An apparatus for applying an adhesive composition to biological tissue and / or prosthetic material, and a kit including the apparatus

Abstract

1. A device for applying an adhesive composition to biological tissue and / or prosthetic material, the device comprising a flexible body (2), the body having an upper surface (14) including a first shoulder (32) defining a first recess, the body adapted to be folded into a folded position in which the body defines a flow path, the first recess configured to form an annular gap between the upper surface (14) and the biological tissue and / or prosthetic material when the biological tissue and / or prosthetic material is disposed within the flow path.

Description

Technical Field

[0001] The present disclosure ,raw relates to an apparatus for The adhesive composition coating body tissues and / or prosthetic materials and a kit including the device. According to certain embodiments, the apparatus of the present invention can be used in neurosurgery and vascular surgery.

Background Art

[0002] Anastomosis is a surgical technique for joining two separate tubular biological structures, such as mammalian nerves and blood vessels, to form a functional element. Suturing is common for anastomosis. However, suturing is generally difficult and requires skilled techniques and experience of surgeons. Also, suturing may cause complications due to tissue damage, leakage, stimulation of inflammatory reactions, and the possibility of infection around the suture material.

[0003] Adhesive compositions have been proposed as an alternative to suturing (see "Tissue engineering and peripheral nerve reconstruction: an overview" by Geuna et al. (2013)), but it has been found that their implementation is not easy. For example, a method of directly applying cyanoacrylate to the nerve stump has been proposed, but since the nerve is very soft, it is difficult to correctly maintain the position of the nerve ends during adhesion. To improve anastomosis without using sutures, the use of a nerve guide or a tubular prosthesis called a "neuroguide" has been proposed. This can fix the nerve ends well and avoid the infiltration of the adhesive into the nerve ends. However, procedures using these conduits become somewhat complicated, reducing the time saving, which is an important feature of the adhesive composition method. Also, when applying the adhesive composition, there is a problem that the distribution of the adhesive becomes inaccurate, such as a part of the adhesive flowing accidentally in front of the nerve stump, blocking the nerve stump and inhibiting the regeneration process.

Summary of the Invention

[0004] The present invention relates to an apparatus for facilitating the application of an adhesive composition to biological tissue and / or a prosthetic material, improving the dispensing of the adhesive composition, and facilitating microsurgery without using sutures.

[0005] A first aspect of the present invention is an apparatus for applying an adhesive composition to biological tissue and / or a prosthetic material, comprising a flexible body, The body has an upper surface including a first shoulder defining a first recess, and two longitudinal edges, The body is adapted to be folded into a folded position in which the body defines a flow path, and the first recess is configured to form an annular gap between the upper surface and the biological tissue and / or the prosthetic material when the biological tissue and / or the prosthetic material is disposed within the flow path. The first recess is an apparatus extending along a first longitudinal edge of the body.

[0006] According to the present invention, "biological tissue, prosthetic material, or a combination thereof" is also referred to as "tubular structure". According to the present invention, "biological tissue" can be a tubular biological structure such as, for example, a nerve, a blood vessel, a tendon, a ligament, etc. According to the present invention, "prosthetic material" can be a scaffold for tissue repair or regeneration, such as a tube or conduit, for example, a guide conduit such as a conduit for assisting in the connection of blood vessels, a nerve guide for nerve regeneration, or a tendon or ligament repair device.

[0007] The apparatus according to the first aspect can have the following features, separately or in combination, as far as technically possible.

[0008] The first recess may have a depth of from about 0.1 mm to about 10 mm.

[0009] The body may further have a curved protrusion defining a concave portion on the upper surface.

[0010] The curved protrusion may have a wavy shape.

[0011] The first shoulder may extend to the curved protrusion.

[0012] The bending protrusion may have a radius of curvature of about 1 mm to about 15 mm, particularly about 1 mm to about 10 mm, and more particularly about 1 mm to about 5 mm.

[0013] The bending protrusion may extend over an angular range of at least 90 degrees, preferably at least 180 degrees.

[0014] The device may include a deformable flap that defines a deformable portion of the body and further defines a first end of the body, and the flow path may be defined by the bending protrusion and the deformable flap.

[0015] The device may further include a gripping flap that defines a second end of the body opposite the first end, and the bending protrusion may connect the gripping flap and the deformable flap.

[0016] The upper surface of the body includes a second shoulder that defines a second recess spaced from the first recess, the second recess extends along the second longitudinal edge of the body, the body is adapted to be folded into a folded position where the body defines a flow path, the first recess is configured to form a first annular gap, the second recess is configured to form a second annular gap, and both annular gaps may be formed between the upper surface of the body and the biological tissue and / or the prosthetic material when the biological tissue and / or the prosthetic material is disposed within the flow path.

[0017] The body may include a rib that separates the first recess and the second recess, and the first and second shoulders may extend along respective longitudinal edges of the rib.

[0018] The rib may have a width of about 1 mm to about 10 mm, measured as the distance between the first recess and the second recess.

[0019] The first recess and / or the second recess may each have a width of about 1 mm to about 10 mm, measured as the distance between the first recess and the first longitudinal edge of the body and / or the distance between the second recess and the second longitudinal edge of the body.

[0020] The body may have a rectangular shape.

[0021] The device may further comprise means for maintaining the body in the folded position, such as at least one magnet and at least one metallic element cooperating with the magnet.

[0022] The upper surface may have an average surface roughness of 1 Ra or less, preferably 0.5 Ra or less.

[0023] The body may be translucent.

[0024] The flexible material of the body may include silicone.

[0025] A second aspect of the invention is a kit comprising the device according to the first aspect of the invention and an adhesive composition, in particular an adhesive composition polymerizable by exposure.

[0026] This kit may further include a patch material, preferably a scaffold for tissue regeneration, such as a nerve guide for nerve regeneration (e.g., a nerve conduit or a nerve wrap) or a tendon repair device. Examples of nerve guides such as nerve conduits and nerve wraps include, respectively, Neuroflex® or Neuromead® of NerveRepair. An example of a tendon repair device is disclosed in US Patent Application Publication No. 2014 / 0024885.

[0027] A third aspect of the invention is the use of the device according to the first aspect or the kit according to the second aspect for connecting / anastomosing tubular structures.

[0028] A fourth aspect of the invention is a method of anastomosing two tubular biological structures in a mammal, placing each end of both tubular biological structures in a tubular patch material such that the end faces face each other in the tubular patch material to form a tubular scaffold; placing the flexible body of the device of the invention in the unfolded state under the tubular scaffold; A step of applying an adhesive composition around a tubular prosthetic material and at least one periphery of a tubular biological structure so as to form a joint between the tubular biological structure and the tubular prosthetic material; A method comprising: folding a flexible body such that a tubular scaffold extends into a flow path defined by a main body, and an annular gap formed by a first recess extends between the tubular scaffold and the upper surface of the main body.

[0029] According to the present invention, the adhesive composition may be an adhesive composition polymerizable by exposure, and the method may further include a step of exposing a layer of the adhesive composition so as to induce polymerization of the adhesive composition.

Brief Description of the Drawings

[0030] Further details, features and advantages of the present invention will be described in more detail below using exemplary embodiments of the present invention shown in the drawings.

[0031] [Figure 1] A perspective view of an apparatus according to a first embodiment in a deployed state. [Diagram 2] A side view of the apparatus shown in FIG. 1. [Diagram 3] Another perspective view of the apparatus shown in FIGS. 1 and 2. [Figure 4] A top view of the apparatus of FIGS. 1 to 3. [Diagram 5] A cross-sectional view of the apparatus of FIGS. 1 to 4. [Figure 6] A perspective view of a curved protrusion of the apparatus of FIGS. 1 to 5. [Figure 7] A side view of the apparatus shown in FIG. 1 in a folded state. [Figure 8] Another top view of the apparatus of FIGS. 1 to 7. [Figure 9] A perspective view of an apparatus according to a second embodiment in a deployed state. [Figure 10] A perspective view of an apparatus according to a third embodiment in a deployed state. [Figure 11] A perspective view of an apparatus according to a third embodiment in a folded state. [Figure 12] Cross-sectional views of elements involved in the method at different stages of the method. [Figure 13] Cross-sectional views of elements involved in the method at different stages of the method. [Figure 14] Cross-sectional views of elements involved in the method at different stages of the method. [Figure 15] Side views of the devices and repair materials of FIGS. 1 to 8. [Figure 16] Cross-sectional views of elements involved in the method at different stages of the method. [Figure 17] Cross-sectional views of elements involved in the method at different stages of the method. [Figure 18] Side views of the devices and repair materials of FIGS. 1 to 8.

[0032] In all the figures, the same reference numerals are assigned to the same features.

DETAILED DESCRIPTION OF THE INVENTION

[0033] FIG. 1 shows a device according to a first embodiment, which is a preferred embodiment. The device 1 according to the preferred embodiment includes a main body 2. The main body 2 is flexible. Due to its flexibility, the main body 2 can be arranged in many positions, including the deployed position as shown in FIG. 1. According to the present invention, "flexible" or "flexibility" means the meaning given in the art, that is, it can be bent without breaking.

[0034] The main body 2 extends in three directions: the longitudinal direction indicated by the axis X, the transverse direction indicated by the axis Y, and the third direction (vertical direction) indicated by the axis Z. The axes X, Y, and Z are orthogonal. In the present disclosure, the length, width, and height of the parts of the device are described. By convention, the length is measured in the longitudinal direction, the width is measured in the transverse direction, and the height is measured in the third (vertical) direction.

[0035] The main body 2 has a first horizontal edge portion 4 and a second horizontal edge portion 6 on the side opposite to the first horizontal edge portion 4. The main body 2 extends in the vertical direction from the first horizontal edge portion 4 to the second horizontal edge portion 6. The horizontal edge portions 4 and 6 are parallel.

[0036] The main body 2 has a length of about 10 mm to about 50 mm, preferably about 20 mm to about 40 mm, more preferably about 30 mm to about 40 mm.

[0037] As used herein, the term "about" means within 20%, preferably within 10%, more preferably within 5%. In certain cases, "about X" means "X".

[0038] The main body 2 has a first vertical edge portion 8 and a second vertical edge portion 10 on the side opposite to the first vertical edge portion 8. The main body 2 extends in the horizontal direction from the first vertical edge portion 8 to the second vertical edge portion 10. The vertical edge portions 8 and 10 are parallel.

[0039] The width of the main body 2 is smaller than the length.

[0040] The width of the main body 2 is about 5 mm to about 30 mm, preferably about 10 mm to about 20 mm, more preferably about 12.5 mm to about 20 mm, for example 16 mm.

[0041] Furthermore, the main body 2 has a lower surface 12 and an upper surface 14 on the side opposite to the lower surface 12. The main body 2 extends in the vertical direction from the lower surface 12 to the upper surface 14. The lower surface 12 and the upper surface 14 are connected by the horizontal edge portions 6, 4 and the vertical edge portions 8, 10.

[0042] The lower surface 12 is flat. The main body 2 may have a rectangular shape (as shown in FIG. 4) in the sense that the lower surface is rectangular.

[0043] The upper surface 14 is non-planar. Therefore, the height of the main body 2 is not constant. Hereinafter, the shape of the upper surface 14 will be described in more detail.

[0044] In a preferred embodiment, the main body 2 includes a first flap 16 and a second flap 18 (FIG. 2).

[0045] The first flap 16 defines the first lateral edge 4 of the main body 2. The first flap 16 is substantially flat.

[0046] The first flap 16 has an upper surface 20, hereinafter referred to as the first upper surface 20. The first upper surface 20 is the first part of the overall upper surface 14 of the main body 2. The upper surface 20 may be planar.

[0047] The second flap 18 defines the second lateral edge 6 of the main body 2.

[0048] The second flap 18 has an upper surface 22, hereinafter referred to as the second upper surface 22. The second upper surface 22 is the second part of the overall upper surface 14 of the main body 2. The second upper surface 22 is non-planar.

[0049] The second flap 18 may have a length greater than that of the first flap 16. Preferably, the length of the second flap 18 is at least twice the length of the first flap 16.

[0050] The length of the second flap 18 is from about 10 mm to about 30 mm, preferably from about 20 mm to about 30 mm.

[0051] The second flap 18 may have a height that varies along the axis Y from about 0.25 mm to about 3 mm, preferably from about 0.3 mm to about 1.5 mm. For example, its maximum height (i.e., the top of the first shoulder 32) may be about 0.8 mm and its minimum height (i.e., the bottom of the first recess) may be about 0.3 mm.

[0052] In a preferred embodiment, the main body 2 further has a curved protrusion 24 that protrudes vertically with respect to the first and second flaps 18.

[0053] The curved protrusion 24 connects the first flap 16 and the second flap 18. When the main body 2 is in the deployed position, the curved protrusion 24 is located between the flaps 16 and 18.

[0054] The curved protrusion 24 has a top 26, an outer surface 28, and an inner surface 30 opposite the outer surface 28.

[0055] The maximum height of the main body 2 measured between the bottom surface 12 and the top 26 is about 8 mm or less, preferably about 7 mm or less, for example about 7 mm or about 4 mm.

[0056] The top 26 of the curved protrusion 24 defines a groove 27.

[0057] The curved protrusion 24 has a wave shape. The waves are hem-shaped and face the second lateral edge 6 of the main body 2. The outer surface 28 forms the back of the wave, and the inner surface 30 forms the front of the wave.

[0058] The outer surface 28 is a curved surface that continuously extends, for example, the first upper surface 20 defined by the first flap 16. Most of the outer surface 28 is convex.

[0059] The inner surface 30 of the curved protrusion 24 is a concave surface that defines an opening cavity extending along the axis Y. This cavity is configured to receive biological tissue and / or prosthetic material.

[0060] The concave surface 30 continuously extends the second upper surface 22 defined by the second flap 18.

[0061] The concave surface 30 has a concave cross-section in a transverse plane perpendicular to the horizontal direction.

[0062] The concave surface 30 has a radius of curvature of about 1 mm to about 15 mm, particularly about 1 mm to about 10 mm, and more particularly about 1 mm to about 5 mm.

[0063] The concave surface 30 extends over an angular range centered on the axis Y. This angular range is greater than 90 degrees, for example 180 degrees (Figure 2).

[0064] According to the present invention, the upper surface 14 of the main body 2 has a first shoulder portion 32 that defines a first recessed portion (as shown in FIGS. 3 to 4) and at least one first recessed surface 34 that forms the bottom of the first recessed portion. The first recessed portion extends along the first longitudinal edge portion 8.

[0065] In a preferred embodiment including the curved protrusion 24, the first shoulder portion 32, the first recessed portion, and the first recessed surface 34 extend to the second upper surface 22 (defined by the second flap 18) and further extend to the curved surface 30 (defined by the curved protrusion 24).

[0066] The first recessed surface 34 may extend horizontally from the first longitudinal edge portion 8 to the first shoulder portion 32.

[0067] Also, the first recessed portion has a width of about 1 mm to about 10 mm. For example, the width of the first recessed portion is 5 ± 0.15 mm.

[0068] According to another embodiment, the present invention relates to the device 1 as described above, in which the upper surface 14 of the main body 2 further has a second shoulder portion 36 that defines a second recessed portion and a second recessed surface 38 that forms the bottom of the second recessed portion. The second recessed portion extends along the second longitudinal edge portion 10. The second recessed portion is disposed spaced apart from the first recessed portion.

[0069] In a preferred embodiment including the curved protrusion 24, the second shoulder portion 36, the second recessed portion, and the second recessed surface 38 extend to the second upper surface 22 (defined by the second flap 18) and further extend to the curved surface 30 (defined by the curved protrusion 24) (FIGS. 1, 3, and 4).

[0070] The second recessed surface 38 may extend horizontally from the second longitudinal edge portion 10 to the second shoulder portion 36.

[0071] Also, the second recessed portion has a width of about 1 mm to about 10 mm. For example, the width of the second recessed portion is 5 ± 0.15 mm.

[0072] According to the present invention, the main body 2 includes a rib 40 along the first recessed portion.

[0073] When the device 1 of the present invention includes the first shoulder 32 and the second shoulder 36, the rib 40 separates the first recessed portion from the second recessed portion. In other words, the rib 40 separates the first recessed surface 34 from the second recessed surface 38.

[0074] The rib 40 protrudes on the upper surface 14. The rib 40 has a top portion 42 that is raised higher than the first recessed surface 34 and the second recessed surface 36.

[0075] The first shoulder 32 forms a first rib longitudinal edge portion of the rib 40 that connects the top portion 40 and the first recessed surface 34. The first rib longitudinal edge portion is a plane perpendicular to the lateral direction.

[0076] The second shoulder 36 is located on the side opposite to the first shoulder 32 with respect to the rib 40. The second shoulder 36 forms a second rib longitudinal edge portion of the rib 40 that connects the top portion 42 and the second recessed surface 38. The second rib longitudinal edge portion is a plane perpendicular to the lateral direction.

[0077] The rib 40 may have a width measured as the distance between the first recessed portion and the second recessed portion (that is, the lateral distance from the first shoulder 32 to the second shoulder 36), which is substantially equal to the width of the groove 27 when there is a groove 27.

[0078] The width of the rib 40 is about 1 mm to about 10 mm, preferably about 2.5 mm to about 7.5 mm.

[0079] FIG. 5 shows a cross-section of the second flap 18 in a plane perpendicular to the longitudinal direction. The second flap 18 defines a planar surface portion 44 of the first recessed surface 34 and a planar surface portion 46 of the second recessed surface 38. These planar surface portions 44 and 46 may be coplanar.

[0080] The first shoulder 32 includes a linear shoulder 48, and the second shoulder 34 includes a linear shoulder 50.

[0081] The rib 40 includes a linear rib portion 49 that extends to the second flap 18. When the device 1 of the present invention includes the first shoulder 32 and the second shoulder 36, the linear rib portion 49 separates the planar surface portions 44, 46 from each other.

[0082] The linear rib portion 49 further defines a planar top 52 that is part of the top 42. The planar top 52 is parallel to the planar surface portions 44, 46.

[0083] The first linear shoulder 48 connects the planar top 52 and the planar surface portion 44. Similarly, the second linear shoulder 50 connects the planar top 52 and the planar surface portion 46.

[0084] The height of the linear rib portion 49 is, for example, half of the maximum height of the second flap 18.

[0085] As shown in FIG. 6, the curved protrusion 24, if present, defines a first concave recessed surface 54. The first recessed surface is the concave portion of the first recessed surface 34.

[0086] The concave recessed surface 54 has a first radius of curvature.

[0087] Similarly, when the device 1 of the present invention includes the first shoulder 32 and the second shoulder 36, the curved protrusion 24 defines a second concave recessed surface 56. The second concave recessed surface is the concave portion of the second recessed surface 38.

[0088] The concave recessed surface 56 has a second radius of curvature. The second radius of curvature may be equal to the first radius of curvature.

[0089] The rib 40 includes a concave rib portion 58 that extends to the curved protrusion 24. The concave rib portion 58 defines an intermediate region of an opening cavity configured to receive the aforementioned biological tissue and / or prosthetic material. The concave rib portion 58 may separate the concave recessed surfaces 54, 56 from each other.

[0090] The concave rib portion 58 further defines a concave top portion 60. The concave top portion 60 is a curved portion of the top portion 42 of the rib 40. The concave top portion 60 has a third radius of curvature smaller than the first and second radii of curvature.

[0091] The height of the concave rib portion 58 measured in the radial direction toward the axis Y is equal to the height of the linear rib portion 49.

[0092] The first shoulder portion 32 includes a first concave shoulder portion 62. The first concave shoulder portion 62 connects the concave top portion 60 and the first concave retreat surface 54.

[0093] Similarly, the second shoulder portion 34 includes a second concave shoulder portion 64. The second concave shoulder portion 64 connects the concave top portion 60 and the second concave retreat surface 56.

[0094] The main body 2 may be a single part. The main body 2 can be obtained by injection molding.

[0095] The main body 2 preferably contains or consists of silicone. Silicone has advantages such as flexibility, elasticity, and biocompatibility.

[0096] The main body 2 is transparent or translucent. Preferably, the main body 2 can transmit radiation having a wavelength of 350 to 670 nm, preferably 405 nm.

[0097] The upper surface 14 may have an average surface roughness of 1 Ra or less, preferably 0.5 Ra or less. Such roughness is advantageous in preventing an object such as a tubular structure placed on the upper surface 14, particularly a biological tissue and / or a prosthetic material, from slipping.

[0098] The main body 2 has flexibility. Thus, as described above and as shown in FIGS. 1 to 6, it can be arranged in many positions including the deployed position.

[0099] The flexible main body 2 can be arranged in a folded position different from the deployed position (as shown in FIG. 7).

[0100] The flexible body 2 can be switched from the deployed position to the folded position by winding the second flap 18 such that the second flap 18 closes the opening cavity defined by the curved protrusion 24. When the body 2 is in the folded position, the second flap 18 can cover the curved protrusion 24 and rest on its top 26. The rib 40, if present, can engage with the groove 27. This engagement is advantageous for aligning the second flap 18 with the curved protrusion 24.

[0101] The second flap 18 has a sufficient length such that when the body 2 is in the folded position, the end portion of the surface 22 crosses over the curved protrusion 24 and faces the upper surface 20 defined by the first flap 16.

[0102] The closed cavity defined by the curved protrusion 24 and the second flap 18 is a generally tubular flow path 65 extending along the transverse axis Y. This flow path 65 has a first opening defined by the first longitudinal edge 8 and a second opening defined by the second longitudinal edge 10.

[0103] In the folded position, the rib 40 is also wound. The first recess defined by the first shoulder 32 and the first retreat surface 34 forms a first annular gap extending around the transverse axis Y. Similarly, if present, the second recess defined by the second shoulder 36 and the second retreat surface 38 forms a second annular gap extending around the transverse axis Y.

[0104] A tubular structure such as a biological tissue and / or a prosthetic material is disposed within the flow path 65 to rest on the wound rib 40 without contacting the first retreat surface 34 and / or the second retreat surface 38. As a result, both annular gaps can extend around the entire circumference of the tubular structure.

[0105] The device 1 may further include retaining means for maintaining the body 2 in the folded state, if necessary. By the device 1 having such means, the user's hands can be freed after the device 1 is folded.

[0106] The retaining means includes at least one first fastening element 66 and at least one second fastening element 68 adapted to cooperate with the first fastening element 66 when the body 2 is in the folded position.

[0107] For example, at least one first fastening element 66 is embedded in the first flap 16 and at least one second fastening element is embedded in the second flap 18.

[0108] For example, the first and second fastening elements 66, 68 are a magnet and a metal element attracted to the magnet.

[0109] A row of N first fastening elements 66 may be arranged on the first flap 16. The fastening elements 66 are arranged side by side horizontally. Further, at least one row of N second fastening elements 68 is arranged on the second flap 18. The fastening elements 68 in each row are also arranged side by side horizontally. In the embodiment shown in FIG. 8, N = 3 and since the number of rows is 3, the total number of second fastening elements 68 is 9. The rows of second fastening elements 68 include a first fastening element arranged on the first recessed surface 34, a second fastening element arranged on the second recessed surface 38, and a third fastening element arranged on the rib 40.

[0110] In another embodiment (not shown), the retaining means includes an attachment detachable from the body 2. This attachment includes at least one third fastening element capable of cooperating with the first fastening element 66 and the second fastening element 68. For example, the first and second fastening elements are female elements and the third fastening element is a male element adapted to simultaneously engage both the first and second fastening elements when the body is in the folded position.

[0111] The apparatus 1' according to the second embodiment is shown in FIG. 9.

[0112] The device 1’ is different from the device 1 mainly in that it consists of a single shoulder 32. The rib 40 extends from the shoulder 32 to the longitudinal edge 10. All other features described above in connection with the device 1 may be included in the device 1’ (including the aforementioned exemplary materials of the flexible body 2, the maintaining means described with respect to FIG. 8).

[0113] The device 1” according to the third embodiment is shown in FIGS. 10 and 11.

[0114] The device 1” is different from the device 1’ mainly in that it does not include the curved protrusion 24.

[0115] As shown in FIG. 11, the device 1” can be regarded as a single flap that is wound in a folded state. Different from the closed cavity defined by the curved protrusion 24 and the second flap 18, which is a substantially tubular flow path, the closed cavity defined by the folded device 1” has a teardrop shape.

[0116] The rib 40 may extend from the first transverse edge 4 to the second transverse edge 6.

[0117] Similar to the device 1’, the device 1” consists of a single shoulder 32.

[0118] Devices 1, 1', and 1'' can be used to improve the dispensing of adhesive compositions and facilitate microsurgery, more preferably microsurgery without using sutures. According to certain embodiments, microsurgery includes repairing damaged biological tissue, particularly anastomosing damaged biological tissue. According to certain embodiments, the damaged biological tissue is a blood vessel, nerve, tendon, ligament, etc. According to the present invention, the damaged biological tissue is a severed or transected blood vessel, tendon, ligament, or nerve. According to the present invention, microsurgery includes a tubular structure that can be a biological tissue, a prosthetic material, or a combination thereof. According to certain embodiments, the prosthetic material can be a guide conduit such as a tube or conduit, for example, a conduit for assisting in the connection of blood vessels or nerve tubes, or a conduit for guiding nerve regeneration (e.g., a nerve conduit, nerve wrap, or shape memory nerve conduit). According to another embodiment, device 1 of the present invention can be used to repair a damaged tubular biological structure (e.g., a nerve, tendon, ligament, or blood vessel) using a tubular prosthetic material, particularly for anastomosing two tubular biological structures (e.g., a nerve, tendon, ligament, or blood vessel).

[0119] The present invention further relates to a method of using any one of devices 1, 1', and 1'' for repairing a damaged tubular biological structure in a mammal.

[0120] According to one embodiment, the damaged tubular biological structure is a damaged blood vessel, a damaged tendon, a damaged ligament, or a damaged nerve.

[0121] The present invention further relates to a method of using any one of devices 1, 1', 1'' for connecting the proximal and distal ends of a tubular biological structure in a mammal, particularly a severed tubular biological structure.

[0122] According to one embodiment, the proximal and distal ends of the tubular biological structure are the proximal and distal ends of a blood vessel. According to another embodiment, the proximal and distal ends of the tubular biological structure are the proximal and distal ends of a tendon or ligament. According to another embodiment, the proximal and distal ends of the tubular biological structure are the proximal and distal stumps of a severed nerve, particularly a severed peripheral nerve.

[0123] According to another embodiment, the proximal and distal ends of the tubular biological structure are the proximal stump A and the distal stump B of the severed nerve, and the method further includes the use of a patch material for nerve regeneration, in particular a nerve conduit, a nerve wrap, or a shape memory nerve conduit 70 (Figure 9). The nerve conduit 70 includes a flexible sheet. The flexible sheet is composed of a polymer that can be wound. The nerve conduit 70 can be inserted into the flow path 65 defined by the main body 2 in a folded state.

[0124] Hereinafter, embodiments of the method including the stumps A and B and the device 1 will be described in more detail. The method includes the following steps. Place the proximal nerve stump A and the distal nerve stump B of the severed nerve on a nerve guide 70 flatly placed on a support such that the ends of the stumps A and B face each other. The support may be, for example, the main body 2. In this case, the nerve guide 70 may be flatly placed on the upper surface 22 defined by the second flap 18.

[0125] Wind the nerve guide 70 around the proximal stump A and the distal stump B such that a tube including both ends facing each other is formed. As shown in Figure 12, both stumps A and B are separated by a nerve regeneration gap 71. The distance between the stump A and the stump B may be 5 mm or less. Alternatively, the nerve guide is a nerve conduit.

[0126] As shown in Figure 13, the first end 72 of the nerve guide 70 surrounds and contacts the proximal stump A. Similarly, the second end 74 of the nerve guide 70 surrounds and contacts the distal stump B. The nerve guide 70 includes an intermediate portion 76 that connects the first and second ends 72 and 74 of the nerve guide 70 to each other. The intermediate portion 76 surrounds the nerve regeneration gap 71. The nerve regeneration gap 71 corresponds to the nerve growth leading to nerve regeneration, that is, the portion of the patch material where anastomosis can occur.

[0127] If the main body 2 is not used as the support in the previous step, place the unfolded main body 2 under the wound nerve guide 70 and both stumps A and B such that at least a part of the nerve guide 70 lies on the upper surface 14.

[0128] As shown in FIGS. 14 and 15, the nerve guide 70 is preferably disposed laterally within the opening cavity defined by the curved protrusion 24 such that the tube formed by the nerve guide 70 is parallel to the axis Y. The nerve guide 70 is placed on the concave rib portion 58. The first end 72 of the nerve guide 70 faces at least partially the first recessed surface 34. However, the first end 72 is spaced from the first recessed surface 34 by a first recess formed by the first shoulder 32. At the same time, the second end 74 faces at least partially the second recessed surface 38. However, the second end 74 is spaced from the second recessed surface 38 by a second recess formed by the second shoulder 36.

[0129] Apply an adhesive composition to both the joint between the nerve guide 70 and the proximal stump A and the joint between the nerve guide 70 and the distal stump B.

[0130] As shown in FIG. 16, apply a first layer 78 of the adhesive composition so as to form a joint between the nerve guide 70 (first end 72) and the proximal stump A. The first layer 78 forms an annular joint between the nerve guide 70 and the proximal stump A. Note that due to the first recess, it is possible to apply the adhesive composition to the entire circumference of the joint between the proximal stump A and the first end 72 with the nerve guide 70 placed on the upper surface 14 of the body 2.

[0131] Similarly, apply a second layer 80 of the adhesive composition so as to form a joint between the nerve guide 70 (second end 74) and the distal stump B. The second layer 80 forms an annular joint between the nerve guide 70 and the distal stump B. Note that due to the second recess, it is possible to apply the adhesive composition to the entire circumference of the joint between the distal stump B and the second end 74 with the nerve guide 70 placed on the upper surface 14 of the body 2.

[0132] As shown in FIG. 18, the flexible body 2 is placed in the folded position by folding the second flap 18 as described above so as to close the opening cavity of the curved projection 24 in which the tubular nerve guide 70 is disposed. During this process, the second flap 18 presses the first layer and / or the second layer, whereby the excess of the applied adhesive can be ejected from the body 2 as indicated by the black arrow in FIG. 17.

[0133] When the flexible body 2 is placed in the folded position (or maintained at that position by the above-described maintaining means or manually), the nerve guide 70 is placed in the flow path 65 defined by the curved projection 24 and the second flap 18. The first recess defined by the first shoulder 32 forms an annular gap separating the first end 72 and the first recessed surface 34. The annular shape of this first recess promotes the uniform distribution of the first adhesive layer 78 around the joint between the proximal stump A and the first end 72 of the nerve guide 70. Similarly, the second recess defined by the second shoulder 36 forms an annular gap separating the second end 74 and the second recessed surface 38. The annular shape of this second recess promotes the uniform distribution of the second adhesive layer 80 around the joint between the distal stump B and the second end 74 of the nerve guide 70.

[0134] Next, the layers 78, 80 are exposed so as to induce the polymerization of the adhesive composition. As a result, the annular joints formed by the layers 78, 80 become rings that respectively maintain the proximal stump A and the distal stump B at predetermined positions of the nerve guide 70.

[0135] Thereafter, the body 2 can be deployed and separated from the stumps A, B and the nerve guide 70.

[0136] The present disclosure is not limited to the embodiments shown in the figures. In FIGS. 9 to 15, the method is disclosed in detail for severed nerves, but it should be understood that the device 1 can also be used when the damaged tubular biological structure is not completely severed, is cut but not severed, or is partially damaged. Similarly, although the device 1 according to the preferred embodiment includes two shoulders and two retreat surfaces, it is also possible to use the device 1' or 1" instead of the device 1 (for example, when a tubular patch structure is not used). According to a particular embodiment, any of the devices 1, 1' and 1" can be used in microsurgery using sutures (a combination of sutures and adhesive compositions), for example for vascular anastomosis.

[0137] According to a preferred embodiment, the adhesive composition can be polymerized by exposure. Before such polymerization, the adhesive composition is fluid or viscous.

[0138] According to an embodiment of the present invention, the adhesive composition comprises a prepolymer comprising polymer units of the general formula (-A-B-)n, where A represents a substituted or unsubstituted ester, B represents a substituted or unsubstituted acid ester containing at least two acid ester functional groups, and n represents an integer of 1 or more.

[0139] Component A can be derived from polyols such as diols, triols, and tetraols such as diols, triols such as glycerol, trimethylolpropane, and triethanolamine, tetraols such as erythritol and pentaerythritol, and higher order polyols such as sorbitol. Unsaturated diols such as tetradeca-2,12-diene-1,14-diol, macromonomer diols such as polyethylene oxide, and other diols including N-methyldiethanolamine (MDEA) can also be used. Preferably, the polyol is substituted or unsubstituted glycerol.

[0140] Component B can be derived from diacids or higher-order acids. A wide variety of diacids or higher-order acids can be used. Exemplary acids include, but are not limited to, citric acid (3 carbon atoms), glutaric acid (5 carbon atoms), adipic acid (6 carbon atoms), pimelic acid (7 carbon atoms), sebacic acid (8 carbon atoms), and azelaic acid (9 carbon atoms). Exemplary long-chain diacids include diacids having 10 or more, 15 or more, 20 or more, or 25 or more carbon atoms. Non-aliphatic diacids can also be used. For example, the above diacids having one or more double bonds can be used to produce polyol-diacid copolymers. Preferably, the diacid is substituted or unsubstituted sebacic acid.

[0141] Some substituents such as amines, aldehydes, hydrazides, acrylates, aromatic groups, etc. can be incorporated into the carbon chain. Exemplary aromatic diacids include terephthalic acid and carboxyphenoxy-propane. Polyacids, such as diacids, can also contain substituents. For example, reactive groups such as amines or hydroxyls can be used to increase the number of sites available for crosslinking. Amino acids or other biomolecules can be used to modify biological properties. Aromatic groups, aliphatic groups, or halogen atoms can be used to modify the intermolecular interactions within the polymer.

[0142] The prepolymer may further include a polyamide backbone or a polyurethane backbone. For example, a polyamine (containing two or more amino groups) can be used to react with a polyol and then with a polyacid, either together with the polyol or after reacting with the polyol. In another example, a polyisocyanate (consisting of two or more isocyanate groups) can be used to react with a polyol and then with a polyacid, either together with the polyol or after reacting with the polyol.

[0143] The prepolymer can preferably be activated. This can be achieved by introducing functional groups that react or are reacted to form crosslinks. Suitable functional groups that can be activated on the prepolymer backbone include hydroxy groups, carboxylic acid groups, amines, and combinations thereof, preferably hydroxy and / or carboxylic acid. The free hydroxyl or carboxylic acid groups on the prepolymer can be activated by functionalizing the hydroxy groups with moieties capable of forming crosslinks between polymer chains. The groups to be activated can be the free hydroxyl or carboxylic acid groups on the A and / or B portions of the prepolymer. Preferably, the functional group is an acrylate group or contains an acrylate group. An acrylate group is a moiety containing a substituted or unsubstituted acryloyl group. Acrylate can contain the following groups: -C(=0)-CR1=CR2R3 (wherein R1, R2, and R3 are independently of each other selected from the group consisting of hydrogen, alkyl such as methyl or ethyl, aryl such as phenyl, substituted alkyl, substituted aryl, carboxylic acid, ester, amide, amine, urethane, ether, and carbonyl. Preferably, R1, R2, and R3 are hydrogen, or R1 is methyl, R2 and R3 are hydrogen, or R1 and R2 are hydrogen, R3 is methyl, or R1 and R2 are hydrogen, R3 is phenyl.)

[0144] According to a preferred embodiment, the adhesive composition is a photocurable compound. A "photocurable compound" refers to a compound configured to polymerize or cure in another way upon receiving appropriate radiation energy, particularly radiation energy in the form of light from a light source.

[0145] Preferably, the photocurable compound comprises a prepolymer and a photoinitiator. The photoinitiator can induce the polymerization of the prepolymer when irradiated with light of a specific wavelength.

[0146] According to a particular embodiment, the photoinitiator is sensitive to ultraviolet (UV) light.

[0147] Examples of suitable photoinitiators sensitive to ultraviolet light include 2-dimethoxy-2-phenyl-acetophenone, 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (Irgacure 2959), 1-hydroxycyclohexyl-1-phenylketone (Irgacure 184), 2-hydroxy-2-methyl-1-phenyl-1-propanone (Darocur 1173), 2-benzyl-2-(dimethylamino)-1-[4-(morpholinyl)phenyl]-1-butanone (Irgacure 369), methyl benzoylformate (Darocur MBF), oxy-phenyl-acetic acid 2-[2-oxo-2-phenyl-acetoxy-ethoxy]-ethyl ester (Irgacure 754), 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone (Irgacure 907), diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide (Darocur TPO), phosphine oxide, phenylbis(2,4,6-trimethylbenzoyl) (Irgacure 819), and combinations thereof, but are not limited thereto. According to another embodiment, the photoinitiator is sensitive to visible light (typically blue light or green light).

[0148] Examples of photoinitiators sensitive to visible light include diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, eosin Y disodium salt, N-vinyl-2-pyrrolidone (NVP), triethanolamine, camphorquinone, and the like, but are not limited thereto.

[0149] In addition, the adhesive composition may contain one or more pharmaceutical, therapeutic, or prophylactic agents released while the material functions as an adhesive. The agent may be, for example, a low-molecular-weight agent having a molecular weight of less than 2000, 1500, 1000, 750, or 500 Da, such as a peptide, protein, enzyme, nucleic acid, polysaccharide, growth factor, cell adhesion sequence such as RGD sequence and integrin, extracellular matrix component, or a combination thereof. Similarly, the adhesive composition may contain cells or biological tissues, particulate bone grafts and / or bone substitutes. Exemplary types of low-molecular-weight agents include, but are not limited to, anti-inflammatory agents, analgesics, antibacterial agents, and combinations thereof. Exemplary extracellular matrix components include, but are not limited to, collagen, fibronectin, laminin, elastin, and combinations thereof.

[0150] Preferably, the adhesive composition is or contains polyglycerol sebacate acrylate (PGSA).

Claims

1. An apparatus for applying an adhesive composition to a biological tissue and / or a prosthetic material (70), comprising: a flexible body (2); the body having an upper surface (14) including a first shoulder (32) defining a first recess, and two longitudinal edges (8, 10); the body being adapted to be folded into a folded position in which the body defines a flow path, the first recess being configured to form an annular gap between the upper surface (14) and the biological tissue and / or prosthetic material (70) when the biological tissue and / or prosthetic material (70) is disposed within the flow path; the first recess being a device extending along a first longitudinal edge (8) of the body.

2. The apparatus according to claim 1, wherein the first recess has a depth of about 0.1 mm to about 10 mm.

3. The apparatus according to claim 1 or 2, wherein the body further has a curved protrusion (24) defining a concave portion of the upper surface.

4. The apparatus according to claim 3, wherein the first shoulder extends to the curved protrusion.

5. The apparatus according to claim 3 or 4, wherein the curved protrusion has a radius of curvature of 1 mm to 15 mm.

6. The apparatus according to claim 3 or 4, wherein the curved protrusion has a radius of curvature of 1 mm to 10 mm.

7. The apparatus according to claim 3 or 4, wherein the curved protrusion has a radius of curvature of 1 mm to 5 mm.

8. The apparatus according to any one of claims 3 to 5, wherein the curved protrusion extends over an angular range of at least 90 degrees.

9. The apparatus according to any one of claims 3 to 5, wherein the curved protrusion extends over an angular range of at least 180 degrees.

10. Comprising a deformable flap that defines a deformable portion of the body and further defines a first end of the body, the flow path being defined by the curved protrusion and the deformable flap, the device according to any one of claims 3 to 9.

11. Further comprising a gripping flap that defines a second end of the body opposite to the first end, the curved protrusion connecting the gripping flap and the deformable flap, the device according to claim 10.

12. The upper surface of the body includes a second shoulder (36) that defines a second recessed portion spaced apart from the first recessed portion, The second recessed portion extends along a second longitudinal edge portion (10) of the body, The body is adapted to be folded into a folded position where the body defines a flow path (65), the first recessed portion is configured to form a first annular gap, the second recessed portion is configured to form a second annular gap, and both the annular gaps are formed between the upper surface of the body and the biological tissue and / or the prosthetic material (70) when the biological tissue and / or the prosthetic material (70) is disposed in the flow path, the device according to any one of claims 1 to 11.

13. The body includes a rib (40) that separates the first recessed portion and the second recessed portion, the first shoulder and the second shoulder extending along respective longitudinal edge portions of the rib, the device according to claim 12.

14. The first recessed portion and / or the second recessed portion has a width of about 1 mm to about 10 mm, the device according to claim 12 or 13.

15. The body is translucent and / or includes silicone, the device according to any one of claims 1 to 14.

16. The device according to any one of claims 1 to 15, An adhesive composition, A kit comprising.

17. The kit according to claim 16, wherein the adhesive composition is an adhesive composition that can be polymerized by exposure to light.

18. The kit according to claim 16 or 17, wherein the repair material (70) is a scaffold for tissue regeneration.

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