Electrospun polymer assemblies for medical implants

Abstract

To provide a medical implant that has a first electrospun component and a second electrospun component with the same type of biodegradable electrospun polymers.SOLUTION: In one example, a second electrospun component is manufactured separately from a first electrospun component. Furthermore, a medical implant is structured such that the first electrospun component and the second electrospun component are assembled or joined together by the same type of biodegradable electrospun polymers as in the first electrospun component and the second electrospun component. The medical implant is a porous, biodegradable medical implant, and can be replaced with a naturally ingrown tissue over time after implantation.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to tissue engineering products and methods. [Background technology]

[0002] Cardiovascular diseases are one of the leading causes of death worldwide. One of the methods to treat at least some of these diseases is tissue engineering. Tissue engineering can be used for the replacement of cardiovascular tissues such as arteries and heart valves. The most commonly used heart valve replacements today are bioprosthetic heart valves, which typically contain tissues, mainly of animal origin, as leaflet material. The leaflet tissues are usually sewn together and joined to the valve by sewing. Furthermore, the animal tissue can be chemically fixed to set the appropriate shape for optimal hemodynamics without compromising the material properties or the durability of the leaflets.

[0003] Currently used cardiovascular substitutes carry risks from clotting, infection, and degeneration, and also lack the potential for growth. Tissue engineering is based on endogenous tissue regeneration (ETR), using the patient's own cells and biodegradable polymer scaffolds to create autologous tissue that can grow, adapt, and repair. To ensure proper cell and tissue growth, the scaffold must be highly porous and match the mechanical properties of the tissue.

[0004] Electrospinning is a technique that utilizes high-voltage electrostatic fields to produce polymer nanofiber materials. This technique results in highly porous nanofiber materials that resemble the extracellular matrix of tissues. Tissue engineering can be used, for example, in coronary artery bypass grafts, heart valve replacements, and AV shunts for dialysis patients.

[0005] When considering bioabsorbable polymer scaffolds as leaflet materials, the usual methods are not necessarily applicable, and the use of sewing techniques shows reduced durability due to tearing, especially in areas of high stress where the sewing is located.

[0006] The appearance and contour of a bioprosthetic surgical aortic valve during diastole dictates the stress concentration at the top of the posts. When the valve is under maximum load, the posts deflect inwards and high shear stresses are generated at the top of the attachment surfaces due to the difference in stiffness between the rigid metal frame and the flexible leaflet material.

[0007] Another possible disadvantage of stitching the struts is the possibility of calcified deposits forming around the struts in vivo due to the laser-cut holes for precise stitching and sewn placement. As the struts are relatively static compared to the leaflets, which are highly mobile, tissue formation is expected to be promoted there. To some extent, it has been observed that calcified deposits appear around the struts at certain stitching locations. This observation may lead to poorer hemodynamic behavior of the valve and reduced durability in vivo.

[0008] The present invention addresses these problems and advances the art by providing a medical implant based on techniques other than sewing. Summary of the Invention [Means for solving the problem]

[0009] The present invention provides a cardiovascular medical implant or medical implant comprising a first electrospun member comprising a biodegradable electrospun polymer and a second electrospun member comprising the same biodegradable electrospun polymer as the first electrospun member. In an embodiment, the second electrospun member is manufactured separately from the first electrospun member. Furthermore, the structure of the cardiovascular medical implant or medical implant of the present invention is such that the first electrospun member and the second electrospun member are welded together or bonded by the same biodegradable electrospun polymer material as the first electrospun member and the second electrospun member to form an assembly or combination. The cardiovascular medical implant or medical implant is configured to be a porous biodegradable medical implant, which can replace naturally ingrown tissue over time after implantation. The assembly or combination of the first electrospun member and the second electrospun member is formed by ultrasonic welding or bonding them together using an adhesive. Examples of such cardiovascular medical implants include those in which the first electrospun member and the second electrospun member are members that comprise a tissue engineered heart valve, a tissue engineered vascular graft, or a tissue engineered blood vessel.

[0010] In one embodiment, the cardiovascular medical implant or medical implant is configured such that the first electrospinning member and the second electrospinning member are not sewn or stitched together, or the first electrospinning member and the second electrospinning member do not have stitched or stitched areas.

[0011] In a further embodiment, the cardiovascular or medical implant includes a support structure assembled or coupled between the first electrospinning member and the second electrospinning member.

[0012] The invention further provides a tissue engineered heart valve comprising two (or more) electrospun heart valve members fabricated separately from the same biodegradable electrospun polymer. The two electrospun heart valve members fabricated separately are assembled by welding together or bonding with the same biodegradable electrospun polymer as an adhesive. The tissue engineered heart valve is thus configured to be a porous biodegradable medical implant after implantation that can be replaced by naturally grown tissue over time. The assembly or combination of the two electrospun heart valve members fabricated separately are bonded together by ultrasonic welding or bonding with an adhesive.

[0013] In one embodiment, the tissue engineered heart valve is configured such that two electrospun heart valve members fabricated as separate entities are not sewn or stitched together, or such that two electrospun heart valve members fabricated as separate entities do not have any stitched or stitched areas.

[0014] In a further embodiment, the tissue engineered heart valve includes a support structure assembled or bonded between two separately manufactured electrospun heart valve members. The invention further provides a method of assembling two separately manufactured electrospun members to form a cardiovascular medical implant or medical implant. A first electrospun member is electrospun using a biodegradable electrospun polymer. A second electrospun member is electrospun separately from the first electrospun member using the same biodegradable electrospun polymer as the first member. The first electrospun member and the second electrospun member are then welded together or glued with the same biodegradable electrospun polymer used for the first electrospun member and the second electrospun member, thereby creating a porous biodegradable medical implant that can be replaced by naturally grown tissue over time after implantation. Examples of assembly methods include ultrasonic welding, gluing, etc. Examples of assembled cardiovascular medical implants or medical implants include where the first electrospun member and the second electrospun member are members that make up a tissue engineered heart valve, a tissue engineered vascular graft, or a tissue engineered vascular member.

[0015] In one embodiment, the method excludes stitching or sewing, i.e., the first and second electrospinning members are not stitched or sewn together, or the first and second electrospinning members are configured to have no stitched or sewn areas.

[0016] In another embodiment, the method includes the further step of assembling a support structure between the first and second electrospun members. Examples of such support structures include stents, frames, braided or mesh structures for supporting cardiovascular or medical implants. In an example of making such a device, the first electrospun member is electrospun, and then the support structure is added on top of the first electrospun member. Then, the second electrospun member is electrospun on top of the support structure and the first electrospun member. The first and second electrospun members are joined to each other by assembly or bonding, such as by ultrasonic welding or gluing, with the support structure laminated therebetween.

[0017] In yet other embodiments, the step of assembling includes patterning the areas where the first and second electrospun members are bonded by welding or gluing. In some variations of the embodiment, the assembling or bonding by welding (e.g., ultrasonic welding) or gluing can be performed in areas that are substantially circumferential, helical, or circular patterns. This can improve the kink resistance of the medical implant in some embodiments.

[0018] Advantages of the present invention include: In medical implant concepts such as heart valves, the use of two electrospun members in the heart valve avoids the use of sutures. This eliminates the disadvantages of sutures such as stress concentration and manual handling. Meanwhile, the microstructure / porosity is only affected locally, even at the interface between materials, so the potential for ETR is maintained. Around the local welds, tissue can be formed inside the scaffold. The assembly or joining of electrospun members according to the present invention by welding or gluing is more accurate, reproducible, and automatable than stitching or sewing. Furthermore, the assembly or joining of electrospun members according to the present invention by welding or gluing is achieved with the same polymers that make up the electrospun structure, so no additional materials such as sutures or other fixatives are required.

[0019] The present invention has the same advantages for medical implant concepts such as vascular grafts or vascular concepts as for heart valves. Furthermore, the absence of sutures eliminates suture holes and improves hemostasis (bleeding rate) during implantation of grafts and vessels. Furthermore, the patterned welded areas allow tuning / optimization of mechanical properties, one example being improved kink resistance. In some aspects, the ultrasonic weld pattern itself may provide a support structure to ensure sufficient kink resistance. [Brief description of the drawings]

[0020] [Figure 1] 1 shows a first electrospun member 110 comprising a biodegradable electrospun polymer and a second electrospun member 120 comprising the same biodegradable electrospun polymer as the first electrospun member 110 according to an exemplary embodiment of the present invention. In one example, the second electrospun member is manufactured separately from the first electrospun member, as shown in the top diagram of FIG. 1. The bottom diagram of FIG. 1 shows the first electrospun member 110 and the second electrospun member 120 joined at the joining sites (both 130) by ultrasonic welding or by gluing using the same biodegradable electrospun polymer as the adhesive as the first and second electrospun members to form an assembly or combination. This assembly forms a medical implant capable of endogenous tissue regeneration (ETR). [Diagram 2]1 shows cross-sectional views of an exemplary embodiment of the present invention, with the arrows pointing from top to bottom, showing the configuration before the circular polymer tube cover and sheet-like polymer leaflets are welded in the top left figure, and the configuration after the polymer tube cover and polymer leaflets are ultrasonically welded in the top right figure. The top figure shows a cross-section of the center of the weld surface, and the bottom figure shows a close-up of the weld cross-section. Also, in the bottom figure, a solid (closely packed welded material) bond is visible between the two components, but the mesh morphology of the polymer tube cover and polymer leaflets is still visible where the welding device contacted the polymer pieces. The solid bond is clearly seen deeper between the components where the change in morphology is less related to ETR. [Diagram 3] 1 shows cross-sectional views of an exemplary embodiment of the invention, with the arrows pointing from right to left. The left image shows a cross-sectional view (SEM photo) of a fully assembled aortic valve leaflet and a tube cover welded thereto. The middle image shows a close-up of the left image to clearly show how the outer regions maintain the mesh morphology while a solid weld is formed inside the joint between the members. The right image shows a side view (along the arrows) of the weld in the area where the welding device contacted the leaflet. Vertical seam marks along the weld line can be seen, but the mesh morphology is almost perfectly maintained. This maintenance of mesh morphology is the basis for successful ETR of the device without changing the outer morphology of the device. [Figure 4] FIG. 1 shows an exemplary laser cut material according to an exemplary embodiment of the present invention, illustrating the manufacturing process of the welding concept (see steps 1-5 in the text). [Diagram 5] FIG. 2 is a cross-sectional view of a post portion of a bonded support structure according to an exemplary embodiment of the present invention as viewed by SEM. [Figure 6]1A-1C show cross-sectional and side views illustrating the formation of a "wedge" weld by ultrasonic welding according to an exemplary embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] An embodiment of the present invention is a medical implant formed by two separate parts made of the same electrospun polymer, assembled or bonded together by welding them together or by gluing them with the same polymer. Two examples are provided here. In the first example, two separate parts made of a polymer are welded together to form an assembly or bond. In the second example, two separate parts made of a polymer are glued together with the same polymer used for them. In other words, the medical implant is composed of two separately manufactured parts assembled or bonded together by welding them together or by gluing them together using the same polymer as the material of the parts. This results in a medical implant manufactured from separate parts, despite using the same polymer. An example of such a medical implant is a heart valve, including one or more leaflet members and possibly one or more support structures, which are assembled in a form without stitches or sewn. The present invention is not limited to this example and applies to any kind of electrospun implant, where the members are manufactured separately and assembled to form the medical implant. Importantly, despite the resulting assembly or bond, the medical implant resulting from the assembly maintains the characteristics of being not only porous, but also biodegradable and / or capable of ETR after implantation in the body.

[0022] In another embodiment of the present invention, a medical implant including a support structure is formed by two electrospun members including the same electrospun polymer, and the two electrospun members are assembled or bonded by welding the polymers of the two electrospun members together or by gluing using the same polymer material of the two electrospun members, and the support structure is sandwiched between the two electrospun members to form a laminate structure. Examples of such support structures include stents, frames, braided structures, or mesh structures for supporting cardiovascular or medical implants. In one example of making such a device, after electrospinning a first electrospun member, a support structure is added on top of the first electrospun member, and then a second electrospun member is electrospun on the support structure and the first electrospun member. The first electrospun member and the second electrospun member are then bonded to each other by welding (e.g., ultrasonic welding) or gluing, forming a laminate structure including the support structure.

[0023] ultrasonic welding

[0024] Ultrasonic welding is an industrial technique in which high frequency ultrasonic acoustic vibrations are applied locally to workpieces held under pressure to weld solid objects together. In ultrasonic welding of thermoplastics, friction-induced heating melts the plastic locally. Ultrasonic welding can theoretically be used with any type of polymer.

[0025] The ultrasonic welding process involves various parameters that must be determined for the specific application to obtain optimal weld quality, such as frequency, amplitude, weld energy, time, pressure, etc. It also requires the development and optimization of the complete process, including dedicated tools (e.g. sonotrodes and boosters) to allow for different weld shapes and sizes. There is no "off-the-shelf solution" available for all materials.

[0026] Known advantages of ultrasonic welding are that it is much faster than traditional adhesives or solvents. Ultrasonic welding has a very short drying time, so parts do not need to be kept in the fixture for long periods of time waiting for the joint to dry and harden. Welding can be easily and fully automated, resulting in clean and precise joints. Welds are considered very clean and repeatable, with very little need for touch-up work. Also, more material can be welded because the heat has less effect on the material.

[0027] The medical industry is exploring the use of ultrasonic welding, as it does not introduce any contaminants or degradation into the weld and can be processed specifically for cleanroom use. The highly automated process allows for tight control of dimensional tolerances and does not interfere with the biocompatibility of the materials used. Nevertheless, nothing is known about the changes in surface morphology during welding, and therefore properties related to biodegradability and ETR.

[0028] In fact, those skilled in the art would discourage the use of welding since the polymer will eventually "melt" and the fine polymer fibers will melt, causing loss of specific structure and mechanical properties, as well as changes in surface morphology.

[0029] In certain cardiac applications where the porous mesh structure of polymer fibers is exposed to blood flow and rapid tissue growth is desired as part of the ETR process, it is crucial to maintain the mechanical properties and morphology of the mesh structure for optimal cell growth. For the purposes of this invention, the inventors have discovered that, macroscopically, welding does not alter the surface properties of the porous polymer structure, and therefore excellent ETR properties are still obtained. It has also been found that the welds formed exhibit surprising durability, which is essential for medical implant applications.

[0030] In one example, ultrasonic welding has been used instead of sewing to the struts of a heart valve. The welded parts of the implantable device are preferably not completely exposed to the biological flow of blood cells. This technique has great potential because localized melted areas of such parts can be created between two layers of polymer, hidden from the outside.

[0031] Preferably, only one polymer is used to manufacture the valve, avoiding the use of additional materials such as suture materials, which is particularly important in this case since the entire device will exhibit the same degradation rate.

[0032] Another example of the use of ultrasonic welding in medical applications is in artificial vascular grafts, where two electrospun tube layers can be bonded in one or more desired locations and in a desired pattern. The welding pattern can be used to embed a support structure with specific mechanical properties (e.g., strain relief properties) between the two electrospun tube layers while reducing the risk of the electrospun tube layers delaminating from each other. The welding pattern can also be used to affect the mechanical properties of the implant. For example, a spiral pattern with continuous welding can help the implant bend without kinking.

[0033] The ultrasonic welding method used in the embodiments of the present specification can be characterized by the following parameters used during the process: The welding frequency is 45-70 kHz, and preferably about 70 kHz. A welding energy of 0.1-5 W*sec is applicable, and a welding energy of 0.3-1.5 W*sec is preferred. As for the welding time, it is 0.1-5 seconds, and preferably 0.1-2 seconds.

[0034] SEM examination of the welds made with the method of the present invention shows that the welded areas are stamped by the horn on the outside of the leaflet. The weld is initiated by the contact of the horn with the outer surface of the leaflet, but the morphology of the mesh (porosity, fiber diameter, etc.) remains surprisingly unchanged in the welded outer surface area. It is therefore concluded that this welding process can be successfully used for ETR applications. The outer surface does not prevent or reduce the ETR effect, but rather may enhance it. This eliminates foreign objects (such as suture wires) and heat-affected zones (such as laser cut holes for suture wires) that may cause lime deposits and reduce the ETR effect around these locations.

[0035] During welding, small mechanical vibrations of a certain frequency are transmitted through a number of "sonotrodes" or horns to the two polymer pieces to be joined together. The horns are in contact with the outside of a first polymer piece and are designed to transmit a certain magnification (gain) of these vibrations to the polymer. The sudden frictional energy generates heat locally between the inside of the first polymer piece and the outside of the second polymer piece. This causes the outer layer of the second polymer piece to shape so that it can be stretched over the metal frame of the surgical valve strut. The metal frame is preferably used as an anvil to provide the initial contact surface between the polymer pieces. This contact, together with the pressure applied to the outer layer of the first polymer piece through the horns, is important for localized and precise welding. The metal frame of surgical prosthetic heart valves is usually made of titanium or a titanium alloy, so the horn is preferably made of titanium as well.

[0036] The heat generated by the aforementioned frictional energy results in a localized melting pattern that creates a robust bond between the two polymer pieces. Surprisingly, this bond has been shown to be strong enough to withstand the conditions of accelerated in vitro wear testing. Additionally, less strut deflection has been repeatedly observed during full valve load. This is because the less stiff bond between the leaflets and frame (compared to prior art sutures) allows the stiffer frame struts to better resist bending, resulting in less deflection. The association between less strut deflection and increased durability indicates less stress concentration on the struts.

[0037] In this pattern, material properties such as porosity and mesh morphology are maintained primarily at the outer surface of the polymer exposed to the blood flow, allowing ETR to occur in vivo.

[0038] When sewing, a lot of force is required to keep the valve in the correct position. Sutures are usually strong and rigid, with no flexibility or bendability. Thus, the leaflets are held in a specific position by the sutures and can hardly move. The inventors have confirmed that it is very important to finally "set" the valve in the right position and adjust it to the optimal shape. By using a welded seam instead of sewing, the optimal position of the valve can finally be found, relieving the entire structure from high stress points that can lead to device rupture and failure. Furthermore, since the welded seam does not contain any additional material (like sutures), it allows for a nearly uniform movement throughout the system.

[0039] The weld area or horn is preferably immersed in fluid and / or water. Since the melting point of the polymer is below 100° C., the water will not evaporate as an inherent attribute, but will still form a specific weld pattern (one that provides sufficient weld durability while also creating a morphology that supports ETR). Thus, one skilled in the art would refrain from welding wet polymer pieces as this would compromise the uniformity of the weld or may not be possible at all.

[0040] The leaflet and frame assembly, other than at the posts, can also be formed by ultrasonically welding the bottom of the polymer leaflet and the PET cover of the metal frame together.

[0041] The embodiments provided herein eliminate the issues associated with sewing, improving the ETR compatibility and hemodynamic performance of the heart valve. Another notable advantage is that by using ultrasonic welding instead of sewing, the time required for assembly is reduced by welding the struts, which typically requires slow and careful stitching to locate the exact stitching location, and this time is reduced by approximately 75%. Ultimately, this allows for faster valve assembly, allowing for faster iterations during the process development phase and subsequently a more cost-effective final product.

[0042] An example of a welding concept manufacturing process is as follows:

[0043] Step 1

[0044] The spinning is performed as usual, but a dedicated design is used with only two laser-cut suture holes on each strut (for fixation sutures). The design can include laser-formed recesses for more precise welding. The suture holes can also be replaced with similar recesses. Please note that if welding is used instead of a running stitch at the bottom of the leaflet, the lower laser-cut holes are not cut, as shown in Figure 4.

[0045] Step 2

[0046] The valve comes partially assembled with a full running stitch around the bottom of the frame and only one fastening stitch on each post, and the running stitch could be replaced with a full circumferential running weld as the PET fabric has been found to weld surprisingly well and provide a sturdy join.

[0047] Step 3

[0048] While the leaflets are forced into a closed configuration, they are ultrasonically welded (twice welded to each strut) to the strut covers (tubes) on the sides of each strut. In other configurations, a similar weld (on both sides of the strut) can be achieved with one weld touch instead of two.

[0049] Step 4 (optional step)

[0050] Remove the fastening stitches from the center of each post. In some configurations, the fastening stitches are retained because they are not located in the highly mobile portions of the leaflets and provide additional strength to attach the leaflets to the posts other than by welding, in such configurations this removal step is not required.

[0051] Step 5 (optional step)

[0052] A second welding step is performed (at the center of each strut) where the fixing stitches were removed. This step is not required, but can be applied to other configurations, including cases where the center of the strut is strong enough not to be welded.

[0053] Step 6

[0054] The final assembled valve has the leaflets held together only by welding. This particular configuration shows that the running stitch on the bottom of the frame has been replaced with a running weld. Thus, this Figure 4 shows a stitchless valve according to the present invention.

[0055] These method steps may be varied depending on the desired purpose or structure, and the invention is not limited to these steps or this sequence of steps.

[0056] Adhesion

[0057] The use of adhesives to join valves and the like has not previously been considered because of known disadvantages such as: The adhesive required for bonding has limited heat resistance, chemical resistance or load bearing capacity (due to its chemical basis). The mechanical properties of the bond are therefore temperature dependent and different compared to the properties of the adhesive material. This results in areas of high stress and low durability. The long-term stability of the bond is subject to aging and will change during the life of the device, which is unacceptable for a medical device. · Adhesive processes require adhesives and auxiliary compounds that are generally not biocompatible or toxic and / or require special precautions.

[0058] Most commercially available tissue valves have a stiffness difference between the tissue covering and the metal frame that can cause wear and lead to failure of the device. Therefore, different materials are used to protect the struts, and they are usually made of softer materials than the frame (e.g., synthetic or plastic liners). Still, improvements and further developments are needed for tissue valves.

[0059] The surgical aortic valve, in its general embodiment, includes three tubular components made of the same polymer that are used as strut covers. These tubular components (strut covers) are placed on the frame of the valve and their purpose is to reduce wear between the leaflets, which move more quickly, and the metal frame, which moves less quickly.

[0060] In embodiments of the present invention, these wear protection components made from electrospun materials produced from polymers are utilized as bonds are created between the leaflet scaffold and the struts in the form of adhesive instead of stitching.

[0061] Adhesion is achieved using the same polymer solution, specifically by applying the solution to the area where a bond is required between the leaflet and the frame struts. The viscous solution is applied topically to the surface of the strut cover, and then the leaflet scaffold is formed by spinning the solution directly onto it while still in a liquid state. When the solution dries and hardens, a robust bond is formed between the leaflet scaffold and the strut cover. The solid polymer layer that forms this bond is not exposed to the bloodstream, so ETR is effectively performed there. Furthermore, there is no stitching around the struts in this configuration, suggesting even faster tissue growth than seen in prior art configurations.

[0062] By using the same polymer for electrospinning and bonding, the bonded joint has similar material properties as the adhesive material, which can potentially distribute stress and ultimately provide greater durability by shifting stress points.

[0063] Good fatigue durability of the prosthetic valve frame is related to the deflection of the frame struts and the inward bending of the frame struts. Too much deflection of the struts can lead to poor leaflet function or even excessive pinwheeling. When this new adhesive method is applied to the leaflet attachment, the struts can more easily withstand the deflection. As a result, less deflection of the struts is measured when measuring the deflection of the struts.

[0064] Surprisingly, the inventors have discovered that valves made in accordance with the present invention are less sensitive to unequal volumes of the bond areas between the struts as an effect on durability both in vitro and in vivo.

[0065] Furthermore, a significant advantage of the present invention is that the assembly process of the scaffold after the bonding process is significantly faster than prior art configurations, with a significantly faster assembly process time of approximately 1 hour suggested for the inventive configuration compared to approximately 4 hours for the prior art configuration.

[0066] An additional benefit of this configuration is the elimination of bottom stitching. In addition to the robust bond at the struts, there is only one circumferential running stitch at the base of the metal frame at the bottom of the leaflet. The lack of bottom stitching at any of the struts allows the polymer scaffold to shape under load for optimal pressure distribution. This results in no stress concentration points around the struts, which increases the durability of the valve.

[0067] An example of the manufacturing steps for the bonded strut concept is as follows:

[0068] Step 1

[0069] Assemble the electrospinning target.

[0070] Step 2

[0071] A post cover made of polymer is attached to each post.The electrospinning target is then reassembled.

[0072] Step 3

[0073] The electrospinning target is fixed into the electrospinning box and each post is thoroughly polished by hand with the wet polymer solution.

[0074] Step 4

[0075] The scaffold is laid down by spinning and once complete, it is removed from the electrospinning box.

[0076] Step 5

[0077] If necessary, cut the scaffold according to the valve design pattern.

[0078] Step 6

[0079] The valve is assembled on a given frame with nothing attached to the supports except for the tube stretched over the frame.

[0080] Step 7

[0081] Apply a running stitch to the bottom of each leaflet to complete the assembly.

[0082] These method steps may vary depending on the desired purpose and structure, and the invention is not limited to these steps or this order.

[0083] Another notable method for strut-attached fabrication is to electrospin the leaflets and strut covers separately and then use a specialized tool to bond the components together. The leaflets are held in an expanded position at the correct location until the strut covers, loaded with the correct amount of adhesive, are inserted at the desired location. Localized pressure is applied to the struts until the adhesive dries completely, after which the leaflets are released. This method facilitates equalizing the amount of adhesive on each strut and eliminates potential variations in the adhesive surface between the struts, improving the durability of the valve.

[0084] Definition of Polymer for the Purposes of the Invention

[0085] The polymer or supramolecular polymer referred to herein may be composed of a ureido-pyrimidinone (UPy) quadruple hydrogen bonding motif (first studied by Sijbesma (1997), Science 278, 1601-1604) and a polymer backbone. For example, it may be selected from the group including biodegradable polyesters, polyurethanes, polycarbonates, poly(orthoesters), polyphosphoesters, polyanhydrides, polyphosphazenes, polyhydroxyalkanoates, polyvinyl alcohols, and polypropylene fumarates. Examples of polyesters include polycaprolactone, poly(L-lactide), poly(DL-lactide), poly(valerolactone), polyglycolide, polydioxanone, and copolyesters thereof. Examples of polycarbonates include poly(trimethylene carbonate), poly(dimethyltrimethylene carbonate), and poly(hexamethylene carbonate).

[0086] Similar results may be obtained with alternative non-supramolecular polymers if the properties are carefully selected and the materials are treated to ensure the required surface properties. Such polymers may consist of biodegradable or non-biodegradable polyesters, polyurethanes, polycarbonates, poly(orthoesters), polyphosphoesters, polyanhydrides, polyphosphazenes, polyhydroxyalkanoates, polyvinyl alcohols, and polypropylene fumarates. Examples of polyesters include polycaprolactone, poly(L-lactide), poly(DL-lactide), poly(valerolactone), polyglycolide, polydioxanone, and their copolyesters. Examples of polycarbonates include poly(trimethylene carbonate), poly(dimethyltrimethylene carbonate), and poly(hexamethylene carbonate). <Reference> The description of the specification before the correction of the mistranslation due to the mistranslation correction notice dated October 11, 2024 of the original application [Technical field]

[0001] The present invention relates to tissue engineering products and methods. [Background technology]

[0002] Cardiovascular diseases are one of the leading causes of death worldwide. One approach to treat at least some of these diseases is tissue engineering. Tissue engineering can be used to replace cardiovascular tissues, such as arteries and heart valves. The most commonly used heart valve replacements today are bioprosthetic heart valves, which typically contain tissues, mainly of animal origin, as leaflet material. The leaflet tissues are usually sewn and attached to the valve by sutures. Furthermore, chemical fixation of the animal tissues allows the appropriate geometry to be set for optimal hemodynamics without compromising the material properties or durability of the leaflets.

[0003] Currently used cardiovascular substitutes carry risks from clotting, infection, and degeneration, and also lack the potential for growth. Tissue engineering is based on endogenous tissue regeneration (ETR), using the patient's own cells and biodegradable polymer scaffolds to create autologous tissue that can grow, adapt, and repair. To ensure proper cell and tissue growth, the scaffold must be highly porous and match the mechanical properties of the tissue.

[0004] Electrospinning is a technique that utilizes high-voltage electrostatic fields to produce polymer nanofiber materials. This technique results in highly porous nanofiber materials that resemble the extracellular matrix of tissues. Tissue engineering can be used, for example, in coronary artery bypass grafts, heart valve replacements, and AV shunts for dialysis patients.

[0005] When considering bioabsorbable polymer scaffolds as leaflet materials, common methods are not necessarily applicable, and suturing techniques show reduced durability due to tearing, especially in areas of high stress where the seams are located.

[0006] The stress concentration at the top of the posts determines the appearance and contour of a bioprosthetic surgical aortic valve during diastole. When the valve is under maximum load, the posts deflect inwards and high shear stresses are generated at the top of the attachment surface due to the difference in stiffness between the rigid metal frame and the flexible leaflet material.

[0007] Another possible disadvantage of suturing the struts is the possibility of calcified deposits forming around the struts in vivo due to the laser-cut holes for precise suturing and stitching. As the struts are relatively static compared to the leaflets, which are highly mobile, it is expected that enhanced tissue formation will begin there. Depending on the suture location, it has been observed to some extent that calcified deposits appear around the struts. This observation may lead to deterioration of the valve's behavior in blood and reduced durability in vivo.

[0008] The present invention addresses these problems and advances the art by providing a medical implant based on techniques other than suturing. [Summary of the Invention] [Means for solving the problem]

[0009] The present invention provides a cardiovascular medical implant or medical implant comprising a first electrospun member comprising a type of biodegradable electrospun polymer and a second electrospun member comprising the same type of biodegradable electrospun polymer as the first electrospun member. In an embodiment, the second electrospun member is manufactured separately from the first electrospun member. Furthermore, the cardiovascular medical implant or medical implant of the present invention is configured such that the first electrospun member and the second electrospun member are held together or bonded together by the same type of biodegradable electrospun polymer as the first electrospun member and the second electrospun member. The cardiovascular medical implant or medical implant is configured to be a porous biodegradable medical implant after implantation that can replace naturally ingrown tissue over time. The assembly or combination of the first electrospun member and the second electrospun member is welded together by ultrasound or adhesive. Examples of such cardiovascular medical implants include those in which the first electrospun member and the second electrospun member are members that comprise a tissue engineered heart valve, a tissue engineered vascular graft, or a tissue engineered blood vessel.

[0010] In one embodiment, the cardiovascular medical implant or medical implant is configured such that the first electrospinning member and the second electrospinning member are not sewn or stitched together, or the first electrospinning member and the second electrospinning member do not have sewn areas or seams.

[0011] In a further embodiment, the cardiovascular or medical implant includes a support structure gathered between the first and second electrospinning members or coupled to one another.

[0012] The present invention further provides a tissue engineered heart valve comprising two (or more) electrospun heart valve members, each separately manufactured from the same type of biodegradable electrospun polymer. The two separately manufactured electrospun heart valve members are held together or bonded together by the same type of biodegradable electrospun polymer. The tissue engineered heart valve is thus configured to be a porous biodegradable medical implant that can replace naturally grown tissue over time after implantation. The assembly or bond of the two separately manufactured electrospun heart valve members is ultrasonically or adhesively welded together.

[0013] In an embodiment, the tissue engineered heart valve is configured such that two separately manufactured electrospun heart valve members are not sewn or sutured together, or such that two separately manufactured electrospun heart valve members do not have any sewn areas or seams.

[0014] In a further embodiment, the tissue engineered heart valve includes a support structure assembled between or bonded to two separately manufactured electrospun heart valve members. The invention further provides a method of assembling two separately manufactured electrospun members to form a cardiovascular medical implant or medical implant. The first member is electrospun using a type of biodegradable electrospun polymer. A second member is electrospun separately from the first member using the same type of biodegradable electrospun polymer as the first member. The first and second electrospun members are then assembled by the same type of biodegradable electrospun polymer used for the first and second electrospun members, thereby creating a porous biodegradable medical implant that can replace naturally grown tissue over time after implantation. Examples of assembling include ultrasonic welding, gluing, or adhesive welding, etc. Examples of assembled cardiovascular medical implants or medical implants include those in which the first electrospun member and the second electrospun member are a tissue engineered heart valve, a tissue engineered vascular graft, or a tissue engineered vascular member.

[0015] In one embodiment, the method is configured such that the first electrospinning member and the second electrospinning member are not sewn or stitched together, or the first electrospinning member and the second electrospinning member do not have sewn areas or seams, excluding sewing or stitching.

[0016] In another embodiment, the method includes the further step of gathering a support structure between the first and second electrospun members. Examples of such support structures include stents, frames, braided or mesh structures for supporting cardiovascular or medical implants. In an example of making such a device, the first electrospun member is electrospun, and then the support structure is added on top of the first electrospun member. Then, two electrospun members are electrospun on top of the support structure and the first electrospun member. Gathering or bonding (e.g., ultrasonic welding) results in the first electrospun member and the second electrospun member being bonded to each other with the support structure laminated therebetween.

[0017] In yet other embodiments, the gathering step includes patterning the area where the first and second electrospun members are gathered or bonded together. In some variations of the embodiment, the gathering or bonding (e.g., ultrasonic welding) can be performed in a substantially circumferential, helical, or circular pattern. This can improve the kink resistance of the medical implant in some embodiments.

[0018] Advantages of the present invention include: In medical implant concepts such as heart valves, the use of two electrospun members in the heart valve avoids the use of sutures. This allows the omission of the disadvantages of sutures such as stress concentration and manual handling. Meanwhile, the potential ETR potential is maintained since the microstructure / porosity is only affected locally, even at the interface between materials. Tissue can be formed inside the scaffold around the localized welds. The assembly and bonding of the electrospun members in the present invention is more accurate, reproducible, and automatable compared to suturing or sewing. Furthermore, the assembly and bonding of the electrospun members in the present invention does not require extra materials such as sutures or other fixatives, since the same polymers that make up the electrospun structure are used.

[0019] The advantages of the present invention for medical implant concepts such as vascular grafts or vascular concepts are the same as for heart valves: the absence of sutures improves hemostasis (bleeding) of the graft or vessel during implantation due to the absence of suture holes; the patterned welding allows tuning / optimization of mechanical properties, such as improved kink resistance. In some aspects, the ultrasonic welding pattern itself may provide a support structure to ensure sufficient kink resistance. [Brief description of the drawings]

[0020] FIG. 1 illustrates a first electrospun member 110 comprising a type of biodegradable electrospun polymer and a second electrospun member 120 comprising the same type of biodegradable electrospun polymer as the first electrospun member 110, according to an exemplary embodiment of the present invention. In one example, the second electrospun member is manufactured separately from the first electrospun member, as shown in the top diagram of FIG. 1. The bottom diagram of FIG. 1 illustrates the first electrospun member 110 and the second electrospun member 120 brought together or bonded together by either ultrasonic or adhesive welding (both 130) using the same type of biodegradable electrospun polymer as the first and second electrospun members. This assembly forms a medical implant capable of endogenous tissue regeneration (ETR). FIG. 2 is a cross-sectional view of an exemplary embodiment of the present invention. The top left image shows the configuration before the circular polymer tube cover and sheet-like polymer leaflets are welded, and the top right image shows the configuration after the polymer tube cover and polymer leaflets have been ultrasonically welded. The top image shows a cross-section of the center of the welded surface, and the bottom image shows a close-up of the welded surface. Also, in the bottom image, a solid bond is visible between the two members, but the mesh morphology of the polymer tube cover and polymer leaflets is still visible at the contact area of ​​the welded device to the polymer piece. The solid bond is clearly seen deeper between the members where the change in morphology is less related to ETR. FIG. 3 is a cross-sectional view of an exemplary embodiment of the present invention. On the left is a cross-sectional view (SEM photo) of a fully assembled aortic valve leaflet and welded tube cover. The middle image is a magnified view of the left image to clearly show how the outer region maintains the mesh morphology while a solid weld is formed inside the joint between the members. On the right is a side view (view along the direction of the arrow) of the weld where the welding device contacts the leaflet. The mesh morphology is almost perfectly maintained, but vertical seam marks can be seen along the weld line. This is the basis for successful ETR of the device without changing the outer morphology of the device. FIG. 4 illustrates an exemplary laser cut material according to an exemplary embodiment of the inventive welding concept at an exemplary manufacturing step (see steps 1-5 in the main text). FIG. 5 is a cross-sectional view showing bonded posts according to an exemplary embodiment of the present invention as viewed by SEM. FIG. 6 illustrates cross-sectional and side views showing an ultrasonically welded "wedge" configuration according to an exemplary embodiment of the present invention. [Mode for carrying out the invention]

[0021] An embodiment of the present invention is a medical implant formed by separate components made of the same electrospun polymer being assembled or bonded together using the polymer of the separate components or the same type of polymer. Two examples are provided here. In the first example, the two separate components are ultrasonically welded together so that the polymer of the two separate components creates an assembly or combination. In the second example, the two separate components are glued together with the same polymer used for the separate polymer. In other words, the medical implant is composed of two separately manufactured components that are assembled or bonded together using the same polymer used to make the components. This results in a separately manufactured medical implant, despite using the same polymer. An example of such a medical implant is a heart valve, including one or more leaflet components and possibly one or more support structures, which are assembled together without sewing or suturing. The present invention is not limited to this example and applies to any kind of electrospun implant where the components are manufactured separately and assembled to form the medical implant. Importantly, despite the assemblies or joints obtained as a result of welding or bonding, the medical implants obtained from the assemblies maintain their structural characteristics in that they are not only porous but also biodegradable and / or capable of ETR after implantation in the body.

[0022] In another embodiment of the present invention, a medical implant including a support structure is formed by members including the same electrospun polymer. Thus, the members are assembled or bonded together using the polymers that compose the members or the same type of polymer, and the support structure is laminated between the two electrospun members. Examples of such support structures include stents, frames, braided structures, or mesh structures for supporting cardiovascular medical implants or medical implants. An example of making such a device is to electrospin a first electrospun member, add a support structure on the first electrospun member, and then electrospin a second electrospun member on the support structure and the first electrospun member. The first electrospun member and the second electrospun member are joined together by assembly or bonding (e.g., by ultrasonic welding), and the support structure is laminated together.

[0023] ultrasonic welding

[0024] Ultrasonic welding is an industrial technique in which high frequency ultrasonic acoustic vibrations are applied locally to workpieces held under pressure to weld solid objects together. In ultrasonic welding of thermoplastics, friction-induced heating melts the plastic locally. Ultrasonic welding can theoretically be used with any type of polymer.

[0025] The ultrasonic welding process involves various parameters that must be determined for the specific application to obtain optimal weld quality, such as frequency, amplitude, weld energy, time, pressure, etc. It also requires a complete process development and optimization, including dedicated tools (e.g. sonotrodes and boosters) to allow for different weld shapes and sizes. There is no "off-the-shelf solution" available for all materials.

[0026] Known advantages of ultrasonic welding are that it is much faster than traditional adhesives or solvents. Ultrasonic welding has a very short drying time, so parts do not need to be kept in the fixture for long periods of time while waiting for the joint to dry and harden. Welding can be easily and fully automated, resulting in clean and precise joints. Welds are considered very clean and repeatable, requiring little touch-up work. Also, more material can be welded because the heat has less effect on the material.

[0027] The medical industry is exploring the use of ultrasonic welding, as it does not introduce any contaminants or degradation into the weld and can be processed specifically for cleanroom use. The highly automated process allows for tight control of dimensional tolerances and does not interfere with the biocompatibility of the materials used. Nevertheless, nothing is known about the changes in surface morphology during welding, and therefore properties related to biodegradability and ETR.

[0028] In fact, those skilled in the art would discourage the use of welding since the polymer will eventually "melt" and the fine polymer fibers will melt, causing a loss of specific structure and mechanical properties as well as altered surface morphology.

[0029] In the particular cardiac application where the porous mesh structure of the polymer fibers is exposed to the bloodstream and rapid tissue growth is desired as part of the ETR process, it is crucial to maintain the mechanical properties and morphology of the mesh structure for optimal cell growth. An advantage of the present invention is that we have found that, macroscopically, the welding does not alter the surface properties of the porous polymer structure, so that it still provides excellent ETR properties. We have also found that the welds produced exhibit surprising durability, which is essential for medical implant applications.

[0030] One example is the replacement of sutures on the struts of heart valves with ultrasonic welding. It is preferable that the welded parts of the implantable device are not completely exposed to the biological flow of blood cells. This technology has great potential because localized melted areas in such parts can occur between two layers of polymer that are not visible from the outside.

[0031] Preferably, only one type of polymer is used to manufacture the valve, avoiding the use of additional materials such as suture materials. This is particularly important since the entire device will exhibit the same rate of degradation.

[0032] Another example of the use of ultrasonic welding in medical applications is in vascular graft applications where two electrospun tube layers can be bonded in one or more desired locations and in a desired pattern. The welding pattern can be used to embed a support structure (e.g., strain relief structure) with specific mechanical properties between the two electrospun tube layers while reducing the risk of the electrospun tube layers delaminating from each other. The welding pattern can also be used to affect the mechanical properties of the graft tissue. For example, a helical pattern with continuous welding can help the graft tissue bend without twisting.

[0033] The ultrasonic welding method used in the embodiments of the present specification can be characterized by the following parameters used during the process: The welding frequency is 45-70 kHz, and preferably about 70 kHz. A welding energy of 0.1-5 W*sec is applicable, and a welding energy of 0.3-1.5 W*sec is preferred. As for the welding time, it is 0.1-5 seconds, and preferably 0.1-2 seconds.

[0034] The welds formed by the method of the present invention were examined by SEM and show that the welded areas are imprinted by the horn on the outside of the leaflet. The weld is initiated by the contact of the horn with the outer surface of the leaflet, but the morphology of the mesh (porosity, fiber diameter, etc.) remains surprisingly unchanged in the welded outer surface area. It is therefore concluded that this welding process can be successfully used for ETR applications. The outer surface does not prevent or reduce the ETR effect, but rather may enhance it. This allows the removal of foreign objects (such as suture wires) and heat-affected zones (such as laser cut holes for suture wires) that may cause calcification deposits and reduce the ETR effect around these locations.

[0035] During welding, small mechanical vibrations of a certain frequency are transmitted through several possible "sonotrodes" or horns to the two polymer pieces to be joined together. The horns are in contact with the outside of a certain first polymer piece and are designed to transmit a certain amplification (gain) of these vibrations to the polymer. A sudden frictional energy generates heat locally between the inside of the first polymer piece and the outside of the second polymer piece. This gives the outer layer of the second polymer piece a shape that allows it to extend against the metal frame of the surgical valve strut. The metal frame is preferably used as an anvil to provide the first contact surface between the polymer pieces. This contact, together with the pressure applied through the horns to the outer layer of the first polymer piece, is important for localized and precise welding. The metal frames of surgical prosthetic heart valves are usually made of titanium or titanium alloys, so the horns are preferably made of titanium as well.

[0036] The heat generated by the aforementioned frictional energy results in a localized melting pattern, creating a robust bond between the two polymer pieces. Surprisingly, this bond has been shown to be strong enough to withstand the conditions of accelerated in vitro wear testing. Additionally, less strut deflection has been repeatedly observed when the valve is under full load. This is because the less stiff bond between the leaflets and frame (compared to state-of-the-art suture configurations) allows the stiffer frame struts to better resist bending, resulting in less deflection. The association between less strut deflection and increased durability indicates less stress concentration on the struts.

[0037] This pattern allows ETR to occur in vivo primarily because the outer surface of the polymer exposed to the blood flow maintains material properties such as porosity and mesh morphology.

[0038] When sutures are used, a lot of force is required to keep the valve in the correct position. Sutures are usually strong and rigid, with no flexibility or yielding. Thus, the leaflets are held in a specific position by the sutures and can hardly move. We found that it is very important to finally "set" the valve in the right position and adjust it to the optimal shape. By using welded seams instead of sutures, we can finally find the optimal position of the valve and free the whole structure from high stress points that can lead to device rupture and failure. Moreover, welded seams do not require additional material (like sutures), so the whole system can move almost uniformly.

[0039] The weld area or horn is preferably immersed in fluid and / or water. The water will not evaporate since the melting point of the polymer is below 10° C., but the inherent property of forming a specific weld pattern provides sufficient durability through the weld while also forming a morphology that supports ETR. Thus, one skilled in the art would refrain from welding wet polymer pieces as it would compromise the uniformity of the weld or would not be able to weld at all.

[0040] Leaflet and frame assemblies other than the struts can also be made by ultrasonically welding the bottom of the polymer leaflet and the PET cover of the metal frame together.

[0041] The embodiments provided herein eliminate suturing issues and improve the ETR compatibility and hemodynamic performance of the heart valve. Another notable benefit is the reduced time required to weld the struts by replacing suturing with ultrasonic welding, which requires approximately 75% less time than the slow and careful stitching required for precise stitch placement. Ultimately, this allows for an increased ability to quickly assemble the valve, allowing for rapid iterations during the process development phase and later cost-effectiveness for the final commercial product.

[0042] An example of a manufacturing process for the fusion concept is as follows:

[0043] Step 1

[0044] The spinning is performed as usual, but a dedicated blueprint is used with only two laser-cut suture holes on each strut (for fixation sutures). The blueprint can include laser markings for more precise welding. The suture holes can also be replaced with similar markings. Please note that if welding is used instead of running stitches at the bottom of the leaflet, the lower laser-cut holes are not cut, as shown in Figure 4.

[0045] Step 2

[0046] The valve is partially assembled, with a full running stitch around the bottom of the frame and only one fastening stitch on each post, and the running stitch could be replaced with a full circumferential running weld, as the PET fabric has been found to weld surprisingly well and provide a sturdy join.

[0047] Step 3

[0048] While the leaflets are forced into a closed configuration, they are ultrasonically welded (twice welded to each strut) to the strut covers (tubes) on the sides of each strut. In other configurations, a similar weld (on both sides of the strut) can be achieved with one weld touch instead of two.

[0049] Step 4 (optional step)

[0050] Remove the fastening stitches from the center of each post. This step is not required in some configurations. The fastening stitches are retained because they are not located in the highly mobile portions of the leaflets and provide additional strength to attach the leaflets to the posts other than by welding.

[0051] Step 5 (optional step)

[0052] A second welding step is performed (in the center of each strut) where the fixing stitches were removed. This step is not mandatory and other configurations can be applied, including cases where the center of the strut is not welded because it is strong enough.

[0053] Step 6

[0054] The final assembled valve has the leaflets held together only by welds. This particular configuration shows that the running stitch on the bottom of the frame has been replaced with a running weld. Thus, this Figure 4 shows a stitchless valve according to the present invention.

[0055] These method steps may be varied depending on the desired purpose or structure, and the invention is not limited to these steps or this sequence of steps.

[0056] Adhesion

[0057] The use of adhesives for joining valves etc. has not been considered due to known disadvantages. The adhesives required for bonding have limited heat and chemical resistance or load bearing capacity (depending on their chemical basis). The mechanical properties of the adhesive are therefore temperature dependent and different compared to the properties of the adhesive material. This results in areas of high stress and low durability. The long-term stability of the adhesive is subject to aging and therefore changes during the life of the device, which is unacceptable for a medical device. Adhesive processes require adhesives and auxiliary compounds that are generally not biocompatible or toxic and / or require special care.

[0058] Most commercially available bioprosthetic valves have a stiffness difference between the tissue covering and the metal frame, which can cause wear and lead to failure of the device. Therefore, different components are used to protect the struts, which are usually made of softer materials than the frame (e.g., synthetic or plastic liners). Still, bioprosthetic valves need improvement and further development.

[0059] A typical embodiment of the surgical aortic valve includes three tubular components made from the same polymer used as strut covers. These tubular components (strut covers) are attached to the frame of the valve and their purpose is to reduce wear between the leaflets, which move more quickly, and the metal frame, which moves less quickly.

[0060] In embodiments of the present invention, these wear protection components made from electrospun materials manufactured from polymers are utilized to create adhesive bonds between the leaflet scaffold and the struts instead of suturing.

[0061] Adhesion is achieved by using the same polymer solution to apply the solution to the areas where a bond is required between the leaflet and the frame struts. The viscous solution is applied topically to the surface of the strut cover, and then the leaflet scaffold is spun directly on top of it while the solution is still in a liquid state. Once the solution dries and hardens, a robust bond is created between the leaflet scaffold and the strut cover. The solid polymer layer that creates this bond is not exposed to the bloodstream, so ETR is effectively achieved. Additionally, there are no seams around the struts in this configuration, suggesting even faster tissue growth than seen with state-of-the-art configurations.

[0062] By using the same polymer for electrospinning and bonding, the bond has similar material properties as the adhesive material, potentially dispersing stress, shifting stress points and ultimately resulting in greater durability.

[0063] Good fatigue durability of the prosthetic valve frame is related to the deflection of the frame struts and the inward bending of the frame struts. Too much deflection of the struts can lead to poor leaflet function or even oversized pinwheels. When this new adhesive method is applied to the leaflet attachment, the struts can more easily withstand the deflection. As a result, the strut deflection value measured during strut deflection measurement is lower.

[0064] Surprisingly, the inventors have discovered that valves made in accordance with the present invention exhibit low sensitivity to unequal volumes of the bond regions between the struts with respect to durability both in vitro and in vivo.

[0065] Moreover, a key advantage of the present invention is that the assembly process of the scaffold after the adhesion process is significantly faster compared to the state of the art configurations, with a significantly faster assembly process time of about 1 hour suggested for the proposed configuration compared to about 4 hours for the state of the art configurations.

[0066] An additional benefit of this configuration is the elimination of bottom seams. In addition to the robust joining of the struts, there is only one circumferential running stitch at the base of the metal frame at the bottom of the leaflet. The lack of bottom seams on all struts allows the polymer scaffold to adjust its shape when loaded for optimal pressure distribution. This results in no stress concentration points around the struts, thereby improving the durability of the valve.

[0067] An example of manufacturing steps for the bonded post concept are as follows:

[0068] Step 1

[0069] Assemble the electrospun targets.

[0070] Step 2

[0071] A polymeric post cover made of a polymer is attached to each post. The electrospinning target is then reassembled.

[0072] Step 3

[0073] The electrospinning target is fixed into the electrospinning box and each post is thoroughly hand polished with the wet polymer solution.

[0074] Step 4

[0075] The scaffold is spun and upon completion is removed from the electrospinning box.

[0076] Step 5

[0077] If desired, the scaffold is cut according to the valve design pattern.

[0078] Step 6

[0079] The valve is gathered up on a given frame with no attachment to any supports other than the tube stretched over the top of the frame.

[0080] Step 7

[0081] Apply a running stitch to the bottom of each leaflet to complete the assemblage.

[0082] These method steps may vary depending on the desired purpose and structure, and the invention is not limited to these steps or this order.

[0083] Another notable method for manufacturing the bonded strut concept is to electrospin the leaflets and strut covers separately and then bond these components together using a dedicated tool. The leaflets are held in an expanded position in the correct position until the strut covers, loaded with the correct amount of adhesive, are inserted at the desired location. Localized pressure is applied to the struts until the adhesive dries completely, after which the leaflets are released. This method facilitates equalizing the amount of adhesive on each strut and eliminates potential variations in the adhesive surface between the struts, improving the durability of the valve.

[0084] Definition of Polymer for the Purposes of the Invention

[0085] The polymers or supramolecular polymers referred to herein may be composed of a polymer backbone with a ureido-pyrimidinone (UPy) quadruple hydrogen bonding motif (first studied by Sijbesma (1997), Science 278, 1601-1604). For example, they may be selected from the group including biodegradable polyesters, polyurethanes, polycarbonates, poly(orthoesters), polyphosphoesters, polyanhydrides, polyphosphazenes, polyhydroxyalkanoates, polyvinyl alcohols, and polypropylene fumarates. Examples of polyesters include polycaprolactone, poly(L-lactide), poly(DL-lactide), poly(valerolactone), polyglycolide, polydioxanone, and copolyesters thereof. Examples of polycarbonates include poly(trimethylene carbonate), poly(dimethyltrimethylene carbonate), and poly(hexamethylene carbonate).

[0086] Similar results may be obtained with alternative non-supramolecular polymers if the properties are carefully selected and the materials are treated to ensure the required surface properties. These polymers may consist of biodegradable or non-biodegradable polyesters, polyurethanes, polycarbonates, poly(orthoesters), polyphosphoesters, polyanhydrides, polyphosphazenes, polyhydroxyalkanoates, polyvinyl alcohols, and polypropylene fumarates. Examples of polyesters include polycaprolactone, poly(L-lactide), poly(DL-lactide), poly(valerolactone), polyglycolide, polydioxanone, and their copolyesters. Examples of polycarbonates include poly(trimethylene carbonate), poly(dimethyltrimethylene carbonate), and poly(hexamethylene carbonate).

Claims

1. 1. A cardiovascular medical implant comprising: (a) a first electrospinning member comprising a type of biodegradable electrospun polymer; (b) a second electrospinning member comprising the same type of biodegradable electrospinning polymer as the first electrospinning member; the first electrospinning member and the second electrospinning member are held together or bonded to each other by the biodegradable electrospinning polymer of the same type as the first electrospinning member and the second electrospinning member; A cardiovascular medical implant, wherein the cardiovascular medical implant is configured such that after implantation, the cardiovascular medical implant becomes a porous biodegradable medical implant that can be replaced over time by naturally grown tissue.

2. 10. The cardiovascular medical implant of claim 1, wherein the assembly or combination of the first electrospinning member and the second electrospinning member are ultrasonically or adhesively welded together.

3. 10. The cardiovascular medical implant of claim 1, wherein the first electrospun member and the second electrospun member comprise a tissue engineered heart valve member, a tissue engineered vascular graft member, or a tissue engineered vascular member.

4. 10. The cardiovascular medical implant of claim 1, wherein the first electrospinning member and the second electrospinning member are not sewn or stitched together, or the first electrospinning member and the second electrospinning member do not have sewn areas or seams.

5. 10. The cardiovascular medical implant of claim 1, further comprising a support structure gathered between or coupled to said first electrospinning member and said second electrospinning member.

6. 10. The cardiovascular medical implant of claim 1, wherein said second electrospun member is manufactured separately from said first electrospun member.

7. 1. A tissue engineered heart valve comprising: two electrospun heart valve members, each made from the same type of biodegradable electrospun polymer; the two separately manufactured electrospun heart valve members being held together or bonded to each other by the same type of biodegradable electrospun polymer; The tissue engineered heart valve is configured such that after implantation, the tissue engineered heart valve becomes a porous, biodegradable medical implant capable of being replaced over time by naturally grown tissue.

8. 8. The tissue engineered heart valve of claim 7, wherein the assembly or combination of the two separately manufactured electrospun heart valve members is ultrasonically or adhesively welded together.

9. 8. The tissue engineered heart valve of claim 7, wherein the two separately manufactured electrospun heart valve members are not sewn or stitched together or the two separately manufactured electrospun heart valve members have no sewn areas or seams.

10. 10. The tissue engineered heart valve of claim 7, further comprising a support structure assembled or bonded to one another between the two separately manufactured electrospun heart valve members.

11. 1. A method for forming a cardiovascular medical implant by bringing together two separately manufactured electrospun members, comprising: (a) electrospinning a first component using a type of biodegradable electrospun polymer; (b) electrospinning a second component using the same type of biodegradable electrospun polymer as the first component; (c) bringing the first and second electrospinning members together with the same type of biodegradable electrospinning polymer used for the first and second electrospinning members; The cardiovascular medical implant is configured to become a porous, biodegradable medical implant after implantation that can be replaced with naturally grown tissue over time.

12. The method of claim 11 , wherein the gathering step is performed by ultrasonic welding, gluing, or adhesive welding.

13. 12. The method of claim 11, wherein the first electrospun member and the second electrospun member comprise a tissue engineered heart valve, a tissue engineered vascular graft, or a tissue engineered vascular member.

14. 12. The method of claim 11, wherein the first electrospinning member and the second electrospinning member are not sewn or stitched together, or the first electrospinning member and the second electrospinning member do not have sewn areas or seams.

15. The method of claim 11 , further comprising gathering a support structure between the first electrospinning member and the second electrospinning member.

16. 12. The method of claim 11, wherein the gathering step further comprises patterning an area where the first electrospinning member and the second electrospinning member are gathered or bonded to one another.

17. 12. The method of claim 11, wherein the second electrospinning member is electrospun separately from the first electrospinning member.

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