IP Library › Granted Patent US 11,324,701
Granted Patent B2
US 11,324,701 · App. 16/468,390 · Granted May 10, 2022

Method for freeze-drying cells in a hydrogel comprising nanofibrillar cellulose and freeze-dried cells in an aerogel comprising nanofibrillar cellulose

Inventors: Heli Paukkonen (Espoo, FI); Vili-Veli Auvinen (Espoo, FI); Marjo Yliperttula (Espoo, FI); Patrick Laurén (Espoo, FI); Arto Urtti (Kuopio, FI); Timo Laaksonen (Hyvinkää, FI); Arto Merivaara (Helsinki, FI); Tiina Hakkarainen (Vantaa, FI); Outi Monni (Espoo, FI); Anne Mäkelä (Espoo, FI); Petter Somersalo (Helsinki, FI); Piia-Riitta Karhemo (Nummela, FI); Heikki Joensuu (Espoo, FI); Raili Koivuniemi (Vantaa, FI); Kari Luukko (Helsinki, FI); Markus Nuopponen (Helsinki, FI)
Assignee: UPM-KYMMENE CORPORATION
A61K9/19A01N1/0221A01N1/0231A61K9/06A61K47/10A61K47/26A61K47/38C12N5/0062C12N5/0693F26B5/06C12N2513/00C12N2533/78
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Quick Facts
Patent No.
US 11,324,701
App. No.
16/468,390
Granted
May 10, 2022
Kind
B2
Abstract

The present disclosure provides a method for freeze-drying cells in a hydrogel comprising nanofibrillar cellulose, the method comprising providing a hydrogel comprising nanofibrillar cellulose, providing cells, combining the cells and the hydrogel comprising nanofibrillar cellulose to form a cell system, and freeze drying the cell system to obtain dried cells in a hydrogel comprising nanofibrillar cellulose. The present disclosure also provides a freeze-dried hydrogel comprising nanofibrillar cellulose and cells.

Claims (32)

1. A method for freeze-drying cells in a hydrogel comprising nanofibrillar cellulose, the method comprising:

providing a hydrogel comprising nanofibrillar cellulose,

providing cells,

combining the cells and the hydrogel comprising nanofibrillar cellulose to form a cell system, and

freeze drying the cell system to obtain dried cells in an aerogel comprising nanofibrillar cellulose;

wherein the cells are eukaryotic cells.

2. The method of claim 1 , further comprising providing one or more cryoprotective agent(s) and/or one or more lyoprotective agent(s), and adding the one or more cryoprotective agent(s) and/or one or more lyoprotective agent(s) to the cell system.

3. The method of claim 1 , further comprising culturing the cells in the cell system.

4. The method of claim 1 , wherein the cells are mammalian cells.

5. The method of claim 4 , wherein the cells are cancer cells.

6. The method of claim 2 , wherein the one or more cryoprotective and/or lyoprotective agent(s) is selected from trehalose, glycerol, and polyethylene glycol.

7. The method of claim 2 , wherein the one or more cryoprotective and/or lyoprotective agent(s) comprise trehalose and glycerol.

8. The method of claim 1 , wherein the nanofibrillar cellulose, when dispersed in water, provides a Brookfield viscosity of at least 2000 mPa·s, measured at 20° C.±1° C., at a consistency of 0.8% (w/w) and at 10 rpm.

9. The method of claim 1 , wherein the concentration of the nanofibrillar cellulose in the hydrogel before the freeze-drying is in the range of 0.1-10% (w/w).

10. The method of claim 1 , wherein the nanofibrillar cellulose is selected from anionically modified nanofibrillar cellulose, cationically modified nanofibrillar cellulose and unmodified nanofibrillar cellulose, and TEMPO oxidized nanofibrillar cellulose.

11. The method of claim 1 , wherein the freeze drying is continued until the dried hydrogel has a moisture content 10% (w/w) or less.

12. The method of claim 1 , wherein the freeze drying comprises first lowering the temperature of the cell system to at least to −20° C., and after that applying lowered pressure to remove water from the cell system.

13. The method of claim 1 , wherein the nanofibrillar cellulose has a number average fibril diameter of 1 to 100 nanometers.

14. The method of claim 1 , wherein the nanofibrillar cellulose, when dispersed in water, provides a zero-shear viscosity of 5000-50000 Pa·s, and a yield stress of 3-15 Pa, determined by rotational rheometer at a consistency of 0.5% (w/w) in aqueous medium at 22° C.

15. A freeze-dried aerogel comprising freeze-dried nanofibrillar cellulose and freeze-dried cells, wherein the moisture content of the freeze-dried aerogel is 10% or less, wherein the freeze-dried cells are eukaryotic cells.

16. The freeze-dried aerogel of claim 15 , further comprising one or more cryoprotective agent(s) and/or one or more lyoprotective agent(s).

17. The freeze-dried aerogel of claim 15 , wherein the freeze-dried cells are mammalian cells.

18. The freeze-dried aerogel of claim 17 , wherein the cells are cancer cells.

19. The freeze-dried aerogel of claim 16 , wherein the one or more cryoprotective and/or lyoprotective agent(s) is selected from trehalose, glycerol, and polyethylene glycol.

20. The freeze-dried aerogel of claim 16 , wherein the one or more cryoprotective and/or lyoprotective agent(s) agents comprise trehalose and glycerol.

21. The freeze-dried aerogel of claim 15 , wherein the content of the cells in the freeze-dried aerogel is in the range of 0.1-65% (w/w).

22. The freeze-dried aerogel of claim 16 , wherein the content of the one or more cryoprotective and/or lyoprotective agent(s) is in the range of 1-10% (w/w) and/or the content of the trehalose is in the range of 0.5-50% (w/w) in the freeze-dried aerogel.

23. The freeze-dried aerogel of claim 15 , wherein the nanofibrillar cellulose, when dispersed in water, provides a Brookfield viscosity of at least 2000 mPa·s, measured at 20° C.±1° C., at a consistency of 0.8% (w/w) and at 10 rpm.

24. The freeze-dried aerogel of claim 15 , wherein the nanofibrillar cellulose is selected from anionically modified nanofibrillar cellulose, cationically modified nanofibrillar cellulose and unmodified nanofibrillar cellulose, and TEMPO oxidized nanofibrillar cellulose.

25. The freeze-dried aerogel of claim 15 , obtained with the method of claim 1 .

26. The freeze-dried aerogel of claim 15 , wherein the freeze-dried nanofibrillar cellulose has a number average fibril diameter of 1 to 100 nanometers.

27. The freeze-dried aerogel of claim 15 , wherein the nanofibrillar cellulose, when dispersed in water, provides a zero-shear viscosity of 5000-50000 Pa·s, and a yield stress of 3-15 Pa, determined by rotational rheometer at a consistency of 0.5% (w/w) in aqueous medium at 22° C.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 19, 2019
From: PAUKKONEN, HELI; AUVINEN, VILI-VELI; YLIPERTTULA, MARJO; LAURÉN, PATRICK; URTTI, ARTO; LAAKSONEN, TIMO; MERIVAARA, ARTO; HAKKARAINEN, TIINA; MONNI, OUTI; MÄKELÄ, ANNE; SOMERSALO, PETTER; KARHEMO, PIIA-RIITTA; JOENSUU, HEIKKI; KOIVUNIEMI, RAILI; LUUKKO, KARI; NUOPPONEN, MARKUS
To: UPM-KYMMENE CORPORATION
Reel/Frame 049515/0485 →
Priority Claims (1)
EP 16397537 · Dec 15, 2016 · regional
Continuity (1)
Related Publication 20210127663A1 · May 6, 2021
Cited By (1)
US 12,359,870