal end surface, which may be advantageous for further improving structural stability.

The depth or thickness of the groove may be essentially constant along the circumference and throughout its longitudinal extension.

The extension and/or the angle of the at least one groove may vary.

Preferably, the at least one groove extends between 0,5 and 10 revolutions around a longitudinal axis defined by the wall, thereby providing a helical structure. Preferably, the groove extends for more than one revolution around the longitudinal axis defined by the wall. In particular, the number of revolutions may be between 2 to 6, preferably 3 to 5 or 4. In some embodiments, the insertion portion may comprise a single groove. In other embodiments, the insertion portion may also comprise at least two grooves. In particular if two or more grooves are provided in the same longitudinal end portion, each groove may extend between 0,5 and 5 revolutions around a longitudinal axis. The at least two grooves may be extending in parallel, for example forming two or more parallel (non-intersecting) helices. Thereby, arc length, curvature and torsion of the parallel grooves/helices are preferably the same, such that they only differ in their location (on the insertion portion). Preferably, the distances between two or more parallel grooves/helices are regular (i.e. about the same).

In some embodiments, at least two grooves may extend in opposing circumferential directions and intersect each other. Both embodiments may also be combined, i.e. with two or more grooves extending in parallel and two or more additional grooves extending in opposing circumferential directions, optionally also in parallel (such that the parallel intersecting grooves provide a "checkered" or "pineapple" pattern). The number of grooves in each circumferential direction may be between 1 and 10 and preferably is between 6 and 8 or 7, depending on the longitudinal extension of the insertion portion and the angle of the grooves. The number of grooves is furthermore preferably equal for each circumferential direction. Moreover, at the insertion portion, the grooves/helices preferably differ only in their direction (and location on the insertion portion), but preferably not in other helix parameters. In other words, arc length, curvature and torsion may be essentially the same for all grooves/helices at the insertion portion (except for the direction of intersecting helices). By providing a plurality of grooves (e.g., two or more grooves) in each circumferential direction a diamond-shaped or rhombicshaped pattern is provided at the outer surface of the respective longitudinal end portion, which may resemble a pineapple surface. Thereby, a plurality of retention surfaces with a large number of edges may be provided, which may be advantageous for securing the medical adhesive to the insertion portion.

In some embodiments, the one or more retention surfaces may be formed as one or more circumferential ribs (elongated protrusions) extending from an outer surface of the wall. The extension of the one or more ribs may be linear (e.g. parallel) to the circumferential direction or comprise an offset to the circumferential direction in a longitudinal direction of the wall (e.g. diagonal, not in parallel with a cross-section and forming an ellipsoid). Preferably, in case of a plurality of ribs, e.g. between 3 and 6, at the insertion portion, the ribs may be equally spaced apart from each other and do not intersect, i.e. are preferably arranged in parallel to each other.

The one or more retention surfaces may generally be provided on a thickened wall portion at the insertion portion that is adapted to the implementation of the desired retention surface and the structural requirements at the insertion portion. Examples of preferred thicknesses or thickness ranges have been described in the above. The thickened wall portion may be brought flush with the outer surface of the central portion by appropriate rounding or provision of fillets, if the insertion portion is arranged adjacent to the central portion.

As a further alternative, the retention surfaces of the insertion portion may be formed as a plurality of (e.g., ellipsoid or circular) holes, that may be arranged in at least one row in a circumferential direction of the wall. The holes may hence be positioned in a linear fashion along the circumference of the wall. The number of rows preferably ranges between 1 and 10 rows. Each row preferably comprises 2 to 20 holes, wherein the holes may advantageously be equally spaced apart in the circumferential direction of the elongate body. Preferably, the holes are arranged in 2 to 4 rows and/or each row comprises 4 to 8 holes, wherein the holes of adjacent rows are preferably arranged in a staggered formation. For example, two rows may be provided at the insertion portion, wherein each row may comprise e.g. six holes.

The one or more holes and, in particular, grooves may also be provided as positive features at the outer surface of the wall having an otherwise essentially continuous thickness. The wall may hence comprise positive protrusions or build-ups at the insertion portion defining the respective groove or hole while the wall portion of the remaining elongate body does not comprise such positive features. In such case, the outer surface of the wall hence preferably defines the inner radius of the respective groove or hole.

As described above, the target site may particularly be a denervated muscle or muscle section (e.g. muscle flap), a nerve side, a bone or an organ. Accordingly, in an embodiment, the outlet portion of the nerve conduit may be configured for attachment to/connection with muscle tissue. Such configuration may be advantageous to facilitate at least partial restoration of motor control and/or restoration of sensory feedback and/or preventing of neuroma development. The muscle tissue may e.g. be a denervated target muscle, which is adjacent to or in proximity of the respective lesioned nerve end and which facilitates motor control of the injured anatomical structure, e.g. a arm. The muscle tissue may furthermore provide an effective tissue for reducing the occurrence of neuroma development, wherein a burying of a respective nerve end within the muscle may be particularly advantageous. In some embodiments, the target muscle is used for efferent signal amplification for prosthesis control.

Accordingly, the outlet portion may be configured for attachment on top of the muscle tissue or within an inner recess or slit within the muscle tissue. As described above, the outlet portion, in particular a flange portion extending therefrom, may e.g. exhibit flexibility, which may be advantageous for (partial) insertion of the outlet portion or flange portion into a slit of the muscle tissue and/or may provide a level of adaptability to the outer surface and corresponding anatomy of the target site. A slit of the muscle tissue may e.g. extend essentially perpendicular to a central axis defined by the elongate body, such that the outlet portion or flange portion thereof may at least partially extend into the slit. The outlet portion or flange portion may hence be configured to be accommodated within the slit and be at least partially covered by the muscle tissue, such that an interference fit or positive locking may be provided.

The elongate body, e.g. as a whole or the central portion and/or outlet portion and/or insertion portion, may contain one or more biologically active agent in its lumen or inner cavity, e.g. by means of coating or integrated in the material, e.g. a wall, of the respective part, which may be released over time and may e.g. facilitate nerve growth. Similarly, its lumen or inner cavity may comprise holes, pores, grooves or particular geometries or surface irregularities, and/or a filler, which may facilitate the insertion, retention and/or growth of the nerve end. Alternatively, the one or more biologically active agent is cross-linked to gel matrices within the nerve conduit of the invention or directly injected into the lumen of the nerve conduit.

The nerve conduit is preferably formed of a biocompatible material, an inert material, a bioimplantable material, and/or a biodegradable material. The material may be chosen so as to provide a predefined structural stability while essentially avoiding or at least reducing the inflammatory response of a patient to be treated. For example, a biocompatible material may be chosen, which is gradually degrading over time after implantation yet which may initially provide sufficient structural support to adequately repair a nerve lesion and ensure that the nerve end is connected properly and with sufficient stability, e.g. during movement of the tissue.

The particular material may furthermore be chosen in order to facilitate or support nerve growth, for example, by comprising or otherwise incorporating or including a corresponding coating, e.g. with one or more biologically active agent (including neurotrophic factors). Other examples of such biologically active surface functionalities include, but are not limited to, e.g. anti-inflammatories, immunosuppressants, and neuroprotective agents. Biologically active agents may be surface bound and/or be entrapped in a structure defining the elongate body, e.g. the wall described in the above.

Examples of biologically active agents are cytokines, nerve growth factor, 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 (a-FGF); a preferred example is tacrolimus.

Preferably, the nerve conduit is formed of a polymer-based material, preferably an elastomer. This has the advantage that a plurality of manufacturing methods may be applied and/or particular characteristics of the material may be provided based on e.g. a polymer unit. In particular, the polymer- based material may be a biocompatible material, which furthermore has elastic properties, such that, in the implanted states, the nerve conduit may adapt to tissue movement surrounding the repaired nerve lesion.

The nerve conduit may be formed of a polymerized and/or crosslinked polymer unit comprising an ester group component and an acid ester group component, the ester group component preferably being a polyol and the acid ester group component preferably being a polyacid.

The material being used for the respective portions of the elongate body may be the same. Thereby, manufacturing may be further facilitated and structural characteristics of the nerve conduit may be essentially homogeneous along the longitudinal direction of the nerve conduit, in this matter, if the nerve conduit system is configured accordingly, biodegradation (and/or bioresorption) may also occur in a predefined or expected manner.

Preferably, the portions are integrally formed or formed of a single piece, e.g. 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 since separate connections between portions are effectively avoided.

Preferably, the nerve conduit is formed by a 3D-printing process. This is particularly advantageous when the material of the nerve conduit is polymer-based, wherein a curing of the material may be provided essentially instantaneously, for example using (UV) light. Furthermore, this provides an accuracy level that may not be (easily) achieved by means of extrusion and/or a dipping process. In particular, the 3-D printing process enables to obtain a particular shape of each nerve conduit, which is particularly advantageous for the preferred transition portion. Furthermore, for example, the printing process may provide that particular biologically active agents are integrated in the 3-D structure according to a predefined pattern, e.g. within a mesh structure and/or in particular pockets or cavities formed by the 3-D structure. Thereby, orchestration and support of the nerve repair may be further improved and/or biodegradation may be achieved in a more controllable matter.

The above object is furthermore achieved by use of a nerve conduit described in the above for repairing, supporting, and/or guiding neural tissue, in particular for connecting a proximal or distal nerve end of a nerve, in particular a lesioned nerve, to target muscle tissue or target organ or to a side of a target nerve. The invention further relates to the use of a nerve conduit described in the above for restoring (partial) motor control and/or sensory function and/or to avoid the development of a neuroma and/or to result in regeneration of the injured nerve. Targeting muscle tissue according to Targeted Muscle Reinnervation (TMR) method is to be understood as targeting muscle tissue as well as nerve end present in the muscle tissue ; Targeted Muscle Reinnervation (TMR) method is well known in the art. According to another aspect of the invention, a method for treating a peripheral nerve lesion is suggested, comprising the steps of: providing a nerve conduit as described in the above; inserting a nerve end of a lesioned nerve into the insertion portion of the nerve conduit; and connecting the outlet portion to a target site, preferably muscle tissue or nerve end present in the muscle tissue or an uninjured nerve.

The securing of the lesioned nerve end may also be performed by applying a medical adhesive outside of the insertion portion and/or within the opening thereof via the corresponding opening. The attachment to the target site is furthermore preferably performed at an outer surface of the target site or by inserting at least a portion of the outlet portion or a flange portion thereof into a slit of the target site, wherein the target site is preferably a (denervated) muscle. The connection of the nerve conduit to the target site preferably includes the application of a medical adhesive along a circumference of the outlet portion, preferably at along an edge portion of a flange portion, and at least at the interface with the target site.

Medical adhesive according to the invention may be any medical adhesive of the art. In some embodiments, the medical adhesive is able to polymerize when exposed to light. Before such polymerization, the medical adhesive may be fluid or viscous. Preferably, the medical adhesive is a light-curable compound. In some embodiments, said photoinitiator is sensitive to ultraviolet (UV) radiations. Preferably, the medical adhesive is or comprises poly glycerol sebacate acrylate (PGSA) or PGSAA (e.g., as described in WO2021/078962).

According to another aspect of the invention, the method for treating a peripheral nerve lesion comprises targeted muscle reinnervation (TMR). In some embodiments, the method maximizes the number of motor axons to innerve a target muscle. In some embodiments, the method improves signal transduction from the target muscle. In some embodiments, the target muscle is used for efferent signal amplification for prosthesis control.

It is understood that the nerve conduit of the invention might (also) be used for a similar application, such as for example connecting a tendon or ligament end with target bone or bone section. In this embodiment, the tendon or ligament end replaces the nerve end in all of the above description and the target site encompasses bone or bone section, and the nerve conduit is called tendon conduit or ligament conduit. Accordingly, instead of (peripheral) nerve applications, the nerve conduit according to the invention may also be applied to provide a supporting structure for tendons, blood vessels (veins and/or arteries), muscle tissue, or small ligaments. Accordingly, such supporting structure may be adapted to the corresponding dimensions, tissue properties and/or level of support to be provided. For example, the diameter of the inner cavity may be chosen so as to ensure direct contact with the tissue accommodated therein, e.g. for very delicate tissue structures, or to provide a predefined radial spacing between the wall and the accommodated tissue, e.g. to provide a buffer upon impact on adjacent tissue. By the same token, the wall thickness may be chosen based on the required structural support and resilience of the wall in view of the tissue to be treated.

Brief description of the drawings

The present disclosure will be more readily appreciated by reference to the following detailed description when being considered in connection with the accompanying drawings in which:

Figure 1 shows a schematic depiction of a nerve conduit according to the invention in a longitudinal section;

Figure 2 schematically shows the nerve conduit according to Figure 1 in a perspective view;

Figure 3 schematically shows the nerve conduit according to Figure 1 in a bottom view;

Figure 4 shows a schematic depiction of an alternative embodiment of a nerve conduit according to the invention in a longitudinal section;

Figure 5 schematically shows the nerve conduit according to Figure 4 in a perspective view;

Figure 6 schematically shows the nerve conduit according to Figure 4 in a bottom view;

Figure 7 schematically shows the nerve conduit according to Figure 4 in a sectional perspective view;

Figure 8 shows a schematic depiction of an alternative embodiment of a nerve conduit according to the invention in a longitudinal section;

Figure 9 schematically shows the nerve conduit according to Figure 8 in a perspective view;

Figure 10 schematically shows the nerve conduit according to Figure 8 in a bottom view;

Figure 11 schematically shows the nerve conduit according to Figure 8 in a sectional perspective view;

Figure 12 shows a schematic depiction of an alternative embodiment of a nerve conduit according to the invention having an elongate body being discontinuous in a circumferential direction in a bottom view;

Figure 13 schematically shows the nerve conduit according to Figure 12 in a longitudinal section;

Figure 14 schematically shows the nerve conduit according to Figure 12 in a perspective view; Figure 15 shows a schematic depiction of an alternative embodiment of a nerve conduit according to the invention having an elongate body being discontinuous in a circumferential direction in a bottom view;

Figure 16 schematically shows the nerve conduit according to Figure 15 in a longitudinal section; and Figure 17 schematically shows the nerve conduit according to Figure 15 in a perspective view.

Detailed ion of

embodiments

In the following, the invention will be explained in more detail with reference to the accompanying figures. In the Figures, like elements are denoted by identical reference numerals and repeated description thereof may be omitted in order to avoid redundancies.

In Figures 1 to 3 an embodiment of a nerve conduit 10 according to the invention is schematically shown, wherein Figure 1 depicts the nerve conduit 10 in a longitudinal section. As shown, the nerve conduit 10 comprises an elongate body 12, which comprises an insertion portion 18 and an outlet portion 19. The insertion portion 18 is configured to receive a respective nerve end (not shown), e.g. a proximal nerve end of a lesioned nerve, which is to be connected to a target site, in particular a (denervated) muscle, via the outlet portion 19. Between the insertion portion 18 and the outlet portion 19, a central portion 14, which is provided in a direct adjacent or contiguous manner to the insertion portion 18. At the opposing end of the central portion 14, a transition portion 24 extends in a direction away from the central portion 14 and forming the outlet portion 19. The transition portion 24 and the central portion 14 together define an inner cavity 16, wherein the central portion 14 is adapted to accommodate the nerve end received via the insertion portion 18.

Both the outlet portion 19 and the insertion portion 18 comprise a respective opening 20, 21 towards the inner cavity 16. Accordingly, a continuous lumen or channel of the nerve conduit 10 is provided from the opening 20 of the insertion portion 18 to the opening 21 of the outlet portion 19. As shown, the elongate body 12 is essentially formed by a tubular wall 22 defining an inner lumen or channel of the nerve conduit 10, wherein the wall 22 preferably comprises an essentially constant thickness (t) along the extension of the elongate body 12.

The central portion 14 and the portion of the inner cavity 16 defined by the central portion are formed as an essentially cylindrical portion having a constant inner and outer diameter, which is adapted to accommodate the received nerve end having a corresponding diameter. Starting from the central portion 14, a wall portion of the transition portion 24 extends in such manner that its cross-sectional area increases towards the outlet opening 21, resulting in an enlarged opening 21 compared with the cross-sectional area or diameter of the inner cavity 16 of the central portion 14 and the diameter of the opening 20 of the insertion portion 18. Furthermore, the wall portion of the transition portion 24 defines a curvature, such that the cross-section of the outlet opening 21 is oriented at an angle relative to the cross-section of the insertion opening 20.

In the present, non-limiting example, said angle is about 90 degrees, such that the openings 20, 21 are oriented essentially perpendicular to each other. Together with the gradually increasing cross-section of the transition portion 24 and the enlarged opening 21, this facilitates growth of an accommodated nerve end towards the outlet portion 19 and towards the target site via the outlet opening 21, as described above. Such configuration may be particularly advantageous for connecting the nerve end to muscle tissue in a Targeted muscle reinnervation (TMR) manner or to an uninjured nerve in an End- to-Side manner.

To facilitate insertion of the nerve end into the inner cavity 16 of the central portion 14, the insertion portion 18 comprises a radially extending opening 20 and cross-sectional area thereof in a direction away from the central portion 14.

The nerve conduit 10 furthermore comprises a flange portion 26 at the level of the outlet opening 21 and retention surfaces 30 at the insertion portion 18, which both facilitate the connection of the nerve end to the target site. Figures 2 and 3 depict further details of these features.

Accordingly, as shown in Figures 1 and 2, the flange portion 26 extends essentially in a plane of the cross-section of the outlet opening 21 and the portion of the wall 22 defining the central portion 14. Thereby, an enlarged surface area of the elongate body 12 is provided at the outlet portion 19, which is advantageous for the connection to the target site, e.g. by increasing the connecting surface and/or surface for applying a medical adhesive. Furthermore, the provision of the flange portion 26 may ensure that no medical adhesive is inadvertently applied at or within the outlet opening 21 so as to avoid a potential blocking of the nerve end towards the target site.

As best shown in the bottom view of Figure 3, the outlet opening 21 is furthermore formed as an ellipsoid, wherein the largest diameter is about two fold the diameter of the inner cavity 16 of the central portion 14 and the smallest diameter essentially corresponds to the diameter of the inner cavity 16 of the central portion 14. Thereby, a directional bias for the growth of the nerve end may be achieved, i.e. in a direction of the largest diameter. The flange portion 26 comprises a rectangular shape with rounded edges and a triangular shape extending therefrom, resembling a rounded block arrow or top view of a simplified boat shape. The triangular portion is directed towards the insertion portion 18, which has the advantage that the flange portion 26 does not impair the handling of the insertion portion 18 and central portion 14, as also shown in Figure 2.

The retention surfaces 30 are formed as a single groove extending in a helical direction along a longitudinal axis defined by the portion of the wall 22 defining the insertion portion 18 and central portion 14. The helical extension comprises two to six revolutions, in the present example four revolutions, providing an optimized balance between structural stability, and an increase in surface area for the application of e.g. a medical adhesive.

By means of the flange portion 26 at the outlet portion 19 and the retention surfaces 30 at the insertion portion 18, secure attachment to the target site may hence be facilitated. Furthermore, this enables that the respective functionality of the end portions may be unambiguously determined during implantation and surgery by a medical professional or surgeon. In Figures 4 to 7 an alternative embodiment of a nerve conduit 10 according to the invention is schematically shown. As shown in the longitudinal section depicted in Figure 1 the insertion portion 18 and the central portion 14 of the nerve conduit 10 essentially correspond to the embodiment depicted in Figures 1 to 3. However, in the present embodiment, the central portion 14 has a more prominent longitudinal extension. Furthermore, the outlet portion 19 is arranged directly adjacent to the central portion 14 at the side of the central portion 14 opposing the insertion portion 18. In this embodiment no transition portion is present. Instead, the outlet portion 19 is formed as a truncated portion of the elongate body 12, such that the cross-section of the outlet opening 21 or the plane defined by the end face of the wall 22 defining the outlet opening 21 is oriented at an angle to the cross-section of the insertion opening 20. In such configuration the elongate body 12 defines an overall longitudinal extension while the openings 20, 21 are arranged at an angle to each other, e.g. between about 50 degrees and 70 degrees as shown in Figure 4.

At the outlet portion 19 the outer diameter of the wall 22 is enlarged in view of the outer diameter of the wall portion defining the central portion 14. Said enlargement is provided by a flange portion 26, similar to the embodiment depicted in Figures 1 to 3. The flange portion 26 accordingly extends radially outward from the outlet portion 19 or the outlet opening 21 thereof, such that the flange portion 26 extends essentially in the same plane as the outlet opening 21 or cross-section thereof. Since the embodiment does not comprise a transition portion defining a curvature of the elongate body 12, the angle of the flange portion 26 relative to the longitudinal axis and/or the adjacent wall portion of the outlet portion 19 and central portion 14 is less than 90 degrees, e.g. between 40 degrees and 20 degrees, as shown in Figure 4.

As shown in Figures 4 to 6, the flange portion 26 furthermore does not surround the entire outlet opening 21, contrary to the embodiment depicted in Figures 1 to 3. Rather, the flange portion 26 surrounds about half of the circumference of the outlet opening 21. The flange portion 26 is furthermore also formed as a rounded rectangular shape with a triangular portion extending from the rectangular portion, wherein the triangular portion merges with the wall portion surrounding the outlet opening 21 in the direction towards the insertion portion 18.

As shown best in Figures 4 and 5, although a sideward connection is possible with the embodiment according to Figures 4 to 6, the configuration of the nerve conduit 10 is particularly suitable for connection of a nerve end to a target site by placement on top of the target site or at a front end face of the target site.

The nerve conduit 10 may furthermore comprise an optional inner rim portion 28, which is depicted in Figures 4 and 7. In the present example, the inner rim portion 28 extends along the inner circumference of the outlet opening 21 in a semicircular manner. The inner rim portion 28 may provide additional support at the target site, in particular at the portion of the outlet opening 21 not being surrounded by a flange portion 26. In Figures 8 to 11 yet another embodiment of a nerve conduit 10 according to the invention is schematically shown. In this embodiment a transition portion 24 extends from the central portion 14, similar to the embodiment depicted in Figures 1 to 3. However, the transition portion 26 does not form a curvature, but instead a wall portion of the transition portion 24 extends at an angle to the central portion 14 starting from the central portion 14. Depicted in Figure 8 at the bottom end, the bottom wall portion of the transition portion 24 extends essentially linearly from the central portion 14, such that the transition portion 24 defines a converging geometry having a conical or funnel shape. Thereby, the cross-section of the transition portion 24 is gradually reduced starting from the central portion 14.

As a result, the outlet opening 19, which is formed by the transition portion 24, is accordingly reduced, such that the diameter or cross-section of the outlet opening 21 is smaller than the diameter of the inner cavity 16 defined by the central portion 14. Accordingly, a nerve end accommodated within the central portion 14 may not extend through the outlet opening 21, and nerve growth is effectively directed towards outlet opening, e.g. to avoid development of a neuroma.

As shown in Figures 8 to 11, the nerve conduit 10 furthermore comprises a flange portion 26, which extends within the plane of the outlet opening 21, similar to the embodiments depicted in Figures 1 to 3 and in Figures 4 to 7. In the present example, the entire outlet opening 21 is surrounded by the flange portion, similar to the embodiment depicted in Figures I to 3. However, since the outlet opening 21 comprises a reduced diameter and is furthermore does not comprise an ellipsoid shape, but a circular shape, the dimensioning of the flange portion may be reduced, as best shown in Figure 10 (see Figure 3 in comparison).

Furthermore, an inner rim portion 28 may be provided, which is depicted in Figure 11. Although said inner rim portion 28 may provide additional support at the target site in addition to the adjacent flange portion 26, said inner rim portion 28 is particularly configured to reduce the diameter of the outlet opening 21.

In Figures 12 to 17 embodiments of the nerve conduit 10 according to the invention are depicted, wherein the elongate body 12 is discontinuous in a circumferential direction. Accordingly, these embodiments depict a configuration of the nerve conduit 10 as a medical tissue wrap. The embodiment depicted in Figures 12 to 14 thereby essentially resembles the embodiment depicted in Figures 8 to 11. However, in the present embodiment the wall is configured to be brought in a coiled state, wherein the wall is at least partially uncoilable and recoilable in the circumferential direction. Accordingly, the wall may be coiled and recoiled only in a circumferential direction, such that in the uncoiled state a nerve end may be placed at the wall surface defining the portion of the inner cavity 16 of the central portion 14 and the insertion portion 18. After proper placement, the wall may then be recoiled so as to define the shape depicted in Figures 12 to 14, wherein the nerve end (not shown) is accordingly accommodated within the inner cavity 16 of the central portion 14 and the insertion portion 18. During the coiling of the wall, a circumferential inner wall portion 32 is covered at least partially by a circumferential outer wall portion 34 so as to form an overlapping structure. As shown best in Figure 13, a (small) gap may exist between the circumferential inner wall portion 32 and the circumferential outer wall portion 34. Due to the overlapping portion, the wall nevertheless forms a sufficient sealing towards the exterior in order to retain the nerve end within the inner cavity 16 and to avoid exterior tissue from penetrating the elongate body 12.

Although the insertion portion 18 may comprise a gradually increasing cross-section, e.g. to facilitate the application of a medical adhesive, such increasing radial extension may be particularly advantageous in a configuration, wherein the wall of the elongate body 12 is continuous in the circumferential direction. This is because the insertion of the nerve end according to the present embodiment is essentially based on the placement of the inner wall surface after uncoiling of the elongate body 12. Accordingly, the embodiment depicted in Figures 12 to 14 comprises an essentially cylindrically shaped insertion portion 18.

The embodiment depicted in Figures 15 to 17 essentially resembles the embodiment depicted in Figures 1 to 3. However, as for the embodiment depicted in Figures 12 to 14, the elongate body 12 is discontinuous in a circumferential direction and is arranged in the coiled state such that a circumferential inner wall portion 32 is covered at least partially by a circumferential outer wall portion 34 so as to form an overlapping structure.

As for the embodiment depicted in Figures 12 to 14, the elongate body 12 comprises an essentially cylindrically shaped insertion portion 18 to facilitate recoiling and uncoiling of the elongate body 12 and/or to provide a more compact design and accommodation of the nerve end being received in the inner cavity 16.

Furthermore, as shown in Figure 16, the elongate body 12 may optionally comprise an inner rim portion 28. Thereby, the cross-sectional area of the ellipsoid may be diminished to the extent that the outlet opening 21 has a smaller diameter than the diameter of the inner cavity 16 defined by the central portion 14.

As shown in Figures 12 to 17, the flange portion 26 resembles the embodiment depicted in Figures 1 to 3; except that it is discontinuous and not overlapping.

It will be obvious for a person skilled in the art that these embodiments and items only depict examples of a plurality of possibilities. Hence, the embodiments shown here should not be understood to form a limitation of these features and configurations. Any possible combination and configuration of the described features can be chosen according to the scope of the invention. List of reference numerals

10 Nerve conduit

12 Elongate body

14 Central portion 16 Inner cavity

18 Insertion portion

19 Outlet portion

20, 21 Opening

22 Wall 24 Transition portion

26 Flange portion

28 Inner rim portion

30 Retention surface

32 Circumferential inner wall portion 34 Circumferential outer wall portion

Claims

1. A nerve conduit (10) for connecting a nerve end to a target site, comprising an elongate body (12) formed by a wall (22) defining an inner cavity (16) and comprising a central portion (14), wherein the inner cavity (16) extends through the central portion (14) and two end portions (18, 19) defining respective openings (20, 21) to the inner cavity (16), wherein one end portion (18) is an insertion portion configured for inserting a respective nerve end (26) and the other end portion (19) is a nerve end outlet portion, wherein the end portions (18, 19) are arranged such that the cross-sections of the openings (20, 21) are oriented at an angle to each other.

2. The nerve conduit (10) according to claim 1, wherein the angle between the cross-sections is between 30 degrees and 90 degrees.

3. The nerve conduit (10) according to claim 2, wherein the angle between the cross-sections is between 50 degrees and 90 degrees, or between 70 degrees and 90 degrees or wherein said angle is about 90 degrees such that the cross-sections of the openings (20, 21) are oriented essentially perpendicular to each other.

4. The nerve conduit (10) according to any of the preceding claims, wherein the insertion portion (18) is arranged adjacent to the central portion (14) and the outlet portion (19) is arranged at an opposing side of the central portion (14).

5. The nerve conduit (10) according to any of the preceding claims, wherein the elongate body (12) comprises a transition portion (24) adjacent to the central portion (14) and forming the outlet portion (19), wherein the transition portion (24) defines a curvature of the elongate body (12) and/or extends at an angle to the central portion (14).

6. The nerve conduit (10) according to claim 5, wherein the cross-section of a portion of the inner cavity (16) defined by the transition portion (24) gradually increases in a direction away from the central portion (14).

7. The nerve conduit (10) according to claim 5, wherein the wall (22) defining the transition portion (24) at least partially converges towards the outlet portion (19).

8. The nerve conduit (10) according to ciaim 7, wherein the outlet portion (19) and/or the transition portion (24) comprises a conical or funnel shape.

9. The nerve conduit (10) according to any of the preceding claims, wherein the opening (21) of the outlet portion (19) is formed as an ellipsoid.

10. The nerve conduit (10) according to claim 8, wherein a ratio between the largest diameter and the smallest diameter of the opening (21) of the outlet portion (19) is between 1:1 to 4:1, preferably between 1.1:1 to 2.5:1.

11. The nerve conduit (10) according to claim 8 or 9, wherein the smallest diameter of the opening (21) of the outlet portion (19) essentially corresponds to a diameter of the inner cavity (16) defined by the central portion (14)

12. The nerve conduit (10) according to any of the preceding claims, wherein the wall (22) of the elongate body (12) is a single tubular wall comprising an essentially continuous thickness.

13. The nerve conduit (10) according to any of the preceding claims, wherein the inner cavity (16) defined by the central portion (14) comprises a continuous cross-section and/or wherein the central portion (14) comprises an essentially cylindrical shape.

14. The nerve conduit (10) according to any of the preceding claims, wherein the diameter of the inner cavity (16) defined by the central portion (14) is between 1 mm and 12 mm, preferably between 1,5 mm and 6,5 mm.

15. The nerve conduit (10) according to any of the preceding claims, wherein a cross-sectional area of the opening (21) of the outlet portion (19) is larger than the cross-sectional area of the inner cavity (16) of the central portion (14).

16. The nerve conduit (10) according to any of the preceding claims, wherein the largest diameter of the opening (21) of the outlet portion (19) is between 1 mm and 15 mm, preferably between 4 mm and 12 mm, larger than the diameter of the inner cavity (16) defined by the central portion (14).

17. The nerve conduit (10) according to any of the preceding ciaims, wherein a cross-sectional area of the opening (21) of the outlet portion (19) is larger than the cross-sectional area of the opening (20) of the insertion portion (18).

18. The nerve conduit (10) according to any of the preceding claims, wherein the cross-sectional area of the opening (21) of the outlet portion (19) increases in a direction away from the central portion (14).

19. The nerve conduit (10) according to any of claims 1 to 14, wherein the cross-sectional area of the opening (21) of the outlet portion (19) is smaller than the cross-sectional area of the inner cavity (16) of the central portion (14) and/or the cross-sectional area of the opening (20) of the insertion portion.

20. The nerve conduit (10) according to any of the preceding claims, wherein a flange portion (26) is formed by the wall (22) at the outlet opening (21), said flange portion (26) extending radially outward from the outlet opening (21).

21. The nerve conduit (10) according to claim 20, wherein the flange portion (26) extends essentially in a plane defined by a cross-section of the outlet opening (21).

22. The nerve conduit (10) according to claim 20 or 21, wherein the flange portion (26) at least partially surrounds the outlet opening (21), the flange portion (26) preferably entirely surrounding the outlet opening (21).

23. The nerve conduit (10) according to any of claims 20 to 22, wherein the flange portion (26) comprises a rectangular portion, preferably having rounded edges.

24. The nerve conduit (10) according to any of claims 20 to 23, wherein the flange portion (26) comprises a triangular portion being oriented in a direction towards the insertion portion (18).

25. The nerve conduit (10) according to claim 24, wherein the triangular portion extends from a rectangular portion.

26. The nerve conduit (10) according to any of the preceding claims, wherein an inner rim portion (28) is formed by the wall (22) at the outlet opening (21), the inner rim portion (28) extending radially inward into the outlet opening (21).

27. The nerve conduit (10) according to claim 26, wherein the inner rim portion (28) extends from between one third and two thirds of the inner circumference of the wall (22).

28. The nerve conduit (10) according to any of the preceding claims, wherein the cross-sectional area of the opening (20) of the insertion portion (18) increases in a direction away from the central portion (14).

29. The nerve conduit (10) according to any of the preceding claims, wherein the insertion portion (18) and the corresponding opening (21) are formed as a rotationally symmetric shape along a longitudinal axis, preferably wherein said shape is selected from the group consisting of a conical shape, concave shape, funnel shape, trumpet shape, or parabolic shape.

30. The nerve conduit (10) according to any of the preceding claims, wherein the wall (22) forming the elongate body (16) is continuous in a circumferential direction.

31. The nerve conduit (10) according to any of claims 1 to 29, wherein the wall (22) forming the elongate body (16) is discontinuous in a circumferential direction and wherein the nerve conduit (10) is formed as a medical tissue wrap, wherein the wall (22) is coiled only in a circumferential direction and wherein the wall (22) is at least partially uncoilable and recoilable in the circumferential direction.

32. The nerve conduit (10) according to any of the preceding claims, wherein the outlet portion (19) and/or the insertion portion (18) comprises a larger surface roughness at the outer surface of the wall (22) compared with the outer surface of the wall (22) defining the central portion (14) and/or wherein the outer surface of the wall (22) defining the insertion portion (18) comprises a structural outer surface modification.

33. The nerve conduit (10) according to claim 32, wherein the structural outer surface modifications are formed as one or more retention surfaces (30) being configured for securing a medical adhesive to the insertion portion (18).

34. The nerve conduit (10) according to claim 33, wherein the one or more retention surfaces (30) are formed as at least one groove extending in a helical direction along a longitudinal axis defined by the wall (22).

35. The nerve conduit (10) according to claim 34, wherein the at least one groove comprises rounded edges and/or wherein the at least one groove defines at least one undercut.

36. The nerve conduit (10) according to claim 34 or 35, wherein the at least one groove extends between 2 and 6 revolutions around the longitudinal axis defined by the wall (22).

37. The nerve conduit (10) according to claim 33, wherein the one or more retention surfaces (30) are formed as one or more circumferential ribs extending from an outer surface of the wall (22).

38. The nerve conduit (10) according to claim 37, wherein the extension of the one or more ribs is linear to the circumferential direction or comprises an offset to the circumferential direction in a longitudinal direction of the wall (12).

39. The nerve conduit (10) according to any of the preceding claims, wherein the outlet portion (19) is configured for attachment to/connection with muscle tissue.

40. The nerve conduit (10) according to claim 39, wherein the outlet portion (19) is configured for attachment on top of the muscle tissue or within an inner recess or slit within the muscle tissue.

41. Use of a nerve conduit (10) according to any of the preceding claims for repairing, supporting, and/or guiding neural tissue, in particular for repairing a peripheral nerve lesion.

42. A method of treating a peripheral nerve lesion, comprising the steps of: providing a nerve conduit according to any of the preceding claims; inserting a nerve end of a lesioned nerve into the insertion portion (18) of the nerve conduit; securing the nerve end within the inner cavity (16) by applying a medical adhesive outside of the wall (22) at the opening (20) of the insertion portion (18); and attaching the outlet portion (19) to a target site, preferably muscle tissue.