Apparatus and method for producing a biocompatible three-dimensional object

Abstract

A method for making a biocompatible three-dimensional heart valve includes delivering, using at least one delivery unit, a biocompatible fluid substance towards a mold having a mold surface to obtain a coating layer of predetermined thickness that coats the mold surface, where the biocompatible fluid substance includes a plurality of particles; handling the mold and the delivery unit to provide a relative movement with at least three degrees of freedom between the mold and the delivery unit, the mold coated with the biocompatible fluid substance that is delivered to obtain a three-dimensional heart valve having a surface corresponding to the mold surface; removing, using a suction and blowing device, from the mold any surplus particles of the biocompatible fluid substance dispensed to make uniform the predetermined thickness of the coating layer; and pressing a counter mold on the coating layer deposited on the mold after delivering the biocompatible fluid substance.

Claims

1. A method for making a biocompatible three-dimensional heart valve, the method comprising: delivering, using at least one delivery unit, at least one biocompatible fluid substance towards a mold having a mold surface to obtain a coating layer of predetermined thickness configured for coating the mold surface, the biocompatible fluid substance including a plurality of particles; handling with a handling unit the mold and the delivery unit to provide a relative movement with at least three degrees of freedom between the mold and the delivery unit, the mold coated with the at least one biocompatible fluid substance that is delivered, to obtain a three-dimensional heart valve having a surface corresponding to the mold surface; removing, using a single suction and blowing device, from the mold any surplus particles of the at least one biocompatible fluid substance dispensed to make uniform the predetermined thickness of the coating layer; and pressing a counter-mold on the coating layer deposited on the mold after delivering the biocompatible fluid substance.

2. The method of claim 1, further comprising determining a size and geometry of the heart valve.

3. The method of claim 2, wherein determining the size of the heart valve is achieved by scanning.

4. The method of claim 3, wherein the scanning is selected from the group consisting of CT, FL, DR and MRI.

5. The method of claim 2, wherein the geometry of the heart valve is selected from the group consisting of narrow orifice, symmetrical leaflets and asymmetrical leaflets.

6. The method of claim 2, further comprising producing, using a computer processor, a virtual three-dimensional model of the heart valve.

7. The method of claim 6, further comprising creating the mold and the counter-mold based on the virtual three-dimensional model of the heart valve.

8. The method of claim 1, wherein the at least one biocompatible fluid substance is selected from the group consisting of biocompatible polymeric resin, elastomer biomaterial, polyurethane, and silicone.

9. The method of claim 1, further comprising curing and drying the mold coated with the at least one biocompatible fluid substance in situ.

10. The method of claim 9, further comprising sterilizing the dry mold coated with the at least one biocompatible fluid substance.

11. The method of claim 10, further comprising extracting the dry mold coated with the at least one biocompatible fluid substance from the counter-mold.

12. The method of claim 11, further comprising removing a dry layer of the biocompatible fluid substance from the mold.

13. The method of claim 1, further comprising delivering a plurality of biocompatible fluid substances towards the mold using a plurality of delivery units.

14. The method of claim 1, wherein the heart valve is selected from the group consisting of a bicuspid valve, single leaflet valve, bileaflet valve, cage and ball valve, and tilting disc valve.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The present disclosure will be now shown with the following description of some exemplary embodiments thereof, exemplifying but not limitative, with reference to the attached drawings in which:

(2) FIG. 1 shows an exemplary embodiment of an apparatus including an anthropomorphic robot arranged to handle the support body;

(3) FIG. 2 shows an exemplary embodiment of an apparatus, which differs from that of FIG. 1 for the presence of a toroidal hood arranged to surround the support body;

(4) FIG. 3 shows an exemplary embodiment of the apparatus, which differs from that of FIG. 2 since the handling unit the support body does not include an anthropomorphic robot, but a plurality of linear actuators;

(5) FIG. 4 shows a counter-mold that allows a hot molding of the coating layer;

(6) FIG. 5 shows a three-dimensional object resulting from the production process;

(7) FIG. 6A shows a cardiac chamber with a heart patch applied to it; and

(8) FIG. 6B shows a support from which the heart patch of FIG. 6A is generated.

(9) FIG. 7 shows an example of workstation for a three-dimensional spraying system including the anthropomorphic robot;

(10) FIGS. 8A and 8B show an exemplary embodiment of an apparatus including an anthropomorphic robot arranged to handle a 3D mold of a heart valve and an exploded view of the 3D mold;

(11) FIG. 9 shows a flow chart for one embodiment of a method for creating a 3D heart valve;

(12) FIGS. 10A and 10B show an example of a heart valve having asymmetric leaflets;

(13) FIGS. 11A and 11B show an example of a heart valve having a narrow orifice;

(14) FIGS. 12A and 12B show an example of a heart valve having symmetric leaflets;

(15) FIGS. 13A and 13B show an one example of an exploded view of a heart valve and stent on a mold and inserted into a mandrel for pressing a counter-mold against the heart valve on the mold.

DETAILED DESCRIPTION

(16) Each of the features and teachings disclosed herein can be utilized separately or in conjunction with other features and teachings to provide an apparatus for and method for producing a biocompatible object. Representative examples utilizing many of these additional features and teachings, both separately and in combination are described in further detail with reference to the attached figures. This detailed description is merely intended to teach a person of skill in the art further details for practicing aspects of the present teachings and is not intended to limit the scope of the claims. Therefore, combinations of features disclosed above in the detailed description may not be necessary to practice the teachings in the broadest sense, and are instead taught merely to describe particularly representative examples of the present teachings.

(17) In the description below, for purposes of explanation only, specific nomenclature is set forth to provide a thorough understanding of the present disclosure. However, it will be apparent to one skilled in the art that each of these specific details are not required to practice the teachings of the present disclosure.

(18) Moreover, the various features of the representative examples may be combined in ways that are not specifically and explicitly enumerated in order to provide additional useful embodiments of the present teachings. It is also expressly noted that all value ranges or indications of groups of entities disclose every possible intermediate value or intermediate entity for the purpose of original disclosure. It is also expressly noted that the dimensions and the shapes of the components shown in the figures are designed to help to understand how the present teachings are practiced, but not intended to limit the dimensions and the shapes shown in the examples. In this document, measurements, values, shapes, angles, and geometric references (such as perpendicularity and parallelism), when associated with words like about or other similar terms such as approximately or substantially, should be construed to allow for measurement errors or others errors due to production and/or manufacture process, and may vary by up to ten percent.

(19) With reference to FIG. 1, an exemplary embodiment of an apparatus 100 for making a biocompatible three-dimensional object 30 provides an anthropomorphic robot 132 having a kinematical chain of pivot joints 133. Such chain of joints 133 is constrained at an end to a fixed base 134, and at another end to a support base 131 on which support body 20 engages in a removable way. The chain of pivot joints 133 of FIG. 1 allows handling the support body according to six degrees of freedom, allowing an optimum precision when generating the sought three-dimensional object 30.

(20) In FIG. 1, three delivery units 110,111,112 are shown that are arranged to deliver three different biocompatible fluid substances. Fewer or more delivery units can be arranged to deliver biocompatible fluid substances. In particular, first delivery unit 110 is adapted to deliver a jet of a biomaterial of synthetic origin towards the support body 20. The second delivery unit 111 is, instead, arranged to deliver a jet of non-solvent, for example water, overlapping to the jet generated by first delivery unit 110, in order to induce a quick deposit of the biopolymeric material supplied onto support body 20 by first delivery unit 110, allowing to obtain a filamentous three-dimensional structure. The third delivery unit, finally, is adapted to deliver a third biocompatible fluid substance diluted in solution, in particular another biomaterial of synthetic or biological origin.

(21) Each delivery unit 110,111,112 also has a hydraulic circuit (not shown in the figure, for example, a cylinder-piston mechanism) consisting of ducts, with possible valves and pumps, which connect the or each delivery unit to reservoirs containing the biocompatible fluid substances.

(22) In this exemplary embodiment, a suction and/or blowing unit 120 is further provided, adapted to generate a suction and/or blowing current. This way, the suction and/or blowing unit 120 makes it possible to level the thickness of the coating layer 35 and to remove from support body 20 any surplus particles of the biocompatible fluid substances supplied by the or each delivery unit 110, 111, 112. The device 120 is also spatially moved by auxiliary moving means 140, in such a way that this device 120 can follow spatially the position of support body 20 during its handling steps by handling unit 130. In some embodiments, the base 134 of the handling unit 130 can be automated or free such that it is controlled by a user. Moreover, the structure of the handling unit 130 is not limited to the structure shown in the figures.

(23) In FIG. 2 a second exemplary embodiment is shown, which differs from an exemplary embodiment of FIG. 1 as from the type of the device 120. In this exemplary embodiment, device 120 includes a toroidal suction hood 121, which is integral to support base 131 and is configured to surround laterally support body 20. Toroidal hood 121 is then joined to a suction tube 122 arranged in turn to connect pneumatically the suction hood 121 with a suction system 123 that has a compressor to generate a suction flow and with a storage reservoir containing any surplus particles of the dispensed fluid substance.

(24) Alternatively, in an exemplary embodiment not shown in the figures, device 120 is a blowing device including a compressor adapted to generate a blowing current for removing any surplus particles of the delivered fluid substance. This way, it is not necessary that the apparatus includes auxiliary handling unit 140, like the exemplary embodiment of FIG. 1, since the toroidal hood 121 surrounds laterally the support body 20, whichever is the position reached by handling unit 130. However, in some embodiments, any surplus particles of the delivered fluid substance can be removed by laser or other abrading method.

(25) In FIG. 3 an exemplary embodiment is shown where handling unit 130, instead of including the anthropomorphic robot 132 of the previous figures, includes a plurality of linear actuators 133, each of which engages, at one end, to fixed base 134, and at another end, to support base 131. Support body 20 engages in a removable way with support base 131, like the previous exemplary embodiments. The handling unit can reach the same degrees of freedom of an anthropomorphic robot, even if with narrower handling range. The advantage offered by this solution is shown by a high reduction of the encumbrance.

(26) In FIG. 4 the step is shown of pressing, in particular to hot pressing, of the coating layer 35 deposited by the or each delivery unit 110,111,112, using a counter-mold 150. The coating layer 35 is then removed from support body 20 and becomes substantially the final biocompatible three-dimensional object 30, visible in FIG. 5.

(27) Owing to the hot pressing an optimum finishing of the shape of the three-dimensional object 30 can be achieved, in such a way that such shape is closest to the designed patch shape, for example provided by CAD or the like. Such pressing operation also gives to the three-dimensional object 30 mechanical improved features, reaching any design standards.

(28) The apparatus 100, as described above, and shown in FIGS. 1 to 5, provides biocompatible three-dimensional objects 30 of whichever shape. In particular, biocompatible three-dimensional objects 30 can be manufactured both of simple and regular shape, such as a tetrahedron or a cone, and of irregular shape and/or with surfaces which cannot worked out in a simple way, such as a concave or convex patch or an ellipsoidal patch. Furthermore, biocompatible three-dimensional objects 30 can be provided having surfaces with different radius of curvature and/or with different angles.

(29) In FIG. 6A a cardiac chamber of a human heart is shown to which a biocompatible three-dimensional object 30 is mounted, in particular a heart patch, consisting of an inner portion 30a and an external portion 30b.

(30) In FIG. 6B part of the apparatus 100 including the support 20 is shown, from which the inner portion 30a of the heart patch of FIG. 6A is generated.

(31) By way of example only, and not by way of limitation, a system for creating a heart valve will now be described. In one embodiment, FIG. 7 discloses a system 700 for making a synthetic, biocompatible three-dimensional (3D) heart valve 701 (shown in FIG. 13A). The system 700 includes an anthropomorphic robot 132 (e.g.; ABB IRB 120 industrial robot or the like), as described above, stationed on a workbench 712. The system also includes a 3D mold 702 mounted on a support body 20. In this example, the 3D mold 702 is for a heart valve, however, the mold maybe shaped to design for any other object. The anthropomorphic robot 132 also includes a chuck 131 to releasably hold the support body 20 and the 3D mold 702. Two spray guns 110 and 111, as described above, are also shown disposed on the workbench 712. However, a person skilled in the art can appreciate that a plurality of spray guns can be used depending on the desired heart valve structure. By way of example only, and not be way of limitation, the system may have up to 10 delivery units or spray guns. Also attached to the workbench 712 are two continuous pumps 704 and an air compressor 705. A chemical container 706 is also shown, and the chemical container 706 may store one or more biocompatible fluid substances, to be sprayed on the 3D mold 702. In certain embodiments, multiple containers may be used to store different biocompatible substances to be sprayed through one or both of the spray guns 110 and 111. The chemical container 706 is attached to one or both of the two continuous pumps 704. An electronic control unit 707 may be disposed on or near the workbench 712 and be in communication with the anthropomorphic robot 132. In one embodiment, the electronic control unit 707 may supply power and operating instructions to the anthropomorphic robot 132, pumps 704, air compressor 705, and/or spray guns 110 and 111. A suction and/or blowing unit 120 (not shown in FIG. 7) may also be provided with the system 700.

(32) FIG. 8A discloses a close up view of the top section of the system 700 including the anthropomorphic robot 132, the 3D mold 702, two spray guns 110 and 111, and a suction and/or blowing unit 120. As mentioned above, the anthropomorphic robot 132 includes a kinematical chain of pivot joints 133. Such chain of joints 133 is constrained at an end to a fixed base 134, and at another end to a support base 131 on which support body 20 engages in a removable way. The support base 131 may be a chuck in certain embodiments. The chain of pivot joints 133 allows handling of the support body according to six degrees of freedom, which in turn allows an optimum precision when generating the sought 3D heart valve 701.

(33) Moreover, as shown in FIG. 8A, two delivery units 110,111 of a spraying group are arranged to deliver two different biocompatible fluid substances. In particular, first delivery unit 110 is adapted to deliver a jet of a biomaterial of synthetic origin towards the 3D mold 702 in the same manner as described above with reference to spray coating the support body 20. The second delivery unit 111 is arranged to deliver a jet of non-solvent, for example, water, overlapping to the jet generated by the first delivery unit 110 in order to induce a quick deposit of the biopolymeric material supplied onto 3D mold 702 by the first delivery unit 110. Subsequently, obtaining a filamentous 3D structure of the desired heart valve 701.

(34) FIG. 8A also shows a suction and/or blowing unit 120 to generate suction and/or blowing current. By using the suction and/or blowing unit 120 the thickness of a coating layer on the 3D mold 702 can be levelled and surplus particles of the biocompatible fluid substances supplied by the each delivery unit 110 and 111 can be removed from support body 20. In one embodiment, the delivery units 110 and 111 are equipped with a 90 degree end axis in order to check the spraying process over a 3D valve shape. The delivery units 110 and 111 may move about an axis during the spraying process to create the 3D valve shape. FIG. 8B shows an exploded view of the 3D mold.

(35) As described above, the suction and/or blowing unit 120 is also spatially moved by auxiliary moving means 140, in such a way that this device 120 can follow spatially the position of 3D mold 702 during its handling steps by handling unit 130 (also as described above). In some embodiments, the suction and/or blowing unit 120 can host a removable platform for maintenance aims.

(36) According to one embodiment, FIG. 9 discloses a method 900 to make the synthetic, biocompatible 3D heart valve 701 of this example using the anthropomorphic robot 133. In one embodiment, the anthropomorphic robot may have three to six degrees of freedom.

(37) At the first step 901 of the method 900, a proper size and geometry of the heart valve 701 of the prospective patient is determined. In one embodiment, sizing the heart valve 701 is achieved by scanning (e.g.; via CT, FL, DR, MRI and the like) or visually inspecting the implantation site (i.e.; prospective patient's heart). The geometry of the heart valve is selected based on the desired characteristic of the heart valve 701 (shown in FIG. 13A). Such geometry may differ depending on the size and condition of the heart of the patient. For example, as shown in FIGS. 10A-10B, a heart valve 701 with asymmetrical leaflets geometry may be chosen. Such design geometry may offer improved valvular closure capability and may preserve opening efficiency. However, other geometrical designs (e.g. narrow orifice, symmetrical leaflets or the like) can be chosen for the heart valve 701 as well, depending on the desired characteristic. For example, as shown in FIGS. 11A-11B, a heart valve with a narrow orifice 1101 geometry may be chosen, which offers biocompatible design, simple leaflets geometry and good closure capability. On the other hand, as shown in FIGS. 12A-12B, a heart valve with a symmetrical leaflets design 1201 may be chosen, which may offer improved valve opening, since the warps in this design increases the surface of each leaflets. It should be understood that various designs may be chosen for the heart valve depending on the desired characteristics for the patient.

(38) Once the proper size and geometry of the desired heart valve 701 is determined, at the next step 902, a virtual 3D model 708 of the heart valve 701 is digitally produced. Although a 3D model 708 of the desired heart valve may be created by hand or other machinery, it is preferred to create a virtual 3D model 708 of the heart valve. In one embodiment, the virtual 3D model 708 may be created using 3D computer-aided design (CAD) software.

(39) At the next step 903, a 3D mold 702 and a counter mold 709 (FIG. 13B) may be created from the virtual 3D model 708. Different techniques, for example, 3D rapid prototyping process, vacuum casting, 3D printing, or the like, can be used to create the 3D mold 702 and the counter mold 709. In some embodiments, the mold and the counter mold can be made of steel to improve the quality of the 3D heart valve architecture.

(40) In some embodiments, a stent 710 can be placed on the 3D mold 702, in order to incorporate the stent into the inner walls of the 3D heart valve 701. A stent 710 incorporated with the heart valve 701 is best shown in the exploded view of FIG. 13A. The stent 710 can be incorporated into the heart valve 701 by forming a coating around the stent 710 and the 3D mold 702 during the spraying process to form the heart valve 701. In other embodiments, the stent 710 can be incorporated into the heart valve 701 after the heart valve 701 is created. This may be done by attaching the stent 710 inside or around the exterior surface of the heart valve 701. A stent 710 maintains the cross-sectional shape of the 3D heart valve 701 and can help secure the 3D heart valve 701 within the patient, e.g., by suturing the stent and valve in position within the patient. As shown in the figures, the cross-sectional shape of the heart valve is generally circular in shape at one end, however the cross sectional shape of the heart valve may take on other shapes. Stents usually are made of metal mesh, but sometimes they can be made of fabric.

(41) Next at step 904, a biocompatible fluid substance is sprayed onto the 3D mold 702 in order to deposit the biocompatible fluid substance on the surface of the 3D mold 702, and in certain embodiments, on the surface of a stent 710 too. The spraying of the biocompatible fluid substance onto the 3D mold 702 is shown in FIGS. 7 and 8. In this embodiment, different biocompatible fluids, for example, biocompatible polymeric resin, elastomer biomaterial, polyurethane, silicone based fluids, or the like can be used depending on the desired characteristics of the heart valve 701.

(42) Once the spraying step is complete, at the next step 905, as shown in FIG. 13A, the 3D mold 702 including the coating forming the heart valve 701, and the stent 710 in certain embodiments, is removed from the chuck 131 of the robot 132 and is inserted in a mandrel 714 including the counter mold 709. The mandrel 714 will accept the mold 702 in a recess.

(43) Once inserted into the mandrel 714, at step 906, jaws 713 of the counter mold 709 are moved from the edge of the mandrel 714 towards the 3D mold 702 via the slots 711 of the mandrel 714 and pressed against the newly created valve on the 3D mold 702. The jaws 713 of the counter mold 709 can be moved towards the 3D mold 702 via the slots 711 manually or automatically. The design of the counter mold 709 can help to obtain a better surface quality and reduced porosity of the 3D heart valve 701. Additionally, as mentioned above, in some embodiments, hot pressing can be used to achieve an optimum finishing of the shape of the 3D heart valve 701, in such a way that such shape is closest to the 3D mold 702. Hot pressing also improves the mechanical features of the 3D valve 701.

(44) Next, at step 907, the biocompatible fluid substance on the 3D mold 702 is cured. In one embodiment, the 3D mold may be cured in an oven between 70 and 90 Celsius for approximately 20 to 40 minutes. It is known that the temperature and time for curing in an oven could vary depending on the type of biocompatible fluid substance being used to form the 3D mold 702. The newly created heart valve 701 can be allowed to cool in situ. In another embodiment, the 3D mold may be cured without using an oven, for example, by cold curing the 3D mold with chemicals or other process.

(45) After the spraying and curing processes, a portion of the mold the may extend past the ends (top side) of the jaws 713 of the counter mold 709. Before or after the curing process, preferably after the curing process, the portion of the mold extending past the jaws 713 is cut in order to form and obtain the desired shape of the valve leaflets. This cut of the mold affects the end portion (distal end) of the valve leaflets. In one embodiment, the cut to form the distal end of the leaflets is made with a blade, such as a scalpel. Also, the cut may be made with a robotic arm or machine using a blade, and in certain embodiments, the cut may be made manually. It has also been contemplated that a laser may be used to cut the distal end of the leaflets. The laser may be manually controlled or controlled by a machine or robotic arm.

(46) Once the curing is complete, at step 908, the dry biocompatible fluid substance layer coated 3D mold 702, and stent in certain embodiments, on the support body 20 is extracted from the counter mold 709. The dry biocompatible fluid substance layer on the 3D mold 702 becomes final biocompatible 3D heart valve 701. Next, at step 909, the newly created 3D heart valve 701 is sterilized. The newly created 3D heart valve 701 includes the dried biocompatible fluid substance layer, and stent in certain embodiments. The valve 701 may be sterilized by wet or steam sterilization, dry heat sterilization, ethylene oxide, sporicidal chemicals, glass plasma, irradiation (gamma rays), or the like.

(47) Next, at step 910, a surgeon may implant the 3D heart valve 701, including the stent in certain embodiments, in the heart of the patient. The synthetic heart valve 701 produced using the method 900, is cost effective, biocompatible, rapidly manufactured, highly customizable, and durable.

(48) In some embodiments, the heart valve 701 can be produced directly from the 3D model 708, via 3D printing, CNC machining, or other methods. However, while typical production process might take several days, the spraying technique, as described in FIG. 9, for a singular valve can be completed less than 30-40 minutes. In addition to the increased speed of production, valves produced by the 3D spraying technique have very high biocompatibility and strong structural resistance. Therefore, the production process 900, as disclosed herein, dramatically decreases costs and permits easy production of variable sizes and geometries, making it suitable for veterinary use. This makes the process 900 ideal to for the application that requires low implant cost and great dimensional to accommodate the greatly varying valves of different species of animal. However, a person skilled in the art can appreciate that a prosthetic 3D human heart valve can also be produced using the process 900. It should also be appreciated that any type of prosthetic heart valve, such as a single leaflet valve, bileaflet valve, tilting disc valve, cage and ball valve, bicuspid valve, a mechanical valve, or the like may be used.

(49) The foregoing description of specific exemplary embodiments will so fully reveal the invention according to the conceptual point of view, so that others, by applying current knowledge, will be able to modify and/or adapt in various applications the specific exemplary embodiments without further research and without parting from the invention, and, accordingly, it is meant that such adaptations and modifications will have to be considered as equivalent to the specific embodiments. The means and the materials to realize the different functions described herein could have a different nature without, for this reason, departing from the field of the invention, it is to be understood that the phraseology or terminology that is employed herein is for the purpose of description and not of limitation.