Patent ID: 12201516

DETAILED DESCRIPTION

Specific embodiments of the present disclosure are now described with reference to the figures, wherein like reference numbers indicate identical or functionally similar elements.

The following detailed description is merely exemplary in nature and is not intended to limit the present technology or the application and uses of the present technology. Although the description of embodiments hereof is in the context of prosthetic valves, the present technology may also be used in other devices. Furthermore, there is no intention to be bound by any expressed or implied theory presented in the preceding technical field, background, brief summary or the following detailed description.

In embodiments hereof, methods are described to manufacture medical devices, such as prosthetic valves, from electrospun fibers in an electrospinning process. The use of the electrospun fibers in the manufacturing of the described prosthetic valves reduces or eliminates the costly and time consuming use of animal tissue in the production of many current prosthetic valves. More specifically, with current animal tissue designs, most of the animal tissue is wasted during the manufacturing process. Further, manufacturing of prosthetic valves with animal tissue is tedious, requiring technicians to manually suture the animal tissue onto biocompatible structures, such as stent-like frames. As a result, current methods of manufacturing animal tissue design prosthetic valves are expensive and time consuming. Further, the manual or hand suturing produces lower than desired yields. The methods and prosthetic valves described herein according to embodiments hereof utilized one or more layers of electrospun fibers that reduces waste as the electrospun fibers are deposited on a valve mold in the desired shape of the valve. Further, in some embodiments, suturing is not required. Further, the use of the electrospun fibers and the electrospinning process in the manufacturing of the electrospun prosthetic valves permits more precise control of the material properties of the electrospun prosthetic valves. Accordingly, the methods described herein result in reduced manufacturing costs, reduced manufacturing time, and improved manufacturing yields.

FIG.1is a flow chart showing a method100of making a medical device such as an electrospun prosthetic valve according to an embodiment hereof. The method as described with respect toFIG.1is a method for making a medical device utilizing an “electrospinning process”. The term “electrospinning process” refers to a process in which a charged polymer jet forms electrospun fibers that are collected on a grounded mold, as described below. The collected electrospun fibers have diameters in the submicron to micron range. As used herein, the term “diameter” and “diameters” does not have to refer to a circular profile, but instead is used generally to refer to a cross-sectional dimension of the electrospun fibers. The electrospun fibers are extremely biocompatible, and form a porous micro-fiber structure that promotes tissue ingrowth in situ. Further, in an embodiment the electrospun fibers may be biodegradable, producing a tissue engineered electrospun prosthetic valve, wherein the electrospun fibers degrade over time and are replaced by the new tissue ingrowth. Stated another way, the electrospun prosthetic valve is implanted, but over time the implanted electrospun prosthetic valve turns into a tissue valve. In embodiments hereof, the electrospun fibers are formed of a polymer as described below.

FIG.2shows an embodiment of a system201for use with the method ofFIG.1. The system201includes a collection assembly203and an electrospinning assembly205. The system201is configured to form an electrospun prosthetic valve according to embodiments hereof.

In the embodiment illustrated inFIG.2, the collection assembly203includes a prosthetic valve mold207, a motor209, a bracket211, and a base213.FIG.3shows an embodiment of the prosthetic valve mold207. The prosthetic valve mold207includes a first end215, a second end217opposite the first end215, a mold base240, and three segments242A,242B, and242C (together referred to as segments242). The prosthetic valve mold207includes an outer surface219. The outer surface219has a shape or geometry of the desired electrospun prosthetic valve. The shape of the prosthetic valve mold207can be selected to improve hydrodynamic properties of the completed electrospun prosthetic valve. Each segment242is shaped to form a corresponding leaflet of an electrospun prosthetic valve thereon. Accordingly, while the prosthetic valve mold207is illustrated inFIG.3with three segments242A,242B,242C, this is by way of example and not limitation. In alternative embodiments, the prosthetic valve mold207may include more or fewer segments242to correspond to the number of leaflets desired for a particular application of the electrospun prosthetic valve. Further, while the prosthetic valve mold207is illustrated as a single unit, this too is by way of example and not limitation. The prosthetic valve mold207may be formed of individual components such that the mold base240, and each of the segments242A,242B, and242C are separate and coupled together to form the prosthetic valve mold207. Methods of coupling the segments242A,242B, and242C to the mold base240can include, but are not limited to adhesives, fusing, welding, mechanical connections, and friction-fit coupling. Further, segments242A,242B,242C, and mold base240may be separable from each other such that the electrospun prosthetic valve deposited thereon may be more easily removed from the prosthetic valve mold.

In the embodiment ofFIG.3, the mold base240includes a central opening (not shown, but similar to the central opening447shown inFIG.3B) for mounting on a shaft of the motor209. A threaded aperture248is disposed laterally or radially from an outer circumferential surface of the mold base to the central opening. A set screw269is disposed through the threaded aperture248to the central opening to couple the mold base240, and hence the prosthetic valve mold207, to the motor209. While the set screw269is illustrated inFIG.3with a specific shape, this is by way of example and not limitation, and the set screw269can have other shapes suitable for the purposes described herein. Moreover, the use of the set screw269to couple the prosthetic valve mold207to the motor209is not meant to be limiting, and the prosthetic valve mold207can be coupled to the motor209by any suitable method such as, but not limited to adhesives, fusing, welding, mechanical coupling, or other suitable methods.

In the embodiment ofFIG.3, the prosthetic valve mold207further includes three (3) channels244A,244B,244C (collectively referred to herein as “channels244”). The channels244form corresponding channels in the precursor electrospun prosthetic valve formed thereon. The channels244are configured to facilitate easy separation of the leaflets of the electrospun prosthetic valve to create free edges for opening and closing of the leaflets, as described below. In the embodiment shown inFIG.3, the channels244form a single contiguous channel. However, this is not required. Further, in other embodiments, the channels244can be omitted.

As noted above, the segments242A,242B,242C of the prosthetic valve mold207may be separable from each other and the mold base240. In a particular embodiment of a prosthetic valve mold407including a mold base440and segments442, shown inFIGS.3A and3B, each segment442includes a leaflet portion443and a stem445. Thus, the segments442A,442B,442C include leaflet portions443A,443B,443C and stems445A,445B,445C, respectively. The mold base440includes stem openings441A,441B,441C that are sized and shaped to receive a respective one of the stems445A,445B,445C to seat the corresponding segment442A,442B,442C therein. The base440also includes threaded openings449A,449B,449C, with each opening extending laterally or radially from a circumferential outer surface of the mold base440to a corresponding one of the stem openings441A,441B,441C. The corresponding stem445A,445B,445C of each segment442A,442B,442C is placed in the corresponding stem opening441A,441B,441C of the base440, and a set screw471A,471B,471C is inserted into the corresponding threaded opening449A,449B,449C to secure the segments442A,442B,442C to the mold base440. While the set screws471A,471B,471C are illustrated inFIGS.3A and3Bwith a specific shape, this is by way of example and not limitation. The set screws471A,471B,471C can each have other shapes suitable for the purposes described herein. Other ways to removably secure the segments442A,442B,442C to the mold base440may be utilized. The mold base440also includes a central opening447which is sized and shaped to fit onto a shaft of the motor209. The mold base440further includes a threaded opening448extending laterally or radially from an outer cylindrical surface of the base440to the central opening447. A set screw469extends through the threaded opening448to the central opening447to secure the valve mold407to the motor209. The set screw469is similar to the set screw269previously described with respect toFIG.3and is not meant to be limiting and other ways to secure the valve mold407to the motor209may be utilized.

The valve mold407has been described with particular reference to separable segments442. However, the features or other embodiments of valve molds described herein, such a valve molds207,507may be utilized with the valve mold407. For example, and not by way of limitation, the valve mold407may include channels such as channels244described with respect to valve mold207. Further, portions of the valve mold407may be heated as described with respect to valve mold507below.

FIG.3Cillustrates a prosthetic valve mold507according to another embodiment hereof. The prosthetic valve mold507is similar to the prosthetic valve mold207described above. Therefore, details of the prosthetic valve mold507not specifically described with respect to this embodiment are as described with respect to prosthetic valve mold207and/or prosthetic valve mold407. In the prosthetic valve mold507, a plurality of heated portions546A,546B,546C,546D,546E, and546F (collectively referred to herein as “heated portions546”) of the prosthetic valve mold507are heated. The heated portions546of the prosthetic valve mold507are configured to melt corresponding selected portions of an electrospun prosthetic valve disposed thereon. The temperature of the heated portions546of the prosthetic valve mold507are precisely controlled. For example, and not by way of limitation, the heated portions546of the prosthetic valve mold507can be heated to a temperature in a range of 60° to 160° Celsius. Areas of the valve mold507may be heated where it is desirable to crystallize the electrospun fibers deposited thereon to improve strength, but not crystallize areas of the valve mold507where it is desirable for the electrospun fibers deposited thereon to maintain the porous, microfiber thereof to promote tissue ingrowth when the electrospun prosthetic valve is deployed. Thus, in one particular embodiment shown inFIG.3C, the heated portions546of the prosthetic valve mold507correspond to free edges and commissures of the electrospun prosthetic valve formed on the prosthetic valve mold507. The heated portions546A,546B,546C of the valve mold507are areas where the free edges of the leaflets of the electrospun prosthetic valve are formed, and heated portions546D,546E,546F are areas of the valve mold507where commissures of the electrospun prosthetic valve are formed. The free edges and commissures of a prosthetic valve endure high stress during use such that increased strength in these areas would be desirable, whereas the body of the leaflets would not crystallize to maintain the porous, microfiber structure of the electrospun fibers. However, this is not meant to be limiting, and other areas of the prosthetic valve mold507can be heated, in any combination.

In a non-limiting example, the heated portions546of the prosthetic valve mold507are precisely and controllably heated via conduction of heat from the motor209(visible inFIG.2) as the prosthetic valve mold507is rotated at high speed. In a non-limiting example for controlling the heat from the motor209, the prosthetic valve mold507can be formed using a combination of insulating and conducting materials. Thus, when in use, the conductive areas of the prosthetic valve mold507heat up due to heat from the motor209, while the insulated areas of the prosthetic valve mold507remain cool. In another non-limiting example, targeted heating elements could be coupled to the heated portions546of the prosthetic valve mold507to heat the heated portions546, while areas without heating elements would not be heated. Alternatively, the heated portions546of the prosthetic valve mold507can be heated by other methods including, but not limited convection, radiation, or any other method suitable for the purposes described herein.

The prosthetic valve mold507ofFIG.3Chas been described with respect to the heated portions546. Thus, the undescribed portions of prosthetic valve mold507may include features and alternatives from the embodiments of the prosthetic valve mold207or the prosthetic valve mold407. For example, and not by way of limitation, the prosthetic valve mold507may include separable portions as described with respect to prosthetic valve mold407. Further, any of the prosthetic valve molds described herein may include heated portions as described with respect to prosthetic valve mold507.

The prosthetic valve molds207,407,507are configured to be rotatable and angularly adjustable. For convenience, when describing the interaction of the prosthetic valve mold with other parts of the system201, the prosthetic valve mold207will be referenced. However, such reference is not meant to be limiting such that any of the valve molds207,407,507may be utilized with the system201. In the embodiment ofFIGS.2-4, the prosthetic valve mold207is rotatable via the motor209and angularly adjustable via the bracket211as described below. The prosthetic valve mold207is further configured to act as a conductive substrate onto which a plurality of electrospun fibers263from the electrospinning assembly205are collected as described below. In an embodiment, the prosthetic valve mold207is metallic and is formed of materials such as, but not limited to stainless steel, aluminum, cobalt chromium, and titanium. The prosthetic valve mold207can be formed by methods such as, but not limited to,3D printing, casting, machining, or any other suitable method.

FIG.4shows the motor209of the system203, which includes a first end221, a second end223opposite the first end221, and an outer surface225. The first end221of the motor209is coupled to the second end217of the prosthetic valve mold207. The motor209is configured to rotate the prosthetic valve mold207to permit desired deposition or distribution of the electrospun fibers263from the electrospinning assembly205onto the outer surface219of the prosthetic valve mold207. The motor209may be of any design suitable for the purposes described herein and capable of rotating the coupled prosthetic valve mold207at desired rotational velocities, for example, and not by way of limitation, in a range of 0-1,000 revolutions per minute (RPM). In an embodiment, the motor209can be a stepper motor precisely controlled using a programmable stepper motor amplifier. Alternatively, in another embodiment the motor209can be a servo motor controlled using a sensor and a servo controller.

The motor209may include an insulating material227on the outer surface225, as shown inFIG.4. The insulating material227is configured to minimize effects of the electric field generated by the motor209that could interfere with the deposition of the electrospun fibers263onto the prosthetic valve mold207in the method ofFIG.1. Non-limiting examples of the insulating material227include rubber, paper, polyvinylchloride, varnish, silicone, and resin. The insulating material227can be coupled to the outer surface225of the motor209by methods such as, but not limited to adhesives, mechanical couplings, or any other suitable coupling methods.

The bracket211includes a first portion229, and second portion231, as illustrated inFIG.4. The first portion229includes a first end233coupled to the second end223of the motor209, and a second end235pivotably coupled to a first end237of the second portion231at a pivot joint241. The second portion231further includes a second end239, which is coupled to the base213. The bracket211is configured to enable the first portion to be angularly adjustable relative to the second portion231, thereby enabling adjustment of the motor209and the rotating prosthetic valve mold207to an angle □ to evenly distribute electrospun fibers263onto the rotating prosthetic valve mold207in an electrospinning process as described below. The bracket211includes a first or unlocked configuration wherein the angle □ can be adjusted, and a second or locked configuration wherein the angle □ is static, fixed, or locked. Accordingly, when the bracket211is in the unlocked configuration, the first portion229is pivotable about the pivot joint241, and moves or pivots relative to the second portion231. When the bracket211is in the locked configuration, the first portion229is not pivotable about the pivot joint241, and does not move or pivot relative to the second portion231. Accordingly, the pivot joint241is lockable via a locking mechanism243such that the bracket211may transition between the unlocked configuration and the locked configuration. Various types of locking mechanisms243can be utilized at the pivot point241, non-limiting example of which include a helical or threaded screw, a cam-lock, or any other suitable locking mechanism. In a non-limiting example, when the bracket211is in the first configuration, the first portion229is pivotable about the pivot point241such that the angle □ of the first portion229, and more precisely the first longitudinal axis LA1of the prosthetic valve mold207, can be adjusted within a range of 0°-180° relative to a second longitudinal axis LA2extending through the pivot point241and parallel to the collection base213, as illustrated inFIG.4.

While the bracket211is illustrated with a specific shape inFIGS.2and4, this is by way of example and not limitation. The shape of the bracket211and the first and second portions229,231can be of any suitable design permitting adjustment of the angle □ as previously described. Further, the bracket211may be formed of any suitable material such as, but not limited to aluminum, stainless steel, or plastics.

As illustrated in the embodiment ofFIG.4, the collection assembly203further includes the base213. The base213is configured to provide a stable platform onto which the second end239of the second portion231of the bracket211is coupled, and accordingly to which the motor209and the prosthetic valve mold207are effectively mounted. In an embodiment, the bracket211may be mounted to the base213in various orientations and locations relative to three planes X1, Y1, and Z1, to enable desired positioning of the prosthetic valve mold207relative to the electrospinning assembly205. Proper positioning and manipulation of the prosthetic valve mold207enables even distribution or deposition of the plurality of electrospun fibers263onto the prosthetic valve mold207. The second portion231of the bracket211may be coupled to a first surface245of the base213by methods such as, but not limited to adhesives, screws, mechanical couplings, or any other methods suitable for the purposes described herein. The base213may be formed of any suitable material, non-limiting examples of which include plastics, aluminum, and wood. In an embodiment, the base213may be a breadboard with multiple openings for mounting the bracket211in various locations, as will be understood by persons knowledgeable in the art. In another embodiment, the base213can be a movable XYZ stage. While the base213is illustrated inFIG.2with a rectangular and planar shape, this is by way of example and not limitation. The base213may have other shapes including, but not limited to a circular shape, an oval shape, or any other suitable shape.

Referring back toFIG.2, the electrospinning assembly205will now be described. The electrospinning assembly205is a simplified exemplary embodiment suitable for the purposes described herein. The electrospinning assembly205includes a needle247, a syringe249, a polymer solution251, a syringe pump253, and a power supply255. The needle247includes a first end257and a second end259. The second end259of the needle247is coupled to a first end261of the syringe249. The polymer solution251is disposed within the syringe249and the needle247. In an embodiment, the polymer solution251includes a polymer and a solvent. The polymer can be any suitable polymer such as, but not limited to polycaprolactone (PCL), polylactic acid (PLLA), polytrimethylene carbonate (PTMC), polyurethane (PU), block copolymers such as polyactic acid-polycaprolactone-polyactic acid (PLLA-PCL-PLLA), and polymer blends such as polycaprolactone/polyactic acid (PCL/PLLA). The solvent can be any suitable solvent, non-limiting examples of which include chloroform, dimethylformamide (DMF) and acetic acid. In a non-limiting example, the polymer solution251is 15% polymer by weight. The syringe pump255is configured to controllably release the polymer solution251from the first end257of the needle247. While the electrospinning process is described as utilizing the polymer solution251, which is a combination of a polymer and a solvent, this is by way of example and not limitation. In an alternative embodiment, an electrospinning process can include melt-spinning wherein the polymer is heated to a liquid state before ejection from the needle247. The power supply255is electrically coupled to the needle247via the first connection265and further electrically coupled to the prosthetic valve mold205of the collection assembly203via the second connection267. In an embodiment, the power supply255is configured to supply a first electrical force to the needle247to charge the polymer solution251dispensed from the needle247. The power supply255is further configured to place a second electrical force on the prosthetic valve mold205. The first and the second electrical forces can each be selected to control the attraction of the polymer solution251to the valve mold205to thereby optimize the even distribution of electrospun fibers263thereon, as described below. For example, and not by way of limitation, the first electrical force on the needle247can be −10 kV and the second electrical force on the prosthetic valve mold205can be 0 kv, or grounded. The first and second connections265,267may be any electrical conductor suitable for the purposes described herein. For example, and not by way of limitation, each of the first and second connections265,267can be a copper wire. While the second connection267is shown disposed external of the collection assembly203, it is understood that the second connection267may be disposed within portions of the collection assembly203.

The operation of the system201to generate the plurality of electrospun fibers263will now be described with reference toFIG.2. The syringe pump253controls the release of the polymer solution251from the first end259of the needle247. The power supply255induces a charge on the polymer solution251at the first end257of the needle247. When the induced charge overcomes the surface tension of the polymer solution251at the first end257of the needle247, a jet or stream of the polymer solution251is ejected. Acceleration of the jet of the polymer solution251through the electric field generated by the power supply255causes elongation and thinning of the jet of the polymer solution251. The electric field generated by the power supply255further causes solvent of the polymer solution251to evaporate and to thereby produce the plurality of electrospun fibers263.

FIGS.5-13illustrate steps of a method of manufacturing an electrospun prosthetic valve according to an embodiment hereof. As noted above, references to the valve mold207is for convenience only and is not meant to be limiting. Any of the valve molds described herein may be used in the method described. In a first step102, a system, such as the system201ofFIG.2, including the electrospinning assembly205and the collection assembly203is utilized. The collection assembly203includes the rotatable and angularly adjustable prosthetic valve mold207. InFIGS.5,6,8, and10, only the needle247of the electrospinning assembly205is illustrated, with the remainder of the electrospinning assembly205omitted for clarity.

Referring toFIG.5, in a next step104the prosthetic valve mold207is positioned at a desired location and angle relative to the electrospinning assembly205. More specifically, the prosthetic valve mold207is adjusted to a first angle □1 and position on the base213at a desired location to enable an even distribution of a first plurality of electrospun fibers263A onto the prosthetic valve mold207of the collection assembly203, as described below. Adjustment of the first angle □1 of the prosthetic valve mold207is accomplished by manipulating the locking mechanism243to transition the bracket211from the second or locked configuration to the first or unlocked configuration. When the bracket211is in the unlocked configuration, the prosthetic valve mold207, the motor209, and the first portion229of the bracket211is pivoted about the pivot joint241to position the prosthetic valve mold207at the first angle □1. When the prosthetic valve mold207is at the first angle □1, the locking mechanism243is manipulated to transition the bracket211from the unlocked configuration to the locked configuration.

In a next step106, with the prosthetic valve mold207is at the desired position and the first angle □1, the motor209is engaged to rotate the prosthetic valve mold207in a first direction, as illustrated by the an arrow582inFIG.5. The prosthetic valve mold207is rotated at a first rotational velocity RV1. The first rotational velocity RV1 is selected to permit the even distribution of the first plurality of electrospun fibers263A onto the outer surface219of the prosthetic valve mold207.

As illustrated inFIG.6, when the prosthetic valve mold207is positioned and rotating as desired, the electrospinning assembly205is engaged to deposit the first plurality of electrospun fibers263A onto the prosthetic valve mold207in a next step108. The first plurality of electrospun fibers263A form a first layer376of an electrospun prosthetic valve350. More specifically, the electrospinning assembly205creates a charge jet of polymer solution251from the needle247. As previously described with respect to the system201ofFIG.2, the charged jet of polymer solution251elongates to form the first plurality of electrospun fibers263A, which are deposited, distributed, or collected on the outer surface219of the rotating prosthetic valve mold207. Stated another way, the first plurality of electrospun fibers263A are collected on the prosthetic valve mold207in an even distribution to form the first layer376, as best illustrated inFIG.7. The first layer376of the electrospun prosthetic valve350may also be referred to as a valve layer or a leaflet layer.

With the first layer376deposited on the prosthetic valve mold207, in a next step110the motor209of the collection assembly203is disengaged such rotation of the prosthetic valve mold207and the first layer376collected thereon is stopped.

In a next step112illustrated inFIG.8, a frame378is positioned on an outer circumferential surface396of the first layer376. Stated another way, the frame378is slipped or slid over the first layer376such that the first layer376is disposed within a lumen382of the frame378. The frame378is a generally tubular structure and includes the lumen382extending from a first or inflow end386to a second or outflow end384. The lumen382of the frame378is configured and sized to receive the first layer376of the electrospun prosthetic valve350. In an embodiment, the frame378further includes a plurality of cells388formed by a plurality of struts390, as shown for example inFIG.9. In an embodiment, the frame378is self-expanding to return to a radially expanded configuration from a radially compressed configuration. The frame378may be formed from a variety of materials including, but not limited to stainless steel, nickel-titanium alloys (e.g. NITINOL), or other suitable materials. “Self-expanding”, as used herein refers to a structure having a mechanical memory to return to the radially expanded configuration. Mechanical memory may be imparted on the structure that forms the378using techniques understood in the art. While the frame378is shown with the plurality of equally sized cells388, this is by way of example and not limitation. In an alternative embodiment, the cells388of the frame378may be of a variety of sizes and may be distributed in any suitable pattern.

Referring next toFIG.10, with the frame378properly positioned about the first layer376, in a next step114the prosthetic valve mold207is again positioned at a desired location and angle relative to the electrospinning assembly205. More specifically, the prosthetic valve mold207is adjusted to a second angle □2 and bracket211is positioned at a desired location and orientation on the base213to enable an even distribution of a second plurality of electrospun fibers263B, as described below. Adjustment of the second angle □2 of the prosthetic valve mold207is accomplished as previously described with respect to step104. In embodiments hereof, the second angle □2 can be the same as the first angle □1, or can be a different angle. The angles □1 and □2 are set to enable even distribution of the first and second layers376,380onto the prosthetic valve mold207.

When the prosthetic valve mold207is adjusted to the second angle □2, in a next step118the motor209is engaged to rotate the prosthetic valve mold207, including the first layer376and the frame378, in the first direction illustrated by the arrow582at a second rotational velocity RV2. As previously described with reference to the step106andFIG.5, the second rotational velocity RV2 is selected to enable the even distribution of the second plurality of electrospun fibers263B. While the step118is described as rotating the prosthetic valve mold207in the first direction, this is by way of example and not limitation. It shall be understood that the step118could alternatively rotate the prosthetic valve mold207in a second direction opposite the first direction. Further, while the method100is described herein with the first and the second rotational velocities RV1 and RV2, the first and second rotational velocities can be equivalent velocities, or they can each be a different velocity.

With the prosthetic valve mold207, including the first layer376and the frame378, positioned and rotating as desired, in a next step120the electrospinning assembly205is engaged. As previously described with respect to the first layer376in step108, engagement of the electrospinning assembly205forms the second plurality of electrospun fibers263B that are deposited on an outer surface392of the first layer376and the outer surface394of the frame378to form the second layer380of the electrospun prosthetic valve350. The second layer380may also be referred to as a skirt or anti-PVL (anti-paravalvular leakage) layer. The second layer380can have a uniform diameter along a length of the prosthetic valve350(FIG.11A) or can be defined as an area of increased thickness383with respect to other regions of the second layer380′ (FIG.11B). The area of increased thickness or anti-PVL layer383can be positioned at any area along the second layer380′, as desired. The prosthetic valve350′ is otherwise identical to and is manufactured in identical ways as compared to prosthetic valve350. In one example, a pore size of the layer383is in the range of 2 to 20 μm, which is believed to result in a layer383that does not allow blood to flow through the layer383as most blood cells are around 10 microns. It is envisioned that some blood may pass but, due to active clotting, this would only occur for approximately 1-30 minutes, which is generally tolerated for most transcatheter prosthetic valves.

The anti-PVL layer383can be spun to have a variety of configurations.FIG.11Cdepicts a prosthetic valve450including an alternate second layer480having a layer or area of increased thickness483having a corrugated configuration including one or more ridges485.FIG.11Ddepicts a prosthetic valve550including an alternate second layer580having a layer or area of increased thickness483having a parachute configuration.FIG.11Edepicts a prosthetic valve650including an alternate second layer680having a layer or area of increased thickness683having a puffy configuration in which a plurality of sections685extend outwardly with respect to cells of the stent frame. It is noted that prosthetic valves450,550,650can otherwise be similarly configured and manufactured in any of the ways disclosed herein with respect to other embodiments.

For example, the layer383can be spun to include a plurality of pleats or can be a parachute style layer, for example. In some embodiments, the layer of increased thickness383is made of the same material as other electrospun components of the prosthetic valve350(e.g., second layer380). Alternatively, the layer of increased thickness383can be made of a different material. The layer of increased thickness383can be made of a biodegradable material such polycaprolactone or polylactic acid (PLLA) or their copolymers. The layer383also be made of bio-stable polymers such as polyurethane or the like. One advantage of prosthetic valves having the anti-PVL layer383is that the anti-PVL layer383can be directly electrospun on the outer surface of the frame378without having to use a tedious suturing process. Another advantage of the electrospun anti-PVL layer383is the microporous structure of the layer383, which will promote tissue growth around the layer383to provide permanent and durable seal.

EXAMPLE

2.4 g of Tecoflex™ 80A polyurethane was dissolved in 1.76 g of dimethyl formamide and 15.8 g of chloroform. The solution was loaded onto a 10 mL syringe and delivery at speed of 6 mL/h. A NITINOL stent frame was loaded onto a 2.5 cm mandrel rotated at 1500 rpm. The height of the 1 8G needle and the stent frame was about 7 cm. The applied voltage was 8.51 kv. After 10 minutes of electrospinning a thin layer of the fabric material was deposited on the stent frame. The stent frame was crimped two times and the fabric material showed good adhesion to the stent frame.

With the second layer380formed on the first layer376and the frame378, the motor209of the collection assembly203is disengaged in a next step126to stop rotation of the prosthetic valve mold207. At this point in the method100, the electrospun prosthetic valve350may be removed from the valve mold207in a step128. As explained above, use of the valve mold407with separable segments442and mold base440makes this step easier. However, non-separable valve molds207and507may also be used. At this step in the method100, the second layer380is disposed over the frame378and the first layer376, and the frame378is disposed over, or more precisely circumferentially around the first layer376of the electrospun prosthetic valve350as illustrated inFIG.11A.

At this point in the method100, the electrospun prosthetic valve350may proceed to the step134of further processing the electrospun prosthetic valve350, as will be described in more detail below. However, in some embodiments of the method100, it may desirable to ensure that the first and second layers376,378are sufficiently adhered to each other and to frame378such that delamination of the layers does not occur. Thus, optionally, further bonding of the first and second layers376,378and the frame378may be performed.

FIG.12illustrates a particular embodiment of an optional step130in the embodiment of the method100to further couple, bond, or adhere the first and second layers376,380and the frame378. In the embodiment of step130shown inFIG.12, the frame378is heated with an induction heater1295. As used herein, “induction heater” is used to describe a system configured to heat an electrically conducting object (i.e. the frame378) by magnetic induction through heat generated in the object by eddy currents. More specifically, the electrospun prosthetic valve350, including the first layer376, the frame378, and the second layer380, is placed within a magnetic field1297generated by a coil1298of the induction heater1295. The induction heater1295heats the frame378to a desired temperature to permit melting of the first and second layers376,380, respectively, in areas adjacent to the struts390of the frame378. The induction heater1295is controlled to heat the frame378to a temperature just above the melting point of the first and second layers376,380. For example, and not by way of limitation, the frame378is heated to a temperature in a range of 60° to 160° Celsius. When the frame378is heated to a temperature above the melting temperature of the first and second layers376,380, the first and the second layers376,380melt or flow adjacent the struts390of the frame378.

When the first and second layers376,380have melted adjacent the struts390of the frame378, in a next step132the induction heater1295is turned off and the first layer376, the frame378, and the second layer380are removed from the induction heater1295. Once removed from the induction heater1295, the frame378cools, and melted portions of the first and second layers376,380adjacent the struts390of the frame378cool and congeal to further bond the first and second layers376,380to each other and around the struts390of the frame378. The coupling of the first layer376and the second layer380provides improved inter-layer strength between the first layer376and the second layer380. The improved inter-layer strength prevents delamination of the first and second layers376,380of the electrospun prosthetic valve350. Because the induction heating heats the struts390of the frame378, areas of the first and second layers376,380spaced from the struts390in the cells do not melt. Thus, the limited melt area adjacent the struts390of the frame378does not sacrifice the overall porous structure of the first and second layers376,380that promote tissue ingrowth in situ.

Although the induction heater1295has been described herein to thermally improve adhesion between the first and second layers376,380, in an alternative embodiment, adhesion between the first and second layers376,380can be improved using other thermal sources. For example, and not by way of limitation, a laser or other suitable thermal device can be utilized. Further, a coupling or adhesion promoter can be utilized on the frame378to promote coupling of the first and/or second layers376,380with the frame378and prevent delamination. In one example, the adhesion promoter is a vapor deposited poly(p-xylylene) (“parylene”) polymer. Parylene is vapor deposited to covalently bonded to the frame. Other polymers or molecules can then be covalently bonded to the parylene adhesion promoter. In this way, the adhesion promoter creates a bridge for functional material to adhere to the metal frame. It is believed that a parylene adhesion promoter provides a stronger, more robust adhesion to the frame.

In a next step134, further processing is performed to finalize the electrospun prosthetic valve350. For example, and not by way of limitation, the further processing may include, but is not limited to, removal of excess material, such as a base portion381(shown inFIG.11A) and separation of the leaflets358,360,362. In an embodiment, a laser cutter (not shown) may be used to remove excess material and to separate the leaflets358,360,362. In a particular embodiment wherein the valve mold207includes channels244described above, the laser or other cutter may cut along the corresponding channels formed in the prosthetic valve350to separate the leaflets358,360,362from each other.

The finalized electrospun prosthetic valve350is shown inFIG.13. The electrospun prosthetic valve350includes the inflow end352, the outflow end354opposite the inflow end352, and a lumen356extending from the inflow end352to the outflow end354. The electrospun prosthetic valve350further includes a radially collapsed configuration for delivery, and a radially expanded configuration when deployed as shown inFIG.13. In an embodiment, the prosthetic valve350is configured as a prosthetic heart valve configured to replace a damaged or diseased native heart valve. In an embodiment, the prosthetic valve350is self-expanding to return to the radially expanded configuration from the radially compressed configuration. In the embodiment ofFIG.13, the three (3) leaflets358,360, and362are formed adjacent the outflow end354of the electrospun prosthetic valve350. Adjoining pairs of leaflets are attached to one another at their lateral ends to form commissures364,366,368, with free edges370,372,374of the leaflets forming coaptation edges. The leaflets358,360,362are configured to permit flow in one direction, from the inflow end352to the outflow end354to regulate flow through the lumen356of the electrospun prosthetic valve350. While the electrospun prosthetic valve350has been described as self-expanding, alternatively the electrospun prosthetic valve350can be balloon expandable.

As explained above, the electrospun prosthetic valve350includes the first or valve layer376, the second or skirt layer380, and the frame378disposed between the first and second layers376,380. The second layer380is configured to act as a paravalvular leakage (PVL) skirt permitting a tight seal with surrounding tissue when the electrospun prosthetic valve350is in the radially expanded configuration and deployed at a desired treatment location. Use of the second layer380as the paravalvular leakage (PVL) skirt reduces or eliminates the need for suturing the valve layer376to the frame378.

While the electrospun prosthetic valve350is described herein and illustrated inFIG.13with the first layer376, the second layer380, and the frame378, and further with the frame378disposed between the first and second layers376,380, this is by way of example and not limitation. In alternative embodiments hereof, the electrospun prosthetic valve350may include the first layer376, the frame378, and/or the second layer380in any combination, and may include more or fewer layers. Further, while the electrospun prosthetic valve350is described herein with three (3) leaflets358,360,362, this too is by way of example and not limitation, and more or fewer leaflets may be formed with embodiments of electrospun prosthetic valves described herein.

FIG.14is a flow chart showing a method1400of making a medical device such as an electrospun prosthetic valve1550according to another embodiment hereof. The method1400is similar to the method100ofFIG.1except that steps to couple a first layer1876to a second layer1880of the electrospun prosthetic valve1550are different. Thus, the steps1402,1404,1406,1408,1410,1412, and1414of the method1400ofFIG.14are similar to the steps102,104,106,108,110,112, and114previously described with respect to the method100ofFIG.1. Therefore, detailed descriptions of the steps1402,1404,1406,1408,1410,1412, and1414of the method1400will not be repeated here, and the description above regarding the method100and the electrospun prosthetic valve350applies to and is incorporated to the method1400and the electrospun prosthetic valve1850. Thus, the electrospun prosthetic valve1550includes a first or valve layer1576, a second or skirt layer1580, and a frame1578disposed between the first layer1576and the second layer1580. The various details and alternatives described above with respect toFIGS.1-13apply equally to the method1400and the electrospun prosthetic valve1550.

Accordingly, after the frame1578has been properly positioned about the first layer1576at the conclusion of the step1412and the second angle □2, has been set, in a next step1416a bonding solvent1599(and/or other adhesion promoter as disclosed herein) is applied to an outer surface1592of the first layer1576and an outer surface1594of the frame1578, an illustrated example of which is illustrated inFIG.15. The bonding solvent1599is configured to control or increase the tackiness of the first layer1576to couple, bond or adhere the second layer1580to the first layer1576when the second layer1580(illustrated inFIG.16) is collected or distributed thereon as described below. Stated another way, the bonding solvent1599is configured to increase adhesion between the first and second layers1576,1580. More specifically, application of the bonding solvent1599wets and thereby increases the tackiness of the first layer1576such that when the second layer1580is distributed or collected thereon, the second layer1580and the first layer1576can flow to thereby couple to one another across the entirety of the first and second layers1576,1580. The bonding solvent1599can be any suitable solvent including, but not limited to chloroform, dimethylformamide (DMF) or acetic acid. The bonding solvent1599can be the same solvent utilized in the polymer solution251, or can be of a lower volatility than the solvent utilized in the polymer solution251. Further, the bonding solvent1599can be of a diluted, low viscosity formulation of the polymer solution251to further promote adhesion between the first layer1576and the second layer1580as described below. For example, and not by way of limitation, the bonding solvent1599can be 2% polymer by weight. Alternatively, an adhesive such as, but not limited to octyl-cyanoacrylate (OCA), or liquid silicone can be utilized in place of the bonding solvent1599.

The bonding solvent1599can be applied to the outer surface1592of the first layer1576and the outer surface1594of the frame1578by various techniques, non-limiting examples of which include an atomizer, an airbrush, a sonic sprayer, vapor activation, electrospray or any other suitable application technique. In the embodiment ofFIG.15, the bonding solvent1599is sprayed onto the first layer1576and the frame1578with a sonic sprayer1589. “Sonic sprayer” as used herein is intended to describe a spray process wherein ultrasonic sensors are utilized to spray precise amounts of a material (i.e. the bonding solvent1599) onto the first layer1576and the frame1578to control the tackiness of the of the first layer1576. Alternatively, the bonding solvent1599can be applied only to the outer surface1592of the first layer1594.

When the bonding solvent1599has been distributed onto the first layer1576and the frame1578, the motor209is engaged in a next step1418. The motor209rotates the prosthetic valve mold207, including the first layer1576and the frame1578, in a first direction illustrated by the arrow1682inFIG.16, at a desired second rotational velocity RV2. The second rotational velocity RV2 is selected to enable the even distribution of a second plurality of electrospun fibers263B onto the outer surface1592of the first layer1576and the outer surface1594of the frame1578, as previously described with reference to the step106andFIG.6.

In a next step1420illustrated inFIG.16, with the prosthetic valve mold207, including the first layer1576and the frame1578is positioned and rotating as desired, the electrospinning assembly205is engaged and the second layer1580is collected and distributed on the rotating outer surfaces1592,1594of the first layer1576and the frame1578, respectively. As the second layer1580is distributed onto the first layer1576, the tackiness of the first layer1576permits the second layer1580to flow and to couple with the first layer1576.

With the second layer1580distributed onto the first layer1576and the frame1578, the motor209of the collection assembly203is disengaged in a next step1426, the steps1426,1428, and1434are similar to the steps126,128, and134described above with respect toFIG.1. Therefore, the details and variations will not be repeated herein and are incorporated into the method ofFIG.14. The electrospun prosthetic valve1450after step1428and prior to step1434is shown inFIG.16. The electrospun prosthetic valve1450after step1434is shown inFIG.17. As can be seen, at least the leaflets of the electrospun prosthetic valve1450have been separated, as described above with respect to the step134of the method100.

FIG.19is a flow chart showing a method1900of making a medical device such as an electrospun prosthetic valve2050ofFIG.21. Steps1902,1904,1906,1908,1910,1912,1914,1916,1918,1920,1926,1928and1934of the method1900ofFIG.19are similar to the steps1402,1404,1406,1408,1410,1412,1414,1416,1418,1420,1426,1428and1434previously described with respect to the method1400ofFIG.14. Therefore, detailed descriptions of the steps1902,1904,1906,1908,1910,1912,1914,1916,1918,1920,1926,1928, and1934will not be repeated here. Accordingly, the electrospun prosthetic valve2050is formed in an electrospinning process and then processed in step1934. However, the method1900ofFIG.19includes the additional steps1922and1924to improve structural strength of selected portions2083of the electrospun prosthetic valve2050.

Picking up after the step1920, in a next step1922, with a second layer2080disposed on a frame2078and a first layer2076of the electrospun prosthetic valve2050, the heated portions546(FIG.3C) of the prosthetic valve mold507(FIG.3C) are heated to melt corresponding selected portions2083A,2083B,2083C,2083D,2083E, and2083F (collectively referred to herein as “selected portions2083”) of the first and a second layer2076,2080. The temperature of the first portions546of the prosthetic valve mold507is precisely controlled to melt the first and second layers2076,2080in the selected portions2083only. Once melted, in a next step1924the first portions246of the prosthetic valve mold507are cooled to crystalize the selected portions2083of the electrospun prosthetic valve2050to improve the strength in the electrospun prosthetic valve2050in the crystalized selected portions2083. Although the steps1922and1924are discussed above as occurring after the second layer2080is deposited on the first layer2076and the frame2078, the step1922may be performed simultaneously with the step1920of depositing the second layer2080on the first layer2076and the frame2078. Thus, as the second layer2080is being deposited, the heated portions546of the valve mold507crystallize the first and second layers2076,2080for improved strength in these areas. The steps1926,1928, and1934are then performed to form the electrospun prosthetic valve2050shown inFIG.20(prior to step1934) andFIG.21(after step1934).

In the embodiment of the electrospun prosthetic valve2050ofFIG.21, the free edges2070,2072,2074and the corresponding commissures2064,2066,2068of the leaflets2058,2060, and2062were heated and crystalized. Accordingly, the crystalized free edges2170,2172,2174and the corresponding commissures2164,2166,2168exhibit improved strength. However, crystallization reduces the porosity of the electrospun fibers263of the electrospun prosthetic valve2050in the crystallized areas, which negatively impacting tissue ingrowth. While it is desirable to maintain the porosity of the electrospun fibers throughout the prosthetic valve2050to promote tissue ingrowth, limited portions of the electrospun prosthetic valve2050can be sacrificed to improve the overall mechanical performance of the electrospun prosthetic valve2050to ensure physiological viability. Stated another way, selected portions of the electrospun prosthetic valve2050can be melted and then crystalized to provide improved structural strength in desired locations while minimizing loss of the overall porous structure of the electrospun prosthetic valve2050that promote tissue ingrowth in situ.

Although the steps1922,1924have been described as improving the strength of the crystallized the free edges2070,2072,2074and the commissures2064,2066,2068of the leaflets2058,2060,2062, of the electrospun prosthetic valve2150, this too is by way of example and not limitation and in alternative embodiments, other portions of the electrospun prosthetic valve2050can be selectively melted and crystallized in any combination.

While various embodiments according to the present disclosure have been described above, it should be understood that they have been presented by way of illustration and example only, and not limitation. It will be apparent to persons skilled in the relevant art that various changes in form and detail can be made therein without departing from the spirit and scope of the disclosure. Thus, the breadth and scope of the present disclosure should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the appended claims and their equivalents. It will also be understood that each feature of each embodiment discussed herein, and of each reference cited herein, can be used in combination with the features of any other embodiment.