Liver-mimetic device and method for simulation of hepatic function using such device

Patent metadata

Field	Value
Publication number	US-2016298087-A1
Application number	US-201414895912-A
Country	US
Kind code	A1
Filing date	Jun 4, 2014
Priority date	Jun 4, 2013
Publication date	Oct 13, 2016
Grant date	—

Abstract

A liver-mimetic device and method include a 3D polymer scaffold having a matrix of liver-like lobules with hepatic-functioning particles encapsulated within the lobules. In some embodiments, each liver-like lobule is hexagonal in structure and the matrix is in a honeycomb arrangement. In some embodiments, the hepatic-functioning particles are hepatic progenitor cells. In other embodiments, the hepatic-functioning particles are polymer nanoparticles adapted to capture pore-forming toxins.

First claim

1 . A liver-mimetic device comprising:
a 3D polymer scaffold comprising a matrix of liver-like lobules; and hepatic-functioning particles encapsulated within the lobules.

2 . The device of claim 1 , wherein each liver-like lobule is hexagonal in structure and the matrix comprises a honeycomb arrangement.

3 . The device of claim 1 , wherein the hepatic-functioning particles comprise hepatic progenitor cells.

4 . The device of claim 3 , wherein the hepatic progenitor cells are derived from human induced pluripotent stem cells (iPSCs).

5 . The device of claim 4 , wherein the iPSCs are patient specific.

6 . The device of claim 5 , wherein the patient specific iPSCs are from subjects having a liver-affecting disease.

7 . The device of claim 3 , wherein the hepatic-functioning particles further comprise mesenchymal stem cells.

8 . The device of claim 3 , wherein the hepatic-functioning particles further comprise endothelial cells.

9 . The device of claim 3 , wherein the 3D polymer scaffold comprises a methacrylated hyaluronic acid prepolymer polymerized using dynamic optical projection stereolithography.

10 . The device of claim 3 , wherein the 3D polymer scaffold comprises a gelatin methacrylate prepolymer polymerized using dynamic optical projection stereolithography.

11 . The device of claim 1 , wherein the hepatic-functioning particles comprise polymer nanoparticles adapted to capture pore-forming toxins.

12 . The device of claim 11 , wherein the polymer nanoparticles comprise polydiacetylene.

13 . The device of claim 11 , wherein the 3D polymer scaffold comprises poly(ethylene glycol) diacrylate hydrogel polymerized using dynamic optical projection stereolithography.

14 . The device of claim 13 , wherein the polymer nanoparticles are chemically tethered to the 3D polymer scaffold.

15 - 29 . (canceled)

30 . A method for in vitro simulation of a hepatic function on a material, comprising:
photopolymerizing a prepolymer to form a 3D polymer scaffold comprising a matrix of liver-like lobules; encapsulating hepatic-functioning particles within the matrix; and exposing the matrix and hepatic-functioning particles to the material.

31 . The method of claim 30 , wherein the step of photopolymerizing comprises using dynamic optical projection stereolithography.

32 . The method of claim 30 , wherein each liver-like lobule is hexagonal in structure and the matrix comprises a honeycomb arrangement.

33 . The method of claim 30 , wherein the hepatic-functioning particles comprise hepatic progenitor cells.

34 . The method of claim 33 , wherein the hepatic progenitor cells are derived from human induced pluripotent stem cells (iPSCs).

35 . The method of claim 34 , wherein the iPSCs are patient specific.

36 . The method of claim 35 , wherein the patient specific iPSCs are from subjects having a liver-affecting disease.

37 . The method of claim 33 , wherein the hepatic-functioning particles further comprise mesenchymal stem cells.

38 . The method of claim 33 , wherein the hepatic-functioning particles further comprise endothelial cells.

39 . The method of claim 33 , wherein the prepolymer comprises a methacrylated hyaluronic acid.

40 . The method of claim 33 , wherein the prepolymer comprises a gelatin methacrylate.

41 . The method of claim 40 , wherein the hepatic-functioning particles comprise polymer nanoparticles adapted to capture pore-forming toxins.

42 . The method of claim 41 , wherein the polymer nanoparticles comprise polydiacetylene.

43 . The method of claim 41 , wherein the prepolymer comprises poly(ethylene glycol) diacrylate hydrogel.

44 . The method of claim 43 , wherein the polymer nanoparticles are chemically tethered to the 3D polymer scaffold.

45 . The method of claim 30 , wherein the hepatic function comprises detoxification and the material is blood or blood cells.

Assignees

• Univ California

Inventors

• Qu Xin
• Gou Maling
• Zhu Wei
• Chen Shaochen

Classifications

• C12N2533/80

  Hyaluronan · CPC title

• C12N2506/45

  from artificially induced pluripotent stem cells · CPC title

• C12N2533/54

  Collagen; Gelatin · CPC title

• C12N5/0671 Primary

  Three-dimensional culture, tissue culture or organ culture; Encapsulated cells · CPC title

• C12N2533/30

  Synthetic polymers · CPC title