WO2025151873A1

WO2025151873A1 - Implant for immediate lymphatic reconstruction (ilr) surgery

Info

Publication number: WO2025151873A1
Application number: PCT/US2025/011405
Authority: WO
Inventors: Sumner A. Barenberg; William ZOUZAS; Ananya MADHUSUDHAN; Mia Caroline BELLINO; Natalie G. SCANLON; Colin LEONELLI
Original assignee: Melorix Inc
Current assignee: Melorix Inc
Priority date: 2024-01-11
Filing date: 2025-01-13
Publication date: 2025-07-17
Anticipated expiration: 2026-07-11

Abstract

A method and device for connecting a vein graft to vessels are described herein. The implant device comprises a body that has a first end, a second end, and an exterior surface. The first end has a concave surface. The body includes a graft channel, a plurality of suture channels, and a plurality of grooves. The graft channel has a first opening on the first end and a second opening on the second end of the body. The plurality of suture channels extend longitudinally through the body. Each suture channel has a first opening in the first end and a second opening. The plurality of grooves extends longitudinally along the transverse surface of the body. Each of the plurality of grooves is aligned with one of the plurality of suture channels.

Description

IMPLANT FOR IMMEDIATE LYMPHATIC RECONSTRUCTION (ILR) SURGERY

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional App. No. 63/619,818, filed on January 11 , 2024. The entire contents of which are hereby incorporated by reference.

BACKGROUND

[0002] Embodiments of the present disclosure relate to an implant device and methods for connecting a vein graft to vessels (e.g., lymph vessels).

BRIEF SUMMARY

[0003] According to embodiments of the present disclosure, an implant device is provided. The implant device comprises a body that has a first end, a second end, and an exterior surface. The first end has a concave surface. The body includes a graft channel, a plurality of suture channels, and a plurality of grooves. The graft channel has a first opening on the first end and a second opening on the second end of the body. The plurality of suture channels extend longitudinally through the body. Each suture channel has a first opening in the first end and a second opening. The plurality of grooves extends longitudinally along the transverse surface of the body. Each of the plurality of grooves is aligned with one of the plurality of suture channels.

[0004] In some embodiments, the second end has a planar surface.

[0005] In some embodiments, the graft channel has a circular cross-section.

[0006] In some embodiments, the body has a circular cross-section.

[0007] In some embodiments, the body comprises silicone. [0008] In some embodiments, the body comprises a layer of polydopamine.

[0009] In some embodiments, the body comprises a layer of polylactic-co-glycolic acid- microsphere-collagen composite.

[0010] In some embodiments, the body comprises a first portion and a second portion, the first portion extending from the first end and the second portion extending from the second end, the first portion having a larger cross-sectional area than the second portion.

[0011] In some embodiments, the transverse surface comprises a curved portion connecting the first portion and the second portion of the body.

[0012] In some embodiments, the second opening of each suture channel is in the curved portion.

[0013] In some embodiments, each suture channel is configured to receive a suture.

[0014] In some embodiments, the graft channel is configured to receive a vein graft.

[0015] In some embodiments, the first openings of the plurality of suture channels are disposed around the first opening of the graft channel.

[0016] In some embodiments, the first opening of the plurality of suture channels are positioned radially around the first opening of the graft channel.

[0017] In some embodiments, the first opening of the graft channel is coaxial with the second opening of the graft channel.

[0018] In some embodiments, each of the plurality of grooves extends from the first end to a position coplanar to the second openings of the plurality of suture channels.

[0019] In some embodiments, each of the plurality of grooves converges with the second opening of one of the plurality of suture channels. [0020] According to embodiments of the present disclosure, methods for implanting an implant device are provided. A vein graft is extended through a graft channel of a body of the implant device. The vein graft is sutured to a first set of suture channels of the body. Tissue surrounding one or more vessels is sutured to a second set of suture channels of the body.

[0021] In some embodiments, the method further comprises extending the one or more vessels within the vein graft.

[0022] In some embodiments, the method further comprises testing for patent flow.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0023] FIGS. 1 A and IB is a view of an implant device, in accordance with one or more embodiments of this disclosure.

[0024] FIG. 1C is a side cross-sectional view of an implant device, in accordance with one or more embodiments of this disclosure.

[0025] FIG. ID is a side view of an implant device, in accordance with one or more embodiments of this disclosure.

[0026] FIG. IE is a front view of an implant device, in accordance with one or more embodiments of this disclosure.

[0027] FIG. 2 is a schematic view illustrating a preparation method of an implant device, in accordance with one or more embodiments of this disclosure.

[0028] FIG. 3A is a schematic view illustrating a method for implanting an implant device, in accordance with one or more embodiments of this disclosure.

[0029] FIG. 3B is a flowchart illustrating a method for implanting an implant device, in accordance with one or more embodiments of this disclosure. DETAILED DESCRIPTION

[0030] Breast cancer -related lymphedema (BCRL) occurs in 20-30% of breast cancer patients who undergo breast cancer treatment, specifically axillary lymph node dissection (ALND) surgery. This surgery removes a minimum of ten lymph nodes in the axillary region (i.e., the area under a patient’s arm) to check whether cancer has spread and also to prevent the spread of breast cancer. However, removing the lymph nodes can often disrupt the lymphatic system preventing adequate draining from lymphatic vessels. Eventually, patients develop lymphedema which is characterized by the buildup lymph fluid in the interstitial space causing swelling and buildup of fat and skin in the affected region.

[0031] To combat the development of lymphedema from ALND, a procedure called immediate lymphatic reconstruction (ILR) was developed. This technique is performed at the same time as ALND. While a surgical oncologist performs ALND, another lymphatic surgeon harvests a lower extremity vein graft (LEVG) which is then used to connect the axillary vein to lymph vessels. This lympho-venous anastomosis helps promote patent lymph flow, reducing the likelihood of developing lymphedema. ILR is a microsurgery and requires a microscope due to the small size of lymph vessels, which are typically less than 1mm in diameter. The larger end of lymph vessels in ILR surgery are only 0.8mm in diameter. In contrast, the lower extremity vein graft (LEVG) is around 2mm. Instead of suturing the vein graft directly to the lymph vessels, surgeons suture the vein graft to the tissue surrounding the lymph vessels, as the lymph vessels are too small, thin, and delicate for suturing. As a result, a risk in this surgery is the puncturing of the lymph vessels, causing damage or accidentally closing lymph vessels.

[0032] It is a challenging technique that only a limited number of lymphatic surgeons in the United States can perform. There remains an unmet clinical need for a reliable, safe, effective, and easy-to-perform ILR procedure. Additionally, the outcomes of this surgery are not well known, and there is an unmet clinical need for a solution to provide long-term patent flow (i.e., flow free of obstruction) in breast cancer patients to prevent lymphedema development and improve their quality of life. The drainage route formed by connecting the lymphatic vessel and vein may not remain patent over a long period of time (e.g., several years). While in the short term, the surgery can be effective, after a year many patients may experience decreased fluid flow and development of swelling. Thus, there also remains a need for a device that can maintain patent flow and prevent the development of lymphedema.

[0033] The present disclosure is directed to an implant device that can connect a vein graft to vessels (e.g., lymphatic vessels).

[0034] The implant device disclosed herein can be used for immediate lymphatic reconstruction surgery (ILR) surgery. ILR surgery is performed on breast cancer patients at the same time as axillary lymph node dissection (ALND) surgery as a preventative measure for lymphedema. The implant device can be implanted during this procedure instead of using conventional devices. Existing devices require two components and are considered “coupler” devices, with one end attached to peri-lymphatic tissue and the other attached to the vein. The implant can create a fluid tight seal for long-term flow of lymph fluid after surgery to prevent the development of lymphedema.

[0035] Embodiments of this implant disclosed herein can be used for lymphovenous bypass surgery which is performed on patients who have already developed lymphedema to reduce swelling to improve the flow of lymph fluid. This is also referred to as delayed lymphatic reconstruction (DLR) surgery. [0036] The implant device disclosed herein can be used for any lymphovenous anastomosis procedure which involves connecting a vein or blood vessel to peri-lymphatic tissue that surrounds lymph vessels.

[0037] Embodiments of the implant disclosed herein can be used in any other surgical applications that require anastomosis between a blood vessel and tissue or a larger vessel with smaller vessels that are too delicate to suture directly.

[0038] In various embodiments, the implant device is a permanent implant device. In various embodiments, the implant device the remains within the patient’s body after the completing the surgical procedure.

[0039] Referring now to FIGS. 1A-1E, various views of an implant device are shown. FIGS. 1A and IB are 3-dimensional views of the implant device. FIGS. 1C and ID are a side cross- sectional view and side view, respectively, of the implant device. FIG. IE is a front view of an implant device. As shown in FIGS. 1A-1E, the implant device 100 includes a body 101 having a first end, a second end positioned opposite of the first end, and a transverse surface. The body 101 can be a singular component. In some aspects, this can streamline the surgical procedure because there are fewer components to handle, mitigating surgery risks. The body can have a circular cross-section.

[0040] The first end has a concave surface 102. The concave surface 102 is configured to receive the tissue surrounding the vessels (e.g., peri-lymphatic soft tissue). The second end can have a planar surface. The body 101 can include a first portion 103 (e.g., a cylindrical portion), extending from the first end, and a second portion 104 (e.g., a cylindrical portion) extending from the second end. The transverse surface of the body 101 can include a curved portion 116 connecting the first portion 103 and the second portion 104. The second portion 104 can have a cross-sectional area larger than the cross-sectional area of the first portion 103. The longitudinal axis of the first portion 103 can be colinear with the longitudinal axis of the second portion 104. In some embodiments, the diameter of the second portion 104 is about 15 mm. In some embodiments, the diameter of the first portion 103 is about 10 mm. In some embodiments, the overall length of the body 101 is about 25 mm. In some embodiments, the overall length of the body 101 is about 10 mm. In some embodiments, the outer diameter of the body 101 is about 4 mm.

[0041] The body 101 can be formed of a biocompatible material, hemocompatible material, and/or a low surface tension material. The body 101 can be formed of a material which minimizes the risk of encrustation when in contact with bodily fluids. The body 101 can be formed of a material. The body 101 can be formed of silicone. Silicone can remain resilient against host tissue responses and can maintain its structural integrity after repeated sterilization due to its chemical and thermal stability. The body 101 can be injection molded, 3D printed or can be formed using other fabrication methods. The edges of the body 101 can be beveled and/or rounded.

[0042] Still referring to FIGS. 1A-1E, the body 101 includes a graft channel 105 having a first opening 106 on the first end and a second opening 114 on the second end of the body. The graft channel 105 extends through the thickness of the body (e.g., extend through the cylindrical portion 102 and the portion 104). The graft channel 105 is configured to receive a vein graft (e.g., lower extremity vein graft (LEVG)). The graft channel 105 can have a circular crosssection, an elliptical cross-section, a rectangular cross-section, or an irregular shaped crosssection. The first opening 106 and second opening 114 can be circular openings. The first opening 106 can be aligned (coaxially) with the second opening 114 of the graft channel 105. In some embodiments, the diameter of the graft channel 105 is uniform throughout its length. In some embodiments, the diameter of the graft channel 105 varies along its length (e.g., tapers from the first opening 106 to the second opening 114 or vice versa). In some embodiments, the diameter of the graft channel 105 is about 5 mm. In some embodiments, the diameter of the graft channel 105 is about 2 mm. In some embodiments, the diameter of the graft channel 105 is about the diameter of a vein graft.

[0043] The body 101 includes multiple suture channels 107 (e.g., eight suture channels) each having a first opening 108 on the concave surface 102 and a second opening 112 positioned between the first and second end of the body 101. The suture channels 107 are configured to receive different needle and suture sizes. The second opening 112 can be positioned on the curved portion 116 of the body 101. In some aspects, the curved portion 112 reduces the overall size of the implant device. In some aspect, the curved portion 112 facilitates the visibility of the second openings 112 from above the implant device (e.g., during the surgical procedure). This can allow a suture and suturing needle to be easily guided through the second opening. The suture channels 107 extend at least partially through the thickness of the body 101 (e.g., extend through the thickness of the portion 104). The suture channels 107 can be disposed around (e.g., radially around) the graft channel 105. The longitudinal axis of the suture channels 107 can be about parallel to the longitudinal axis of the graft channel 105. The first openings 108 of each suture channel 107 can be positioned radially around the first opening 106 of the graft channel 105. In another example, the first openings 108 of each suture channel 107 can be arranged in an arcuate pattern around the first opening 106 of the graft channel 105. The first opening 108 and second opening 112 of each suture channel 107 can be aligned (coaxially) with each other. The first openings 108 and second openings 112 of each suture channel 107 can be angled relative to a transverse plane of the body 101. The first openings 108 and second openings 112 of each suture channel 107 can be angled relative to the first opening 106 of the graft channel 105. Each suture channel 107 can have a circular cross-section, an elliptical cross-section, a rectangular cross-section, or an irregular shaped cross-section. The first openings 108 can be D-shaped openings. The second openings 112 can be curved openings. The edges of the first opening 108 and/or the second opening 112 can beveled and/or rounded. In some embodiments, the length of each suture channel 107 is about 7 mm. In some embodiments, the diameter of the first openings 108 is about 6 mm.

[0044] Multiple grooves 110 (e.g., eight grooves) are formed in the transverse surface of the body 101 and extend longitudinally along the surface. The number of grooves 110 can correspond to the number of suture channels 107. The grooves 110 can extend from a first end of the body 101 to a position between the first end and the second end of the body. The grooves 110 can extend from a first end of the body 101 to a position coplanar to the second openings 112 of the suture channels. Each one of the grooves 110 can be aligned with one of the suture channels 107. Each groove defines a groove path aligned with a longitudinal axis of one of the suture channels 107. Each of the grooves 110 converges with the second opening 112 of one the suture channels 107. In some embodiments, the grooves 110 are V-shaped grooves. In some embodiments, the grooves 110 are U-shaped grooves.

[0045] In operation, a first set of suture channels 107 is used to secure the vein graft to the body 101 and a second set of suture channels 107 is used to suture the tissue surrounding the vessels (e.g., lymph vessels) to the body. Due to the small size of the lymph vessels, suturing directly to the lymph vessel can cause damage and can be technically challenging. In some aspects, the suture channels 107 enable the implant device to engage with the tissue surrounding the vessels which pulls the lymph vessels towards the concave surface 102 of the body 101. A fluid-tight seal may be formed between the first end of the body 101 and the tissue surrounding the vessels (e.g., peri-lymphatic soft tissue) when the tissue is sutured to the body 101. In some aspects, the seal prevents lymph fluid leakage and ensures long-term patent flow.

[0046] Referring to Fig. IE, from a group of suture channels 107a-h, alternating suture channels (e.g., suture channels 107a, 107c, 107e, 107g) can be used to secure the vein graft to the body 101, while the remaining suture channels (e.g., suture channels 107b, 107d, 107f, 107h) can be used to secure the tissue surrounding the vessels to the body 101. Each suture channel 107a-h can have a corresponding groove 110a- 11 Oh. A suture can extend through each suture channel 107 and extend into the corresponding groove 110. The tip of a suture needle, with the suture attached, can be inserted through the second opening 112 of the suture channel 107, through the first opening 108 of the suture channel, and over the groove 110 corresponding to that suture channel. In some aspects, the grooves 110 prevent the tied sutures from shifting after placement. [0047] Referring now to Fig. 2, a schematic view illustrating a preparation method 200 of an implant device is shown. At step 202, the body can be treated with a plasma discharge of oxygen. At step 204, the body can be coated with polydopamine (PDA). At step 206, the body can be coated with growth factors. In some embodiments, the growth factors are suspended in a hydrogel. In some embodiments, the growth factors are encapsulated in microspheres. Prior to step 206, step 208 and step 210 can be performed to prepare a microsphere-collagen composite.

At step 208, growth factors are encapsulated in microspheres (e.g., poly lactic-co-gly colic acid microspheres). At step 210, the microspheres containing the growth factors are suspended in a hydrogel (e.g., collagen hydrogel). [0048] The body 101 can be surface treated. Surface treatments may prevent inflammation and the formation of fibrous capsule around the body. The body 101 can be treated to modify the binding affinity of its surface. For example, the body 101 can be surface treated to modify its binding affinity for growth factors. Oxygen plasma treatment can be applied for 3 minutes with a fixed oxygen flow rate and pressure set at 20 standard cubic centimeter per minute and 5X1 O'² - torr for durations of 1 to 3 minutes.

[0049] The body 101 can be coated with polydopamine (PDA) following oxygen plasma treatment. Coating the body with PDA can facilitate a strong bond with the hydrogel, further enhancing its interaction with growth factors. The body 101 can be coated with PDA using a static coating method or a dynamic coating method. Static coating includes exposing the body to PDA solution, followed by storing the body at room temperature for about 24 hours to about 48 hours. Exposing the body to PDA solution can include submerging the body in a container containing a volume of PDA solution. Dynamic coating includes continuously perfusing PDA solution through the body (e.g., over the transverse surface and through the channels).

[0050] The body 101 can be coated with a hydrogel (e.g., collagen hydrogel) of growth factors after oxygen plasma treatment. Growth factors can include vascular endothelial growth factors (VEGF) such as VEGF-A, VEGF-B, VEGF-C, VEGF-D, which promote the growth of blood vessels, as a well as lymphangiogenesis. In some aspects, a combination of growth factors can benefit both lymph vessels and blood vessels which are anastomosed using the implant device. [0051] Poly lactic-co-gly colic acid (PLGA) microspheres containing VEGF-C and VEGF-D can be prepared using a double emulsion-solvent evaporation technique. To stabilize VEGF during encapsulation and release, Bovine Serum Albumin (BSA) and heparin can be co-encapsulated, and a primary emulsion can be generated using a high-speed homogenizer for approximately 2 minutes. Subsequently, the emulsion can be added to aqueous PVA (polyvinyl alcohol) and emulsified to produce a multiple emulsion. Solvent evaporation and subsequent microsphere hardening can be achieved by magnetic stirring at room temperature. After 3 hours, microspheres can be collected, washed thrice with distilled water by centrifugation, and freeze-dried for 24 hours. A collagen solution can be prepared and cooled to 39°C. The microspheres generated can then be resuspended with the cooled collagen solution. Employing this method of encapsulating microspheres and disposing the hydrogel on the surface of the body can ensure controlled and sequential release of growth factors.

[0052] Referring now to Figs. 3A and 3B, a schematic view 300 and flow chart 350, respectively, illustrating a method for implanting an implant device are shown. At step 302, a vein graft (e.g., LEVG) is extended through the graft channel (e.g., graft channel 105) of the implant device. Step 302 may include pulling the vein graft through the graft channel. The vein graft can be fed through the graft channel from the second opening (e.g, second opening 112) towards the first opening (e.g, first opening 106). At least a portion of the vein graft may extend out of the first opening of the graft channel. The end of the vein graft distal from the second opening of the graft channel can be attached to a vein (e.g., the axillary vein) using a vein coupler.

[0053] At step 304, the vein graft is sutured to a first set of suture channels (e.g., suture channels 107) of the body (e.g., body 101). The first set of suture channels can include alternating suture channels of a group of suture channels which surround (e.g., radially surrounding) the graft channel. Step 304 may include suturing the vein graft to four alternating suture channels. Steps 302 and 304 may be performed prior to insertion of the implant device in the patient’s body. [0054] At step 306, tissue (e.g., peri-lymphatic tissue) is sutured to a second set of suture channels. The tissue can be positioned against the concave surface (e.g., concave surface 102 of the body. Step 306 can include suturing the tissue to a first suture channel of the second set of suture channels, pulling the vessels inside of the vein graft. After suturing the first suture, a surgeon may visibly check that the vessels extend within the vein graft. Step 306 may include moving the vessels relative to the vein graft such that they extend within the vein graft. Step 306 can include suturing the tissue to the remaining suture channels of the second set (e.g., a second, third, and fourth suture channel of the second set).

[0055] The method 300 may include testing for patent flow. Testing for patent flow of the implant device includes verifying that there are no obstructions, blockages, or leaks that could impede flow through the device. Indocyanine green dye (ICG) can be used to assess blood or lymphatic vessel patency. ICG can be injected prior to the procedure. Once injected, ICG circulates through the vessel or graft and can be detected under near-infrared light. ICG can be visualized under a thermal camera or a fluorescence imaging system. By monitoring the fluorescent signature of ICG, any discrepancies in flow or patency can be detected early, allowing for immediate correction or adjustments.

[0056] Reference has been made in detail herein to the exemplary embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings. The systems, devices, and methods disclosed herein are described in detail by way of examples, and with reference to the figures. The examples discussed herein are examples only and are provided to assist in the explanation of the apparatuses, devices, systems, and methods described herein.

None of the features or components shown in the drawings or discussed below should be taken as mandatory for any specific implementation of any of these devices, systems, or methods unless specifically designated as mandatory.

[0001] For any methods described, regardless of whether the method is described in conjunction with a flow diagram, it should be understood that unless otherwise specified or required by context, any explicit or implicit ordering of steps performed in the execution of a method does not imply that those steps must be performed in the order presented but instead may be performed in a different order or in parallel.

[0002] As used herein, the term “exemplary” is used in the sense of “example,” rather than “ideal.” Moreover, the terms “a” and “an” herein do not denote a limitation of quantity, but rather denote the presence of one or more of the referenced items.

[0003] As used herein, the term “about” means a range of values inclusive of the specified value that a person of ordinally skill in the art would reasonably consider to be comparable to the specified value. In some embodiments, “about” means within a standard deviation using measurements generally accepted by a person of ordinary skill in the art. In some embodiments, “about” means ranging up to ±10% of the value. In some embodiments, “about” means ranging up to ±5% of the value. In some embodiments, “about” means the specified value.

[0057] The descriptions of the various embodiments of the present disclosure have been presented for purposes of illustration, but are not intended to be exhaustive or limited to the embodiments disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terminology used herein was chosen to best explain the principles of the embodiments, the practical application or technical improvement over technologies found in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

CLAIMS What is claimed is:

1. An implant device, comprising: a body having a first end, a second end, and a transverse surface, wherein the first end has a concave surface, the body including: a graft channel having a first opening at the first end and a second opening at the second end of the body; a plurality of suture channels extending longitudinally through the body, each suture channel having a first opening in the first end and a second opening; and a plurality of grooves extending longitudinally along the transverse surface of the body, wherein each one of the plurality of grooves is aligned with one of the plurality of suture channels.

2. The implant device of claim 1, wherein the second end has a planar surface.

3. The implant device of claim 1, wherein the graft channel has a circular cross-section.

4. The implant device of claim 1, wherein the body has a circular cross-section.

5. The implant device of claim 1, wherein the body comprises silicone.

6. The implant device of claim 1, the body further comprising a layer of polydopamine.

7. The implant device of claim 1, the body further comprising a layer of polylactic-co- glycolic acid-microsphere-collagen composite.

8. The implant device of claim 1, wherein the body comprises a first portion and a second portion, the first portion extending from the first end and the second portion extending from the second end, the first portion having a larger cross-sectional area than the second portion.

9. The implant device of claim 8, wherein the transverse surface comprises a curved portion connecting the first portion and the second portion of the body.

10. The implant device of claim 9, wherein the second opening of each suture channel is in the curved portion.

11. The implant device of claim 1, wherein each suture channel is configured to receive a suture.

12. The implant device of claim 1, wherein the graft channel is configured to receive a vein graft.

13. The implant device of claim 1, wherein the first openings of the plurality of suture channels are disposed around the first opening of the graft channel.

14. The implant device of claim 12, wherein the first openings of the plurality of suture channels are positioned radially around the first opening of the graft channel.

15. The implant device of claim 1, wherein the first opening of the graft channel is coaxial with the second opening of the graft channel.

16. The implant device of claim 8, wherein each of the plurality of grooves extends from the first end to a position coplanar to the second openings of the plurality of suture channels.

17. The implant device of claim 1, wherein each of the plurality of grooves converges with the second opening of one of the plurality of suture channels.

18. The implant device of claim 1, wherein the first opening and the second opening of each suture channel are coaxial.

19. A method for implanting an implant device, comprising: extending a vein graft through a graft channel of a body of the implant device; suturing the vein graft to a first set of suture channels of the body; and suturing tissue surrounding one or more vessels to a second set of suturing channels of the body.

20. The method of claim 18, further comprising extending the one or more vessels within the vein graft.

21. The method of claim 18, further comprising testing for patent flow.