KR20230007372A - Method for manufacturing a naturally designed personalized mitral valve prosthesis - Google Patents

Abstract

Provides a naturally designed personalized mitral valve prosthesis and a manufacturing method that is precisely tailored to the specific patient who manufactures it. The method includes an operation of measuring the size and shape of the mitral valve of a specific patient using an imaging means, an operation of constructing a 3D model of a personalized mitral valve prosthesis, an operation of optimizing the 3D model using the FEM method, and an annular ring, leaflet and fabricating a personalized mitral valve prosthesis by cutting and splicing the scapula and nerves to form a personalized prosthesis mitral valve.

Description

Method for manufacturing a naturally designed personalized mitral valve prosthesis

The following embodiments relate to a technique for fabricating a naturally designed personalized mitral valve prosthesis.

A bicuspid valve (i.e., a valve containing two leaflets), the mitral valve or left atrioventricular valve, is the valve in the heart that separates the left atrium from the left ventricle. . The mitral valve allows blood to flow from the left atrium to the left ventricle during ventricular diastole and prevents retrograde flow during systole. The naturally occurring mitral valve consists of an annulus, two leaflets, atrial myocardium, chordae tendinae, pupillary muscles, and ventricular myocardium.

Mitral valve replacement is a procedure designed to be performed to replace a diseased or non-functioning valve. During a mitral valve replacement procedure, a patient's mitral valve is removed and replaced with a prosthesis. The unique configuration of the mitral valve presents challenges in making a long lasting and normally functioning mitral valve prosthesis.

Biological and mechanical mitral valve prostheses are commercially available. In contrast to the soft tissue and asymmetrical shape of the human mitral valve, both biological and mechanical prostheses have rigid circular shapes. Another disadvantage of mechanical valves is that blood tends to clot in the mechanical components of the valve, causing the valve to function abnormally. Patients with mechanical valves must take anticoagulants to prevent the risk of a stroke due to the formation of blood clots in the valves. Biological valves have a low risk of clot formation, but have limited durability and require more frequent replacement than mechanical valves. Like mechanical valves, biological valves contain a rigid metal skeleton and a metal ring covered with silicone or other synthetic material through which implantation sutures can pass. characterized by

Currently available mitral valve prostheses are generally manufactured in an unnatural circular shape and are often made of hard materials. They are also often characterized by three symmetric leaflets, whereas natural human mitral valves contain only two leaflets, a larger anterior leaflet and a smaller posterior leaflet. These mitral valve prostheses distort the natural anatomy of the heart due to their rigid and unnatural structure. The heart muscle surrounding these prostheses does not recover well after implant surgery. Since the lifespan of prostheses is only 7 to 10 years on average, patients have to undergo secondary and sometimes tertiary surgeries throughout their lifetime, which exposes patients to high risks of open heart surgery repeatedly.

Commercially available prostheses do not achieve the hemodynamic performance of a healthy native human mitral valve. This results in significant energy loss in the left ventricle, significant strain over time, and eventual heart failure and other adverse phenomena.

Other available mitral valve prostheses may be formed by strengthening a homograft as described in US 6,074,417, which would require the surgeon to scan valves of various sizes to find the best fit for each patient, while at the same time obtaining valves. It means sacrificing animals. Other available mitral valve prostheses may be formed by sewing together several layers of the pericardium as described in US 5,415,667, which may cause coagulation in areas where multiple sutures are present. .

Other types of atrioventricular valves, including mitral valves, are disclosed in US Pat. No. 6,358,277 in which a template of membrane material is sutured to the patient's mitral annulus. These valves are characterized by a high, unnaturally shaped annulus, which makes the circumference of the prosthetic valve bulky and raised like a collar. Templates are also provided in standard sizes and must be trimmed to fit the patient.

We provide a method for manufacturing a personalized naturally designed mitral valve prosthesis that fits and functions precisely with each patient. Specifically, the method receives a customized/personalized order of a mitral valve prosthesis together with diagnosing the imaging and analyzing the imaging results, and uses a validated algorithm to determine the geometry of the valve prosthesis. quantify geometry and dimensions, produce valves according to the recipient patient's individualized geometry and dimensions, and adapt to the specific patient's anatomy and clinical condition A series of steps beginning with assembling a personalized valve prosthesis specifically designed to fit, packaging and sterilizing the personalized valve prosthesis into the final mitral valve prosthesis, sending it to a specific patient for implantation and implanting the personalized mitral valve into the patient. Includes operations or procedures of

A method for fabricating a personalized mitral valve prosthesis that is naturally designed to precisely fit the specific patient for which the valve prosthesis is to be fabricated is provided. The method measures the size and shape of the native mitral valve of a specific patient using imaging methods, and for each specific patient based on a verified algorithm. Calculating the geometry and dimensions of the annular ring, anterior leaflet, posterior leaflet and nerves, and forming a personalized prosthesis mitral valve by cutting and connecting the annular ring, anterior leaflet, posterior leaflet and nerves. can include

According to some embodiments, imaging methods include 2D or 3D echocardiography, computed tomography (CT), cardiac magnetic resonance (CMR), or a combination thereof. can do.

According to some embodiments, measuring the size and shape of the patient's own mitral valve may include measuring mitral valve-related parameters, the parameters being: annular ring circumference (AC); annulus area (AA), anterior-posterior (A-P) diameter, anterolateral-posteromedial (AL-PM) diameter, commissural diameter diameter (C-C), anterior leaflet length (ALL), posterior leaflet length (PLL), shape of the mitral valve and length of chordae tendineae (ACL and PCL). can do.

According to some embodiments, a method provides specific patient physical information for use during a computational operation to predict the geometry of the heart after implantation with improved heart valve function. Information) may be further included, and the body information includes body height, body weight, age, race, and gender.

A personalized mitral valve prosthesis is a flexible annular ring dimensioned to match a specific patient's unique mitral annulus, a specific patient's unique mitral leaflet and Flexible anterior leaflets and posterior leaflets dimensioned to match, leaflets connected to an annular ring, and chords dimensioned to match the specific patient's unique mitral leaflet. It contains nerves that connect to the papillary muscles of the heart. A personalized mitral valve prosthesis can be formed by:

measuring the size and shape of a specific patient's native mitral valve using imaging methods;

calculating the geometry and dimensions of the annular ring, leaflets and nerves for a particular patient based on a validated algorithm; and

The operation of cutting and joining the annular ring, leaflets and nerves to form a personalized prosthesis mitral valve.

According to some embodiments, imaging methods include 2D or 3D echocardiography, computed tomography (CT), cardiac magnetic resonance (CMR), or a combination thereof. can do.

According to some embodiments, measuring the size and shape of the patient's own mitral valve may include measuring mitral valve-related parameters, the parameters being: annular ring circumference (AC); annulus area (AA), anterior-posterior (A-P) diameter, anterolateral-posteromedial (AL-PM) diameter, commissural diameter diameter (C-C), anterior leaflet length (ALL), posterior leaflet length (PLL), shape of the mitral valve and length of chordae tendineae (ACL and PCL). can do.

In accordance with some embodiments, the personalized mitral valve prosthesis provides specific patient body information for use during calculations to predict the geometry of the heart after implantation with improved heart valve function. An operation of collecting physical information may be further included, and the body information includes body height, body weight, age, race, and gender.

According to some embodiments, the operation of calculating an annular ring circumference (AC) is a combination of an anterior leaflet annular ring circumference (AAC) and a posterior leaflet annular ring circumference (PAC). ), wherein the preleaflet annular ring circumference is the top edge of the preleaflet, and the posterior leaflet annular ring circumference is the top edge of the posterior leaflet based on equation (3). According to some embodiments, the annular ring may be formed into a multi-layered reinforced structure by folding or overlapping the top edges of the anterior and posterior leaflets.

According to some embodiments, the top edge of each of the anterior and posterior leaflets may be straight or curved, in order to properly fit the personalized mitral valve prosthesis to the natural geometry of the particular patient's left ventricle. can be

According to some embodiments, joining may include joining an edge of the preleaflet with an edge of the posterior leaflet to create a coptation between the preleaflet and the posterior leaflet. According to some embodiments, bonding may control the function and performance of the personalized mitral valve prosthesis by controlling the size of the valve orifice, thus affecting the trans-mitral pressure gradient. can affect

According to some embodiments, joining may include joining two leaflets together to form two commissures, the two commissures tilting inward at a cone angle δ ₁ to form a specific A slight cone shape is created in the body of the personalized mitral valve prosthesis to properly fit the unique left ventricle according to the patient's shape and contour.

According to some embodiments, the cone angle δ ₁ may be determined by the inclination angle δ ₀ of each commissure edge of the two leaflets based on Equation (10).

According to some embodiments, connecting may include connecting an anterior leaflet to a posterior leaflet by connecting anterolateral to anterolateral and posteromedial to posteromedial.

According to some embodiments, connecting the anterior leaflet to the posterior leaflet may be by stitching.

According to some embodiments, the operation of measuring may include the size and shape of a particular patient's unique annular ring, commissure height (CH) inclination angle ( and measuring commissure height inclined angle (δ ₀ ), anterior leaflet length (ALL), posterior leaflet length (PLL), and coaptation height (Coapt H).

According to some embodiments, the height of the reinforced annular ring may be between 1 mm and 4 mm.

According to some embodiments, the height of the reinforced annular ring may be between 2 mm and 3 mm.

According to some embodiments, the annular ring circumference AC can be a function of an anterior-posterior diameter (A-P) and an anterior-posterior-medial diameter (AL-PM) based on Equation (3).

According to some embodiments, the operation of measuring the anterior-posterior diameter (AP) and anterolateral posterior-medial diameter (AL-PM) may be when the mitral valve is closed during left ventricular systole.

According to some embodiments, calculating the annular ring circumference (AC) of the prosthesis may be based on the original annular ring width (d) of leaflets preserved during clinical surgery.

)에 기초할 수 있다.According to some embodiments, calculating the annular ring circumference (AC) of the prosthesis is the ratio of Equation (3) (

) can be based on.

According to some embodiments, the annular ring may be asymmetrical. According to some embodiments, the annular ring may be formed from a combination of a preleaflet annulus and a posterior leaflet annulus, whereby the preleaflet annular circumference (AAC) may be smaller than the posterior leaflet annular circumference (PAC), and AAC The ratio (R) between /PAC may be 49/51 to 30/70.

According to some embodiments, the ratio (R) between AAC/PAC may be 35/65 to 42/58.

According to some embodiments, the ratio (R) between AAC/PAC may be 40/60.

According to some embodiments, the ratio (R) between AAC/PAC may be between the anterior leaflet length (ALL) and the posterior leaflet length (PLL) to ensure that the prosthesis valve opens and closes properly. can be important for

According to some embodiments, the operation of calculating (a) the anterior-posterior diameter (A-P), which is the theoretical minimum distance for bonding; (b) the ratio between AL and PL (r); (c) Coaptation depth (Cd); (d) joint height (Coapt H); and (e) calculating an anterior leaflet length (ALL) and a posterior leaflet length (PLL) based on Equations (8) and Equations (9) based on the chord length (Lc). can include

According to some embodiments, connecting may include connecting two leaflets together to form the body of a personalized mitral valve prosthesis.

According to some embodiments, each of the anterior leaflets and each of the posterior leaflets include two sets of nerves, the two sets of nerves being the anterolateral nerves and the posteromedial nerves. According to some embodiments, each of the anterior lateral nerves and posteromedial nerves include three sub-chords whereby the cords extend from each end to each edge. Evenly distributed along at least 3/8.

According to some embodiments, the calculating may include calculating the length of each nerve to properly open and close the personalized mitral valve prosthesis, and calculating the length of each nerve may include the length of the leaflet, the junction It is based on several parameters including height and bonding depth.

According to some embodiments, measuring may include measuring a distance from a papillary muscle apex to a junction edge to indicate a prosthesis chord length, and a set of nerves It may further include on-site measurement and adjustment of a pledget such as a chord cap where nerves are integrated and merged at each end. .

According to some embodiments, a personalized mitral valve prosthesis can be configured as inputs to engineering drawing software or drawing tools, such as an annular ring, anterior leaflet, posterior leaflet, and specific patient-specific mitral valve prosthesis. It can be further formed by implementing the computed geometry and dimensions of the nerves.

According to some embodiments, engineering drawing software or drawing tools may output a template for manually cutting leaflets of a valve prosthesis.

According to some embodiments, the engineering drawing software or drawing tool may output a template for machine cut leaflets.

According to some embodiments, the personalized mitral valve prosthesis is packaged, labeled, and sterilized prior to release for use. more can be formed.

According to some embodiments, the personalized mitral valve prosthesis may be further formed by assembling the personalized mitral valve prosthesis to a valve holder prior to the packaging operation.

According to some embodiments, the personalized mitral valve prosthesis may be further formed by implanting the personalized mitral valve prosthesis into a specific patient.

A prosthetic valve designed to resemble a patient's natural mitral valve is provided. The two flexible leaflets and the asymmetric, flexible ring can move with the natural twist of the heart muscle during the cardiac cycle. Similar to a patient's native tendon, nerves are included in the prosthetic valve to mimic preventing the natural backflow of blood into the atrium and to support the left ventricle during systole.

According to some embodiments, a mitral valve prosthesis to be implanted in the heart includes an asymmetric ring, an anterior flexible leaflet and a posterior flexible leaflet and at least two sets of nerves, the asymmetric ring dimensioned to mimic the patient's native mitral annular shape. is adjusted, the asymmetric ring is composed of a flexible material rolled toward the outside of the valve, the anterior and posterior leaflets are suspended from the asymmetric ring and configured to substantially engage each other, and the shape of each anterior and posterior leaflet is unique. Constructed to mimic the shape of a mitral valve, whereby the anterior and posterior leaflets create an orifice through which blood flows in one direction, each set of nerves being attached to the anterior or posterior leaflets at a first end and to the cap at a second end. attached, the cap is configured to be attached to the papillary muscle of the heart at the other end.

According to some embodiments, the mitral valve prosthesis continues to each of the anterior and posterior leaflets and may further include a coupling surface attached to each set of nerves, the coupling surface sealing the mitral valve prosthesis. It is configured to improve sealing.

According to some embodiments, the asymmetric ring may further include at least two strands composed of a coiled coil structure.

According to some embodiments, an asymmetric ring can include two layers of material folded together to provide elasticity and a third layer to provide structural stability.

According to some embodiments, the asymmetric ring comprises two layers of bovine pericardium; and a third layer of Glycine or Proline to provide strength.

According to some embodiments, the layers may be joined together via sutures stapler pins, glue, or any combination thereof.

According to some embodiments, the asymmetric ring, anterior flexible leaflet and posterior flexible leaflet, at least two nerves, cap or any combination thereof may be fabricated from a bovine pericardium.

According to some embodiments, the leaflet shape can be elongated 1-5 mm to allow for better junction and nerve attachment.

According to some embodiments, the leaflet shape can be designed in a semicircular fashion along half the length of the anterior and posterior flexible leaflets to create an 'S' shaped seal when the two leaflets are joined. .

According to some embodiments, the mitral valve may further include at least one secondary cord; The at least one secondary nerve may have one end attached to a mid-section of the posterior leaflet and the other end attached to a mid-section of the primary cord.

According to some embodiments, at least two sets of nerves may be attached to an opening of the cap, the opening being located in the center of the cap.

According to some embodiments, each of the at least two sets of nerves may be attached to a middle section of either the anterior leaflet or the posterior leaflet to mimic a naturally occurring mitral valve.

According to some embodiments, the anterior and posterior leaflets may be fabricated as a single unit connected to an asymmetric ring and attached to at least two sets of nerves.

According to some embodiments, the mitral valve is an extension connected to the anterior flexible leaflet at one end and to two or more sets of nerves at the other end and configured to allow junctions between the anterior and posterior flexible leaflets. ) may further include.

According to some embodiments, a mitral valve prosthesis to be implanted in the heart comprises an asymmetric ring dimensioned to mimic the patient's native mitral annulus; two leaflets suspended from an asymmetric ring; comprising at least two sets of nerves and a cap, wherein the asymmetric ring is made of a flexible material that is rolled toward the outer side of the valve, and the leaflets are made through an incision made along a material similar to the material of which the asymmetric ring is constructed ( an incision, the incision creating an orifice through which blood flows in one direction, each set of nerves being attached at a first end to one of the two leaflets and attached at a second end in a bundle. and the cap is configured to be connected to at least two sets of nerves at one end of the cap and sutured to the papillary muscle of the heart at the other end of the cap.

According to some embodiments, each set of nerves is attached to one of the two leaflets via extensions configured to allow junctions between the two leaflets.

According to some embodiments, a method of fabricating a mitral valve prosthesis may include:

measuring the size and shape of the patient's mitral valve through imaging methods;

cutting a mitral valve replica of a subject from a single piece of material;

cutting an incision along a single piece of material to create an orifice for blood flow and two leaflets, one on each side of the orifice;

An operation of measuring the length of nerves required through imaging methods;

attaching nerves to one of the two caps; and

The act of attaching flexible rings to the leaflets to create a full mitral valve prosthesis that mimics a particular patient's unique mitral valve.

According to some embodiments, an operation of measuring the length of necessary nerves may be performed simultaneously with an operation of measuring the size and shape of the subject's mitral valve.

According to some embodiments, the method may further include attaching an extension to each of the two leaflets to carry the nerves prior to attaching the nerves to one of the two caps.

A method for fabricating a personalized mitral valve prosthesis that is naturally designed to precisely fit the specific patient for which the valve prosthesis is to be fabricated is provided. Methods may include:

The operation of measuring the size and shape of a specific patient's native mitral valve using imaging means, the material from which a personalized mitral valve prosthesis is made An operation of providing data of

Building a 3D model of a personalized mitral valve prosthesis based on the data of the size, shape and material of the specific patient's unique mitral valve;

the act of optimizing the 3D model using the FEM method;

Operation of fabricating a personalized mitral valve prosthesis based on the optimized FEM model.

According to some embodiments, an operation of visualizing the personalized mitral valve prosthesis model may be further included after the operation of optimizing.

According to some embodiments, the imaging means includes 2D or 3D echocardiography, computed tomography (CT), cardiac magnetic resonance (CMR), or a combination thereof. can do.

According to some embodiments, measuring the size and shape of the patient's own mitral valve includes measuring mitral valve-related parameters, the parameters being: annular ring circumference (AC), annular area (annulus area) (AA), anterior-posterior (A-P) diameter, anterolateral-posteromedial (AL-PM) diameter, commissural diameter (C–C), anterior leaflet length (AL), posterior leaflet length (PL), morphology of the mitral valve and length of chordae tendineae (ACL and PCL).

According to some embodiments, the method further comprises collecting physical information of a particular patient to predict the geometry of the heart after implantation of the personalized mitral valve prosthesis, wherein the physical information is (body height), body weight (body weight), age (age), race (race) and gender (gender).

In some embodiments, a personalized mitral valve prosthesis is provided. A personalized mitral valve prosthesis is a flexible annular ring dimensioned to match a specific patient's unique mitral annulus, a specific patient's unique mitral leaflet and flexible anterior leaflets and posterior leaflets dimensioned to match, and chords dimensioned to match the specific patient's unique mitral leaflets, the leaflets comprising: Connected to the annular ring, the nerves are connected to the flexible anterior leaflet and the flexible posterior leaflet, and the nerves are further configured to connect the flexible anterior leaflet and the flexible posterior leaflet with papillary muscles of the heart. In some embodiments, a personalized mitral valve prosthesis may be formed by:

measuring the size and shape of a native mitral valve of a particular patient using imaging means;

providing data of a material from which the personalized mitral valve prosthesis is made;

Building a 3D model of a personalized mitral valve prosthesis based on data on the size, shape and material of the mitral valve unique to a specific patient;

optimizing the 3D model using the FEM method;

and

cutting the material into an annular ring, flexible anterior leaflet and flexible posterior leaflet and nerves, connecting the flexible anterior leaflet and flexible posterior leaflet to the annular ring, and connecting the nerves to the flexible anterior leaflet and flexible posterior leaflet By doing so, an operation of fabricating a personalized mitral valve prosthesis based on the optimized FEM model. In some embodiments, the personalized prosthetic mitral valve may optionally be further formed by including an operation of visualizing the personalized mitral valve prosthesis model prior to the operation of fabrication.

According to some embodiments, the imaging means includes 2D or 3D echocardiography, computed tomography (CT), cardiac magnetic resonance (CMR), or a combination thereof. do.

According to some embodiments, measuring the size and shape of the patient's own mitral valve includes measuring mitral valve-related parameters, the parameters being: annular ring circumference (AC), annular area (annulus area) (AA), anterior-posterior (A-P) diameter, anterolateral-posteromedial (AL-PM) diameter, commissural diameter (C-C), anterior leaflet length (ALL), posterior leaflet length (PLL), morphology of the mitral valve and length of chordae tendineae (ACL and PCL).

According to some embodiments, the personalized artificial mitral valve may be further formed by collecting physical information of a specific patient to predict the geometry of the heart after implantation of the personalized mitral valve prosthesis. and body information includes body height, body weight, age, race, and gender.

According to some embodiments, the operation of measuring may include a combination of an anterior leaflet annular ring circumference (AAC) and a posterior leaflet annular ring circumference (PAC) to determine an annular ring circumference ( AC), where the preleaflet annular ring circumference is the top edge of the preleaflet, and the posterior leaflet annular ring circumference is the top edge of the posterior leaflet based on equation (3).

According to some embodiments, the annular ring is formed into a multi-layered reinforced structure by folding or overlapping the top edges of the anterior and posterior leaflets.

According to some embodiments, the top edge of each of the anterior and posterior leaflets may be straight or curved, in order to properly fit the personalized mitral valve prosthesis to the natural geometry of the particular patient's left ventricle. )to be.

According to some embodiments, connecting includes joining an edge of the preleaflet with an edge of the posterior leaflet to create a coptation between the preleaflet and the posterior leaflet.

According to some embodiments, connecting includes joining the flexible anterior leaflet and the flexible posterior leaflet together to form two commissures, the two commissures being medial at a cone angle δ ₁ . tilted to create a conical shape on a personalized mitral valve prosthesis to fit a particular patient's unique left ventricle.

According to some embodiments, the cone angle (δ ₁ ) is determined by the inclined angle (δ ₀ ) of each commissure edge of the flexible anterior and posterior leaflets based on Equation (10): do.

According to some embodiments, connecting includes connecting an anterior leaflet to a posterior leaflet by connecting anterolateral to anterolateral and posteromedial to posteromedial.

Connecting the anterior leaflet to the posterior leaflet, according to some embodiments, includes stitching.

According to some embodiments, the operation of measuring may include the size and shape of a particular patient's unique annular ring, commissure height (CH) inclination angle ( and measuring commissure height inclined angle (δ ₀ ), anterior leaflet length (ALL), posterior leaflet length (PLL), and coaptation height (Coapt H).

According to some embodiments, the reinforced annular ring height is between 1 mm and 4 mm.

According to some embodiments, the reinforced annular ring height is between 2 mm and 3 mm.

According to some embodiments, the annular ring circumference AC is a function of an anterior-posterior diameter (A-P) and an anterior-posterior-medial diameter (AL-PM) based on Equation (3).

According to some embodiments, the measuring operation includes measuring the anterior-posterior diameter (A-P), and the anterior-posterior-medial diameter (AL-PM) is determined when the mitral valve closes during left ventricular systole. performed in case

)에 기초한다.According to some embodiments, calculating the annular ring circumference (AC) of the prosthesis is the ratio of Equation (3) (

) is based on

According to some embodiments, the annular ring is asymmetrical, the annular ring is formed from a combination of a preleaflet annulus and a posterior leaflet annulus, and the preleaflet annular circumference (AAC) is a posterior leaflet annular circumference (PAC). It is smaller and the ratio (R) between AAC/PAC is 49/51 to 30/70.

According to some embodiments, the ratio (R) between AAC/PAC is between 35/65 and 42/58.

According to some embodiments, the ratio (R) between AAC/PAC is 40/60.

According to some embodiments, the ratio (R) between AAC/PAC is between the preleaflet length (ALL) and the posterior leaflet length (PLL).

According to some embodiments, the operation of building a 3D model of a personalized mitral valve prosthesis includes calculating an anterior leaf circular circumference (AAC) and a posterior leaf circular circumference (PAC) based on suture positions (A and B). include action

According to some embodiments, the operation of building a 3D model of a personalized mitral valve prosthesis includes (a) an anterior-posterior diameter (A-P), which is a theoretical minimum distance for bonding; (b) the ratio between ALL and PLL (r); (c) Coaptation depth (Cd); (d) joint height (Coapt H); and (e) calculating an anterior leaflet length (ALL) and a posterior leaflet length (PLL) based on equation (8) and equation (9) based on the chord length (Lc). include action

According to some embodiments, connecting includes connecting the anterior and posterior leaflets together to form the body of the personalized mitral valve prosthesis.

According to some embodiments, each of the anterior leaflets and each of the posterior leaflets include two sets of nerves, the two sets of nerves being the anterolateral nerves and the posteromedial nerves, and the anterolateral nerves and the posteromedial nerve, according to some embodiments. Each of the s contains three sub-chords, the nerves being evenly distributed along at least 3/8 of each edge from each side.

According to some embodiments, the operation of building the 3D model includes the operation of calculating the length of each, and the operation of calculating the length of each nerve depends on parameters including leaflet length, junction height and junction depth. based on

According to some embodiments, measuring includes measuring a distance from a papillary muscle apex to a junction edge to indicate a prosthesis chord length, each set of nerves and on-site measurement and adjustment of a pledget such as a chord cap where nerves are integrated and merged at the end of the .

According to some embodiments, the operation of building a 3D model involves taking the calculated geometry and dimensions of the annular ring, anterior leaflet, posterior leaflet, and nerves for a particular patient into engineering drawing software or drawing tools. Includes actions provided as inputs to the tool.

According to some embodiments, the engineering drawing software or drawing tool outputs a template for manually cutting the leaflets of the valve prosthesis.

According to some embodiments, the engineering drawing software or drawing tool outputs a template for machine cut leaflets.

According to some embodiments, the method further includes packing, labeling, and sterilizing the personalized mitral valve prosthesis prior to release for use.

According to some embodiments, the method further includes assembling the personalized mitral valve prosthesis to a valve holder prior to packaging.

According to some embodiments, the method further includes implanting the personalized mitral valve prosthesis into the particular patient.

1A and 1B are schematic diagrams of embodiments of the present invention. 1A shows an artificial mitral valve in an open position and shows the notochord prior to being attached to the leaflets, in accordance with some embodiments of the present disclosure. 1B shows an artificial mitral valve in a closed position and shows the notochord after being attached to leaflets, according to some embodiments of the present disclosure.
2 is a schematic diagram of an embodiment of the present invention implanted in a heart, according to some embodiments of the present disclosure.
3 is an image of a 3D reconstruction of a mitral valve region in 3D CT image analysis software, in accordance with some embodiments of the present disclosure.
4 is a photograph of a 3D printed valve mold and porcine pericardial mitral valve leaflets, in accordance with some embodiments of the present disclosure.
5 is a photograph of a prosthetic valve under ex vivo testing, in accordance with some embodiments of the present disclosure.
6A-6B are schematic diagrams of side views of the anterior and posterior leaflets of an artificial mitral valve and a top view of the leaflets when bonded together, according to some embodiments of the present disclosure.
6C is a schematic diagram of a top view of a mitral valve prosthesis looking downward from the left atrium to the left ventricle (during diastole, when the valve opens to allow blood into the left ventricle), in accordance with some embodiments of the present disclosure.
6D is a schematic diagram of a single piece of material comprising an anterior leaflet and a posterior leaflet, in accordance with embodiments of the present disclosure.
7A-7B are schematic diagrams of a mitral valve prosthesis having a cap for connecting nerves to the papillary muscles of the heart, and two caps attached to the nerves according to embodiments of the present disclosure.
8A-8B are respective schematic views of cross-sections of nerves and possible locations of nerves relative to the leaflet when attached to the leaflet, according to some embodiments of the present disclosure.
9A-9B are schematic diagrams of a prosthetic mitral valve with two leaflets attached in an alternative design each featuring a curved (ellipsoid/droplet) configuration to enlarge the abutment surface and a possible abutment surface configuration.
10 is a schematic diagram of a measured copy of a patient's mitral valve, derived from a 2D or 3D echocardiographic image, in accordance with some embodiments of the present disclosure.
11 is a schematic diagram of formation of a two leaflet prosthesis, in accordance with some embodiments of the present disclosure.
12 is a schematic diagram of an opening formed along a leaflet section according to some embodiments of the present disclosure.
13 is a schematic diagram of an echocardiogram or MRI scan of a left ventricle or ventricles of a patient, in accordance with some embodiments of the present disclosure.
14A-14B are schematic diagrams of a patient's left ventricle during diastole and systole, respectively, according to some embodiments of the present disclosure.
15A-15B are schematic views of extensions attached to each of the anterior and posterior leaflets in accordance with some embodiments of the present disclosure.
16A-16B are schematic diagrams of side views of a mitral valve prosthesis having extensions and attached nerves during diastole and systole, respectively, according to some embodiments of the present disclosure.
17 is a schematic diagram of attachment of an asymmetric flexible ring on the perimeter of a valve prosthesis to mimic the inherent annular shape, in accordance with some embodiments of the present disclosure.
18A-18B are schematic diagrams of an elastic material to be inserted into a rolled valve ring before and after the ring is rolled, respectively, according to some embodiments of the present disclosure.
19 is a schematic flow diagram illustrating a method for fabricating a mitral valve prosthesis according to some embodiments of the present disclosure.
20A is a schematic diagram illustrating a method for fabricating a personalized mitral valve prosthesis in accordance with some embodiments of the present disclosure.
20B is a schematic flow diagram illustrating a method for fabricating a personalized mitral valve prosthesis according to some embodiments of the present disclosure.
21A is a schematic diagram of a ring shaped valve edge preserved upon removal of an inherent mitral valve in clinical practice, in accordance with some embodiments of the present disclosure.
21B is a diagram with the AL-PM diameter as the major axis and the AP diameter as the minor axis used to calculate the annular ring circumference (AC) of a valve prosthesis according to some embodiments of the present disclosure. It is a schematic diagram of an elliptical annular model.
22A-22C are schematic diagrams of an exemplary design of an anterior leaflet, an exemplary design of a posterior leaflet, and an exemplary design of a mitral valve prosthesis assembly, respectively, in accordance with some embodiments of the present disclosure.
22D is a schematic diagram of an annular model indicating two papillary muscles, in accordance with some embodiments of the present disclosure.
22E-22F are schematic diagrams of customized pre-leaflet and posterior leaflet models according to some embodiments of the present disclosure.
23A-23B are schematic diagrams of two examples of anterior or posterior leaflets, illustrating the theoretical length of a leaflet's free edge, according to some embodiments of the present disclosure.
23C is a schematic diagram of the relationship of multiple parameters that affect each other when leaflets of a prosthesis are bonded, according to some embodiments of the present disclosure.
23D is a schematic flow diagram illustrating a method for designing a customized mitral valve using FEM, according to some embodiments of the present disclosure.
24A-24B are schematic diagrams of side and perspective views of bonding of mitral valve leaflets according to some embodiments of the present disclosure.
FIG. 25 is an echocardiogram of an ovine heart implanted with a naturally designed personalized mitral valve prosthesis fabricated according to the method of the present disclosure.
26A-26B are schematic diagrams of posterior leaflets and preleaflets, respectively, according to some embodiments of the present disclosure.
27 is a schematic diagram of a final customized 3D model of an artificial mitral valve in accordance with some embodiments of the present disclosure.
28 is a schematic diagram of FEM simulation optimization results of a customized artificial mitral valve model according to some embodiments of the present disclosure.
29A-29B are schematic views of a prosthetic mitral valve inside a hydrodynamic test chamber in open and closed configurations according to some embodiments of the present disclosure.
30 is an echocardiogram of a customized prosthetic mitral valve during closed configuration after implantation into a porcine heart.
31 is a blood pressure gradient of a porcine heart after implantation of a customized prosthetic mitral valve.
The foregoing will be apparent from the following more specific description of exemplary embodiments of the present invention as illustrated in the accompanying drawings in which like reference signs designate like parts throughout different fields of view. The drawings are not necessarily to scale; Emphasis is instead placed on illustrating embodiments of the present invention.

The mitral valve prosthesis of the present invention is illustrated in FIGS. 1A and 1B. The mitral valve prosthesis 100 has a physiological shape similar to that of a natural human mitral valve. The mitral valve prosthesis includes a flexible asymmetric ring (1) and two flexible membrane-like leaflets (2) suspended from the asymmetric ring (1). The mitral valve prosthesis also contains two sets of nerves 3 that mimic the tendons of the heart. Each set of nerves 3 is attached at one end to the margins and/or bodies of leaflets 2 and converges into a fixation cap 8 at the other end. It consists of The fixing cap 8 is configured to be sutured to the papillary muscles of the left ventricle.

Mitral valve 100 is shown with nerves 3 unattached to leaflets 2 in FIG. 1A and attached in FIG. 1B. Nerves 3 may be attached to leaflets 2 prior to surgery or may be attached during surgery. For example, attachments 9 between nerves 3 and leaflets 2 may be sutures or may be en-block engineered. The mitral valve 100 is shown open in FIG. 1A and closed in FIG. 1B. In the closed state the leaflets 2 are shown abutting.

2 shows the mitral valve 100 implanted in the heart. The mitral valve 100 is shown implanted in the position of the intrinsic mitral annulus 12, on one side adjacent to the aortic valve 6, where the root of the aorta 7 is It is connected to the left ventricle and the other side is connected to the opposing ventricular wall (5). Nerves 3 are shown attached to papillary muscles 4 .

The flexible ring 1 may be custom-made after echocardiography of the patient. In particular, a three-dimensional echocardiography study is performed to obtain detailed anatomical measurements and/or render a three-dimensional model of the patient's heart that can produce a customized or personalized mitral valve. It can be. Leaflets 2 and nerves 3 may also be customized based on ultrasound imaging of the subject's unique mitral valve and surrounding anatomy. Customized/personalized mitral valves can also be produced from data obtained by other imaging modalities that provide three-dimensional information, including cardiac CT and cardiac MRI. As such, mitral valve prostheses of the present invention may be selected or designed to match a patient's particular anatomy.

The flexible ring 1 can be formed, for example, from an elastic annuloplasty ring. The leaflets 2 may be formed of a natural material or a biocompatible composite material capable of resisting clotting and functioning similarly to the patient's own anterior and posterior leaflets. there is. At least two sets of nerves are provided that are attached to one of the two leaflets at a first end and to the papillary muscles at a second end to function similarly to the patient's own tendons. The nerves 3 that bind the leaflets 2 to the patient's papillary muscles support the left ventricle wall throughout the cardiac cycle and prevent the leaflets from opening into the atrium cavity.

Mitral valve comprising flexible ring (1), leaflets (2) and nerves (3)

The prosthesis 100 appears and behaves similar to a healthy native mitral valve. In addition, the mitral valve prostheses of the present invention can be produced from natural materials, and the incorporation of foreign substances such as plagits can be prevented. Flexible rings, leaflets, nerves and caps may be fabricated using composite materials and/or allograft materials including various combinations of homograft, xenograft and/or autograft materials. can Materials forming the valve rings and leaflets include human, bovine or porcine pericardium, decellularized bioprosthetic material, woven biodegradable polymers integrated with cells, and extracellular materials ( extracellular materials), but is not limited thereto. Biodegradable natural polymers may include, but are not limited to, tofibrin, collagen, chitosan, gelatin, hyaluronan, and similar materials thereof. A biodegradable synthetic polymer scaffold that can infiltrate into cells and extracellular matrix material is poly(L-lactide), polyglycolide, poly(lactic-co-glycolic acid), poly(caprolactone), polyorthoesters, poly(dioxanone) ), poly(anhydrides), poly(trimethylene carbonate), polyphosphazenes and similar materials thereof. Flexible rings may be further customized to provide individualized flexibility or rigidity to the patient. Additionally, some components of the mitral valve prosthesis, including the nerves 3, may be formed intraoperatively by the patient's own pericardium.

For example, a mitral valve prosthesis can be fabricated from a patient's own pericardium. Alternatively, the mitral valve prosthesis can be fabricated from xenogeneic materials (eg, animal tissues like conventional valves) to which a layer of the patient's own cultured cells is applied via tissue engineering. .

Artificial valves are immobilized with glutaraldehyde, a commonly known toxin that promotes regeneration. Mitral valve prostheses of the present invention can be fixed by non-glutaraldehyde-based methods such as dye-mediated photofixation. The mitral valves of the present invention also contain epoxy compounds, carbodiimide, diglycidyl, reuterin, genipin, diphenylphosphorylazide, Fixation using alternative cross-linking agents such as acyl azides and cyanamide or by physical methods such as ultraviolet light and dehydration It can be.

Mitral valve prostheses or some components of prostheses can be produced directly with biological three-dimensional (3D) printing using biological materials. Alternatively, mitral valve prostheses or some components of prostheses may be produced using a template or mold constructed from 3D printing based on detailed dimensions obtained from 3D imaging performed prior to surgery.

A method of implanting a mitral valve prosthesis is also provided. An echocardiogram (or other imaging test) of the patient is obtained prior to implantation. In an imaging study, atrial dimensions and movements are measured. Detailed dimensions of the patient's mitral annulus, leaflets and nerves are also measured in the acquired images. A three-dimensional depiction of the valve to be replaced may also be rendered. Through measurements and three-dimensional modeling of the patient's unique valve, a mitral valve prosthesis can be produced that closely matches the patient's unique mitral valve corrected for the existing pathology.

Three-dimensional echocardiography can be performed using, for example, a transesophageal echocardiography (TEE) probe or a transthoracic echocardiography (TTE) probe. Segments of the mitral valve can be modeled and measured in three and four dimensions using software such as eSieValves.TM (Siemens Medical Solutions USA, Inc., Malvern, PA). Relevant measurements may include annular outer and inner diameters, annular areas, intertrigonal and intercomm distances, lengths along various axes of anterior and posterior leaflets.

Additionally or alternatively, three-dimensional examination of the mitral valve may be performed with computed tomography (CT) or magnetic resonance imaging (MRI). For example, as shown in Figure 3, a 3D reconstruction of a porcine heart was obtained using CT imaging (SOMATOM.RTM. Definition Flash, Siemens Healthcare, Erlangen, Germany), and the mitral valve region of the heart is shown on the right side of the image. do. Segmentation of the mitral valve region can be performed using image analysis software and relevant measurements obtained.

The mitral valve prosthesis can be fully customized for a patient, with each component (eg, ring, leaflets, nerves, caps) fabricated to have dimensions that match the patient's unique valve. For example, as shown in FIG. 4 , a 3D printed mold of a mitral valve was created based on a 3D reconstruction of an imaged valve. The 3D printed valve shown in Figure 4 was modeled during the diastolic or open phase of the cardiac cycle. A prosthetic valve based on a 3D mold is also shown in FIG. 4 . This mold can lead to cutting of the porcine pericardium to leaflets and notochordal attachment sites. Alternatively, a prefabricated (or prefabricated) mitral valve or a prefabricated (or prefabricated) component of a mitral valve is closest in shape and size to the patient's native valve or native valve components. may be selected for transplantation.

5 shows an image of a prosthetic valve prototype sealed in an in vitro test system. The valve prototype is shown sutured to an explanted whole heart. Saline boluses are injected into the left ventricle of the heart through a tube with the aorta fixed to contain saline and create pressure in the left ventricle. The injection pressure can be monitored, for example, on a pressure gauge connected to the injection line. The competency of the valve prototype (eg, absence of regurgitation and valve leaflet prolapse) under physiological pressure can then be monitored. The function of the valve can be measured or monitored during contraction of the left ventricle and at the systolic pressure at which the proper valve closes.

6A-6B are schematic views of the anterior and posterior mitral leaflets of an artificial mitral valve, and schematic views of the leaflets when bonded together, in accordance with some embodiments of the present disclosure. According to FIGS. 6A and 6B , the artificial mitral valve may be an artificial mitral valve 600 . According to some embodiments, valve 600 may include two leaflets, for example an anterior mitral leaflet 602A and a posterior mitral leaflet 602P. Each of the mitral posterior and anterior leaflets 602P and 602A can be designed and created as a monocoque (single piece), respectively, to fit the specific physiology and anatomy of the patient based on cross-sectional images of the patient's heart. Measurements taken from the patient's own heart can be used to determine, for example, the length, width, and height of each leaflet 602A, 602P so that each leaflet is substantially identical to the patient's native leaflets. Each leaflet may contain additional material to form nerves (eg, nerves 604, 606, 608, 610) and a ring portion (eg, anterior ring portion 601A and posterior ring portion 601P). It can be formed to include. The length of the notochord may be determined by the surgeon to suit the patient, as further described below. The leaflets may be cut from a single piece of material using a knife or scissors and sutured by a surgeon during mitral valve replacement surgery to form a mitral valve similar to the patient's natural mitral valve.

For example, the preleaflet (AL) height can be about 30 mm, the AL length can be about 45mm, the posterior leaflet (PL) height can be about 15mm, and the posterior leaflet length can be about 60mm. As shown in FIG. 6A, the medical community refers to 630A as the height of the anterior leaflet 602A and 630P as the height of the posterior leaflet 602P, while the length of each leaflet is referred to as the leaflet circumference, for example, 632A refers to the length of the anterior leaflet 602A, and 632P refers to the length of the posterior leaflet 602P.

According to some embodiments, individually cutting each of the ring portions 601A and 601P as well as individually cutting each of the leaflets 602A and 602P from the same or different pieces of material can be used for implantation. It may be convenient for the person preparing the prosthetic mitral valve, for example a surgeon. Cutting the leaflets into two separate parts, cutting the ring parts into two separate parts, and attaching the leaflets to the ring and attaching more nerves to each tip, is to make the leaflets and nerves into one piece from a single piece of material. Reduces the preparation time required to perform the surgical procedure of prosthetic valve implantation compared to cutting into units. Severing the leaflets and nerves as a single unit and implanting a single-piece prosthesis is the method disclosed herein because of the high accuracy required to sever the nerves of each of the leaflets while keeping the connection between the leaflet portion and the nerve portion intact. more complex and time consuming.

In some embodiments, each ring portion 601A and 601P is such that each leaflet posterior side is folded toward the outside of the valve, or folded or rolled on itself (e.g., rolled anterior section 605A). and a rolled posterior section 605P) created through rolling of each leaflet posterior side. According to this embodiment, the size of the posterior end of each leaflet can be increased by 5-10 mm of additional material, which is the ring portion (ring portion 601A of the anterior mitral leaflet and ring portion of the posterior mitral leaflet ( 601P)) can be used when rolling the trailing edge of a leaflet over it. Rolling or folding the ring (or each ring portion 601A and 601P) on its own toward the outside of the valve 600 can help prevent clot formation on the inside of the valve 600, if it does. Appears on the outside of the valve 600 in the region of the fold or roll of the ring or ring portion, which is less likely to impair the efficient operation of the valve 600. According to some further embodiments, the ring (or each ring portion 601A and 601P) is formed by the addition of suitable biomedical fibers or strips (not shown) of material such as polymers. can be further strengthened. Such strips may be made from pieces of material from which valve 600 is made and sized to fit within each ring portion 601A, 601P.) Preferably such strips are 1-3 mm wide and 10-3 mm wide. It has a length of 20 mm. Strips of this material may be added to the valve 600 as each ring portion 601A, 601P is rolled, and the strips are disposed within each ring portion 601A, 601P. These strips of material may be elastic and may be made of various compositions such as biocompatible rubbers, recoiling metal wires or synthetic materials.

According to FIG. 6B, leaflet 602A may have a half ellipsoid or plano-convex shape, while leaflet 602P may have a plano-concave shape. there is. In some embodiments, valve 600 may include at least two sets of nerves. In some embodiments, each of the two sets of nerves is attached to the middle section of each leaflet to mimic a unique mitral valve. For example, in some embodiments, leaflet 602A may be connected to a middle section of leaflet 602A at one end of leaflet 602A opposite the end at which ring portion 601A is connected to leaflet 602A. at least one set of nerves 603A that can be In some embodiments, at least one set of nerves 603A includes at least two sub-sets of nerves, such as a sub-set of nerves 604 and a sub-set of nerves 606 . can include According to some embodiments, these sub-sets of nerves 604 and 606 are spaced such that a gap of about 3-5 millimeters is maintained between the two sub-sets of nerves to allow more efficient bonding. The gap between the sub-sets of nerves 604 and 606 also serves to create a more homogenous distribution of tension across the leaflets and potentially reduce wear and tear. do. These sub-sets of nerves 604 and 606 may be connected to different, separate caps to connect the sub-set of nerves to the papillary muscles of the heart, as described in detail with respect to FIGS. 7A-7B .

In some embodiments, leaflet 602P has a nerve that can connect to a middle section of leaflet 602P at one end of leaflet 602P opposite the end where ring portion 601P connects to leaflet 602P. may include at least one set of s 603P.

In some embodiments, at least one set of nerves 603P includes at least two sub-sets of nerves, such as a sub-set of nerves 608 and a sub-set of nerves 610 . can include These sub-sets of nerves 608, 610 are spaced such that a gap of about 5-8 millimeters is maintained between the two sub-sets of nerves to allow more efficient junctions. These sub-sets of nerves 608, 610 may be connected to different separate caps for connecting the sub-set of nerves to the papillary muscles of the heart, as will be described in detail with respect to FIGS. 7A-7B. .

In some embodiments, the width of nerves 603A and/or nerves 603P may be between 1 mm and 2 mm, although other widths may be implemented. In some embodiments, posterior mitral leaflet 602P may be connected on one side to ring portion 601P of the asymmetric ring. If ring portion 601A is attached to ring portion 601P via, for example, sutures, fasteners, or the like, a fully asymmetric and flexible ring may be formed.

According to some embodiments, the interchodal distance at anterior mitral leaflet 634A may be between 8-10 mm. In some embodiments, the intervertebral distance of posterior mitral leaflet 634A may be between 10 mm and 15 mm. In some embodiments, the intervertebral distance between the anterior and posterior leaflets in the commissure area indicated by distances 636 and/or 638 may be 5-7 mm.

According to some embodiments, and as shown in FIG. 6B , the anterior leaflet 602A can be connected to the posterior leaflet 602P to construct the artificial mitral valve 600, and the ring portion 601A is a ring portion ( 601P) can be connected. When leaflet 602A is connected to leaflet 602P, an orifice 620 created between leaflet 602A and leaflet 602P may allow blood to flow in one direction, from the left atrium to the left ventricle. Thus, orifice 620 created between leaflet 602A and leaflet 602P may be configured to prevent backflow, ie, backflow from the left ventricle to the left atrium. Leaflets 602A, leaflets 602P and the manner in which they are connected to each other with specific joints, as well as ring portion 601A and ring portion 601P may be configured to mimic the shape, size, and function of a natural human mitral valve. there is. Specifically, ring portion 601A may be configured to mimic the anterior annular shape, while annular portion 601P may be configured to mimic the posterior annular shape of a natural mitral valve. In some embodiments, each leaflet extends approximately 1 to 5 mm located between the ring portion and the nerve to allow for better adhesion between the two leaflets and better nerve attachment to each leaflet. form may be included.

In some embodiments, preleaflet 602A may include at least two sub-sets of nerves, e.g., a sub-set of nerves 604, that may be connected to leaflet 602A at different ends of leaflet 602A. set and sub-set of neurons 606 . In some embodiments, posterior leaflet 602P may include at least two sub-sets of nerves, such as a sub-set of nerves 608 and a sub-set of nerves 610; It may be connected to different ends of leaflet 602P. As in the natural mitral valve, the nerves must connect to the papillary muscles of the heart. More specifically, each sub-set of nerves in the native human mitral valve attaches to a different region of the papillary muscles. Thus, the prosthetic valve 600 may include at least two sub-sets of nerves per each leaflet, whereby each sub-set of nerves is directed to a different papillary muscle region to closely mimic the construction and operation of a natural mitral valve. should be attached As described with respect to FIGS. 6C and 7A-7B , each sub-set of nerves may be connected to the papillary muscles via caps ensuring an easy, sufficiently stable and durable attachment between the sub-set of nerves and the papillary muscles. The number of nerves in each sub-set of nerves (eg, such as 604, 606, 608 and 610) may be different or the same. In some embodiments, each sub-set of nerves may include at least two nerves.

6C is a schematic diagram of a top view of a mitral valve prosthesis looking downward from the left atrium towards the left ventricle, in accordance with embodiments of the present disclosure. According to FIG. 6C , posterior leaflet 602P may be attached to anterior leaflet 602A via attachment lines, eg, suture lines 609 . In some embodiments, ring portion 601A may be attached to ring portion 601P, for example along lines 609 and may roll itself toward the outside of valve 600 . In some embodiments, preleaflet 602A may include two sub-sets of nerves, for example, sub-sets 604 and 606, whereby each of these sub-sets of nerves is a separate cap. It can be connected to other papillary muscles 720 through a cap element 700 . Thus, posterior leaflet 602P may include two sub-sets of nerves 608, 610, whereby each sub-set of nerves connects papillary muscles 720 via a different cap element 700. can be attached to For example, anterior nerves 604 can connect to a first papillary muscle 720 through a first cap 700, while posterior nerves 608 can connect to the same first papillary muscle through the same first cap 700. It can be connected to the papillary muscles. Similarly, the anterior nerves 606 can connect to the second papillary muscle 720 through a second cap 700, while the posterior nerves 610 can connect to the same second papillary muscle through the same second cap 700. can be connected to

According to FIG. 6D , in some embodiments leaflets 602P and 602A may be cut from a single monocoque and a joint, eg, a suture to form a complete valve, may be performed along suture lines 609. . According to some embodiments, the nerves may be adjusted according to the transplant recipient/patient's individual optimal nerve length based on the patient's pre-surgery scans.

7A-7B are schematic diagrams of a mitral valve prosthesis having a cap for connecting nerves to the papillary muscles of the heart and two caps each attached to the nerves according to embodiments of the present disclosure. In some embodiments, the shape of the cap 700 when in the layout configuration may be an arc shape. In some embodiments, the shape of the cap 700 in a closed configuration can resemble that of a tapered cone with a small opening 730 at the top 702 and a wider opening at the bottom 704. and thus the ends of the arcs may be sutured to each other or one on top of the other using surgical suture 706 to create a closed configuration. Sutures 706 may be performed prior to placing cap 700 on top of papillary muscles 720 . In some embodiments, cap 700 can measure anywhere from 5 mm to 10 mm in diameter and 5 mm to 10 mm in height. According to some embodiments, cap 700 can be made from a single piece of material in the form of a cap, while according to other embodiments, cap 700 can be sewn together and in one go with the same parts that can be sewn to the papillary muscles. It can be made of either a piece of material or two open leaflets. For example, a suture may be started on one side of the two pieces of material of the cap 700 until the two parts of the cap 700 are fully connected to each other and connected to the papillary muscles of the heart, then attach the cap 700 to the papillary muscles of the heart. It can come out through a part of the cap 700 like attaching.

According to some embodiments, cap 700 of prosthetic valve 600 may be formed by rolling a pericardium (eg, from a human source, bovine or porcine) into a closed configuration. In some other configurations the cap may be formed by a biomedical polymer. The size of the cap 700 may be 5 mm to 5 mm in some embodiments. In some embodiments, the notochord of the prosthetic mitral valve may be made of the same material as the leaflet and/or cap. In some embodiments, the chordate may be chordate from the same source where cap 700, anterior leaflet 602A, and posterior leaflet 602P are taken, for example, from the same animal, e.g., the same cow; This is to add the advantage of having the same cellular structure and origin as the cap 700, the anterior leaflets 602A and the posterior leaflets 602P.

Once cap 700 is placed on papillary muscle 720, nerves such as sub-set nerves 604 and 608 are connected using sutures 710 that can connect cap 700 and papillary muscle 720 together. It may be connected to the cap 700. According to some embodiments, cap opening 730 achieves a good fit between cap 700 and papillary muscle 720 because cap opening 730 can adjust the shape of the cap to the shape of papillary muscle 720. can make it possible In some embodiments, cap 700 may be attached to sub-set nerves 604, 608 of one of its ends, for example via sutures 710, whereas cap 700 may be eg It can be attached to the papillary muscles of the heart from the opposite end of the cap 700 very close to the bottom end 704 via sutures 706, for example. While cap 700 may be connected to papillary muscle 720 through the entire circumference of lower end 704 of cap 700, in some embodiments cap 700 may extend around the circumference of lower end 704 of cap 700. Accordingly, it may be connected to the papillary muscles 720 through specific parts.

According to some embodiments, nerves may be connected to each other to form a bundle of nerves. Nerves can be bundled at the ends of the nerves that will connect to cap 700 (eg, the ends of sub-set nerves 604 and 608 connected to leaflet 602). According to some embodiments, connecting nerves, e.g., sub-set nerves 604, 608 to papillary muscles 720 through cap 700, directly connects nerves to papillary muscles 720. It is easier than doing it, as it requires a more extensive attachment procedure. For example, if the attachment method is suturing, suturing the nerves to the papillary muscles 720 is suturing the nerves to the layout cap 700, and suturing the suture cap 700, which is one large piece, to the papillary muscles 720. ) is more complicated and time-consuming than suturing. Since patients receiving the prosthesis of the present invention are generally connected to cardiopulmonary bypass, also known as a heart-lung machine, it is desirable to perform mitral valve replacement quickly.

Although FIG. 7A shows only two sub-set nerves 604 and two sub-set nerves 608 attached to cap 700, it should be understood that additional nerves may be connected to cap 700. Sub-sets of nerves 604 and 608 may include more than one nerve. In some embodiments, as shown in FIG. 6C , four nerves 604 from the right scallop of the anterior mitral leaflet 602A and the cap 700 from the left scallop of the mitral leaflet 602P Connected.

In some embodiments each of a sub-set of nerves 604 , 606 , 608 and 610 may connect to cap 700 along an external side of cap 700 . In another embodiment, the nerves of the prosthetic valve or at least some of the nerves may be attached to the cap 700 through an opening 730 that may be located in the center of the cap 700 . That is, the nerves may pass through the opening 730 and be attached to the inside of the cap 700 .

In some embodiments each sub-set of nerves 604 , 606 , 608 , 610 may first be connected together to form a bundle and then connected to cap 700 .

As shown in FIG. 7B , artificial mitral valve 600 may include a flexible asymmetric ring 601 attached to two leaflets (eg, leaflets 602A and 602P). In some embodiments, each of the two leaflets may attach a set of nerves, for example sub-sets of nerves 604 (not shown), 606 (not shown) 608 and 610. In some embodiments, each set of nerves to each of the two leaflets may be attached to a single cap 700, whereas each cap 700 may have a set of nerves 610 to each cap 700. Each sub-set of connections may connect the mitral valve prosthesis 600 to the papillary muscles 720 of the heart.

As noted above, according to some embodiments, each sub-set of nerves 604 (not shown), 606 (not shown), 608, 610 are identical to the material that makes up the anterior and posterior leaflets. It can be made up of pieces of matter. These nerves, each of which may be considered an extension of leaflets 602A and 602P, may be referred to as primary cords. According to some embodiments, additional nerves may be attached to both the anterior leaflet 602A and the posterior leaflet 602P. Each of these secondary nerves may be made from a separate piece of material different from that used to construct the leaflets and primary nerves. Secondary nerves may be configured to connect the bottom side of each leaflet 602A, 602P to a point along the primary nerves. The junction of the secondary nerve along the primary nerve may be midway along the primary nerve, but other locations along the primary nerve may be implemented as junction points to achieve better splicing of the leaflets. The secondary nerve may typically be sutured at one of its ends to either the anterior leaflet 602A or the posterior leaflet 602P, and at the other end the secondary nerve may be sutured to the primary nerve. When attaching the secondary nerve to the anterior leaflet 602A or the posterior leaflet 602A or 602P, respectively, via, for example, sutures, to prevent coagulation along the line of attachment, for example, the suture line, to the outside of the anterior leaflet 602A. Injury to the surface or outer surface of posterior leaflet 602P should be avoided. For example, there is less chance of damaging the leaflets 602A and 602P when using microscopic sutures. The purpose of the secondary nerves is to further support the prosthetic valve against the pressure exerted on the ventricular side of the prosthetic valve during the systolic phase.

8A-8B are respective schematic diagrams of possible locations of secondary nerves relative to the posterior leaflet, and cross-sections of the primary and secondary nerves, when attached to the posterior leaflet, according to some embodiments of the present disclosure. As shown in FIG. 8A , posterior leaflet 602P may be rolled at its posterior end to form ring 601 . In some embodiments, posterior mitral leaflet 602P may be divided into several regions. Areas 812 and 814 may be areas to which secondary nerves, for example nerves 603, may connect. However, there may be a region 816 along posterior leaflet 602P that should be free of nerves, ie, no secondary nerves should be connected to region 816. This is due to the fact that region 816 is the region to which high pressure is applied once posterior leaflet 602P is connected to the heart as part of a prosthetic valve during ventricular systole. In some embodiments, region 816 extends approximately 2-5 mm to the right of midline 810 of posterior leaflet 602P and approximately 2-5 mm to the left of midline 810 of posterior leaflet 602P. can include In some embodiments, region 816 may be 3 mm to the right and 3 mm to the left of midline 810 of posterior leaflet 602P. The secondary nerves may be designed to help provide additional support to the posterior leaflet 602P as the pressure gradient increases during ventricular systole.

In some embodiments, secondary nerves 603 should not reach the ends of regions 812, 814 of posterior leaflet 602P when in the deployed configuration. In some embodiments, nerves should not be connected to the ends of regions 812 and 814 in close proximity to ring 601 . For example, nerves may be located along one of regions 812 and 814 along approximately 20 to 70 degrees of the entire posterior leaflet 602P layout relative to the midline 810 of the posterior leaflet 602P. . Otherwise, regions of posterior leaflet 602P located between midline 810 and about 15-20 degrees from either side of midline 810 may remain free of secondary nerves.

8B schematically depicts a cross section of the posterior mitral valve showing the primary and secondary nerves when attached to the posterior leaflet 602P. 8B shows primary nerves 608 made from a piece of the same material as the leaflets. Primary nerves 608 extending from posterior leaflet 602P at one of its ends are attached to cap 700 at the other end. In some embodiments the primary nerves 608 can be connected together to form a bundle (not shown) and then connected to the outside of the cap 700 . Cap 700 may be coupled to papillary muscles 720 .

According to some embodiments, primary nerves 608 can connect to secondary nerves 603 whereby secondary nerves 603 are posterior at one end, for example, end 823. It may be connected to leaflet 602P and to a point of contact along the primary nerve at the opposite end of each of the secondary nerves 603, eg, end 825. According to some embodiments, secondary nerves 603 should be about 30-40% thicker and wider than primary nerves 608 . Depending on the prosthesis desired, one to four secondary nerves may be used for each leaflet scallop of the posterior mitral leaflet 602P.

9A-9B are schematic diagrams of a prosthetic mitral valve with two leaflets attached in an alternative design each featuring a curved (ellipsoid/droplet) configuration to enlarge the abutment surface and a possible abutment surface configuration. According to FIG. 9A , artificial mitral valve 1100 may include two leaflets, for example an anterior leaflet 1602A and a posterior leaflet 1602P, whereby each leaflet 1602A and 1602P has a semicircular shape. (semi-circular shape) and these two leaflets together can create a 'yin and yang' shape. In some embodiments, the leaflet shape can be designed in a semicircular fashion along half the length of each leaflet to create an 'S' shaped seal when the two leaflets are joined.

This unique shape may enable sufficient bonding between the anterior leaflet 1602A and the posterior leaflet 1602P, particularly in region 1120 . In some embodiments, there may be a junction or overlap between the anterior leaflet 1602A and the posterior leaflet 1602P along region 1120 . Symmetrically, there may be a similar region of junction or overlap between posterior leaflet 1602P and anterior leaflet 1602A (not shown). Similarly, for valve 600 detailed above, each leaflet may be formed by rolling itself an end of the material that makes up each leaflet, such as ring 601A and ring 601P. ) may be included.

According to FIG. 9B , there may be two configurations of bonding between the anterior leaflet 1602A and the posterior leaflet 1602P in close proximity to the bonding area. In some embodiments, with respect to prosthetic valve 600, prosthetic valve 1100 may include two types of nerves; primary nerves and secondary nerves. According to some embodiments, the primary nerve may be configured as an extension to the anterior or posterior leaflets 1602A and 1602P, respectively. That is, the primary nerves, eg, primary nerves 1102A and 1102P, may be constructed from the same piece of material as each leaflet, anterior leaflet 1602A, and posterior leaflet 1602P. Primary nerves 1102A and/or 1102P may extend at one end in the mid-section of each leaflet and connect to the cap at the other end. According to some embodiments, secondary nerves, eg nerves 1104P, may attach only to posterior leaflet 1602P. Secondary nerves, such as nerve 1104P, may connect at one end to the mid-section of posterior leaflet 1602P and at the other end to the mid-section of primary nerve 1102P. According to some embodiments, secondary nerves 1104P may be added to better mimic the native mitral valve, including additional short nerves connecting between the posterior leaflet and the posterior primary nerves. The addition of secondary nerves can allow the posterior leaflets to withstand the pressure exerted on the posterior leaflets during the systolic phase, create proper splicing (or closure) of the leaflets during the systolic phase of the cardiac cycle, and further allow the anterior leaflets to open during the diastolic phase.

For example, posterior leaflet 1602P may attach secondary nerve 1104P to the posterior edge of leaflet 1602P. Secondary nerve 1104P may further connect to the mid-section of primary nerve 1102P.

In some embodiments, a bundle of nerves and/or each nerve may be attached to a cap, such as cap 700, that may connect the nerves to the papillary muscles of the heart.

10 is a schematic diagram of a measured copy of a patient's mitral valve, in accordance with some embodiments of the present disclosure. In some embodiments, measurements of the length, width and height of the leaflet section may be obtained via echocardiography, although other imaging methods may be used, such as cardiac CT or cardiac MRI. Accordingly, the dimensions and shape of artificial mitral valve 1200 may be a substantially exact copy of the patient's natural or native mitral valve.

11 schematically illustrates the formation of a two leaflet prosthesis, in accordance with some embodiments of the present disclosure. In some embodiments, the valve's basis, or leaflet section, can be cut from a single piece of material 1210 based on a cross-sectional image of the intended transplant recipient's heart, as illustrated in FIG. 12 . In order to provide an opening 1230 and definition of two leaflets, e.g., an anterior leaflet 1202A and a posterior leaflet 1202P as shown in FIG. The size of the leaflet section may be cut in such a way as to replicate the prosthesis image at a 1:1 scale.

12 schematically illustrates an opening formed along a leaflet section according to some embodiments of the present disclosure. In some embodiments, opening or orifice 1230 can be formed (eg, cut) from a single piece of material 1210, with two leaflets 1202A and 1202P on opposite sides of opening 1230. can be formed When orifice 1230 is present by cutting a single piece of material 1210, two leaflets, e.g., anterior leaflet 1202A and posterior leaflet 1202P, form a flap that collapses into orifice 1230. s, thus further creating unidirectional flow of blood through orifice 1230, ie from the left atrium to the left ventricle of the heart.

13 schematically illustrates an echocardiogram or MRI scan of a patient's left ventricle or ventricles, in accordance with some embodiments of the present disclosure. In some embodiments, the patient's left ventricle 1500 may be imaged or scanned by echocardiography, CT or MRI, or other imaging techniques. This image or scan of the left ventricle 1500 can provide an exact or substantially accurate length of the patient's nerves as needed from the tip of the papillary muscles 1520 to the valve leaflets 1502A and 1502P. Through this, it is possible to manufacture an artificial mitral valve customized according to the patient's anatomical and physiological requirements.

14A-14B are schematic diagrams of a patient's left ventricle during diastole and systole, respectively, according to some embodiments of the present disclosure. In some embodiments, as illustrated in FIG. 14B , the left ventricle, left ventricle 1610 , during the systolic phase is compared to the annulus diameter 1650 of the left ventricle 1612 during the diastolic phase illustrated in FIG. 14A . A smaller annular diameter 1640 may be included. When blood flows into the left ventricle during diastole, the left ventricle 1612 is filled with blood and the annular diameter 1650 increases. After blood flows from the left ventricle to the patient's body blood system to reach the organs, the blood leaves the left ventricle 1610 during the systolic phase. Thus, the volume of the left ventricle 1610 during the systolic phase is smaller compared to the volume of the left ventricle 1612 during diastole, which means that the annular diameter 1640 during the systolic phase is larger than the annular diameter 1650 during diastole. make it smaller

During recurrent phases of cardiac function (i.e., systole and diastole), the annulus and leaflets 1502A and 1502P are required to allow flexibility as they repeatedly change diameter and size, so that the tissue that makes up the natural mitral valve and Similarly, it is desirable to make the annulus and leaflets of an elastic material. Accordingly, a prosthesis without stents, without metal rings, and without hard material is disclosed, which, depending on the materials selected for fabricating the leaflets 1502A, 1502P and the ring, has a certain degree of compliance and elasticity is required.

15A-15B are schematic views of extensions attached to each of the anterior and posterior leaflets in accordance with some embodiments of the present disclosure. In some embodiments, as illustrated in FIG. 15A , preleaflet 1202A may include extensions 1703 that include additional material to extend the size of preleaflet 1202A. Extension 1703 is about 1-5 mm long and is sized to substantially the width of the incision made to form the anterior leaflet (eg, incision 1220 in FIG. 11 ). In some embodiments, extension 1703 is sutured at one end to the edge of anterior leaflet 1202A (see incision 1220 in FIG. 11 ) and at the other end to nerves 604, 606 in FIG. 6A. nerves 1704, which may be similar to

As illustrated in FIG. 15B , posterior leaflet 1202P may include an extension 1709 comprising additional material to extend the size of anterior leaflet 1202P. Extension 1709 is about 1-5 mm long and is sized to substantially the width of the incision made to form the anterior leaflet (eg, incision 1220 in FIG. 11 ). In some embodiments, the extension 1709 is sutured at one end to the edge of the anterior leaflet 1202P (see incision 1220 in FIG. 11 ) and at the other end to the nerves 608, 610 in FIG. 6A. nerves 1708, which may be similar to

As shown in FIG. 15B , posterior leaflet 1202P has extensions 1709 attached to one end (leaflet end) and nerves 1708 attached to the other end. Nerves 1708 are connected to extension 109 at one end and to cap 1870 at the other end, which may be similar to the cap structure described with respect to FIG. 7A. The anterior leaflet 1202A has extensions 1703 attached to one end (leaflet end) and nerves 1704 attached to the other end. Nerves 1704 are connected at one end to extension 1703 and at the other end to cap 1870, which may be similar in structure to the cap described with respect to FIG. 7A.

Each of the nerves 1704, 1708 may include several nerves, also described herein as primary nerves (e.g., four primary nerves), but any number depending on the specific requirements for each patient. Other numbers of nerves may be implemented. In some embodiments, nerves may also include secondary nerves (not shown) as described herein.

16A-16B are schematic diagrams of side views of a mitral valve prosthesis having extensions and attached nerves during diastole and systole, respectively, according to some embodiments of the present disclosure. Referring now to FIG. 16A , a side view of the mitral valve prosthesis showing the profile of the mitral valve prosthesis when the heart is in diastole and referring to FIG. 16B , a side view of the mitral valve prosthesis when the heart is in diastole. The anterior leaflet 1202A and posterior leaflet 1202P are positioned apart from each other so that blood can flow through the orifice between the leaflets 1202A and 1202P into the left ventricle. The extensions 1703 and 1709 allow the valve prosthesis to have an improved bonding profile. Each leaflet 1202A, 1202P has an attached extension providing additional material to the anterior leaflet and posterior leaflet providing necessary bonding during systole to prevent back flow of blood into the atrium and to provide support to the left ventricle during systole. It may have parts 1703 and 1709.

In some embodiments, extension 1703 and extension 1709 are prepared in different sizes (eg, length, width and shape). In some embodiments nerves 1704 and 1708 may be tied together and secured via sutures prior to being attached to cap 1870.

Extensions 1703 and 1709 configured to carry the respective nerves 1704 and 1708 are similar to the nerves of a unique heart valve and are inserted into the heart chamber to stimulate the heart wall muscles. or attached to the papillary muscles. For example, extension 1703 can carry nerves or set of nerves 1704 while extension 1709 can carry nerves or set of nerves 1708 . Each of the at least two nerves may be connected at the other end (opposite the end connected to each of the extensions) to a cap 1870 configured to attach the valve to the papillary muscles.

In some embodiments, during the diastolic phase, leaflets 1202A and 1202P, as well as respective extensions 1703 and 1709, allow blood flow in one direction from the left atrium towards the left ventricle, as illustrated in FIG. 16A. are placed at a distance from each other in order to

In some embodiments, during the systolic phase, as illustrated in FIG. 16B, leaflets 1202A and 1202P, as well as their respective extensions 1703 and 1709, i.e., reflux or leakage of blood from the left ventricle into the left atrium. They are placed very close to each other to prevent leakage of blood. According to some embodiments, the extension, eg, extensions 1703 and 1709, provides the necessary bonding or closure of the valve to prevent leakage of back flow of blood from the left ventricle to the atrium.

According to some embodiments, the extensions can be cut to fit the edges of the leaflets and measure different widths of 5 mm or more to ensure sufficient bonding. The extensions must be attached to the leaflets by being sutured, glued, stapled or otherwise attached to the edges of the leaflets.

According to some embodiments, the nerves, eg, nerves 1704 and 1708, may be individually attached, eg, sutured, to the heart chamber wall or papillary muscle, according to a design that is optimally determined for the particular patient; For example, they may be strung together in pairs, tetrads, etc.

According to some embodiments, the nerves may be asymmetric. That is, the nerves can vary in size because there are two papillary muscles in the left ventricle and the nerves originating at various points of the leaflet extensions can cover a variety of lengths and distances from the top edge of those muscles. Thus, each nerve or nerve bundle may be individualized and of different lengths compared to the others. This ensures perfect closure of the prosthetic valve and sufficient bond length.

In some embodiments, nerves arising from leaflet extensions, e.g., extensions 1703 and 1709, respectively, e.g., nerves 1704 and 1708, allow the valve to function in-vivo. It may be distributed along the edges of the anterior leaflet extension and the posterior leaflet extension to reduce wear of the prosthetic valve by ensuring that tension is evenly distributed along the margins of the leaflets as they move.

17 is a schematic diagram of attachment of an asymmetric flexible ring on the perimeter of a valve prosthesis to mimic the inherent annular shape, in accordance with some embodiments of the present disclosure. According to some embodiments, the flexible ring 1901 rolls an elongated piece of material onto itself and closes it into a ring shape, or rolls a piece of material with a hole in the middle onto itself toward the outside of the material. It can be formed by rolling. In some embodiments, rolled ring 1901 is made of an elastic material to allow for better stiffness of the annulus, for example to allow surgical attachment to suture to a patient's annulus. When in use, it may be attached around the circumference of the mitral valve prosthesis 1200 to provide better elasticity during cardiac cycles that change between systole and diastole. The rolled ring 1901 may initially fit around the perimeter of the cut valve 1200 (FIG. 10).

According to some embodiments, outer ring reinforcement 1901 is made of an elastic material that includes variable elasticity to allow for variable relaxation and contraction of the prosthetic valve during diastolic and systolic cardiac cycles, respectively. It can be. In some embodiments, the elasticity of the ring 1901 may be derived from an ongoing study (or study) of the patient's unique annular motion based on 3D echocardiography.

In some embodiments, the stiffening ring 1901 can be exposed to the blood environment inside the heart or rolled into a sandwich wrapped around an elastic material that can be made of the same material as the leaflets that surround it.

As shown in FIG. 17 , prosthetic valve 1200 includes nerves 1704 and 1706 that can be attached to an anterior leaflet 1202A (with or without extensions) and a posterior leaflet (with or without extensions). nerves 1708 and 1710 that can be attached to 1202P. 16A-16B, the nerves can be attached to at least two caps configured to attach the valve 1200 to the papillary muscles of the heart, thus depending on the particular anatomical and physiological requirements of a particular patient. , the mitral prosthetic valve 1200 can be properly attached to the patient's left ventricle.

18A-18B are schematic diagrams of an elastic material to be inserted into a rolled valve ring before and after the ring is rolled, respectively, according to some embodiments of the present disclosure. According to some embodiments, as shown in FIGS. 18A-18B , valve ring 2201 is such that ring 2201 is rolled over elastic material 2205 and elastic material 2205 is “sandwiched” within ring 2201 . "It may include the addition of an elastic material 2205 that may be inserted into the ring 2201. Adding elastic material 2205 within ring 2201 is to provide additional elasticity to ring 2201, which may help to better mimic the elastic properties of the natural mitral valve. In some embodiments, elastic material 2205 may be rubber or any other biocompatible synthetic material. In some embodiments, the shape of the elastic material 2205 is similar to the shape of the inserted ring 2201 to facilitate insertion of the elastic material 2205 into the ring 2201 .

The ring 2201 (which may be made of the same material as the leaflets or from alternative material extensions attached to the outer rims of the leaflets) is the two leaflets defined by the incision 2220. For example, to provide an opening between the anterior leaflet 2202A and the posterior leaflet 2202P, which may be made along the center of the leaflet section towards the inside of the composite valve, for example in the shape of a crescent or semicircle. It can be rolled over the elastic material 2205 towards the incision 2220 . Incision 2220 is actually an actual mitral valve prosthesis orifice where blood flows from the left atrium to the left ventricle. Thus, the outer margins of the mitral valve prosthesis can include a ring 2201, and then the main surface of the leaflets connected to the ring 2201, for example, leaflets 2201A and 2202P, are the nerves. (e.g. via nerves 2204 and via cap 2270 to the papillary muscles.

19 is a schematic flow diagram illustrating a method for fabricating a mitral valve prosthesis according to some embodiments of the present disclosure. According to some embodiments, method 2000 for fabricating a mitral valve prosthesis that is customized per patient may include operation 2002, which may include measuring the size and shape of a patient's mitral valve via imaging methods. can Imaging methods for measuring the shape and size of the mitral valve of a specific patient include echocardiography, cardiac CT, and cardiac MRI. The method 2000 may further include an operation 2004 of cutting a replica of the patient's mitral valve from a single piece of material on a 1:1 scale. In some embodiments, method 2000 can include operation 2006 of cutting an incision along a single piece of material to create an orifice for blood flow and creating two leaflets, one on each side of the orifice. Method 2000 may include an act 2008 of measuring the length of the required nerves via imaging methods that may be similar to imaging methods for measuring the shape and size of the mitral valve as in act 2002.

In some embodiments, method 2000 may further include act 2010 attaching nerves to one of two caps configured to attach nerves to papillary muscles of the heart.

In some embodiments, method 2000 will include an operation 2012, which can include creating a full mitral valve prosthesis that mimics a mitral valve unique to a particular patient by attaching a flexible ring on the leaflets. can

In some embodiments, method 2000 may further include an optional action that may include attaching extensions to each of the two leaflets to carry nerves as measured in action 2008. . These extensions may help provide proper closure and closure during the systolic phase of the cardiac cycle.

According to one embodiment of the present invention, the motivation for implementing a method for manufacturing a personalized mitral valve prosthesis is that the valve is currently manufactured because the personalized valve is manufactured to the exact anatomical dimensions and limitations of each patient. It is expected that the lifespan of valve prostheses will last longer. An individualized prosthesis will outperform the best prosthesis available because it is made to fit the patient and allows for superior hemodynamic performance and faster or better cardiac recovery after prosthesis implementation.

Referring to FIG. 20A , FIG. 20A is a schematic diagram illustrating a method 2020 for fabricating a personalized mitral valve prosthesis in accordance with some embodiments of the present disclosure. According to Method 2020, the valve prosthesis is not an off-the-shelf product as is currently practiced. Instead, after ordering a personalized mitral valve prosthesis in operation 2022, the remote diagnosis imaging scans performed in operation 2024 are used as a basis for individualizing the mitral valve prosthesis dimensions in operation 2026. can be used accordingly to fabricate a more accurate personalized valve prosthesis for an individual patient in operation 2028. In some embodiments, method 2020 may include packaging and shipping a personalized mitral valve prosthesis naturally designed for implantation in a particular patient at operation 2030 . In some embodiments, the scan is made a very short time prior to fabrication operation 2028 to ensure that the personalized mitral valve prosthesis is fully compatible with the patient.

Referring to FIG. 20B , FIG. 20B is a schematic flow diagram illustrating a method for fabricating a personalized mitral valve prosthesis according to some embodiments of the present disclosure. Method 2040 is similar to method 2020 but may include other actions. In some embodiments, method 2040 may include operation 2042, which may include measuring the size and shape of the patient's inherent mitral valve via imaging methods. Diagnostic imaging techniques may be current imaging techniques including, but not limited to, 2D and 3D echocardiography, computed tomography (CT) or cardiac magnetic resonance (CMR).

In some embodiments, method 2040 may further include operation 2044, which may include calculating geometry and dimensions of the annular ring, leaflets, and nerves for a particular patient based on a validated algorithm. there is. Validated algorithms, eg calculations that help define the dimensions of a mitral valve prosthesis suitable for each particular patient, are detailed below.

In some embodiments, method 2040 may include operation 2046 , which may be performed for each patient, according to the patient's particular anatomy and individual physiology, a personalized prosthesis mitral valve ( ie the annular ring), leaflets and nerves, cutting and connecting all parts based on the calculations, thus forming a personalized mitral valve prosthesis.

In some embodiments, method 2040 may include operation 2048, which may include implanting the personalized prosthesis mitral valve into the heart of a patient in which the personalized mitral valve prosthesis has been fabricated. may include operation 2048.

Referring now to FIGS. 21A-21B , FIGS. 21A-21B illustrate schematic diagrams of a ring-shaped valve edge preserved upon removal of an inherent mitral valve in clinical practice, and a valve prosthesis, in accordance with some embodiments of the present disclosure. Schematic diagram of an elliptical annular model with the AL-PM diameter as the major axis and the AP diameter as the minor axis used to calculate the annular ring circumference (AC) of

In some embodiments, the following abbreviations are used in reference to mitral valve prosthesis annular components:

mitral annular (MA);

annular ring circumference (AC);

anterior-posterior diameter (AP);

anterior lateral posteromedial diameter (AL-PM);

commissure diameter (CC); and

Annular area (AA).

Mitral valve prosthesis annular:

According to some embodiments, the personalized mitral valve prosthesis of the present disclosure includes a flexible annular ring dimensioned to match the patient's unique mitral annulus. According to the present invention, the mitral valve prosthesis can be individualized or personalized based on the following characteristics.

The first feature is that the annular ring of the prosthesis is made without the constraints of a rigid frame and is compatible with the patient's mitral annulus.

The second characteristic is that the dimensions of the circumference of the prosthesis annular ring are individualized according to the diagnosis imaging result of a specific patient, as shown in 2022 of FIG. 20B. In some embodiments, the dimensions of the prosthesis annular ring are a function of the anterior-posterior diameter (AP) illustrated in FIG. 21A and the anterolateral posterior medial diameter (AL-PM) illustrated in FIG. 21A when the mitral valve is closed during left ventricular systole. is calculated as

A third feature is that the ring-shaped valve edge is preserved when the native mitral valve is removed in clinical practice (FIG. 21A), and the annular ring of the prosthesis is attached to the native valve edge, i. annulus). The annular ring dimension of a personalized prosthesis in terms of the annular ring circumference (AC) can be calculated according to Equation (1):

hereby

AP diameter is the anterior-posterior diameter;

AL-PM diameter is the anterolateral posteromedial diameter; and

는 환형 링의 에지의 너비이다.

is the width of the edge of the annular ring.

An approximate formula (FIG. 21B) derived from an elliptical annulus with the AL-PM diameter as the major axis and the AP diameter as the minor axis is calculated to calculate the AC(1) of the valve prosthesis based on Equation (2). used for:

)은 환자의 심장 회복 가능성(potential of recovery of the patient's heart)에 따라 달라진다. 결론적으로 개인 맞춤형 승모판 인공삽입물의 보다 정확한 환형 원주의 값인 승모판 인공삽입물의 AC(2)는 수학식 (3)에 따라 계산될 수 있다:In some embodiments, the annular ring circumference (AC) of the mitral valve prosthesis requires additional adjustment compared to the patient's native annulus, which adjustment generally results in a reduction in the size of the annular ring circumference (AC). refers to In these circumstances, the annular ring of the mitral valve prosthesis can serve as an annuloplastic treatment of the extended annular in some patients suffering from this problem. In one aspect, the percentage of AC reduction may range from 0% to 20%, and the actual value is preferably determined by existing clinical diagnosis or by a mathematical model established by big data analysis. It can be determined or, more simply and realistically, based on comparison with index values for the body surface area (BSA) of a healthy population. In another aspect, AC reduction is also required by the tendency for annular remodeling after prosthesis implantation when leaflet junctions are improved by the new valve prosthesis; Therefore, the reduction ratio (

) depends on the potential of recovery of the patient's heart. In conclusion, AC(2) of the mitral valve prosthesis, which is a more accurate value of the annular circumference of the personalized mitral valve prosthesis, can be calculated according to equation (3):

는 AC 감소의 비율이다(고유한 환형 링 원주에서부터 개인 맞춤형 인공삽입물의 환형 링까지).hereby

is the rate of AC reduction (from the original annular ring circumference to the annular ring of the personalized prosthesis).

According to some embodiments, an annular plication technique may be used when AC reduction is desired. Annular wrinkles may result in uniform annular wrinkles along the annulus instead of localized annular wrinkles commonly performed during annuloplasty. Annular folds according to embodiments of the present disclosure may be more concentrated in the posterior valve annulus due to the fact that the posterior valve constitutes a larger portion of the overall mitral valve circumference. In addition, since the posterior annulus of the human heart does not have a fibrous skeleton, it is prone to dilatation, symmetrical or asymmetrical, and the posterior annulus may expand, causing leaflet distancing and leakage.

A fourth feature is based on the fact that the mitral valve prosthesis according to the present invention can refer to a prosthetic valve comprising two leaflets consisting of an anterior leaflet 2210 (FIG. 22A) and a posterior leaflet 2220 (FIG. 22B). can Thus, the annular ring of the valve prosthesis can also include two parts: an anterior leaflet annulus and a posterior leaflet annulus. The upper edges of the anterior and posterior leaflets may be joined together along anterolateral to anterolateral and posteromedial to posteromedial directions to form the annular ring 2230 of the mitral valve prosthesis (FIG. 22C). That is, the anterior and outer sides of the preleaflet 2210 are attached to the anterior and outer sides of the posterior leaflet 2220, and the posterior inner side of the preleaflet 2210 is attached to the posterior inner side of the posterior leaflet 2220.

Annular ring 2230 may have a reinforced structure and is composed of multiple layers of leaflet material. The height of the annular ring 2230 may range from 1 mm to 4 mm, and more preferably from 2 mm to 3 mm, which may allow a clinical surgeon to stitch the valve annulus to the mitral annulus of a patient's heart. The number of layers can be 2-4 by folding or overlapping the top edges of the anterior and posterior leaflets. In some embodiments, the annular ring may include surgical suture 2316 for annular ring reinforcement.

The mitral valve prosthesis of the present invention may have an asymmetrical annular ring formed by a combination of anterior leaflet annulus and posterior leaflet annulus, which are the reinforced top edges of the leaflets. An example of such an asymmetrical annular ring is shown in FIGS. 22A and 22B , where the anterior leaflet annular circumference (AAC) 2212 is less than the posterior leaflet annular circumference (PAC) 2222 and the ratio AAC/PAC (R) is 49 /51 to 30/70, more preferably 35/65 to 42/58. The preleaflet annular circumference (AAC) 2212 and the posterior leaflet annular circumference (PAC) 2222 can be calculated according to Equations (4) and (5), respectively:

Referring now to Figures 22D and 22E-22F, which show an annular model pointing to two papillary muscles, and a customized anterior leaflet and posterior leaflet model, respectively. In some embodiments, the anterior leaflet annular circumference (AAC) and posterior leaflet annular circumference (PAC) can be defined using the new suture positions (A and B) shown in FIG. 22D. The new suture positions (A and B) can be selected based on the position of each of the two papillary muscles (PM1, PM2), which are separated from each other to determine the AAC and PAC, e.g., the anterior leaflet ( 602A) (FIG. 6A) and a posterior leaflet, eg, posterior leaflet 602P (FIG. 6A). The anterior, posterior, and valve nerves (e.g., nerves 604, 606, 608, and 610 (FIG. 6A), which may be fabricated based on the new suture positions A and B, are PM1 and PM2) may cause less distortion after implantation compared to prosthetic valves based on different suture positions, for example along an annular ring. In some embodiments, FIGS. Illustrates the anterior leaflet and posterior leaflet model after implementing the new suture positions A and B. According to the current annular model, the anterior leaflet circular circumference (AAC) is slightly longer than the posterior leaflet circular circumference (PAC). 22a-22b where the PAC is longer than the AAC In the current annular model the surface areas of the anterior and posterior leaflets are similar to each other to provide adequate closure of the leaflets under blood pressure.

Mitral Valve Prosthesis Leaflets:

Referring now to FIG. 23C , FIG. 23C is a schematic diagram of the relationship of a number of parameters that affect each other when the leaflets of a prosthesis are bonded, and with reference to FIGS. 24A-24B , in accordance with some embodiments of the present disclosure. 24A-24B are schematic diagrams of side and perspective views of bonding of mitral valve leaflets in accordance with some embodiments of the present disclosure. According to some embodiments, the mitral valve prosthesis of the present invention may include two flexible membrane-like leaflets suspended from an asymmetrical annular ring 2230. During the diastolic cycle, the two leaflets are opened to allow blood to flow from the left atrium to the left ventricle, and then both leaflets are tightly closed to allow blood flow through the heart to flow in one direction during the systolic cycle, rather than backward through the valves. The dimensions of the two leaflets are important for prosthetic valves to open and close properly.

In the case of a healthy mitral valve, the valve prosthesis can be tailored with the leaflet length replicated in the diagnostic imaging results. However, in patients with mitral valve malfunction requiring replacement, measuring anterior leaflet length (La) and posterior leaflet length (Lp) is neither suitable nor useful for individualizing or personalizing a new valve prosthesis. Instead, the anterior-posterior diameter (AP, which may be referred to as A2P2) can be used as a reference to indicate the minimum distance or length for leaflet bonding. The ratio (r) of preleaflet length to posterior leaflet length can vary from 1/1 to 2/1 (reference ratios).

In some embodiments, in addition to anterior-posterior diameter (AP) and ratio (r), leaflet length is also influenced by junction depth (Cd), junction height (Coapt H) and nerve length (Lc). Thus, the preleaflet length (ALL) and the posterior leaflet length (PLL) can be a function of all the parameters mentioned above as expressed by equations (6) and (7):

According to some embodiments, empirical formulas are used to calculate anterior leaflet length (ALL) and posterior leaflet length (PLL) for an animal model when the anterior-posterior diameter (AP) is less than 28 mm. These formulations have been demonstrated to work in a porcine or ovine model that exhibits low mean intermitral pressure gradients and accepted leaflet junctions (FIG. 24). Equations (8) and (9) are:

In some embodiments, the top edges of the anterior and posterior leaflets form a multi-layered reinforced annular ring of a valve prosthesis, eg, asymmetric annular ring 2230. The top edge of the leaflets may be straight or curved, i.e. semi-elliptical, allowing the completed valve prosthesis to more accurately fit the natural geometry of the left ventricle. Downward from the annular ring, two commissures are formed when the two leaflets are joined together, for example commissures 2310 and 2312 (FIG. 22C). The commissures are tilted inward to give the body of the valve prosthesis a slight conical shape to better fit the left ventricle with respect to shape and contour. The inclined angle (δ ₀ ) may range from 5 degrees to 20 degrees. The cone angle (δ ₁ ) is determined by the inclination angle (δ ₀ ) of the commissure edge of the leaflets according to equation (10):

According to some embodiments, the inclination angles δ ₀ are the same for both leaflets, and thus the cone angle δ ₁ is the same for both leaflets. According to some embodiments, another element of the prosthesis leaflet that is to be individualized or personalized is the free edges. The edge to edge coaptation between the anterior and posterior leaflets controls the function and performance of the prosthetic valve. Geometrically, the leaflet free edge of the present invention is semi-elliptical. The length of the free edge can be calculated according to Equation (11).

where CH denotes the length of the commissure edges 2214 and 2216 as shown in FIGS. 22A and 22B respectively.

Parameters “a” and “b” are the geometrical parameters needed to form the shape of the top edge of the anterior leaflet or posterior leaflet, which are the long axis “a” and the short axis as shown in FIG. 23A. ) as a semi-ellipse with “b” or as a straight line as shown in FIG. 23B.

"이고, "

"인 첨판의 상단 에지가 직선인 극단적인 예시이고, 첨판의 자유변은 다음과 같이 수학식 (12)에 따라 계산될 수 있다:Figure 23b shows "

"ego, "

" is an extreme example where the top edge of the leaflet is straight, and the free edge of the leaflet can be calculated according to Equation (12) as:

According to some embodiments, an improved algorithm for calculating customized mitral valve prosthesis leaflet length may be provided. Leaflet length is a key factor influencing valve closing and opening in an efficient and effective manner. In some embodiments of the present disclosure, finite element method (FEM) may be used to optimize and calculate optimal pre- and post-leaflet lengths to increase adhesion and reduce valve leakage. In these embodiments, variations in imported bovine pericardial data or imported data of other materials that may make up the prosthetic mitral valve, such as thickness and material properties, are first introduced to calculate the customized valve design. The thickness, material properties and other characteristics of the bovine pericardium or other material can also affect the way the valve closes and opens.

Reference is now made to FIG. 23D , which is a schematic flow chart illustrating a customized mitral valve design method using FEM. According to some embodiments, method 2300 may include act 2320, which may include providing data related to the patient's mitral valve, such as providing the size and shape of a particular patient's natural mitral valve. there is. Data related to the patient's mitral valve may include, for example, annular circumference length, annular diameter, papillary muscle position, and the like. Method 2300 may further include an operation 2330 that may include providing incoming bovine pericardial data regarding the material properties of the fed (or incoming) bovine pericardium. In some embodiments, the imported data of the material from which the prosthetic mitral valve may be constructed, for example imported bovine pericardium data, may include, for example, bovine pericardial thickness, tensile testing data, such as Young's modulus, stress- strain curves and the like.

In some embodiments, method 2300 can include operation 2340, which builds a customized 3D model of a prosthetic mitral valve and inputs imported bovine pericardial data and patient data, which can be used as inputs. An operation of optimizing the mitral valve data through FEM analysis may be included. In some embodiments, optimal preleaflet length, optimal posterior leaflet length, optimal nerve width, etc. may be determined by studying valve parameters selecting different preleaflet lengths, posterior leaflet lengths, nerve widths, and any additional ones and combinations thereof ( It can be determined by FEM optimization through valve parameter studies. Leaflet deformation, maximum principle stress, equivalent (von-Mises) stress, and leaflet contact detection area are the optimal values for optimal valve performance. It can be used to evaluate valve performance when the mentioned valve parameters and other valve parameters are changed until the parameters of .

In some embodiments, method 2300 can optionally include an operation 2350 that can include an operation of visualizing the customized prosthetic mitral valve. In some embodiments, method 2300 does not require operation 2350. Operation 2350 includes the dimensions of the prosthetic mitral valve performed during operation 2340, such as anterior leaflet, posterior leaflet, anterior circumference, posterior circumference, annular diameters, anterior leaflet height, posterior leaflet height, nerve width, etc. It may include an operation of visualizing a 3D model of the artificial mitral valve customized after formulating the mitral valve. In some embodiments, method 2300 can include operation 2360, which includes fabricating an artificial mitral valve according to the built 3D model and following visualization of the model in operation 2350. can do.

In some embodiments, after the customized prosthetic mitral valve design has been completed, visualized and fabricated, method 2300 may include performing a performance verification test on the customized prosthetic mitral valve, for example inside an in vitro hydrodynamic chamber test. It may include an additional operation 2370 that includes.

According to some embodiments, the customized valve design method may include providing patient mitral valve parameters and imported bovine pericardium data according to operations 2320 and 2330, respectively. An example of such data is provided in Table 1 below. The patient valve commissure diameter in this example is 36 mm.

Patient mitral valve parameters valve [mm] Drill diameter (CC) (CC) 36.0 Distance offset (DPM) between the PMs and the center line of the annulus 6.0 Distance between two PMs (DBPM) 24.0 Z height from PM to annular (ZH) 30.0 Bovine pericardium thickness (BPTH) 0.28 Bovine pericardium Young's modulus (BPYM) 30.0 MPa

Table 1: Patient mitral valve data and inflow bovine pericardium data

In the method, customized posterior and anterior leaflet parameters implemented according to operation 2340 by FEM parameter optimization and tailored to the patient are provided in Table 2 below.

Customized valve leaflets valve [mm] Drill Diameter C-C(CC) 36.0 Posterior Annular Circumference (PAC) 51.6 Anterior Annular Circumference (AAC) 63.2 Posterior leaflet length (PLL) 25.0 Preleaflet Length (ALL) 25.0

Table 2: Customized valve leaflet parameters

In some embodiments, the anterior leaflet length (ALL) and posterior leaflet length (PLL) may be influenced by patient mitral valve data such as commissure diameter, papillary muscle distance, etc., as well as imported bovine pericardial data such as bovine pericardial thickness and Young's modulus. there is. That is, ALL and PLL may be functions of the above-mentioned parameters and additional parameters according to equations (13) and (14), respectively.

hereby

CC represents the commissure diameter;

DBPM represents the distance between papillary muscles;

ZH represents the Z height from the papillary muscles to the annular ring;

BPTH represents bovine pericardial thickness; and

BPYM stands for bovine pericardial Young's modulus.

In some embodiments, an empirical formula for calculating the anterior leaflet length (ALL) and posterior leaflet length (PLL) for different patients based on the CC 36.0 mm FEM related data above may be proposed. The final preleaflet length and posterior leaflet length should be verified by the FEM method. In some embodiments, ALL and PLL may be calculated by Equations (15) and (16), respectively:

hereby

α is the anterior leaflet length amplification factor, for example 0.1033; and

는 후첨판 길이 증폭 인자, 예를 들어 0.1033이다.

is the posterior leaflet length amplification factor, eg 0.1033.

Mitral valve prosthesis nerves:

In a normal mitral valve, the nerves emerge from the papillary muscles and insert into the leaflets in a fan-shaped fashion. It is divided into primary, secondary, and tertiary nerves according to the location of attachment.

The mitral valve prosthesis of the present disclosure includes primary nerves merely attached to the free edge of either the anterior leaflet or the posterior leaflet. Two sets of nerves (FIG. 24A) and three nerves (FIG. 24B) of each set are evenly distributed along 3/8 of the free edge at each end, they are the anterolateral nerves and the posteromedial nerves.

Nerves play an important role in ensuring proper opening and closing of the valve prosthesis. Compared to other geometrical features of the mitral valve, the length of nerves, especially nerves, is currently not well studied during clinical prediagnosis, especially for valve replacement. A neural measure may be defined as the distance from the apex of the papillary muscle to the annular plane, the distance from the apex of the papillary muscle to the junctional edge, or the distance from the apex of the papillary muscle to the annular plane.

To personalize the nerve length of the prosthesis, the leaflet length (ALL or PLL), leaflet junction height (Coapt H), leaflet junction depth (Cd), and distance from the apex of the papillary muscle to the leaflet junction edge (Lc) were determined for complex structures. Correlation is necessary to ensure the function of the prosthesis. Thus, the length of the anterior cingulate nerves (ACL) and the length of the posteromedial nerves (PCL) can be expressed as a function of several parameters according to equations (17) and (18) below:

및

또한 본 개시에서 소개된다; 설계 수준에서, 각 세트의 3개의 신경들은 자유 단부(free end)에서 병합되고 신경 캡(2240)(도 22a 및 도 22b)과 같은 플레짓으로 융합된다. 임상 외과 의사는 현장 측정 및 조정을 수행하여 승모판 인공삽입물의 개인화 또는 맞춤화(customization)의 마지막 부분을 완료할 수 있다. 도 25는 본 개시의 방법에 따라 제작된 자연적으로 설계된 개인 맞춤형 승모판 인공삽입물이 이식된 양(ovine) 심장의 심장초음파 사진이다.A simplified method using the distance measured from the apex of the papillary muscle to the junction edge as the prosthesis nerve length, i.e.

and

Also introduced in this disclosure; At the design level, the three nerves of each set are merged at the free end and fused into a flange such as nerve cap 2240 ( FIGS. 22A and 22B ). The clinical surgeon may perform on-site measurements and adjustments to complete the final piece of personalization or customization of the mitral valve prosthesis. FIG. 25 is an echocardiogram of an ovine heart implanted with a naturally designed personalized mitral valve prosthesis fabricated according to the method of the present disclosure.

Referring now to FIGS. 26A-26B , FIGS. 26A-26B are schematic diagrams of posterior and anterior leaflets illustrating respective nerve widths and nerve distances, according to embodiments of the present disclosure. In some embodiments, chord width (CW) and chord distance per posterior leaflet (DCPL) and chord distance per anterior leaflet (DCAL) are measured by FEM method can be determined by Regarding the example where CC is 36.0 mm, CW is 3 mm for both the anterior and posterior leaflets. In some embodiments, nerve width (CW) can be calculated by Equation (19) based on a CC36.0 mm valve:

hereby

γ represents the nerve width amplification factor, for example 0.0124.

In some embodiments, the final nerve width needs to be verified using the FEM method.

According to some embodiments, the posterior leaflet nerve distance (DCPL) and the anterior leaflet nerve distance (DCAL) may depend on the distance between the two papillary muscles (DBPM).

27 is a schematic diagram of a final customized 3D model of an artificial mitral valve comprising a D-shaped annular ring. A 3D model of the prosthetic mitral valve may be built based on the patient mitral valve data provided in operation 2320 and may further be based on the imported bovine pericardium data provided in operation 2330 of method 2300.

28 is a schematic diagram of FEM simulation optimization results of a customized prosthetic mitral valve model according to operation 2340 of method 2300. 28 shows a FEM model of a prosthetic mitral valve in a closed configuration. It is clear that the annular ring of the valve model is D-shaped, similar to the annular ring shape of the natural mitral valve.

After the customized artificial mitral valve is visualized in operation 2350, and then the customized artificial mitral valve is manufactured in operation 2360, a performance verification test of the customized artificial mitral valve may be performed in operation 2370. 29A-29B are schematic views of a prosthetic mitral valve inside a hydrodynamic test chamber in open and closed configurations.

30 and 31 are echocardiograms of a customized prosthetic mitral valve during closed configuration after implantation into a porcine heart, respectively, and are images illustrating blood pressure gradients of a porcine heart after implantation. The customized prosthetic mitral valve can be closed and opened in a very efficient and effective manner and no leakage occurs. The maximum pressure gradient may be 3.87 mmHg and the average pressure gradient may be 1.61 mmHg, similar to the pressure experienced by a natural human mitral valve.

The personalized geometries and dimensions discussed above can be taken as input to various engineering drawing software or drawing tools.

The drawing can be printed as a template for manually cutting the leaflets of the valve prosthesis (eg, by hand cutting under a microscope).

The drawing can be programmed into a laser cutting machining tool to cut leaflets much more accurately and efficiently than manual cutting.

The drawing also shows a personalized mold cutter or die cutter used for leaflet cutting at temperatures lower than those at which laser cutting occurs, to minimize thermal effects on the material being cut for the valve prosthesis. ) can be programmed into machining tools to make

A mitral valve prosthesis can be created by joining together the annular and commissural edges of the anterior and posterior leaflets along the anterolateral to anterolateral and posteromedial to posteromedial directions (FIG. 22C). One way to join the two leaflets together may be to stitch them with a surgical suture, such as stitching 2314 in FIG. 22C.

The aforementioned valve prosthesis may be further packaged, labeled, and sterilized prior to release for use, i.e., implantation in patients who have personally fabricated the valve prosthesis.

For ease of operation, the aforementioned valve prosthesis can be assembled to the valve holder prior to packaging.

A valve prosthesis of the present disclosure may be shipped or otherwise transferred as a complete product for individualized implantation for a particular patient.

According to some embodiments, any of the disclosed anterior and posterior leaflets, any ring, any nerves (and any sub-set of nerves), any cap, and/or any combination thereof It can be produced from natural materials and avoids the inclusion of foreign substances such as pledgets. Fabrication of flexible rings, leaflets, nerves and caps using allograft and/or composite materials, including various combinations of homograft, xenograft and/or autograft materials can be used more for Materials forming the valve rings and leaflets include human, bovine or porcine pericardium, decellularized bioprosthetic material, woven biodegradable polymers integrated with cells, and extracellular materials ( extracellular materials), but is not limited thereto. Biodegradable natural polymers may include, but are not limited to, tofibrin, collagen, chitosan, gelatin, hyaluronan, and similar materials thereof. A biodegradable synthetic polymer scaffold that can infiltrate into cells and extracellular matrix material is poly (L-lactide), polyglycolide, poly(lactic-co-glycolic acid), poly(caprolactone), polyorthoesters, poly(dioxanone) ), poly(anhydrides), poly(trimethylene carbonate), polyphosphazenes and similar materials thereof. Flexible rings may be further customized to provide individualized flexibility or stiffness to the patient. Additionally, some components of the mitral valve prosthesis, including the nerves, may be formed intraoperatively by the patient's own pericardium.

According to some embodiments, any of the disclosed asymmetric flexible rings, which may include an anterior ring portion and a posterior ring portion, or may be fabricated as a single unit, is formed by rolling or folding the edge of the leaflet(s) onto itself. It can be. In other embodiments, the flexible ring may further comprise at least two or more strands or layers of material, such as human, bovine or porcine pericardium, or any of the materials listed above, whereby two or more The strands or layers may be wound, twisted, braided or looped together. A ring of coiled coil construction may have higher strength than a ring formed by rolling the edge of the leaflet itself, but the coiled ring must remain elastic.

According to some embodiments, the ring may include two strands or layers of material folded together to provide elasticity, and a third layer may be added to provide structural stability. In some embodiments, a ring may include two layers made of bovine pericardium, while a third strand or layer may be made of glycine or proline to provide strength to the ring.

In some embodiments, two or more layers or strands may be attached, for example sewn together. In some embodiments, the third layer can be attached, eg, sutured to two or more layers of a ring.

According to some embodiments, the components of the prosthetic mitral valve may be attached or connected to each other through various connection methods. For example, the components of the prosthetic mitral valve may be connected to each other via stitches, stapler pins, adhesive or any other means of attachment.

In some embodiments, the sutures or stitches may be made of non-biodegradable synthetic materials such as nylon (ethylon), prolene (polypropylene), novafil, polyester, and the like. In some embodiments, the sutures or stitches may be made from a non-biodegradable natural material such as surgical silk or surgical cotton.

In some embodiments, stapler pins may be made of a biocompatible material, such as stainless steel or titanium.

In some embodiments, the adhesive may be made of a biocompatible material such as an aldehyde-based adhesive, a fibrin sealant, a collagen-based adhesive, polyethylene glycol polymers (hydrogels), or cyanoacrylates.

According to some embodiments, any leaflets, any ring, any nerves (and any sub-set of nerves), and/or any combination thereof may be used for ultrasound imaging of the patient's unique mitral valve and surrounding anatomy. It can be customized for each patient based on the imaging. Customized mitral valves can be further produced based on data obtained by other imaging modalities that provide three-dimensional information, including echocardiography, cardiac CT and cardiac MRI. As such, mitral valve prostheses of the present disclosure may be selected or designed to match a patient's particular anatomy, thereby providing high acceptance of the prosthesis by the patient's surrounding tissue, eg, cardiac muscle surrounding the prosthesis. can increase your chances.

To prepare the patient for implantation, the patient's heart is stopped, as in mitral valve surgeries. During implantation, the flexible ring of the prosthesis is secured to the intrinsic annulus with sutures and the nipple caps are sutured to the intrinsic papillary muscles. For example, two sutures can be applied to the end of each unique papillary muscle to attach the cap to the muscle. The clinician fills the ventricular chamber with saline at an appropriate pressure and checks the movement and competency of the replaced valve as it closes under the applied pressure, ensuring that the valve opens and closes completely. After the heart closes and resumes beating after implantation, the valve is examined by transesophageal echocardiography (TEE).

If necessary, the subject may receive anticoagulation medication post transplant. Given the natural form and natural materials used to construct the mitral valve prosthesis of the present invention, it is expected that most patients will not have low doses of anticoagulation medication or no anticoagulants.

Currently available biological and mechanical prostheses have several disadvantages: they contain a bulky foreign body, require strong anticoagulants, have a short useful life requiring follow-up surgeries when the patient needs to be replaced, It does not help you recover efficiently. The present invention provides several advantages over the biological and mechanical prostheses described above. Mitral valve prostheses, which have a design that more closely matches the patient's native mitral valve and are made of natural materials, require less recovery time for the patient, provide a longer useful life, and reduce or eliminate the need for anticoagulants. expected to do

The teachings of all patents, published applications and references cited herein are incorporated by reference in their entirety.

While this invention has been particularly shown and described with reference to illustrative embodiments thereof, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as covered by the appended claims. will be.

Claims (39)

A method for manufacturing a naturally designed personalized mitral valve prosthesis so that the mitral valve prosthesis manufactured for a specific patient fits the specific patient precisely,
measuring the size and shape of the unique mitral valve of the specific patient using an imaging means;
providing data of a material from which the personalized mitral valve prosthesis is made;
constructing a 3D model of the personalized mitral valve prosthesis based on the data of the material and the size and shape of the unique mitral valve of the specific patient;
optimizing the 3D model using the FEM method; and
Manufacturing the personalized mitral valve prosthesis based on the optimized FEM model
including,
Way. According to claim 1,
Visualizing the personalized mitral valve prosthesis model after the optimizing operation
Including more,
Way. According to claim 1 or 2,
The imaging means,
including 2D or 3D echocardiography, computed tomography (CT), cardiac magnetic resonance (CMR), or a combination thereof;
Way. According to any one of claims 1 to 3,
The operation of measuring the size and shape of the patient's unique mitral valve,
Including an operation of measuring parameters related to the mitral valve,
These parameters are
annular ring circumference (AC);
annular area (AA);
anterior-posterior (AP) diameter,
Anterior lateral-postinternal (AL-PM) diameter,
drill diameter (CC),
preleaflet length (AL),
posterior leaflet length (PL),
Mitral valve shape and tendon length (ACL and PCL)
including,
Way. According to any one of claims 1 to 4,
Collecting body information of the specific patient to predict the geometric structure of the heart after implantation of the personalized mitral valve prosthesis
Including more,
The body information,
including height, weight, age, race and sex;
Way. In the personalized mitral valve prosthesis,
A flexible annular ring sized to match the specific patient's unique mitral annulus;
flexible anterior and posterior leaflets, dimensioned to match the unique mitral leaflets of said particular patient, and
Codes dimensioned to match the unique mitral leaflets of the particular patient
including,
The leaflets,
connected to the annular ring;
these nerves,
connected to the flexible preleaflet and the flexible posterior leaflet;
these nerves,
further configured to connect the flexible anterior leaflets and the flexible posterior leaflets with papillary muscles of the heart;
The personalized mitral valve prosthesis,
An operation of measuring the size and shape of the unique mitral valve of the specific patient using an imaging means;
An operation of providing data of a material from which the personalized mitral valve prosthesis is made;
constructing a 3D model of the personalized mitral valve prosthesis based on data of the material and size and shape of the unique mitral valve of the specific patient;
optimizing the 3D model using the FEM method; and
cutting the material into the annular ring, the flexible anterior leaflet and the flexible posterior leaflet and the nerves, connecting the flexible anterior leaflet and the flexible posterior leaflet to the annular ring, and connecting the nerves to the flexible manufacturing the personalized mitral valve prosthesis based on the optimized FEM model by connecting to the sexual anterior leaflet and the flexible posterior leaflet.
formed by
Personalized mitral valve prosthesis. According to claim 6,
The personalized mitral valve prosthesis,
Further formed by visualizing the personalized mitral valve prosthesis model after the optimizing operation,
Personalized mitral valve prosthesis. According to claim 6 or 7,
The imaging means,
including 2D or 3D echocardiography, computed tomography (CT), cardiac magnetic resonance (CMR), or a combination thereof;
Personalized mitral valve prosthesis. According to any one of claims 6 to 8,
The operation of measuring the size and shape of the patient's unique mitral valve,
Including an operation of measuring parameters related to the mitral valve,
These parameters are
annular ring circumference (AC);
annular area (AA);
anterior-posterior (AP) diameter,
Anterior lateral-postinternal (AL-PM) diameter,
drill diameter (CC),
preleaflet length (ALL);
posterior leaflet length (PLL);
Mitral valve shape and tendon length (ACL and PCL)
including,
Personalized mitral valve prosthesis. According to any one of claims 6 to 9,
Collecting body information of the specific patient to predict the geometric structure of the heart after implantation of the personalized mitral valve prosthesis
Including more,
The body information,
including height, weight, age, race and sex;
Personalized mitral valve prosthesis. According to claim 9,
The measuring operation is
Measuring the annular ring circumference (AC) as a combination of the anterior leaflet annular ring circumference (AAC) and the posterior leaflet annular ring circumference (PAC),
The preleaflet annular ring circumference is,
a top edge of the leaflet;
The posterior leaflet annular ring circumference,
is the top edge of the posterior leaflet based on equation (3);
[Equation 3]

The annular ring,
Formed into a multi-layer reinforced structure by folding or overlapping the top edges of the anterior and posterior leaflets,
Personalized mitral valve prosthesis. According to claim 11,
The top edge of each of the anterior leaflet and the posterior leaflet,
Straight or curved, to properly fit the personalized mitral valve prosthesis to the natural geometry of the left ventricle of the particular patient.
Personalized mitral valve prosthesis. According to claim 11,
connecting is,
joining the edge of the anterior leaflet with the edge of the posterior leaflet to create a bond between the anterior leaflet and the posterior leaflet.
Personalized mitral valve prosthesis. According to any one of claims 6 to 13,
connecting is,
joining the flexible anterior leaflet and the flexible posterior leaflet together to form two commissures;
The two drills,
tilting inward at a cone angle (δ ₁ ) to create a conical shape in the personalized mitral valve prosthesis to fit the unique left ventricle of the particular patient;
Personalized mitral valve prosthesis. According to claim 14,
The cone angle (δ ₁ ) is,
Determined by the inclination angle (δ ₀ ) of each commissure edge of the flexible anterior leaflet and the flexible posterior leaflet based on Equation (10),
[Equation 10]

Personalized mitral valve prosthesis. According to any one of claims 6 to 15,
connecting is,
connecting the anterior leaflet to the posterior leaflet by connecting the anterior lateral to the anterolateral and connecting the posteromedial to the posteromedial.
Personalized mitral valve prosthesis. According to claim 16,
Connecting the anterior leaflet to the posterior leaflet,
Including stitching,
Personalized mitral valve prosthesis. According to claim 13,
The measuring operation is
To calculate the length of each leaflet edge based on Equation (12), the size and shape of the unique annular ring of the particular patient,
commissure height (CH) inclination angle (δ ₀ ),
preleaflet length (ALL);
Posterior leaflet length (PLL), and junction height (Coapt H)
Including the operation of measuring
Equation (12) above is,

sign,
Personalized mitral valve prosthesis. According to any one of claims 11 to 13,
wherein the reinforced annular ring height is between 1 mm and 4 mm;
Personalized mitral valve prosthesis. According to any one of claims 11 to 13,
wherein the reinforced annular ring height is between 2 mm and 3 mm;
Personalized mitral valve prosthesis. According to any one of claims 11 to 13,
The annular ring circumference AC,
which is a function of the anterior-posterior diameter (AP) and the anterolateral-postinternal diameter (AL-PM) based on Equation (3),
Personalized mitral valve prosthesis. According to claim 21,
The action to be measured is
Operation of measuring the anterior-posterior diameter (AP)
including,
The anterior lateral posterior medial diameter (AL-PM) is,
Performed when the mitral valve closes during left ventricular systole,
Personalized mitral valve prosthesis. According to any one of claims 11 to 13,
Calculating the annular ring circumference (AC) of the prosthesis is
The ratio of Equation (3) (

) based on,
Personalized mitral valve prosthesis. According to claim 6,
The annular ring,
is asymmetric,
The annular ring,
formed from a combination of a preleaflet annulus and a posterior leaflet annulus;
The preleaflet annular circumference (AAC) is
smaller than posterior leaf annular circumference (PAC),
The ratio (R) between AAC/PAC is
49/51 to 30/70;
Personalized mitral valve prosthesis. According to claim 24,
The ratio (R) between AAC/PAC is
35/65 to 42/58;
Personalized mitral valve prosthesis. According to claim 24,
The ratio (R) between AAC/PAC is
40/60 people,
Personalized mitral valve prosthesis. According to claim 24,
The ratio (R) between AAC/PAC is
Between the preleaflet length (ALL) and the posterior leaflet length (PLL),
Personalized mitral valve prosthesis. The method of any one of claims 6 to 27,
The operation of building a 3D model of the personalized mitral valve prosthesis,
Calculating anterior leaflet circular circumference (AAC) and posterior leaflet circular circumference (PAC) based on suture positions (A and B)
including,
Personalized mitral valve prosthesis. According to claim 18,
The operation of building a 3D model of the personalized mitral valve prosthesis,
(a) the anterior-posterior diameter (AP), which is the theoretical minimum distance for bonding;
(b) the ratio between ALL and PLL (r);
(c) bonding depth (Cd);
(d) the junction height (Coapt H); and
(e) based on nerve length (Lc),
An operation of calculating the anterior leaflet length (ALL) and the posterior leaflet length (PLL) based on Equations (8) and (9)
including,
Equation (8) above is,

ego,
Equation (9) above is,

sign,
Personalized mitral valve prosthesis. The method of any one of claims 6 to 29,
connecting is,
connecting the anterior leaflet and the posterior leaflet together to form the body of the personalized mitral valve prosthesis.
Personalized mitral valve prosthesis. The method of any one of claims 6 to 30,
Each of the anterior leaflets and each of the posterior leaflets,
contains two sets of nerves,
The two sets of nerves are
anterior lateral nerves and posteromedial nerves,
Each of the anterior lateral nerves and posterolateral nerves,
contains 3 sub-nerves,
these nerves,
uniformly distributed along at least 3/8 of each edge from each side,
Personalized mitral valve prosthesis. According to claim 31,
The operation of building the 3D model,
Including the operation of calculating the length of each,
The operation of calculating the length of each nerve,
Based on parameters including leaflet length, bond height and bond depth,
Personalized mitral valve prosthesis. 33. The method of any one of claims 6 to 32,
The action to be measured is
measuring the distance from the papillary muscle apex to the junction edge to indicate the prosthesis nerve length;
Further comprising in-situ measurement and adjustment of a platform such as a nerve cap into which the nerves are integrated and merged at each end of the set of nerves.
Personalized mitral valve prosthesis. 34. The method of any one of claims 6 to 33,
The operation of building the 3D model,
providing the calculated geometry and dimensions of the annular ring, the anterior leaflet, the posterior leaflet and the nerves for the particular patient as inputs to an engineering drawing software or drawing tool.
including,
Personalized mitral valve prosthesis. 35. The method of claim 34,
The engineering drawing software or drawing tool,
outputting a template for manually cutting the leaflets of the valve prosthesis;
Personalized mitral valve prosthesis. 35. The method of claim 34,
The engineering drawing software or drawing tool,
outputting a template for machine cutting the leaflets;
Personalized mitral valve prosthesis. 37. The method of any one of claims 6 to 36,
Further comprising packaging, labeling, and sterilizing the personalized mitral valve prosthesis prior to shipment for use.
Personalized mitral valve prosthesis. 38. The method of any one of claims 6 to 37,
Further comprising an operation of assembling the personalized mitral valve prosthesis to the valve holder before the packaging operation.
Personalized mitral valve prosthesis. 39. The method of any one of claims 6 to 38,
Further comprising the operation of transplanting the personalized mitral valve prosthesis to the specific patient,
Personalized mitral valve prosthesis.

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