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WO2024254588A2 - Bio-impression multi-échelle adaptable rapide avec incorporation de capillaires pour l'ingénierie de grands tissus vascularisés - Google Patents

Bio-impression multi-échelle adaptable rapide avec incorporation de capillaires pour l'ingénierie de grands tissus vascularisés Download PDF

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Publication number
WO2024254588A2
WO2024254588A2 PCT/US2024/033235 US2024033235W WO2024254588A2 WO 2024254588 A2 WO2024254588 A2 WO 2024254588A2 US 2024033235 W US2024033235 W US 2024033235W WO 2024254588 A2 WO2024254588 A2 WO 2024254588A2
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WIPO (PCT)
Prior art keywords
bioprinting
electrospinning
hydrogel
spinneret
microtubes
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WO2024254588A3 (fr
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George Zhuo TAN
Imtiaz QAVI
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Texas Tech University TTU
Texas Tech University System
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Texas Tech University TTU
Texas Tech University System
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Publication of WO2024254588A2 publication Critical patent/WO2024254588A2/fr
Publication of WO2024254588A3 publication Critical patent/WO2024254588A3/fr
Anticipated expiration legal-status Critical
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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
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y10/00—Processes of additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y30/00—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • 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
    • C12M21/00—Bioreactors or fermenters specially adapted for specific uses
    • C12M21/08—Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
    • 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

  • TITLE Capillary-Embedded Rapid Adaptable Multiscale Bioprinting for Engineering Large
  • the present disclosure relates to the field of three-dimensional (3D) bioprinting and electrospinning.
  • the present disclosure relates to the combination of 3D bioprinting and electrospinning for the fabrication of multi-scale scaffolds integrated with artificial capillary vessels.
  • the cells need to be within approximately 200 microns (pm) from the engineered tissue surface.
  • pm microns
  • Decellularized allogenic or xenogenic grafts may provide naturally and intact vascular conduits. But, nonetheless, these grafts have associated difficulties, such as limits in obtaining personalized organ scaffolds, limited types of organs, and potential disruption to the extracellular matrix (ECM).
  • ECM extracellular matrix
  • the present disclosure is directed to systems and a method for capillary-incorporated bioprinting that combines electrospinning and 3D bioprinting for fabricating multi-scale scaffolds integrated with biomimetic porous microtubes that function as capillary vessels.
  • the present disclosure provides a hybrid bioprinting technology that can incorporate thousands of porous microtubes to a centimeter sized 3D printed scaffold within several minutes.
  • the present disclosure allows for a high resolution with a rapid speed of printing.
  • the present disclosure provides a multi-scale biofabrication process for optimal tissue regeneration.
  • the subsystem of porous microtube electrospinning can be incorporated into a wide range of additive manufacturing processes, including stereolithography, inkjet bioprinting, and fused deposition modeling.
  • the disclosure features a capillary-incorporated bioprinting system for rapid engineering of vascularized tissues.
  • the system can include a three-dimensional printing head.
  • the three-dimensional printing head can be configured on a three-axis linear stage.
  • the system can also include a spinneret.
  • the spinneret can be configured on a horizontal linear stage.
  • the spinneret attached to the three-dimensional printing head can be retracted above or below the printing head.
  • the system can also include a UV light source.
  • the UV light source can be operatively coupled to the three-dimensional printing head and the spinneret.
  • the UV light source can be adjacent to the spinneret.
  • the system can also include a pair of distance adjustable parallel bars.
  • the pair of parallel bars can be configured to collect a plurality of electrospun aligned microtubes.
  • the disclosure features a method for engineering vascularized tissues using a capillary-incorporated bioprinting system.
  • the method can include printing a first layer of a hydrogel onto a printing area using a three-dimensional printing head.
  • the method can include returning the three-dimensional printing head to a home position.
  • the method can include electrospinning microfibers onto a pair of parallel bars.
  • the electrospinning can align the microfibers on top of the first layer of the hydrogel.
  • the parallel bars can rotate and align the fiber in any angle from 0 to 360 degrees on the printed layers.
  • the method can include submerging, due to gravitational forces, the microfibers in the first layer of the hydrogel.
  • the method can include, resultant from the submerging, forming porous microtubes in the first layer of hydrogel.
  • the method can include cross-linking the first layer of the hydrogel by exposing the first layer of the hydrogel to a UV light source. The cross-linking can create a cross-linked base of the hydrogel.
  • the disclosure features a bioprinting electrospinning hybrid printer including a parallel plate collector.
  • the parallel plate collector can include one or more plates with an adjustable distance and an adjustable angle.
  • the bioprinting electrospinning hybrid printer can also include an electronic control module.
  • the electronic control module can be configured to control one or more major stage-motion servos and one or more flow-control servos.
  • the bioprinting electrospinning hybrid printer can also include a hybrid electrospinning bioprinting nozzle including one or more electrospinning syringes and one or more bioprinting syringes.
  • FIG. 1 depicts a prior capillary-incorporated system in a hydrogel scaffold.
  • FIG. 2A depicts sequential bioprinting-electrospinning-bioprinting operations, in accordance with certain embodiments of the present disclosure.
  • FIG. 2B depicts a capillary-incorporated bioprinting system, in accordance with certain embodiments of the present disclosure.
  • FIG. 3 depicts the capillary-incorporated bioprinting process for a scaffold with embedded fibrous networks and cells, in accordance with certain embodiments of the present disclosure.
  • FIG. 4 depicts a bioprinting electrospinning hybrid printer, in accordance with certain embodiments of the present disclosure.
  • FIGS. 5A-5E depict components in the bioprinting electrospinning hybrid printer, in accordance with certain embodiments of the present disclosure.
  • FIG. 5A depicts a perspective view of the complete bioprinter electrospinning hybrid printer.
  • FIG. 5B depicts an isometric view of a parallel plate collector.
  • FIG. 5C depicts a side view of a parallel plate collector.
  • FIG. 5D depicts an isometric view of a hybrid printhead.
  • FIG. 5E depicts a side view of a hybrid printhead.
  • FIG. 6 depicts a variable angle parallel plate collector mechanism, in accordance with certain embodiments of the present disclosure.
  • FIG. 7A depicts a hybrid electrospinning bioprinting nozzle system, in accordance with certain embodiments of the present disclosure.
  • FIG. 7B depicts a hybrid electrospinning bioprinting nozzle system, with each component of the system depicted separately, which when configured together are in accordance with certain embodiments of the present disclosure.
  • FIG. 8 depicts a hybrid printhead three-axis motion system, in accordance with certain embodiments of the present disclosure.
  • FIG. 9 depicts a servo control connection layout, in accordance with certain embodiments of the present disclosure.
  • first, second, third, etc. may be used herein to describe various elements, components, regions, layers and/or sections; however, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms may be only used to distinguish one element, component, region, layer, or section from another region, layer, or section. Terms such as “first,” “second,” and other numerical terms, when used herein, do not imply a sequence or order unless clearly indicated by the context. Thus, a first element, component, region, layer, or section discussed below could be termed a second element, component, region, layer, or section without departing from the teachings of the example embodiments.
  • phrases “at least one of,” when used with a list of items, means that different combinations of one or more of the listed items may be used, and only one item in the list may be needed.
  • the term “and/or” when used in the context of a listing of entities refers to the entities being present singly or in combination.
  • the phrase “A, B, C, and/or D” includes A, B, C, and D individually, but also includes any and all combinations and subcombinations of A, B, C, and D.
  • “at least one of: A, B, and C” includes any of the following combinations: A, B, C, A and B, A and C, B and C, and A and B and C.
  • the phrase “one or more” when used with a list of items means there may be one item or any suitable number of items exceeding one.
  • spatially relative terms such as “inner,” “outer,” “beneath,” “below,” “lower,” “above,” “upper,” “top,” “bottom,” and the like, may be used herein. These spatially relative terms can be used for ease of description to describe one element’s or feature’s relationship to another element(s) or feature(s) as illustrated in the figures.
  • the spatially relative terms may also be intended to encompass different orientations of the device in use, or operation, in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the example term “below” can encompass both an orientation of above and below.
  • the device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptions used herein interpreted accordingly.
  • the present disclosure provides systems and methods for capillary-incorporated bioprinting combineing electrospinning and 3D bioprinting for fabricating multi-scale scaffolds integrated with biomimetic porous microtubes that function as capillary vessels.
  • the capillary-incorporated bioprinting system can include a scalable 3D bioprinted molecular scaffold that incorporates the blood vascular architecture to support tissue regeneration and organ development. Specifically, the system may allow for the incorporation of thousands of porous microtubes over an area of 1 cm 2 that function as capillary vessels and maintain a requisite diameter of approximately 5 to 10 pm in length. [0037] The incorporation of the microtubes can generate a centimeter-sized 3D-printed scaffold a rate approximately ten times faster and with approximately 10-fold higher resolution than the present 3D printing technologies in the field. As such, the 3D bioprinting process may rapidly incorporate thousands of porous microtubes that function as capillary vessels to a centimeter-sized 3D printed scaffold within several minutes. From this, the system for porous microtube electrospinning can be incorporated into a wide range of additive manufacturing processes, including for example but not limited to stereolithography, inkjet bioprinting, and fused deposition modeling.
  • the adaptable 3D bioprinting process may, in some embodiments, allow for engineering large, vascularized tissues and capillaries.
  • the process for capillaryincorporated bioprinting can combine electrospinning and 3D bioprinting.
  • the 3D bioprinting may be extrusion-based in some embodiments. In other embodiments, the 3D bioprinting may be inkjetbased.
  • the capillary-incorporated bioprinting system may be used to fabricate multiscale scaffolds integrated with biomimetic porous microtubes.
  • the biomimetic porous microtubes may function as capillary vessels.
  • FIG. 1 depicts a prior capillary-incorporated system in a hydrogel scaffold.
  • the capillary-incorporated system can be generated on a 3D printed microtube-embedded hydrogel scaffold.
  • the system depicted in FIG. 1 may be enhanced through the use of a three-axis linear stage, as depicted in FIG. 2.
  • FIG. 2A depicts sequential bioprinting-electrospinning-bioprinting operations, in accordance with certain embodiments of the present disclosure.
  • a layer of co-axially electrospun core-sheath microtube can be sandwiched between alternate layers of 3D bio-compatible extrusion-printed hydrogels.
  • automated alternate hydrogel-microtube-hydrogel fabrication can be accomplished without any manual handling that would potentially damage the fine electrospun microtube structure.
  • the operations may include switching between random and highly aligned microtube orientations as per the design requirements.
  • the system may have full control over microtube morphology (diameter, wall thickness, orientation) and the option to change fiber orientation direction.
  • FIG. 2B depicts a capillary-incorporated bioprinting system, in accordance with certain embodiments of the present disclosure.
  • the capillary-incorporated bioprinting system can include a 3D printing head.
  • the 3D printing head may be a mechanical-driven or a pneumatic- driven extrusion-based 3D printing head.
  • the 3D printing head may be located on a 3-axis, 4-axis, or 5-axis motorized stage.
  • the capillary-incorporated bioprinting system can include a concentric dual-channel spinneret on a horizontal linear stage.
  • the concentric dual-channel spinneret may be set above the 3D printing head.
  • the capillary-incorporated bioprinting system may also include a UV light source.
  • the UV light source in certain embodiments, may be adjacent to the spinneret.
  • the UV light source may also be a 395nm UV light.
  • the capillary-incorporated bioprinting system provides enhanced capabilities based on the use of a three-axis linear stage and concentric dual-channel spinneret.
  • the capillary-incorporated bioprinting system may also include working cycle for UV-curable hydrogels to support the polyethylene glycol diacrylate (PEGDA) or gelatin methacryloyl tissue scaffolds.
  • a height-adjustable table may be included in the capillaryincorporated bioprinting system.
  • FIG. 3 depicts the capillary-incorporated bioprinting process for a scaffold with embedded fibrous networks and cells, in accordance with certain embodiments of the present disclosure.
  • the working cycle for UV-curable hydrogels can begin by one layer of hydrogel being 3D printed. Following this, in such an embodiment as shown in FIG. 3 through use of the system in FIG. 2, the printing head can return to the home position. Before cross-linking, in such an embodiment, core-sheath microfibers will be electrospun onto two parallel collector bars. In this embodiment, the electrospinning of the core-sheath microfibers allows for forming aligned microfibers on top of the hydrogel. Due to gravity, microfibers, in the capillaryincorporated bioprinting system of FIG. 2 for use in the process of FIG. 3, can immediately submerge in the hydrogel and turn into porous microtubes.
  • the hydrogel can then be cross-linked by UV exposure or other crosslinking mechanisms.
  • the printing table can be lowered, and the second layer of hydrogel can be printed on the cross-linked base.
  • the excess microtubes outside the hydrogel can be trimmed.
  • FIG. 4 depicts a bioprinting electrospinning hybrid printer, in accordance with certain embodiments of the present disclosure.
  • the hybrid printer of FIG. 4 can be designed to allow for tissue engineered production of perfused scaffold structures.
  • the motion system may be enclosed within a closed chamber to ensure sterile environment for cell encapsulated bioprinting.
  • a control module may be present at the bottom of the bioprinting electrospinning hybrid printer.
  • the control module may provide high voltage potential difference for electrospinning, control for all the servos in the system, USB connection to control the stage motions and flowrates using standard G-codes, and combinations thereof.
  • the bioprinting electrospinning hybrid printer of FIG. 4 can allow simultaneous bioprinting and electrospinning operations for biofabrication of microtube encapsulated 3D hydrogel structures.
  • the bioprinting electrospinning hybrid printer can include a parallel plate collection system with retractable distance and variable angle adjustment. The parallel plate collection system can allow for deposition of aligned microtubes along any desired angle along the XY-axis.
  • FIGS. 5A-5E depict components in the bioprinting electrospinning hybrid printer, in accordance with certain embodiments of the present disclosure.
  • FIG. 5A depicts a perspective view of the complete bioprinter electrospinning hybrid printer.
  • FIG. 5B depicts an isometric view of a parallel plate collector.
  • FIG. 5C depicts a side view of a parallel plate collector.
  • FIG. 5D depicts an isometric view of a hybrid printhead.
  • FIG. 5E depicts a side view of a hybrid printhead.
  • the bioprinting electrospinning hybrid printer can be sterile and fully servo-controlled.
  • the bioprinting electrospinning hybrid printer may be designed to provide electronic servo-controlled flow systems for the bioprinting and electrospinning solution.
  • the design would eliminate the need for auxiliary components, such as for example syringe pumps.
  • a single electronic control module can control the major stage-motion servos and the flow-control servos.
  • the system can be a sterile environment for biofabrication operations with cell incorporated bio-inks.
  • the bioprinting electrospinning hybrid printer can include an adjustable distance and angle parallel plate collector.
  • the parallel plate collectors in such an embodiment, may collect highly aligned electrospun microfibers or microtubes.
  • the overall fabrication process of aligned fiber and microtubes can depend on the distance of the plates from the electrospinning nozzle and the distance between the plates.
  • repeated opening and closing of the enclosure could introduce risks of contaminations.
  • manual tweaking of the plates introduces more process variability.
  • the bioprinting electrospinning hybrid printer may include a computer controlled parallel plate collection system that can control the inter-plate distance.
  • a secondary servo attached to the system allows changing the angle of the plates with respect to the bio-print bed, thus adding more design variability in the fabrication of the microtube incorporated hydrogel structures.
  • the plates may also have a resistive heating option to melt off the collected fibers and microtubes and deposit them directly on the hydrogel layer without any manual handling.
  • the bioprinting electrospinning hybrid printer can include a hybrid electrospinning bioprinting nozzle.
  • the electrospinning syringes and bioprinting syringes may be combined into a single and common hybrid nozzle system. Accordingly, all the nozzles may be controlled using miniscale, high precision servos instead of the traditional pneumatic or hydraulic systems.
  • the bioprinting nozzle can be extended or retracted along the z-axis using a separate bioprinthead control servo, which may reduce the interference of the bioprinting nozzle with the electrospinning nozzle during each of their individual operation procedures.
  • each of the servos may be individually controlled, triggered, stopped, and initiated using servo control systems running on G-codes.
  • the bioprinter and the electrospinning syringes can be switched off individually when the other nozzles are operational, thus reducing the impact of material dripping.
  • FIG. 6 depicts a variable angle parallel plate collector mechanism, in accordance with certain embodiments of the present disclosure.
  • the parallel plate collection system allows for the combined flexibility of handling-free microtube deposition with precision and control over fiber morphology and alignment angle.
  • a rack-pinion gear system coupled with a servo motor at the bottom of the system can control the gap between the parallel plates.
  • the precise gap control can be a fabrication parameter that varies with different electrospinning polymer solutions, and other process parameters, such as collector-nozzle distance and operating voltage.
  • the gap between the plates can be controlled using the rotational angle position of the parallel plate retraction servo using a standard G-code program, which can ensure repeatability of the same gap position down to the mm-scale and thus a more precise microtube fabrication method.
  • a secondary servo may function as a parallel plate rotation servo.
  • the parallel plate rotation servo may be positioned directly beneath the housing for the retraction servo.
  • the parallel plate rotation servo can, in certain embodiments, rotate all the attachments, including but not limited to the parallel plate retraction servo, rack/pinion gear system, parallel plates, above the parallel plate rotation servo along the XY-plane.
  • the parallel plate rotation servo can allow the collection of the fibers and microtubes in any angular position with respect to the X or Y-axis on the build-plate. Therefore, the parallel plate rotation servo can provide more design options to generate complex fiber and microtube infused hydrogel structure designs for research applications.
  • the print plate may be mounted on a servo system that can move the print plate along the Z-axis.
  • the aligned microtubes can be collected between the build plates keeping a certain gap from the hydrogel layer.
  • the print-bed Z-axis servo may lift the print-bed up so that the hydrogel layer just touches the aligned fibers. The precise position of this Z-travel can be controlled using G-codes to ensure that the fibers are positioned precisely at the interface of the hydrogel.
  • the parallel plates can have two operation modes.
  • the first operation mode may allow the parallel plate to be connected in the negative/ground terminal and thus act as collector surfaces for the electrospinning operation.
  • the second operation mode for example, may switch the connection to the plates from a single potential to a series-connected system, turning the parallel plates into resistive heating sources.
  • the second operation mode in some embodiments, may melt the fibers from the ridges of the plates and softly allow them to land on the hydrogel surface under gravitational forces without any other external forces, which may ensure that the fibers are not deformed from handling.
  • a separate precision spray nozzle may be added to the system.
  • the separate precision spray nozzle may allow chemical crosslinking without manual-handling.
  • FIG. 7A depicts a hybrid electrospinning bioprinting nozzle system, in accordance with certain embodiments of the present disclosure.
  • FIG. 7B depicts a hybrid electrospinning bioprinting nozzle system, with each component of the system depicted separately, which when configured together are in accordance with certain embodiments of the present disclosure.
  • the hybrid nozzle system can eliminate the problem of mounting the two different fabrication nozzles onto separate motion-axis systems and combines them under the same three- axis motion system, thus allowing the easy operation of both the nozzles using the same control system platform.
  • a core-sheath syringe holder system can consist of two syringe holders.
  • the core-sheath syringe holder system can also consist of two mechanical servo systems to individually control the flowrates of the two solutions.
  • the polymer solution holder system can also consist of a single-syringe holder that can be mechanically controlled using a servo mounted at the back of the syringe holder.
  • a sliding channel Positioned in the back of the bioprinting syringe holder, in some embodiments, a sliding channel can exist for attachment with the bioprint head and electrospinning head junction body.
  • the junction body can be fixed to the coaxial syringe system on one side.
  • the junction body can have sliding channels that attach to the bioprinting syringe holder system.
  • a servo mounted on the top of the junction body can controls the Z-axis motion of the bioprinting nozzle.
  • the bioprint head can be moved up and down during the toggling operation between electrospinning and bioprinting mode.
  • the bioprinting nozzle system can include a heating pad operatively connected to the bioprinting extruder.
  • FIG. 8 depicts a hybrid printhead three-axis motion system, in accordance with certain embodiments of the present disclosure.
  • the z-axis slider arm can be mounted between the aluminum housing frames to support the weight of the system during the motion.
  • Two y-axis slider arms can be bolted or welded to the z-axis slider arm. Both of the slider arms can have channel grooves to support the sliding of the x-axis slider arm over each slider arm.
  • one of the y-axis slider arms can host the y-axis control servo system.
  • the x-axis slider arm can rest between the two y-axis slider arms.
  • the hybrid printhead can be mounted directly on the x-axis slider arm and slide along the slider arm when the x-axis servos are engaged. Accordingly, in some embodiments, the x-axis servo screw-rod can run directly through the junction body in the hybrid printhead system and control the motion via screw-driven motion.
  • FIG. 9 depicts a servo control connection layout, in accordance with certain embodiments of the present disclosure. Specifically, FIG. 9 depicts the connection layout for the logical servo control systems. All of the servo connections can originate from the servo control module system, which can be located at the base of the printer housing. In some embodiments, the same module system controls the high-voltage for the electrospinning operation and acts as a USB interface for computer G-codes and software connection. The six red connection lines, as shown in FIG. 9, can indicate logical control connection of the major power-driven servos in the assembly.
  • Embodiments can include a system, a method, and/or a computer program product.
  • the computer program product may include a computer readable storage medium (or media) having computer readable program instructions thereon for causing a processor to carry out aspects of the present disclosure.
  • a capillary -incorporated bioprinting system for rapid engineering of vascularized tissues including a three-dimensional printing head, where the three-dimensional printing head is configured on a three-axis linear stage; a spinneret, where the spinneret is configured on a horizontal linear stage and the spinneret is affixed above the three-dimensional printing head; a UV light source, where the UV light source is operatively coupled to the three- dimensional printing head and the spinneret, and adjacent to the spinneret; and a pair of parallel bars, where the pair of parallel bars are configured to collect a plurality of electrospun aligned microtubes.
  • Clause 7 The system of any foregoing clause further including one or more hydrogels, where the hydrogels are operatively configured to support a tissue scaffold.
  • Clause 8 The system of any foregoing clause further including a printing area, where the printing area is configured to support a bioprinted vascularized tissue.
  • a method for engineering vascularized tissues using a capillary -incorporated bioprinting system including printing a first layer of a hydrogel onto a printing area using a three-dimensional printing head; returning the three-dimensional printing head to a home position; electrospinning microfibers onto a pair of parallel bars, where the electrospinning aligns the microfibers on top of the first layer of the hydrogel; submerging, due to gravitational forces, the microfibers in the first layer of the hydrogel; resultant from the submerging, forming porous microtubes in the first layer of hydrogel; and cross-linking the first layer of the hydrogel by exposing the first layer of the hydrogel to a UV light source, where the cross-linking creates a cross-linked base of the hydrogel.
  • Clause 18 The method of any foregoing clause further including printing a second layer of the hydrogel on the cross-linked base of the hydrogel.
  • a bioprinting electrospinning hybrid printer including a parallel plate collector, where the parallel plate collector including one or more plates with an adjustable distance and an adjustable angle; an electronic control module, where the electronic control module is configured to control one or more major stage-motion servos and one or more flow-control servos; and a hybrid electrospinning bioprinting nozzle including one or more electrospinning syringes and one or more bioprinting syringes.

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Abstract

L'invention concerne un système de bio-impression avec incorporation de capillaires pour l'ingénierie rapide de tissus vascularisés, le système comprenant une tête d'impression tridimensionnelle, la tête d'impression tridimensionnelle étant configurée sur une platine linéaire à trois axes ; une filière, la filière étant configurée sur une platine linéaire horizontale et la filière étant fixée au-dessus de la tête d'impression tridimensionnelle ; une source de lumière UV, la source de lumière UV étant couplée de manière fonctionnelle à la tête d'impression tridimensionnelle et à la filière, et adjacente à la filière ; et une paire de barres parallèles, la paire de barres parallèles étant conçue pour collecter une pluralité de microtubes alignés électrofilés.
PCT/US2024/033235 2023-06-08 2024-06-10 Bio-impression multi-échelle adaptable rapide avec incorporation de capillaires pour l'ingénierie de grands tissus vascularisés Pending WO2024254588A2 (fr)

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US63/507,065 2023-06-08

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WO2024254588A2 true WO2024254588A2 (fr) 2024-12-12
WO2024254588A3 WO2024254588A3 (fr) 2025-04-10

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PCT/US2024/033235 Pending WO2024254588A2 (fr) 2023-06-08 2024-06-10 Bio-impression multi-échelle adaptable rapide avec incorporation de capillaires pour l'ingénierie de grands tissus vascularisés

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Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009102484A2 (fr) * 2008-02-14 2009-08-20 Wake Forest University Health Sciences Impression par jet d’encre de tissus et de cellules
WO2010096469A2 (fr) * 2009-02-17 2010-08-26 William Marsh Rice University Fabrication d'une vasculature modèle interconnectée
WO2015066705A1 (fr) * 2013-11-04 2015-05-07 University Of Iowa Research Foundation Bio-imprimante et procédés pour l'utiliser
US10730928B2 (en) * 2014-09-26 2020-08-04 University Of South Carolina Biofabrication techniques for the implementation of intrinsic tissue geometries to an in vitro collagen hydrogel
EP4039475A1 (fr) * 2021-02-03 2022-08-10 AJL Ophthalmic, S.A. Imprimante 3d permettant de générer des tissus biologiques incurvés

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