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

Patent metadata

Field	Value
Publication number	US-10954489-B2
Application number	US-201414895912-A
Country	US
Kind code	B2
Filing date	Jun 4, 2014
Priority date	Jun 4, 2013
Publication date	Mar 23, 2021
Grant date	Mar 23, 2021

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

The invention claimed is:

1. A method for in vitro simulation of a hepatic function on a material, comprising:
suspending biological hepatic-functioning particles (bHFPs) in a prepolymer and photopolymerizing the prepolymer by bioprinting using maskless dynamic optical projection stereolithography (DOPsL) to form a biomimetic 3D polymer scaffold comprising a matrix of liver-like lobules encapsulating the bHFPs therein, the matrix comprising a plurality of layers of honeycomb patterns with channels and central conduits;
printing supportive cells onto the matrix using DOPsL to spatially localize the supportive cells to align in the channels and central conduits to spatially control cell-cell interactions between the bHFPs and the supportive cells; and
exposing the matrix to the material, wherein the matrix mimics a tissue with bHFPs and supportive cells in three dimensions.

2. The method of claim 1 , wherein 3D bioprinting comprises using dynamic optical projection stereolithography.

3. The method of claim 1 , wherein each liver-like lobule is hexagonal in structure.

4. The method of claim 1 , wherein the bHFPs are hepatic progenitor cells (HPCs) derived from human induced pluripotent stem cells (iPSCs).

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

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

7. The method of claim 1 , wherein the supportive cells comprise mesenchymal stem cells (MSCs).

8. The method of claim 1 , wherein the supportive cells comprise endothelial cells (ECs).

9. The method of claim 1 , wherein the prepolymer comprises a methacrylated hyaluronic acid (MeHA).

10. The method of claim 1 , wherein the prepolymer comprises a gelatin methacrylate (GelMA).

11. The method of claim 10 , wherein the prepolymer further comprises polymer nanoparticles.

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

13. The method of claim 1 , wherein the prepolymer comprises poly(ethylene glycol) diacrylate hydrogel (PEGDA).

14. The method of claim 11 , wherein the polymer nanoparticles are chemically tethered to the 3D polymer scaffold.

15. The method of claim 1 , wherein the hepatic function comprises detoxification.

16. The method of claim 1 , wherein the bHFPs are encapsulated within the center portions and the supportive cells are disposed in the channels.

17. The method of claim 16 , wherein the bHFPs are co-cultured with additional supportive cells prior to encapsulation into the center conduits.

18. The method of claim 1 , wherein the supportive cells comprise endothelial cells (ECs) and mesenchymal stem cells (MSCs).

19. The method of claim 18 , wherein the ECs are bioprinted into patterns configured to mimic vascular structures.

20. A method for simulation of a hepatic function on a material, comprising:
suspending biological hepatic-functioning particles (bHFPs) in a prepolymer solution and photopolymerizing the prepolymer by bioprinting using maskless dynamic optical projection stereolithography (DOPsL) to form a biomimetic 3D polymer scaffold comprising a matrix of hexagonal liver-like lobules encapsulating the bHFPs therein, each lobule having a center portion and a channel surrounding the center portion, wherein the bHFPs are encapsulated within the center portions;
printing supportive cells onto the matrix using DOPsL to spatially localize the supportive cells to align in the channels and in conduits within the central portions to spatially control cell-cell interactions between the bHFPs and the supportive cells;
exposing the matrix to the material, wherein the matrix mimics a tissue with bHFPs and supportive cells in three dimensions.

21. The method of claim 20 , wherein the co-culture comprises a tri-culture, and wherein the supportive cells comprise endothelial cells (ECs) and mesenchymal stem cells (MSCs).

22. The method of claim 20 , wherein the bHFPs are co-cultured with additional supportive cells prior to encapsulation into the center portions.

23. The method of claim 20 , wherein the matrix comprises a honeycomb arrangement.

24. The method of claim 20 , wherein the bHFPs are hepatic progenitor cells (HPCs) derived from human induced pluripotent stem cells (iPSCs).

25. The method of claim 24 , wherein the iPSCs are patient specific.

26. The method of claim 25 , wherein the patient specific iPSCs are from subjects having a liver-affecting disease.

27. The method of claim 20 , wherein the supportive cells comprise mesenchymal stem cells (MSCs).

28. The method of claim 20 , wherein the prepolymer further comprises polymer nanoparticles.

Assignees

• Univ California
• Nat Institutes Of Health Nih U S Dept Of Health And Human Services Dhhs

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

• C12N5/0671 Primary

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

• C12N2533/30

  Synthetic polymers · CPC title

• C12N2533/54

  Collagen; Gelatin · CPC title