EP4313597A1 - Extrusionsbasierter und tragbarer dreidimensionaler handbiodrucker - Google Patents

Extrusionsbasierter und tragbarer dreidimensionaler handbiodrucker

Info

Publication number
EP4313597A1
EP4313597A1 EP23765135.1A EP23765135A EP4313597A1 EP 4313597 A1 EP4313597 A1 EP 4313597A1 EP 23765135 A EP23765135 A EP 23765135A EP 4313597 A1 EP4313597 A1 EP 4313597A1
Authority
EP
European Patent Office
Prior art keywords
bioink
cartridge
linear piston
micro linear
temperature
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP23765135.1A
Other languages
English (en)
French (fr)
Inventor
Ayca Bal ÖZTÜRK
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Adbioink Biyosistem Teknoloji AS
Original Assignee
Adbioink Biyosistem Teknoloji AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Adbioink Biyosistem Teknoloji AS filed Critical Adbioink Biyosistem Teknoloji AS
Priority claimed from PCT/TR2023/050343 external-priority patent/WO2023244197A1/en
Publication of EP4313597A1 publication Critical patent/EP4313597A1/de
Pending legal-status Critical Current

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y30/00Apparatus for additive manufacturing; Details thereof or accessories therefor
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y50/00Data acquisition or data processing for additive manufacturing
    • B33Y50/02Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M33/00Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus

Definitions

  • the invention relates to an extrusion-based and portable handheld three- dimensional bioprinter designed for use in tispsue engineering applications, artificial organ and tissue production, musculoskeletal injuries, tissue damage, bum treatment, tissue regeneration, controlled release system and three- dimensional cell culture applications, as well as cosmetics and drug discovery.
  • three-dimensional bioprinters are the common solution for bioprinting.
  • Such systems are high-tech biomedical devices that are used especially in the field of tissue engineering and enable the imitation of natural tissues by creating tissue-like structures via depositing biomaterials, also known as bio-ink, which can mimic natural tissues.
  • biomaterials also known as bio-ink
  • the material to be bioprinted is mixed with the relevant cells depending on the area of use, transferred to the apparatus called barrel (cartridge) and placed in the three- dimensional bioprinter.
  • the shape in the drawing file uploaded to the system is produced thanks to the motor connection moving in three axes.
  • the bioprinted material can be cured and hardened thanks to the integrated light source.
  • Bioprinting can be defined as the layer-by-layer creation of complex biological structures (tissues, organs) by precise positioning of living cells. When creating biological structures, the most important requirement is that cells can maintain their viability during the process. Three-dimensional bioprinters can also be used to reconstruct tissue in various parts of the body. In this sense, new applications are being realized every day in the medical field and the potential for the use of these systems is increasing. The application in the medical field is possible by first making a three-dimensional drawing of the body part to be filled with the biomaterial and uploading the drawing file to the three-dimensional bioprinter and realizing the production. System features do not allow for direct body application.
  • inkjet printer the printhead is heated electrically and generates pulses of air pressure, causing the bio-ink to drip.
  • Extrusion-based printers use either pneumatic systems or mechanical systems in which gas pressure is translated into mechanical motion.
  • laser-assisted printers pulses are generated by using a focused laser on the absorbent surface, pushing the cells towards a collector surface at the bottom. In each case, the printing mechanism is based on different physical phenomena, but the goal is the same.
  • the proposed biopencil structure consists of a casing, an ink cartridge located in the casing, a blue-ray photocuring system located at the head of the ink cartridge and a pen tip located at the tip of the ink cartridge.
  • a curing system consisting of a large number of LEDs with a wavelength of 465 nm to 485 nm, which is presented as green technology.
  • the lack of a heating/cooling system and the lack of information on whether different light sources can be integrated are considered as disadvantages thereof.
  • our invention has a heating/cooling system, which is very important for bioprinting, and a modular structure where different light sources can be integrated.
  • the proposed structure is a portable three-dimensional printer system. Bioprinting is not performed. Thanks to the heating system at the tip thereof, it melts and deposits the thermoplastic material and forms a three-dimensional structure by depositing layer by layer. Although similar in name, the printing mechanism is different. The melting/deposition concept is not used for printing biomaterials because of the negative impact on cell viability.
  • bioprinters that enable in situ formation of structured biomaterials and tissues by rotating a printhead across a deposition surface (e.g. a skin wound, etc.).
  • a deposition surface e.g. a skin wound, etc.
  • biopolymer solution containing the cell is dispensed by moving a micro-processed printhead and deposited onto a fixed flat surface or wound.
  • This patent introduces a portable three-dimensional bioprinter system that allows cells to be printed directly at the injured site in the appropriate solution. This system refers to multiple extrusion channels and allows simultaneous printing of different solutions.
  • the biopolymer solution is dispensed from the printhead and deposited on the damaged area, the biopolymer solution is polymerized and solidified.
  • Solidification can occur through different mechanisms, including coagulation, ion-induced, pH- induced and temperature-induced solidification, as well as enzymatic reactions and ultraviolet light-induced polymerization and combinations thereof.
  • UV light can be supplied from outside if needed.
  • the outlet of the bioprinter is of a lamellar structure with a width.
  • heating and cooling system there is no heating and cooling system.
  • CA3050385A 1 “Devices and methods for wound-conformal guidance of bioprinter printhead”
  • Described herein is a device that enables in situ formation of structured planar biomaterials and tissues by rotating a printhead along a deposition surface in a burn-injured patient.
  • cell-loaded biopolymer solutions are perfused through a moving microfabricated printhead and deposited onto a fixed planar surface or a wound.
  • the printhead can be turned by means of a drive mechanism.
  • a soft deformable roller reduces further damage to the injured area of skin as it rotates over it, and a gimbal mechanism to which the printhead is attached is in contact with the injured tissue but does not exert excessive pressure on the area while the printhead is in contact with the tissue.
  • the system consists of the following components:
  • a drive mechanism with a soft roller that, when activated by the operator, drives the biomaterial across the surface at a preselected V speed.
  • the present invention relates to medical devices for the treatment of musculoskeletal and skin disorders, and more particularly to devices, systems and methods that utilize bioprinters to create scaffolds in situ to facilitate the treatment of musculoskeletal and skin disorders in patients.
  • the method includes extruding a hydrogel formulation and curing it in situ. It is an extrusion-based device capable of continuously extruding biomaterials and includes an integrated light source for crosslinking the extruded bioink.
  • the platform can print photo-crosslinkable hydrogels such as gelatin methacryloyl (GelMA) for VML injuries instantly in situ.
  • GelMA is a collagen-derived biomaterial that closely mimics the extracellular matrix (ECM) of natural skeletal muscles. It is noted here that the integrated light source is UV.
  • the present invention relates to the additive manufacturing of biocompatible materials.
  • it concerns hand-held three-dimensional printing of biocompatible materials for surgical biofabrication.
  • This prototype system has two cartridge compartments that separately store two reagent containers (stem cells and biomaterial) as hydrogels, a mechanical extrusion system is used to extract the reagents from the three-dimensionally printed titanium extruder nozzle, and a UV light source is used. It is used to cross-link the hydrogels immediately after extrusion, thus forming a stable structure that encapsulates and supports the stem cells.
  • a foot pedal is used to control the extrusion of the reagent and the extrusion speed is controlled using an electronic control interface.
  • Each extruder has a circular cross-section and is coaxially arranged with a core material containing stem cells and a shell material encapsulating and supporting the core material.
  • the prototype device has limited freedom of movement as it is connected to the foot pedal and the electronic control interface by a cable.
  • the nozzle is a 3D printing titanium nozzle, which is expensive and not suitable for mass production.
  • the subject matter of the invention we have applied for is made of aluminum material. This selection of material is advantageous in terms of being cheaper, easier to process and having a high coefficient of thermal conductivity.
  • the problem in materials affected by temperature can be adjusted by speed control. This is an indirect control and the flow behaviors due to temperature differences cannot be fully controlled in this way.
  • ensuring the mixing within the prototype may lead to the appearance of inhomogeneous defects.
  • mixing is performed outside and a single-channel piston structure can be used to print the relevant region in a temperature-controlled manner. This makes the mechanism user-friendly and eliminates the problems of mixture homogenization.
  • the present disclosure relates to an extrusion-based and portable handheld three-dimensional bioprinter developed for eliminating the aforementioned disadvantages and providing new advantages to the respective technical field.
  • the portable three-dimensional bioprinter system of the invention allows the biomaterial to be printed in the desired area by pushing the cartridge (barrel) containing the biomaterial consisting of a mixture of bioink and cells in a controlled manner with its sensitive piston structure that can move electrically.
  • the biomaterial can be brought to the desired temperature between 20 and 40 °C, and the biomaterial temperature can be precisely monitored with the temperature meter integrated into the system.
  • the light source has a modular plug-in mechanism and can be easily integrated by the user with light sources including, but not limited to, 405 nm or 445 nm light sources consisting of visible region LEDs and 360 nm UV light source. Thanks to the light on/off feature, it is possible to print by turning off the light source if desired.
  • the presence of the heating/cooling system in our invention can provide high cell viability in terms of the cells being able to mimic physiological temperature during printing and increase the efficacy of the treatment, especially if applied directly to the body. Since the printing properties (rheology) of bioinks are affected by very small temperature differences, temperature differences make it difficult to obtain reproducible data and lead to misinterpretations. Maintaining constant temperature by providing temperature control will offer significant advantages in the optimization process and will contribute to obtaining reproducible results.
  • the invention does not require a PC connection and has a motor that can move in three axes, a portable size that can be controlled manually has been obtained.
  • the system of the invention provides the advantage of being able to print directly on a desired area thanks to the control of the geometry of the material produced by hand movement.
  • Figure-1 It is a representative view of the product of the invention.
  • Figure-2 It is representative view of the biopencil body and the bioink cartridge of the invention.
  • Figure-3 It is a representative view of the electrical cables, hot/cold liquid inlet/outlet lines and the tube casing enclosing them.
  • the invention relates to an extrusion-based and portable handheld three- dimensional bioprinter designed for use in tissue engineering applications, artificial organ and tissue production, musculoskeletal injuries, tissue damage, bum treatment, tissue regeneration, controlled release system and three- dimensional cell culture applications, as well as cosmetics and drug discovery.
  • the bioprinter of the invention generally includes at least one biopencil body (1 ) with ergonomics to allow the bioprinter to be carried by hand, made of aluminum alloy to provide high thermal conductivity, anodized and ground on the outer surface to ensure a long service life and a modem appearance, at least one bioink cartridge (4) in which the bioink solution is placed and which has a hot/cold liquid inlet (4.1), a hot/cold liquid outlet (4.2) and an electrical cable inlet (4.3), at least one LCD display (2) to display the temperature information of the bioink contained in the bioink cartridge (4) and the pressure information applied by the bioink to the micro linear piston (3), at least one micro linear piston (3) to push the rear plug of the bioink cartridge (4) forward to allow the bioink solution contained in the bioink cartridge (4) to be ejected from the end of the bioink cartridge (4), at least one push button (5) to cause the micro linear piston (3) to move forward when bioprinting is to be performed so that the bioink solution contained in the bioink cartridge (4) is ej
  • the pressure exerted by the bio-ink solution in the bio-ink cartridge (4) on the micro linear piston (3) is calculated through the strain in the movement of the micro linear piston (3) and the change in the current value drawn by the micro linear piston (3) and with an algorithmic software.
  • the micro linear piston (3) In order to insert the bioink cartridge (4), the micro linear piston (3) must be pulled back by means of the pull button (6). If a continuous forward or backward movement is desired for the micro linear piston (3), the push or pull buttons (5, 6) are kept pressed.
  • the LEDs (9) used in the invention have wavelengths of 360 nm, 405 nm and 445 nm and can be replaced with LEDs (9) having different wavelengths.
  • the control unit box (11 ) within the invention divides the electricity coming from the city network into two parts, one of which is used for the micro linear piston (3) and the other for the LEDs (9).
  • the heating and cooling units are also located in the control unit box (11 ).
  • the electrical energy required for the micro linear piston (3) is converted from 220V to 12V.
  • the voltage level is ranged between 0V and 12V.
  • the present micro linear piston (3) used in the invention has a movement speed of 0-5 mm/s and can be made to operate in a wider range.
  • the biopencil structure proposed by the invention is suitable for bioprinting at room temperature even without features such as heating/cooling system, infrared sensor (7), LCD display (2) and pressure measurement.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Manufacturing & Machinery (AREA)
  • Materials Engineering (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
EP23765135.1A 2022-06-13 2023-04-12 Extrusionsbasierter und tragbarer dreidimensionaler handbiodrucker Pending EP4313597A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR202209769 2022-06-13
PCT/TR2023/050343 WO2023244197A1 (en) 2022-06-13 2023-04-12 Extrusion-based and portable handheld three-dimensional bioprinter

Publications (1)

Publication Number Publication Date
EP4313597A1 true EP4313597A1 (de) 2024-02-07

Family

ID=89473496

Family Applications (1)

Application Number Title Priority Date Filing Date
EP23765135.1A Pending EP4313597A1 (de) 2022-06-13 2023-04-12 Extrusionsbasierter und tragbarer dreidimensionaler handbiodrucker

Country Status (1)

Country Link
EP (1) EP4313597A1 (de)

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