# US 11,299,705 B2 · System and method for creating tissue

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,299,705 B2
- Document ID: US11299705B2
- Status: Granted
- Kind: B2
- Application number: 15/805,790
- Filed: 2017-11-07
- Published: 2018-05-10
- Granted: 2022-04-12
- Earliest claimed: 2016-11-07
- Assignees: DEKA Products Limited Partnership
- Applicants: DEKA Products Limited Partnership
- Inventors: Christopher C. Langenfeld; David D. B. Cannan; Dirk A. van der Merwe; Dean Kamen; Jason A. Demers; Frederick Morgan; Timothy D. Moreau; Brian D. Tracey; Matthew Ware; Richard J. Lanigan; Michael A. Baker; David Blumberg, Jr.; Richard E. Gautney; Derek G. Kane; Dane Fawkes; Thomas J. Bollenbach; Michael C. Tilley; Stuart A. Jacobson; John F. Mannisto
- Web page: https://patentgrep.com/patent/US11299705B2

## CPC

- C12M 41/48: {Automatic or computerized control (automatic analysis G01N35/00)}
- A01N 1/143: for organ perfusion
- A61L 27/3895: {using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions}
- 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
- C12M 21/08: {for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00)}
- C12M 23/22: {Transparent or translucent parts (glassware for laboratory use B01L3/00)}
- C12M 23/38: {Caps; Covers; Plugs; Pouring means}
- C12M 25/02: {Membranes; Filters (filters or filtration in general B01D24/00-B01D41/00)}
- C12M 27/18: {Flow directing inserts}
- C12M 29/00: {Means for introduction, extraction or recirculation of materials, e.g. pumps (pumps per se F04B)}
- 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)}
- C12M 37/02: {Filters}
- C12M 41/12: {of temperature (controlling the temperature of chemical or physical processes B01J19/0013, heating or cooling apparatus for laboratory use B01L7/00)}
- C12M 41/40: {of pressure}
- C12M 41/46: {of cellular or enzymatic activity or functionality, e.g. cell viability}
- C12N 5/0018: {Culture media for cell or tissue culture (media for specific animal cell type C12N5/06)}
- C12N 5/0062: {General methods for three-dimensional culture}
- C12N 2533/00: Supports or coatings for cell culture, characterised by material
- C12N 2533/50: Proteins
- C12N 2533/90: Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
- 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}
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- 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)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A system and method for growing and maintaining biological material including producing a protein associated with the tissue, selecting cells associated with the tissue, expanding the cells, creating at least one tissue bio-ink including the expanded cells, printing the at least one tissue bio-ink in at least one tissue growth medium mixture, growing the tissue from the printed at least one tissue bio-ink, and maintaining viability of the tissue.

## Claims

### Claim 1

A system for automatically growing tissue comprising:
a controller providing commands to the system;
a first subsystem responding to the commands, the first subsystem producing dissociated cells associated with the tissue and growth medium associated with the dissociated cells;
a second subsystem responding to the commands, the second subsystem creating the tissue based at least on the dissociated cells and the growth medium;
a third subsystem responding to the commands, the third subsystem growing the created tissue into a pre-selected mature tissue;
a fourth subsystem responding to the commands, the fourth subsystem maintaining the viability of the pre-selected mature tissue, the fourth subsystem including:
a fifth subsystem responding to the commands, the fifth subsystem receiving the tissue from the second subsystem, the fifth subsystem transmitting viability and nutrition status of the tissue;
a sixth subsystem responding to the commands, the sixth subsystem receiving the viable tissue from the fifth subsystem, the sixth subsystem incubating the viable tissue received from the fifth subsystem, at least in the growth medium received from the first subsystem, supplements, diluent, and basal media, the sixth subsystem providing viable incubated tissue; and
a seventh subsystem enabling transport of the viable incubated tissue; and
a eighth subsystem responding to the commands, the eighth subsystem enabling transport of the viable mature tissue to a patient.

### Claim 2 (depends on 1)

The system as in claim 1 wherein the growth medium comprises indicators, support materials, gel, protein, and basal medium.

### Claim 3 (depends on 2)

The system as in claim 2 wherein the second subsystem creates the protein.

### Claim 4 (depends on 2)

The system as in claim 2 wherein the protein comprises commercially-available protein.

### Claim 5 (depends on 1)

The system as in claim 1 wherein the second subsystem comprises:
a ninth subsystem responding to the commands, the ninth subsystem receiving cells, the indicators, growth medium, and the support materials, the ninth subsystem creating a bio-ink;
a tenth subsystem responding to the commands, the tenth subsystem receiving the bio-ink, the tenth subsystem printing the bio-ink; and
a eleventh subsystem responding to the commands, the eleventh subsystem receiving the printed bio-ink, the eleventh subsystem receiving the growth medium from the first subsystem, the eleventh subsystem providing the tissue to the fourth subsystem.

### Claim 6 (depends on 1)

The system as in claim 1 wherein the controller comprises:
a feedback controller controlling the flow and composition of fluid to and through the tissue, the feedback controller communicating through the commands formatted according to a communications protocol, the feedback controller receiving sensed information from at least one sensor, the feedback controller basing the commands at least on the sensed information.

### Claim 7 (depends on 6)

The system as in claim 6 further comprising:
a ninth subsystem cleansing the fluid after the fluid has passed through the tissue and returning the fluid to the tissue.

### Claim 8 (depends on 5)

The system as in claim 5 wherein the tenth subsystem comprises:
a multi-dimensional printer printing the tissue into the cavity.

### Claim 9

A system for automatically growing tissue comprising:
a controller providing commands to the system;
a first subsystem responding to the commands, the first subsystem producing dissociated cells associated with the tissue and growth medium associated with the dissociated cells, the first subsystem including:
a second subsystem responding to the commands, the second subsystem creating disassociated cells based at least on incoming cells, viral vectors, and commercial protein, the second subsystem providing the disassociated cells to a fifth subsystem;
a third subsystem responding to the commands, the third subsystem creating the growth medium based at least on indicators, support materials, carbomer, basal media, and protein; and
a fourth subsystem responding to the commands, the fourth subsystem receiving the protein from the fifth subsystem and supplying the protein to the third subsystem;
the fifth subsystem responding to the commands, the fifth subsystem creating the tissue based at least on the dissociated cells and the growth medium;
a sixth subsystem responding to the commands, the sixth subsystem growing the created tissue into a pre-selected mature tissue;
a seventh subsystem responding to the commands, the seventh subsystem maintaining the viability of the pre-selected mature tissue; and
a eighth subsystem responding to the commands, the eighth subsystem enabling transport of the viable mature tissue to a patient.

### Claim 10

A system for automatically growing tissue comprising:
a controller providing commands to the system;
a first subsystem responding to the commands, the first subsystem producing dissociated cells associated with the tissue and growth medium associated with the dissociated cells;
a second subsystem responding to the commands, the second subsystem creating the tissue based at least on the dissociated cells and the growth medium;
a third subsystem responding to the commands, the third subsystem growing the created tissue into a pre-selected mature tissue;
a fourth subsystem responding to the commands, the fourth subsystem maintaining the viability of the pre-selected mature tissue; and
a fifth subsystem responding to the commands, the fifth subsystem enabling transport of the viable mature tissue to a patient;
a tissue enclosure housing the tissue, the tissue enclosure including:
a core including a cavity, the core having at least one monitoring area and at least one opening into the cavity, one of the at least one openings receiving the tissue, the core accommodating at least one material ingress and at least one material egress; and
at least one filter assembly operably coupled with the core;
wherein the tissue is confined within the cavity by the at least one filter assembly,
wherein the life of the tissue is maintained by the maintenance subsystem at least by fluid flowing through the cavity between the at least one material ingress and the at least one material egress, and
wherein the tissue is monitored through the at least one monitoring area.

### Claim 11 (depends on 10)

The system as in claim 10 further comprising:
at least one plenum operably coupled with the at least one filter assembly, the at least one plenum enabling the application of pressure to the fluid and to the tissue.

### Claim 12 (depends on 10)

The system as in claim 10 further comprising:
at least one heater maintaining the temperature of the tissue.

### Claim 13 (depends on 10)

The system as in claim 10 wherein the growth medium surrounds the tissue.

### Claim 14 (depends on 10)

The system as in claim 10 wherein the at least one filter assembly comprises:
at least one filter;
at least one filter support operably coupled with the at least one filter; and
at least one filter frame operably coupling the at least one filter and the at least one filter support with the at least one plenum.

### Claim 15 (depends on 10)

The system as in claim 10 further comprising:
a tissue enclosure top removably enclosing the tissue within the core.

### Claim 16 (depends on 10)

The system as in claim 10 wherein the at least one monitoring area comprises a transparent window.

### Claim 17

A system for automatically growing tissue comprising:
a controller providing commands to the system;
a first subsystem responding to the commands, the first subsystem producing dissociated cells associated with the tissue and growth medium associated with the dissociated cells;
a second subsystem responding to the commands, the second subsystem creating the tissue based at least on the dissociated cells and the growth medium;
a third subsystem responding to the commands, the third subsystem growing the created tissue into a pre-selected mature tissue;
a fourth subsystem responding to the commands, the fourth subsystem maintaining the viability of the pre-selected mature tissue; and
a fifth subsystem responding to the commands, the fifth subsystem enabling transport of the viable mature tissue to a patient;
a tissue enclosure housing the tissue, the tissue enclosure including:
an incoming chamber admitting a first material, the incoming chamber emitting the first material in response to a differential pressure within the tissue enclosure;
a core including a cavity, the core having at least one monitoring area and at least one opening into the cavity, the core accommodating at least one material ingress and at least one material egress, the core containing the tissue, the growth medium, and metabolism products from the tissue;
at least one first filtration zone operably positioned between the incoming chamber and the core, the filtration zone subjecting the first material to at least one filter having a first pore size based at least on the first material, the filtration zone emitting first filtered contents to the core based at least on the first material and the first pore size;
at least one second filtration zone operably coupled with the core, the at least one second filtration zone subjecting the first filtered material, the growth medium, the tissue, and the metabolism products to at least one filter having a second pore size based at least on the first filtered material, the growth medium, the tissue, and the metabolism products, the filtration zone emitting second filtered contents based at least on the first filtered material, the growth medium, the tissue, the metabolism products, and the second pore size; and
an effluent chamber admitting the second filtered contents, the effluent chamber managing the filtered contents,
wherein the tissue enters the cavity through the at least one opening, and
wherein the tissue is confined within the cavity by the at least one first filtration zone and the at least one second filtration zone, and
wherein the life of the tissue is maintained by the first material entering the cavity through the at least one material ingress and by the metabolism products exiting the cavity through the at least one material egress, and
wherein the tissue is monitored through the at least one monitoring area.

### Claim 18 (depends on 17)

The system as in claim 17 wherein the at least one opening enables printing of the tissue.

### Claim 19 (depends on 17)

The system as in claim 17 wherein the at least one monitoring area comprises:
a transparent window disposed opposite the at least one opening.

### Claim 20 (depends on 17)

The system as in claim 17 further comprising:
at least one mount button accommodating kinematic mounting of the tissue enclosure upon a tissue enclosure holder having corresponding mount wells.

### Claim 21

A system for automatically growing tissue comprising:
a controller providing commands to the system;
a first subsystem responding to the commands, the first subsystem producing dissociated cells associated with the tissue and growth medium associated with the dissociated cells the first subsystem including:
an organ scaffold hosting the tissue, the organ scaffold including:
a fluid cavity enabling receiving and emitting fluids into the interior of the organ scaffold, the fluid cavity including an inner surface and an outer surface, the inner surface providing a boundary for the received fluids;
a compliant wrapper operably coupled with the outer surface, the compliant wrapper enabling inflation and deflation of the fluid cavity;
at least one layer of fiber disposed upon the compliant wrapper, the at least one layer of fiber disposed in the shape of the tissue; and
a plurality of cells disposed upon the at least one layer of fiber, the plurality of cells being associated with the biology of the tissue;
a tube operably coupled with the organ scaffold, the tube providing a conduit between a fluid source and the organ scaffold; and
a chamber housing the organ scaffold, the chamber including at least one inlet and at least one outlet, the at least one inlet receiving fluids, the fluids maintaining viability of the tissue, the at least one outlet evacuating wastes from metabolism of the tissue;
a second subsystem responding to the commands, the second subsystem creating the tissue based at least on the dissociated cells and the growth medium;
a third subsystem responding to the commands, the third subsystem growing the created tissue into a pre-selected mature tissue;
a fourth subsystem responding to the commands, the fourth subsystem maintaining the viability of the pre-selected mature tissue;
a fifth subsystem responding to the commands, the fifth subsystem enabling transport of the viable mature tissue to a patient.

### Claim 22 (depends on 21)

The system as in claim 21 further comprising:
at least one pump operably coupled with the at least one inlet, the at least one pump pumping fluids into the chamber through the at least one inlet, the at least one pump enabling pressure to be applied to the fluids and the wastes, the at least pump enabling the movement of the fluids and the wastes through the chamber.