Extruded hydrogel tubes and coaxial fibers and applications thereof

Patent metadata

Field	Value
Publication number	US-12138843-B2
Application number	US-201917251735-A
Country	US
Kind code	B2
Filing date	Jun 13, 2019
Priority date	Jun 13, 2018
Publication date	Nov 12, 2024
Grant date	Nov 12, 2024

Abstract

Methods of fabricating a hydrogel tube, and related systems, employ extrusion of a cross-linkable hydrogel solution from an annular outer nozzle of a nozzle assembly to form a cross-linkable hydrogel tube. The cross-linkable hydrogel tube is cured to form a cross-linked hydrogel tube. A second hydrogel solution can be coextruded via the axial inner nozzle to form an inner hydrogel filament coaxially positioned within the cross-linkable hydrogel tube. The cross-linked hydrogel tube can be functionalized with collagen to enable cell adhesion, and cells can be cultured on the luminal surfaces of these tubes to yield tubular endothelial layers. A 3D printed coaxial nozzle can be used to fabricate biofunctional tubular conduits that can be utilized for engineering in vitro models of tubular biological structures.

First claim

What is claimed is:

1. A method of fabricating a hydrogel tube, the method comprising:
extruding a hollow cylindrical sheet of a first cross-linkable hydrogel solution from a bell nozzle of a nozzle assembly at room temperature to form a cross-linkable hydrogel tube; and
curing the cross-linkable hydrogel tube to form a cross-linked hydrogel tube, wherein curing the cross-linkable hydrogel tube comprises photo-curing the cross-linkable hydrogel tube by exposure to UV light.

2. The method of claim 1 , wherein:
the nozzle assembly further comprises an axial inner nozzle circumscribed by the bell nozzle; and
the method further comprises coextruding a second hydrogel solution via the axial inner nozzle while extruding the first cross-linkable hydrogel solution to form an inner hydrogel filament coaxially positioned within the cross-linkable hydrogel tube.

3. The method of claim 2 , further comprising:
prior to coextruding the second hydrogel solution,
cooling the second hydrogel solution to cause the second hydrogel solution to transition from a gel state to a sol state;
loading the second hydrogel solution in the sol state into a second pneumatic syringe barrel; and
causing the second hydrogel solution in the second pneumatic syringe barrel to transition from the sol state to the gel state.

4. The method of claim 2 , further comprising:
while coextruding the second hydrogel solution, increasing a wall thickness of the cross-linkable hydrogel tube by increasing a first pressure of extrusion of the first cross-linkable hydrogel solution from the bell nozzle.

5. The method of claim 2 , further comprising:
while coextruding the second hydrogel solution, increasing a luminal diameter of the cross-linkable hydrogel tube by increasing a second pressure of extrusion of the second hydrogel solution from the axial inner nozzle.

6. The method of claim 2 , wherein the inner hydrogel filament comprises poloxamer 407, poly(alkyl glycidyl ether)s hydrogels, or other shear-thinning hydrogel, or other shear-thinning and cross-linkable hydrogel.

7. The method of claim 1 , further comprising:
prior to extruding the first cross-linkable hydrogel solution,
cooling the first cross-linkable hydrogel solution to 1-20 degrees Celsius;
loading the cooled first cross-linkable hydrogel solution into a first pneumatic syringe barrel fluidly connected with the bell nozzle; and
warming the first cross-linkable hydrogel solution to between 18-50 degrees Celsius.

8. A method of fabricating a hydrogel tube, the method comprising:
cooling a first hydrogel solution to a first temperature of less than or equal to 20 degrees Celsius;
loading the first hydrogel solution into a first pneumatic syringe barrel;
cooling a second hydrogel solution to a second temperature of less than or equal to 20 degrees Celsius;
loading the second hydrogel solution into a second pneumatic syringe barrel;
warming the first hydrogel solution within the first pneumatic syringe barrel to a third temperature that is greater than the first temperature;
warming the second hydrogel solution within the second pneumatic syringe barrel to a fourth temperature that is greater than the second temperature;
attaching the first pneumatic syringe barrel to a first inlet of a concentric nozzle assembly, the first inlet being fluidly connected with an annular nozzle outlet of the concentric nozzle assembly;
attaching the second pneumatic syringe barrel to a second inlet of the concentric nozzle assembly, the second inlet being fluidly connected with an axial nozzle outlet of the concentric nozzle assembly that is circumscribed by the annular nozzle outlet;
coextruding the first hydrogel solution from the annular nozzle outlet and the second hydrogel solution from the axial nozzle outlet to form a coaxial hydrogel filament comprising a cross-linkable hydrogel tube surrounding an inner support hydrogel filament;
curing the cross-linkable hydrogel tube to form a durable hydrogel tube, wherein curing the cross-linkable hydrogel tube comprises photo-curing the cross-linkable hydrogel tube by exposure to UV light; and
removing the inner support hydrogel filament from the durable hydrogel tube.

9. The method of claim 8 wherein the first hydrogel solution comprises at least one of poloxamer 407-DMA, poloxamer 407-UDM, poloxamer 407-UUDM, or poloxamer 407-UDA polymers dissolved in an aqueous solution at a concentration of 20-35% weight percent.

10. The method of claim 8 wherein the first temperature is less than or equal to 6 degrees Celsius.

11. The method of claim 8 wherein the second temperature is less than or equal to 6 degrees Celsius.

12. The method of claim 8 , wherein the inner support hydrogel filament comprises poloxamer 407, poly(alkyl glycidyl ether)s hydrogels, or other shear-thinning hydrogel, or other shear-thinning and cross-linkable hydrogel.

Assignees

• Univ Washington

Inventors

• Nelson Alshakim
• Millik Siyami
• Smith Patrick
• Karis Dylan
• Theberge Ashleigh
• Dostie Ashley

Classifications

• C12M25/14

  Scaffolds; Matrices (in general C12N5/0068) · CPC title

• C12M23/06

  Tubular (C12M23/08, C12M23/16 take precedence) · CPC title

• B29K2105/258

  Tubular · CPC title

• B29K2105/243

  Partially cured · CPC title

• B29K2105/0061

  Gel or sol · CPC title