Workflow for valve reconstruction based on engineering design

Abstract

An engineering workflow for the future design of cardiac valve leaflet grafts for surgical cardiac valve reconstruction is disclosed. [Solution] The engineering workflow involves defining the size and / or shape of the materials by utilizing quantitative descriptions of one or more mechanical properties of one or more materials used in the reconstruction of a heart valve, thereby achieving a predetermined configuration of the final reconstructed heart valve in a specific patient's physiological operating state.

Description

TECHNICAL FIELD

[0001] Cross-Reference to Related Applications This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 63 / 088,663, filed October 7, 2020, entitled "Engineering-Design-Based Workflow for Aortic Valve Reconstruction", the entire contents of which are incorporated herein by reference.

[0002] The disclosed embodiments relate to engineering workflows for preparing materials for implantation in a subject, such as heart valve leaflet implants for surgical heart valve reconstruction. BACKGROUND ART

[0003] A normal human heart has four valves that control the direction of blood flow through the heart. The valves open and close passively in response to pressure gradients generated as the muscular walls of the heart chambers contract and relax. The aortic valve is located at the junction of the left ventricle and the aorta. It consists of three thin flaps called leaflets, which open to allow blood ejected from the left ventricle to enter the systemic arteries, and close when the left ventricle relaxes to maintain pressure within the aorta while the left ventricle refills. In a healthy valve, the closed leaflets meet with some degree of overlap or redundancy. This region where adjacent closed leaflets overlap is referred to as the coaptation region.

[0004] Valvular disease refers to a condition in which a valve fails to open properly, close properly, or both. Severe valvular disease can be treated by replacing the valve with a prosthetic valve or surgically modifying the valve. The decision to replace or surgically repair a valve is multi-factorial, and valve repair also includes reconstructing one or more leaflets using certain non-growing patch materials, which is often a treatment option selected not only for some adult patients but also for pediatric patients. In many cases, it is a treatment option selected not only for pediatric patients but also for some adult patients.

[0005] Traditional approaches to heart valve reconstruction are subjective and based on the experience and preferences of individual surgeons. According to this traditional approach, single or multiple pieces of material are freehand cut in the operating room during surgery, according to an individualized method, from a larger portion of autograft, allograft, xenograft, or composite material. Surgeons often take one or more measurements of the patient's cardiovascular anatomy to help determine the size of the components. [Overview of the project] [Problems that the invention aims to solve]

[0006] In one embodiment, a method for preparing an implantable material includes: obtaining a target configuration of a bioprosthetic valve; obtaining one or more features of the bioprosthetic valve to be reconstructed; obtaining one or more mechanical features of the implantable material; and determining a pattern of the implantable material configured to reconstruct a bioprosthetic valve, at least in part, based on the target configuration, one or more features of the bioprosthetic valve, and one or more mechanical features of the implantable material.

[0007] In one embodiment, a non-temporary computer-readable storage medium containing processor-executable instructions, when executed, performs a method for preparing an implantable material, which includes the following steps: obtaining a target configuration of a bioprosthetic valve; obtaining one or more features of the bioprosthetic valve to be reconstructed; obtaining one or more mechanical features of an implantable material; and determining a pattern of the implantable material configured to reconstruct a bioprosthetic valve, at least in part, based on the target configuration, one or more features of the bioprosthetic valve, and one or more mechanical features of the implantable material.

[0008] This disclosure is not limited thereto, and it should be understood that the concepts described above, and any additional concepts described below, can be formed in any suitable combination. Furthermore, other advantages and novel features of this disclosure will become apparent from the following detailed description of various non-limiting embodiments, in conjunction with the accompanying drawings. [Brief explanation of the drawing]

[0009] Non-limiting embodiments of this disclosure are illustrative and are described by reference to accompanying drawings, which are schematic and not intended to be drawn to any particular scale. In the drawings, each identical or substantially identical component shown is usually represented by a single number. For clarity, not all components are labeled in all drawings, and not all components of each embodiment of the invention are shown where it is not necessary to illustrate so that those skilled in the art can understand the invention. In the drawings:

[0010] [Figure 1A] Figure 1A is a top view of the aortic valve when the aorta is cut above or distal to the valve level. [Figure 1B] Figure 1B is a side view showing a cross-section of the aortic valve cut at the position of the cutting line 1B-1B shown in Figure 1A. [Figure 2] Figure 2 shows an engineering workflow according to an exemplary embodiment. [Figure 3] Figure 3 is a flowchart showing the steps of an engineering workflow according to an exemplary embodiment. [Figure 4] Figure 4 is a top view of a patterned implantable material configured to repair a defective aortic valve, according to an exemplary embodiment. [Modes for carrying out the invention]

[0011] Generally speaking, to treat a patient's bioprosthetic valve (e.g., a heart valve), a clinician may choose to surgically repair such a defective heart valve by implanting material into the patient's defective site. To implant such material, a clinician may want to prepare the material by cutting an appropriate pattern for its size and shape before surgical implantation. However, a major challenge associated with conventional implantable materials is determining the shape and / or size of the implantable material or any part thereof.

[0012] In particular, clinicians may need to estimate the three-dimensional properties of two-dimensional implantable materials (e.g., those exhibited after implantation in the patient). Especially after implantation, implantable materials may stretch between the zero-pressure state during surgery and one or more physiological states (e.g., pressurized state). Therefore, it may be desirable to consider such stretchability for the size and / or shape of the material.

[0013] Traditionally, clinicians may apply a qualitative approach to select and prepare implantable materials for reconstructing bioprosthetic valves. For example, a clinician may examine the bioprosthetic valve pre- or during surgery and qualitatively select an implantable restorative material (e.g., a commercially available product). Such an approach may result in variations in fit, potentially leading to premature wear or failure of the restorative material. Therefore, the inventors recognized the advantages of a quantitative and personalized workflow for preparing implantable materials for reconstructing bioprosthetic valves in individual patients.

[0014] Furthermore, clinicians may also want to consider how much the material stretches between its prepared state and the state in which the reconstructed valve is configured to function (for example, if hemodynamic forces or pressures can cause the material to stretch, it may stretch by more than 40 percent compared to its unstretched, resting state). Additionally, suitable and / or widely used implantable materials may exhibit some degree of anisotropy (for example, a material may exhibit different stress-strain characteristics in different deformation directions). Some conventionally used valve reconstruction materials are highly anisotropic, stretching up to four times in the direction of minimum stiffness compared to the direction of maximum stiffness.

[0015] The inventors also recognized that valve reconstruction in children may present further challenges, including the desire to reconstruct the valve (e.g., to match the child's growth) so that the valve retains its function for as long as possible, thereby avoiding the need for additional surgery during childhood.

[0016] Traditionally, implantable materials are prepared subjectively (e.g., according to the clinician's qualitative training and / or experience). For example, when surgically reconstructing a bioprosthetic valve, a clinician may consider many variables that could affect the function of the reconstructed valve after surgery. These may include: the three-dimensional spatial details of the patient's anatomical structure; the mechanical properties of the original valve and its surroundings (e.g., the aortic root); the mechanical properties of the material selected to reconstruct the valve; the size, shape, and / or orientation of the material piece used to reconstruct the valve; the method of surgically implanting the material piece; and physiological variables that relate to the conditions under which the valve functions after surgical repair.

[0017] Clinicians typically attempt to integrate all these complex variables in the operating room without using quantitative methods or tools, instead relying primarily on experience and intuition to determine material selection and component size and shape. Therefore, the outcomes of valve reconstruction using conventional surgical techniques can vary significantly depending on the individual clinician's experience.

[0018] To standardize bioprosthetic valve reconstruction methods, a series of devices have been developed and commercialized that utilize a set of devices for determining the patient's valve size and a corresponding set of templates for tracing and / or cutting material for valve reconstruction. However, significant limitations remain with such products. For example, the material used for valve reconstruction may vary from patient to patient depending on factors such as the availability of autologous tissue for harvesting and the clinician's preference.

[0019] Conventional standardization approaches may not take into account the mechanical properties of both the inherent structure (such as the valve and supporting tissue to be repaired) and the specific valve reconstruction material when cutting material pieces to reconstruct the valve to a predetermined size and shape.

[0020] Furthermore, current approaches to standardization may not take into account the anisotropy of materials, that is, the existence of a direction along the material under a given strain in which the deformation of the material is minimized relative to all other directions of the material. Accordingly, these current approaches may be unable to predict the size and / or shape of the piece of material used to reconstruct a particular patient's valve with respect to its ability to withstand and function under various physiological conditions that may be present in the patient's body. Moreover, conventional products and / or methods may be unable to account for or adapt to changes in physiological demands on the valve, such as those imposed by patient growth.

[0021] In view of the above, the inventors have recognized the advantages of a quantitative method for specifying the shape and / or size of a piece or multiple pieces of material used to reconstruct a heart valve, such that a heart valve reconstructed from this piece or multiple pieces of material can achieve a target open and closed configuration while allowing the mechanical properties of the reconstruction material to be taken into account. Furthermore, in growing patients (e.g., children), it is desirable that the method of preparing the material piece for valve reconstruction produces a reconstructed valve that adapts to the patient's growth.

[0022] Accordingly, the workflows disclosed herein relate to a fully quantitative approach for the surgical reconstruction of a biological valve (e.g., a cardiac aortic valve). When surgically reconstructing a biological valve, a clinician may consider many variables that can affect the function of the reconstructed valve after surgery. As described herein, these may include: three-dimensional spatial details of the patient's anatomy; mechanical properties of the native valve and its surroundings (such as the aortic root); mechanical properties of the material selected to reconstruct the valve; size, shape, and / or orientation of the piece of material used to reconstruct the valve; the method of surgically implanting the material piece; and physiological variables related to the conditions under which the valve functions after surgical repair.

[0023] Variables including the variables listed above are quantifiable and can be directly measured or estimated before or during surgery. Further, the variables relate to the post-operative function of the valve, for example according to mechanical physical laws. The workflow described herein can provide a clinician with a quantitatively determined pattern for use in cutting a piece of material used to reconstruct a biological valve, such that patient-specific features and dimensions of the valve are achieved post-operatively when the valve is operating under physiological conditions. As will be appreciated by those skilled in the art, in some embodiments, the pattern may be configured to reconstruct the valve such that a desired coaptation height and / or area is achieved between two or more leaflets of the valve.

[0024] According to one embodiment, the engineering workflow method may include utilizing a quantitative description of the mechanical properties of the material used for the reconstructed valve to determine the size and / or shape of the reconstructive material, such that after implantation, the reconstructive material is configured to repair the biological valve so that the valve is appropriately configured to operate in a desired operating state in a given patient.

[0025] For example, in some embodiments, a method of preparing an implantable material (e.g., for use by a clinician when repairing a biological valve) is disclosed. The method may include obtaining a target configuration of the implantable material. The target configuration may include target size, target shape, target maximum and / or minimum elasticity, target deformation characteristics, coaptation height and / or area (e.g., the overlapping height and / or area between two or more leaflets that make up the reconstructed valve), curvature, angle relative to the periphery, tissue strength, and / or other suitable metrics. The method may further include obtaining one or more characteristics (e.g., mechanical characteristics) of the biological valve to be reconstructed.

[0026] One or more features of a bioprosthetic valve may include size, shape, elastic profile, stress-strain relationship of the bioprosthetic valve, joint height and / or area (e.g., overlapping height and / or area between two or more valve leaflets constituting the reconstructed valve), curvature, angle to the periphery, tissue strength, and / or other appropriate features. In connection with this, features of the implantable material (e.g., mechanical features) such as size, shape, elastic profile, stress-strain relationship of the implantable material, joint height and / or area (e.g., overlapping height and / or area between two or more valve leaflets constituting the reconstructed valve), curvature, angle to the periphery, tissue strength, and / or other appropriate features can be obtained.

[0027] Next, the pattern (for example, for cutting the implantable material) can be determined at least in part on the target configuration of the implantable material, the characteristics of the bioprosthetic valve, and the characteristics of the implantable material. In some embodiments, this method can be embodied by a non-temporary computer-readable storage medium containing processor-executable instructions that, when executed, implement the method disclosed herein.

[0028] As those skilled in the art will understand, the characteristics of bioprosthetic valves and / or implantable materials (e.g., size, shape, elastic profile, and / or stress-strain relationship) can be obtained by any suitable method. For example, in some cases, characteristics can be measured using mechanical tools (e.g., calipers, rulers, measuring tapes, etc.). In other cases, characteristics may be obtained electronically.

[0029] For example, a computer model of a relevant structure (e.g., a bioprosthetic valve or implantable material) can be generated so that relevant measurements can be obtained. While the computer model is generally constructed as a three-dimensional model, embodiments including two-dimensional computer models are also conceivable. Needless to say, this disclosure is not limited in this respect, and features can be obtained in other appropriate ways depending on the application.

[0030] As those skilled in the art will understand, the stress-strain relationship of bioprosthetic valves and / or implantable materials can be obtained by any suitable method. For example, in some embodiments, the stress-strain relationship of bioprosthetic valves and / or implantable materials involves relating the force per unit cross section of the bioprosthetic valve and / or implantable material to a measured mean deformation normalized to the size of the bioprosthetic valve and / or implantable material, respectively.

[0031] Alternatively or additionally, the stress-strain relationships of bioprosthetic valves and / or implantable materials can be obtained in various regions of the bioprosthetic valves and / or implantable materials, respectively. For example, in some embodiments, bioprosthetic valves and / or implantable materials may exhibit anisotropic material properties (e.g., a bioprosthetic valve and / or implantable material may have a direction in which each stress-strain relationship exhibits maximum in-plane stiffness compared to all other directions). Thus, in some embodiments, the stress-strain relationships of bioprosthetic valves and / or implantable materials can be obtained in two or more different directions (e.g., axes).

[0032] As those skilled in the art will understand, the stress-strain relationship of bioprosthetic valves and / or implantable materials can be measured using manual qualitative and quantitative measurements. In some embodiments, the stress-strain relationship of bioprosthetic valves and / or implantable materials can be measured using either contact or non-contact measurement methods known in the art. Needless to say, this disclosure is not limited in this respect, and the stress-strain relationship of bioprosthetic valves and / or implantable materials can be measured by any suitable method depending on the application.

[0033] In some embodiments, one or more characteristics of the bioprosthetic valve and / or implantable material may be measured preoperatively and / or during surgery. Once a pattern is determined, it can be used as a template for cutting or otherwise shaping the implantable material before or during surgery. The implantable material can be cut in any suitable way. For example, in some embodiments, the material can be cut by one or more of the following tools: scissors, knives, scalpels, laser cutters, electrochemical cutters, die cutters, and / or any other suitable tools.

[0034] In some specific embodiments, the implantable material may be laser-cut into a predetermined pattern. In some embodiments, the pattern may be projected onto the implantable material by a projector or other suitable display to indicate how the material should be cut (e.g., using light or other suitable medium). Needless to say, the disclosure is not limited in this respect, and the implantable material may be cut by other suitable methods, including both automated and / or manual processes.

[0035] As described herein, patterns of implantable materials may be configured to function in a variety of and / or changing physiological states within a given patient. For example, in the context of heart valves, physiological states may include atrial systole, atrial diastole, ventricular systole, ventricular diastole, and / or any other appropriate physiological state. Furthermore, in some embodiments, the pattern may be configured so that the reconstructed valve maintains function under both high stress (e.g., high heart rate and / or blood pressure) and low stress (e.g., low heart rate and / or blood pressure).

[0036] Alternatively or additionally, physiological conditions may include expected patient growth (e.g., stretching of the valve and / or around the valve due to patient growth and / or aging). Needless to say, this disclosure is not limited in this respect, and the functionality of the heart valve under other physiological conditions will also be considered, depending on the application.

[0037] The workflow described here includes specifications for the function of a reconstructed valve operating under physiological conditions. For example, in some embodiments, the functional valve may function to selectively separate a high-pressure biological area from a low-pressure biological area. The functional valve may be able to take on both closed and open configurations.

[0038] A functional valve can separate two or more regions in a closed configuration, while in an open configuration, it can allow open fluid communication between two or more regions. In some embodiments, the functional valve is passive and opens and closes in response to external pressure.

[0039] For example, a valve may open due to the pressure difference created when an adjacent cardiac chamber (e.g., the left ventricle in the case of the aorta) contracts. In relation to this, in some embodiments, when an adjacent cardiac chamber relaxes, back pressure between the regions may function to close the functional valve. Furthermore, the functional valve may be able to open rapidly to prevent pressure and / or flow loss between the regions. In some embodiments, the functional valve may not obstruct other biological structures (e.g., coronary ossae) during opening and closing.

[0040] In some embodiments, it may be desirable that the implantable material used for the reconstructed valve be configured to adapt to the patient's growth. For example, in some cases, a bioprosthetic valve may be reconstructed in a pediatric patient using an implantable material that can function in the patient's body until the patient is fully grown or for another appropriate period. Thus, in such embodiments, the implantable material used for valve reconstruction may be oversized to adapt to the patient's growth (while maintaining, for example, the functions described herein).

[0041] In some embodiments, the method may include acquiring (e.g., measuring) the characteristics of the reconstructed bioprosthetic valve and / or the surrounding tissue of the bioprosthetic valve under various physiological conditions. In particular, in some embodiments, the target configuration of the implantable material (e.g., as described herein) can be based at least in part on the acquired characteristics of the reconstructed bioprosthetic valve and / or its surrounding tissue under various physiological conditions. Therefore, it may be desirable to measure the characteristics of the bioprosthetic valve and / or its surrounding tissue under a static state (e.g., without stress or pressure).

[0042] Therefore, the resting state of the bioprosthetic valve and / or its surrounding tissue can be compared to the resting state (e.g., unstressed or under no pressure) of the implantable material to determine an appropriate target configuration, for example, as described herein. Needless to say, the characteristics of the bioprosthetic valve and / or its surrounding tissue can be obtained under any suitable physiological conditions depending on the application, and this disclosure is not limited in this respect.

[0043] As those skilled in the art will understand, the characteristics of the reconstructed bioprosthetic valve and / or the surrounding tissue of the bioprosthetic valve under various physiological conditions can be measured by any suitable method. In some embodiments, the characteristics of the reconstructed bioprosthetic valve and / or the surrounding tissue of the bioprosthetic valve can be measured using magnetic resonance imaging, computed tomography, in vivo imaging, ultrasound, three-dimensional scanners, optical detection and ranging systems, other methods for generating three-dimensional images, mechanical testing, and / or other suitable characterization methods.

[0044] Needless to say, this disclosure is not limited in this respect, and the characteristics of the reconstructed bioprosthetic valve and / or the surrounding tissue of the bioprosthetic valve under various physiological conditions may be measured by other appropriate methods depending on the application.

[0045] Certain non-limiting embodiments are described in further detail with reference to the drawings. Since this disclosure is not limited to the specific embodiments described herein, it should be understood that the various systems, components, features, and methods described in relation to these embodiments may be used individually and / or in any desired combination.

[0046] Figure 1A shows a normal (e.g., defect-free) aortic valve 100 according to the prior art. When a normal aortic valve 100 is closed and pressurized at physiological levels of diastolic pressure, such a normally functioning valve may have one or more valve leaflets 1 arranged to bond or join with adjacent leaflets to form a non-breakable seal 2. The seal 2 can be selectively opened under any suitable conditions, including those described herein.

[0047] Figure 1B shows a side view of the aortic valve 100, showing a cross-section of the aortic valve 100 cut at the cutting line 1B-1B shown in Figure 1A. As shown in Figure 1B, a closed valve 100 separates the high-pressure region of the aortic root 3 from the low-pressure region of the left ventricle 4. A well-functioning valve may exhibit a minimum junction height A near the overlap point 5. This is the distance at which adjacent valve leaflets overlap. Alternatively or additionally, a well-functioning valve may have an occluding leaflet whose free end forms a downward angle 6 (referred to herein as the free-end angle) from its attachment point to the aortic root 3 toward the left ventricle of the patient's heart.

[0048] Referring to Figure 2, the target specifications of a reconstructed valve under physiological loading conditions can be based at least partially on the free end angle 7 and the height of the inter-leaflet joint (e.g., overlap) 8. The goals of the valve reconstruction workflow described herein include calculating the shape 9 that can be cut (e.g., in an operating room) of implantable material in a static, stress-free state to achieve the target closure valve configuration under the physiological conditions of a particular patient (e.g., as described herein). To determine the pattern, the change in the dimensions of the valve leaflets of the reconstructed valve can be calculated from the pressurized state. From there, the target dimensions of the valve are obtained by comparing them to the unpressurized or static state from which the implantable material needs to be cut.

[0049] For example, in some embodiments, a finite element method may be used to obtain the valve target dimensions, which may be based on a numerical approximation of the equations of continuous mechanics. Alternatively or additionally, a mechanical model of a solid structure using a network of masses and springs may also be used. Needless to say, this disclosure is not limited in this respect, and the valve target dimensions may be obtained by any suitable method depending on the application.

[0050] Such exemplary methods for obtaining structural deformation data may be applied to models of valves in a static or unstressed state to obtain stresses and strains throughout the valve in response to applied loads and / or deformations. In some embodiments of the workflows described herein, the goal is to calculate the static configuration of the valve structure after the load has been removed, for example by applying the inverse finite element method. The discrete mass spring method can also be applied using this inverse modeling approach, but other approaches are contemplated as this disclosure is not limited thereto.

[0051] Referring again to Figure 2, the disclosed method for obtaining the static configuration of the valve structure can be based on a quantitative description of the mechanical properties 10 of the transplantable material used to reconstruct the valve. The mechanical properties of such a material can be expressed in the form of a constitutive equation relating stress, i.e., the force per unit cross-section of the material, to strain, which is a measure of deformation normalized to the size of the structure (e.g., average deformation in a particular direction or axis).

[0052] This stress-strain relationship can be determined experimentally using established mechanical testing procedures. In some cases, in the workflow proposed herein, the stress-strain relationship of the implantable material used to reconstruct the valve may be obtained from published data or experiments performed before surgery. Alternatively or additionally, the stress-strain relationship of the implantable material used to reconstruct the valve may be estimated at the time of surgery.

[0053] The stress-strain relationship of implantable materials used in heart valve reconstruction is generally anisotropic, meaning that there exists a direction within the material in which the stress-strain relationship exhibits maximum in-plane stiffness compared to all other material directions. This direction of maximum in-plane stiffness is called the principal material direction. Therefore, changing the orientation of the principal material direction of the material or material piece implanted at the valve root can change the direction in which the material deforms least relative to the implantation site.

[0054] The workflow proposed herein involves specifying the primary material orientation of the material used for reconstruction relative to the reference orientation of the innate structure at the transplantation site (e.g., the innate bioprosthetic valve). Alternatively or additionally, the primary material orientation of the transplantable material or a portion thereof used for valve reconstruction may be configured to determine the orientation of the primary material orientation that results in the expected valve function.

[0055] Referring again to Figure 2, the methods herein for obtaining a stationary valve configuration may include a quantitative description of the size and shape around the innate valve (e.g., aortic root) of a given patient to which the implantable material or a portion thereof will be implanted. This quantitative description may include, for example, a series of discrete measurements of the features of the aortic root 11 of a given patient. Alternatively or additionally, the measurements may take the form of a three-dimensional model of the anatomical structure of the aortic root 11 of the patient.

[0056] The methods herein for obtaining the static configuration of the valve may also include a quantitative description 12 of the mechanical properties of the aortic root 11 of a given patient. With regard to the stress-strain relationship of the implantable material used for valve reconstruction, the stress-strain relationship of the aortic root 11 of the patient can be obtained from published data or experiments performed before surgery, the disclosure in this regard is not so limited, it can be estimated at the time of surgery, or obtained by other appropriate means.

[0057] As described herein, the size and shape of the implantable material or part thereof used to reconstruct the valve may be calculated based on a number of inputs. Such inputs include: a set of quantitative features describing a target configuration or multiple target configurations of the valve under physiological conditions; a set of discrete measurements of features around the patient (e.g., the patient's aortic root); stress-strain relationships around the patient (e.g., the patient's aortic root); stress-strain relationships of the implantable material or part thereof used to reconstruct the valve; and / or other appropriate parameters.

[0058] In some embodiments, the workflow output includes a pattern or multiple patterns of the implantable material or a portion thereof. Alternatively or additionally, further output may include the angular orientation of the pattern or multiple patterns relative to the primary material direction of the implantable material (e.g., in the case of anisotropic implantable material).

[0059] In pediatric valve repair, the durability of conventionally surgically reconstructed valves may be limited by the patient's growth. Specifically, as the pediatric patient's natural aortic root grows, the reconstructed valve leaflets attached to it may not grow. Therefore, in some cases, the reconstructed valve leaflets may be pulled away from the center of the valve root and from each other. Such detachment may continue as the patient grows until the valve leaflets of the reconstructed valve can no longer properly fuse together, potentially resulting in a dysfunctional or leaky valve.

[0060] Referring again to Figure 2, in the case of a growing child, the workflow described here can be applied, and as a result, the target configuration of the reconstructed valve is associated with a valve configuration of a size corresponding to the patient's predicted size following the patient's target growth rate 13. The exemplary computational modeling method described herein can be used to calculate the valve configuration in a stress-free state for the patient's predicted size following the patient's target growth rate 13.

[0061] When determining the pattern of a transplantable material or part thereof, it may be desirable to transform the valve leaflet configuration under stress-free conditions, and the inverse modeling method described herein can be used to fabricate a planar shape that can be traced or applied as a pattern on the material used to reconstruct the valve.

[0062] This step, referred to herein as planarization, can be achieved using exemplary computational mechanics approaches, such as the finite element method described herein, which can explain the mechanical properties of the material in the planarization process. Alternatively or additionally, computer graphics techniques can also be used, which include methods for approximating and / or ignoring the mechanical properties of the material.

[0063] In some embodiments, pattern determination may be obtained by searching a parameter space of all possible shapes, sizes, and / or directions. The parameter space may be constructed considering the desired values ​​of the joint and / or the degree of patient growth.

[0064] The pattern of the material piece used for valve reconstruction can be transferred to the material using any suitable method. Referring again to Figure 2, one or more patterns can be projected directly onto the implantable material using a laser 14 or other light-based projector. Alternatively or additionally, the pattern can be used to fabricate a physical template that can be used with a sterile marker or other method of transferring the pattern onto the implantable material.

[0065] In either case, after the pattern is projected onto the implantable material, the implantable material can be cut to provide the desired patterned implantable material. For implantable materials having anisotropic mechanical properties, the pattern of each piece can be aligned with respect to the main material direction of the material from which the piece or more pieces are cut.

[0066] Additional outputs of the workflows described herein may include instructions used to implant the implantable material into the patient. If one or more portions are implanted with sutures, the workflow output may include specifications of patterns for where the sutures are placed on the implantable material and where the corresponding sutures are placed in the patient.

[0067] In some cases, sutures may advance at different rates on one implantable material, on another implantable material, and / or within the patient's body (for example, to guide a predictable three-dimensional shape of the reconstructed valve, or to incorporate redundancy between one material and the other within the suture line).

[0068] The workflows disclosed herein can be embodied as methods. Figure 3 shows one such exemplary method. In step 300, the target mechanical characteristics of the bioprosthetic valve are obtained. In step 302, the current mechanical characteristics of the bioprosthetic valve are obtained (e.g., in a defective state). In step 304, one or more mechanical characteristics of the implantable material (e.g., the material used to repair the bioprosthetic valve) are obtained.

[0069] In step 306, the pattern of the implantable material is determined based at least in part on the acquired target features, bioprosthetic valve features, and implantable material features. Then, in step 308, the implantable material is cut according to the determined pattern. In some cases, this may include projecting the pattern onto the implantable material, as described above.

[0070] The methods described herein can be carried out in any suitable manner. For example, in some cases, the method may be carried out using one or more processors configured to perform the steps described herein. Alternatively or additionally, the method may be embodied as processor-executable instructions stored in a non-temporary computer-readable medium.

[0071] As described herein, the disclosed workflow can be used to produce quantitatively fitted implantable material pieces 400 for the reconstruction of bioprosthetic valves. Figure 4 shows one such example. In particular, the first end 404 of the implantable material piece 400 can be fitted to overlap sufficiently with the other parts of the bioprosthetic valve in question, as described herein.

[0072] Furthermore, the second end 406 of the implantable material piece 400 opposite the first end 404 may be fitted to conform to the valve and surrounding tissue at an appropriate angle, as described herein. Furthermore, as described herein, the implantable material piece 400 may include indicator marks 402 that provide a pattern for where the clinician sutures the implantable material piece in the patient's body.

[0073] The embodiments of the technology described herein can be implemented in any of many ways. For example, the embodiments can be implemented using hardware, software, or a combination thereof. If implemented in software, the software code can run on any suitable processor or set of processors, whether provided on a single computing device or distributed across multiple computing devices.

[0074] Such processors can be implemented as integrated circuits, which include one or more processors within an integrated circuit component, including commercially available integrated circuit components known in the art as CPU chips, GPU chips, microprocessors, microcontrollers, or coprocessors.

[0075] Alternatively, the processor can be implemented in custom circuitry such as ASICs, or in semi-custom circuitry derived from the configuration of programmable logic devices. Yet another alternative is that the processor may be part of a larger circuit or semiconductor device, whether commercial, semi-custom, or custom. For example, some commercial microprocessors have multiple cores, and one or a subset of those cores can constitute the processor. However, the processor can be implemented using any suitable form of circuitry.

[0076] Furthermore, a processor may have one or more input / output devices. These devices can, among other things, be used to display a user interface. Examples of output devices that can be used to provide a user interface include display screens for visually displaying output and speakers or other speech-generating devices for audibly displaying output. Examples of input devices that can be used for a user interface include keyboards, individual buttons, and pointing devices such as mice, touchpads, and digitizing tablets. As another example, a computing device may receive input information in the form of speech recognition or other audible forms.

[0077] Such processors can be interconnected by one or more networks of any suitable form, including local area networks or wide area networks such as corporate networks or the Internet. Such networks can be based on any suitable technology, operate according to any suitable protocol, and may include wireless networks, wired networks, or fiber optic networks.

[0078] Furthermore, the various methods or processes outlined herein can be coded as software executable on one or more processors using a variety of operating systems or platforms. Moreover, such software can be written using a number of suitable programming languages ​​and / or programming or scripting tools, and can also be compiled as executable machine code or intermediate code that runs on a framework or virtual machine.

[0079] In this regard, embodiments described herein may be embodied as computer-readable storage media (or more computer-readable media) encoded by one or more programs that, when executed on one or more computers or other processors, perform methods for implementing the various embodiments described above (e.g., computer memory, one or more floppy disks, compact discs (CDs), optical discs, digital video discs (DVDs), magnetic tape, flash memory, RAM, ROM, EEPROM, semiconductor devices such as circuit configurations of field-programmable gate arrays, or other tangible computer storage media).

[0080] As is evident from the examples above, a computer-readable storage medium can hold enough time information to provide computer-executable instructions in a non-temporary form. Such a computer-readable storage medium may be portable, and as a result, programs stored therein can be loaded onto one or more different computing devices or other processors to implement the various embodiments of the present disclosure described above.

[0081] As used herein, the term “computer-readable storage medium” encompasses only non-transient computer-readable media that can be considered as a product (i.e., manufactured goods) or machine. Alternatively or additionally, this disclosure may be embodied as computer-readable media other than computer-readable storage medium, such as propagated signals.

[0082] The terms “program” or “software” are used herein in a general sense and refer to any type of computer code or set of computer executable instructions that can be used to program a computing device or other processor for implementing the various aspects of the present disclosure described above. Furthermore, it should be understood that, according to one aspect of this embodiment, one or more computer programs that perform the methods of the present disclosure at runtime do not need to reside on a single computing device or processor, but may be distributed in a modular manner across a number of different computers or processors for implementing the various aspects of the present disclosure.

[0083] Computer executable instructions can take many forms, including program modules executed by one or more computers or other devices. Generally, program modules include routines, programs, objects, components, and data structures that perform specific tasks or implement specific abstract data types. Typically, the functions of program modules can be combined or distributed as needed in various embodiments.

[0084] Various aspects of this disclosure can be used individually, in combination, or in various configurations not specifically described in the embodiments described above, and therefore their application is not limited to the details and arrangement of components shown in the foregoing description or drawings. For example, an aspect described in one embodiment can be combined in any way with an aspect described in another embodiment.

[0085] The embodiments described herein can be embodied as methods, and an example thereof is provided. The operations performed as part of the method can be ordered in any suitable manner. Thus, although shown as sequential operations in the exemplary embodiments, embodiments can be constructed in which the operations are performed in a different order than shown, which may include performing several operations simultaneously.

[0086] Furthermore, some actions are described as being performed by a “user.” It should be understood that a “user” does not necessarily have to be a single individual; in some embodiments, actions attributed to a “user” may be performed by a team of individuals and / or individuals in combination with computer-aided tools or other mechanisms.

[0087] The use of ordinal terms such as “first,” “second,” and “third” to modify claim elements in the claims does not, in itself, imply priority, order, or temporal sequence of one claim element relative to another, but rather serves only as labels to distinguish one or more claim elements with a particular name from another element with the same name, even though the action of the method is performed on them (however, due to the use of ordinal numbers).

[0088] Furthermore, the expressions and terms used herein are for illustrative purposes only and should not be considered limiting. The use of “includes,” “contains,” “has,” “contains,” “involves,” and variations thereof herein means that the items listed thereafter and their equivalents, as well as additional items, are included.

[0089] While this instruction has been described in relation to various embodiments and examples, it is not intended to be limited to such embodiments or examples. On the contrary, as those skilled in the art will understand, this instruction encompasses a variety of alternatives, modifications, and equivalents. Therefore, the foregoing description and drawings are merely illustrative.

Claims

1. A method for preparing transplantable material, which includes: To obtain the target configuration of the bioprosthetic valve; To obtain one or more characteristics of the reconstructed bioprosthetic valve; To obtain one or more mechanical properties of a transplantable material; and The method comprising determining a pattern of implantable material configured to reconstruct a bioprosthetic valve, at least in part on a target configuration, one or more features of a bioprosthetic valve, and one or more mechanical features of the implantable material.

2. The method according to claim 1, wherein obtaining a target configuration of a bioprosthetic valve includes obtaining a target size and / or shape of an implantable material.

3. The method according to claim 1 or 2, further comprising cutting the implantable material into a determined pattern.

4. The method according to any one of claims 1 to 3, wherein measuring one or more characteristics of the reconstructed bioprosthetic valve includes measuring one or more characteristics of the bioprosthetic valve in a resting state.

5. The method according to any one of claims 1 to 4, wherein measuring one or more features of the bioprosthetic valve to be reconstructed is a means of constructing a three-dimensional model of the bioprosthetic valve.

6. The method according to any one of claims 1 to 5, wherein measuring one or more features of the reconstructed bioprosthetic valve is a means of obtaining the stress-strain relationship of the bioprosthetic valve.

7. The method according to any one of claims 1 to 6, wherein the pattern is further configured to improve the postoperative function of the bioprosthetic valve, based at least in part on the three-dimensional spatial geometric shape of the bioprosthetic valve, the mechanical characteristics of the bioprosthetic valve, the mechanical characteristics of the implantable material, the size of the implantable material, the shape of the implantable material, and / or the orientation of the implantable material.

8. The method according to any one of claims 1 to 7, wherein obtaining one or more mechanical characteristics of the transplantable material includes obtaining the stress-strain relationship of the transplantable material.

9. The method according to claim 8, wherein obtaining a stress-strain relationship of the transplantable material involves relating the force per unit cross section of the transplantable material to a measured value of the average deformation normalized with respect to the size of the transplantable material.

10. The method according to claim 8, wherein obtaining the stress-strain relationship of the transplantable material includes obtaining stress-strain measurements of the transplantable material in two or more different directions.

11. The method according to claim 1, wherein the implantable material is anisotropic.

12. The method according to claim 6, wherein obtaining the stress-strain relationship of a bioprosthetic valve involves relating the force per unit cross-section of the bioprosthetic valve to a measured value of the average deformation normalized with respect to the size of the bioprosthetic valve.

13. The method according to claim 6, wherein obtaining the stress-strain relationship of a bioprosthetic valve includes obtaining stress-strain measurements of the bioprosthetic valve in two or more different directions.

14. The method according to claim 1, wherein the bioprosthetic valve is anisotropic.

15. The method according to any one of claims 1 to 4, further comprising projecting the determined pattern onto a transferable material.

16. The method according to any one of claims 1 to 15, wherein the biological valve is configured to separate a high-pressure biological region from a low-pressure biological region.

17. A patterned, implantable material prepared according to the method described in any one of claims 1 to 16.

18. The method according to any one of claims 1 to 17, further comprising the step of obtaining one or more characteristics of the patient's growth, wherein the pattern determination is further based at least in part on the characteristics of the patient's growth.

19. The method according to claim 18, wherein determining the pattern based at least in part on the growth characteristics of the patient includes oversizing the pattern.

20. A non-temporary computer-readable storage medium containing processor-executable instructions, which, when executed, performs the following steps: To obtain the target configuration of the bioprosthetic valve; To obtain one or more characteristics of the reconstructed bioprosthetic valve; To obtain one or more mechanical properties of a transplantable material; and A non-temporary computer-readable storage medium that performs a method for preparing an implantable material, comprising determining a pattern of implantable material configured to reconstruct a bioprosthetic valve, based at least in part on a target configuration, one or more features of a bioprosthetic valve, and one or more mechanical features of the implantable material.

21. The method according to claim 20, wherein obtaining a target configuration of a bioprosthetic valve includes obtaining a target size and / or shape of an implantable material.

22. The method according to claim 20 or 21, further comprising cutting the implantable material into a determined pattern.

23. The method according to any one of claims 20 to 22, wherein measuring one or more characteristics of the reconstructed bioprosthetic valve includes measuring one or more characteristics of the bioprosthetic valve in a resting state.

24. The method according to any one of claims 20 to 23, wherein measuring one or more features of the bioprosthetic valve to be reconstructed is a means of constructing a three-dimensional model of the bioprosthetic valve.

25. The method according to any one of claims 20 to 24, wherein measuring one or more features of the reconstructed bioprosthetic valve is a means of obtaining the stress-strain relationship of the bioprosthetic valve.

26. The method according to any one of claims 20 to 25, wherein the pattern is further configured to improve the postoperative function of the bioprosthetic valve, based at least in part on the three-dimensional spatial geometric shape of the bioprosthetic valve, the mechanical characteristics of the bioprosthetic valve, the mechanical characteristics of the implantable material, the size of the implantable material, the shape of the implantable material, and / or the orientation of the implantable material.

27. The method according to any one of claims 20 to 26, wherein obtaining one or more mechanical properties of the implantable material is a means of obtaining the stress-strain relationship of the implantable material.

28. The method according to claim 27, wherein obtaining a stress-strain relationship of the transplantable material involves relating the force per unit cross section of the transplantable material to a measured value of the average deformation normalized with respect to the size of the transplantable material.

29. The method according to claim 27, wherein obtaining the stress-strain relationship of the transplantable material includes obtaining stress-strain measurements of the transplantable material in two or more different directions.

30. The method according to any one of claims 20 to 29, wherein the implantable material is anisotropic.

31. The method according to claim 25, wherein obtaining the stress-strain relationship of a bioprosthetic valve involves relating the force per unit cross-section of the bioprosthetic valve to a measured value of the average deformation normalized with respect to the size of the bioprosthetic valve.

32. The method according to claim 25, wherein obtaining the stress-strain relationship of a bioprosthetic valve includes obtaining stress-strain measurements of the bioprosthetic valve in two or more different directions.

33. The method according to any one of claims 20 to 32, wherein the bioprosthetic valve is anisotropic.

34. The method according to any one of claims 20 to 33, comprising projecting the determined pattern onto a transferable material.

35. The method according to any one of claims 20 to 34, wherein the bioprosthetic valve is configured to separate a high-pressure biological region from a low-pressure biological region.

36. A patterned, implantable material prepared according to the method described in any one of claims 20 to 35.

37. The method according to any one of claims 20 to 36, further comprising the step of obtaining one or more characteristics of the patient's growth, wherein the pattern determination is further based at least in part on the characteristics of the patient's growth.

38. The method according to claim 37, wherein determining the pattern based at least in part on the growth characteristics of the patient includes oversizing the pattern.

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