Nested strain relief systems

Abstract

A nested in-series strain relief system (SRS) is provided and is defined by a first strain relief system with at one end a first crown which is nested with a second strain relief system with at one end a second crown. The first crown has a first closed zig-zag pattern and the second crown has a second closed zig-zag pattern substantially mirroring the first closed zig-zag pattern. The first and second crown are nested together yet without making contact with each other while spaced at a distance in a longitudinal direction of both the first strain relief system and the second strain relief system. The nested in-series SRS system results in various advantages such as simplification of the SRS manufacturing process, making it easier and more cost-effective, as well as scalability of SRS systems and other advantages detailed herein.

Description

[0001] NESTED STRAIN RELIEF SYSTEMS

[0002] FIELD OF THE INVENTION

[0003] This invention relates to grafts with embedded (nitinol) strain relief systems (SRSs), grafts with in-series but nested strain relief systems, or grafts for connecting two blood vessels.

[0004] BACKGROUND OF THE INVENTION

[0005] Nitinol strain relief systems (SRS) measuring over e.g. 16 cm in length cannot be easily manufactured using the existing nitinol lasering manufacturing process. The extended length of these strain relief systems presents challenges during the manufacturing process, as supporting them adequately during lasering becomes problematic.

[0006] The manufacturing of longer nitinol structures with minimal self-support, characterized by a "flimsy" zigzag coil design lacking bridges, proves to be challenging due to lower yield rates.

[0007] SUMMARY OF THE INVENTION

[0008] A nested in-series strain relief system is provided. The system has a first strain relief system with at one end a first crown, where the first crown has a first closed zig-zag pattern. The system further has a second strain relief system with at one end a second crown, where the second crown has a second closed zig-zag pattern substantially mirroring the first closed zig-zag pattern. The first crown and the second crown are nested together yet without making contact with each other while spaced at a distance in a longitudinal direction of both the first strain relief system and the second strain relief system. In one example, the distance could be substantially similar to the distance between struts within a single strain relief system. Noted is that this distance is defined herein as ‘axial pitch’. The then nested first strain relief system and the second strain relief system define the nested in-series strain relief system.

[0009] In one variation, the axial pitch is defined between the first crown of a first strain relief system and the second crown a second strain relief system, where the axial pitch is substantially similar to an axial pitch defined for the nested in-series strain relief system.

[0010] In another variation, the second crown is rotated with respect to the first crown, where an axial pitch is defined between the first crown of a first strain relief system and the second crown a second strain relief system, where the axial pitch is substantially similar to an axial pitch defined for either the first strain relief system or the second strain relief systems.

[0011] In still another variation, the first crown and the second crown are symmetric or substantially symmetric.

[0012] In still another variation, the first strain relief system and the second strain relief system are nitinol strain relief systems, polymer strain relief systems or metal strain relief systems. In still another variation, the nested in-series strain relief system is embedded by an inner layer and an outer layer. The inner layer and the outer layer could be electrospun layers, polymeric layers, fibrous layers, or porous layers, or a combination thereof.

[0013] In still another variation, the inner layer and the outer layer could be layers produced by electrospinning, electro-writing, 3D printing, freeze drying, solvent casting, particle leaching, gas foaming, thermal-induced phase separation, selective laser sintering, stereolithography, fused deposition modelling, multiphase jet solidification, precise extrusion deposition, 3D bioplotting, inkjet printing, or bacterial cellulose synthesis, or a combination thereof.

[0014] In yet another variation, the inner layer and the outer layer could be layers enabling endogenous tissue restoration, tissue ingrowth, or a combination thereof.

[0015] BRIEF DESCRIPTION OF THE DRAWINGS

[0016] FIG. 1 shows according to an exemplary embodiment of the invention a longitudinal cross section of SRS embedded members within an electrospun vascular prosthesis. [Left]: example of a perfectly nested SRS members part A and B; [Right] example of overlapping members A & B creating a local larger outer diameter and internally, higher ‘tenting’ of the coating material over the SRS frame. 101 is cross-section of strut of SRS A. 102 is polymer matrix in which the SRS is embedded. 103 is cross-section of strut of SRS B. 104 is open tubular section of the graft allowing the blood flow. FIG. 2 shows according to an exemplary embodiment of the invention two nested SRS’s without polymer matrix. 201 is SRS element A. 202 is SRS element B. 203 is crown section of SRS element A. 204 is crown section of SRS element B. 205 a main body of SRS element A. 206 a main body of SRS element B. 207 is nesting area between SRS element A and B.

[0017] FIGs. 3A-C show according to exemplary embodiments of the invention zoomed-in images of nested SRS’s. A single SRS element (FIG. 3A), a zoom-in of a crown section containing a closed ring (303) (FIG. 3B) and a nesting area between two individual SRS elements at the nesting area (FIG. 3C). In a perfect nesting area, the axial pitch between the crowns of the individual SRS elements (304) is substantially similar to the axial pitch within a single SRS element (301). 301 is axial pitch within a single SRS element. 302 is transition from helical to closed loop at crown section. 303 is closed loop at the end of the crown. 304 is axial pitch within the nesting area.

[0018] FIGs. 4A-B show according to exemplary embodiments of the invention a portion of an SRS flat pattern with pitch identification for two different SRS designs. 401 is circumferential pitch between struts of the SRS main body.

[0019] FIG. 5A shows according to an exemplary embodiment of the invention a rotational translation of the crowns resulting in perfect nesting. The SRS elements can be rotated with respect to one another as a result of the repeating zig-zag at the crown. SRS element B (204) with strut points (point 2, 3, or 4) can be rotated with respect to strut (1) of the SRS element A (203) and nested in several configurations resulting from rotational translation of SRS element B, while maintaining the axial pitch (304). In all cases, the axial pitch it parallel to the dashed line.

[0020] FIG. 5B shows according to an exemplary embodiment of the invention incorrect rotational translation, resulting in an axial misalignment, illustrated by a nonzero angle (501) between the axial orientation of the device and the relative axial orientation of struts from SRS element A (203) and B (204). 501 is angle with axial orientation within nesting area due to incorrect rotational alignment. FIG. 6 shows according to an exemplary embodiment of the invention when the SRS is symmetric or substantially symmetric, perfect nesting can be achieved independent of the longitudinal orientation of the second SRS element. Side 2 of the SRS element A can be positioned next to side A or side B of SRS element B.

[0021] FIGs. 7A-C show according to exemplary embodiments of the invention positioning of the two individual SRS elements resulting in different axial pitch between the individual SRS elements at the nesting area. A perfect nesting between the SRS elements A and B is achieved when the axial pitch in the nesting area (304) is the highly similar to the axial pitch within a single SRS element (301), FIG. 7A. When the SRS elements are too far (FIG. 7B) the axial pitch in the nesting area (304) is larger than the axial pitch within a single SRS element (301). When the SRS elements are too close (FIG. 7C) the axial pitch in the nesting area (304) is shorter than the axial pitch within a single SRS element (301). Only FIG. 7A will result in good kink resistance. DETAILED DESCRIPTION

[0022] There is a need in the art to provide a graft device for restoring a vessel by being capable of promoting endogenous tissue restoration or growth, while maintaining the structural and dynamical requirements desired for a graft device. The present invention provides a graft device that addresses this need.

[0023] In a case when multiple shorter nitinol SRSs are used one has to be cautious about some of the following issues such as the risk of i) kinking at the transition point (if there is a gap, too far, between the two parts) or ii) metal-to-metal abrasion (if the two parts are touching), thereby complicating the precise positioning required during assembly. Therefore, multiple supporting devices could be placed overlapping or could be connected by some “connecting members”. There is a drawback that important features like kinking-resistance or / and flexibility are not the same in these regions compared to the other part of the supporting device.

[0024] In addition, the positioning of the two individual SRS elements is absolutely crucial to ensure the required mechanical properties of the device. For example, when the SRSs are positioned too close to each other, this could result in some overlap between the individual SRS’s, and therefore, for example, a local thickness increase of the device (cross-sectional). In turn, this can result in a higher delamination risk of the layer surrounding the SRS - illustrated in FIG. 1 (referred to as a ‘tent’). Furthermore, when the individual SRSs are positioning in such a way that there is physical overlap of the nitinol material, the SRS’s could be damaged due to friction during movement of the graft.

[0025] The embodiments of this invention are intended to address these concerns and / or problems.

[0026] In one embodiment, the graft device is a tubular implant for making an anastomotic connection in between two tubular structures. Examples of tubular implants include, without limitation, a vein, an artery, a urethra, an intestine, an esophagus, a trachea, a bronchus, a ureter, or a fallopian tube. The graft device could be used to create a connection between 2 blood vessels, which could be a bypass graft, a (arteriovenous) shunt, an interposition graft, end-to-end, side-to-end, end-to-side, side-to-side, including snake and jump grafts (where several bypasses are made with one graft). In such cases, the device wall thickness would typically be between 0.3 and 1.5mm, and preferably between 0.4 and 1mm. Optionally, the graft device intended in this invention could also be used for other applications, such as a device for endoluminal placement - i.e. inside the lumen of an existing tubular structure - such as a covered stent. It should be noted that there are structural design characteristics that are required to make it work as a graft device that do not necessarily work for endoluminal devices. For example, for endoluminal placement, device wall thickness should typically be below 0.2 mm, more preferably between 0.05 mm and 0.15 mm.

[0027] Nitinol is used as a strain relief system in exemplary embodiments. Nitinol is most commonly used in (self-expandable) stents, or external or internal support structures. Laser- cutting is standard technique for manufacturing (nitinol-based) support structures. Accurate positioning during laser cutting is of crucial importance to meet precise tolerances on e.g. strut width. Therefore, manufacturability challenges increase with increase length of support structure, especially for (helical) designs with limited self-support. It is desirable to overcome manufacturing challenges with longer support structures. The solution provided herein is to make shorter devices that act as if they were one device (by properly nesting them). While the use of nitinol is preferred, similar challenges would exist with other metal stents, possibly also to polymeric stents. Hence embodiments other than nitinol for an SRS are encompassed in the scope of this invention such as metal SRSs.

[0028] DEFINITIONS

[0029] • SRS = Strain Relief System, which is a mechanical support system embedded in a graft to enhance kink resistance. Such graft could be produced by e.g, electrospinning, melt electro-writing, 3D printing, freeze drying, solvent casting, particle leaching, gas foaming, thermal-induced phase separation, selective laser sintering, stereolithography, fused deposition modelling, multiphase jet solidification, precise extrusion deposition, 3D bioplotting, inkjet printing, or bacterial cellulose synthesis.

[0030] • Strut = Structural component of the SRS.

[0031] • Axial pitch = Distance between the strut elements of individual SRS components or within an SRS component along the axial axis of the SRS.

[0032] • Circumferential pitch = Distance between the strut elements of individual SRS components or within an SRS component along the circumferential axis of the SRS.

[0033] • Crown = End of the SRS when the nitinol configuration changes from continuous helical structure to a closed structure. • Nesting region = Region where two SRS crowns are set side by side to create a contactless connection.

[0034] • A nitinol structure with minimal self-support that is more than 10 cm long would be considered challenging for manufacturing, while more than 16 cm would be considered even more challenging. A short SRS segment would therefore be 10 cm or less.

[0035] • It should be noted that the nested strain relief system may not be particularly suitable for use as a bare / uncovered stent for endoluminal application. A (bare) stent for luminal application will need to have sufficient self-support to allow maneuvering and deployment with a catheter. Further, a stent for endoluminal application would need to provide sufficient radial force to anchor itself inside a native vessel. Therefore, an endoluminal bare stent must have sufficient self-support by definition, and therefore the problem of limited self-support that is solved by the invention does not exist for endoluminal bare stents.

[0036] See FIGs. 2, 3A-C and 4A-B for explanation of the structural elements and nesting region.

[0037] To ensure axial and circumferential alignment between the crowns, a solution is to use a series of short strain relief systems (referred to as SRS). These exemplary SRS’s have a zigzag helix design with limited to no bridging, along with a zig-zag straight crown that is partially nested within a neighboring SRS. This nesting arrangement facilitates the desired alignment between the crowns, ensuring proper functionality and performance of the SRS supported device. When the axial pitch of the nested region between the SRS’s falls within a specified range, as shown in FIGs. 7A-C, the assembly of the nested region exhibits comparable kink resistance to that of each individual SRS.

[0038] Using several short (more than one, usually two, but possible to expand to more) SRS components instead of a single long SRS offers notable advantages. Firstly, it simplifies the manufacturing process of the SRS, making it easier and potentially more cost-effective. Shorter SRS are typically easier to produce, reducing the complexity and potential challenges associated with manufacturing longer structures. Additionally, the cost of producing shorter SRS may be lower, resulting in potential cost savings compared to manufacturing a single long SRS. Furthermore, manufacturing process for the graft may be easier and more cost-effective because of reduction in yield loss and processing time by removing complexities associated with precise placement of a long SRS within the graft.

[0039] Furthermore, adopting a modular approach with short SRS allows for future scalability. The ability to easily increase the length of the SRS supported device in the future becomes feasible by adding more short SRS units.

[0040] In addition, the use of a carefully positioned individual SRS, without any physical connections, lowers the risk of damaging compared to a single, long length SRS. In other words, if a physical connection is not present, it also cannot be broken or damaged.

[0041] Another advantage is the cross-sectional uniformity when the nesting is performed correctly, as it would result in uniform cross-sectional thickness along the length of the device. When the pitch is too long, the graft will have a thinner cross-section between the individual SRSs, whereas when the pitch is too short, the cross-section will be thicker at that particular location.

[0042] This thickness uniformity, as result of the ideal nesting area has several mechanical advantages for the final device. First of all, the graft receives equal strength support across the graft length. Secondly, the reinforcement is uniform along the entire length of the graft, without any local differences in dilation upon pressure (such as during blood flow), which can be characterized as a uniform burst strength along the graft length. Lastly, the delamination strength (the force needed to delaminate the sequentially electrospun fibrous layers) will be uniform across the graft length.

[0043] Furthermore, the nesting configuration also results in more design flexibility in other graft parameters, in particular in relation to MRI compatibility. For a graft having individual SRS’s instead of a single, longer or shorter individual SRS can be nested to segment and alter the effective length of the device, which results in less risk of overheating and therefore lower risk for the patient at certain magnetic fields (this relates to radiofrequency induced heating in the MRI scanner). This advantage holds for metal (conductive) SRSs in general.

[0044] ESSENTIAL ELEMENTS OF EMBODIMENTS

[0045] 1. No physical contact between the individual SRSs in the final device.

[0046] 2. Crown structure to prevent flapping during graft manufacturing (e.g electrospinning): it makes a closed ring at least at one of the ends of the SRS (reader is referred to US 2023 / 0346537). 3. The crown has to be continuous, connected to itself, terminating the SRS in closed loop, but does not have to be straight, (i.e. fully perpendicular to the main body of the SRS) (oblique with respect to the main body of the SRS is also possible).

[0047] 4. The axial pitch has to be equal, or highly similar for every point between the two individual SRS elements (the nesting area), which is the same axial pitch as between struts within a single SRS element (FIGs. 7A-C).

[0048] Some other considerations:

[0049] 1. The SRS element can rotationally translate with respect to each other, resulting in multiple ideal nesting configuration (FIGs. 5A-B).

[0050] 2. When the SRS is symmetrical, perfect nesting can be achieved independent of the longitudinal orientation of the second SRS element (FIG. 6).

[0051] Manufacturing and deployment

[0052] The example provided here is for an electrospun graft. However, as noted earlier, electrospinning is not the only relevant manufacturing technique for the manufacturing of the polymeric layers of the graft.

[0053] 1. An inner layer of polymer is electrospun on a target.

[0054] 2. To deploy the first SRS element, a single SRS element is loaded onto a deployment tube.

[0055] 3. The deployment tube with the SRS element is slid over the inner layer of the graft.

[0056] 4. Very slowly, the SRS is slid from the deployment guiding tube, so that the SRS is then placed in direct contact with the spun inner layer, without the deployment tube. 5. The deployment tube is then removed from the graft, so that the inner layer is partly covered by the first SRS element.

[0057] 6. To deploy the second SRS element another SRS element is loaded onto a deployment tube.

[0058] 7. The deployment tube with the second SRS element is slid over the inner layer in close proximity of the first SRS element.

[0059] 8. Very slowly, the second SRS element is slid from the deployment guiding tube, so that the SRS is then placed in direct contact with the spun inner layer, without the deployment tube.

[0060] 9. The second SRS element is positioned in such a way that a constant pitch is achieved between the first and second SRS element. This is resulting in a nesting area with a pitch equal to the pitch of the struts within a single SRS element.

[0061] 10. The resulting inner layer of the graft is now covered by two SRS elements directly onto the electrospun layer, whereby an equal pitch is achieved within the nest of the individual SRS elements.

[0062] 11. The process above can be repeated depending on the required final number of SRS elements.

[0063] 12. Next, the device is completed by electrospinning the final polymer layers, so that the SRS is fully embedded within the polymer matrix.

[0064] Visual inspection

[0065] To confirm the positioning and the pitch of the SRS components, visual inspection is performed using a microscope directly after SRS deployment. The pitch between a series of struts is then measured. Kink resistance

[0066] The test sample is pre-conditioned at 37°C in aqueous solution. The graft is wrapped around a calibrated cylinder with specific radii, so that this cylinder is in the middle of the graft, ISO 7198-2016. This test is then repeated using smaller cylinders. The smallest radius at which kink is first observed, is registered as the kink resistance. This protocol is based on ISO 7198-2016.

[0067] For an application where a graft needs to bend, for example a looped graft in the forearm for arteriovenous access, a loop diameter of 4 cm may be needed. In this case, the test specimen should pass a kink radius of 2 cm.

[0068] The desired pitch within the nest (where the two SRS elements would meet) is equal to the pitch between struts of the individual SRS elements. For example, the pitch between struts may be 2.4+ / -0.3mm within the SRS elements; thus, the spacing of the nested region (pitch between the neighboring SRS elements) should also be 2.1 -2.7mm. A nest pitch of >2.7mm or <2.1 mm will have mechanical consequences such as kinking (if too far) or metal to metal abrasion (if too close).

[0069] It is important for the embodiments that the inner and outer tubular layer are each porous polymer layers with a porosity large enough to allow for cell ingrowth upon implantation to promote the endogenous tissue restoration or growth. The inner and outer tubular layers are functionally replaced over time by the endogenous tissue restoration or growth as a result of the cell (in)growth. In an additional embodiment, the inner and / or outer tubular layer comprises a biodegradable polymer. In one embodiment, a nested in-series strain relief system is embedded by an inner layer and an outer layer. In one example therewith, the inner layer and the outer layer are electrospun layers, polymeric layers, fibrous layers, or porous layers, or a combination thereof. In another example therewith, the inner layer and the outer layer are layers produced by electrospinning, electro-writing, 3D printing, freeze drying, solvent casting, particle leaching, gas foaming, thermal -induced phase separation, selective laser sintering, stereolithography, fused deposition modelling, multiphase jet solidification, precise extrusion deposition, 3D bioplotting, inkjet printing, or bacterial cellulose synthesis, or a combination thereof. In still another example therewith the inner layer and the outer layer are layers enabling endogenous tissue restoration, tissue ingrowth, or a combination thereof.

[0070] The graft material referenced in this document may be a polymer comprising the ureido- pyrimidinone (UPy) quadruple hydrogen-bonding motif (pioneered by Sijbesma (1997), Science 278, 1601-1604) and a polymer backbone, for example selected from the group of biodegradable polyesters, polyurethanes, polycarbonates, poly(orthoesters), polyphosphoesters, polyanhydrides, polyphosphazenes, polyhydroxyalkanoates, polyvinylalcohol, polypropylenefumarate. Examples of polyesters are polycaprolactone, poly(L-lactide), poly(DL-lactide), poly(valerolactone), polyglycolide, polydioxanone, and their copolyesters.

[0071] Examples of polycarbonates are: poly (trimethylenecarbonate), poly(dimethyltrimethylenecarbonate), poly(hexamethylene carbonate). The same result may be obtained with alternative, non-supramolecular polymers, if properties are carefully selected and material processed to ensure required surface characteristics. These polymers may comprise biodegradable or non-biodegradable polyesters, polyurethanes, polycarbonates, poly(orthoesters), polyphosphoesters, polyanhydrides, polyphosphazenes, polyhydroxyalkanoates, polyvinylalcohol, polypropylenefumarate. Examples of polyesters are polycaprolactone, poly(L-lactide), poly(DL-lactide), poly(valerolactone), polyglycolide, polydioxanone, and their copolyesters. Examples of polycarbonates are poly(trimethylenecarbonate), poly(dimethyltrimethylenecarbonate), poly(hexamethylene carbonate).

[0072] Embodiments of the invention can be considered, in various forms, as open-ended language like comprising, but also as consisting essentially of, consisting of as well as a nested inseries strain relief system wherein the improvement comprises.

Claims

CLAIMSWhat is claimed is:

1. A nested in-series strain relief system, comprising:(a) a first strain relief system with at one end a first crown, wherein the first crown has a first closed zig-zag pattern; and(b) a second strain relief system with at one end a second crown, wherein the second crown has a second closed zig-zag pattern substantially mirroring the first closed zig-zag pattern, wherein the first crown and the second crown are nested together yet without making contact with each other while spaced at a distance in a longitudinal direction of both the first strain relief system and the second strain relief system, and wherein the nested first strain relief system and the second strain relief system define the nested in-series strain relief system.

2. The nested in-series strain relief system as set forth in claim 1, wherein an axial pitch is defined between the first crown of a first strain relief system and the second crown a second strain relief system, wherein the axial pitch is substantially similar to an axial pitch defined for the nested in-series strain relief system.

3. The nested in-series strain relief system as set forth in claim 1, wherein the second crown is rotated with respect to the first crown, wherein an axial pitch is defined between the first crown of a first strain relief system and the second crown a second strain relief system, wherein the axial pitch is substantiallysimilar to an axial pitch defined for either the first strain relief system or the second strain relief systems.

4. The nested in-series strain relief system as set forth in claim 1, wherein the first crown and the second crown are symmetric or substantially symmetric.

5. The nested in-series strain relief system as set forth in claim 1, wherein the first strain relief system and the second strain relief system are nitinol strain relief systems, polymer strain relief systems or metal strain relief systems.

6. The nested in-series strain relief system as set forth in claim 1, wherein the nested in-series strain relief system is embedded by an inner layer and an outer layer.

7. The nested in-series strain relief system as set forth in claim 6, wherein the inner layer and the outer layer are electrospun layers, polymeric layers, fibrous layers, or porous layers, or a combination thereof.

8. The nested in-series strain relief system as set forth in claim 6, wherein the inner layer and the outer layer are layers produced by electrospinning, electro-writing, 3D printing, freeze drying, solvent casting, particle leaching, gas foaming, thermal-induced phase separation, selective laser sintering, stereolithography, fused deposition modelling, multiphase jetsolidification, precise extrusion deposition, 3D bioplotting, inkjet printing, or bacterial cellulose synthesis, or a combination thereof.

9. The nested in-series strain relief system as set forth in claim 6, wherein the inner layer and the outer layer are layers enabling endogenous tissue restoration, tissue ingrowth, or a combination thereof.

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