US20210178678A1 - Bioprinting platform, method for using the same and 3d bioprinter - Google Patents
Bioprinting platform, method for using the same and 3d bioprinter Download PDFInfo
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- US20210178678A1 US20210178678A1 US17/183,584 US202117183584A US2021178678A1 US 20210178678 A1 US20210178678 A1 US 20210178678A1 US 202117183584 A US202117183584 A US 202117183584A US 2021178678 A1 US2021178678 A1 US 2021178678A1
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- platform
- lumen tissue
- bioprinting
- rotary rod
- block
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Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
- B29C64/205—Means for applying layers
- B29C64/209—Heads; Nozzles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
- A61F2/06—Blood vessels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/24—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
- A61F2/2412—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body with soft flexible valve members, e.g. tissue valves shaped like natural valves
- A61F2/2415—Manufacturing methods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/10—Processes of additive manufacturing
- B29C64/106—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
- B29C64/124—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using layers of liquid which are selectively solidified
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
- B29C64/245—Platforms or substrates
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
- B29C64/295—Heating elements
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y10/00—Processes of additive manufacturing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y30/00—Apparatus for additive manufacturing; Details thereof or accessories therefor
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
- B29L2031/00—Other particular articles
- B29L2031/753—Medical equipment; Accessories therefor
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y80/00—Products made by additive manufacturing
Definitions
- the present application relates to the technical field of 3D bioprinting, and especially relates to a bioprinting platform, a method for using the same and a 3D bioprinter.
- the prior art cannot externally compress the artificial blood vessels so that the bio-block is completely evenly, intactly, and flatly attached on the inner wall of the artificial blood vessels.
- the technical problem solved by the present application is to provide a bioprinting platform, a method for using the same and a 3D bioprinter, aiming at improving the biological reliability of the lumen tissue.
- a bioprinting platform includes a platform base, a rotary part on the platform base and a butt-jointed part movable relative to the rotary part, the rotary part includes a rotary rod for placing the bio-block and the medical adhesive to form a biological construct, and the butt-jointed part includes a hollow rod having an outer wall for placing the lumen tissue.
- the outer wall of the rotary rod is covered with an elastic film.
- an interior of the rotary rod is hollow, and the outer wall of the rotary rod is provided with a vent communicating with the interior, for exhausting air inside the rotary rod to balloon the elastic film.
- the interior of the rotary rod is provided with a heating unit.
- the heating unit includes a heating section and a spacing section that are spacedly arranged, wherein the heating section has a surface wound with a resistance wire, and the heating section has a diameter that is less than that of the spacing section.
- a temperature detecting unit is provided at one end of the heating unit proximate to the butt-jointed part, for detecting the temperature of the heating unit.
- the bioprinting platform includes a gripping mechanism for gripping the lumen tissue to make it disengaged from the hollow rod and socketed to the biological construct.
- the gripping mechanism includes a first gripping block and a second gripping block which are movable relatively.
- the gripping mechanism includes a retaining unit for acting on a tail end of the lumen tissue so that it is disengaged from the hollow rod.
- the retaining unit is cooperatively provided with a retaining ring acting on the tail end of the lumen tissue.
- the gripping mechanism includes a limiting block provided at the bottom of the first gripping block and the second gripping block, for limiting relative movement of the first gripping block and the second gripping block, so that the first gripping block and the second gripping block are both tangent to the outer wall of the lumen tissue.
- the gripping mechanism includes a support platform provided at the bottom of the first gripping block and the second gripping block, for supporting the lumen tissue.
- the platform base includes an optical probe movable inside the rotary rod, for detecting the flatness of the inner wall of the biological construct, wherein the rotary rod is made of a transparent material.
- optical probe is movably disposed within the rotary rod or the hollow rod.
- optical probe is fixedly disposed within the hollow rod.
- platform base further includes a reservoir provided below the rotary rod, for bearing a bioprinting construct disengaged and falling from the gripping mechanism.
- the present application further provides a 3D bioprinter, which includes the aforementioned platform base.
- the present invention further correspondingly provides a method of printing lumen tissue construct using the aforementioned platform base, which includes a mantling step: cladding a layer of elastic film on the outer wall of the rotary rod before printing the biological construct.
- the method further includes a ballooning step: ventilating into the elastic film to balloon the elastic film so that the biological construct is attached to the inner wall of the lumen tissue, after the lumen tissue is sleeved outside the biological construct.
- the bioprinting platform of the present application cooperates with a nozzle assembly to print the biological construct on the inner surface of the lumen tissue by the bioprinting platform, thus avoid such problems as recurrence of thrombus and restenosis of a lumen after the lumen tissue has been transplanted for a long time, thereby improving the biological reliability of the lumen tissue.
- the method of printing lumen tissue construct and the 3D bioprinter provided by the present application also correspondingly have the advantageous technical effects described above.
- FIG. 1 illustrates an overall structure of the device for printing lumen tissue construct according to an embodiment of the present application
- FIG. 2 illustrates an overall structure of a sprayhead assembly of the device according to an embodiment of the present application
- FIG. 3 illustrates an interior structure of a sprayhead assembly of the device according to an embodiment of the present application
- FIG. 4 illustrates a sectional structure of a screw pump of the device according to an embodiment of the present application
- FIG. 5 illustrates a sectional structure of a bio-block nozzle of the device according to an embodiment of the present application
- FIG. 6 is a locally enlarged schematic view of a circled portion in FIG. 5 ;
- FIG. 7 illustrates an overall structure of a bioprinting platform of the device according to an embodiment of the present application
- FIG. 8 illustrates a local structure of a bioprinting platform of the device according to an embodiment of the present application
- FIG. 9 illustrates the structure of a rotary rod of the device according to an embodiment of the present application.
- FIG. 10 illustrates the structure of a heating unit of the device according to an embodiment of the present application
- FIG. 11 illustrates the structure of a heating unit disposed inside the rotary rod of the device according to an embodiment of the present application
- FIG. 12 illustrates an interior structure of a rotary part of the device according to an embodiment of the present application
- FIG. 13 illustrates the structure of a first embodiment of a gripping mechanism of the device according to the present application
- FIG. 14 illustrates the structure of a first embodiment of a gripping mechanism of the device according to the present application in another angle of view
- FIG. 15 illustrates the structure of a second embodiment of a gripping mechanism of the device according to the present application
- FIG. 16 illustrates the structure of a second embodiment of a gripping mechanism when gripping the lumen tissue of the device according to the present application.
- heating section 2122 . connecting groove; 2123 . spacing section; 213 . temperature detecting unit; 214 . sealing ring; 22 . gripping mechanism; 221 , 221 ′. first gripping block; 222 , 222 ′. second gripping block; 223 , 223 ′. retaining unit; 224 . support platform; 225 . limiting block; 23 . butt-jointed part; 231 . hollow rod; 232 . displacement mechanism.
- the device comprises a sprayhead assembly 1 and a bioprinting platform 2 , the sprayhead assembly 1 prints a biological construct on an inner surface of a lumen tissue by the bioprinting platform 2 .
- the device provides the sprayhead assembly 1 and the bioprinting platform 2 , and the sprayhead assembly 1 prints the biological construct on the inner surface of the lumen tissue by the bioprinting platform 2 , thus avoid such problems as recurrence of thrombus and restenosis of a lumen after the lumen tissue has been transplanted for a long time, thereby improving the biological reliability of the lumen tissue.
- the lumen tissue is especially an artificial blood vessel, such as a commercial blood vessel of Gore, and the occurrence of thrombus after an artificial blood vessel has been transplanted for a long time may be avoided by printing the biological construct on the inner surface of the artificial blood vessel.
- the sprayhead assembly 1 includes a medical adhesive sprayhead 11 , which consist of a medical adhesive container 111 and a medical adhesive nozzle 112 , wherein the medical adhesive container 111 is used for containing a medical adhesive, the medical adhesive nozzle 112 is directly connected with the medical adhesive container 111 , a top of the medical adhesive container 111 is connected with an air pump through an air path, in which a vacuum generator is provided for generating a negative pressure for the medical adhesive container 111 in a non-printing state. Since the medical adhesive presents an excellent fluidity, in a non-printing state, the medical adhesive may also drip slowly due to the effect of gravity.
- a vacuum generator is added in the air path, where certain negative pressure is present in a non-printing state, and the negative pressure counteracts with the gravity so that the medical adhesive no longer drips freely.
- a top of the medical adhesive container 111 is provided with a medical adhesive piston 113 which is connected with the air pump through an air path.
- the air pump is pressurized to extrude the medical adhesive from an ink bladder, and the vacuum generator is located between the air pump and the medical adhesive piston 113 .
- the sprayhead assembly 1 includes a bio-block sprayhead 12 which consist of a screw pump 121 , a bio-block nozzle 122 , and a bio-block container 125 .
- the bio-block container 125 is used for containing bio-ink (bio-block).
- the outlet at the bottom of the bio-block container 125 communicates with the bio-block inlet 128 of the screw pump 121 through the connecting tube 127 and the inlet connecting piece 1213 .
- the top of the bio-block container 125 is provided with a bio-block piston 124 which is connected with the air pump through an air path.
- the air pump is pressurized to extrude the bio-ink from the bio-block container 125 into the screw pump 121 .
- the screw pump 121 includes a spiral stator 1211 and a spiral rotor 1212 for extruding a bio-block entering the screw pump 121 to the bio-block nozzle 122 , wherein the spiral stator 1211 is made of a silicone material.
- the bio-block Due to the physical properties of the bio-block, when it is very small at the outlet of the bio-block container 125 , the bio-block cannot be extruded and may form an accumulation at the outlet. Even if the pressure is increased, the bio-block cannot be extruded even if it is crushed. Likewise, even if such means as angular design is performed at the outlet of the bio-block container 125 , the bio-block still cannot be extruded.
- the printing requirement defines that the bio-block cannot be extruded in large quantities, and only a few amount can be extruded at a time. Therefore, the bio-blocks can only be conveyed from the bio-block container 125 to the screw pump 121 and extruded by the screw pump 121 . As the outlet of the screw pump 121 itself is very large, and the amount of the bio-blocks extruded each time is still greater than the operational requirement, a bio-block nozzle 122 is provided at the outlet of the screw pump 121 .
- the spiral stator 1211 cannot rotate, the spiral rotor 1212 rotates relative to the spiral stator 1211 , and the groove on the spiral rotor 1212 forms a chamber in which only a few amount of bio-blocks can be loaded within each chamber.
- the bio-blocks are conveyed out to the bio-block nozzle 122 along with rotation of the spiral rotor 1212 .
- Due to the physical properties of the current bio-ink materials the printing needs to be performed at a low temperature (4° C.).
- the screw stators of the existing screw pumps are made of a rubber material, which may rapidly age at a low temperature, so that black powder appears during the printing.
- the present application makes a modification by making the spiral stator 1211 of silicone, thus avoiding the appearance of black powder during the printing.
- a printing outlet end of the bio-block nozzle 122 has a chamfer, which has a chamfered surface defining an included angle of 10° to 30° with a center line of a printing outlet of the bio-block nozzle 122 . Even further, the included angle is 20°, such design can effectively avoid the phenomenon of “hanging droplets”.
- an outer surface at the printing outlet end of the bio-block nozzle 122 has a roughness Ra ⁇ 0.4.
- the outer surface of the bio-block nozzle 122 may be plated/polished so as to increase the surface smoothness, and such design can be able to better avoid the phenomenon of “hanging droplets”.
- the bio-block sprayhead 12 also includes a semiconductor cooling plate 126 located behind the screw pump 121 and the bio-block container 125 , which can cool the bio-block sprayhead 12 by heat transfer.
- the bio-block nozzle 122 is externally provided with a thermal insulation sleeve 129 . There is certain gap between the thermal insulation sleeve 129 and an exterior of the bio-block nozzle 122 , in which an air thermal insulation layer can be formed. Further, as shown in FIG.
- the screw pump 121 and the bio-block container 125 are externally sleeved with a thermal insulation shell 123 including a box cover and thermal insulation cotton covered on the outer surface of the box cover.
- the thermal insulation cotton can further improve the thermal insulation effect, and reduce the heat exchange between the sprayhead and the environment.
- the box cover is provided with a transparent window for observing the containing condition of the bio-ink in the bio-block container 125 .
- the device further comprises a displacement assembly for moving the sprayhead assembly 1 , and an entirety of the sprayhead assembly 1 (the bio-block sprayhead 12 and the medical adhesive sprayhead 11 ) may be displaced in a vertical direction and a horizontal direction, and the medical adhesive sprayhead 11 may be lifted independently.
- the sprayhead assembly 1 is in the initial state, the horizontal position at the outlet of the bio-block sprayhead 12 is below the horizontal position at the outlet of the medical adhesive sprayhead 11 .
- the displacement assembly lowers the sprayhead assembly 1 to certain height during the printing, the bio-block sprayhead 12 extrudes the bio-block, and wholly ascends a segment after the printing of the lumen tissue is accomplished, then the medical adhesive sprayhead 11 descends independently, to print the medical adhesive.
- the bioprinting platform 2 includes a platform base, a rotary part 21 and a butt-jointed part 23 movable relative to the rotary part 21 , wherein the rotary part 21 includes a rotary rod 211 for placing the bio-block and the medical adhesive to form a biological construct, and the butt-jointed part 23 includes a displacement mechanism 232 and a hollow rod 231 having an outer wall for placing the lumen tissue and having an inner cavity for containing the rotary rod 211 with the biological construct.
- the hollow rod 231 is displaced toward a direction of the rotary part 21 driven by the displacement mechanism 232 .
- the rotary rod 211 together with the biological construct enter the inner cavity of the hollow rod 231 , and the lumen tissue sleeved outside the hollow rod 231 is displaced to the outside of the biological construct along with the hollow rod 231 .
- the surface of the hollow rod 231 is plated with a Teflon layer, which is capable of avoiding that the medical adhesive contacts and reacts with the metal surface.
- the hollow rod 231 is further displaced in an opposite direction driven by the displacement mechanism 232 , and the lumen tissue is removed from the hollow rod 231 , and then sleeved on the outer surface of the biological construct, so that the assembly is accomplished to obtain an artificial tissue precursor.
- the outer wall of the rotary rod 211 is covered with an elastic film.
- the elastic film presents a natural state and clads on the surface of the rotary rod 211 .
- the bio-block makes up a biological construct on the surface of the elastic film, thus favorable for removing the biological construct. Further, as shown in FIG.
- an interior of the rotary rod 211 is hollow, and the outer wall of the rotary rod 211 is provided with a vent communicating with the interior, for exhausting air inside the rotary rod 211 to balloon the elastic film.
- the rotary rod 211 is internally ventilated so that air expands outwards from the air outlet to balloon the elastic film (conceivably like a balloon is blown up).
- the biological construct on the surface of the elastic film is displaced outwards along with the expansion of the elastic film, and finally in contact with the inner wall of the lumen tissue and then adhered onto the inner wall of the lumen tissue, to obtain an artificial tissue precursor. It is demonstrated in practice that, the embodiment is easy to operate and implement, and presents a high implementability.
- a sealing ring 214 is provided inside the rotary part 21 .
- the rotary rod 211 is detachably connected with the sealing ring 214 , and the sealing ring 214 is used for sealing the inner cavity of the rotary rod 211 , so that the process of balloon the elastic film is more controllable.
- the interior of the rotary rod 211 is further provided with a heating unit 212 .
- the heating unit 212 can accelerate the coagulation rate of the bio-ink and shorten the preparation time of the bio-construct.
- the heating unit 212 needs to maintain the surface temperature of the rotary rod at 37° C.-38° C.
- a temperature detecting unit 213 is provided at one end of the heating unit 212 proximate to the butt-jointed part 23 , for detecting the temperature of the heating unit 212 , so as to maintain the surface temperature of the rotary rod in real time.
- the heating unit 212 includes a heating section 2121 and a spacing section 2123 that are spacedly arranged, wherein a connecting groove 2122 is opened in the surface of the spacing section 2123 , and the surface of the heating section 2121 is wounded with a resistance wire, the surface of the spacing section 2123 is not wounded with a resistance wire, the resistance wire between adjacent heating sections 2121 passes through the connecting groove 2122 , and the diameter of the heating section 2121 is less than that of the spacing section 2123 .
- the heating unit 212 is in clearance fit with the rotary rod 211 , and the outer wall of the spacing section 2123 is in contact with the inner wall of the rotary rod 211 .
- the purpose of providing the spacing section is to protect the resistance wire when the heating unit 212 is inserted into the rotary rod 211 , so as to avoid that the resistance wire is damaged during the assembly.
- the bioprinting platform 2 further includes a gripping mechanism 22 for gripping the lumen tissue to make it disengaged from the hollow rod 231 and socketed to the biological construct when the hollow rod 231 is displaced in an opposite direction.
- the embodiment is easy to implement and has a high reliability.
- the gripping mechanism 22 includes a first gripping block 221 , 221 ′ and a second gripping block 222 , 222 ′ which are movable relatively.
- the relative movement of the first gripping block 221 and the second gripping block 222 may be preferably realized by providing a guide rail.
- the relative movement of the first gripping block 221 ′ and the second gripping block 222 ′ may also be preferably realized by providing a leadscrew nut mechanism. Even further, as shown in FIG.
- the gripping mechanism 22 further includes a limiting block 225 provided at the bottom of the first gripping block 221 and the second gripping block 222 , for limiting relative movement of the first gripping block 221 and the second gripping block 222 , so that the first gripping block 221 and the second gripping block 222 are both tangent to the outer wall of the lumen tissue, and it is possible to produce certain limiting effect for the lumen tissue during assembling the artificial tissue precursor.
- the gripping mechanism 22 further includes a retaining unit 223 , 223 ′ for acting on a tail end of the lumen tissue so that it is disengaged from the hollow rod 231 to prevent the lumen tissue from following the hollow rod 231 when the hollow rod 231 is displaced in an opposite direction.
- the retaining units 223 , 223 ′ may be disposed at a tail end of the first gripping blocks 221 , 221 ′ and/or the second gripping blocks 222 , 222 ′, and may also be directly disposed on the gripping mechanism independent of the first gripping block and the second gripping block.
- the retaining unit 223 is cooperatively provided with a retaining ring acting on the tail end of the lumen tissue, so that the lumen tissue is more easily disengaged from the hollow rod 231 .
- the gripping mechanism 22 further includes a support platform 224 provided at the bottom of the first gripping block 221 and the second gripping block 222 , for supporting the lumen tissue. In the process of the lumen tissue socketing the biological construct, the support platform 224 is exactly tangent to the outer wall at the bottom of the lumen tissue, for providing an upward force for the lumen tissue and avoiding the sinking of the lumen tissue.
- the device further comprises a reservoir provided below the rotary rod 211 , for bearing a bioprinting construct disengaged and falling from the gripping mechanism 22 .
- the bioprinting construct is gripped by the gripping mechanism 22 , and an entirety of the rotary rod 211 is withdrawn towards an opposite direction.
- the bioprinting construct is located immediately above the reservoir, and is supported by the gripping mechanism 22 .
- the gripping mechanism 22 withdraws the gripping force, so that the bioprinting construct falls vertically into the reservoir.
- the present application correspondingly provides a method for printing lumen tissue construct using the aforementioned bioprinting platform, which comprises a mantling step: cladding a layer of elastic film on the outer wall of the rotary rod 211 before printing the biological construct.
- the elastic film presents a natural state, and clads on the surface of the rotary rod 211 .
- the bio-block makes up a biological construct on the surface of the elastic film, thus favorable for removing the biological construct.
- the printing method of the lumen tissue construct printing device further comprises a film ballooning step: ventilating into the elastic film to balloon the elastic film so that the biological construct is attached to the inner wall of the lumen tissue, after the lumen tissue is sleeved outside the biological construct.
- the biological construct on the surface of the elastic film is displaced outwards along with the expansion of the elastic film, and finally in contact with the inner wall of the lumen tissue and adhered onto the inner wall of the lumen tissue, so that the biological construct is completely evenly, intactly, and flatly attached on the inner wall of the lumen tissue, such as to obtain an artificial tissue precursor. It is demonstrated in practice that, the embodiment is easy to operate and implement, and presents a high implementability.
- the bio-ink construct s a biological construct on the surface of the elastic film by means of the bio-block sprayhead 12 , and then a medical adhesive layer for adhering the bio-block and the lumen tissue is uniformly extruded on the surface of the biological construct by means of the medical adhesive sprayhead 11 .
- the hollow rod 231 moves toward the rotary rod 211 until the hollow rod 231 is completely sleeved outside the rotary rod 211 .
- the lumen tissue is completely outside the biological construct, and the hollow rod 231 moves towards a direction away from the rotary rod 211 , then the gripping mechanism 22 prevents the lumen tissue from following the movement of the hollow rod 231 .
- the hollow rod 231 is completely separated from the rotary rod 211 , but the lumen tissue remains outside the biological construct.
- the rotary rod 211 is internally ventilated to balloon the elastic film, so that the biological construct is completely attached onto the inner wall of the lumen tissue.
- the heating unit 212 heats to accelerate the coagulation of the bio-ink, to finally obtain an artificial tissue precursor, which is removed from the rotary rod 211 .
- the device may further comprise an optical probe movable inside the rotary rod 211 , for detecting the flatness of the inner wall of the biological construct, wherein the rotary rod 211 is made of a transparent material.
- the optical probe is fixedly disposed in the hollow rod 231 .
- the hollow rod 231 is designed in a double-layer embedded structure, in which the first layer is used for embedding an artificial blood vessel, and the front end of the second layer is provided with an optical probe.
- the rotary rod 211 may also be a double-layer structure, in which ventilation is performed within the sandwich for ballooning the elastic film.
- the elastic film only covers the surface of the rotary rod 211 but does not cover the front end, such as to enable the optical probe to extend into the rotary rod 211 .
- the lumen tissue is sleeved on the surface of the biological construct, and the optical probe also moves along with the hollow rod 231 to the furthest end of the biological construct.
- the optical probe also moves along with the hollow rod 231 to the foremost end of the artificial precursor tissue, so as to accomplish the flatness detection in the assembly process.
- the optical probe is movably disposed in the hollow rod 231 , that is, the optical probe moves independently with respect to the hollow rod 231 , and the flatness detection can also be accomplished.
- the optical probe is movably disposed in the rotary rod 211 , and the optical probe moves from one end to the other within the rotary rod 211 to accomplish the flatness detection.
- the present application further provides a 3D bioprinter, which comprises the aforementioned device for printing lumen tissue construct.
- a 3D bioprinter which comprises the aforementioned device for printing lumen tissue construct.
- the 3D bioprinter of the present application also has the advantageous technical effects described above, and thus will no longer be repeated here.
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Abstract
A device and method for printing lumen tissue constructs and a 3D bioprinter are disclosed. The device has a spray sprayhead assembly and a bioprinting platform. The spray sprayhead assembly prints a biological construct on an inner surface of a lumen tissue by the bioprinting platform. Problems, such as, recurrence of thrombus and restenosis of a lumen after the lumen tissue has been transplanted for a long time, can be avoided. The biological reliability of the lumen tissue can be improved.
Description
- The present application is a continuation application of U.S. patent application No. U.S. 15/964,214, filed Apr. 27, 2018, which claims priority to Chinese Patent Application No. CN 201810048700.6, filed Jan. 18, 2018, both of which are herein incorporated by reference in their entireties.
- The present application relates to the technical field of 3D bioprinting, and especially relates to a bioprinting platform, a method for using the same and a 3D bioprinter.
- In the prior art, common artificial blood vessels are made from polymer fibers (e.g., nylon, dacron), silk, or ePTFE. In the case of vascular transplantation, intact artificial blood vessels may be used to replace lesioned or damaged blood vessels. Although the replacement of lesioned or damaged blood vessels with such artificial blood vessels has attained great clinical achievement, it is still confronted with difficult problems, including recurrence of thrombus and appearance of restenosis of a lumen after transplantation for a long time. The root of these problems lies in the lack of a complete endothelial cell layer on the inner surface of such artificial blood vessels.
- In addition, since the artificial blood vessels can hardly deform in a radial direction, the prior art cannot externally compress the artificial blood vessels so that the bio-block is completely evenly, intactly, and flatly attached on the inner wall of the artificial blood vessels.
- In order to overcome the above technical defects, the technical problem solved by the present application is to provide a bioprinting platform, a method for using the same and a 3D bioprinter, aiming at improving the biological reliability of the lumen tissue.
- In order to solve the above technical problem, the present application provides a bioprinting platform includes a platform base, a rotary part on the platform base and a butt-jointed part movable relative to the rotary part, the rotary part includes a rotary rod for placing the bio-block and the medical adhesive to form a biological construct, and the butt-jointed part includes a hollow rod having an outer wall for placing the lumen tissue.
- Further, the outer wall of the rotary rod is covered with an elastic film.
- Further, an interior of the rotary rod is hollow, and the outer wall of the rotary rod is provided with a vent communicating with the interior, for exhausting air inside the rotary rod to balloon the elastic film.
- Further, the interior of the rotary rod is provided with a heating unit.
- Further, the heating unit includes a heating section and a spacing section that are spacedly arranged, wherein the heating section has a surface wound with a resistance wire, and the heating section has a diameter that is less than that of the spacing section.
- Further, a temperature detecting unit is provided at one end of the heating unit proximate to the butt-jointed part, for detecting the temperature of the heating unit.
- Further, the bioprinting platform includes a gripping mechanism for gripping the lumen tissue to make it disengaged from the hollow rod and socketed to the biological construct.
- Further, the gripping mechanism includes a first gripping block and a second gripping block which are movable relatively.
- Further, the gripping mechanism includes a retaining unit for acting on a tail end of the lumen tissue so that it is disengaged from the hollow rod.
- Further, the retaining unit is cooperatively provided with a retaining ring acting on the tail end of the lumen tissue.
- Further, the gripping mechanism includes a limiting block provided at the bottom of the first gripping block and the second gripping block, for limiting relative movement of the first gripping block and the second gripping block, so that the first gripping block and the second gripping block are both tangent to the outer wall of the lumen tissue.
- Further, the gripping mechanism includes a support platform provided at the bottom of the first gripping block and the second gripping block, for supporting the lumen tissue.
- Further, the platform base includes an optical probe movable inside the rotary rod, for detecting the flatness of the inner wall of the biological construct, wherein the rotary rod is made of a transparent material.
- Further, the optical probe is movably disposed within the rotary rod or the hollow rod.
- Further, the optical probe is fixedly disposed within the hollow rod.
- Further, platform base further includes a reservoir provided below the rotary rod, for bearing a bioprinting construct disengaged and falling from the gripping mechanism.
- The present application further provides a 3D bioprinter, which includes the aforementioned platform base.
- The present invention further correspondingly provides a method of printing lumen tissue construct using the aforementioned platform base, which includes a mantling step: cladding a layer of elastic film on the outer wall of the rotary rod before printing the biological construct.
- Further, the method further includes a ballooning step: ventilating into the elastic film to balloon the elastic film so that the biological construct is attached to the inner wall of the lumen tissue, after the lumen tissue is sleeved outside the biological construct.
- Therefore, based on the aforementioned technical solution, the bioprinting platform of the present application cooperates with a nozzle assembly to print the biological construct on the inner surface of the lumen tissue by the bioprinting platform, thus avoid such problems as recurrence of thrombus and restenosis of a lumen after the lumen tissue has been transplanted for a long time, thereby improving the biological reliability of the lumen tissue. The method of printing lumen tissue construct and the 3D bioprinter provided by the present application also correspondingly have the advantageous technical effects described above.
- The drawings described herein are used to provide a further understanding of the present application and constitute a part of the present application. The illustrative embodiments of the present application as well as the descriptions thereof, which are merely used for explaining the present application, and do not constitute improper definitions on the present application. In the drawings:
-
FIG. 1 illustrates an overall structure of the device for printing lumen tissue construct according to an embodiment of the present application; -
FIG. 2 illustrates an overall structure of a sprayhead assembly of the device according to an embodiment of the present application; -
FIG. 3 illustrates an interior structure of a sprayhead assembly of the device according to an embodiment of the present application; -
FIG. 4 illustrates a sectional structure of a screw pump of the device according to an embodiment of the present application; -
FIG. 5 illustrates a sectional structure of a bio-block nozzle of the device according to an embodiment of the present application; -
FIG. 6 is a locally enlarged schematic view of a circled portion inFIG. 5 ; -
FIG. 7 illustrates an overall structure of a bioprinting platform of the device according to an embodiment of the present application; -
FIG. 8 illustrates a local structure of a bioprinting platform of the device according to an embodiment of the present application; -
FIG. 9 illustrates the structure of a rotary rod of the device according to an embodiment of the present application; -
FIG. 10 illustrates the structure of a heating unit of the device according to an embodiment of the present application; -
FIG. 11 illustrates the structure of a heating unit disposed inside the rotary rod of the device according to an embodiment of the present application; -
FIG. 12 illustrates an interior structure of a rotary part of the device according to an embodiment of the present application; -
FIG. 13 illustrates the structure of a first embodiment of a gripping mechanism of the device according to the present application; -
FIG. 14 illustrates the structure of a first embodiment of a gripping mechanism of the device according to the present application in another angle of view; -
FIG. 15 illustrates the structure of a second embodiment of a gripping mechanism of the device according to the present application; -
FIG. 16 illustrates the structure of a second embodiment of a gripping mechanism when gripping the lumen tissue of the device according to the present application. - Various reference signs respectively represent:
- 1. sprayhead assembly; 11. medical adhesive sprayhead; 111. medical adhesive container; 112. medical adhesive nozzle; 113. medical adhesive piston; 12. bio-block sprayhead; 121. screw pump; 1211. spiral stator; 1212. spiral rotor; 1213. inlet connecting piece; 122. bio-block nozzle; 123. thermal insulation shell; 124. bio-block piston; 125. bio-block container; 126. semiconductor cooling plate; 127. connecting tube; 128. bio-block inlet; 129. thermal insulation sleeve; 2. bioprinting platform; 21. rotary part; 211. rotary rod; 212. heating unit; 2121. heating section; 2122. connecting groove; 2123. spacing section; 213. temperature detecting unit; 214. sealing ring; 22. gripping mechanism; 221, 221′. first gripping block; 222, 222′. second gripping block; 223, 223′. retaining unit; 224. support platform; 225. limiting block; 23. butt-jointed part; 231. hollow rod; 232. displacement mechanism.
- Next, the technical solution of the present application is further described in detail by means of the drawings and embodiments.
- The specific embodiments of the present application are further described in order to facilitate understanding of the concept of the present application, the technical problem to be solved, the technical features constituting the technical solution and the technical effect produced therefrom. It is necessary to explain that, the explanations for such embodiments do not constitute definitions on the present application. In addition, the technical features involved in the embodiments of the present application described below may be combined with each other as long as they do not constitute a conflict therebetween.
- In an illustrative embodiment of the device for printing lumen tissue construct of the present application, as shown in
FIG. 1 , the device comprises asprayhead assembly 1 and a bioprinting platform 2, thesprayhead assembly 1 prints a biological construct on an inner surface of a lumen tissue by the bioprinting platform 2. - In the illustrative embodiment, the device provides the
sprayhead assembly 1 and the bioprinting platform 2, and thesprayhead assembly 1 prints the biological construct on the inner surface of the lumen tissue by the bioprinting platform 2, thus avoid such problems as recurrence of thrombus and restenosis of a lumen after the lumen tissue has been transplanted for a long time, thereby improving the biological reliability of the lumen tissue. Among them, the lumen tissue is especially an artificial blood vessel, such as a commercial blood vessel of Gore, and the occurrence of thrombus after an artificial blood vessel has been transplanted for a long time may be avoided by printing the biological construct on the inner surface of the artificial blood vessel. - In an improved embodiment of the device for printing lumen tissue construct of the present application, as shown in
FIGS. 2 and 3 , thesprayhead assembly 1 includes amedical adhesive sprayhead 11, which consist of a medicaladhesive container 111 and a medicaladhesive nozzle 112, wherein the medicaladhesive container 111 is used for containing a medical adhesive, the medicaladhesive nozzle 112 is directly connected with the medicaladhesive container 111, a top of the medicaladhesive container 111 is connected with an air pump through an air path, in which a vacuum generator is provided for generating a negative pressure for the medicaladhesive container 111 in a non-printing state. Since the medical adhesive presents an excellent fluidity, in a non-printing state, the medical adhesive may also drip slowly due to the effect of gravity. Thus, a vacuum generator is added in the air path, where certain negative pressure is present in a non-printing state, and the negative pressure counteracts with the gravity so that the medical adhesive no longer drips freely. Specifically or further, as shown inFIG. 3 , a top of the medicaladhesive container 111 is provided with amedical adhesive piston 113 which is connected with the air pump through an air path. The air pump is pressurized to extrude the medical adhesive from an ink bladder, and the vacuum generator is located between the air pump and themedical adhesive piston 113. - In an improved embodiment of the device for printing lumen tissue construct of the present application, as shown in
FIGS. 2 to 4 , thesprayhead assembly 1 includes abio-block sprayhead 12 which consist of ascrew pump 121, abio-block nozzle 122, and abio-block container 125. Thebio-block container 125 is used for containing bio-ink (bio-block). The outlet at the bottom of thebio-block container 125 communicates with thebio-block inlet 128 of thescrew pump 121 through the connectingtube 127 and theinlet connecting piece 1213. The top of thebio-block container 125 is provided with abio-block piston 124 which is connected with the air pump through an air path. The air pump is pressurized to extrude the bio-ink from thebio-block container 125 into thescrew pump 121. Thescrew pump 121 includes aspiral stator 1211 and aspiral rotor 1212 for extruding a bio-block entering thescrew pump 121 to thebio-block nozzle 122, wherein thespiral stator 1211 is made of a silicone material. - Due to the physical properties of the bio-block, when it is very small at the outlet of the
bio-block container 125, the bio-block cannot be extruded and may form an accumulation at the outlet. Even if the pressure is increased, the bio-block cannot be extruded even if it is crushed. Likewise, even if such means as angular design is performed at the outlet of thebio-block container 125, the bio-block still cannot be extruded. However, the printing requirement defines that the bio-block cannot be extruded in large quantities, and only a few amount can be extruded at a time. Therefore, the bio-blocks can only be conveyed from thebio-block container 125 to thescrew pump 121 and extruded by thescrew pump 121. As the outlet of thescrew pump 121 itself is very large, and the amount of the bio-blocks extruded each time is still greater than the operational requirement, abio-block nozzle 122 is provided at the outlet of thescrew pump 121. - As shown in
FIG. 4 , thespiral stator 1211 cannot rotate, thespiral rotor 1212 rotates relative to thespiral stator 1211, and the groove on thespiral rotor 1212 forms a chamber in which only a few amount of bio-blocks can be loaded within each chamber. The bio-blocks are conveyed out to thebio-block nozzle 122 along with rotation of thespiral rotor 1212. Due to the physical properties of the current bio-ink materials, the printing needs to be performed at a low temperature (4° C.). The screw stators of the existing screw pumps are made of a rubber material, which may rapidly age at a low temperature, so that black powder appears during the printing. The present application makes a modification by making thespiral stator 1211 of silicone, thus avoiding the appearance of black powder during the printing. - In order to avoid the phenomenon of “hanging droplets” (Due to high viscosity of the bio-ink, the bio-block after being extruded may not drip directly, but hang at the nozzle outlet. When a following bio-block is extruded, a previous bio-block that does not drip is piled up with the following to become a large droplet hanging at the outlet of the nozzle which may drip when the gravity of such large droplet is greater than the frictional force) appearing at a front end outlet (a circled portion in
FIG. 5 ) of thebio-block nozzle 122 when printing the bio-block. In an improved embodiment, on one hand, as shown inFIGS. 5 and 6 , a printing outlet end of thebio-block nozzle 122 has a chamfer, which has a chamfered surface defining an included angle of 10° to 30° with a center line of a printing outlet of thebio-block nozzle 122. Even further, the included angle is 20°, such design can effectively avoid the phenomenon of “hanging droplets”. On the other end, an outer surface at the printing outlet end of thebio-block nozzle 122 has a roughness Ra≤0.4. The outer surface of thebio-block nozzle 122 may be plated/polished so as to increase the surface smoothness, and such design can be able to better avoid the phenomenon of “hanging droplets”. - Since the currently used bio-ink may tend to coagulate in the case of a temperature greater than 4° C., it is very necessary to maintain the bio-block sprayhead at an ambient temperature of 4° C. In some improved embodiments, as shown in
FIG. 3 , thebio-block sprayhead 12 also includes asemiconductor cooling plate 126 located behind thescrew pump 121 and thebio-block container 125, which can cool thebio-block sprayhead 12 by heat transfer. Further, as shown inFIG. 3 , thebio-block nozzle 122 is externally provided with athermal insulation sleeve 129. There is certain gap between thethermal insulation sleeve 129 and an exterior of thebio-block nozzle 122, in which an air thermal insulation layer can be formed. Further, as shown inFIG. 2 , thescrew pump 121 and thebio-block container 125 are externally sleeved with athermal insulation shell 123 including a box cover and thermal insulation cotton covered on the outer surface of the box cover. The thermal insulation cotton can further improve the thermal insulation effect, and reduce the heat exchange between the sprayhead and the environment. The box cover is provided with a transparent window for observing the containing condition of the bio-ink in thebio-block container 125. - In some improved embodiments, the device further comprises a displacement assembly for moving the
sprayhead assembly 1, and an entirety of the sprayhead assembly 1 (thebio-block sprayhead 12 and the medical adhesive sprayhead 11) may be displaced in a vertical direction and a horizontal direction, and themedical adhesive sprayhead 11 may be lifted independently. When thesprayhead assembly 1 is in the initial state, the horizontal position at the outlet of thebio-block sprayhead 12 is below the horizontal position at the outlet of themedical adhesive sprayhead 11. After the displacement assembly lowers thesprayhead assembly 1 to certain height during the printing, thebio-block sprayhead 12 extrudes the bio-block, and wholly ascends a segment after the printing of the lumen tissue is accomplished, then themedical adhesive sprayhead 11 descends independently, to print the medical adhesive. - In an improved embodiment of the device for printing lumen tissue construct of the present application, as shown in
FIGS. 7 and 8 , the bioprinting platform 2 includes a platform base, arotary part 21 and a butt-jointedpart 23 movable relative to therotary part 21, wherein therotary part 21 includes arotary rod 211 for placing the bio-block and the medical adhesive to form a biological construct, and the butt-jointedpart 23 includes adisplacement mechanism 232 and ahollow rod 231 having an outer wall for placing the lumen tissue and having an inner cavity for containing therotary rod 211 with the biological construct. - After the biological construct is manufactured on the
rotary rod 211, thehollow rod 231 is displaced toward a direction of therotary part 21 driven by thedisplacement mechanism 232. Therotary rod 211 together with the biological construct enter the inner cavity of thehollow rod 231, and the lumen tissue sleeved outside thehollow rod 231 is displaced to the outside of the biological construct along with thehollow rod 231. Further, the surface of thehollow rod 231 is plated with a Teflon layer, which is capable of avoiding that the medical adhesive contacts and reacts with the metal surface. Thehollow rod 231 is further displaced in an opposite direction driven by thedisplacement mechanism 232, and the lumen tissue is removed from thehollow rod 231, and then sleeved on the outer surface of the biological construct, so that the assembly is accomplished to obtain an artificial tissue precursor. Further, the outer wall of therotary rod 211 is covered with an elastic film. During the printing of the biological construct, the elastic film presents a natural state and clads on the surface of therotary rod 211. The bio-block makes up a biological construct on the surface of the elastic film, thus favorable for removing the biological construct. Further, as shown inFIG. 9 , an interior of therotary rod 211 is hollow, and the outer wall of therotary rod 211 is provided with a vent communicating with the interior, for exhausting air inside therotary rod 211 to balloon the elastic film. During the assembly of the biological construct and the lumen tissue, therotary rod 211 is internally ventilated so that air expands outwards from the air outlet to balloon the elastic film (conceivably like a balloon is blown up). The biological construct on the surface of the elastic film is displaced outwards along with the expansion of the elastic film, and finally in contact with the inner wall of the lumen tissue and then adhered onto the inner wall of the lumen tissue, to obtain an artificial tissue precursor. It is demonstrated in practice that, the embodiment is easy to operate and implement, and presents a high implementability. Specifically or further, as shown inFIG. 12 , a sealingring 214 is provided inside therotary part 21. Therotary rod 211 is detachably connected with the sealingring 214, and thesealing ring 214 is used for sealing the inner cavity of therotary rod 211, so that the process of balloon the elastic film is more controllable. - As an improvement to the above embodiment, as shown in
FIGS. 10 and 11 , the interior of therotary rod 211 is further provided with aheating unit 212. Theheating unit 212 can accelerate the coagulation rate of the bio-ink and shorten the preparation time of the bio-construct. Theheating unit 212 needs to maintain the surface temperature of the rotary rod at 37° C.-38° C. Further, as shown inFIG. 11 , atemperature detecting unit 213 is provided at one end of theheating unit 212 proximate to the butt-jointedpart 23, for detecting the temperature of theheating unit 212, so as to maintain the surface temperature of the rotary rod in real time. - In a specific or improved embodiment, as shown in
FIGS. 10 and 11 , theheating unit 212 includes aheating section 2121 and aspacing section 2123 that are spacedly arranged, wherein a connectinggroove 2122 is opened in the surface of thespacing section 2123, and the surface of theheating section 2121 is wounded with a resistance wire, the surface of thespacing section 2123 is not wounded with a resistance wire, the resistance wire betweenadjacent heating sections 2121 passes through the connectinggroove 2122, and the diameter of theheating section 2121 is less than that of thespacing section 2123. Theheating unit 212 is in clearance fit with therotary rod 211, and the outer wall of thespacing section 2123 is in contact with the inner wall of therotary rod 211. The purpose of providing the spacing section is to protect the resistance wire when theheating unit 212 is inserted into therotary rod 211, so as to avoid that the resistance wire is damaged during the assembly. - As to how to remove the lumen tissue from the
hollow rod 231, in an improved embodiment, as shown inFIG. 7 , the bioprinting platform 2 further includes agripping mechanism 22 for gripping the lumen tissue to make it disengaged from thehollow rod 231 and socketed to the biological construct when thehollow rod 231 is displaced in an opposite direction. The embodiment is easy to implement and has a high reliability. - Specifically or further, as shown in
FIGS. 13-16 , the grippingmechanism 22 includes a firstgripping block gripping block FIGS. 13 and 14 , the relative movement of the firstgripping block 221 and the secondgripping block 222 may be preferably realized by providing a guide rail. As shown inFIGS. 15 and 16 , the relative movement of the firstgripping block 221′ and the secondgripping block 222′ may also be preferably realized by providing a leadscrew nut mechanism. Even further, as shown inFIG. 14 , the grippingmechanism 22 further includes a limitingblock 225 provided at the bottom of the firstgripping block 221 and the secondgripping block 222, for limiting relative movement of the firstgripping block 221 and the secondgripping block 222, so that the firstgripping block 221 and the secondgripping block 222 are both tangent to the outer wall of the lumen tissue, and it is possible to produce certain limiting effect for the lumen tissue during assembling the artificial tissue precursor. - In order to ensure that the lumen tissue is removed from the
hollow rod 231 as much as possible, in one further embodiment, as shown inFIGS. 13 to 16 , the grippingmechanism 22 further includes a retainingunit hollow rod 231 to prevent the lumen tissue from following thehollow rod 231 when thehollow rod 231 is displaced in an opposite direction. The retainingunits gripping blocks gripping blocks unit 223 is cooperatively provided with a retaining ring acting on the tail end of the lumen tissue, so that the lumen tissue is more easily disengaged from thehollow rod 231. Still further, as shown inFIG. 14 , the grippingmechanism 22 further includes asupport platform 224 provided at the bottom of the firstgripping block 221 and the secondgripping block 222, for supporting the lumen tissue. In the process of the lumen tissue socketing the biological construct, thesupport platform 224 is exactly tangent to the outer wall at the bottom of the lumen tissue, for providing an upward force for the lumen tissue and avoiding the sinking of the lumen tissue. - In an improved embodiment of device for printing the lumen tissue construct of the present application, the device further comprises a reservoir provided below the
rotary rod 211, for bearing a bioprinting construct disengaged and falling from the grippingmechanism 22. After the printing assembly is completed, the bioprinting construct is gripped by the grippingmechanism 22, and an entirety of therotary rod 211 is withdrawn towards an opposite direction. The bioprinting construct is located immediately above the reservoir, and is supported by the grippingmechanism 22. At this time, the grippingmechanism 22 withdraws the gripping force, so that the bioprinting construct falls vertically into the reservoir. This design can avoid the introduction of new contamination in the transfer operation process implemented manually or by robotic arm after the completion of printing, or the damage caused for printing the inner wall of a blood vessel due to inappropriate operation in the operational process, and facilitate the packaging of a finished product. - The present application correspondingly provides a method for printing lumen tissue construct using the aforementioned bioprinting platform, which comprises a mantling step: cladding a layer of elastic film on the outer wall of the
rotary rod 211 before printing the biological construct. During the printing of the biological construct, the elastic film presents a natural state, and clads on the surface of therotary rod 211. The bio-block makes up a biological construct on the surface of the elastic film, thus favorable for removing the biological construct. Further, the printing method of the lumen tissue construct printing device further comprises a film ballooning step: ventilating into the elastic film to balloon the elastic film so that the biological construct is attached to the inner wall of the lumen tissue, after the lumen tissue is sleeved outside the biological construct. The biological construct on the surface of the elastic film is displaced outwards along with the expansion of the elastic film, and finally in contact with the inner wall of the lumen tissue and adhered onto the inner wall of the lumen tissue, so that the biological construct is completely evenly, intactly, and flatly attached on the inner wall of the lumen tissue, such as to obtain an artificial tissue precursor. It is demonstrated in practice that, the embodiment is easy to operate and implement, and presents a high implementability. - Next, the construction process of the artificial tissue precursor of the lumen tissue construct printing device of the present application is explained by exemplifying the embodiments shown in
FIGS. 1 to 14 as follows: - The bio-ink constructs a biological construct on the surface of the elastic film by means of the
bio-block sprayhead 12, and then a medical adhesive layer for adhering the bio-block and the lumen tissue is uniformly extruded on the surface of the biological construct by means of themedical adhesive sprayhead 11. - After the biological construct is made, the
hollow rod 231 moves toward therotary rod 211 until thehollow rod 231 is completely sleeved outside therotary rod 211. At this time, the lumen tissue is completely outside the biological construct, and thehollow rod 231 moves towards a direction away from therotary rod 211, then thegripping mechanism 22 prevents the lumen tissue from following the movement of thehollow rod 231. Finally, thehollow rod 231 is completely separated from therotary rod 211, but the lumen tissue remains outside the biological construct. Limited by the mechanical structure, there is inevitably a gap between the lumen tissue and the biological construct at this time, then an upward force is provided to the lumen tissue by means of thesupport platform 224, so as to avoid uneven attachment between the biological construct and the artificial blood vessel resulting from a downward movement due to the effect of gravity. Then, therotary rod 211 is internally ventilated to balloon the elastic film, so that the biological construct is completely attached onto the inner wall of the lumen tissue. Theheating unit 212 heats to accelerate the coagulation of the bio-ink, to finally obtain an artificial tissue precursor, which is removed from therotary rod 211. - Since the printed artificial tissue precursor needs to detect the flatness of its inner wall, in an improved embodiment of the device for printing lumen tissue construct of the present application, the device may further comprise an optical probe movable inside the
rotary rod 211, for detecting the flatness of the inner wall of the biological construct, wherein therotary rod 211 is made of a transparent material. There is a high implementability to design the optical probe in such a form as to be movable inside therotary rod 211, and to move the optical probe and photograph the internal wall of the biological construct by an image acquisition software before the artificial tissue precursor is removed from therotary rod 211, so as to judge whether the printed bio-block coating is intact, smooth and flat or not, and the embodiment adequately utilize the hollow structure inside therotary rod 211 to improve the structural utilization rate, which presents a high implementability. - For how to effectuate that the optical probe is movable inside the
rotary rod 211, in some improved embodiments, the optical probe is fixedly disposed in thehollow rod 231. For example, thehollow rod 231 is designed in a double-layer embedded structure, in which the first layer is used for embedding an artificial blood vessel, and the front end of the second layer is provided with an optical probe. Therotary rod 211 may also be a double-layer structure, in which ventilation is performed within the sandwich for ballooning the elastic film. The elastic film only covers the surface of therotary rod 211 but does not cover the front end, such as to enable the optical probe to extend into therotary rod 211. In the assembly process, the lumen tissue is sleeved on the surface of the biological construct, and the optical probe also moves along with thehollow rod 231 to the furthest end of the biological construct. When the lumen tissue is removed, the optical probe also moves along with thehollow rod 231 to the foremost end of the artificial precursor tissue, so as to accomplish the flatness detection in the assembly process. Certainly, in other improved embodiments, the optical probe is movably disposed in thehollow rod 231, that is, the optical probe moves independently with respect to thehollow rod 231, and the flatness detection can also be accomplished. In some other modified embodiments, the optical probe is movably disposed in therotary rod 211, and the optical probe moves from one end to the other within therotary rod 211 to accomplish the flatness detection. - The present application further provides a 3D bioprinter, which comprises the aforementioned device for printing lumen tissue construct. As the device of the present application can improve the biological reliability of the lumen tissue, correspondingly, the 3D bioprinter of the present application also has the advantageous technical effects described above, and thus will no longer be repeated here.
- The above-combined embodiments make detailed explanations for the embodiments of the present application, but the present application is not limited to the embodiments described. For a person skilled in the art, multiple changes, modifications, equivalent replacements, and variations made to such embodiments still fall within the protection scope of the present application without departing from the principles and substantive spirit of the present application.
Claims (20)
1-26. (canceled)
27. The bioprinting platform comprising:
a platform base;
a rotary part on the platform base, comprising a rotary rod for placing a bio-block and a medical adhesive to form a biological construct; and
a butt-jointed part movable relative to the rotary part, comprising a hollow rod having an outer wall for placing lumen tissue.
28. The bioprinting platform of claim 27 , wherein the outer wall of the rotary rod is covered with an elastic film.
29. The bioprinting platform of claim 28 , wherein an interior of the rotary rod is hollow, and the outer wall of the rotary rod is provided with a vent communicating with the interior, for exhausting air inside the rotary rod to balloon the elastic film.
30. The bioprinting platform of claim 27 , wherein an interior of the rotary rod is provided with a heating unit.
31. The bioprinting platform of claim 30 , wherein the heating unit includes a heating section and a spacing section that are spacedly arranged, the heating section has a surface wound with a resistance wire, and the heating section has a diameter that is less than that of the spacing section.
32. The bioprinting platform of claim 30 , wherein a temperature detecting unit is provided at one end of the heating unit proximate to the butt-jointed part, for detecting a temperature of the heating unit.
33. The bioprinting platform of claim 27 , wherein the bioprinting platform includes a gripping mechanism for gripping the lumen tissue to make the lumen tissue disengaged from the hollow rod and socketed to the biological construct.
34. The bioprinting platform of claim 33 , wherein the gripping mechanism includes a first gripping block and a second gripping block which are movable relatively.
35. The bioprinting platform of claim 34 , wherein the gripping mechanism includes a retaining unit for acting on a tail end of the lumen tissue so that the lumen tissue is disengaged from the hollow rod.
36. The bioprinting platform of claim 35 , wherein the retaining unit is cooperatively provided with a retaining ring acting on the tail end of the lumen tissue.
37. The bioprinting platform of claim 34 , wherein the gripping mechanism includes a limiting block provided at a bottom of the first gripping block and the second gripping block, for limiting relative movement of the first gripping block and the second gripping block, so that the first gripping block and the second gripping block are both tangent to an outer wall of the lumen tissue.
38. The bioprinting platform of claim 34 , wherein the gripping mechanism includes a support platform provided at a bottom of the first gripping block and the second gripping block, for supporting the lumen tissue.
39. The bioprinting platform of claim 27 , further comprising an optical probe movable inside the rotary rod, for detecting a flatness of an inner wall of the biological construct, wherein the rotary rod is made of a transparent material.
40. The bioprinting platform of claim 39 , wherein the optical probe is movably disposed within the rotary rod or the hollow rod.
41. The bioprinting platform of claim 39 , wherein the optical probe is fixedly disposed within the hollow rod.
42. The bioprinting platform of claim 33 , further comprising a reservoir provided below the rotary rod, for bearing a bioprinting construct disengaged and falling from the gripping mechanism.
43. A 3D bioprinter comprising the bioprinting platform of claim 27 .
44. A method of printing lumen tissue construct using the bioprinting platform of claim 27 , comprising a mantling step comprising: cladding a layer of elastic film on an outer wall of the rotary rod before printing the biological construct.
45. The method of claim 44 , further comprising a ballooning step comprising: ventilating into the layer of elastic film to balloon the layer of elastic film so that the biological construct is attached to the inner surface of the lumen tissue, after the lumen tissue is sleeved outside the biological construct.
Priority Applications (1)
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US17/183,584 US20210178678A1 (en) | 2018-01-18 | 2021-02-24 | Bioprinting platform, method for using the same and 3d bioprinter |
Applications Claiming Priority (4)
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CN201810048700.6 | 2018-01-18 | ||
CN201810048700 | 2018-01-18 | ||
US15/964,214 US10967570B2 (en) | 2018-01-18 | 2018-04-27 | Device for printing lumen tissue construct, method for using the same and 3D bioprinter |
US17/183,584 US20210178678A1 (en) | 2018-01-18 | 2021-02-24 | Bioprinting platform, method for using the same and 3d bioprinter |
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US15/964,214 Continuation US10967570B2 (en) | 2018-01-18 | 2018-04-27 | Device for printing lumen tissue construct, method for using the same and 3D bioprinter |
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US17/183,584 Abandoned US20210178678A1 (en) | 2018-01-18 | 2021-02-24 | Bioprinting platform, method for using the same and 3d bioprinter |
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WO2018050092A1 (en) * | 2016-09-14 | 2018-03-22 | 四川蓝光英诺生物科技股份有限公司 | Artificial tissue precursor and preparation method therefor |
CN106944626B (en) * | 2017-04-14 | 2019-10-18 | 华南理工大学 | A kind of complicated flow tube and manufacturing method for the thin Hermetic coating PVC material of automobile |
US10967570B2 (en) * | 2018-01-18 | 2021-04-06 | Revotek Co., Ltd | Device for printing lumen tissue construct, method for using the same and 3D bioprinter |
USD924281S1 (en) * | 2018-03-19 | 2021-07-06 | Revotek Co., Ltd | Device for synthesizing bio-ink |
USD900892S1 (en) * | 2018-04-03 | 2020-11-03 | Revotek Co., Ltd | Device for synthesizing bio-ink |
CN110614765B (en) * | 2018-06-19 | 2021-08-17 | 四川蓝光英诺生物科技股份有限公司 | Method for producing lumen tissue construct |
CN111037916B (en) * | 2019-12-03 | 2023-05-30 | 中国科学院重庆绿色智能技术研究院 | Additive manufacturing forming method of non-planar hot bed |
CN111037924A (en) * | 2019-12-03 | 2020-04-21 | 中国科学院重庆绿色智能技术研究院 | Non-planar hot bed for additive manufacturing and application thereof |
CN113059793A (en) * | 2019-12-30 | 2021-07-02 | 四川蓝光英诺生物科技股份有限公司 | Biological printer nozzle, biological printer and method for printing lumen tissue construct |
USD926236S1 (en) * | 2020-04-28 | 2021-07-27 | Revotek Co., Ltd | Instrument for preparing bio-ink |
CN113578614A (en) * | 2020-04-30 | 2021-11-02 | 四川蓝光英诺生物科技股份有限公司 | Body duct repairing device and method of operating body duct repairing device |
CN114683541A (en) * | 2020-12-30 | 2022-07-01 | 四川蓝光英诺生物科技股份有限公司 | Lumen tissue construct printing device, 3D biological printer and printing method |
CN114393826B (en) * | 2021-12-16 | 2023-08-08 | 浙江大学滨海产业技术研究院 | Double-temperature-control coaxial flow printing head device and method for biological 3D printer |
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Also Published As
Publication number | Publication date |
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CN209738289U (en) | 2019-12-06 |
EP3513948A1 (en) | 2019-07-24 |
CN110053255A (en) | 2019-07-26 |
US20190217537A1 (en) | 2019-07-18 |
US10967570B2 (en) | 2021-04-06 |
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