Methods, devices, and systems for the fabrication of materials and tissues utilizing electromagnetic radiation

• US 10,512,552 B2
• Filed: 03/25/2015
• Issued: 12/24/2019
• Est. Priority Date: 03/25/2014
• Status: Active Grant

• Current Assignee: 3D Systems, Inc. (3D Systems Corporation)
• Original Assignee: BioBots, Inc.
• Inventors: Solorzano, Ricardo D., Hashmi, Sohaib K., Cabrera, Daniel
• Primary Examiner(s): Sultana, Nahida
• Application Number:
  US15/128,632
• Publication Number:
  US 20170172765A1
• Time in Patent Office: 1,735 Days
• CPC Class Codes: A61F 2/5044 Designing or manufacturing processes
• CPC Class Codes: A61F 2002/505 using CAD-CAM techniques or NC-techniques
• CPC Class Codes: A61L 2430/14 for ear reconstruction or ear implants, e.g. implantable hearing aids
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: B29C 64/112 using individual droplets, e.g. from jetting heads
• CPC Class Codes: B29C 64/20 Apparatus for additive manufacturing; Details thereof or accessories therefor
• CPC Class Codes: B29C 64/255 Enclosures for the building material, e.g. powder containers
• CPC Class Codes: B29C 64/264 Arrangements for irradiation
• CPC Class Codes: B29C 64/295 Heating elements
• CPC Class Codes: B29K 2071/02 Polyalkylene oxides, e.g. PEO, i.e. polyethylene oxide, or derivatives thereof
• CPC Class Codes: B29K 2995/0056 Biocompatible, e.g. biopolymers or bioelastomers
• CPC Class Codes: B29L 2031/7532 Artificial members, protheses
• CPC Class Codes: B33Y 70/00 Materials specially adapted for additive manufacturing
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: B41J 2/04 generating single droplets or particles on demand
• CPC Class Codes: B41J 2002/041 Electromagnetic transducer
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 33/00 Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus chemical or physical laboratory apparatus in general B01L, devices for taking cell samples A61B10/0045, withdrawing or distributing predetermined quantities of fluid B01L99/00
• CPC Class Codes: C12M 33/04 by injection or suction, e.g. using pipettes, syringes, needles pipettes in general B01L3/02
• CPC Class Codes: C12N 2513/00 : 3D culture
• CPC Class Codes: C12N 2533/30 : Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 5/0062 : General methods for three-dimensional culture
• CPC Class Codes: C12N 5/0662 : Stem cells

Abstract

The present invention provides a three-dimensional bioprinter for fabricating cellular constructs such as tissues and organs using electromagnetic radiation (EMR) at or above 405 nm. The bioprinter includes a material deposition device comprising a cartridge for receiving and holding a composition which contains biomaterial that cures after exposure to EMR. The bioprinter also includes an EMR module that emits EMR at a wavelength of about 405 nm or higher. Also provided is a bioprinter cartridge which contains cells and a material curable at a wavelength of about 405 nm or greater. The cells are present in a chamber and are extruded through an orifice to form the cellular construct.

Claims

1. A three-dimensional bioprinter comprising:

a material deposition device comprising;

a cartridge for receiving and holding a composition comprising biomaterial that cures after exposure to electromagnetic radiation (EMR) at or above 405 nm, and

an extruder configured to engage with the cartridge and extrude the composition;

a receiving plate positioned below the cartridge configured to receive the composition; and

an EMR module configured to emit EMR at a wavelength of about 405 nm or higher, wherein the EMR module is integrated with the cartridge and configured to emit EMR towards at least one of the receiving plate and the cartridge.

2. The bioprinter of claim 1, wherein the material deposition device is configured to extrude simultaneously as the EMR module emits the EMR.

3. The bioprinter of claim 1, wherein the EMR module is configured to emit EMR for about 1 to about 5 seconds.

4. The bioprinter of claim 1, wherein the extruder comprises a syringe, capillary tube, or micropipette.

5. The bioprinter of claim 1, wherein said bioprinter comprises a first opening which permits insertion of said cartridge and a second opening which permits a portion of said cartridge to exit said bioprinter.

6. The bioprinter of claim 5, wherein said first opening is about 1 μ

m to about 10 cm and said second opening is about 1 μ

m to about 10 cm.

7. The bioprinter of claim 5, wherein said cartridge has a capacity of about 1 μ

L to about 100 mL and diameter of about 1 μ

m to about 10 cm.

8. The bioprinter of claim 1, wherein said cartridge houses dispensing means contains comprising a needle having a luminal diameter of about 10μ

to about 5 cm.

9. The bioprinter of claim 5, further comprising adhesive foil over said second opening.

10. The bioprinter of claim 1, wherein said EMR module is adjacent to or houses said cartridge.

11. The bioprinter of claim 1, wherein said EMR module comprises an attenuation filter which lowers or raises the intensity of the EMR emittance.

12. The bioprinter of claim 1, further comprising a printer stage.

13. The bioprinter of claim 1, further comprising a temperature means for adjusting the temperature of said bioprinter to about −

10 to about 300°

C.

14. The bioprinter of claim 1, wherein said composition is dispensed using pressure or electrical current, wherein said pressure is generated using a piston, compressed gas, hydraulics, or any combination thereof.

15. The bioprinter of claim 1, wherein said EMR module exposes said composition to EMR of a wavelength of about 405 nm or greater prior to, during, or after dispersion.

16. The bioprinter of claim 1, comprising two or more cartridges.

17. The bioprinter of claim 1, wherein said receiving plate is leveled to 0°

relative to the flat bottom of said cartridge.

18. The bioprinter of claim 1, further comprising a computer module including at least one of a processor and a non-transitory computer readable storage media encoded with computer readable program code configured to operate the bioprinter.

19. The bioprinter of claim 1, wherein said biomaterial comprises cells.

20. The bioprinter of claim 1, wherein said composition further comprises an extrusion agent which is curable at a wavelength of about 405 nm or greater, a photo-initiator, viscosity agent, or biocompatible agent.

21. The bioprinter of claim 20, wherein said extrusion agent is a polyoxyalkylene, diacrylate, methacrylate, norbornene, gelatin, methacrylate, methacrylated hyaluronic acid, hydroxyethyl-methacrylate-derivatized-dextran, p(HPMAm-lactate)-PEG, gold nanorods, carbon nanotubes, collagen, polyethylene oxide, poly-caprolactone, poly(L)-lactic acid, or any combination thereof.

22. The bioprinter of claim 20, wherein said photo-initiator is lithium phenyl-2,4,6-trimethylbenzoylphosphinate or one or more of the following:

23. The bioprinter of claim 20, wherein said viscosity agent is poly(ethylene oxide), gelatin, Pluronic F-127, hyaluronic acid, or any combination thereof.

24. The bioprinter of claim 1, wherein said composition further comprises a wetting agent, antioxidant, agent that inhibits cell death, an agent that encourages cell adhesion, cell-binding factors, or any combination thereof.

25. The bioprinter of claim 24, wherein said cell-binding factor is fibronectin, a lectin, a cadherin, a claudin, laminin, or any combination thereof.

26. The bioprinter of claim 1, wherein said composition is dispensed with an accuracy of about ±

50 p.m on one or more axis.