WO2021136297A1 - 生物打印机喷头、生物打印机和管腔组织构建体打印方法 - Google Patents

生物打印机喷头、生物打印机和管腔组织构建体打印方法 Download PDF

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Publication number
WO2021136297A1
WO2021136297A1 PCT/CN2020/141029 CN2020141029W WO2021136297A1 WO 2021136297 A1 WO2021136297 A1 WO 2021136297A1 CN 2020141029 W CN2020141029 W CN 2020141029W WO 2021136297 A1 WO2021136297 A1 WO 2021136297A1
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WIPO (PCT)
Prior art keywords
nozzle
medical glue
bioprinter
ink
bio
Prior art date
Application number
PCT/CN2020/141029
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English (en)
French (fr)
Inventor
左潇
何峻轩
李意军
向杰
许子卿
蒋智
Original Assignee
四川蓝光英诺生物科技股份有限公司
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Application filed by 四川蓝光英诺生物科技股份有限公司 filed Critical 四川蓝光英诺生物科技股份有限公司
Priority to JP2022540446A priority Critical patent/JP2023508715A/ja
Priority to US17/789,903 priority patent/US20230054757A1/en
Priority to EP20910234.2A priority patent/EP4086063A1/en
Publication of WO2021136297A1 publication Critical patent/WO2021136297A1/zh

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/10—Processes of additive manufacturing
    • B29C64/106—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • B29C64/112—Processes 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/205—Means for applying layers
    • B29C64/209—Heads; Nozzles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/227—Driving means
    • B29C64/232—Driving means for motion along the axis orthogonal to the plane of a layer
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30—Auxiliary operations or equipment
    • B29C64/386—Data acquisition or data processing for additive manufacturing
    • B29C64/393—Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y30/00—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y40/00—Auxiliary operations or equipment, e.g. for material handling
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y50/00—Data acquisition or data processing for additive manufacturing
    • B33Y50/02—Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/10—Processes of additive manufacturing
    • B29C64/106—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30—Auxiliary operations or equipment
    • B29C64/307—Handling of material to be used in additive manufacturing
    • B29C64/321—Feeding
    • B29C64/336—Feeding of two or more materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/753—Medical equipment; Accessories therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/753—Medical equipment; Accessories therefor
    • B29L2031/7532—Artificial members, protheses
    • B29L2031/7534—Cardiovascular protheses
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y10/00—Processes of additive manufacturing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus

Definitions

  • the present disclosure relates to the field of bioprinting technology, and in particular to a method for printing a bioprinter nozzle, a bioprinter, and a luminal tissue construct.
  • the luminal tissue construct is a substitute for the body's own luminal tissue.
  • artificial blood vessels are used as a substitute for the body's own blood vessels when the body's own blood vessels are severely narrowed or occluded.
  • Luminal tissue construct printing device and its printing method and 3D bioprinter proposes a printing technology that can convert biological inks (including biological bricks, and the definition of biological bricks can be Refer to Patent Document 201610211570.4) printed on the inner wall of the artificial lumen of an artificial lumen (such as an artificial blood vessel) to form a lumen tissue construct, so that the prepared lumen tissue construct has the biological properties of a real blood vessel.
  • the current printing technology is difficult to prepare luminal tissue constructs with a length of more than 10 cm. In order to adapt to clinical indications (for example, arteriovenous fistula), it is necessary to prepare a longer (for example, 30 cm in length) luminal tissue construct.
  • the Chinese patent application with the publication number CN109514858A and the invention titled "a multi-channel 3D printing nozzle and a method for manufacturing pipes using the nozzle” discloses a 3D printing nozzle including multiple extrusion pipes and multiple extrusion pipes. Coaxially and arranged in layers from the inside to the outside, different extrusion pipes input different printing materials, and the outlet end of the inner extrusion pipe extends out of the outlet end of the outer extrusion pipe.
  • the Chinese patent application with the publication number CN107411844A and the invention title "Lumen tissue construct and its preparation method and preparation device” discloses a bioprinter 1000 that coats the outer wall of the lumen tissue construct with an adhesive.
  • the printer 1000 is provided with a container for holding an adhesive, a conveying channel, and an adhesive outlet. During the specific coating, the adhesive outlet does not move.
  • the adhesive outlet does not move.
  • the adhesive is continuously squeezed out of the orifice under pressure to apply the adhesive on the inner surface of the outer wall.
  • the inner wall of the printed biological tissue and the outer wall coated with the adhesive are set to obtain a biological construct.
  • the Chinese patent application with the publication number CN105647804A and the invention title "Bioprinter Nozzle and Bioprinter” discloses a coaxial double-channel nozzle for a bioprinter, in which the first flow channel is for the main material fluid (biological ink) to pass through.
  • the second flow channel (that is, the outer flow channel) allows the auxiliary material fluid to pass through, and the inner and outer flow channels are reduced toward the nozzle outlet, so that the auxiliary material can wrap the outflowing main material to form a granular bioprinting material that meets the printing requirements.
  • the nozzle in this document forms micro-droplets required for printing, and cannot realize the simultaneous coating of biological ink and medical glue.
  • the purpose of the present disclosure is to provide a bioprinter nozzle, a bioprinter, and a method for printing a luminal tissue construct.
  • the first aspect of the present disclosure provides a bio-printer nozzle, the bio-printer nozzle has:
  • the biological ink flow channel is arranged inside the nozzle of the biological printer
  • the biological ink nozzle is connected with the biological ink flow channel and is located on the side of the ejection end of the nozzle of the biological printer;
  • the medical glue flow channel is arranged inside the nozzle of the bioprinter and is isolated from the biological ink flow channel;
  • the medical glue nozzle is connected with the medical glue flow channel and is located on the side of the spray end, and along the axial direction of the bioprinter nozzle, the medical glue nozzle and the biological ink nozzle are arranged in a staggered manner.
  • the biological ink nozzle is closer to the top surface of the ejection end than the medical glue nozzle along the axial direction of the nozzle of the bioprinter.
  • the bio-printer nozzle includes a plurality of the biological ink nozzles evenly distributed along the circumferential direction of the bio-printer nozzle; and/or
  • the bioprinter nozzle includes a plurality of the medical glue nozzles evenly distributed along the circumferential direction of the bioprinter nozzle or the medical glue nozzle includes an annular nozzle arranged around the axial direction of the bioprinter nozzle.
  • a medical squeegee coating part is provided on the side of the bioprinter nozzle. Along the axial direction of the bioprinter nozzle, the medical squeegee coating part is located between the biological ink nozzle and the Between the medical glue nozzles.
  • the medical squeegee applicator includes an annular protrusion or a brush head arranged on the side of the nozzle of the bioprinter.
  • the bioprinter nozzle includes:
  • An ink nozzle main body, the biological ink nozzle is arranged on the ink nozzle main body;
  • the main body of the medical glue nozzle is arranged on the outer periphery of the main body of the ink nozzle, the medical glue nozzle is arranged on the body of the medical glue nozzle, or the medical glue nozzle is arranged on the main body of the ink nozzle and the body of the medical glue nozzle between.
  • the biological ink flow channel is arranged in the main body of the ink nozzle;
  • the medical glue flow channel is arranged between the medical glue spray head main body and the ink spray head main body.
  • the bioprinter nozzle includes a connecting piece connected between the ink nozzle main body and the medical glue nozzle main body.
  • the biological ink flow channel is arranged in the main body of the ink nozzle;
  • the medical glue flow channel is arranged in the ink jet head body, and the side wall of the ink jet head body has a communication port communicating with the medical glue flow channel;
  • the medical glue nozzle includes an annular nozzle formed by the ink nozzle main body and an end of the medical glue nozzle main body close to the ejection end and arranged around the axial direction of the bioprinter nozzle, and the communication port is connected to the annular nozzle.
  • the spout is connected.
  • the bio-printer nozzle further includes a nozzle mounting seat, wherein:
  • the biological ink flow channel includes a first biological ink flow channel arranged in the main body of the ink nozzle and a second biological ink flow channel arranged in the nozzle mounting seat, or the biological ink flow channel is arranged in the In the nozzle mounting seat;
  • the medical glue flow channel includes a first medical glue flow channel arranged in the main body of the medical glue spray head and a second medical glue flow channel arranged in the spray head mounting seat.
  • the medical glue flow channel further includes a first annular buffer groove, and the first medical glue flow channel and the second medical glue flow channel are connected through the first annular buffer groove.
  • the first annular buffer groove is formed between the main body of the medical glue spray head and the spray head mounting seat.
  • the medical glue flow channel includes a second annular buffer groove provided between the medical glue nozzle and the first medical glue flow channel.
  • a second aspect of the present disclosure provides a bioprinter, including:
  • a bio-printer nozzle includes the bio-printer nozzle according to the first aspect of the present disclosure
  • a feeding component connected to the bio-printer nozzle, and configured to supply bio-ink to the bio-ink flow channel of the bio-printer nozzle and to supply medical glue to the medical glue flow channel;
  • the artificial lumen mounting assembly includes an artificial lumen mounting cavity for accommodating an artificial lumen of a luminal tissue construct, the artificial lumen mounting assembly is configured to be able to move along the artificial tube relative to the bioprinter nozzle The axial reciprocating movement of the cavity installation cavity.
  • the feeding component includes:
  • a medical glue injector configured to supply medical glue to the medical glue runner
  • a biological ink injector configured to supply biological ink to the biological ink flow channel
  • a syringe fixing assembly configured to fix the medical glue syringe and the biological ink syringe
  • the pushing mechanism is configured to be drivingly connected with the plunger of the medical glue syringe and the plunger of the biological ink syringe to push the two plungers to move.
  • the pushing mechanism includes:
  • the syringe plunger fixing piece is provided with a notch for the end disc of the plunger
  • the plunger fixed spring component includes a component housing, a guide post and a spring.
  • the component housing has a spring installation cavity, and the guide post movably penetrates the component housing and the middle part is located in the spring installation cavity Inside, the first end of the guide post is connected with the syringe plunger fixing piece, the middle part of the guide post has a protruding part facing the radially outer side, and the spring is sleeved on the outer periphery of the guide post and is located in the Between the inner wall of the spring mounting cavity near the first end of the guide post and the protrusion;
  • a spring push piece located at the end of the plunger fixing spring assembly far away from the plunger
  • the push-pull mechanism which is drivingly connected to the component housing, is configured to drive the component housing to move so that the second end of the guide post and the spring push piece switch between the abutting state and the separated state, wherein In the abutting state, a space for installing the end disc is formed between the syringe plunger fixing piece and the plunger fixing spring assembly, and in the separated state, the plunger fixing spring assembly is pressed The end disc is tightened and fixed on the syringe plunger fixing piece, and the push-pull mechanism is configured to drive the plunger to move through the plunger fixing spring assembly.
  • the bioprinter includes a driving assembly that is drivingly connected to the artificial lumen mounting assembly and is configured to drive the artificial lumen mounting assembly along the axis of the artificial lumen mounting cavity To reciprocate.
  • the bioprinter includes a detection module configured to detect the relative position of the nozzle of the bioprinter and the installation cavity of the artificial lumen.
  • the bioprinter includes a temperature control module configured to control the temperature of the artificial lumen installation cavity.
  • the bioprinter further includes:
  • the centralizing rod is extended and movably arranged along the axial direction of the artificial lumen installation cavity;
  • a centralizing plate is arranged at the top end of the centralizing rod, the centralizing plate includes a nozzle mounting opening that is gap-fitted with the outer wall of the bioprinter nozzle, and the nozzle mounting opening of the centralizing plate is configured to be kept installed in the nozzle mounting opening
  • the nozzle of the bioprinter is coaxial with the installation cavity of the artificial lumen.
  • the third aspect of the present disclosure provides a method for printing a luminal tissue construct.
  • the printing of the luminal tissue construct using the bioprinter according to the second aspect of the present disclosure includes:
  • Filling printing materials including filling printing materials to the feeding component
  • Installing the artificial lumen of the lumen tissue construct includes installing the artificial lumen in the artificial lumen installation cavity of the artificial lumen installation component;
  • the initial positioning of the nozzle of the bioprinter includes making the nozzle of the bioprinter extend into the artificial lumen and be in the initial position;
  • Printing material coating includes moving the artificial lumen mounting assembly relative to the bio-printer nozzle along the axial direction of the artificial lumen mounting cavity, and while moving, to the biological ink of the bio-printer nozzle
  • the flow channel supplies biological ink and supplies medical glue to the medical glue flow channel.
  • the method further includes adjusting the temperature of the artificial lumen of the luminal tissue construct after installing the artificial lumen of the artificial lumen.
  • the bio-ink nozzle and the medical glue nozzle are staggered along the axial direction of the bio-printer nozzle.
  • the bio-printer nozzle can be extended into the artificial tube of the luminal tissue construct In the cavity, the artificial lumen mounting assembly that drives the artificial lumen carrying the luminal tissue construct moves axially relative to the bio-printer nozzle, so that the medical glue is ejected first, as the bio-printer nozzle and the luminal tissue construct are combined
  • the artificial lumen moves relatively, and the medical glue is coated on the inner wall of the artificial lumen of the lumen tissue construct to form a medical glue layer.
  • Biological ink is ejected within a short time from the ejection time of medical glue. Due to the adhesive effect of the medical glue, the biological ink can be adhered to the medical glue layer immediately after being ejected, which can realize the simultaneous coating of medical glue and biological ink on the inner wall of the artificial lumen of the elongated luminal tissue construct. Thereby, it is beneficial to ensure that the medical glue layer and the biological ink layer are formed on the inner wall of the artificial lumen of the lumen tissue construct at the same time to form the required lumen tissue construct.
  • bioprinter and luminal tissue construct printing method provided by the present disclosure have corresponding advantages with the nozzle of the bioprinter of the present disclosure.
  • FIG. 1 is a schematic diagram of a three-dimensional structure of a nozzle of a bioprinter according to an embodiment of the present disclosure.
  • FIG. 2 is a schematic cross-sectional view of the nozzle of the bioprinter of the embodiment shown in FIG. 1 from one angle.
  • FIG. 3 is a schematic cross-sectional view of the nozzle of the bioprinter of the embodiment shown in FIG. 1 from another angle.
  • Fig. 4 is a schematic view of the A-A cross-sectional structure of Fig. 3.
  • FIG. 5 is a schematic diagram of a three-dimensional structure of a nozzle of a bioprinter according to an embodiment of the disclosure.
  • FIG. 6 is a schematic cross-sectional view of the nozzle structure of the bioprinter of the embodiment shown in FIG. 5.
  • FIG. 7 is a schematic diagram of a three-dimensional structure of a nozzle of a bioprinter according to an embodiment of the present disclosure.
  • FIG. 8 is a schematic cross-sectional structure diagram of the nozzle of the bioprinter of the embodiment shown in FIG. 7.
  • FIG. 9 is a schematic diagram of the three-dimensional structure of the ink jet head main body of the bioprinter jet head of the embodiment shown in FIG. 7.
  • FIG. 10 is a schematic cross-sectional view of the main body of the ink jet head shown in FIG. 9.
  • FIG. 11 is a schematic diagram of the three-dimensional structure of the main body of the medical glue nozzle of the nozzle of the bioprinter shown in FIG. 7.
  • Fig. 12 is a schematic cross-sectional view of the main body of the medical glue spray head of Fig. 11.
  • FIG. 13 is a schematic diagram of a three-dimensional structure of the nozzle mounting seat of the nozzle of the bioprinter of the embodiment shown in FIG. 7.
  • Fig. 14 is a schematic cross-sectional view of the nozzle mounting seat of Fig. 13.
  • Fig. 15 is a schematic top view of the structure of the nozzle mounting seat of Fig. 13.
  • FIG. 16 is a schematic diagram of a three-dimensional structure of a nozzle of a bioprinter according to an embodiment of the disclosure.
  • FIG. 17 is a schematic cross-sectional structure diagram of the nozzle of the bioprinter of the embodiment shown in FIG. 16.
  • FIG. 18 is a schematic diagram of the three-dimensional structure of the ink jet head body of the bioprinter jet head of the embodiment shown in FIG. 16.
  • FIG. 19 is a schematic cross-sectional view of the main body of the ink jet head shown in FIG. 18.
  • FIG. 20 is a schematic diagram of the three-dimensional structure of the main body of the medical glue nozzle of the nozzle of the bioprinter shown in FIG. 16.
  • 21 is a schematic cross-sectional structure diagram of the main body of the medical glue spray head of FIG. 20.
  • FIG. 22 is a schematic diagram of the three-dimensional structure of the nozzle mounting seat of the nozzle of the bioprinter of the embodiment shown in FIG. 16.
  • FIG. 23 is a schematic cross-sectional structure view of the nozzle mounting seat of FIG. 22.
  • FIG. 24 is a schematic diagram of a three-dimensional structure of a bioprinter according to an embodiment of the disclosure.
  • FIG. 25 is a schematic diagram of a partial structure of the bioprinter of the embodiment shown in FIG. 24.
  • FIG. 26 is a schematic diagram of a partial structure of the bioprinter of the embodiment shown in FIG. 24.
  • FIG. 27 is a cross-sectional view of the plunger fixing spring assembly and other structures of the bioprinter of the embodiment shown in FIG. 24.
  • some embodiments of the present disclosure provide a bioprinter nozzle.
  • the nozzle of the bio-printer has a bio-ink flow path P1, a bio-ink nozzle J1, a medical glue flow path P2, and a medical glue nozzle J2.
  • the bio-ink flow path P1 is arranged inside the nozzle of the bioprinter.
  • the biological ink nozzle J1 communicates with the biological ink flow channel P1, and is located on the side of the ejection end of the nozzle of the biological printer.
  • the medical glue flow path P2 is arranged inside the nozzle of the bioprinter, and is isolated from the biological ink flow path P1.
  • the medical glue nozzle J2 communicates with the medical glue flow channel P2, and is located on the side of the spray end of the nozzle of the bioprinter. And along the axial direction of the nozzle of the bio-printer, the medical glue nozzle J2 and the biological ink nozzle J1 are arranged in a staggered position.
  • the bio-ink nozzle J1 and the medical glue nozzle J2 are staggered along the axis of the bio-printer nozzle.
  • the bio-printer nozzle can be inserted into the luminal tissue construct.
  • the artificial lumen mounting assembly that drives the artificial lumen carrying the luminal tissue construct moves axially relative to the bioprinter nozzle, so that the medical glue is ejected first, along with the bioprinter nozzle and the luminal tissue construct
  • the artificial lumen moves relatively, and the medical glue is coated on the inner wall of the artificial lumen of the lumen tissue construct to form a medical glue layer.
  • Bio ink is ejected within a short time from the ejection time of medical glue. Due to the adhesive effect of the medical glue, the biological ink can be immediately adhered to the medical glue layer after being ejected, which helps to ensure that both the medical glue layer and the biological ink layer are formed on the inner wall of the artificial lumen of the luminal tissue construct.
  • the bioprinter nozzle of the embodiment of the present disclosure can realize the simultaneous coating of medical glue and biological ink on the inner wall of the artificial lumen of the elongated lumen tissue construct.
  • the bio-ink nozzle J1 along the axial direction of the bio-printer nozzle is closer to the top surface of the ejection end than the medical glue nozzle J2.
  • the bioprinter nozzle of this structure can be inserted from the first end of the artificial lumen of the luminal tissue construct to the second end, starting from the second end in the artificial tube
  • the inner wall of the cavity prints the medical glue layer and the biological ink layer.
  • the bioprinter nozzle gradually moves from the second end of the artificial lumen to the first end, so that the bioprinter nozzle is in the lumen when printing luminal tissue constructs.
  • the artificial lumen of the tissue construct is exited while printing, and it can be completely exited after printing.
  • the plurality of biological ink nozzles J1 are evenly distributed along the circumferential direction of the bioprinter nozzle; and/or the medical glue nozzle J2 is an annular nozzle or the plurality of medical glue nozzles J2 are along the circumferential direction of the bioprinter nozzle Evenly distributed.
  • the above arrangement of the biological ink nozzle J1 and the medical glue nozzle J2 facilitates uniform coating of the printing material biological ink and medical glue.
  • the bioprinter nozzle it includes a medical squeegee coating part M arranged on the side of the bioprinter nozzle.
  • the medical squeegee coating part M is located between the biological ink nozzle J1 and the medical glue nozzle J2. between.
  • the medical squeegee coating part includes an annular protrusion or brush head arranged on the side of the nozzle of the bioprinter.
  • the medical glue scraping part M facilitates uniform application of the medical glue, thereby facilitating the uniform and firm adhesion of the biological ink on the inner wall of the artificial lumen.
  • FIGS. 1 to 4 show a bioprinter nozzle 100 according to an embodiment of the present disclosure.
  • the bioprinter nozzle 100 has an ejection end for ejecting printing materials, and has a bio-ink flow channel P1, a bio-ink nozzle J1, a medical glue flow channel P2, and a medical glue nozzle J2.
  • the biological ink flow path P1 is arranged inside the nozzle 100 of the biological printer.
  • the biological ink nozzle J1 communicates with the biological ink flow channel P1 and is located on the side of the ejection end.
  • the medical glue flow path P2 is arranged inside the nozzle 100 of the bioprinter, and is isolated from the biological ink flow path P1.
  • the medical glue nozzle J2 communicates with the medical glue flow channel P2 and is located on the side of the spray end.
  • the medical glue nozzle J2 and the biological ink nozzle J1 are arranged in a staggered manner along the axial direction of the nozzle 100 of the bioprinter.
  • the biological ink nozzle J1 along the axial direction of the nozzle 100 of the bioprinter is closer to the top surface of the ejection end than the medical glue nozzle J2.
  • the plurality of biological ink nozzles J1 are evenly distributed along the circumferential direction of the nozzle 100 of the biological printer.
  • the medical glue nozzle J2 is an annular nozzle.
  • the bioprinter nozzle 100 also includes a medical squeegee coating part M arranged on the side of the bioprinter nozzle 100.
  • the medical squeegee coating part M is located at the biological ink nozzle J1.
  • the medical squeegee coating part M includes an annular protrusion arranged on the side of the nozzle of the bioprinter. In order to facilitate coating, the side of the annular protrusion close to the medical glue nozzle J2 is inclined from the radial inner side to the radial outer side of the bioprinter nozzle 100 toward the biological ink nozzle J1 side.
  • the bioprinter nozzle 100 includes an ink nozzle body 110 and a medical glue nozzle body 120.
  • the biological ink nozzle J1 is arranged on the main body 110 of the ink nozzle.
  • the main body 120 of the medical glue spray head is arranged on the outer periphery of the main body 110 of the ink spray head.
  • the medical glue nozzle J2 is arranged between the ink nozzle main body 110 and the medical glue nozzle main body 120.
  • the medical glue nozzle J2 is arranged between the outer circumferential wall of the ink spray head body 110 and the inner wall of the medical glue nozzle body 120 close to the spray end.
  • the biological ink flow path P1 is arranged in the main body 110 of the ink jet head.
  • a plurality of biological ink nozzles J1 communicate with the biological ink flow channel P1.
  • the medical glue flow channel P2 is arranged between the medical glue spray head main body 120 and the ink spray head main body 110.
  • the medical glue flow channel P2 is an annular flow channel arranged on the outer periphery of the biological ink flow channel P1 as a whole, and the medical glue flows along the axial direction of the annular flow channel.
  • the outlet of the medical glue flow channel P2 (medical glue discharge outlet) is the medical glue nozzle J2.
  • the bioprinter nozzle 100 further includes a connecting piece 130 connected between the ink nozzle body 110 and the medical glue nozzle body 120.
  • the bioprinter nozzle 100 includes an ink nozzle body 110 and a medical glue nozzle body 120 that are coaxially arranged.
  • the ink nozzle main body 110 is inserted into the medical glue nozzle main body 120.
  • the ink nozzle main body 110 and the medical glue nozzle main body 120 are fixed by a connecting piece 130.
  • the connecting piece 130 is used to fix the inner ink spray head main body 110 and the outer medical glue spray head main body 120 so as to maintain the coaxiality of the ink spray head main body 110 and the medical glue spray head main body 120.
  • the upper end of the ink nozzle main body 110 is the ejection end of the bio-printer nozzle 100, and the upper end of the ink nozzle main body 110 is provided with a plurality of bio-ink nozzles J1, and the plurality of bio-ink nozzles J1 are evenly arranged along the circumferential direction of the bio-printer nozzle 100
  • the biological ink can be ejected from each biological ink nozzle J1 respectively. Since the biological ink nozzles J1 are evenly distributed on the side wall of the upper end of the ink nozzle main body 110, the biological ink can be turned into several streams of fluid to be evenly ejected.
  • a biological ink flow channel P1 is arranged inside the ink nozzle main body 110.
  • One end (upper end in the figure) of the biological ink flow channel P1 is a biological ink outlet, and the other end (the lower end in the figure) is a biological ink inlet.
  • the bio-ink outlet is connected with the bio-ink outlet J1.
  • the annular space between the inner wall of the medical glue nozzle main body 120 and the outer wall of the ink nozzle main body 110 forms a medical glue runner P2.
  • One end of the medical glue runner P2 (upper end in the figure) is the medical glue discharge port, which is the medical glue nozzle J2 ,
  • the other end (the lower end in the figure) is the medical glue inlet.
  • a medical glue scraper M is provided at a position of the ink nozzle main body 110 close to the medical glue nozzle J2.
  • the medical squeegee application part M has an inverted tapered shape.
  • the nozzle 100 of the bioprinter of the embodiment of the present disclosure is beneficial to solve the technical problem of how to simultaneously coat the medical glue and the biological ink on the inner wall of the elongated luminal tissue structure.
  • first extend the bioprinter nozzle 100 into the artificial lumen of the luminal tissue construct, and align the position of the medical glue nozzle J2 with the upper edge of the artificial lumen of the luminal tissue construct refer to the figure 24 to FIG. 26 shows the bio-printer 1000, at this time the feeding component 1005 of the bio-printer 1000 starts to provide medical glue and bio-ink, and the driving component 1009 of the bio-printer 1000 drives the artificial lumen of the luminal tissue construct relative to the biological The printer nozzle 100 moves upwards.
  • the position of the bio-ink nozzle J1 and the medical glue nozzle J2 are staggered, and the medical glue can be sprayed onto the inner wall of the artificial lumen first, as the bio-printer nozzle 100 and the artificial lumen
  • the relative movement of the bio-ink jet continues to coat the medical adhesive layer.
  • the biological ink can be immediately adhered to the medical adhesive layer.
  • a medical glue layer and a biological ink layer can be formed on the inner wall of the artificial lumen at the same time, thereby forming the required lumen tissue construct.
  • FIG. 5 and 6 show a bioprinter nozzle 200 according to an embodiment of the present disclosure.
  • the bioprinter nozzle 200 has an ejection end for ejecting printing materials, and has a biological ink flow path P1, a biological ink nozzle J1, a medical glue flow path P2, and a medical glue nozzle J2.
  • the biological ink flow path P1 is arranged inside the nozzle 200 of the biological printer.
  • the biological ink nozzle J1 communicates with the biological ink flow channel P1 and is located on the side of the ejection end.
  • the medical glue flow path P2 is arranged inside the nozzle 200 of the bioprinter, and is isolated from the biological ink flow path P1.
  • the medical glue nozzle J2 communicates with the medical glue flow channel P2 and is located on the side of the jetting end.
  • the medical glue nozzle J2 and the biological ink nozzle J1 are arranged in a staggered manner along the axial direction of the nozzle 200 of the bioprinter.
  • the biological ink nozzle J1 along the axial direction of the nozzle 200 of the bioprinter is closer to the top surface of the ejection end than the medical glue nozzle J2.
  • the plurality of biological ink nozzles J1 are evenly distributed along the circumferential direction of the nozzle 200 of the biological printer.
  • the medical glue nozzle J2 is an annular nozzle.
  • the bioprinter nozzle 200 includes an ink nozzle main body 210 and a medical glue nozzle main body 220.
  • the biological ink nozzle J1 is arranged on the main body 210 of the ink nozzle.
  • the medical glue spray head main body 220 is arranged on the outer periphery of the ink spray head main body 210.
  • the biological ink flow path P1 is arranged in the main body 210 of the ink jet head.
  • a plurality of biological ink nozzles J1 communicate with the biological ink flow channel P1.
  • the medical glue flow path P2 is arranged in the ink jet head main body 210, and the side wall of the ink jet head main body 210 has a communication port N communicating with the medical glue flow path P2.
  • the medical glue nozzle J2 is arranged between the ink nozzle main body 210 and the medical glue nozzle main body 220.
  • the medical glue nozzle J2 includes an annular nozzle formed by the ink nozzle body 210 and the end of the medical glue nozzle body 220 close to the spraying end and arranged around the axial direction of the bioprinter nozzle, and the communication port N communicates with the annular nozzle.
  • the medical glue nozzle J2 is provided between the circumferential outer wall of the ink spray head main body 210 and the inner wall of the medical glue nozzle main body 220 close to the spray end.
  • the nozzle 200 of the bioprinter according to the embodiment of the present disclosure will be described in more detail below in conjunction with FIG. 5 and FIG. 6.
  • the bioprinter nozzle 200 includes an ink nozzle main body 210 and a medical glue nozzle main body 220.
  • the ink nozzle main body 210 is provided with a bio-ink flow channel P1 and a medical glue flow channel P2 in parallel.
  • One end of the bio-ink flow channel P1 (the upper end in the figure) is the bio-ink outlet, and the other end (the lower end in the figure) is the bio-ink inlet.
  • the feed port, one end of the medical glue flow channel P2 (upper end in the figure) is the medical glue discharge port, and the other end (the lower end in the figure) is the medical glue feed port.
  • the upper end of the ink nozzle body 210 is provided with a plurality of biological ink nozzles J1, and the plurality of biological ink nozzles J1 are evenly arranged on the side wall of the upper end of the ink nozzle body 210 along the circumferential direction of the bioprinter nozzle 200, and the biological ink nozzles J1 and the biological ink nozzles
  • the ink outlet is connected.
  • a boss is provided in the middle of the ink spray head main body 210, and a sleeve-shaped medical glue spray head main body 220 is sleeved on the boss.
  • the annular nozzle between the main body 220 of the medical glue nozzle and the outer wall of the main body 210 of the ink nozzle is the medical glue nozzle J2.
  • the medical glue nozzle J2 is connected with the medical glue discharge port of the medical glue flow channel P2.
  • the working principle of the bioprinter nozzle 200 is the same as the working principle of the bioprinter nozzle 100, and the description will not be repeated here.
  • the pipe diameters of the biological ink flow channel P1 and the medical glue flow channel P2 can be set smaller than the pipe diameters of the corresponding flow channels of the bioprinter nozzle 100, so that the biological ink and medical glue can be saved during the printing process.
  • the dosage can be set smaller than the pipe diameters of the corresponding flow channels of the bioprinter nozzle 100, so that the biological ink and medical glue can be saved during the printing process. The dosage.
  • FIGS. 7 to 15 show a bioprinter nozzle 300 according to an embodiment of the present disclosure.
  • the bioprinter nozzle 300 has an ejection end (upper end in the figure) for ejecting printing materials, and has a bio-ink flow channel P1, a bio-ink nozzle J1, a medical glue flow channel P2, and a medical glue nozzle J2.
  • the biological ink flow path P1 is arranged inside the nozzle 300 of the biological printer.
  • the biological ink nozzle J1 communicates with the biological ink flow channel P1 and is located on the side of the ejection end.
  • the medical glue flow path P2 is arranged inside the nozzle 300 of the bioprinter, and is isolated from the biological ink flow path P1.
  • the medical glue nozzle J2 communicates with the medical glue flow channel P2 and is located on the side of the spray end.
  • the medical glue nozzle J2 and the biological ink nozzle J1 are arranged in a staggered manner along the axial direction of the nozzle 300 of the bioprinter.
  • the biological ink nozzle J1 along the axial direction of the nozzle 300 of the bioprinter is closer to the top surface of the ejection end than the medical glue nozzle J2.
  • the plurality of biological ink nozzles J1 are evenly distributed along the circumferential direction of the nozzle 300 of the biological printer.
  • the medical glue nozzle J2 is an annular nozzle.
  • the bioprinter nozzle 300 includes an ink nozzle body 310, a medical glue nozzle body 320 and a nozzle mounting seat 330.
  • the ink nozzle main body 310 and the medical glue nozzle main body 320 are arranged on the nozzle mounting seat 330.
  • the biological ink nozzle J1 is arranged on the main body 310 of the ink nozzle.
  • the main body 320 of the medical glue spray head has a sleeve-like structure and is arranged on the outer periphery of the main body 310 of the ink spray head.
  • the medical glue nozzle J2 includes an annular nozzle formed by the ink nozzle body 310 and the end of the medical glue nozzle body 320 close to the spraying end, and the communication port is in communication with the annular nozzle. As shown in FIG. 8, the medical glue nozzle J2 is arranged between the bottom wall of the middle protruding part of the ink nozzle main body 310 and the end wall of the medical glue nozzle main body 320 close to the ejection end of the bioprinter nozzle 300.
  • the biological ink flow path P1 includes a first biological ink flow path P11 provided in the ink nozzle main body 310 and a second biological ink flow path P12 provided in the nozzle mounting seat 300.
  • the medical glue flow channel P2 includes a first medical glue flow channel P21 arranged in the medical glue spray head main body 320 and a second medical glue flow channel P22 arranged in the spray head mounting seat. As shown in FIG. 8, the medical glue flow channel P2 further includes a first annular buffer groove G, and the first medical glue flow channel P21 and the second medical glue flow channel P22 are connected through the first annular buffer groove G. As shown in FIG. 8, the first annular buffer groove G is formed between the medical glue spray head main body 320 and the spray head mounting seat 330.
  • the nozzle 300 of the bioprinter according to the embodiment of the present disclosure will be further described below with reference to FIGS. 7 to 15.
  • the bioprinter nozzle 300 includes an ink nozzle body 310, a medical glue nozzle body 320 and a nozzle mounting seat 330.
  • the spray head mounting seat 330 is provided with a medical glue spray head main body 320 and an ink spray head body 310 in sequence, and the ink spray head body 310 passes through the medical glue spray head body 320 and is inserted into the spray head mounting seat 330.
  • the nozzle mounting seat 330 is provided with a second bio-ink flow channel P12, one end of the second bio-ink flow channel P12 is a feed port of the second bio-ink flow channel P12, and the other end is a second bio-ink flow channel P12 discharge port.
  • the second bio-ink flow channel P12 is provided with a second medical glue flow channel P22 symmetrically on both sides.
  • the number of the second medical glue flow channel P22 can be set to one.
  • One end of the second medical glue flow path P22 is a discharge port of the second medical glue flow path P22, and the other end is a feed port of the second medical glue flow path P22.
  • the ink jet head body 310 includes a mounting post 311 arranged at the lower part, and a mounting cavity C2 is arranged in the middle of the medical glue jet head body 320.
  • the mounting cavity C2 is used for allowing the mounting post 311 of the ink jet head body 310 to pass therethrough.
  • a plurality of first medical glue runners P21 are evenly arranged outside the installation cavity C2.
  • One end of the first medical glue flow channel P21 is the first medical glue outlet O2, and the other end is the first medical glue inlet.
  • the upper surface of the main body 320 of the medical glue nozzle is provided with a plurality of first medical glue outlets O2, and the plurality of first medical glue outlets O2 are evenly arranged along the circumferential direction.
  • the first medical glue discharge port O2 (as a communicating port) is connected with the medical glue nozzle J2 (annular nozzle), and the first medical glue feed port is connected with the second medical glue discharge port.
  • a second medical glue flow channel P22 is symmetrically provided on both sides of the second biological ink flow channel P12, and a first annular buffer groove G is provided above the second medical glue flow channel P22.
  • One end of the second medical glue flow path P22 is the second medical glue discharge port, and the other end is the second medical glue feed port.
  • the second medical glue discharge port is in communication with the first annular buffer groove G.
  • a mounting cavity C2 is provided in the middle of the main body 320 of the medical glue nozzle.
  • a number of first medical glue flow channels P21 are evenly arranged on the periphery of the mounting cavity C2.
  • One end of the first medical glue flow channel P21 is the first medical glue discharge communicating with the medical glue nozzle. O2, the other end is the first medical glue feed port, the first medical glue feed port is in communication with the first annular buffer tank G.
  • a plurality of biological ink nozzles J1 are arranged on the upper end of the ink nozzle body 310, and the plurality of biological ink nozzles J1 are evenly arranged on the side wall of the upper end of the ink nozzle body 310.
  • the lower end of the ink nozzle body 310 is provided with a mounting post 311.
  • the ink nozzle body 310 is provided with a first biological ink flow channel P11.
  • One end of the first biological ink flow channel P11 is a first biological ink discharge port, and the other end is a first biological ink outlet.
  • the first bio-ink outlet is in communication with the bio-ink spout J1
  • the first bio-ink inlet is in communication with the second bio-ink outlet.
  • the working principle of the bio-printer nozzle 300 is the same as that of the bio-printer nozzle 100, and the description will not be repeated here.
  • the diameter of the bio-ink flow channel and the medical glue flow channel is smaller than that of the bio-printer nozzle 100, thereby saving the amount of bio-ink and medical glue in the printing process.
  • the upper end of the nozzle mounting seat 330 and the lower end of the mounting post 311 may have a threaded connection structure, which facilitates the assembly and disassembly of the nozzle mounting seat 330, the ink nozzle body 310, and the medical glue nozzle body 320.
  • FIGs 16 to 23 show a bioprinter nozzle 400 according to an embodiment of the present disclosure.
  • the bioprinter nozzle 400 has an ejection end (upper end in the figure) for ejecting printing materials, and has a biological ink flow path P1, a biological ink nozzle J1, a medical glue flow path P2, and a medical glue nozzle J2.
  • the biological ink flow path P1 is arranged inside the nozzle 400 of the biological printer.
  • the biological ink nozzle J1 communicates with the biological ink flow channel P1 and is located on the side of the ejection end.
  • the medical glue flow path P2 is arranged inside the nozzle 400 of the bioprinter, and is isolated from the biological ink flow path P1.
  • the medical glue nozzle J2 communicates with the medical glue flow channel P2 and is located on the side of the jetting end.
  • the medical glue nozzle J2 and the biological ink nozzle J1 are arranged in a staggered manner along the axial direction of the nozzle 400 of the bioprinter.
  • the biological ink nozzle J1 along the axial direction of the nozzle 400 of the bioprinter is closer to the top surface of the ejection end than the medical glue nozzle J2.
  • a plurality of biological ink nozzles J1 are evenly distributed along the circumferential direction of the nozzle 400 of the bioprinter, and the medical glue nozzle J2 is an annular nozzle.
  • the bioprinter nozzle includes an ink nozzle body 410, a medical glue nozzle body 420, and a nozzle mounting seat 430.
  • the ink nozzle main body 410 and the medical glue nozzle main body 420 are arranged on the nozzle mounting seat 430.
  • the biological ink nozzle J1 is arranged on the main body 410 of the ink nozzle.
  • the main body 420 of the medical glue spray head has a sleeve-like structure and is arranged on the outer periphery of the main body 410 of the ink spray head.
  • the medical glue nozzle J2 includes an annular nozzle formed by the ink nozzle body 410 and the end of the medical glue nozzle body 420 close to the spraying end. As shown in FIG. 17, the medical glue nozzle J2 is arranged between the bottom wall of the middle protruding part of the ink nozzle main body 410 and the end wall of the medical glue nozzle main body 420 close to the ejection end of the bioprinter nozzle 400.
  • the biological ink flow path P1 is arranged in the nozzle mounting seat 430.
  • the medical glue flow channel P2 includes a first medical glue flow channel P21 arranged in the medical glue spray head main body 420 and a second medical glue flow channel P22 arranged in the spray head mounting seat 430. As shown in FIG. 17, the medical glue flow channel P2 further includes a first annular buffer groove G, and the first medical glue flow channel P21 and the second medical glue flow channel P22 are connected through the first annular buffer groove G. As shown in FIG. 17, the first annular buffer groove G is formed between the medical glue spray head main body 420 and the spray head mounting seat 430.
  • the medical glue flow channel P2 includes a second annular buffer groove L provided between the medical glue nozzle J2 and the first medical glue flow channel P21.
  • the bioprinter nozzle 400 includes an ink nozzle body 410, a medical glue nozzle body 420, and a nozzle mounting seat 430.
  • the nozzle mounting seat 430 is provided with a medical glue nozzle main body 420 and an ink nozzle main body 410 in sequence.
  • the nozzle mounting seat 430 is provided with a biological ink flow channel P1.
  • One end (upper end in the figure) of the biological ink flow channel P1 is a biological ink outlet O1, and the other end (the lower end in the figure) is a biological ink inlet.
  • a second medical glue flow channel P22 is symmetrically provided on both sides of the biological ink flow channel P1 in the nozzle mounting seat 430, respectively.
  • One end of the second medical glue flow channel P22 is the second medical glue discharge port O22, and the other end is the second medical glue feed port.
  • the number of the second medical glue runner P22 can be set to one.
  • the nozzle mounting seat 430 is respectively provided with a first mounting post 431 for mounting the ink nozzle body 410, a second mounting post 432 for mounting the medical glue nozzle body 420, and a mounting seat body 433 from top to bottom.
  • the outer wall above the first mounting post 431 is provided with a first external thread
  • the outer wall of the second mounting post 432 is provided with a second external thread.
  • the second medical glue outlet O22 is located on the upper end surface of the second mounting post 432.
  • the bio-ink outlet O1 is located on the upper end surface of the first mounting post 431.
  • a first installation cavity C21 for passing the first installation post 431 and a second installation cavity C22 for passing the second installation post 432 are sequentially arranged inside the main body 420 of the medical glue spray head.
  • a second internal thread T2 is provided on the inner wall of the second mounting cavity C22, and the detachable connection between the medical glue spray head main body 420 and the spray head mounting seat 430 is realized through the threading of the second internal thread T2 and the second external thread.
  • the upper end surface of the medical glue nozzle main body 420 is provided with a second annular buffer groove L, and the bottom surface of the second annular buffer groove L is provided with a plurality of first medical glue outlets O21, and the plurality of first medical glue outlets O21 are evenly distributed On the bottom surface of the second annular buffer groove L.
  • a plurality of first medical glue flow passages P21 are provided below the second annular buffer groove L corresponding to the plurality of medical glue discharge ports O21.
  • One end (upper end in the figure) of the first medical glue flow channel P21 is the first medical glue outlet O21, and the other end (the lower end in the figure) is the first medical glue inlet.
  • the first medical glue discharge port O21 is connected with the medical glue nozzle J2.
  • the first medical glue inlet is connected to the second medical glue outlet O22.
  • a mounting cavity C1 for cooperating with the first mounting post 431 is provided in the main body 410 of the ink jet head.
  • a first internal thread T1 is provided on the inner wall of the installation cavity C1.
  • the detachable connection between the ink spray head main body 410 and the spray head mounting seat 430 is realized by the thread cooperation of the first internal thread T1 and the first external thread.
  • the medical glue spray head main body 420 and the ink spray head main body 410 can be easily disassembled and cleaned.
  • the upper end of the ink nozzle body 410 is provided with a plurality of biological ink nozzles J1, and the plurality of biological ink nozzles J1 are evenly arranged on the side wall of the upper end of the ink nozzle body 410 along the circumferential direction, and the biological ink nozzle J1 is in communication with the biological ink outlet O1 .
  • a sponge is set in the gap between the lower end of the ink nozzle body 410 and the upper end of the medical glue nozzle body 420 Brush head.
  • the sponge brush head can be used to infiltrate the medical glue sprayed from the medical glue nozzle J2 first, soak the sponge brush head, and then contact and squeeze the sponge brush head with the artificial lumen inner wall of the luminal tissue construct, thereby squeezing the medical glue.
  • the glue is evenly coated on the inner wall of the artificial lumen of the lumen tissue construct.
  • the working principle of the bioprinter nozzle 400 is the same as the working principle of the bioprinter nozzle 100, and the description will not be repeated here.
  • the biological ink and medical can be saved during the printing process.
  • the amount of glue By changing the structure of the medical glue nozzle J2 in the main body 420 of the medical glue nozzle and adding a sponge brush head, the medical glue can be coated on the inner wall of the artificial lumen of the luminal tissue construct more uniformly during the spraying process of the medical glue.
  • an embodiment of the present disclosure also provides a bioprinter 1000.
  • the bioprinter 1000 of the embodiment of the present disclosure mainly includes a bioprinter nozzle 1001, a feeding assembly 1005, and an artificial lumen mounting assembly 1030.
  • the bioprinter nozzle 1001 includes the bioprinter nozzle of the foregoing embodiment.
  • the bio-printer nozzle 1001 may be the aforementioned bio-printer nozzle 100, 200, 300, or 400 and their deformation modes.
  • the feeding component 1005 is connected to the bio-printer nozzle 1001, and is configured to supply bio-ink to the bio-ink flow channel P1 of the bio-printer nozzle 1001 and to supply the medical glue to the medical glue flow channel P2.
  • the artificial lumen installation assembly 1030 includes an artificial lumen installation cavity 1014 for accommodating the artificial lumen of the lumen tissue construct.
  • the artificial lumen mounting assembly 1030 is configured to be able to reciprocate along the axial direction of the artificial lumen mounting cavity 1014 relative to the nozzle 1001 of the bioprinter.
  • the artificial lumen is, for example, an artificial blood vessel, an artificial bile duct, an artificial urinary tube, and the like.
  • the feeding component 1005 mainly includes a medical glue injector 1003, a bio-ink injector 1004, a syringe fixing component, and a pushing mechanism.
  • the medical glue injector 1003 is configured to supply medical glue to the medical glue flow path P2.
  • the biological ink injector 1004 is configured to supply biological ink to the biological ink flow path P1.
  • the syringe fixing assembly is configured to fix the medical glue syringe 1003 and the biological ink syringe 1004.
  • the pushing mechanism is configured to be drivingly connected with the plunger of the medical glue injector 1003 and the plunger of the biological ink injector 1004 to push the two plungers to move.
  • the pushing mechanism mainly includes a syringe plunger fixing piece 1024, a plunger fixing spring assembly 1029, a spring pushing piece 1025, and a push-pull mechanism 1026.
  • the syringe plunger fixing piece 1024 is provided with a notch for placing the end disc of the plunger.
  • the plunger fixing spring assembly 1029 includes an assembly housing 10291, a guide post 10292, and a spring 10293.
  • the component housing 10291 has a spring mounting cavity 10294 inside.
  • the guide post 10292 is movably penetrated on the component housing 10291 and the middle part is located in the spring installation cavity 10294.
  • the first end of the guide post 10292 is connected to the syringe plunger fixing piece 1024.
  • the middle part of the guide post 10292 has a protruding part facing radially outward.
  • the spring 10293 is sleeved on the outer circumference of the guide post 10292 and is located between the inner wall of the spring mounting cavity 10294 close to the first end of the guide post 10292 and the protruding part.
  • the spring push piece 1025 is located at an end of the plunger fixing spring assembly 1029 away from the plunger.
  • the push-pull mechanism 1026 is drivingly connected to the component housing 10291, and is configured to drive the component housing 10291 to move so that the second end of the guide post 10292 and the spring push piece 1025 switch between the abutting state and the separated state.
  • abutting state a space for installing the end disc is formed between the syringe plunger fixing piece 1024 and the plunger fixing spring assembly 1029.
  • the plunger fixing spring assembly 1029 compresses and fixes the end disc on the syringe plunger fixing piece 1024, and the push-pull mechanism 1026 is configured to drive the plunger to move through the plunger fixing spring assembly 1029.
  • the bioprinter 1000 includes a driving assembly 1009.
  • the driving assembly 1009 is drivingly connected to the artificial lumen mounting assembly 1030, and is configured to drive the artificial lumen mounting assembly 1030 to reciprocate along the axial direction of the artificial lumen mounting cavity 1014.
  • the bioprinter 1000 includes a detection module 1012.
  • the detection module 1012 is configured to detect the relative position of the nozzle 1001 of the bioprinter and the installation cavity 1014 of the artificial lumen.
  • the bioprinter includes a temperature control module 1013.
  • the temperature control module 1013 is configured to control the temperature of the artificial lumen mounting cavity 1014.
  • the temperature control module 1013 can also be separately arranged on the syringe compression plate 1018 and the pipe clamping block 1028 to realize the control of the medical glue syringe 1003 and the biological ink The temperature control of the syringe 1004, the biological ink connection pipe 1015, and the medical glue connection pipe 1016.
  • the bioprinter includes a righting rod 1021 and a righting plate 1027.
  • the centralizing rod 1021 extends along the axial direction of the artificial lumen mounting cavity 1014 and is movably arranged.
  • the centralizing plate 1027 is arranged at the top of the centralizing rod 1021, and the centralizing plate 1027 includes a nozzle mounting opening that fits with the outer wall of the bioprinter nozzle 1001.
  • the nozzle mounting opening of the centralizing plate 1027 is configured to maintain the bioprinter nozzle 1001 installed in the nozzle mounting opening.
  • the artificial lumen installation cavity 1014 is coaxial.
  • the bioprinter 1000 according to the embodiment of the present disclosure will be described in more detail below with reference to FIGS. 24 to 26.
  • the “front” used when describing the bioprinter 1000 refers to the direction of movement of the plunger of the syringe of the bioprinter 1000 when the bio-ink and medical glue is transported outward, and the “rear” refers to the movement direction The opposite direction.
  • "front” is on the left and “rear” is on the right.
  • the bioprinter 1000 includes a mounting base 1002, and a bioprinter nozzle 1001, a feeding assembly 1005, an artificial lumen mounting assembly 1030, a driving assembly 1009, and a detection module 1012 arranged on the mounting base 1002.
  • the feeding assembly 1005 includes a medical glue injector 1003, a biological ink injector 1004, a syringe mounting plate 1017, a syringe pressing assembly, a pressing plate driving mechanism, and a pushing mechanism.
  • the syringe compression assembly includes a syringe compression plate 1018, a rotating shaft, and a rack and pinion assembly.
  • the syringe pressing plate 1018 is fixedly connected with the rotating shaft, and the rotating shaft is fixedly connected with the gear.
  • the syringe pressing plate 1018 is driven by the cooperation of the rotating shaft, gear and rack, and the gear connected with the rotating shaft drives the rotating shaft to rotate when moving on the rack, thereby moving the syringe pressing plate 1018, and pressing the two syringes on the syringe mounting plate 1017 on.
  • a push mechanism is provided at the rear of the two syringes, and the push mechanism includes a plunger fixing mechanism arranged at the front end and a push-pull mechanism 1026 arranged at the rear end.
  • the plunger fixing mechanism includes a syringe plunger fixing piece 1024, a plunger fixing spring assembly 1029, and a spring pushing piece 1025.
  • the syringe plunger fixing piece 1024 is provided with a notch for placing a disc at the end of the plunger.
  • the syringe plunger fixing piece 1024 is located in front of the plunger fixing spring assembly 1029 and connected with the plunger fixing spring assembly 1029.
  • the spring push plate 1025 is located behind the plunger fixing spring assembly 1029.
  • the plunger fixing spring assembly 1029 has a block structure as a whole.
  • the syringe plunger fixing piece 1024 includes a component housing 10291, upper and lower guide posts 10292 arranged on the component housing 10291, and two spring mounting cavities 10294 respectively arranged in the upper and lower spring mounting cavities 10294 of the component housing 10291.
  • Spring 10293 Each spring 10293 is located in the corresponding spring mounting cavity 10294 and sleeved on the outer periphery of the corresponding guide post 10292.
  • the spring 10293 is located between the protrusion of the corresponding guide post 10292 and the inner wall of the spring mounting cavity 10294 near the first end of the guide post 10292. between.
  • the two ends of the guide post 10292 extend out of the component housing 10291.
  • the front end (first end) of the guide post 10292 is connected to the syringe plunger fixing piece 1024.
  • the push-pull mechanism 1026 is drivingly connected with the component housing 10291.
  • the push-pull mechanism 1026 drives the plunger fixing spring assembly 1029 to move backwards
  • the rear end (second end) of the guide post 10292 is in abutment state with the spring push plate 1025, which prompts the guide post 10292 to move forward and drives the syringe plunger to be fixed.
  • the distance between the sheet 1024 and the assembly housing 10291 of the plunger fixing spring assembly 1029 is increased, leaving a space for inserting the plunger end disc.
  • the push-pull mechanism 1026 can then drive the plunger fixing spring assembly 1029 to move back and forth, thereby driving the plunger of the syringe to squeeze out the bio-ink or medical glue in the syringe, completing the feeding assembly 1005 to feed the bio-printer nozzle 1001 .
  • the plunger fixing spring assembly 1029 is arranged on the guide rail 1031, and the plunger fixing spring assembly 1029 reciprocates along the guide rail 1031.
  • the front end of the medical glue injector 1003 is connected to the medical glue flow channel of the bio-printer nozzle 1001 through a medical glue connection pipe 1016, and the front end of the biological ink injector 1004 is connected to the biological ink flow channel of the bio-printer nozzle 1001 through a biological ink connection pipe 1015.
  • a syringe compression tablet 1022 is provided at the exit of the syringe barrel.
  • a pipe clamping block 1028 and a pipe fixing block 1020 for fixing the bioprinter nozzle 1001
  • the biological ink connection pipe 1015 and the medical glue connection pipe 1016, and the syringe tablet 1022 is pressed in the pipe clamping block 1028, And it is fixed by its matched pins to prevent the whole syringe from being pulled back when the plunger is pulled.
  • the pipe clamping block 1028 is compressed on the pipe fixing block 1020 by a pipe clamping block pressing plate 1019 that moves vertically up and down relative to the pipe clamping block 1028.
  • the pipe fixing block 1020 and the syringe mounting plate 1017 are both fixed on the movable bottom plate provided on the side of the pipe fixing block 1020.
  • the pipe fixing block 1020 is provided with a chute on the side surface, and a centralizing rod 1021 that can slide along the chute is provided in the chute.
  • the centralizing rod 1021 is arranged in parallel with the bioprinter nozzle 1001, and on its top is provided with a clearance fit with the outer wall of the bioprinter nozzle 1001
  • the centralizer 1027 The centralizing rod 1021 and the centralizing plate 1027 determine the moving direction of the nozzle 1001 of the bioprinter, so that the nozzle 1001 of the bioprinter maintains straightness.
  • the artificial lumen installation assembly 1030 includes two clamping blocks with semi-circular grooves.
  • the side surface of a clamping block is connected with the driving assembly 1009 as a fixed clamping block.
  • the other clamping block serves as the cover clamping block and is connected to the fixed clamping block through a hinge.
  • Both the fixed clamp block and the cover clamp block are provided with a temperature control module 1013, and the temperature control module 1013 can adjust the temperature of the artificial lumen installation cavity 1014.
  • the two semicircular grooves are combined to form a cylindrical hollow cavity with a diameter slightly larger than the outer diameter of the bioprinter nozzle 1001 as an artificial lumen installation cavity 1014.
  • the length of the artificial lumen mounting cavity 1014 is slightly smaller than the length of the medical glue flow channel of the bioprinter nozzle 1001.
  • the driving assembly 1009 includes a driving motor 1006, a screw rod 1008, a sliding block 1010, a connecting plate 1011, and a sliding rail 1007.
  • the output shaft of the drive motor 1006 is connected with a screw rod 1008, the screw rod 1008 is provided with a sliding block 1010 which is movably matched with the screw rod 1008, a section of the sliding block 1010 is connected with a connecting plate 1011, and a sliding rail 1007 is provided under the connecting plate 1011, and the connecting plate 1011 is connected with the fixed clamp block.
  • the drive motor 1006 drives the screw 1008 to rotate.
  • the screw 1008 rotates to drive the slider 1010 to move on the screw 1008.
  • the slider 1010 moves, it drives the connecting plate 1011 to move on the slide rail 1007, thereby driving the artificial tube through the connecting plate 1011.
  • the cavity mounting assembly 1030 moves.
  • a detection module 1012 is fixed at the top position of the artificial lumen installation cavity 1014 of the artificial lumen installation assembly 1030.
  • the detection module 1012 includes a bracket and a camera fixed on the bracket. The camera faces the upper area of the artificial lumen mounting cavity 1014 and is used to detect whether the bioprinter nozzle 1001 reaches the initial position.
  • the initial position may be a position where the medical glue nozzle of the bioprinter nozzle 1001 is aligned with the upper edge of the artificial lumen of the lumen tissue construct.
  • the artificial lumen mounting assembly 1030 and the detection module 1012 are both drivingly connected with the driving assembly 1009 to move up and down on the sliding rail 1007.
  • the bio-printer nozzle 1001 and the artificial lumen mounting assembly 1030 can move relative to each other along the axial direction of the artificial lumen mounting cavity 1014.
  • the medical glue and biological ink are formed in the lumen tissue construct. Uniform, uniform and synchronous coating on the inner wall of the artificial lumen.
  • the detection module 1012 can ensure that the medical glue and biological ink are in a critical overflow state, so that when the coating operation starts, the medical glue and biological ink can immediately leave the medical glue nozzle and the biological ink nozzle to ensure the overall coating No deviation in length.
  • the embodiments of the present disclosure also provide a method for printing a luminal tissue construct using the aforementioned bioprinter to print the luminal tissue construct.
  • the artificial lumen of the luminal tissue construct is, for example, an artificial blood vessel.
  • the printing method of the luminal tissue construct includes the following steps:
  • Filling the printing material includes filling the feeding component 1005 with printing material.
  • Installing the artificial lumen of the lumen tissue construct includes installing the artificial lumen in the artificial lumen installation cavity 1014 of the artificial lumen installation assembly 1030. Put the artificial lumen of the luminal tissue construct into the artificial lumen installation cavity and clamp and fix it.
  • Adjust the temperature of the artificial lumen installation cavity 1014 Adjusts the temperature of the artificial lumen installation cavity 1014. Set the temperature control module 1013 to a suitable temperature.
  • the initial positioning of the nozzle of the bioprinter includes making the nozzle 1001 of the bioprinter extend into the artificial lumen and be in the initial position.
  • the driving assembly 1009 is controlled to drive the artificial lumen mounting assembly 1030 to move downward.
  • the centralizing plate 1027 drives the centralizing rod 1021 to move downward.
  • the centralizer 1027 can ensure that the bioprinter nozzle 1001 is coaxial with the artificial lumen of the luminal tissue construct when it is in contact with the artificial lumen of the luminal tissue construct, so that the bioprinter nozzle 1001 can smoothly enter the luminal tissue construct and Continue to maintain the relative movement until the top of the bioprinter nozzle 1001 protrudes from the luminal tissue construct.
  • the detection module 1012 When the detection module 1012 detects that the bioprinter nozzle 1001 reaches the initial position (for example, the top of the bioprinter nozzle 1001 just protrudes from the artificial lumen), it controls the push-pull mechanism 1026 to push the medical glue and biological ink.
  • the camera detects that there is medical glue and biological ink overflowing from the bioprinter nozzle 1001, the push-pull mechanism 1026 is suspended, and the medical glue and biological ink are injected into the bioprinter nozzle 1001 in advance, and monitored by the camera, before printing starts. , Make a pre-determination whether each flow channel of the bioprinter head 1001 is unobstructed.
  • Printing material coating Control the driving assembly 1009 to move in the reverse direction.
  • the bioprinter nozzle 1001 moves to a certain set position of the artificial lumen (for example, the position where the medical glue nozzle is aligned with the upper edge of the artificial lumen)
  • the push-pull mechanism 1026 is activated to push forward, Make the bio-printer nozzle 1001 squeeze out the medical glue and biological ink at the same time.
  • the medical glue is smeared on the inner wall of the artificial lumen from top to bottom to form a medical glue layer, biological ink It is also applied to the inner wall of the medical glue layer from top to bottom, and the medical glue layer and the biological ink layer are processed simultaneously until the set coating length is completed, and the movement of the pushing mechanism is stopped.
  • the driving assembly 1009 continues to drive the artificial lumen mounting assembly 1030 to move upwards to make the bioprinter nozzle 1001 leave the artificial lumen mounting cavity, open the cover clamp, and take out the biological construct layer (including the medical glue layer and the biological ink layer) Luminal tissue construct.
  • the push-pull mechanism 1026 is stretched backward to drive the plunger of the syringe to move backward.
  • the coating of medical glue and biological ink can be synchronously completed on the inner wall of the artificial lumen of the luminal tissue construct, so that the biological construct layer prepared in the artificial lumen of the luminal tissue construct can be formed at one time, ensuring The effect of sticking bio-ink.
  • coating can be started from a specific location. The coating material is pushed to the nozzle before coating inside the pipe, and the material can be discharged directly when the coating is started, and there will be no delay in discharging.
  • bio-printer nozzle Using the bio-printer nozzle, bio-printer, and luminal tissue construct printing method of the embodiments of the present disclosure, it is possible to realize simultaneous coating of medical glue and biological ink on the inner wall of the artificial luminal cavity of artificial biological constructs such as luminal tissue constructs, forming one-time molding
  • a bioprinter nozzle and an artificial lumen installation cavity that meet the requirements can be used according to the required length. Therefore, it is possible to process more slender luminal tissue constructs, which is beneficial to avoid the need for luminal tissue constructs. If it is too long, the medical glue and bio-ink are printed multiple times, and the viscosity of the medical glue drops.

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Abstract

一种生物打印机喷头（100，200，300，400，1001）、生物打印机（1000）和管腔组织构建体打印方法。生物打印机喷头具有：生物墨汁流道（P1），设置于生物打印机喷头（100，200，300，400，1001）内部；生物墨汁喷口（J1），与生物墨汁流道（P1）连通，位于生物打印机喷头（100，200，300，400，1001）的喷射端的侧面；医用胶流道（P2），设置于生物打印机喷头（100，200，300，400，1001）内部，与生物墨汁流道（P1）隔离；医用胶喷口（J2），与医用胶流道（P2）连通，位于喷射端的侧面，并且，沿生物打印机喷头（100，200，300，400，1001）的轴向，医用胶喷口（J2）与生物墨汁喷口（J1）错位布置。生物打印机（1000）包括该生物打印机喷头（100，200，300，400，1001）。管腔组织构建体打印方法采用该生物打印机（1000）进行打印。该生物打印机喷头、生物打印机和管腔组织构建体打印方法，适于制备长度大于等于30cm的管腔组织构建体。

Description

生物打印机喷头、生物打印机和管腔组织构建体打印方法
相关申请
本公开是以申请号为201911389611.9，申请日为2019年12月30日，发明名称为“生物打印机喷头、生物打印机和管腔组织构建体打印方法”的中国专利申请为基础，并主张其优先权，该中国专利申请的公开内容在此作为整体引入本公开中。
技术领域
本公开涉及生物打印技术领域，特别涉及一种生物打印机喷头、生物打印机和管腔组织构建体打印方法。
背景技术
管腔组织构建体是人体自身管腔组织的替代品，例如，人工血管是在人体自身血管发生严重狭窄或闭塞时作为人体自身血管的替代品。
现有技术中的人工血管大部分是采用尼龙、涤纶(Dacron)、聚四氟乙稀(PTFE)等合成材料制成，由于人工血管内壁不具有天然血管的内皮细胞，在长期使用后容易再次发生堵塞。
申请号为CN201910025832.1，发明名称为“管腔组织构建体打印装置及其打印方法和3D生物打印机”的中国专利申请提出一种打印技术，可以将生物墨汁(包含生物砖，生物砖定义可以参考专利文献201610211570.4)打印于人工管腔(例如人工血管)的人工管腔内壁进行贴附，形成管腔组织构建体，使制备得到的管腔组织构建体具备真实血管的生物学性能。但是目前该打印技术制备超过10cm长度的管腔组织构建体有一定难度。为了适应临床的适应症(例如动静脉内瘘)，就需要制备更长(例如长度大于等于30cm)的管腔组织构建体。
公开号为CN109514858A，发明名称为“一种多通道3D打印喷头及采用该喷头制造管道的方法”的中国专利申请中公开了一种3D打印喷头，包括多个挤出管道，多个挤出管道同轴且从内到外分层间隔设置，不同的挤出管道输入不同的打印材料，内侧的挤出管道的出口端伸出外侧的挤出管道的出口端。
公开号为CN107411844A、发明名称为“管腔组织构建体及其制备方法、制备装置”的中国专利申请公开了一种在管腔组织构建体的外壁涂覆粘合剂的生物打印机 1000，该生物打印机1000具备盛放粘合剂的容器、输送通道和粘合剂出口。具体涂覆时，粘合剂出口不动，通过使外壁相对孔口运动，粘合剂在压力作用下不断被挤出孔口以实现在外壁的内表面涂抹粘合剂。该专利申请中，采用将打印好的生物组织内壁与上述涂覆了粘合剂的外壁套装以得到生物构建体。
公开号为CN105647804A、发明名称为“生物打印机喷头及生物打印机”的中国专利申请公开了一种生物打印机的同轴的双层流道喷头，其中第一流道供主材流体(生物墨汁)通过，第二流道(即外层流道)供辅材流体通过，内、外层流道朝向喷嘴出口方向减缩，从而方便辅材将流出的主材包裹以形成满足打印要求的颗粒状生物打印材料。即该文献中的喷头是形成打印所需的微液滴，无法实现生物墨汁与医用胶的同步涂覆。
发明内容
本公开的目的在于提供一种生物打印机喷头、生物打印机和管腔组织构建体打印方法。
本公开第一方面提供一种生物打印机喷头，所述生物打印机喷头具有：
生物墨汁流道，设置于所述生物打印机喷头内部；
生物墨汁喷口，与所述生物墨汁流道连通，位于所述生物打印机喷头的喷射端的侧面；
医用胶流道，设置于所述生物打印机喷头内部，与所述生物墨汁流道隔离；
医用胶喷口，与所述医用胶流道连通，位于所述喷射端的侧面，并且，沿所述生物打印机喷头的轴向，所述医用胶喷口与所述生物墨汁喷口错位布置。
在本公开一些实施例中，沿所述生物打印机喷头的轴向所述生物墨汁喷口相对于所述医用胶喷口更靠近所述喷射端的顶面。
在本公开一些实施例中，
所述生物打印机喷头包括沿所述生物打印机喷头的周向均匀分布的多个所述生物墨汁喷口；和/或
所述生物打印机喷头包括沿所述生物打印机喷头的周向均匀分布的多个所述医用胶喷口或所述医用胶喷口包括绕所述生物打印机喷头的轴向布置的环形喷口。
在本公开一些实施例中，包括设置于所述生物打印机喷头侧面的医用胶刮涂部，沿所述生物打印机喷头的轴向，所述医用胶刮涂部位于所述生物墨汁喷口和所述医用 胶喷口之间。
在本公开一些实施例中，所述医用胶刮涂部包括设置于所述生物打印机喷头侧面的环形凸起或刷头。
在本公开一些实施例中，所述生物打印机喷头包括：
墨汁喷头主体，所述生物墨汁喷口设置于所述墨汁喷头主体上；
医用胶喷头主体，设置于所述墨汁喷头主体的外周，所述医用胶喷口设置于所述医用胶喷头主体上，或所述医用胶喷口设置于所述墨汁喷头主体与所述医用胶喷头主体之间。
在本公开一些实施例中，
所述生物墨汁流道设置于所述墨汁喷头主体内；
所述医用胶流道设置于所述医用胶喷头主体与所述墨汁喷头主体之间。
在本公开一些实施例中，所述生物打印机喷头包括连接片，所述连接片连接于所述墨汁喷头主体和所述医用胶喷头主体之间。
在本公开一些实施例中，
所述生物墨汁流道设置于所述墨汁喷头主体内；
所述医用胶流道设置于所述墨汁喷头主体内，所述墨汁喷头主体的侧壁具有与所述医用胶流道连通的连通口；
所述医用胶喷口包括由所述墨汁喷头主体和所述医用胶喷头主体的靠近所述喷射端的一端形成的绕所述生物打印机喷头的轴向布置的环形喷口，所述连通口与所述环形喷口连通。
在本公开一些实施例中，所述生物打印机喷头还包括喷头安装座，其中，
所述生物墨汁流道包括设置于所述墨汁喷头主体内的第一生物墨汁流道和设置于所述喷头安装座内的第二生物墨汁流道，或者所述生物墨汁流道设置于所述喷头安装座内；
所述医用胶流道包括设置于所述医用胶喷头主体内的第一医用胶流道和设置于所述喷头安装座内的第二医用胶流道。
在本公开一些实施例中，所述医用胶流道还包括第一环形缓冲槽，所述第一医用胶流道和所述第二医用胶流道通过所述第一环形缓冲槽连通。
在本公开一些实施例中，所述第一环形缓冲槽形成于所述医用胶喷头主体与所述喷头安装座之间。
在本公开一些实施例中，所述医用胶流道包括设置于所述医用胶喷口与所述第一医用胶流道之间的第二环形缓冲槽。
本公开第二方面提供一种生物打印机，包括：
生物打印机喷头，所述生物打印机喷头包括本公开第一方面所述的生物打印机喷头；
供料组件，与所述生物打印机喷头连接，被配置为向所述生物打印机喷头的所述生物墨汁流道供应生物墨汁和向所述医用胶流道供应医用胶；
人工管腔安装组件，包括用于容置管腔组织构建体的人工管腔的人工管腔安装腔，所述人工管腔安装组件被配置为能够相对于所述生物打印机喷头沿所述人工管腔安装腔的轴向往复运动。
在本公开一些实施例中，所述供料组件包括：
医用胶注射器，被配置为向所述医用胶流道供应医用胶；
生物墨汁注射器，被配置为向所述生物墨汁流道供应生物墨汁；
注射器固定组件，被配置为固定所述医用胶注射器和所述生物墨汁注射器；和
推送机构，被配置为与所述医用胶注射器的柱塞和所述生物墨汁注射器的柱塞驱动连接以推动两个柱塞运动。
在本公开一些实施例中，所述推送机构包括：
注射器柱塞固定片，设有用于放置柱塞的端部圆盘的缺口；
柱塞固定弹簧组件，包括组件壳体、导向柱和弹簧，所述组件壳体内具有弹簧安装腔，所述导向柱可移动地穿设于所述组件壳体上且中部位于所述弹簧安装腔内，所述导向柱的第一端与所述注射器柱塞固定片连接，所述导向柱的中部具有朝向径向外侧的突出部，所述弹簧套设于所述导向柱外周并位于所述弹簧安装腔的靠近所述导向柱的第一端的内壁与所述突出部之间；
弹簧推送片，位于所述柱塞固定弹簧组件的远离所述柱塞的一端；和
推拉机构，与所述组件壳体驱动连接，被配置为带动所述组件壳体移动以使所述导向柱的第二端与所述弹簧推送片在抵接状态和分离状态之间切换，其中，在所述抵接状态，所述注射器柱塞固定片与所述柱塞固定弹簧组件之间形成安装所述端部圆盘的空间，在所述分离状态，所述柱塞固定弹簧组件压紧并固定所述端部圆盘于所述注射器柱塞固定片上，且所述推拉机构被配置为通过所述柱塞固定弹簧组件带动所述柱塞运动。
在本公开一些实施例中，生物打印机包括驱动组件，所述驱动组件与所述人工管腔安装组件驱动连接，被配置为驱动所述人工管腔安装组件沿所述人工管腔安装腔的轴向往复运动。
在本公开一些实施例中，生物打印机包括检测模块，所述检测模块被配置为检测所述生物打印机喷头与所述人工管腔安装腔的相对位置。
在本公开一些实施例中，生物打印机包括温控模块，所述温控模块被配置为控制所述人工管腔安装腔的温度。
在本公开一些实施例中，生物打印机还包括：
扶正杆，沿所述人工管腔安装腔的轴向延伸并可移动地设置；
扶正板，设置于所述扶正杆的顶端，所述扶正板包括与所述生物打印机喷头的外壁间隙配合的喷头安装口，所述扶正板的喷头安装口被配置保持安装于所述喷头安装口内的所述生物打印机喷头与所述人工管腔安装腔同轴。
本公开第三方面提供一种管腔组织构建体打印方法，采用本公开第二方面所述的生物打印机打印管腔组织构建体，包括：
加注打印材料，包括向所述供料组件加注打印材料；
安装管腔组织构建体的人工管腔，包括将所述人工管腔安装在所述人工管腔安装组件的人工管腔安装腔内；
生物打印机喷头初始定位，包括使所述生物打印机喷头伸入所述人工管腔内并处于初始位置；
打印材料涂覆，包括使所述人工管腔安装组件相对于所述生物打印机喷头沿所述人工管腔安装腔的轴向运动，并且在运动的同时向所述生物打印机喷头的所述生物墨汁流道供应生物墨汁以及向所述医用胶流道供应医用胶。
在本公开一些实施例中，还包括在安装管腔组织构建体的人工管腔后调节所述人工管腔安装腔的温度。
基于本公开提供的生物打印机喷头，沿生物打印机喷头的轴向错开设置的生物墨汁喷口和医用胶喷口，打印管腔组织构建体时，可以将生物打印机喷头伸入管腔组织构建体的人工管腔内，并驱动携带管腔组织构建体的人工管腔的人工管腔安装组件相对于生物打印机喷头沿轴向移动，使医用胶先行喷出，随着生物打印机喷头与管腔组织构建体的人工管腔相对移动，医用胶涂覆在管腔组织构建体的人工管腔的内壁上形成医用胶层。生物墨汁在与医用胶喷出时间相隔较短的时间内喷出。由于医用胶的粘 附作用，生物墨汁喷出后能立刻被粘附到医用胶层上，能够实现在细长管腔组织构建体的人工管腔的内壁上同时涂覆医用胶和生物墨汁，从而利于保证在管腔组织构建体的人工管腔内壁上同时形成医用胶层和生物墨汁层，形成所需的管腔组织构建体。
本公开提供的生物打印机和管腔组织构建体打印方法有与本公开的生物打印机喷头相应的优点。
通过以下参照附图对本公开的示例性实施例的详细描述，本公开的其它特征及其优点将会变得清楚。
附图说明
此处所说明的附图用来提供对本公开的进一步理解，构成本公开的一部分，本公开的示意性实施例及其说明用于解释本公开，并不构成对本公开的不当限定。在附图中：
图1为本公开一实施例的生物打印机喷头的立体结构示意图。
图2为图1所示实施例的生物打印机喷头的一个角度的剖视结构示意图。
图3为图1所示实施例的生物打印机喷头的另一个角度的剖视结构示意图。
图4为图3的A-A剖面结构示意图。
图5为本公开一实施例的生物打印机喷头的立体结构示意图。
图6为图5所示实施例的生物打印机喷头的剖视结构示意图。
图7为本公开一实施例的生物打印机喷头的立体结构示意图。
图8为图7所示实施例的生物打印机喷头的剖视结构示意图。
图9为图7所示实施例的生物打印机喷头的墨汁喷头主体的立体结构示意图。
图10为图9的墨汁喷头主体的剖视结构示意图。
图11为图7所示实施例的生物打印机喷头的医用胶喷头主体的立体结构示意图。
图12为图11的医用胶喷头主体的剖视结构示意图。
图13为图7所示实施例的生物打印机喷头的喷头安装座的立体结构示意图。
图14为图13的喷头安装座的剖视结构示意图。
图15为图13的喷头安装座的俯视结构示意图。
图16为本公开一实施例的生物打印机喷头的立体结构示意图。
图17为图16所示实施例的生物打印机喷头的剖视结构示意图。
图18为图16所示实施例的生物打印机喷头的墨汁喷头主体的立体结构示意图。
图19为图18的墨汁喷头主体的剖视结构示意图。
图20为图16所示实施例的生物打印机喷头的医用胶喷头主体的立体结构示意图。
图21为图20的医用胶喷头主体的剖视结构示意图。
图22为图16所示实施例的生物打印机喷头的喷头安装座的立体结构示意图。
图23为图22的喷头安装座的剖视结构示意图。
图24为本公开一实施例的生物打印机的立体结构示意图。
图25为图24所示实施例的生物打印机的局部结构示意图。
图26为图24所示实施例的生物打印机的局部结构示意图。
图27为图24所示实施例的生物打印机的柱塞固定弹簧组件等结构的剖视图。
具体实施方式
下面将结合本公开实施例中的附图，对本公开实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本公开一部分实施例，而不是全部的实施例。以下对至少一个示例性实施例的描述实际上仅仅是说明性的，决不作为对本公开及其应用或使用的任何限制。基于本公开中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本公开保护的范围。
除非另外具体说明，否则在这些实施例中阐述的部件和步骤的相对布置、数字表达式和数值不限制本公开的范围。同时，应当明白，为了便于描述，附图中所示出的各个部分的尺寸并不是按照实际的比例关系绘制的。对于相关领域普通技术人员已知的技术、方法和设备可能不作详细讨论，但在适当情况下，所述技术、方法和设备应当被视为授权说明书的一部分。在这里示出和讨论的所有示例中，任何具体值应被解释为仅仅是示例性的，而不是作为限制。因此，示例性实施例的其它示例可以具有不同的值。应注意到：相似的标号和字母在下面的附图中表示类似项，因此，一旦某一项在一个附图中被定义，则在随后的附图中不需要对其进行进一步讨论。
在本公开的描述中，需要理解的是，使用“第一”、“第二”等词语来限定零部件，仅仅是为了便于对相应零部件进行区别，如没有另行声明，上述词语并没有特殊含义，因此不能理解为对本公开保护范围的限制。
如图1至图23所示，本公开一些实施例提供一种生物打印机喷头。该生物打印机喷头具有生物墨汁流道P1、生物墨汁喷口J1、医用胶流道P2和医用胶喷口J2。生 物墨汁流道P1设置于生物打印机喷头内部。生物墨汁喷口J1与生物墨汁流道P1连通，位于生物打印机喷头的喷射端的侧面。医用胶流道P2设置于生物打印机喷头内部，与生物墨汁流道P1隔离。医用胶喷口J2与医用胶流道P2连通，位于生物打印机喷头的喷射端的侧面。并且沿生物打印机喷头的轴向医用胶喷口J2与生物墨汁喷口J1错位布置。
本公开实施例的生物打印机喷头，沿生物打印机喷头的轴向错开设置生物墨汁喷口J1和医用胶喷口J2，打印管腔组织构建体时，可以将生物打印机喷头伸入管腔组织构建体的人工管腔内，并驱动携带管腔组织构建体的人工管腔的人工管腔安装组件相对于生物打印机喷头沿轴向移动，使医用胶先行喷出，随着生物打印机喷头与管腔组织构建体的人工管腔相对移动，医用胶涂覆在管腔组织构建体的人工管腔的内壁上形成医用胶层。生物墨汁在与医用胶喷出时间相隔较短的时间内喷出。由于医用胶的粘附作用，生物墨汁喷出后能立刻被粘附到医用胶层上，从而利于保证在管腔组织构建体的人工管腔内壁上同时形成医用胶层和生物墨汁层，形成所需的管腔组织构建体。本公开实施例的生物打印机喷头能够实现在细长管腔组织构建体的人工管腔的内壁上同时涂覆医用胶和生物墨汁。
在一些实施例的生物打印机喷头中，沿生物打印机喷头的轴向生物墨汁喷口J1相对于医用胶喷口J2更靠近喷射端的顶面。使用该结构的生物打印机喷头打印管腔组织构建体时，可以使生物打印机喷头从管腔组织构建体的人工管腔的第一端伸入，到达第二端，从第二端开始在人工管腔的内壁打印医用胶层和生物墨汁层，打印过程中，生物打印机喷头逐渐从人工管腔的第二端移动至第一端，从而利于在打印管腔组织构建体时生物打印机喷头在管腔组织构建体的人工管腔中边打印边退出，打印完毕即可完全退出。
在一些实施例的生物打印机喷头中，多个生物墨汁喷口J1沿生物打印机喷头的周向均匀分布；和/或医用胶喷口J2为环形喷口或多个医用胶喷口J2沿生物打印机喷头的周向均匀分布。以上生物墨汁喷口J1和医用胶喷口J2的设置利于打印材料生物墨汁和医用胶均匀涂覆。
在一些实施例的生物打印机喷头中，包括设置于生物打印机喷头侧面的医用胶刮涂部M，沿生物打印机喷头的轴向，医用胶刮涂部M位于生物墨汁喷口J1和医用胶喷口J2之间。医用胶刮涂部包括设置于生物打印机喷头侧面的环形凸起或刷头。医用胶刮涂部M利于医用胶涂覆均匀，从而利于生物墨汁均匀牢固地粘贴于人工管腔内 壁上。
以下结合图1至图23对本公开一些实施例的生物打印机喷头进行详细说明。
图1至图4示出了本公开一实施例的生物打印机喷头100。如图1至图4所示，该生物打印机喷头100具有喷射打印材料的喷射端以及具有生物墨汁流道P1、生物墨汁喷口J1、医用胶流道P2和医用胶喷口J2。生物墨汁流道P1设置于生物打印机喷头100内部。生物墨汁喷口J1与生物墨汁流道P1连通，位于喷射端的侧面。医用胶流道P2设置于生物打印机喷头100内部，与生物墨汁流道P1隔离。医用胶喷口J2与医用胶流道P2连通，位于喷射端的侧面，沿生物打印机喷头100的轴向医用胶喷口J2与生物墨汁喷口J1错位布置。
沿生物打印机喷头100的轴向生物墨汁喷口J1相对于医用胶喷口J2更靠近喷射端的顶面。多个生物墨汁喷口J1沿生物打印机喷头100的周向均匀分布。医用胶喷口J2为环形喷口。
如图1和图2所示，生物打印机喷头100还包括设置于生物打印机喷头100侧面的医用胶刮涂部M，沿生物打印机喷头100的轴向，医用胶刮涂部M位于生物墨汁喷口J1和医用胶喷口J2之间。医用胶刮涂部M包括设置于生物打印机喷头侧面的环形凸起。为便于涂覆该环形凸起靠近医用胶喷口J2的一侧从生物打印机喷头100的径向内侧至径向外侧朝向生物墨汁喷口J1一侧倾斜。
如图1至图4所示，生物打印机喷头100包括墨汁喷头主体110和医用胶喷头主体120。生物墨汁喷口J1设置于墨汁喷头主体110上。医用胶喷头主体120设置于墨汁喷头主体110的外周。医用胶喷口J2设置于墨汁喷头主体110与医用胶喷头主体120之间。如图2所示，本实施例中，医用胶喷口J2设置于墨汁喷头主体110的周向外壁与医用胶喷头主体120的靠近喷射端的一端的内壁之间。
生物墨汁流道P1设置于墨汁喷头主体110内。多个生物墨汁喷口J1与生物墨汁流道P1连通。
医用胶流道P2设置于医用胶喷头主体120与墨汁喷头主体110之间。医用胶流道P2整体上为设置于生物墨汁流道P1外周的环形流道，医用胶沿该环形流道的轴向流动。医用胶流道P2的出口(医用胶排出口)即为医用胶喷口J2。
如图3和图4所示，生物打印机喷头100还包括连接片130，连接片130连接于墨汁喷头主体110和医用胶喷头主体120之间。
以下结合图1至图4对本公开实施例的生物打印机喷头100作更详细地说明。
如图1至图4所示，生物打印机喷头100包括同轴设置的墨汁喷头主体110和医用胶喷头主体120。墨汁喷头主体110插入医用胶喷头主体120内。墨汁喷头主体110与医用胶喷头主体120之间通过连接片130固定。连接片130用于固定内层的墨汁喷头主体110和外层的医用胶喷头主体120，从而保持墨汁喷头主体110和医用胶喷头主体120的同轴度。
本实施例中，墨汁喷头主体110上端即生物打印机喷头100的喷射端，墨汁喷头主体110上端设置有若干个生物墨汁喷口J1，若干个生物墨汁喷口J1沿生物打印机喷头100的周向均匀的设置在墨汁喷头主体110上端的侧壁上，从而使生物墨汁能够从各个生物墨汁喷口J1分别喷出。由于生物墨汁喷口J1是均匀的分布在墨汁喷头主体110上端的侧壁，所以可以使生物墨汁变成几股流体均匀的喷出。
墨汁喷头主体110内部设置有生物墨汁流道P1，生物墨汁流道P1一端(图中上端)为生物墨汁出料口，另一端(图中下端)为生物墨汁进料口。生物墨汁出料口与生物墨汁喷口J1连通。医用胶喷头主体120的内壁与墨汁喷头主体110外壁之间的环形空间形成医用胶流道P2，医用胶流道P2的一端(图中上端)为医用胶出料口，即为医用胶喷口J2，另一端(图中下端)为医用胶进料口。
为了使喷涂在管腔组织构建体的人工管腔的内壁上的医用胶更加平整，在墨汁喷头主体110的靠近医用胶喷口J2的位置设置医用胶刮涂部M。在图1和图2中，医用胶刮涂部M为倒锥形形状。
本公开实施例的生物打印机喷头100利于解决如何在细长管腔组织构建体内壁上同时涂覆医用胶和生物墨汁的技术问题。在开始涂覆时，首先将生物打印机喷头100伸入管腔组织构建体的人工管腔的内部，将医用胶喷口J2的位置与管腔组织构建体的人工管腔的上边缘对齐，参考图24至图26所示的生物打印机1000，此时生物打印机1000的供料组件1005开始提供医用胶和生物墨汁，并且生物打印机1000的驱动组件1009驱动管腔组织构建体的人工管腔相对于生物打印机喷头100向上移动，在移动过程中由于生物墨汁喷口J1和医用胶喷口J2位置错开，医用胶喷出后能够先行涂覆到人工管腔的内壁上，随着生物打印机喷头100与人工管腔的相对移动，生物墨汁喷出继续在医用胶层上涂覆，同时由于医用胶的粘附作用，就能立刻将生物墨汁粘附到医用胶层上，当生物打印机喷头100完全从人工管腔内退出时，就可以在人工管腔内壁上同时形成医用胶层和生物墨汁层，从而形成所需的管腔组织构建体。
图5和图6示出了本公开一实施例的生物打印机喷头200。如图5和图6所示， 该生物打印机喷头200具有喷射打印材料的喷射端以及具有生物墨汁流道P1、生物墨汁喷口J1、医用胶流道P2和医用胶喷口J2。生物墨汁流道P1设置于生物打印机喷头200内部。生物墨汁喷口J1与生物墨汁流道P1连通，位于喷射端的侧面。医用胶流道P2设置于生物打印机喷头200内部，与生物墨汁流道P1隔离。医用胶喷口J2与医用胶流道P2连通，位于喷射端的侧面，沿生物打印机喷头200的轴向医用胶喷口J2与生物墨汁喷口J1错位布置。
沿生物打印机喷头200的轴向生物墨汁喷口J1相对于医用胶喷口J2更靠近喷射端的顶面。多个生物墨汁喷口J1沿生物打印机喷头200的周向均匀分布。医用胶喷口J2为环形喷口。
如图5和图6所示，生物打印机喷头200包括墨汁喷头主体210和医用胶喷头主体220。生物墨汁喷口J1设置于墨汁喷头主体210上。医用胶喷头主体220设置于墨汁喷头主体210的外周。
生物墨汁流道P1设置于墨汁喷头主体210内。多个生物墨汁喷口J1与生物墨汁流道P1连通。
医用胶流道P2设置于墨汁喷头主体210内，墨汁喷头主体210的侧壁具有与医用胶流道P2连通的连通口N。
医用胶喷口J2设置于墨汁喷头主体210与医用胶喷头主体220之间。医用胶喷口J2包括由墨汁喷头主体210和医用胶喷头主体220的靠近喷射端的一端形成的绕生物打印机喷头的轴向布置的环形喷口，连通口N与环形喷口连通。如图6所示，本实施例中，医用胶喷口J2设置于墨汁喷头主体210的周向外壁与医用胶喷头主体220的靠近喷射端的一端的内壁之间。
以下结合图5和图6对本公开实施例的生物打印机喷头200作更详细地说明。
如图5和图6所示，生物打印机喷头200包括墨汁喷头主体210和医用胶喷头主体220。墨汁喷头主体210内部平行设置有生物墨汁流道P1和医用胶流道P2，生物墨汁流道P1的一端(图中上端)为生物墨汁出料口，另一端(图中下端)为生物墨汁进料口，医用胶流道P2的一端(图中上端)为医用胶出料口，另一端(图中下端)为医用胶进料口。墨汁喷头主体210的上端设置有若干个生物墨汁喷口J1，若干个生物墨汁喷口J1沿生物打印机喷头200的周向均匀的设置在墨汁喷头主体210上端的侧壁上，并且生物墨汁喷口J1与生物墨汁出料口连通。墨汁喷头主体210的中部设置有凸台，凸台上套装有套筒状的医用胶喷头主体220。医用胶喷头主体220与墨汁 喷头主体210外壁之间的环形喷口即医用胶喷口J2。医用胶喷口J2与医用胶流道P2的医用胶出料口连通。
生物打印机喷头200的工作原理与生物打印机喷头100的工作原相同，在此不作重复描述。
生物打印机喷头200中可以将生物墨汁流道P1和医用胶流道P2的管径设置得比生物打印机喷头100的对应流道的管径更小，从而在打印过程中可以节约生物墨汁和医用胶的用量。
图7至图15示出了本公开一实施例的生物打印机喷头300。如图7至图15所示，该生物打印机喷头300具有喷射打印材料的喷射端(图中上端)以及具有生物墨汁流道P1、生物墨汁喷口J1、医用胶流道P2和医用胶喷口J2。
生物墨汁流道P1设置于生物打印机喷头300内部。生物墨汁喷口J1与生物墨汁流道P1连通，位于喷射端的侧面。医用胶流道P2设置于生物打印机喷头300内部，与生物墨汁流道P1隔离。医用胶喷口J2与医用胶流道P2连通，位于喷射端的侧面，沿生物打印机喷头300的轴向医用胶喷口J2与生物墨汁喷口J1错位布置。
沿生物打印机喷头300的轴向生物墨汁喷口J1相对于医用胶喷口J2更靠近喷射端的顶面。多个生物墨汁喷口J1沿生物打印机喷头300的周向均匀分布。医用胶喷口J2为环形喷口。
如图7至图15所示，生物打印机喷头300包括墨汁喷头主体310、医用胶喷头主体320和喷头安装座330。墨汁喷头主体310和医用胶喷头主体320设置于喷头安装座330上。
生物墨汁喷口J1设置于墨汁喷头主体310上。医用胶喷头主体320为套筒状结构，设置于墨汁喷头主体310的外周。
医用胶喷口J2包括由墨汁喷头主体310和医用胶喷头主体320的靠近喷射端的一端形成的环形喷口，连通口与环形喷口连通。如图8所示，医用胶喷口J2设置于墨汁喷头主体310的中部凸出部的底壁与医用胶喷头主体320的靠近生物打印机喷头300的喷射端的端壁之间。
生物墨汁流道P1包括设置于墨汁喷头主体310内的第一生物墨汁流道P11和设置于喷头安装座300内的第二生物墨汁流道P12。
医用胶流道P2包括设置于医用胶喷头主体320内的第一医用胶流道P21和设置于喷头安装座内的第二医用胶流道P22。如图8所示，医用胶流道P2还包括第一环形 缓冲槽G，第一医用胶流道P21和第二医用胶流道P22通过第一环形缓冲槽G连通。如图8所示，第一环形缓冲槽G形成于医用胶喷头主体320与喷头安装座330之间。
以下结合图7至图15对本公开实施例的生物打印机喷头300作进一步说明。
如图7至图15所示，生物打印机喷头300包括墨汁喷头主体310、医用胶喷头主体320和喷头安装座330。喷头安装座330上依次套装有医用胶喷头主体320和墨汁喷头主体310，并且墨汁喷头主体310穿过医用胶喷头主体320并插入喷头安装座330。
喷头安装座330内设置有第二生物墨汁流道P12，第二生物墨汁流道P12一端为第二生物墨汁流道P12进料口，另一端为第二生物墨汁流道P12出料口。第二生物墨汁流道P12两侧对称设置有第二医用胶流道P22。在未图示的实施例中，为了节约医用胶的用量，可以将第二医用胶流道P22的数量设置为一根。第二医用胶流道P22一端为第二医用胶流道P22出料口，另一端为第二医用胶流道P22进料口。
墨汁喷头主体310包括设置于下部的安装柱311，医用胶喷头主体320中部设置有安装腔C2，安装腔C2用于使墨汁喷头主体310的安装柱311从其内穿过。安装腔C2外侧均匀设置有多个第一医用胶流道P21。第一医用胶流道P21的一端为第一医用胶出料口O2，另一端为第一医用胶进料口。医用胶喷头主体320上端表面设置有若干个第一医用胶出料口O2，若干个第一医用胶出料口O2沿圆周方向均匀设置。并且第一医用胶出料口O2(作为连通口)与医用胶喷口J2(环形喷口)连通，第一医用胶进料口与第二医用胶出料口连通。
如图8所示，第二生物墨汁流道P12两侧对称设置有第二医用胶流道P22，第二医用胶流道P22上方设置有第一环形缓冲槽G。第二医用胶流道P22一端为第二医用胶出料口，另一端为第二医用胶进料口。第二医用胶出料口与第一环形缓冲槽G连通。医用胶喷头主体320中部设置有安装腔C2，安装腔C2外围均匀设置有若干根第一医用胶流道P21，第一医用胶流道P21一端为与医用胶喷口连通的第一医用胶出料口O2，另一端为第一医用胶进料口，第一医用胶进料口与第一环形缓冲槽G连通。
墨汁喷头主体310上端设置有若干个生物墨汁喷口J1，若干个生物墨汁喷口J1均匀的设置在墨汁喷头主体310上端的侧壁上。墨汁喷头主体310下端设置有安装柱311，墨汁喷头主体310内设置有第一生物墨汁流道P11，第一生物墨汁流道P11的一端为第一生物墨汁出料口，另一端为第一生物墨汁进料口，第一生物墨汁出料口与生物墨汁喷口J1连通，第一生物墨汁进料口与第二生物墨汁出料口连通。
该生物打印机喷头300的工作原理与生物打印机喷头100的工作原相同，在此不 再重复描述。
生物打印机喷头300中，通过将生物墨汁流道和医用胶流道的管径变得比生物打印机喷头100的管径更小，从而使打印过程中节约了生物墨汁和医用胶的用量。
生物打印机喷头300中，喷头安装座330上端与安装柱311下端可以为螺纹连接的结构，便于喷头安装座330、墨汁喷头主体310、医用胶喷头主体320组装和拆卸。
图16至图23示出了本公开一实施例的生物打印机喷头400。如图16至图23所示，该生物打印机喷头400具有喷射打印材料的喷射端(图中上端)以及具有生物墨汁流道P1、生物墨汁喷口J1、医用胶流道P2和医用胶喷口J2。
生物墨汁流道P1设置于生物打印机喷头400内部。生物墨汁喷口J1与生物墨汁流道P1连通，位于喷射端的侧面。医用胶流道P2设置于生物打印机喷头400内部，与生物墨汁流道P1隔离。医用胶喷口J2与医用胶流道P2连通，位于喷射端的侧面，沿生物打印机喷头400的轴向医用胶喷口J2与生物墨汁喷口J1错位布置。
沿生物打印机喷头400的轴向生物墨汁喷口J1相对于医用胶喷口J2更靠近喷射端的顶面。多个生物墨汁喷口J1沿生物打印机喷头400的周向均匀分布，医用胶喷口J2为环形喷口。
如图16至图23所示，生物打印机喷头包括墨汁喷头主体410、医用胶喷头主体420和喷头安装座430。墨汁喷头主体410和医用胶喷头主体420设置于喷头安装座430上。
生物墨汁喷口J1设置于墨汁喷头主体410上。医用胶喷头主体420为套筒状结构，设置于墨汁喷头主体410的外周。
医用胶喷口J2包括由墨汁喷头主体410和医用胶喷头主体420的靠近喷射端的一端形成的环形喷口。如图17所示，医用胶喷口J2设置于墨汁喷头主体410的中部凸出部的底壁与医用胶喷头主体420的靠近生物打印机喷头400的喷射端的端壁之间。
生物墨汁流道P1设置于喷头安装座430内。
医用胶流道P2包括设置于医用胶喷头主体420内的第一医用胶流道P21和设置于喷头安装座430内的第二医用胶流道P22。如图17所示，医用胶流道P2还包括第一环形缓冲槽G，第一医用胶流道P21和第二医用胶流道P22通过第一环形缓冲槽G连通。如图17所示，第一环形缓冲槽G形成于医用胶喷头主体420与喷头安装座430之间。
如图17所示，医用胶流道P2包括设置于医用胶喷口J2与第一医用胶流道P21之间的第二环形缓冲槽L。
以下结合图16至图23对本公开实施例的生物打印机喷头400作进一步说明。
如图16至图23所示，生物打印机喷头400包括墨汁喷头主体410、医用胶喷头主体420和喷头安装座430。喷头安装座430上依次套装有医用胶喷头主体420和墨汁喷头主体410。
喷头安装座430内设置有生物墨汁流道P1，生物墨汁流道P1的一端(图中上端)为生物墨汁出料口O1，另一端(图中下端)为生物墨汁进料口。
喷头安装座430内生物墨汁流道P1两侧分别对称设置有第二医用胶流道P22。第二医用胶流道P22一端为第二医用胶出料口O22，另一端为第二医用胶进料口。在一些未图示的实施例中，为了节约医用胶的用量可以将第二医用胶流道P22的数量设置为一根。
喷头安装座430从上至下分别设置有用于安装墨汁喷头主体410的第一安装柱431、用于安装医用胶喷头主体420的第二安装柱432和安装座主体433。第一安装柱431上方的外壁上设置有第一外螺纹，第二安装柱432的外壁上设置有第二外螺纹。第二医用胶出料口O22位于第二安装柱432的上端面上。生物墨汁出料口O1位于第一安装柱431的上端面。
医用胶喷头主体420内部依次设置有用于使第一安装柱431穿过的第一安装腔C21和用于使第二安装柱432穿过的第二安装腔C22。第二安装腔C22的内壁上设置有第二内螺纹T2，通过第二内螺纹T2与第二外螺纹螺纹配合实现医用胶喷头主体420与喷头安装座430之间的可拆卸连接。
医用胶喷头主体420的上端面开设有第二环形缓冲槽L，第二环形缓冲槽L的底面设置有若干个第一医用胶出料口O21，若干个第一医用胶出料口O21均匀分布在第二环形缓冲槽L的底面。第二环形缓冲槽L下方与若干个医用胶出料口O21对应地设置有若干第一医用胶流道P21。第一医用胶流道P21一端(图中上端)为第一医用胶出料口O21，另一端(图中下端)为第一医用胶进料口。第一医用胶出料口O21与医用胶喷口J2连通。第一医用胶进料口与第二医用胶出料口O22连通.
墨汁喷头主体410内设置有用于与第一安装柱431配合安装的安装腔C1。安装腔C1内壁上设置有第一内螺纹T1。通过第一内螺纹T1和第一外螺纹螺纹配合实现墨汁喷头主体410与喷头安装座430之间的可拆卸连接。
通过将医用胶喷头主体420和墨汁喷头主体410分别与喷头安装座430可拆卸连接，可以方便拆装和清洗医用胶喷头主体420和墨汁喷头主体410。
墨汁喷头主体410上端设置有若干个生物墨汁喷口J1，若干个生物墨汁喷口J1沿周向均匀的设置在墨汁喷头主体410上端的侧壁上，并且生物墨汁喷口J1与生物墨汁出料口O1连通。
为了使从医用胶喷口J2喷出的医用胶在管腔组织构建体的人工管腔内壁上涂覆的更加均匀，在墨汁喷头主体410下端与医用胶喷头主体420上端之间的缝隙处设置海绵刷头。可以通过海绵刷头首先将从医用胶喷口J2喷出的医用胶进行浸润，将海绵刷头浸湿，然后通过海绵刷头和管腔组织构建体的人工管腔内壁接触挤压，从而将医用胶均匀的涂覆在管腔组织构建体的人工管腔内壁上。
生物打印机喷头400的工作原理与生物打印机喷头100的工作原相同，在此不再重复描述。
在生物打印机喷头400中，通过将生物墨汁流道P1和医用胶流道P2的管径变得比生物打印机喷头100的对应流道的管径更小，可以使打印过程中节约生物墨汁和医用胶的用量。通过改变医用胶喷头主体420中医用胶喷口J2的结构，并增加海绵刷头，可以在医用胶喷涂过程中能够更加均匀的涂覆在管腔组织构建体的人工管腔内壁上。
如图24至图26所示，本公开实施例还提供一种生物打印机1000。本公开实施例的生物打印机1000主要包括生物打印机喷头1001、供料组件1005和人工管腔安装组件1030。
生物打印机喷头1001包括前述实施例的生物打印机喷头。例如，生物打印机喷头1001可以为前述的生物打印机喷头100、200、300或400以及它们的变形方式。
供料组件1005与生物打印机喷头1001连接，被配置为向生物打印机喷头1001的生物墨汁流道P1供应生物墨汁和向医用胶流道P2供应医用胶。
人工管腔安装组件1030包括用于容置管腔组织构建体的人工管腔的人工管腔安装腔1014。人工管腔安装组件1030被配置为能够相对于生物打印机喷头1001沿人工管腔安装腔1014的轴向往复运动。人工管腔例如为人工血管，人工胆管，人工尿管等等。
在一些实施例的生物打印机1000中，供料组件1005主要包括医用胶注射器1003、生物墨汁注射器1004、注射器固定组件和推送机构。医用胶注射器1003被配置为向 医用胶流道P2供应医用胶。生物墨汁注射器1004被配置为向生物墨汁流道P1供应生物墨汁。注射器固定组件被配置为固定医用胶注射器1003和生物墨汁注射器1004。推送机构被配置为与医用胶注射器1003的柱塞和生物墨汁注射器1004的柱塞驱动连接以推动两个柱塞运动。
在一些实施例的生物打印机1000中，推送机构主要包括注射器柱塞固定片1024、柱塞固定弹簧组件1029、弹簧推送片1025和推拉机构1026。
注射器柱塞固定片1024设有用于放置柱塞的端部圆盘的缺口。
如图27所示，柱塞固定弹簧组件1029包括组件壳体10291、导向柱10292和弹簧10293。组件壳体10291内具有弹簧安装腔10294。导向柱10292可移动地穿设于组件壳体10291上且中部位于弹簧安装腔10294内。导向柱10292的第一端与注射器柱塞固定片1024连接。导向柱10292的中部具有朝向径向外侧的突出部，弹簧10293套设于导向柱10292外周并位于弹簧安装腔10294的靠近导向柱10292的第一端的内壁与突出部之间。
弹簧推送片1025位于柱塞固定弹簧组件1029的远离柱塞的一端。
推拉机构1026与组件壳体10291驱动连接，被配置为带动组件壳体10291移动以使导向柱10292的第二端与弹簧推送片1025在抵接状态和分离状态之间切换。在抵接状态，注射器柱塞固定片1024与柱塞固定弹簧组件1029之间形成安装端部圆盘的空间。在分离状态，柱塞固定弹簧组件1029压紧并固定端部圆盘于注射器柱塞固定片1024上，且推拉机构1026被配置为通过柱塞固定弹簧组件1029带动柱塞运动。
在一些实施例中，生物打印机1000包括驱动组件1009。驱动组件1009与人工管腔安装组件1030驱动连接，被配置为驱动人工管腔安装组件1030沿人工管腔安装腔1014的轴向往复运动。
在一些实施例中，生物打印机1000包括检测模块1012。检测模块1012被配置为检测生物打印机喷头1001与人工管腔安装腔1014的相对位置。
在一些实施例中，生物打印机包括温控模块1013。温控模块1013被配置为控制人工管腔安装腔1014的温度，同时温控模块1013也可以分别单独设置在注射器压紧板1018和管道夹持块1028上，实现对医用胶注射器1003、生物墨汁注射器1004、生物墨汁连接管道1015、医用胶连接管道1016的温度控制。
在一些实施例中，生物打印机包括扶正杆1021和扶正板1027。扶正杆1021沿人工管腔安装腔1014的轴向延伸并可移动地设置。扶正板1027设置于扶正杆1021的顶 端，扶正板1027包括与生物打印机喷头1001的外壁间隙配合的喷头安装口，扶正板1027的喷头安装口被配置保持安装于喷头安装口内的生物打印机喷头1001与人工管腔安装腔1014同轴。
以下结合图24至图26对本公开实施例的生物打印机1000做更详细地说明。其中，在本公开实施例中描述生物打印机1000时所称的“前”指的是生物打印机1000的注射器的柱塞向外输送生物墨汁和医用胶时的移动方向，“后”是指与移动方向相反的方向。在24至图26中，“前”位于左侧，“后”位于右侧。
如图24至图26所示，生物打印机1000包括安装座1002，以及设置于安装座1002上的生物打印机喷头1001、供料组件1005、人工管腔安装组件1030、驱动组件1009和检测模块1012。
供料组件1005包括医用胶注射器1003、生物墨汁注射器1004、注射器安装板1017、注射器压紧组件、压紧板驱动机构和推送机构。
医用胶注射器1003、生物墨汁注射器1004两个注射器安装在注射器安装板1017上。注射器压紧组件包括注射器压紧板1018、转轴和齿轮齿条组件。注射器压紧板1018与转轴固定连接，转轴与齿轮固定连接。通过转轴和齿轮、齿条配合进行驱动注射器压紧板1018，与转轴连接的齿轮在齿条上移动时带动转轴转动，从而使注射器压紧板1018移动，将两个注射器压紧在注射器安装板1017上。
两个注射器的后方都设有推送机构，推送机构包括设置于前端的柱塞固定机构和设置于后端的推拉机构1026。
柱塞固定机构包括注射器柱塞固定片1024、柱塞固定弹簧组件1029和弹簧推送片1025。
注射器柱塞固定片1024上设有用于放置柱塞端部圆盘的缺口。注射器柱塞固定片1024位于柱塞固定弹簧组件1029前方并与柱塞固定弹簧组件1029连接。弹簧推送片1025位于柱塞固定弹簧组件1029后方。
如图25所示，柱塞固定弹簧组件1029整体为方块结构。注射器柱塞固定片1024包括组件壳体10291和设置于组件壳体10291上的上、下两个导向柱10292及分别设置于组件壳体10291的上、下两个弹簧安装腔10294内的两个弹簧10293。每个弹簧10293位于对应的弹簧安装腔10294内并套设于对应的导向柱10292外周，弹簧10293位于对应导向柱10292的突出部和靠近导向柱10292的第一端的弹簧安装腔10294的内壁之间。导向柱10292两端伸出组件壳体10291。导向柱10292的前端(第一端) 连接注射器柱塞固定片1024。
推拉机构1026与组件壳体10291驱动连接。当推拉机构1026带动柱塞固定弹簧组件1029向后移动时，导向柱10292的后端(第二端)与弹簧推送片1025处于抵接状态，促使导向柱10292向前移动，带动注射器柱塞固定片1024与柱塞固定弹簧组件1029的组件壳体10291之间间距增大，留出空间用于放入柱塞端部圆盘。在柱塞固定弹簧组件1029的导向柱10292的后端(第二端)离开弹簧推送片1025后，即处于分离状态时，通过弹簧10293回弹，导向柱10292相对与组件壳体10291向其后端移动，注射器柱塞固定片1024与柱塞固定弹簧组件1029的组件壳体10291之间间距变小，压紧固定柱塞的端部圆盘，从而完成柱塞固定弹簧组件1029与注射器的柱塞的安装。
然后可通过推拉机构1026，带动柱塞固定弹簧组件1029前后移动，从而带动注射器的柱塞运动，从而将注射器中的生物墨汁或者医用胶挤出，完成供料组件1005对生物打印机喷头1001供料。优选地柱塞固定弹簧组件1029设置在导轨1031上，柱塞固定弹簧组件1029沿导轨1031往复移动。
医用胶注射器1003前端通过医用胶连接管道1016连接到生物打印机喷头1001的医用胶流道，生物墨汁注射器1004前端通过生物墨汁连接管道1015连接到生物打印机喷头1001的生物墨汁流道。在注射器的针筒出口处设有注射器压片1022。在注射器前方还设有用于固定生物打印机喷头1001、生物墨汁连接管道1015和医用胶连接管道1016的管道夹持块1028和管道固定块1020，注射器压片1022被压在管道夹持块1028中，并通过其配套设置的销钉固定，以避免柱塞被拉动的时候，注射器整体被向后拉动。
管道夹持块1028通过相对于管道夹持块1028垂直上下移动的管道夹持块压紧板1019将其压紧在管道固定块1020上。管道固定块1020和注射器安装板1017都固定在其侧面设置的活动底板上。
管道固定块1020侧面设有滑槽，滑槽内设有可沿滑槽滑动的扶正杆1021，扶正杆1021与生物打印机喷头1001平行设置，且在其顶部设有与生物打印机喷头1001外壁间隙配合的扶正板1027。扶正杆1021和扶正板1027确定生物打印机喷头1001的移动方向，使生物打印机喷头1001保持直线度。
人工管腔安装组件1030包括两块带有半圆形槽的夹块。一个夹块的侧面与驱动组件1009连接，作为固定夹块。另一个夹块作为盖板夹块，通过合页与固定夹块连 接。固定夹块和盖板夹块内都设有温控模块1013，温控模块1013可调节人工管腔安装腔1014的温度。两个夹块合并后，两个半圆形槽合并形成一个直径略大于生物打印机喷头1001外径的圆柱形中空腔体作为人工管腔安装腔1014。人工管腔安装腔1014的长度略小于生物打印机喷头1001的医用胶流道的长度。人工管腔安装腔1014在安装好管腔组织构建体的人工管腔后，管腔组织构建体的人工管腔的内径略大于生物打印机喷头1001的外径。
驱动组件1009包括驱动电机1006、丝杆1008、滑块1010、连接板1011和滑轨1007。驱动电机1006的输出轴上连接有丝杆1008，丝杆1008上设置有与其活动配合的滑块1010，滑块1010一段连接有连接板1011，连接板1011下方设置有滑轨1007，并且连接板1011与固定夹块连接。通过驱动电机1006带动丝杆1008转动，丝杆1008转动带动滑块1010在丝杆1008上移动，滑块1010移动时就带动连接板1011在滑轨1007上移动，从而通过连接板1011带动人工管腔安装组件1030移动。
在人工管腔安装组件1030的人工管腔安装腔1014的顶部位置固定有检测模块1012。检测模块1012包括支架和固定在支架上的摄像头，摄像头正对人工管腔安装腔1014上部区域，用于检测生物打印机喷头1001是否达到初始位置。初始位置可以为生物打印机喷头1001的医用胶喷口与管腔组织构建体的人工管腔上边缘对齐的位置。
人工管腔安装组件1030和检测模块1012都与驱动组件1009驱动连接，以在滑轨1007上上下移动。
本实施例的生物打印机中，生物打印机喷头1001和人工管腔安装组件1030能够沿人工管腔安装腔1014的轴向相对运动，在运动的过程中进行医用胶和生物墨汁在管腔组织构建体的人工管腔内壁上的匀速、均匀、同步涂覆。通过设置检测模块1012，能够确保医用胶和生物墨汁都处于临界溢出状态，以便在涂覆作业开始的时候，能立刻让医用胶和生物墨汁离开医用胶喷口和生物墨汁喷口，确保涂覆的整体长度无偏差。
本公开实施例还提供一种采用前述生物打印机打印管腔组织构建体的管腔组织构建体打印方法。管腔组织构建体的人工管腔例如为人工血管。
该管腔组织构建体打印方法包括如下步骤：
加注打印材料，包括向供料组件1005加注打印材料。
在医用胶注射器1003、生物墨汁注射器1004两个注射器内加注相应的打印材料， 并使各自的柱塞处于伸出状态。将生物打印机喷头1001与两个注射器连接，然后将生物打印机喷头1001安装到管道固定块1020上，注射器也同步安装到注射器安装板1017上。再将管道夹持块1028安装到管道固定块1020上。然后将带有管道固定块1020、管道夹持块1028和注射器安装板1017、注射器、生物打印机喷头1001的活动底板整体放到安装座1002上，并通过注射器压紧板1018和管道夹持块压紧板1019固定注射器和管道夹持块1028，此时注射器柱塞固定片1024处于伸出状态。在安装过程中，柱塞端部圆盘能放入注射器柱塞固定片1024与柱塞固定弹簧组件1029之间的空隙。
安装管腔组织构建体的人工管腔，包括将人工管腔安装在人工管腔安装组件1030的人工管腔安装腔1014内。将管腔组织构建体的人工管腔放入人工管腔安装腔并夹紧固定。
调节人工管腔安装腔1014的温度。设置温控模块1013到合适的温度。
生物打印机喷头初始定位，包括使生物打印机喷头1001伸入人工管腔内并处于初始位置。控制驱动组件1009带动人工管腔安装组件1030向下移动。当人工管腔安装组件1030接触到扶正板1027，此时扶正板1027带动扶正杆1021向下移动。扶正板1027可以确保生物打印机喷头1001在与管腔组织构建体的人工管腔接触的时候与管腔组织构建体的人工管腔同轴，从而生物打印机喷头1001能顺利进入管腔组织构建体内并继续保持相对运动，直到生物打印机喷头1001顶部伸出管腔组织构建体。当检测模块1012检测到生物打印机喷头1001到达初始位置(例如，生物打印机喷头1001顶部刚好伸出人工管腔)时，控制推拉机构1026推送医用胶和生物墨汁。当摄像头监测到有医用胶和生物墨汁从生物打印机喷头1001溢出后，暂停推拉机构1026，通过预先向生物打印机喷头1001中通入医用胶和生物墨汁，并通过摄像头进行监测，可以在打印开始之前，对生物打印机喷头1001的各个流道是否通畅进行预先的判断。
打印材料涂覆。控制驱动组件1009反向运动，当生物打印机喷头1001移动到人工管腔的某一设定位置(例如为医用胶喷口与人工管腔上边缘对齐的位置)时，启动推拉机构1026向前推送，使生物打印机喷头1001同时挤出医用胶和生物墨汁，在人工管腔沿着生物打印机喷头1001向上运动的过程中，让医用胶自上而下涂抹在人工管腔内壁形成医用胶层，生物墨汁也自上而下的抹在医用胶层的内壁，同步加工出医用胶层和生物墨汁层，直到设定的涂覆长度完成，停止推送机构运动。
取出管腔组织构建体。驱动组件1009继续带动人工管腔安装组件1030向上移动， 使生物打印机喷头1001离开人工管腔安装腔，翻开盖板夹块，取出带有生物构建体层(包括医用胶层和生物墨汁层)的管腔组织构建体。
作业完成后，将推拉机构1026向后拉伸，带动注射器的柱塞向后运动。
通过上述步骤，能在管腔组织构建体的人工管腔内壁同步完成医用胶和生物墨汁的涂覆，使其在管腔组织构建体的人工管腔内制备生物构建体层能一次成型，确保粘附生物墨汁的效果。并且能从具体的位置开始涂覆，管道内部在涂覆前即将涂覆材料推送至喷口，在开始涂覆的时候即可直接出料，不会出现出料延后的情况。
采用本公开实施例的生物打印机喷头、生物打印机和管腔组织构建体打印方法，能够实现在管腔组织构建体等人工生物构建体的人工管腔内壁同步涂覆医用胶和生物墨汁，一次成型生物构建体层，根据需要制备的长度采用符合要求的生物打印机喷头和人工管腔安装腔即可，因此能够加工更细长的管腔组织构建体，利于避免因为所需的管腔组织构建体过长，分多次打印医用胶和生物墨汁而出现的如医用胶粘度下降等问题。
采用本公开的实施例的生物打印机喷头、生物打印机和管腔组织构建体打印方法，能够制备长度大于等于30cm的管腔组织构件体。
最后应当说明的是：以上实施例仅用以说明本公开的技术方案而非对其限制；尽管参照较佳实施例对本公开进行了详细的说明，所属领域的普通技术人员应当理解：依然可以对本公开的具体实施方式进行修改或者对部分技术特征进行等同替换，其均应涵盖在本公开请求保护的技术方案范围当中。

Claims (22)

  1. 一种生物打印机喷头，所述生物打印机喷头具有：
    生物墨汁流道(P1)，设置于所述生物打印机喷头内部；
    生物墨汁喷口(J1)，与所述生物墨汁流道(P1)连通，位于所述生物打印机喷头的喷射端的侧面；
    医用胶流道(P2)，设置于所述生物打印机喷头内部，与所述生物墨汁流道(P1)隔离；
    医用胶喷口(J2)，与所述医用胶流道(P2)连通，位于所述喷射端的侧面，并且，沿所述生物打印机喷头的轴向，所述医用胶喷口(J2)与所述生物墨汁喷口(J1)错位布置。
  2. 根据权利要求1所述的生物打印机喷头，其中，沿所述生物打印机喷头的轴向所述生物墨汁喷口(J1)相对于所述医用胶喷口(J2)更靠近所述喷射端的顶面。
  3. 根据权利要求1或2所述的生物打印机喷头，其中，
    所述生物打印机喷头包括沿所述生物打印机喷头的周向均匀分布的多个所述生物墨汁喷口(J1)；和/或
    所述生物打印机喷头包括沿所述生物打印机喷头的周向均匀分布的多个所述医用胶喷口(J2)或所述医用胶喷口(J2)包括绕所述生物打印机喷头的轴向布置的环形喷口。
  4. 根据权利要求1至3中任一项所述的生物打印机喷头，包括设置于所述生物打印机喷头侧面的医用胶刮涂部(M)，沿所述生物打印机喷头的轴向，所述医用胶刮涂部(M)位于所述生物墨汁喷口(J1)和所述医用胶喷口(J2)之间。
  5. 根据权利要求4所述的生物打印机喷头，其中，所述医用胶刮涂部(M)包括设置于所述生物打印机喷头侧面的环形凸起或刷头。
  6. 根据权利要求1至5中任一项所述的生物打印机喷头，其中，所述生物打印机 喷头包括：
    墨汁喷头主体，所述生物墨汁喷口(J1)设置于所述墨汁喷头主体上；
    医用胶喷头主体，设置于所述墨汁喷头主体的外周，所述医用胶喷口(J2)设置于所述医用胶喷头主体上，或所述医用胶喷口(J2)设置于所述墨汁喷头主体与所述医用胶喷头主体之间。
  7. 根据权利要求6所述的生物打印机喷头，其中，
    所述生物墨汁流道(P1)设置于所述墨汁喷头主体内；
    所述医用胶流道(P2)设置于所述医用胶喷头主体与所述墨汁喷头主体之间。
  8. 根据权利要求7所述的生物打印机喷头，其中，所述生物打印机喷头包括连接片，所述连接片连接于所述墨汁喷头主体和所述医用胶喷头主体之间。
  9. 根据权利要求6所述的生物打印机喷头，其中，
    所述生物墨汁流道(P1)设置于所述墨汁喷头主体内；
    所述医用胶流道(P2)设置于所述墨汁喷头主体内，所述墨汁喷头主体的侧壁具有与所述医用胶流道(P2)连通的连通口(N)；
    所述医用胶喷口(J2)包括由所述墨汁喷头主体和所述医用胶喷头主体的靠近所述喷射端的一端形成的绕所述生物打印机喷头的轴向布置的环形喷口，所述连通口(N)与所述环形喷口连通。
  10. 根据权利要求6所述的生物打印机喷头，还包括喷头安装座，其中，
    所述生物墨汁流道(P1)包括设置于所述墨汁喷头主体内的第一生物墨汁流道(P11)和设置于所述喷头安装座内的第二生物墨汁流道(P12)，或者所述生物墨汁流道(P1)设置于所述喷头安装座内；
    所述医用胶流道(P2)包括设置于所述医用胶喷头主体内的第一医用胶流道(P21)和设置于所述喷头安装座内的第二医用胶流道(P22)。
  11. 根据权利要求10所述的生物打印机喷头，其中，所述医用胶流道(P2)还包括第一环形缓冲槽(G)，所述第一医用胶流道(P21)和所述第二医用胶流道(P22) 通过所述第一环形缓冲槽(G)连通。
  12. 根据权利要求11所述的生物打印机喷头，其中，所述第一环形缓冲槽(G)形成于所述医用胶喷头主体与所述喷头安装座之间。
  13. 根据权利要求10所述的生物打印机喷头，其中，所述医用胶流道(P2)包括设置于所述医用胶喷口(J2)与所述第一医用胶流道(P21)之间的第二环形缓冲槽(L)。
  14. 一种生物打印机，包括：
    生物打印机喷头(1001)，所述生物打印机喷头(1001)包括权利要求1至13中任一项所述的生物打印机喷头；
    供料组件(1005)，与所述生物打印机喷头(1001)连接，被配置为向所述生物打印机喷头(1001)的所述生物墨汁流道(P1)供应生物墨汁和向所述医用胶流道(P2)供应医用胶；
    人工管腔安装组件(1030)，包括用于容置管腔组织构建体的人工管腔的人工管腔安装腔(1014)，所述人工管腔安装组件(1030)被配置为能够相对于所述生物打印机喷头(1001)沿所述人工管腔安装腔(1014)的轴向往复运动。
  15. 根据权利要求14所述的生物打印机，其中，所述供料组件(1005)包括：
    医用胶注射器(1003)，被配置为向所述医用胶流道(P2)供应医用胶；
    生物墨汁注射器(1004)，被配置为向所述生物墨汁流道(P1)供应生物墨汁；
    注射器固定组件，被配置为固定所述医用胶注射器(1003)和所述生物墨汁注射器(1004)；和
    推送机构，被配置为与所述医用胶注射器(1003)的柱塞和所述生物墨汁注射器(1004)的柱塞驱动连接以推动两个柱塞运动。
  16. 根据权利要求15所述的生物打印机，其中，所述推送机构包括：
    注射器柱塞固定片(1024)，设有用于放置柱塞的端部圆盘的缺口；
    柱塞固定弹簧组件(1029)，包括组件壳体(10291)、导向柱(10292)和弹簧 (10293)，所述组件壳体(10291)内具有弹簧安装腔(10294)，所述导向柱(10292)可移动地穿设于所述组件壳体(10291)上且中部位于所述弹簧安装腔(10294)内，所述导向柱(10292)的第一端与所述注射器柱塞固定片(1024)连接，所述导向柱(10292)的中部具有朝向径向外侧的突出部，所述弹簧(10293)套设于所述导向柱(10292)外周并位于所述弹簧安装腔(10294)的靠近所述导向柱(10292)的第一端的内壁与所述突出部之间；
    弹簧推送片(1025)，位于所述柱塞固定弹簧组件(1029)的远离所述柱塞的一端；和
    推拉机构(1026)，与所述组件壳体(10291)驱动连接，被配置为带动所述组件壳体(10291)移动以使所述导向柱(10292)的第二端与所述弹簧推送片(1025)在抵接状态和分离状态之间切换，其中，在所述抵接状态，所述注射器柱塞固定片(1024)与所述柱塞固定弹簧组件(1029)之间形成安装所述端部圆盘的空间，在所述分离状态，所述柱塞固定弹簧组件(1029)压紧并固定所述端部圆盘于所述注射器柱塞固定片(1024)上，且所述推拉机构(1026)被配置为通过所述柱塞固定弹簧组件(1029)带动所述柱塞运动。
  17. 根据权利要求14至16中任一项所述的生物打印机，包括驱动组件(1009)，所述驱动组件(1009)与所述人工管腔安装组件(1030)驱动连接，被配置为驱动所述人工管腔安装组件(1030)沿所述人工管腔安装腔(1014)的轴向往复运动。
  18. 根据权利要求14至17中任一项所述的生物打印机，其中，包括检测模块(1012)，所述检测模块(1012)被配置为检测所述生物打印机喷头(1001)与所述人工管腔安装腔(1014)的相对位置。
  19. 根据权利要求14至18中任一项所述的生物打印机，包括温控模块(1013)，所述温控模块(1013)被配置为控制所述人工管腔安装腔(1014)的温度。
  20. 根据权利要求14至19中任一项所述的生物打印机，还包括：
    扶正杆(1021)，沿所述人工管腔安装腔(1014)的轴向延伸并可移动地设置；
    扶正板(1027)，设置于所述扶正杆(1021)的顶端，所述扶正板(1027)包括 与所述生物打印机喷头(1001)的外壁间隙配合的喷头安装口，所述扶正板(1027)的喷头安装口被配置保持安装于所述喷头安装口内的所述生物打印机喷头(1001)与所述人工管腔安装腔(1014)同轴。
  21. 一种管腔组织构建体打印方法，采用根据权利要求14至20中任一项所述的生物打印机打印管腔组织构建体，包括：
    加注打印材料，包括向所述供料组件(1005)加注打印材料；
    安装管腔组织构建体的人工管腔，包括将所述人工管腔安装在所述人工管腔安装组件(1030)的人工管腔安装腔(1014)内；
    生物打印机喷头初始定位，包括使所述生物打印机喷头(1001)伸入所述人工管腔内并处于初始位置；
    打印材料涂覆，包括使所述人工管腔安装组件(1030)相对于所述生物打印机喷头(1001)沿所述人工管腔安装腔(1014)的轴向运动，并且在运动的同时向所述生物打印机喷头(1001)的所述生物墨汁流道(P1)供应生物墨汁以及向所述医用胶流道(P2)供应医用胶。
  22. 根据权利要求21所述的管腔组织构建体打印方法，还包括在安装管腔组织构建体的人工管腔后调节所述人工管腔安装腔(1014)的温度。
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