# US 11,305,480 B2 · Methods and apparatus for 3D printed hydrogel materials

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- Number: US 11,305,480 B2
- Document ID: US11305480B2
- Status: Granted
- Kind: B2
- Application number: 16/843,492
- Filed: 2020-04-08
- Published: 2020-07-23
- Granted: 2022-04-19
- Earliest claimed: 2016-01-28
- Assignees: 3D Systems, Inc.
- Applicants: 3D Systems, Inc.
- Inventors: Charles W. Hull
- Web page: https://patentgrep.com/patent/US11305480B2

## CPC

- A61L 27/52: Hydrogels or hydrocolloids
- A61L 27/24: Collagen
- A61L 27/38: {containing added animal cells (organs or tissue containing native cells A61L27/36)}
- B29C 35/0805: {using electromagnetic radiation}
- B29C 64/106: using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
- B29C 64/112: using individual droplets, e.g. from jetting heads
- B29C 64/129: characterised by the energy source therefor, e.g. by global irradiation combined with a mask
- B29C 64/188: involving additional operations performed on the added layers, e.g. smoothing, grinding or thickness control (surface shaping B29C59/00; after-treatment of articles without altering their shape B29C71/00)
- B29C 64/194: during lay-up
- B29C 64/35: Cleaning
- B29C 64/386: Data acquisition or data processing for additive manufacturing
- B29C 64/40: Structures for supporting 3D objects during manufacture and intended to be sacrificed after completion thereof
- B33Y 10/00: Processes of additive manufacturing
- B33Y 30/00: Apparatus for additive manufacturing; Details thereof or accessories therefor
- B33Y 70/00: Materials specially adapted for additive manufacturing
- B33Y 80/00: Products made by additive manufacturing
- C12M 21/00: {Bioreactors or fermenters specially adapted for specific uses (digesters for manure A01C3/023; apparatus for PCR B01L7/52; destroying or transforming solid waste B09B3/00; methods for genetic engineering C12N15/00, C12Q1/68; nucleic acid amplification reactions C12Q1/6844)}
- C12M 21/08: {for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00)}
- B29C 2035/0833: {using actinic light}
- B29K 2105/0061: {Gel or sol}
- B29K 2995/0056: Biocompatible, e.g. biopolymers or bioelastomers
- B29L 2031/7532: {Artificial members, protheses}
- 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 (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- 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 (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00)
- B33Y: 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
- 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}
- B29K: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR {MOULDS, } REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
- B29L: INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES

## Abstract

There is provided a 3D printing system, methods, and materials for the 3D printing of objects that include a cured hydrogel material, an uncured hydrogel material, and a support material. The cured hydrogel material may define a scaffold for organs or other biological structures. The 3D printing system selectively deposits the hydrogel material and support material, dries the hydrogel material, and selectively applies a catalyst to the hydrogel material to selectively cure the hydrogel material. Once the 3D printing has completed, the uncured hydrogel material may be drained and the support material may be melted or dissolved leaving a scaffold of cured hydrogel material that may be infused with living cells of the desired organ or biological structure.

## Claims

### Claim 1

A method of forming a biological scaffold configured to be infused with living cells, the method comprising:
(1) selectively jetting hydrogel material from one or more printheads onto a build platform according to electronic design data of the scaffold to form a layer of hydrogel having a first thickness of from about 25-30 micrometers;
(2) drying the layer of hydrogel to remove excess water, thereby reducing a thickness of the layer of hydrogel to a second thickness that is less than the first thickness;
(3) selectively imaging the dried layer of hydrogel to provide cured portions and uncured portions of the dried layer of hydrogel, the cured portions forming structures of the scaffold on the order of one micrometer; and
(4) repeating steps (1)-(3) a plurality of times to complete formation of the scaffold.

### Claim 2 (depends on 1)

The method of claim 1 wherein the one or more printheads are one or more ink jet printheads.

### Claim 3 (depends on 1)

The method of claim 1 wherein the hydrogel material being jetted comprises a hydrogel solubilized in a water-based solution.

### Claim 4 (depends on 3)

The method of claim 3 wherein the water-based solution includes the hydrogel solubilized in an acid.

### Claim 5 (depends on 4)

The method of claim 4 further comprising selectively depositing a buffer onto the layer of hydrogel so as to increase the pH of the water-based solution to a range between 6 and 8 such that the hydrogel material self-assembles into a gel.

### Claim 6 (depends on 4)

The method of claim 4 wherein the acid is acetic acid.

### Claim 7 (depends on 1)

The method of claim 1 wherein the hydrogel material being jetted has a viscosity in the range of 10.0 and 19.0 centipoise.

### Claim 8 (depends on 1)

The method of claim 1 wherein the hydrogel material being jetted includes one or more hydrogels selected from a list consisting of collagen type I, collagen type II, fibrillin, and elastin.

### Claim 9 (depends on 1)

The method of claim 1 wherein the second thickness is from about 0.8-1 micrometers.

### Claim 10 (depends on 1)

The method of claim 1 further comprising depositing support material for supporting the layer of hydrogel.

### Claim 11 (depends on 10)

The method of claim 10 wherein the support material is printed around a border of the layer of hydrogel.

### Claim 12 (depends on 11)

The method of claim 11 wherein repeated layers of the support material are printed around layers of the hydrogel to form a vat.

### Claim 13 (depends on 10)

The method of claim 10 wherein the support material includes a hydrocarbon wax.

### Claim 14 (depends on 10)

The method of claim 10 wherein the support material is a phase change support material not requiring curing by actinic radiation.

### Claim 15 (depends on 1)

The method of claim 1 wherein the biological scaffold is a lung scaffold.

### Claim 16

A method of forming a biological scaffold configured to be infused with living cells, the method comprising:
(1) forming a layer of hydrogel having a first thickness on a build platform, wherein said forming comprises jetting a water-based solution comprising a hydrogel material on the build platform and adjusting the pH of the water-based solution to cause the hydrogel material to self-assemble into a gel, and wherein the first thickness is from about 25-30 micrometers;
(2) drying the layer of hydrogel to remove excess water, thereby reducing a thickness of the layer of hydrogel to a second thickness that is less than the first thickness;
(3) selectively imaging the dried layer of hydrogel to provide cured portions and uncured portions of the dried layer of hydrogel, the cured portions forming structures of the scaffold on the order of one micrometer; and
(4) repeating steps (1)-(3) a plurality of times to complete formation of the scaffold.

### Claim 17 (depends on 16)

The method of claim 16 wherein adjusting the pH of the water-based solution is via addition of a buffer to the water-based solution.

### Claim 18 (depends on 17)

The method of claim 17 wherein the buffer is selectively deposited in areas of the build platform containing the water-based solution.

### Claim 19 (depends on 16)

The method of claim 16 wherein the biological scaffold is a lung scaffold.

### Claim 20 (depends on 16)

The method of claim 16 wherein the second thickness is from about 0.8-1 micrometers.
