Methods and composition for the fabrication of 3d perfusable networks

Patent metadata

Field	Value
Publication number	US-2023398803-A1
Application number	US-202318142931-A
Country	US
Kind code	A1
Filing date	May 3, 2023
Priority date	May 4, 2022
Publication date	Dec 14, 2023
Grant date	—

Abstract

Methods and compositions for fabricating 3D perfusable networks are described. The methods utilize (1) printable compositions comprising gelatin microgels or Pluronic F-127, and crosslinking initiators; and (2) support materials comprising crosslinkable polymers and gelling agents. In some embodiments, the support material further comprises a co-initiator.

First claim

What is claimed is:

1 . A method for fabricating a 3D perfusable network, the method comprising:
(i) contacting a support material with an injection means, wherein the support material comprises a crosslinkable monomer or polymer and a gelling agent; (ii) injecting a printable composition into the support material using the injection means; wherein the printable composition comprises a sacrificial ink, and a crosslinking initiator; (iii) moving the injection means in a desired 3D shape wherein the injection means is continuously injecting the printable composition into the support material, and (iv) altering the temperature of the support material to melt the sacrificial ink.

2 . The method of claim 1 wherein the sacrificial ink comprises gelatin that melts at a temperature of from about 25° C. to about 37° C.

3 . The method of claim 1 , wherein the sacrificial ink comprises poloxamer 470 that melts at a temperature of from about 0° C. to about 10° C.

4 . The method of claim 1 , wherein the crosslinkable polymer is a photocrosslinking polymer selected from the group of gelatin methacryloyl (GelMA), hyaluronic acid methacrylate (HAMA), and poly(ethylene glycol) diacrylate (PEGDA); and the crosslinking initiator is LAP.

5 . The method of claim 4 , further comprising exposing the support material to ultraviolet radiation.

6 . The method of claim 1 , wherein the crosslinkable polymer is a small molecule crosslinkable monomer or polymer, selected from alginate and polyacrylamide.

7 . The method of claim 6 , wherein the crosslinking initiator is CaCl 2 or ammonium persulfate (APS).

8 . The method of claim 6 , wherein the support material comprises polyacrylamide, tetramethylethylenediamine (TEMED) and bis acrylamide.

9 . The method of claim 1 , wherein the crosslinkable polymer is an enzymatic crosslinking polymer selected from fibrinogen and gelatin.

10 . The method of claim 9 , wherein the crosslinking initiator is thrombin or transglutaminase.

11 . The method of claim 1 , wherein the gelling agent is aristoflex AVC.

12 . The method of claim 1 , wherein the 3D perfusable network comprises fused intersections.

13 . The method of claim 1 , wherein the 3D perfusable network comprises non-fused intersections.

14 . The method of claim 1 , wherein the exterior of the 3D perfusable network is smooth and continuous.

15 . The method of claim 1 , wherein the 3D perfusable network further comprises cells.

16 . The method of claim 1 , wherein the method produces a hollow 3D structure with a variable diameter, wherein the diameter varies from about 2000 μm to about 50 μm.

17 . The method of claim 1 , wherein the method produces a hollow 3D structure comprising angles from at least about 10° to at least about 180°.

18 . A composition comprising the printable composition of claim 1 .

19 . A composition, the composition comprising the 3D perfusable network of claim 1 .

20 . A kit, the kit comprising:
(i) the composition of claim 18 , and (ii) a support material comprising a crosslinkable polymer and a gelling agent.

Assignees

• Univ Leland Stanford Junior

Inventors

• Roth Julien G
• Shin Sungchul
• Seymour Alexis J
• Heilshorn Sarah C

Classifications

• B41M5/5254 Primary

  characterised by the use of polymers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. vinyl polymers · CPC title

• C09D11/03

  characterised by features other than the chemical nature of the binder · CPC title

• C09D11/04

  based on proteins · CPC title

• B41M5/5218 Primary

  characterised by inorganic additives, e.g. pigments, clays · CPC title

• C09D11/101

  Inks specially adapted for printing processes involving curing by wave energy or particle radiation, e.g. with UV-curing following the printing · CPC title