CN114683541A - Lumen tissue construct printing device, 3D biological printer and printing method - Google Patents

Lumen tissue construct printing device, 3D biological printer and printing method Download PDF

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Publication number
CN114683541A
CN114683541A CN202011631507.9A CN202011631507A CN114683541A CN 114683541 A CN114683541 A CN 114683541A CN 202011631507 A CN202011631507 A CN 202011631507A CN 114683541 A CN114683541 A CN 114683541A
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CN
China
Prior art keywords
assembly
biological
luminal tissue
printing device
glue
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202011631507.9A
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Chinese (zh)
Inventor
许子卿
何峻轩
李意军
向杰
蒋智
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sichuan Revotek Co ltd
Original Assignee
Sichuan Revotek Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sichuan Revotek Co ltd filed Critical Sichuan Revotek Co ltd
Priority to CN202011631507.9A priority Critical patent/CN114683541A/en
Priority to PCT/CN2021/139249 priority patent/WO2022143229A1/en
Publication of CN114683541A publication Critical patent/CN114683541A/en
Pending legal-status Critical Current

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive 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
    • B29C64/20Apparatus for additive manufacturing; Details thereof or accessories therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06Blood vessels
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive 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
    • B29C64/10Processes of additive manufacturing
    • B29C64/106Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • B29C64/112Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using individual droplets, e.g. from jetting heads
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C69/00Combinations of shaping techniques not provided for in a single one of main groups B29C39/00 - B29C67/00, e.g. associations of moulding and joining techniques; Apparatus therefore
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE 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
    • B33Y30/00Apparatus for additive manufacturing; Details thereof or accessories therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2240/00Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001Designing or manufacturing processes

Abstract

The application relates to a lumen tissue construct printing device, a 3D bioprinter and a printing method. The luminal tissue construct printing device comprises: hollow pole subassembly, rubber coating subassembly, shower nozzle subassembly and biological printing subassembly. The bio-printing assembly receives bio-ink ejected from the ejection head assembly and forms a bio-construct. The lumen tissue is fixed inside the hollow rod component, and medical glue is arranged on the inner surface of the lumen tissue through the gluing component. The biological construct is then applied to the inner surface of the luminal tissue by the bioprinting assembly. Because the medical glue is arranged on the inner surface of the lumen tissue and then contacts with the biological construct, the problem that the medical glue is not firmly adhered to the artificial blood vessel due to the polymerization reaction between the medical glue and hydroxide anions in water in biological ink can be avoided. In addition, the medical glue is arranged on the inner surface of the lumen tissue, the thickness is uniform, and the problem that the toxicity is caused to cells in biological ink due to overlarge use amount caused by the overlarge local medical glue is avoided.

Description

Lumen tissue construct printing device, 3D biological printer and printing method
Technical Field
The application relates to the technical field of 3D biological printing, in particular to a tube cavity tissue construct printing device, a 3D biological printer and a printing method.
Background
At present, when the artificial blood vessel is printed, biological ink is printed on a rotating rod, then medical glue is printed on the biological ink, then the artificial blood vessel is sleeved, and finally the biological ink is adhered to the inner wall of the artificial blood vessel through the expansion of an air bag, however, the artificial blood vessel printed by the method has poor reliability, and if the medical glue is not firmly adhered to the artificial blood vessel; the problem that the excessive use amount of the local medical adhesive has great toxicity to cells in the biological ink.
Disclosure of Invention
The application provides a lumen tissue construct printing device, a 3D bioprinter and a printing method, and aims to solve the problem of poor reliability of printed lumen tissue.
In one aspect, an embodiment of the present application provides a lumen tissue construct printing device, including:
a hollow shaft assembly for securing luminal tissue;
the gluing component is used for arranging medical glue on the inner surface of the lumen tissue fixed by the hollow rod component;
a nozzle assembly for ejecting biological ink;
a bioprinting assembly for receiving a biological ink and forming a biological construct, and for applying the biological construct on an interior surface of luminal tissue.
According to one embodiment of the application, the lumen tissue construct printing device further comprises a mechanical arm, wherein the mechanical arm of the mechanical arm is provided with a first matching part for picking and placing the hollow rod assembly and a second matching part for picking and placing the spray head assembly;
and the moving range of the manipulator comprises the working positions of the hollow rod component, the gluing component, the spray head component and the biological printing component.
According to one embodiment of the present application, the hollow rod assembly includes an outer sleeve and an inner sleeve disposed within the outer sleeve, the inner sleeve being provided with a fixation mechanism for fixation of luminal tissue.
According to one embodiment of the application, the fixing means are arranged at both ends of the inner sleeve.
According to an embodiment of the application, fixed establishment includes clamp ring and elasticity clamping piece, and the clamp ring sets up in interior sheathed tube tip, and the clamp ring has the ring chamber that communicates with interior sheathed tube inner chamber, and the elasticity clamping piece cover is located outside the clamp ring and is used for making the clamp ring along self radial compression in order to fix lumen tissue.
According to one embodiment of the application, the wall of the inner casing is provided with through holes.
According to one embodiment of the application, the through holes are evenly distributed with equal distance along the axial direction of the inner sleeve.
According to one embodiment of the application, the through holes are arranged in groups, the through holes of each group are uniformly distributed at equal intervals along the axial direction of the inner sleeve, and the through holes of any group are uniformly distributed at equal intervals along the circumferential direction of the inner sleeve.
According to one embodiment of the application, the inner sleeve is received within the outer sleeve, and at least one end of the outer sleeve is provided with a removable plug.
According to one embodiment of the application, the gluing assembly comprises a glue solution adsorption piece and a pushing piece; the glue solution adsorption piece is of a structure capable of adsorbing the glue solution and can be inserted into the tube cavity tissue, and the pushing piece can be inserted into the tube cavity tissue, is connected with the glue solution adsorption piece and moves along the axial direction of the tube cavity tissue.
According to one embodiment of the application, the gluing assembly further comprises a first mounting plate, a pusher mounting seat and a first driving member;
the pushing piece is arranged on the pushing piece mounting seat, and the pushing piece mounting seat is movably arranged on the first mounting plate, is connected with the working end of the first driving piece and is used for driving the pushing piece to axially reciprocate relative to the lumen tissue.
According to one embodiment of the present application,
the gluing assembly further comprises a consumable mounting seat provided with a pushing piece placing position, the consumable mounting seat can reciprocate along the length direction of the consumable mounting seat, and the pushing piece placing position passes through a working path of the pushing piece mounting seat under the first driving piece.
According to an embodiment of the application, the consumable mounting seat further comprises a pushing part recovery position, and the pushing part recovery position and the pushing part placement position are arranged along the movement direction of the consumable mounting seat.
According to an embodiment of this application, the rubber coating subassembly still includes the mechanism of glue dripping, and the play jiao kou that drips the mechanism and glue solution adsorb the piece and correspond the setting.
According to one embodiment of the application, the glue dripping mechanism comprises a liquid transfer device and a second driving part used for driving the liquid transfer device to work.
According to one embodiment of the application, the pipettors and the pusher mounting seat are arranged in a staggered manner along the width direction of the consumable mounting seat; the pipettor comprises a body and a sample adding needle; the body is detachably connected with the sample adding needle;
the consumable mounting seat also comprises a sample adding needle placing position; the sample adding needle placing position passes through the working path of the pipettor under the second driving piece.
According to an embodiment of the application, the consumable mounting further comprises a loading needle retrieval location and/or a medical gel reservoir, the loading needle retrieval location and/or the medical gel reservoir passing through a working path of the pipette under the second drive.
According to one embodiment of the application, the biological printing assembly comprises a platform base, a clamping block mounting seat and a rotary rod mounting seat, wherein the clamping block mounting seat and the rotary rod mounting seat are arranged on the platform base;
the rotating rod mounting seat is provided with a rotating rod which can rotate around the central axis of the rotating rod mounting seat;
the clamping block mounting seat is provided with a first clamping block and a second clamping block which can move relatively to open and close; the first clasping block and the second clasping block surround to form an area capable of accommodating the rotating rod; the side walls of the first clamping and holding block and the second clamping and holding block are provided with heating mechanisms.
According to one embodiment of the application, the outer sleeve of the rotating rod is provided with an elastic membrane, the rotating rod is hollow inside, the outer wall of the rotating rod is provided with an air outlet communicated with the inside, and the air outlet is used for discharging air in the rotating rod to support the elastic membrane;
the rotary rod mounting seat is provided with a third driving mechanism for driving the rotary rod to rotate around the central axis of the rotary rod.
According to an embodiment of the application, the clamping and holding block mounting seat is provided with two meshed driving gears and a fourth driving mechanism for driving the two driving gears to rotate in opposite directions, and the two driving gears are respectively in transmission with the first clamping and holding block and the second clamping and holding block.
According to one embodiment of the application, the spray head assembly is a biological ink spray head, the biological ink spray head comprises an injector, an injector mounting seat and a biological ink spray nozzle which are connected in sequence, and the discharge end of the injector is communicated with the biological ink spray nozzle;
the second matching part comprises a plunger mounting groove and a first connecting piece, the plunger mounting groove is matched with a plunger of the syringe, and the first connecting piece is matched with the syringe mounting seat.
According to an embodiment of the application, the manipulator further comprises a fixing plate and a fifth driving mechanism, wherein the plunger mounting groove is movably arranged on the fixing plate and is connected with the working end of the fifth driving mechanism for pushing the plunger.
According to one embodiment of the present application, the luminal tissue construct printing device further comprises a calibration assembly for calibrating the position of the biological ink jet nozzle and the biological printing assembly.
According to one embodiment of the application, the calibration assembly comprises a camera, a light source board and an electric cabinet; light source board and camera all set up near biological printing assembly position, electric cabinet one end and camera electric connection, the other end and arm electric connection.
According to one embodiment of the application, the printing device for the lumen tissue construct further comprises a temperature and humidity control assembly, wherein the temperature and humidity control assembly comprises a shell, a temperature and humidity control mechanism arranged in an inner cavity of the shell, and a sprayer storage chamber extending from the surface of the shell to the inner cavity, and the sprayer storage chamber is used for placing a biological ink sprayer; and a hinge cover plate capable of opening or closing the opening is arranged at the opening of the spray head storage chamber.
According to one embodiment of the application, a sixth driving mechanism for controlling the sprayer storage chamber to ascend and descend relative to the shell is arranged in the shell, the hinge cover plate is linked with the sprayer storage chamber, and the hinge cover plate is opened when the sprayer storage chamber ascends and is closed when the sprayer storage chamber descends.
According to one embodiment of the application, a mounting plate with a cover plate transmission assembly is arranged on the side face of the shell, and the hinge cover plate is linked with the spray head storage chamber through the cover plate transmission assembly;
the cover plate transmission assembly comprises a transmission mechanism, a sliding block and a linkage plate, the sliding block is arranged on the mounting plate in a sliding mode and is connected with the sixth driving mechanism through the linkage plate to lift relative to the shell, one end of the transmission mechanism is connected with the rotating shaft of the hinge cover plate, and the other end of the transmission mechanism is connected with the sliding block.
According to one embodiment of the application, the sliding block comprises convex edges arranged at two ends and a guide post clamped between two protruding sheets;
the linkage plate is movably sleeved on the guide post, and both sides of the linkage plate are connected with the two convex edges through elastic pieces sleeved on the guide post;
the transmission mechanism is connected with one side of the adjacent convex edge, which is far away from the guide post.
According to an embodiment of the application, transport mechanism is including setting up the first transfer wheel on the mounting panel respectively, the second transfer wheel and around the apron hold-in range of rolling up between first transfer wheel, second transfer wheel, first transfer wheel and axis of rotation coaxial coupling are connected with the linkage on the apron hold-in range, and the linkage is connected through spliced pole and the chimb one side of keeping away from the guide post.
According to one embodiment of the application, the temperature and humidity control mechanism comprises a temperature control assembly and a humidity control assembly, wherein the temperature control assembly comprises a cooling pipe arranged in the spray head storage chamber;
the humidity control mechanism includes an air drying mechanism in communication with the spray head storage chamber.
According to one embodiment of the application, the lumen tissue construct printing device further comprises a glue wiping assembly, wherein the working position of the glue wiping assembly is positioned in the moving range of the manipulator;
the frictioning assembly comprises a frictioning mounting seat and a frictioning motor arranged on the frictioning mounting seat, a frictioning rod is arranged on the frictioning motor, and frictioning sponge is arranged on the frictioning rod.
According to one embodiment of the application, a lumen tissue construct printing device comprises a lumen detector for detecting the flatness of lumen tissue; the working position of the cavity detector is positioned in the moving range of the manipulator.
In another aspect, the present application provides a 3D bioprinter, which includes the above-mentioned luminal tissue construct printing device.
In another aspect, an embodiment of the present application provides a printing method of a printing apparatus for a luminal tissue construct, including the following steps:
fixing the lumen tissue inside the hollow rod assembly;
medical glue is arranged on the inner surface of the lumen tissue fixed by the hollow rod component through the gluing component;
the biological printing component receives biological ink sprayed by the spray head component and forms a biological construct;
matching the hollow rod component with the biological printing component, and sleeving the biological construction body in the lumen tissue with the medical glue on the inner surface;
the biological construct is applied to the inner surface of the luminal tissue by the bioprinting assembly.
On the other hand, this application embodiment provides a hollow rod subassembly, and hollow rod subassembly includes the outer tube and sets up the interior sleeve pipe in the outer tube, and interior sleeve pipe is equipped with the fixed establishment that is used for the lumen tissue.
According to one embodiment of the application, the fixing means are arranged at both ends of the inner sleeve.
According to an embodiment of the application, fixed establishment includes clamp ring and elasticity clamping piece, and the clamp ring sets up in interior sheathed tube tip, and the clamp ring has the ring chamber that communicates with interior sheathed tube inner chamber, and the elasticity clamping piece cover is located outside the clamp ring and is used for making the clamp ring along self radial compression in order to fix lumen tissue.
According to one embodiment of the application, the wall of the inner casing is provided with through holes.
According to one embodiment of the application, the through holes are evenly distributed with equal distance along the axial direction of the inner sleeve.
According to one embodiment of the application, the through holes are arranged in groups, the through holes of each group are uniformly distributed at equal intervals along the axial direction of the inner sleeve, and the through holes of any group are uniformly distributed at equal intervals along the circumferential direction of the inner sleeve.
According to one embodiment of the application, the inner sleeve is received within the outer sleeve, and at least one end of the outer sleeve is provided with a removable plug.
In another aspect, the present application provides a printing apparatus for a lumen tissue construct, where the printing apparatus for a lumen tissue construct includes the hollow rod assembly described above.
On the other hand, the embodiment of the application provides a gluing assembly, which comprises a glue solution adsorption piece and a pushing piece; the glue solution adsorption piece is of a structure capable of adsorbing the glue solution and can be inserted into the tube cavity tissue, and the pushing piece can be inserted into the tube cavity tissue, is connected with the glue solution adsorption piece and moves along the axial direction of the tube cavity tissue.
According to one embodiment of the application, the gluing assembly further comprises a first mounting plate, a pusher mounting seat and a first driving member;
the pushing piece is arranged on the pushing piece mounting seat, and the pushing piece mounting seat is movably arranged on the first mounting plate, is connected with the working end of the first driving piece and is used for driving the pushing piece to axially reciprocate relative to the lumen tissue.
According to one embodiment of the application, the pusher member mount is removably coupled to the pusher member;
the gluing assembly further comprises a consumable mounting seat provided with a pushing piece placing position, the consumable mounting seat can reciprocate along the length direction of the consumable mounting seat, and the pushing piece placing position passes through a working path of the pushing piece mounting seat under the first driving piece.
According to an embodiment of the application, the consumable mounting seat further comprises a pushing part recovery position, and the pushing part recovery position and the pushing part placement position are arranged along the movement direction of the consumable mounting seat.
According to an embodiment of the application, the rubber coating subassembly still includes and drips gluey mechanism, drips gluey mechanism's the mouth of gluing and corresponds the setting with the glue solution absorption piece.
According to one embodiment of the application, the glue dripping mechanism comprises a liquid transfer device and a second driving part used for driving the liquid transfer device to work.
According to one embodiment of the application, the pipettors and the pusher mounting seat are arranged in a staggered manner along the width direction of the consumable mounting seat; the pipettor comprises a body and a sample adding needle; the body is detachably connected with the sample adding needle;
the consumable mounting seat also comprises a sample adding needle placing position; the sample adding needle placing position passes through the working path of the pipettor under the second driving piece.
According to an embodiment of the application, the consumable mounting seat further comprises a sampling needle recovery position and/or a medical glue storage groove, and the sampling needle recovery position and/or the medical glue storage groove pass through a working path of the pipettor under the second driving part.
In another aspect, an embodiment of the present application provides a lumen tissue construct printing device, where the lumen tissue construct printing device includes the foregoing glue spreading assembly.
On the other hand, the embodiment of the application provides a temperature and humidity control assembly, which comprises a shell, a temperature and humidity control mechanism arranged in an inner cavity of the shell, and a spray head storage cavity extending from the surface of the shell to the inner cavity, wherein the spray head storage cavity is used for placing a biological ink spray head; and a hinge cover plate capable of opening or closing the opening is arranged at the opening of the spray head storage chamber.
According to one embodiment of the application, a sixth driving mechanism for controlling the sprayer storage chamber to ascend and descend relative to the shell is arranged in the shell, the hinge cover plate is linked with the sprayer storage chamber, and the hinge cover plate is opened when the sprayer storage chamber ascends and is closed when the sprayer storage chamber descends.
According to one embodiment of the application, a mounting plate with a cover plate transmission assembly is arranged on the side face of the shell, and the hinge cover plate is linked with the spray head storage chamber through the cover plate transmission assembly;
the cover plate transmission assembly comprises a transmission mechanism, a sliding block and a linkage plate, the sliding block is arranged on the mounting plate in a sliding mode and is connected with the sixth driving mechanism through the linkage plate to lift relative to the shell, one end of the transmission mechanism is connected with the rotating shaft of the hinge cover plate, and the other end of the transmission mechanism is connected with the sliding block.
According to one embodiment of the application, the sliding block comprises convex edges arranged at two ends and a guide post clamped between two protruding sheets;
the linkage plate is movably sleeved on the guide post, and both sides of the linkage plate are connected with the two convex edges through elastic pieces sleeved on the guide post;
the transmission mechanism is connected with one side of the adjacent convex edge, which is far away from the guide post.
According to an embodiment of the application, transport mechanism is including setting up the first transfer wheel on the mounting panel respectively, the second transfer wheel and around the apron hold-in range of rolling up between first transfer wheel, second transfer wheel, first transfer wheel and axis of rotation coaxial coupling are connected with the linkage on the apron hold-in range, and the linkage is connected through spliced pole and the chimb one side of keeping away from the guide post.
According to one embodiment of the application, the temperature and humidity control mechanism comprises a temperature control assembly and a humidity control assembly, wherein the temperature control assembly comprises a cooling pipe arranged in the spray head storage chamber;
the humidity control mechanism includes an air drying mechanism in communication with the spray head storage chamber.
On the other hand, the embodiment of the present application provides a lumen tissue construct printing device, and the lumen tissue construct printing device includes the foregoing temperature and humidity control assembly.
According to the lumen tissue construct printing device of the embodiment of the application, the biological printing component receives biological ink sprayed by the spray head component and forms the biological construct. The lumen tissue is fixed inside the hollow rod component, and medical glue is arranged on the inner surface of the lumen tissue through the gluing component. The biological construct is then applied to the inner surface of the luminal tissue by the bioprinting assembly. Because the medical adhesive is arranged on the inner surface of the lumen tissue and then contacts with the biological construct, and does not directly contact with the biological ink, the problem that the medical adhesive and the artificial blood vessel are not firmly adhered enough due to the polymerization reaction of the medical adhesive and hydroxide anions in water in the biological ink can be avoided. In addition, the medical glue is arranged on the inner surface of the lumen tissue, the thickness is uniform, and the problem that the toxicity is caused to cells in biological ink due to overlarge use amount caused by the overlarge local medical glue is avoided.
Drawings
Features, advantages and technical effects of exemplary embodiments of the present application will be described below with reference to the accompanying drawings.
FIG. 1 is a schematic illustration of a device for printing a luminal tissue construct as disclosed in one embodiment of the present application;
FIG. 2 is a schematic diagram of a glue dispensing assembly according to an embodiment of the present disclosure;
FIG. 3 is a schematic structural diagram of a rubbing assembly, a cavity detector and a calibration assembly according to an embodiment of the present disclosure;
FIG. 4 is a schematic view of a glue application assembly according to an embodiment of the present disclosure;
FIG. 5 is a schematic view of an inner sleeve according to an embodiment of the present disclosure;
FIG. 6 is a schematic structural diagram of a bioprinting assembly as disclosed in one embodiment of the present application;
figure 7 is a schematic view of a robot cooperating with a hollow bar assembly according to an embodiment of the present disclosure;
FIG. 8 is a schematic view of the robot of FIG. 7 engaged with the showerhead post assembly;
fig. 9 is a schematic view of an internal structure of a temperature and humidity control assembly disclosed in an embodiment of the present application;
FIG. 10 is a schematic view of the temperature and humidity control assembly of FIG. 9 from a perspective external view;
fig. 11 is an external view of the temperature and humidity control assembly of fig. 9 from another perspective.
In the drawings, the drawings are not necessarily drawn to scale.
Detailed Description
Embodiments of the present application will be described in further detail below with reference to the drawings and examples. The following detailed description of the embodiments and the accompanying drawings are provided to illustrate the principles of the application, but are not intended to limit the scope of the application, i.e., the application is not limited to the described embodiments.
In the description of the present application, it is to be noted that, unless otherwise specified, "a plurality" means two or more; the terms "upper," "lower," "left," "right," "inner," "outer," and the like, indicate an orientation or positional relationship that is merely for convenience in describing the application and to simplify the description, and do not indicate or imply that the referenced devices or elements must have a particular orientation, be constructed and operated in a particular orientation, and thus should not be construed as limiting the application. Furthermore, the terms "first," "second," and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance. "vertical" is not strictly vertical, but is within the tolerance of the error. "parallel" is not strictly parallel but within the tolerance of the error.
In the description of the present application, it is also to be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; may be directly connected or indirectly connected through an intermediate. The specific meaning of the above terms in the present application can be understood as appropriate by one of ordinary skill in the art.
The applicant notices that the reliability of the existing printed artificial blood vessel is poor, and the adhesion between the medical glue and the artificial blood vessel is not firm enough; local medical glue use amount is too big after the great problem of toxicity of cell in the biological chinese ink, study artificial blood vessel, and then in the discovery current printing mode, on printing the rotary rod with biological chinese ink earlier, print biological chinese ink with medical glue again. The medical adhesive can be contacted with the biological ink firstly, and if the biological ink contains more water, the medical adhesive can generate polymerization reaction with hydroxide anions in the water in the biological ink, so that the reaction of the medical adhesive and the artificial blood vessel is influenced, and the medical adhesive and the artificial blood vessel are possibly not firmly adhered; meanwhile, by adopting the printing mode, as the medical adhesive is directly printed on the biological Chinese ink, if the surface of the Chinese ink layer is uneven, the use amount of the local medical adhesive is possibly larger (for example, more medical adhesive is needed to fill up uneven areas), and the larger the use amount of the medical adhesive is, the larger the toxicity to cells in the biological Chinese ink is.
Based on the above-identified problems discovered by the applicant, the applicant has developed a device for printing a luminal tissue construct, which is further described below with respect to embodiments of the present application.
For a better understanding of the present application, embodiments of the present application are described below with reference to fig. 1 to 11.
An embodiment of the present application provides a lumen tissue construct printing device, referring to fig. 1, including:
a hollow shaft assembly 100 for use in securing luminal tissue.
And a glue applying assembly 200 for applying medical glue to the inner surface of the lumen tissue fixed by the hollow rod assembly 100.
A showerhead assembly 300 for use in ejecting biological ink.
A bioprinting assembly 400 for receiving a biological ink and forming a biological construct, and for applying the biological construct to an interior surface of a luminal tissue.
The lumen tissue comprises human body pipelines such as blood vessels, trachea, esophagus, intestinal canal, ureter and the like. The luminal tissue is, inter alia, an artificial blood vessel, such as the commercially available gore blood vessel. For simplicity, the lumen tissue of the present embodiment is described by taking an artificial blood vessel as an example.
Biological ink is ink that can be used in 3D printers. The biological ink of the present invention includes biological tiles, as well as other substances used to modulate the performance of biological tiles. The biological brick (please refer to document CN106039419B) includes: the core layer and the shell layer are each independently made of biodegradable materials. The biodegradable materials in the core and shell layers can reduce or prevent cells within the bio-brick from mechanical damage during manipulation (e.g., bioprinting) and can provide controlled release of substances (e.g., nutrients, extracellular matrix, cytokines, pharmaceutically active ingredients, etc.) to promote cellular activity and function (proliferation, differentiation, migration, secretion, or metabolism).
The lumen tissue is disposed within the hollow shaft assembly 100, and the hollow shaft assembly 100 can secure the lumen tissue such that the position of the lumen tissue is fixed. Therefore, the lumen tissue is not displaced when medical glue is arranged on the inner surface (such as coated medical glue) or the biological construct is applied on the inner surface of the lumen tissue, thereby ensuring the corresponding effect. The internal surface of lumen tissue is comparatively level and smooth, directly sets up medical glue at the internal surface of lumen tissue, and glue film thickness also can be comparatively even. In contrast, biological constructs, whether on an ink surface or formed from an ink, can have areas of relative unevenness. The medical glue has certain fluidity, and is easy to flow to an uneven area to fill the uneven area, so that the thickness of the medical glue in the partial area is larger, and the toxicity to cells in the biological ink in the area is higher.
The inkjet head assembly 300 stores biological ink, and the biological ink is ejected to the biological printing assembly 400 by pushing, pulling, squeezing or the like, which is performed manually or mechanically automatically. The biological ink forms a biological construct on the bioprinting assembly 400. The biological construct may be applied to the inner surface of the luminal tissue under the action of the bioprinting assembly 400. The inner surface of the lumen tissue is provided with medical glue, and the biological construct can be tightly combined with the inner surface of the lumen tissue.
According to the device for printing the luminal tissue construct, the bio-printing component 400 receives bio-ink ejected by the nozzle component 300 and forms the biological construct. The lumen tissue is fixed inside the hollow rod assembly 100, and medical glue is provided on the inner surface of the lumen tissue through the glue coating assembly 200. The biological construct is then applied to the inner surface of the luminal tissue by the bioprinting assembly 400. Because the medical glue is arranged on the inner surface of the lumen tissue and then is contacted with the biological construct, and is not directly contacted with the biological ink, the problem that the medical glue and the artificial blood vessel are not firmly adhered enough due to the polymerization reaction of the medical glue and hydroxide anions in water in the biological ink can be avoided. In addition, the medical glue is arranged on the inner surface of the lumen tissue, the thickness is uniform, and the problem that the toxicity is caused to cells in biological ink due to overlarge use amount caused by the overlarge local medical glue is avoided.
In one embodiment, referring to fig. 1, the luminal tissue construct printing device further comprises a robotic arm 500, the robotic arm 510 of the robotic arm 500 having a first mating portion 520 for accessing the hollow shaft assembly 100 and a second mating portion 530 for accessing the showerhead assembly 300. And the range of motion of the robot 510 includes the operating positions of the hollow bar assembly 100, the glue application assembly 200, the spray head assembly 300, and the bioprinting assembly 400.
The operating positions of the hollow bar assembly 100, the glue application assembly 200, the spray head assembly 300, and the bioprinting assembly 400 may include a working position and an assembly position of the respective assemblies. The operative position of the components, such as the hollow shaft assembly 100, for example, is the work site involved in the lumen tissue securing process, the applicator assembly 200 for the applicator process, the nozzle assembly 300 for the applicator process, and the bio-ink printing assembly 400 for the bio-ink receiving process. The hollow bar assembly 100, the glue application assembly 200, the head assembly 300, and the bio-printing assembly 400 may need to be assembled during use, and the range of motion of the robot arm 510 of the robot arm 500 may be related to the assembly position of the above-mentioned components, which may be assisted by the assembly.
Referring to fig. 8 and 9, and the printing device for the luminal tissue construct has more steps in the printing process, and consumables and components are transferred for a plurality of times, particularly, the hollow rod assembly 100 and the nozzle assembly 300 are involved in a plurality of processes, which involve more working positions and a relatively larger moving range, so that the robot 510 of the robot arm 500 is provided with a first matching part 520 for taking and placing the hollow rod assembly 100 and a second matching part 530 for taking and placing the nozzle assembly 300. The consumable and component operation and transfer through the mechanical arm 500 reduces the human participation steps, reduces the risk of pollution, and has controllable printing process, thereby improving the stability of the printing process.
In one embodiment, referring to fig. 3-5, the hollow shaft assembly 100 includes an outer sleeve 110 and an inner sleeve 120 disposed within the outer sleeve 110, the inner sleeve 120 being provided with a securing mechanism 130 for luminal tissue.
The lumen of the inner cannula 120 fits the luminal tissue, which extends into the lumen of the inner cannula 120 and is fixed by the fixing mechanism 130. The lumen tissue is not displaced when medical glue is arranged on the inner surface (such as coated medical glue) or the biological construct is applied on the inner surface of the lumen tissue, so that the corresponding effect is ensured.
In one embodiment, referring to fig. 3-5, the securing mechanisms 130 are disposed at both ends of the inner sleeve 120.
The fixing mechanisms 130 are disposed at two ends of the inner sleeve 120, and stretch two ends of the lumen tissue mounted in the inner sleeve 120, so that the lumen tissue is in a stretched state, which is beneficial to uniformly coating the medical adhesive and applying the biological construct to the inner surface of the lumen tissue.
In one embodiment, referring to fig. 5, the fixing mechanism 130 includes a clamping ring 131 and elastic clips 132, the clamping ring 131 is disposed at the end of the inner cannula 120, the clamping ring 131 has an annular cavity communicated with the inner cavity of the inner cannula 120, and the elastic clips 132 are sleeved outside the clamping ring 131 for radially compressing the clamping ring 131 along itself to fix the luminal tissue.
For simplicity, the lumen tissue of the present embodiment and the following embodiments are described by taking the artificial blood vessel as an example. The both ends of interior sleeve pipe 120 are equipped with elasticity clamping piece 132, then suit clamp ring 131 on elasticity clamping piece 132, apply force to elasticity clamping piece 132 through clamp ring 131, will install the both ends of the artificial blood vessel in interior sleeve pipe 120 and stretch, thereby make artificial blood vessel be in tensile state, specifically install as follows, at first install artificial blood vessel in interior sleeve pipe 120, it is fixed through clamp ring 131 to pass through the elasticity clamping piece 132 of interior sleeve pipe 120 one end earlier, thereby fix artificial blood vessel's one end, through tweezers at the other end of interior sleeve pipe 120 to the other end of artificial blood vessel stretch, then it is fixed through clamp ring 131 with elasticity clamping piece 132, thereby be in tensile state when making artificial blood vessel install in interior sleeve pipe 120.
In one embodiment, referring to FIG. 5, the wall of the inner sleeve 120 is provided with through holes 140.
When the existing printer is used for printing the artificial blood vessel, biological ink is firstly printed on a rotating rod, then medical glue is printed on the biological ink, then the artificial blood vessel is sleeved on a hollow rod component, and finally the biological ink is adhered to the inner wall of the artificial blood vessel through the expansion of an air bag.
However, through a lot of researches, the applicant finds that air between the air bag and the artificial blood vessel sleeved on the inner wall of the hollow rod assembly can be discharged only through one end of the hollow rod assembly in the process of inflating the air bag because the surface of the existing hollow rod assembly is not provided with the vent hole, so that part of the air is discharged firstly, and part of the air is discharged afterwards. Therefore, when the air bag is expanded, part of the area is expanded first, and part of the area is expanded later, so that the thickness of the biological ink layer is not uniform after the biological ink is adhered to the artificial blood vessel.
Based on this, the applicant has made improvements to the inner sleeve 120. Through holes 140 are formed in the wall of the inner sleeve 120, and the through holes 140 penetrate through the wall of the inner sleeve 120, so that the inner cavity of the inner sleeve 120 is communicated with the outside. In the air bag supporting process, air between the air bag and the artificial blood vessel can be discharged through the vent hole, so that the air bag can be uniformly supported. After the biological ink is adhered to the artificial blood vessel, the thickness of the biological ink layer is uniform.
In one embodiment, referring to fig. 5, the through holes 140 are uniformly distributed at equal intervals along the axial direction of the inner sleeve 120.
The inner sleeve 120 has a certain axial length, and the through holes 140 are uniformly distributed along the axial direction of the inner sleeve 120 at equal intervals, so that all parts of the air bag can be uniformly supported along the axial direction of the inner sleeve 120, and after the biological ink adheres to the artificial blood vessel, the axial thickness of the biological ink layer along the artificial blood vessel is more uniform.
In one embodiment, referring to fig. 5, the through holes 140 are arranged in groups, the through holes 140 of each group are uniformly distributed at equal intervals in the axial direction of the inner sleeve 120, and the through holes 140 of any group are uniformly distributed at equal intervals in the circumferential direction of the inner sleeve 120.
The balloon is also inflated along the circumferential direction of the inner tube 120 during the inflation process, so that the through holes 140 are equally spaced and evenly distributed around the circumference of the inner tube 120, and the through holes 140 are equally spaced and evenly distributed along the axial direction of the inner tube. In the process of expanding the air bag, air between the air bag and the artificial blood vessel is uniformly discharged through the vent holes, so that all parts of the air bag can be uniformly supported. After the biological ink is adhered to the artificial blood vessel, the thickness of the biological ink layer is more uniform.
In one embodiment, referring to FIG. 4, the inner sleeve 120 is received within the outer sleeve 110, and at least one end of the outer sleeve 110 is provided with a removable plug.
The length of the inner sleeve 120 is less than the length of the outer sleeve 110. The inner sleeve 120 is received in the outer sleeve 110, i.e. the inner sleeve 120 has one end flush with the outer sleeve 110 and one end completely received in the outer sleeve 110, or both ends received in the outer sleeve 110. The outer tube 110 is provided with a detachable plug at an end portion thereof for completely receiving the inner tube 120, and the plug is used for plugging the end portion of the balloon when the balloon is expanded in the process of assembling the artificial blood vessel, so as to prevent the balloon from expanding and extending in the axial direction of the rotating rod 431.
In one embodiment, referring to fig. 2, the glue application assembly 200 includes a glue solution suction member and a pushing member 210. The glue solution adsorption piece is of a structure capable of adsorbing the glue solution and can be inserted into the tube cavity tissue, and the pushing piece 210 can be inserted into the tube cavity tissue, is connected with the glue solution adsorption piece and moves along the axial direction of the tube cavity tissue.
The glue solution adsorption piece is a structure capable of adsorbing glue solution, such as cotton balls, sponges, brush heads and other materials capable of adsorbing medical glue. The glue solution adsorption piece can be directly inserted into the medical glue to absorb the glue solution and then inserted into the lumen tissue. Of course, the glue solution adsorbing member may be inserted into the lumen tissue first, and then the glue solution may be added to the glue solution adsorbing member by the medical glue adding device.
The pushing piece 210 can be inserted into the lumen tissue and connected with the glue solution adsorption piece, and the pushing piece 210 pushes the glue solution adsorption piece to move along the axial direction of the lumen tissue by pushing at least one of the pushing piece 210 and the hollow rod assembly 100 to move, so that the glue solution is coated on the inner surface of the lumen tissue, and the inner surface of the lumen tissue has more uniform medical glue.
In one embodiment, the glue solution adsorbing member is a sponge.
For simplicity of description, the glue solution adsorbing member in this embodiment and the following embodiments is described by taking a sponge as an example. The sponge is a flexible porous material, the specific type of the sponge is not limited, and the sponge is harmless to human bodies and can adsorb medical adhesive. The pores of the sponge are uniformly distributed and the pore diameter uniformity is good, so that the medical adhesive is uniformly dispersed in the sponge. When the pushing piece 210 pushes the sponge to move on the inner surface of the lumen tissue, the medical glue uniformly flows out of the sponge and is smeared on the inner surface of the lumen tissue.
It can be understood that the sponge has a certain amount of glue absorption, and the specific values thereof are different due to the difference between the sponge volume and the material (such as porosity) of the sponge. Take the example of inserting a sponge into the lumen tissue and adding the glue to the sponge. When the glue sucking amount of the sponge is smaller than the adding amount of the medical glue, the redundant medical glue can stay on the surface of the sponge, the medical glue flows out unevenly, and the medical glue on the inner surface of the lumen tissue is uneven in thickness. When the glue absorption amount of the sponge is larger than the addition amount of the medical glue, the outflow amount of the medical glue from the sponge is insufficient. With the advancement of the sponge, the outflow volume of the medical glue is gradually reduced, and the thickness of the medical glue on the inner surface of the lumen tissue is also uneven. Thus, sponges with different specifications, such as sponges with different volumes and sponges with different porosities can be arranged, so that the sponges have different glue absorption amounts. And then the corresponding sponge can be selected according to the thickness of the medical glue (namely the thickness of the medical glue layer formed on the inner wall of the artificial blood vessel) to be coated. The quantity of the medical glue coated on the inner wall of the artificial blood vessel can be stably controlled.
In one embodiment, referring to FIG. 2, the glue assembly 200 includes a first mounting plate 220, a pusher mount 230, and a first drive member 240. The pushing member 210 is disposed on the pushing member mounting seat 230, and the pushing member mounting seat 230 is movably disposed on the first mounting plate 220 and connected to the working end of the first driving member 240 for driving the pushing member 210 to reciprocate axially relative to the lumen tissue.
The pusher mount 230 and the first drive member 240 are both disposed on the first mounting plate 220. The pusher member mount 230 is movably disposed on the first mounting plate 220, such as in a sliding connection. The working end of the first driving member 240 is connected to the driving member mounting seat 230 to drive the driving member mounting seat 230 to reciprocate, so that the driving member 210 can reciprocate. The pushing member 210 can be detachably connected with the sponge by clamping, hooking and the like, and further drives the sponge to move in a reciprocating manner. The first driving member 240 may be a cylinder or a linear driving motor, etc.
The gluing process comprises the following steps: when the sponge is saturated, the end of the hollow rod assembly 100 with the sponge is moved to the lower part of the pushing member 210 by the mechanical arm 500 or manually, and the first driving member 240 drives the pushing member 210 to reciprocate towards the hollow rod assembly 100 to drive the sponge to reciprocate, so that the coating effect of the medical gel is improved.
Of course, in other embodiments, the pushing member 210 may not be connected to the sponge, but only abut against the sponge. The first driving member 240 drives the pushing member 210 to move toward the hollow bar assembly 100, and the sponge is moved from the first end to the second end of the hollow bar assembly 100. The hollow bar assembly 100 is then removed from the pusher member 210 by the robotic arm 500 or manually, reversing the direction to align the second end of the hollow bar assembly 100 with the pusher member 210, and the pusher member 210 moves the sponge from the second end to the first end of the hollow bar assembly 100.
In one embodiment, referring to FIG. 2, the pusher shoe 230 is removably coupled to the pusher 210. The gluing assembly 200 further comprises a consumable mounting seat 250 provided with a pushing member placing position 251, the consumable mounting seat 250 can reciprocate along the length direction of the consumable mounting seat, and the pushing member placing position 251 passes through the working path of the pushing member mounting seat 230 under the first driving member 240.
The pusher mount 230 is detachably connected to the pusher 210, such as by magnetic attraction, clamping, or the like. The number of pusher placing locations 251 of the consumable mount 250 is plural, such as 4, and one pusher 210 is placed in each pusher placing location 251. The consumable mount 250 can reciprocate along its length, such as the X-axis shown in fig. 2, through the movement path of the pusher mount 230. After the pusher member mount 230 unloads the pusher member 210, it can be combined with the pusher member 210 of the pusher member placing position 251 to replace the pusher member 210 with a new one. The consumable mount 250 can provide the pusher mount 230 with the pusher 210 in time. Therefore, after the glue coating assembly 200 coats the medical glue on each lumen tissue, the pushing element 210 is replaced, and the phenomenon of pollution caused by repeated use of the pushing element 210 is avoided.
In one embodiment, referring to fig. 2, the consumable mount 250 further includes a pusher recovery station 252, and the pusher recovery station 252 and the pusher placement station 251 are disposed along the moving direction of the consumable mount 250.
Since the pusher recovery station 252 and the pusher placing station 251 are disposed along the moving direction of the consumable mount 250, the pusher recovery station 252 may also reach the working path of the pusher mount 230 under the first driving member 240, so as to receive the pusher 210 unloaded from the pusher mount 230. The pusher recovery station 252 receives the unloaded pushers 210, so that the lumen tissue construct printing device is neater and more orderly, and consumable materials are prevented from being polluted.
In one embodiment, the glue dispensing assembly 200 further includes a glue dispensing mechanism 260, and a glue outlet of the glue dispensing mechanism 260 is disposed corresponding to the glue solution adsorbing member.
The glue dripping mechanism 260 may be a dropper, a graduated syringe 310, a pipette 261, or the like, which can control the amount of the medical glue added to some extent. After the sponge is placed into the inner cannula 120 for fixation, the medical gel is dripped into the sponge through the gel dripping mechanism 260. The glue dripping mechanism 260 can better control the adding amount of the medical glue in the sponge, so that the amount of the medical glue coated on the inner wall of the artificial blood vessel can be more stably controlled.
In one embodiment, referring to fig. 2, the glue dropping mechanism 260 includes a pipette 261 and a second driver 262 for driving the pipette 261 to operate.
The second driving piece 262 drives the liquid transferring device 261 to drop the medical glue, and the automation degree is high. And the pipette 261 can precisely control the amount of the medical gel added to the sponge, so that the amount of the medical gel coated on the inner wall of the artificial blood vessel can be stably controlled.
In one embodiment, referring to fig. 2, pipettor 261 and pusher mount 230 are staggered along the width of consumable mount 250. Pipette 261 includes a body 263 and a sample application needle 264. The body 263 and the sample addition needle 264 are detachably connected. Consumable mounting receptacle 250 also includes a sample application needle placement site 253. The loading needle placement position 253 passes through the working path of pipette 261 under second drive member 262.
Pipettor 261 and pusher mount 230 are staggered along the width direction of consumable mount 250 (the Y-axis direction shown in fig. 2), reducing the probability of interference between the two. The pipettor 261 is detachably connected to the sampling needle 264, for example, by magnetic attraction, clamping, or the like. The number of the sample needle placement positions 253 of the consumable holder 250 is plural, for example, 4, and one sample needle 264 is placed in each sample needle placement position 253. The consumable mounting base 250 may reciprocate along its length, passing through the movement path of the pipette 261. After the sample addition needle 264 is removed from the pipette 261, the pipette can be bonded to the sample addition needle 264 in the sample addition needle placement position 253, and a new sample addition needle 264 is replaced. Consumable mount 250 can provide a sample addition needle 264 for a pipette 261 in a timely manner. Therefore, after the pipette 261 coats the medical glue on each lumen tissue, the sampling needle 264 is replaced, and the phenomenon of pollution caused by repeated use of the sampling needle 264 is avoided.
In one embodiment, referring to fig. 2, the consumable mounting receptacle 250 further comprises a loading needle recovery site 254 and/or a medical gel reservoir 255, the loading needle recovery site 254 and/or the medical gel reservoir 255 passing through the working path of the pipettor 261 under the second driver 262.
Likewise, the loading needle recovery site 254 and/or the medical gel reservoir 255 can reach the corresponding working position of the pipettor 261 under the second drive member 262. After the medical glue storage groove 255 arrives, the liquid shifter 261 precisely sucks the glue solution, and the automation degree is higher. After the sampling needle recovery position 254 arrives, the used sampling needle 264 is collected, so that the tube cavity tissue construct printing device is more tidy and ordered, and consumable materials are prevented from being polluted mutually.
In one embodiment, referring to fig. 6, bioprinting assembly 400 includes a platform base 410, a clasping block mount 420, and a rotating rod mount 430, both clasping block mount 420 and rotating rod mount 430 disposed on platform base 410. The rotating rod mounting seat 430 is provided with a rotating rod 431 capable of rotating around the central axis of the rotating rod mounting seat; the clasping block mounting seat 420 is provided with a first clasping block 421 and a second clasping block 422 which can move relatively to open and close; the first clasping block 421 and the second clasping block 422 surround an area which can accommodate a rotating rod 431; the side walls of the first clasping block 421 and the second clasping block 422 are provided with heating mechanisms 423.
The rotating rod mounting seat 430 is provided with a rotating rod 431 capable of rotating around a central axis thereof, and the rotating rod 431 is driven to rotate by a driving mechanism. The clasping block mounting seat 420 is provided with a first clasping block 421 and a second clasping block 422 which can move relatively. The first clasping block 421 and the second clasping block 422 can move relatively in a translation or rotation manner. The first clasping block 421 and the second clasping block 422 are partially folded or completely folded to form an area. This region, at the end remote from the drive mechanism, may receive a rotating rod 431. The side walls of the first clasping block 421 and the second clasping block 422 are respectively provided with a heating mechanism 423, such as an electric heating plate, which can heat the region.
When the bio-ink printing process is performed, the head assembly 300 is moved to the position of the rotation rod 431 by the robot 510 or manually. The head assembly 300 ejects the bio-ink onto the rotating rod 431 while moving the head assembly 300 from one end of the rotating rod 431 to the other end of the rotating rod 431, thereby completing the printing of the bio-ink. By adopting the rotary printing mode of the rotary rod 431, the bio-ink can be completely covered on the rotary rod 431, and the thickness of the bio-ink on the rotary rod 431 is uniform. After the printing of the biological ink is completed, the first clamping and holding block 421 and the second clamping and holding block 422 are partially folded, for example, the first clamping and holding block 421 and the second clamping and holding block 422 are folded by rotating, one end of the first clamping and holding block is folded, the other end of the first clamping and holding block is opened, or the first clamping and holding block 421 and the second clamping and holding block 422 are folded by translating, and a certain interval is formed between the first clamping and holding block 421 and the second clamping and holding block 422. At this time, a bio-ink forming region is formed between the first holding block 421 and the second holding block 422, and then the bio-ink forming is completed by controlling the temperature of the heating mechanism 423. Of course, in order to make the heat preservation effect in the molding region better in the molding process, the first clasping block 421 and the second clasping block 422 may be completely closed to form a completely closed region therebetween.
The first clamping and holding block 421 and the second clamping and holding block 422 can move relatively, and the size and the sealing degree of a clamping and holding area between the first clamping and holding block and the second clamping and holding block can be controlled, so that different requirements of biological ink forming on forming speed and heat preservation effect can be met.
In one embodiment, the outer sleeve of the rotating rod 431 is provided with an elastic membrane, the inside of the rotating rod 431 is hollow, and the outer wall of the rotating rod 431 is provided with an air outlet communicated with the inside, and the air outlet is used for discharging air in the inside of the rotating rod 431 to support the elastic membrane. The rotating rod mounting seat 430 is provided with a third driving mechanism 433 for driving the rotating rod 431 to rotate around the central axis thereof.
The elastic membrane is of a bag structure with an opening at one end, is made of materials with certain elasticity, can expand outwards under certain pressure, and has an integral structure similar to a balloon. The elastic membrane may be a balloon. The elastic membrane is sleeved on the rotating rod 431, one end, far away from the elastic membrane, of the rotating rod 431 can be communicated with a gas source, and gas is discharged from the gas outlet hole to support the elastic membrane.
When the bio-ink printing process is performed, the head assembly 300 ejects the bio-ink onto the elastic membrane. After the biological ink is printed, heat preservation forming is carried out, so that a biological construct is formed on the surface of the air sac. Then, the artificial blood vessel assembling process is performed, and the hollow rod assembly 100 is moved manually or by a robot 510, and the hollow rod assembly 100 is fitted around the rotating rod 431 to ventilate the rotating rod 431. When the air sac is propped, the biological construct on the surface of the air sac displaces outwards along with the expansion of the elastic membrane, and finally contacts with the inner wall of the artificial blood vessel and is adhered to the inner wall of the artificial blood vessel, so that the printed artificial blood vessel is obtained.
The elastic membrane may expand more uniformly with the aeration of the rotating rod 431. The biological construct on the surface of the elastic membrane is uniformly stressed and can almost simultaneously contact with the inner wall of the artificial blood vessel, so that the adhesion effect is good. And the expansion speed of the elastic membrane can be adjusted according to the requirement through the ventilation speed, so that the process is more controllable. In addition, the elastic membrane has certain flexibility and can better form protection to a biological structure in the expansion process.
In one embodiment, referring to fig. 6, the clasping block mounting seat 420 is provided with two meshed driving gears 424 and a fourth driving mechanism for driving the two driving gears 424 to rotate in opposite directions, and the two driving gears 424 are respectively in transmission with the first clasping block 421 and the second clasping block 422.
The two drive gears 424 are identically sized to engage one another. The fourth driving mechanism may be a driving motor, and the driving motor may drive the two driving gears 424 to rotate synchronously in opposite directions through the transmission gear. Each driving gear 424 rotates one first clasping block 421. The first clamping and holding block 421 and the second clamping and holding block 422 can be synchronously rotated to uniformly adjust the size of the surrounding area, and the adjusting effect is good.
In one embodiment, referring to fig. 7-8, the inkjet head assembly 300 is a biological ink inkjet head including an injector 310, an injector mount 320, and a biological ink jet nozzle 330 connected in series, with an outfeed end of the injector 310 communicating with the biological ink jet nozzle 330. The second fitting part 530 includes a plunger mounting groove 531 and a first connector 532, the plunger mounting groove 531 being fitted with the plunger of the syringe 310, and the first connector 532 being fitted with the syringe mounting seat 320.
The bio-ink jet head includes an injector 310, an injector mount 320, and a bio-ink jet nozzle 330, the injector mount 320 being connected in series. The injector 310 and the bio-ink jet nozzle 330 are both mounted to the injector mount 320. The biological ink sprayer and the injector mounting seat 320 are detachably connected in a threaded or clamping manner and the like. The syringe 310 stores bio-ink therein, the discharge end of the syringe 310 communicates with a bio-ink nozzle 330, and the plunger extends out of the syringe mount 320. By pushing the plunger, bio-ink can be ejected from the bio-ink nozzle 330.
The second fitting part 530 of the robot 510 includes a plunger mounting groove 531 and a first connector 532, the plunger mounting groove 531 may fix the plunger of the syringe 310, and the first connector 532 may fix the syringe mounting seat 320. The robot 510 is coupled to the bio-ink nozzle at two points by the second coupling portion 530 for quick release connection, so as to grab and fix the bio-ink nozzle, and further carry the bio-ink nozzle to a corresponding working position, such as near the bio-printing assembly 400. Specifically, the injector mounting base 320 is provided with a second connector for quick release connection with the first connector 532.
In one embodiment, the manipulator further comprises a fixing plate 533 and a fifth driving mechanism 535, and the plunger mounting groove 531 is movably disposed on the fixing plate 533 and connected to a working end of the fifth driving mechanism 535 for pushing the plunger.
Referring to fig. 7 to 8, in order to improve the automation degree of the robot 510, the second engagement portion 530 is further provided with a bio-ink nozzle driving assembly for pushing the plunger to eject bio-ink. The biological ink nozzle driving assembly comprises a fixing plate 533 installed on the manipulator 510, a sliding groove is installed on the fixing plate 533, a sliding block 534 movably matched with the sliding groove is installed on the sliding groove, and a plunger installation groove 531 is arranged on the sliding block 534. A fifth driving mechanism 535, such as a bio-ink nozzle driving motor, is installed at one end of the plunger installation groove 531, and the bio-ink nozzle driving motor drives the plunger installation groove 531 to move along the sliding groove, so as to push the plunger to eject the bio-ink in the injector 310.
In one embodiment, referring to fig. 3, the luminal tissue construct printing device further comprises a calibration assembly 600 for calibrating the position of the biological ink jet nozzle 330 with the biological printing assembly 400.
The bio-ink jet head may be removably coupled to the injector mount 320, such as by a threaded connection, and each time the bio-ink jet head is coupled to the injector mount 320, the bio-ink jet nozzle 330 may be coupled to the injector mount 320 at a different location due to the different amount of force applied during the coupling process. Without prior calibration of the bio-ink nozzle 330, the bio-ink nozzle 330 may be lowered to a level at which the rotary rod 431 is unstable during the bio-ink printing process. It is therefore necessary to provide a calibration assembly 600 that ensures that the bio-ink nozzles 330 are in line with the position of the bio-ink printing assembly 400 each time the bio-ink is printed.
Calibration assembly 600 may be calibrated in a variety of ways, such as by setting a standard position of bio-ink nozzle 330 to injector mount 320, thereby adjusting the position of bio-ink nozzle 330 to injector mount 320 to the standard position, or by setting a standard position of bio-ink nozzle 330 to bio-printing assembly 400, thereby adjusting the position of bio-ink nozzle 330 to bio-printing assembly 400 to the standard position.
In one embodiment, referring to fig. 3, calibration assembly 600 includes a camera 610, a light source board 620, and an electrical cabinet. Light source board 620 and camera 610 all set up near biological printing assembly 400 position, electric cabinet one end and camera 610 electric connection, the other end and arm 500 electric connection.
Light source board 620 and camera 610 are both disposed near the location of bioprinting assembly 400. The light source board 620 may provide good light to facilitate taking a clear picture. The camera 610 may take a picture of the biological ink jet nozzle 330.
Realize biological chinese ink nozzle 330 calibration process through the cooperation that sets up camera 610, light source board 620 and electric cabinet, specifically as follows: firstly, the manipulator 510 drives the biological ink nozzle to move to the position of the camera 610, at the moment, the camera 610 collects picture information of the initial position of the biological ink nozzle 330 and feeds the picture information back to the electric cabinet, the electric cabinet sets the initial height value of the biological ink nozzle 330 which descends when the biological ink is printed according to the initial position of the biological ink nozzle 330, secondly, after the manipulator 510 replaces another biological ink nozzle, the manipulator 510 drives the biological ink nozzle to move to the position of the camera 610, at the moment, the camera 610 collects picture information of the current position of the biological ink nozzle and feeds the picture information back to the electric cabinet, the electric cabinet obtains a calibrated height value after comparing the picture information of the initial position with the picture information of the current position, and the electric cabinet calibrates the descending height of the biological ink nozzle 330 according to the calibrated height value, thereby ensuring that the height of the drop to the rotating rod 431 is stable each time the bio-ink jet 330 is lowered during bio-printing. This type of calibration is highly automated, allowing the bio-ink jet nozzle 330 to be lowered to a high degree of stability at the rotary rod 431.
In one embodiment, referring to fig. 9 to 11, the printing apparatus for a lumen tissue construct further includes a temperature and humidity control assembly 700, the temperature and humidity control assembly 700 includes a housing 710, a temperature and humidity control mechanism 720 disposed in an inner cavity of the housing 710, and a nozzle storage chamber 730 extending from a surface of the housing 710 to the inner cavity, and a hinge cover 740 capable of opening or closing an opening is disposed at an opening of the nozzle storage chamber 730.
The bio-ink head is placed in the head storage chamber 730, and the bio-ink is in a proper storage condition by controlling the temperature and humidity in the head storage chamber 730. The inner cavity of the housing 710 is a relatively closed space, the temperature and humidity control mechanism 720 is disposed in the inner cavity of the housing 710, and the showerhead storage chamber 730 extends to the inner cavity of the housing 710, so that the temperature and humidity of the showerhead storage chamber 730 are relatively suitable. The biological ink jets are disposed within the jet storage chamber 730. A hinged cover 740 capable of opening or closing the opening is provided at the opening of the head storage chamber 730, and the hinged cover 740 is provided directly on the head storage chamber 730 or on the case 710. When the hinged cover plate 740 is opened, the biological ink nozzle can be conveniently taken out. When closed, the nozzle storage chamber 730 forms a relatively closed space that provides suitable storage conditions for the bio-ink nozzles.
In one embodiment, the showerhead storage chamber housing 710 is further provided with a showerhead temporary storage chamber 731. The head buffer chamber 731 may be disposed in parallel with the head storage chamber 730 to temporarily store used bio ink heads.
In one embodiment, referring to fig. 9-10, a sixth drive mechanism 750 is provided within housing 710 to control the raising and lowering of showerhead storage chamber 730 relative to housing 710. hinged cover 740 is coupled to showerhead storage chamber 730, and hinged cover 740 is opened when showerhead storage chamber 730 is raised and closed when showerhead storage chamber 730 is lowered.
The showerhead storage chamber 730 and the housing 710 are of a split structure, and a sixth driving mechanism 750, such as an air cylinder mechanism, a motor, etc., is connected to the showerhead storage chamber 730 to drive the showerhead storage chamber 730 to extend from or retract into the housing 710. The hinge cover 740 is coupled to the showerhead storage chamber 730 and may be lifted and lowered along with the showerhead storage chamber 730. Hinge cover 740 opens when the spray head storage chamber 730 is raised and closes when the spray head storage chamber 730 is lowered. When the head storage chamber 730 rises, the biological ink head is taken out with high effect. The hinge cover plate 740 is linked with the spray head storage chamber 730, and the automation degree is high.
In one embodiment, the side of the housing 710 is provided with a mounting plate 711 having a cover plate actuator assembly 760, and the hinged cover plate 740 is coupled to the spray head storage chamber 730 via the cover plate actuator assembly 760. The cover plate transmission assembly 760 comprises a transmission mechanism 770, a sliding block 761 and a linkage plate 762, wherein the sliding block 761 is slidably disposed on the mounting plate 711 and connected to the sixth driving mechanism 750 through the linkage plate 762 to be lifted relative to the housing 710, one end of the transmission mechanism 770 is connected to a rotating shaft 774 of the hinge cover plate 740, and the other end of the transmission mechanism 770 is connected to the sliding block 761.
The mounting plate 711 is fixed to a side surface of the housing 710, and the sliding block 761 is slidably disposed on the mounting plate 711 in a direction in which the head storage chamber 730 moves up and down, for example, the mounting plate 711 is provided with a sliding groove extending in the direction in which the head storage chamber 730 moves up and down, and the sliding block 761 is disposed in the sliding groove. The sixth driving mechanism 750 drives the sliding block 761 to move through the linkage plate 762 when pushing the nozzle storage chamber 730 to move. The slider 761 is lifted along the head storage chamber 730, and the transmission mechanism 770, such as a gear transmission mechanism or a belt transmission mechanism, drives the rotation shaft 774 to rotate, so as to open and close the hinge cover 740, thereby opening the hinge cover 740 when the head storage chamber 730 is lifted and closing the head storage chamber 730 when the head storage chamber 730 is lowered.
Referring to fig. 9-10, of course, the sixth driving mechanism 750 may be connected to the showerhead storage chamber 730 through other means, such as a pneumatic cylinder, which includes a corresponding guiding rod 751 beside the pneumatic cylinder, and the showerhead storage chamber 730 is disposed on a chamber mount 752 and carried by the chamber mount 752. The output end of the cylinder is connected with the mounting seat, and the nozzle storage chamber 730 is driven to move by pushing the mounting seat.
The sixth driving mechanism 750 drives the hinge cover 740 to open and close in a linkage manner through a cover driving assembly 760 consisting of the transmission mechanism 770, the sliding block 761 and the linkage plate 762, so that the automation degree is high, the driving efficiency is high, and the reliability is high.
In one embodiment, referring to fig. 9 to 11, the sliding block 761 includes flanges disposed at two ends and a guiding post 765 sandwiched between two tabs, the linkage plate 762 is movably sleeved on the guiding post 765, and two sides of the linkage plate are connected with the two flanges through elastic members sleeved on the guiding post 765; the transport mechanism 770 is coupled to the side of the rim remote from the guide post 765.
The two flanges of slider 761 extend away from mounting plate 711, and slider 761 is generally arcuate. The guiding column 765 is arranged between the two convex edges, and two ends of the guiding column 765 are fixedly connected with the different convex edges respectively. In view of the compact structure and high transmission efficiency of the temperature and humidity control assembly 700, the sixth driving mechanism 750 is disposed below the housing 710 and faces the head storage chamber 730. And the sliding block 761 is disposed on the mounting plate 711 of the mounting plate 711 on the side of the housing 710, so that a through slot can be disposed on the mounting plate 711 to facilitate the linkage plate 762 to simultaneously connect the sixth driving mechanism 750 and the guiding post 765 on the sliding block 761. The linkage plate 762 is movably sleeved on the guide post 765, and the guide post 765 is sleeved with an elastic piece. Two sides of the linkage plate 762 opposite to the convex edge are connected with the convex edge through elastic pieces. The elastic member may be a spring.
The connection relationship between the link plate 762 and the spring will be described in detail below by taking the spring as an example. For ease of description, the two springs are distinguished by a first spring 766 and a second spring 767, respectively, the flange proximate the opening of the hinge cover plate 740 is designated an upper flange 763 and the flange distal the opening of the hinge cover plate 740 is designated a lower flange 764. One end of the linkage plate 762 is sleeved on the guide post 765, and the other end is connected with the sixth driving mechanism 750. A second spring 767 is sleeved between the upper convex edge 763 and the linkage plate 762 of the guide post 765, and a first spring 766 is connected between the linkage plate 762 and the lower convex edge 764 of the guide post 765. The flexible connection is formed between the linkage plate 762 and the sliding block 761, and through the arrangement of the first spring 766 and the second spring 767, when the hinge cover 740 is opened or closed (i.e. the rotation angle is between 0 and 180 °), the force applied to the hinge cover 740 in rotation (the force drives the linkage plate 762 through the sixth driving mechanism 750, the linkage plate 762 drives the sliding block 761, and the sliding block 761 drives the transmission mechanism 770 to provide) is smaller than the sum of the deformation forces of the first spring 766 and the second spring 767. When the linkage plate 762 moves upward or downward, the first spring 766 and the second spring 767 are not deformed. That is, when the link plate 762 moves upward, the sliding block 761 is driven to move by the second spring 767, thereby opening the cover plate, and when the link plate 762 moves downward, the sliding block 761 is driven to move by the first spring 766, thereby closing the cover plate. When the rotation angle of the hinge cover 740 is greater than 180 degrees or less than 0 degree, the force applied to the rotation of the hinge cover 740 is greater than the sum of the deformation forces of the first spring 766 and the second spring 767, that is, when the linkage plate 762 moves upwards or downwards, the first spring 766 and the second spring 767 deform simultaneously, and the linkage plate 762 does not drive the sliding block 761 continuously. That is, when the hinge cover 740 is rotated more than 180 ° to be completely opened, even if the sixth driving mechanism 750 continues the upward movement of the link plate 762, the link plate 762 does not continue to drive the slide block 761, and the rotation angle of the hinge cover 740 can be maintained at 180 °. When the hinge cover 740 is rotated by 0 °, i.e., completely closed, even if the sixth driving mechanism 750 continues to move the link plate 762 downward, the link plate 762 does not continue to drive the slide block 761, and the hinge cover 740 can be rotated by 0 °. Flexible connection is formed between the linkage plate 762 and the sliding block 761, so that damage to the hinge cover plate 740 is avoided, and the temperature and humidity control assembly 700 is high in reliability and long in service life.
In one embodiment, referring to fig. 11, the transport mechanism 770 includes a first conveyor 771 and a second conveyor 772 respectively disposed on the mounting plate 711, and a cover plate timing belt 773 wound between the first conveyor 771 and the second conveyor 772, the first conveyor 771 being coaxially connected with the rotation shaft 774; a linkage 776 is connected to the cover synchronous belt 773, and the linkage 776 is connected to the side of the flange away from the guide post 765 through a connecting post 777.
One end of the link 776 is fixed to the cover synchronous belt 773, and the other end is connected to the flange of the sliding block 761. When the convex edge moves upward, the link 776 drives the cover synchronous belt 773 to move upward, pushing the first transmission wheel 771 to rotate counterclockwise, and further driving the hinge cover 740 to rotate in the same direction. Similarly, when the flange moves downward, the link 776 drives the cover plate synchronous belt 773 to move downward, pushing the first transmission wheel 771 to rotate clockwise, and further driving the hinge cover plate 740 to rotate in the same direction. In this way, the rotation angle of the hinged cover plate 740 can be adjusted in a large range in multiple stages, while other transmission mechanisms 770 can only be adjusted in fixed angle steps.
In one embodiment, referring to fig. 9-11, the transport mechanism 770 also includes a limit wheel 775. The limiting wheel 775 is arranged on one side of the cover plate synchronous belt 773 and limits the cover plate synchronous belt 773. In one embodiment, the temperature and humidity control mechanism 720 includes a temperature control assembly including a cooling tube 721 disposed within the showerhead storage chamber 730 and a humidity control assembly. The humidity control mechanism includes an air drying mechanism in communication with the spray head storage chamber 730.
The showerhead storage chamber 730 has a cooling tube 721 extending therethrough, such as where the cooling tube 721 is disposed on an inner wall, bottom, or cavity of the showerhead storage chamber 730. The cooling tube 721 includes a cooling medium such as cooling water circulating therein to adjust the temperature of the bio-ink head disposed in the head storage chamber 730. The cooling pipe 721 may form a closed loop with an external water cooler, and the cooling water flows out of the water cooler to the cooling pipe 721 and then returns to the water cooler. When a chamber mount 752 is provided below the showerhead storage chamber 730, the circulation line 722 may also be provided on the chamber mount 752. The water cooler, the cooling pipe 721 and the circulation pipeline 722 form a closed loop, the water cooler adjusts the temperature of the cooling water, and the cooling water flows out of the water cooler, flows through the cooling pipe 721 and the circulation pipeline 722 in sequence and then returns to the water cooler. Of course, the cooling water may flow through the circulation line 722, then through the cooling tube 721, and then back to the water cooler. Regardless of the flow pattern of the cooling water, the chamber mount 752 may be cooled to control the temperature of the bottom of the showerhead storage chamber 730. The showerhead storage chamber 730 has two structures for directly or indirectly adjusting the temperature of the cooling pipe 721 and the circulation pipe 722, so that the temperature adjustment is faster and the indoor temperature is more uniform.
The air drying mechanism includes a drying chamber 723 and a drying assembly disposed within the drying chamber 723. The showerhead storage chamber 730 is communicated with the drying chamber 723, and air in the showerhead storage chamber 730 enters the drying chamber 723, is dried and dehumidified by the drying assembly, and then returns to the showerhead storage chamber 730. For example, the drying chamber 723 includes a first inlet and a second outlet, and the showerhead storage chamber 730 is provided with a first outlet and a second inlet. The first air inlet is communicated with the first air outlet, and the second air outlet is communicated with the second air inlet. The dry component includes a TEC (semiconductor cooler) and a heat sink 724. The TEC and the heat sink 724 are installed in the drying chamber 723, and a first fan is installed at one end of the drying chamber 723 and a second fan is installed at the other end thereof. The air inlet end of the first fan is communicated with the nozzle storage chamber 730 through a first air outlet, and the air outlet end of the first fan is close to the radiating fins 724. The showerhead storage chamber 730 air (higher humidity) is exhausted from the first exhaust port by the first fan and then cooled by the TEC to condense the air and obtain dry air. The air inlet end of the second fan is close to the heat sink 724, the air outlet end of the second fan is communicated with the second air outlet, and dry air is returned to the nozzle storage chamber 730 through the second air inlet. The air is circulated to thereby maintain a dry environment in the head storage chamber 730.
In one embodiment, referring to fig. 11, a drain 725 is opened at the bottom of the drying chamber 723. The TEC cools the air to condense the air into water droplets, which are collected and discharged from the water outlet 725, thereby helping to keep the air in the drying chamber 723 dry.
In one embodiment, referring to fig. 11, a cover plate 726 is disposed on a side of the drying chamber 723. The closure plate 726 is openable to facilitate servicing of the drying chamber 723.
In one embodiment, referring to fig. 9 to 10, the photo sensor 727 is disposed at one end of the temporary storage chamber 731. The photosensor 727 is used for detecting whether a biological ink jet head is placed in the head storage chamber 730.
In one embodiment, referring to fig. 3, the luminal tissue construct printing device further comprises a wipe assembly 800, the working position of the wipe assembly 800 being within the range of motion of the robotic arm 510. The frictioning assembly 800 comprises a frictioning mounting seat 810 and a frictioning motor 820 arranged on the frictioning mounting seat 810, a frictioning rod 830 is arranged on the frictioning motor 820, and a frictioning sponge 840 is arranged on the frictioning rod 830.
After the medical glue is arranged on the inner surface of the lumen tissue, the medical glue remained at the end part of the hollow rod assembly 100 needs to be erased, the manipulator 510 is required to move the hollow rod assembly 100 to the position of the glue wiping sponge 840, and the erasing of the medical glue remained at the end part of the hollow rod assembly 100 is completed through the glue wiping sponge 840. The rubbing motor 820 drives the rubbing rod 830 to rotate, and the rubbing sponge 840 is used for rubbing off the redundant medical glue.
It is understood that, in order to improve the printing efficiency, i.e., to realize printing of a plurality of, e.g., 4, artificial blood vessels in one printing process, all consumable components (e.g., the hollow rod assembly 100, the glue wiping assembly 800, the biological ink jet head, the pushing member 210, the sample adding needle 264, etc.) can be set to 4 sets, and the jet head storage chamber 730, the cover plate transmission assembly 760 and the sixth driving mechanism 750 can also be set to 4 sets. Thus, the printing of 4 artificial blood vessels can be completed on one printer at the same time.
In one embodiment, referring to fig. 3, the luminal tissue construct printing device comprises a luminal analyzer 900 for detecting the flatness of luminal tissue. The operating position of the chamber detector 900 is within the range of motion of the robot 510.
The lumen examination instrument 900 comprises a lumen examination installation seat 910, an endoscope installation rod 920 is installed on the lumen examination installation seat 910, an endoscope 930 is installed on the endoscope installation rod 920 to detect the flatness of the inner wall of the artificial blood vessel, the manipulator 510 moves the artificial blood vessel which is finally printed to the position of the endoscope 930, and the image of the inner wall of the artificial blood vessel is collected through the endoscope 930, so that whether the inner wall is finished or not is judged.
In another aspect, embodiments of the present application provide a 3D bioprinter, including the luminal tissue construct printing apparatus described above.
Which comprises the luminal tissue construct printing device described above. The printing device for the lumen tissue construct can improve the biological reliability of the lumen tissue, and accordingly, the 3D bioprinter also has the beneficial technical effects, and is not described again. In yet another aspect, embodiments of the present application provide a method for printing a luminal tissue construct printing device, comprising the steps of:
securing luminal tissue within the hollow shaft assembly 100.
Medical glue is applied to the inner surface of the lumen tissue fixed to the hollow shaft assembly 100 by the glue applying assembly 200.
The bio-printing assembly 400 receives bio-ink ejected by the inkjet head assembly 300 and forms a bio-construct.
The hollow shaft assembly 100 is mated with the bioprinting assembly 400 and the biological construct is sheathed within the luminal tissue with the inner surface having the medical grade glue.
The biological construct is applied to the inner surface of the luminal tissue by the bioprinting assembly 400.
The printing device for the lumen tissue construct can improve the biological reliability of the lumen tissue, so the printing method adopting the printing device for the lumen tissue construct also has the beneficial effects.
For clarity of description of the printing method of the printing device for the luminal tissue construct, a more clear and complete embodiment is described as an example.
The working process is as follows:
firstly, assembling consumable materials.
The vascular prosthesis is first nested within the inner cannula 120 of the hollow shaft assembly 100 and then the inner cannula 120 is nested within the outer cannula 110 of the hollow shaft assembly 100. When the artificial blood vessel is sleeved, the artificial blood vessel is required to be kept in a stretched state in the inner sleeve 120, the artificial blood vessel is installed in the inner sleeve 120, the elastic clip 132 at one end of the inner sleeve 120 is fixed through the clip ring 131, so that one end of the artificial blood vessel is fixed, the other end of the inner sleeve 120 is stretched through the forceps at the other end of the inner sleeve 120, and then the elastic clip 132 at the other end of the inner sleeve 120 is fixed through the clip ring 131.
Then, consumables such as the pushing piece 210 and the sample adding needle 264 are installed on the consumable installing seat 250, and the medical glue is put into the medical glue storing groove 255 for standby.
Then, biological ink is filled into an injector 310 of the biological ink sprayer, the injector 310 is installed in an injector installation seat 320, the injector installation seat 320 is connected with the biological ink nozzle 330 to form the biological ink sprayer, the biological ink sprayer is placed in a sprayer storage chamber 730, and the temperature and the humidity in the sprayer storage chamber 730 are controlled through a temperature and humidity control assembly 700 to enable the biological ink to be in a proper storage condition. The specific adjustment process of the temperature and humidity is described in detail in the foregoing embodiments, and will not be described in detail.
When printing is needed, the biological ink nozzle is taken out of the nozzle storage chamber 730, and the hinged cover plate 740 is linked with the nozzle storage chamber 730 through the cover plate transmission assembly 760 and the sixth driving mechanism 750 in the taking-out process, so that the biological ink nozzle is automatically taken out of the nozzle storage chamber 730, namely, the biological ink nozzle is opened when the nozzle storage chamber 730 is lifted and is closed when the nozzle storage chamber 730 is lowered. The specific implementation process is described in detail in the foregoing embodiments, and is not described again. Second, bio-ink jet nozzle 330 calibration procedure
The robot 510 removes the bio-ink nozzle 330 from the raised head storage chamber 730 and moves the bio-ink nozzle 330 to the vicinity of the rotation shaft 431 of the bio-printing assembly 400, and the alignment is performed by the alignment assembly 600, so that the bio-ink nozzle 330 is stably lowered to the height of the rotation shaft 431 each time during the bio-printing process. The specific calibration process is described in detail in the foregoing embodiments, and is not described again. Thirdly, biological ink printing process
After the bio-ink nozzle 330 is calibrated, the robot 510 moves the bio-ink nozzle to the position of the rotary rod 431, and before that, the air bag is sleeved on the rotary rod 431, and then the rotary rod 431 drives the motor to drive the rotary rod 431 to rotate. During the rotation of the rotary rod 431, the bio-ink head driving unit controls the bio-ink head to eject the bio-ink in the bio-ink nozzle 330, and then the robot 510 moves the bio-ink nozzle 330 from one end of the rotary rod 431 to the other end of the rotary rod 431, thereby completing the printing of the bio-ink. The specific printing and heat-insulating forming processes are described in detail in the foregoing embodiments, and are not described in detail. Fourth, medical glue coating process
Because the heat preservation shaping of biological chinese ink needs certain time, in order to improve the efficiency of production, just begin medical glue coating process in this period. The robot arm 510 is first moved to a position where the hollow rod assembly 100 is placed, such as a position of a mount of the hollow rod assembly 100, the grasping of the hollow rod assembly 100 is achieved by the first fitting part 520, and then a sponge as a glue solution adsorbing member is placed in the inner sleeve 120.
For convenience of description, the moving direction of the consumable mounting base 250 is defined as X direction, and the moving direction of the pushing member 210 by the first driving member 240 is defined as Z direction. Meanwhile, the first driving member 240 is defined as a first Z-axis driving assembly, and the second driving member 262 is defined as a second Z-axis driving assembly. The consumable mounting base 250 is driven to move by the first X-axis driving assembly.
The first X-axis driving assembly drives the consumable mounting seat 250 to move, so that the pushing member 210 moves to the lower end of the pushing member mounting seat 230. The first Z-axis driving assembly drives the pushing member mounting base 230 to move downwards, and the pushing member 210 is assembled through the matching of the pushing member 210 connecting piece 1 and the pushing member 210 connecting piece 2. Then, the first X-axis driving component drives the consumable mounting seat 250 to move, so that the sample injection needle 264 moves to the lower end of the liquid transfer device 261. The second Z-axis driving assembly drives the pipettor 261 to move downwards, the pipettor 261 completes the assembly with the sampling needle 264, the first X-axis driving assembly drives the consumable mounting seat 250 to move, the medical glue storage tank 255 is moved to the lower part of the pipettor 261, the second Z-axis driving assembly drives the pipettor 261 to move downwards into the medical glue storage tank 255, according to the usage amount of the medical glue, a corresponding amount of the medical glue is sucked into the sampling needle 264, then the manipulator 510 moves the end, with the sponge, of the hollow rod assembly 100 to the sampling needle 264, the sampling needle 264 drips the sponge at the moment, after the sponge is saturated, the manipulator 510 moves the end, with the sponge, of the hollow rod assembly 100 to the lower part of the pusher 210, the first Z-axis driving assembly drives the pusher 210 to move towards the hollow rod assembly 100, the sponge is moved from the end of the hollow rod assembly 100 to the other end, and simultaneously, in order to improve the coating effect, can make the sponge make a round trip once at hollow rod subassembly 100 internal motion to accomplish the coating of medical glue on the artificial blood vessel inner wall, accomplish medical glue coating back, owing to need will remain and erase at the medical glue of hollow rod subassembly 100 tip, need manipulator 510 to remove hollow rod subassembly 100 to rubber sponge 840 department, accomplish through rubber sponge 840 and remain the erasing of medical glue at hollow rod subassembly 100 tip.
Fifth, an artificial blood vessel assembling step
The manipulator 510 moves the hollow rod assembly 100, the hollow rod assembly 100 is sleeved on the rotating rod 431, after the biological ink is subjected to heat preservation and molding, the biological ink forms a biological construct on the surface of the air bag, then the air bag is ventilated, and when the air bag is propped up, the biological construct on the surface of the air bag outwards displaces along with the expansion of the elastic membrane, finally contacts with the inner wall of the artificial blood vessel and is adhered to the inner wall of the artificial blood vessel, so that the artificial blood vessel which is printed is obtained.
In the process of detecting the flatness of the inner wall of the artificial blood vessel, the manipulator 510 moves the artificial blood vessel which is finally printed to the position of the endoscope 930, and the endoscope 930 collects the image of the inner wall of the artificial blood vessel, thereby determining whether the inner wall is finished.
Through installing the manipulator 510 subassembly in the frame among this technical scheme, and install rubber coating subassembly 200 in proper order in the operation space of manipulator 510 subassembly, atmospheric control subassembly 700, print platform and annex subassembly, through reasonable spatial layout, just so can be through each functional module of manipulator 510 linkage in the manipulator 510 subassembly, thereby with the equipment process of consumptive material, biological chinese ink nozzle 330 calibration process, biological chinese ink printing process, medical gluey coating process and artificial blood vessel equipment process integration accomplish at a printer, thereby the degree of automation of printing has been improved, artificial participation is reduced.
The problem that the lumen tissue is easy to displace when medical glue is arranged on the inner surface of the lumen tissue or a biological construct is applied on the inner surface of the lumen tissue is solved. Referring to fig. 3-5, embodiments of the present application provide a hollow shaft assembly 100, the hollow shaft assembly 100 including an outer sleeve 110 and an inner sleeve 120 disposed within the outer sleeve 110, the inner sleeve 120 being provided with a securing mechanism 130 for luminal tissue.
The lumen of the inner cannula 120 fits into the luminal tissue, which extends into the lumen of the inner cannula 120 and is secured by the securing mechanism 130. The lumen tissue is not displaced when the inner surface is provided with medical glue (such as coated medical glue) or the biological construct is applied to the inner surface of the lumen tissue, thereby ensuring the corresponding effect.
In one embodiment, referring to fig. 3-5, the securing mechanisms 130 are disposed at both ends of the inner sleeve 120.
The fixing mechanisms 130 are disposed at two ends of the inner sleeve 120, and stretch two ends of the lumen tissue mounted in the inner sleeve 120, so that the lumen tissue is in a stretched state, which is beneficial to uniformly coating the medical adhesive and applying the biological construct to the inner surface of the lumen tissue.
In one embodiment, referring to fig. 5, the fixing mechanism 130 includes a clamping ring 131 and elastic clips 132, the clamping ring 131 is disposed at the end of the inner sleeve 120, the clamping ring 131 has an annular cavity communicating with the inner cavity of the inner sleeve 120, and the elastic clips 132 are sleeved outside the clamping ring 131 for compressing the clamping ring 131 in a radial direction to fix the luminal tissue.
The fixing mechanism 130 of this structure can fix the lumen tissue quickly and firmly.
In one embodiment, referring to FIG. 5, the wall of the inner sleeve 120 is provided with through holes 140.
Through holes 140 are formed in the wall of the inner sleeve 120, and the through holes 140 penetrate through the wall of the inner sleeve 120, so that the inner cavity of the inner sleeve 120 is communicated with the outside. In the air bag supporting process, air between the air bag and the artificial blood vessel can be discharged through the vent hole, so that the air bag can be uniformly supported. After the biological ink is adhered to the artificial blood vessel, the thickness of the biological ink layer is uniform.
In one embodiment, referring to fig. 5, the through holes 140 are uniformly distributed at equal intervals along the axial direction of the inner sleeve 120.
The inner sleeve 120 has a certain axial length, and the through holes 140 are uniformly distributed along the axial direction of the inner sleeve 120 at equal intervals, so that all parts of the air bag can be uniformly supported along the axial direction of the inner sleeve 120, and after the biological ink adheres to the artificial blood vessel, the axial thickness of the biological ink layer along the artificial blood vessel is more uniform.
In one embodiment, referring to fig. 5, the through holes 140 are arranged in groups, the through holes 140 of each group are uniformly distributed at equal intervals in the axial direction of the inner sleeve 120, and the through holes 140 of any group are uniformly distributed at equal intervals in the circumferential direction of the inner sleeve 120.
In the inner tube 120 having such a structure, air between the balloon and the artificial blood vessel is uniformly discharged through the vent holes, so that each part of the balloon can be uniformly supported. After the biological ink is adhered to the artificial blood vessel, the thickness of the biological ink layer is more uniform.
In one embodiment, referring to FIG. 4, the inner sleeve 120 is received within the outer sleeve 110, and at least one end of the outer sleeve 110 is provided with a removable plug.
The length of the inner sleeve 120 is less than the length of the outer sleeve 110. The inner sleeve 120 is received within the outer sleeve 110, i.e., the inner sleeve 120 has one end flush with the outer sleeve 110 and one end received completely within the outer sleeve 110, or both ends received within the outer sleeve 110. The outer tube 110 is provided with a detachable plug at an end portion thereof for completely receiving the inner tube 120, and the plug is used for plugging the end portion of the balloon when the balloon is expanded in the process of assembling the artificial blood vessel, so as to prevent the balloon from expanding and extending in the axial direction of the rotating rod 431.
In another aspect, embodiments of the present application provide a luminal tissue construct printing device, which includes the hollow rod assembly 100 described above. Due to the use of the hollow shaft assembly 100, the luminal tissue construct printing device prints a uniform thickness layer of vascular prosthesis bio-ink.
Aiming at the problem of uneven smearing of medical glue on the inner surface of the artificial blood vessel. The embodiment of the application provides a gluing component 200, wherein the gluing component 200 comprises a glue solution adsorption piece and a pushing piece 210; the glue solution adsorption piece is of a structure capable of adsorbing the glue solution and can be inserted into the tube cavity tissue, and the pushing piece 210 can be inserted into the tube cavity tissue, is connected with the glue solution adsorption piece and moves along the axial direction of the tube cavity tissue.
In one of the embodiments, with reference to fig. 2, the gluing assembly 200 further comprises a first mounting plate 220, a pusher 210 mount and a first drive 240; the pushing member 210 is disposed on a mounting seat of the pushing member 210, and the mounting seat of the pushing member 210 is movably disposed on the first mounting plate 220 and connected to a working end of the first driving member 240 for driving the pushing member 210 to reciprocate axially relative to the lumen tissue.
The pushing member 210 can be inserted into the lumen tissue to be connected with the glue solution adsorbing member, and by pushing at least one of the pushing member 210 and the hollow rod assembly 100 to move, the pushing member 210 pushes the glue solution adsorbing member to move along the axial direction of the lumen tissue, so that the glue solution is coated on the inner surface of the lumen tissue, and the inner surface of the lumen tissue has relatively uniform medical glue.
In one embodiment, referring to fig. 2, the gluing assembly 200 further comprises a consumable mount 250 provided with a pusher 210 placement site, the consumable mount 250 is capable of reciprocating along its length, and the pusher 210 placement site passes through a working path of the pusher 210 mount under the first driving member 240.
The consumable mount 250 can provide the pusher mount 230 with the pusher 210 in time. Therefore, after the glue coating assembly 200 coats the medical glue on each lumen tissue, the pushing element 210 is replaced, and the phenomenon of pollution caused by repeated use of the pushing element 210 is avoided.
In one embodiment, referring to fig. 2, the consumable mount 250 further includes a pusher 210 recovery position, and the pusher 210 recovery position and the pusher 210 placement position are arranged along the moving direction of the consumable mount 250.
The pusher recovery station 252 receives the unloaded pushers 210, so that the lumen tissue construct printing device is neater and more orderly, and consumable materials are prevented from being polluted.
In one embodiment, referring to fig. 2, the glue spreading assembly 200 further includes a glue dripping mechanism 260, and a glue outlet of the glue dripping mechanism 260 is disposed corresponding to the glue solution adsorbing member.
The glue dripping mechanism 260 can better control the adding amount of the medical glue in the sponge, so that the amount of the medical glue coated on the inner wall of the artificial blood vessel can be more stably controlled.
In one embodiment, referring to fig. 2, the glue dropping mechanism 260 includes a pipette 261 and a second driver 262 for driving the pipette 261 to operate.
The second driving piece 262 drives the liquid transferring device 261 to drop the medical glue, and the automation degree is high. And the pipette 261 can precisely control the amount of the medical gel added to the sponge, so that the amount of the medical gel coated on the inner wall of the artificial blood vessel can be stably controlled.
In one embodiment, referring to fig. 2, pipettor 261 and pusher 210 mount are staggered along the width of consumable mount 250; pipette 261 comprises body 263 and sample addition needle 264; the body 263 and the sample adding needle 264 are detachably connected; the consumable mounting seat 250 further comprises a sample adding needle 264 placing position 253; the position 253 of the loading needle 264 is located through the working path of the pipettor 261 under the second drive member 262.
After the pipette 261 coats the medical glue on each lumen tissue, the sampling needle 264 is replaced, and the phenomenon of pollution caused by repeated use of the sampling needle 264 is avoided.
In one embodiment, referring to fig. 2, the consumable mounting receptacle 250 further comprises a sampling needle 264 recovery site 254 and/or a medical gel holding reservoir 255, the sampling needle 264 recovery site 254 and/or the medical gel holding reservoir 255 passing through the working path of the pipettor 261 under the second driver 262.
Consumable mount 250 provides the glue solution for pipettor 261, and degree of automation is higher. Consumable mount 250 can collect the sample addition needle 264 that has been used for lumen tissue constructs printing device is more neat and orderly, avoids the consumptive material to pollute each other.
On the other hand, the embodiment of the present application provides a lumen tissue construct printing apparatus, which includes the foregoing glue spreading assembly 200. Due to the adoption of the gluing component 200, the glue on the inner surface of the lumen tissue is more uniformly applied.
Aiming at the problem that the storage environment of a biological ink sprayer is poor, the embodiment of the application provides a temperature and humidity control assembly 700, the temperature and humidity control assembly 700 comprises a shell 710, a temperature and humidity control mechanism 720 arranged in an inner cavity of the shell 710 and a sprayer storage chamber 730 extending from the surface of the shell 710 to the inner cavity, and the sprayer storage chamber 730 is used for placing the biological ink sprayer; a hinge cover 740 capable of opening or closing the opening is provided at the opening of the head storage chamber 730.
The bio-ink head is placed in the head storage chamber 730, and the bio-ink is in a proper storage condition by controlling the temperature and humidity in the head storage chamber 730. When the hinged cover plate 740 is opened, the biological ink nozzle can be conveniently taken out. When closed, the nozzle storage chamber 730 forms a relatively closed space that provides suitable storage conditions for the bio-ink nozzles.
In one embodiment, referring to fig. 9-11, a sixth driving mechanism 750 is disposed within the housing 710 to control the movement of the showerhead storage chamber 730 with respect to the housing 710, a hinged cover 740 is coupled to the showerhead storage chamber 730, and the hinged cover 740 is opened when the showerhead storage chamber 730 is raised and closed when the showerhead storage chamber 730 is lowered.
The hinge cover 740 is linked with the showerhead storage chamber 730, the hinge cover 740 is opened when the showerhead storage chamber 730 is raised and is closed when the showerhead storage chamber 730 is lowered, and the degree of automation of the temperature and humidity control assembly 700 is high.
In one embodiment, referring to FIGS. 9-11, the housing 710 has a mounting plate 711 with a cover plate actuator 760 on a side thereof, and the hinged cover plate 740 is coupled to the showerhead storage chamber 730 via the cover plate actuator 760; the cover plate transmission assembly 760 comprises a transmission mechanism 770, a sliding block 761 and a linkage plate 762, wherein the sliding block 761 is slidably disposed on the mounting plate 711 and connected to a sixth driving mechanism 750 through the linkage plate 762 to move up and down relative to the housing 710, one end of the transmission mechanism 770 is connected to a rotation shaft 774 of the hinge cover plate 740, and the other end of the transmission mechanism is connected to the sliding block 761. The temperature and humidity control assembly is high in automation degree, high in transmission efficiency and more reliable.
In one embodiment, referring to fig. 9-11, slider 761 includes flanges disposed at both ends and a guide post 765 disposed between two tabs; the linkage plate 762 is movably sleeved on the guide post 765, and two sides of the linkage plate are connected with the two convex edges through elastic pieces sleeved on the guide post 765; the transport mechanism 770 is connected to the side of the adjacent rim remote from the guide post 765.
A flexible connection is formed between the linkage plate 762 and the sliding block 761, so that damage to the hinge cover plate 740 is avoided, and the temperature and humidity control assembly 700 has high reliability and long service life.
In one embodiment, referring to fig. 9 to 11, the transmission mechanism 770 includes a first transmission wheel 771, a second transmission wheel 772 and a cover timing belt 773 wound between the first transmission wheel 771 and the second transmission wheel 772 and respectively disposed on the mounting plate 711, the first transmission wheel 771 is coaxially connected to the rotating shaft 774, a linking member 776 is connected to the cover timing belt 773, and the linking member 776 is connected to a side of the flange away from the guide post 765 through a connecting post 777.
This way can make a wide range of multi-stage adjustments to the angle of rotation of the hinged cover plate 740.
In one embodiment, referring to fig. 9-11, the temperature and humidity control mechanism 720 includes a temperature control assembly including a cooling tube 721 disposed within the showerhead storage chamber 730; the humidity control mechanism includes an air drying mechanism in communication with the spray head storage chamber 730.
The showerhead storage chamber 730 has two structures for directly or indirectly adjusting the temperature of the cooling pipe 721 and the circulation pipe 722, so that the temperature adjustment is faster and the indoor temperature is more uniform. The air drying mechanism provides a dry environment within the spray head storage chamber 730 by the circulation of air.
On the other hand, the embodiment of the present application provides a lumen tissue construct printing device, which includes the foregoing temperature and humidity control assembly 700. Due to the adoption of the temperature and humidity control assembly 700, the storage environment of the biological ink jet head is good, and therefore the biological reliability of the printed lumen tissue construct is good.
While the present application has been described with reference to preferred embodiments, various modifications may be made and equivalents may be substituted for elements thereof without departing from the scope of the present application, and in particular, features shown in the various embodiments may be combined in any manner as long as there is no structural conflict. The present application is not intended to be limited to the particular embodiments disclosed herein but is to cover all embodiments that may fall within the scope of the appended claims.

Claims (34)

1. A luminal tissue construct printing device comprising:
a hollow shaft assembly for securing luminal tissue;
the gluing component is used for arranging medical glue on the inner surface of the lumen tissue fixed by the hollow rod component;
a nozzle assembly for ejecting biological ink;
a bioprinting component for receiving biological ink and forming a biological construct, and for applying the biological construct on an inner surface of luminal tissue.
2. The device of claim 1, further comprising a robotic arm having a manipulator with a first engagement for accessing the hollow rod assembly and a second engagement for accessing the showerhead assembly;
and the moving range of the manipulator comprises the working positions of the hollow rod assembly, the gluing assembly, the spray head assembly and the biological printing assembly.
3. The luminal tissue construct printing device of claim 1, wherein the hollow rod assembly comprises an outer sleeve and an inner sleeve disposed within the outer sleeve, the inner sleeve being provided with a fixation mechanism for fixing the luminal tissue.
4. The luminal tissue construct printing device of claim 3, wherein the securing mechanism is disposed at both ends of the inner cannula.
5. The printing device for luminal tissue constructs as claimed in claim 4 wherein the fixation mechanism comprises a clamping ring and a resilient clip, the clamping ring is disposed at the end of the inner cannula, the clamping ring has an annular cavity communicating with the inner lumen of the inner cannula, the resilient clip is sleeved outside the clamping ring for radially compressing the clamping ring upon itself to fix the luminal tissue.
6. The luminal tissue construct printing device of claim 3 wherein the wall of the inner cannula is provided with through holes.
7. The luminal tissue construct printing device of claim 6 wherein the through holes are evenly distributed with equal distance along the axial direction of the inner cannula.
8. The luminal tissue construct printing device of claim 7 wherein the through holes are arranged in groups, each group of through holes are evenly distributed along the axial direction of the inner sleeve at equal distances, and any group of through holes are evenly distributed along the circumferential direction of the inner sleeve at equal distances.
9. The device for printing luminal tissue construct as claimed in claim 3 wherein the inner cannula is received within the outer cannula, at least one end of the outer cannula being provided with a removable plug.
10. The luminal tissue construct printing device of claim 1, wherein the glue application assembly comprises a glue solution adsorbing member and a pushing member; the glue solution adsorption piece is of a structure capable of adsorbing glue solution and can be inserted into the tube cavity tissue, and the pushing piece can be inserted into the tube cavity tissue, is connected with the glue solution adsorption piece and moves along the axial direction of the tube cavity tissue.
11. The luminal tissue construct printing device of claim 10, wherein the glue assembly further comprises a first mounting plate, a pusher mount, and a first drive;
the pushing piece is arranged on the pushing piece mounting seat, and the pushing piece mounting seat is movably arranged on the first mounting plate, is connected with the working end of the first driving piece and is used for driving the pushing piece to axially reciprocate relative to the lumen tissue.
12. The luminal tissue construct printing device of claim 11, wherein the gluing assembly further comprises a consumable mount provided with a pusher placement site, the consumable mount being capable of reciprocating along its length, and the pusher placement site passing through a working path of the pusher mount under the first driving member.
13. The luminal tissue construct printing device of claim 12, wherein the consumable mount further comprises a pusher recovery site, the pusher recovery site and the pusher placement site being disposed along a direction of motion of the consumable mount.
14. The device for printing the luminal tissue construct according to claim 12, wherein the glue spreading assembly further comprises a glue dripping mechanism, and a glue outlet of the glue dripping mechanism is arranged corresponding to the glue solution adsorbing member.
15. The luminal tissue construct printing device of claim 14, wherein the dispensing mechanism comprises a pipette and a second drive for driving the pipette in operation.
16. The luminal tissue construct printing device of claim 15, wherein the pipettor and the pusher mount are staggered along a width direction of the consumable mount; the pipettor comprises a body and a sample adding needle; the body is detachably connected with the sample adding needle;
the consumable mounting seat also comprises a sample adding needle placing position; the sample adding needle placing position passes through a working path of the pipettor under the second driving piece.
17. The luminal tissue construct printing device of claim 16, wherein the consumable mount further comprises the loading needle retrieval site and/or the medical gel reservoir via a working path of a pipette under a second drive.
18. The luminal tissue construct printing device of claim 1, wherein the bioprinting assembly comprises a platform base, a clasping block mount, and a rotating rod mount, both of the clasping block mount and the rotating rod mount disposed on the platform base;
the rotating rod mounting seat is provided with a rotating rod capable of rotating around the central axis of the rotating rod mounting seat;
the clamping block mounting seat is provided with a first clamping block and a second clamping block which can move relatively to open and close; the first clamping block and the second clamping block surround to form an area capable of accommodating a rotating rod; the side walls of the first clamping and holding block and the second clamping and holding block are provided with heating mechanisms.
19. The luminal tissue construct printing device according to claim 18, wherein the rotating rod is sleeved with an elastic membrane, the rotating rod is hollow inside, and an air outlet communicated with the inside is formed on the outer wall of the rotating rod and used for discharging air inside the rotating rod to support the elastic membrane;
the rotary rod mounting seat is provided with a third driving mechanism for driving the rotary rod to rotate around the central axis of the rotary rod.
20. The luminal tissue construct printing device of claim 18 wherein the clasping block mounting base is provided with two meshed drive gears and a fourth drive mechanism that drives the two drive gears to rotate in opposite directions, the two drive gears being in transmission with the first clasping block and the second clasping block respectively.
21. The luminal tissue construct printing device of claim 2 wherein the jet assembly is a biological ink jet head comprising an injector, an injector mount, and a biological ink jet nozzle connected in series, and wherein an outfeed end of the injector is in communication with the biological ink jet nozzle;
the second matching part comprises a plunger mounting groove and a first connecting piece, the plunger mounting groove is matched with the plunger of the syringe, and the first connecting piece is matched with the syringe mounting seat.
22. The luminal tissue construct printing device of claim 21 wherein the manipulator further comprises a fixed plate and a fifth drive mechanism, the plunger mounting slot is movably disposed in the fixed plate and is connected to a working end of the fifth drive mechanism for pushing the plunger.
23. The luminal tissue construct printing device of claim 21, further comprising a calibration assembly for calibrating a biological ink jet nozzle to the position of the biological printing assembly.
24. The luminal tissue construct printing device of claim 23 wherein the calibration assembly comprises a camera, a light source board, and an electrical control box; the light source board with the camera all set up in near biological printing subassembly position, electric cabinet one end with camera electric connection, the other end with arm electric connection.
25. The device for printing a luminal tissue construct as recited in claim 21, further comprising a temperature and humidity control assembly, the temperature and humidity control assembly comprising a housing, a temperature and humidity control mechanism disposed within an interior cavity of the housing, and a showerhead storage chamber extending from a surface of the housing to the interior cavity, the showerhead storage chamber configured to house the biological ink showerhead; and a hinge cover plate capable of opening or closing the opening is arranged at the opening of the spray head storage chamber.
26. The device for printing a luminal tissue construct as defined in claim 25 wherein a sixth drive mechanism is provided within the housing to control the elevation of a nozzle storage chamber relative to the housing, the hinged cover plate is in linkage with the nozzle storage chamber and the hinged cover plate is open when the nozzle storage chamber is elevated and closed when the nozzle storage chamber is lowered.
27. The luminal tissue construct printing device of claim 26 wherein a side of the housing is provided with a mounting plate having a cover plate drive assembly, the hinged cover plate being in linkage with the nozzle storage chamber through the cover plate drive assembly;
the cover plate transmission assembly comprises a transmission mechanism, a sliding block and a linkage plate, the sliding block is arranged on the mounting plate in a sliding mode and connected with the sixth driving mechanism through the linkage plate to be opposite to the shell body to lift, one end of the transmission mechanism is connected with a rotating shaft of the hinge cover plate, and the other end of the transmission mechanism is connected with the sliding block.
28. The luminal tissue construct printing device of claim 27, wherein the sliding block comprises convex edges disposed at both ends and a guide post sandwiched between two tabs;
the linkage plate is movably sleeved on the guide post, and both sides of the linkage plate are connected with the two convex edges through elastic pieces sleeved on the guide post;
the transmission mechanism is connected with one side, far away from the guide post, of the adjacent convex edge.
29. The printing device for luminal tissue constructs according to claim 28, wherein the transmission mechanism comprises a first transmission wheel, a second transmission wheel and a cover synchronous belt wound between the first transmission wheel and the second transmission wheel respectively disposed on the mounting plate, the first transmission wheel is coaxially connected with the rotation shaft, the cover synchronous belt is connected with a linkage piece, and the linkage piece is connected with one side of the convex edge far away from the guide post through the connecting post.
30. The luminal tissue construct printing device of claim 25, wherein the temperature and humidity control mechanism comprises a temperature control assembly and a humidity control assembly, the temperature control assembly comprising a cooling tube disposed within a showerhead storage chamber;
the humidity control mechanism includes an air drying mechanism in communication with the spray head storage chamber.
31. The device for printing a luminal tissue construct as claimed in any one of claims 2 to 30 wherein the device further comprises a frictioning assembly, the working position of the frictioning assembly being within the range of motion of the manipulator;
the frictioning assembly comprises a frictioning mounting seat and a frictioning motor arranged on the frictioning mounting seat, a frictioning rod is arranged on the frictioning motor, and frictioning sponge is arranged on the frictioning rod.
32. The device for printing a luminal tissue construct as claimed in any one of claims 2 to 30 wherein the device for printing a luminal tissue construct comprises a luminal detector for detecting the flatness of luminal tissue; the working position of the cavity detector is positioned in the moving range of the manipulator.
33. A 3D bioprinter comprising the luminal tissue construct printing apparatus of any one of claims 1 to 32.
34. A method of printing a luminal tissue construct printing device, comprising the steps of:
fixing the lumen tissue inside the hollow rod assembly;
medical glue is arranged on the inner surface of the lumen tissue fixed by the hollow rod component through a gluing component;
the biological printing component receives biological ink sprayed by the spray head component and forms a biological construct;
matching the hollow rod component with the biological printing component, and sleeving the biological construction body in the lumen tissue with the medical glue on the inner surface;
the biological construct is applied to the inner surface of the luminal tissue by a bioprinting assembly.
CN202011631507.9A 2020-12-30 2020-12-30 Lumen tissue construct printing device, 3D biological printer and printing method Pending CN114683541A (en)

Priority Applications (2)

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CN202011631507.9A CN114683541A (en) 2020-12-30 2020-12-30 Lumen tissue construct printing device, 3D biological printer and printing method
PCT/CN2021/139249 WO2022143229A1 (en) 2020-12-30 2021-12-17 Lumen tissue construct printing device, 3d bioprinter and printing method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011631507.9A CN114683541A (en) 2020-12-30 2020-12-30 Lumen tissue construct printing device, 3D biological printer and printing method

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