Hydrogel constructs using stereolithography

• US 7,780,897 B2
• Filed: 04/22/2005
• Issued: 08/24/2010
• Est. Priority Date: 04/22/2005
• Status: Active Grant

• Current Assignee: Keck Graduate Institute, Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Keck Graduate Institute, Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Medina, Francisco, Elkins, Christopher, Ochoa, Luis, Wicker, Ryan, Arcaute, Karina, Mann, Brenda
• Primary Examiner(s): Tentoni; Leo B
• Application Number:
  US10/907,984
• Publication Number:
  US 20060237880A1
• Time in Patent Office: 1,950 Days
• Field of Search: 264/233, 264/236, 264/401
• US Class Current: 264/401
• CPC Class Codes: B29C 64/106 using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
• CPC Class Codes: B29C 64/124 using layers of liquid which are selectively solidified
• CPC Class Codes: B29L 2031/7532 Artificial members, protheses
• CPC Class Codes: B33Y 10/00 Processes of additive manufacturing
• CPC Class Codes: B33Y 30/00 Apparatus for additive manufacturing; Details thereof or accessories therefor
• CPC Class Codes: B33Y 70/00 Materials specially adapted for additive manufacturing
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068
• CPC Class Codes: Y10T 428/24322 Composite web or sheet

Abstract

A preferred embodiment of the present invention provides a method and system for building cost-efficient biocompatible hydrogel constructs using stereolithography. Hydrogel constructs may be used in, for example, multi-lumen nerve regeneration conduits and other tissue engineering scaffolds with embedded channel architecture that facilitate tissue regeneration through possible incorporation of precisely located bioactive agents, cells, and other desired inert and/or active chemical agents and devices. Another preferred embodiment of the present invention provides a method of fabricating a hydrogel construct comprising: solidifying a first solution into a first construct layer with a first energy dosage using stereolithography, the first solution comprising: a first polymer; and a first photoinitiator, wherein the first polymer and first photoinitiator are of a first concentration.

Claims

1. A method of fabricating a hydrogel construct comprising:

solidifying a first solution into a first hydrogel construct layer with a first energy dosage using stereolithography, the first solution comprising;

a first hydrogel polymer having a first polymer concentration; and

a first photoinitiator having a first photoinitiator concentration;

where the first polymer concentration, first photoinitiator concentration, and first energy dosage are configured such that the cure depth of the first solution is less than or equal to two millimeters; and

forming a second hydrogel construct layer using stereolithography.

2. The method of claim 1, wherein forming the second construct layer comprises solidifying a second solution into a second hydrogel construct layer, the second solution being different than the first solution.

3. The method of claim 1, wherein the first hydrogel polymer is a derivative of poly(ethylene glycol).

4. The method of claim 3, wherein the derivative of poly(ethylene glycol) has a weight average molecular weight between about 1,000 and about 10,000.

5. The method of claim 1, wherein the first hydrogel polymer is selected from the group consisting of natural polymers, synthetic polymers and any combination thereof.

6. The method of claim 1, wherein the first photoinitiator is a UV photoinitiator.

7. The method of claim 1, wherein the first photoinitiator is selected from the group consisting of:

2-hydroxy-2-methyl-1 phenyl-1-propanone, 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone, 2,2-dimethoxy-2-phenyl-acetophenone, and any combination thereof.

8. The method of claim 1, wherein the first photoinitiator is a visible light photoinitiator.

9. The method of claim 1, wherein the first solution further comprises one or more materials selected from the group consisting of:

biocompatible media, water, a buffer, phosphate-buffered saline, cell culture media, and any combination thereof.

10. The method of claim 1, wherein the first solution has a pH of about 7.0 to about 7.8.

11. The method of claim 1, wherein the construct is cytocompatible.

12. The method of claim 1, wherein the construct is selected from the group consisting of a tissue scaffold, a single-lumen nerve guidance conduit, a multi-lumen nerve guidance conduit, an angiogenic structure, a scaffold for promoting adipose tissue population and growth, and any combination thereof.

13. The method of claim 1, wherein the first hydrogel construct layer comprises a first portion having a first thickness and a second portion having a second thickness.

14. The method of claim 1, wherein the thickness of the second hydrogel construct layer is different from the thickness of the first hydrogel construct layer.

15. The method of claim 1 further comprising a cross-layer disposed between the first hydrogel construct layer and the second hydrogel construct layer and further disposed in any dimension.

16. The method of claim 1, wherein the second hydrogel construct layer is a partial layer.

17. The method of claim 1, wherein fabricating the second hydrogel construct layer is accomplished using a second energy dosage.

18. The method of claim 2, wherein the second solution comprises a second hydrogel polymer that is different than the first hydrogel polymer.

19. The method of claim 2, wherein the second solution comprises the first hydrogel polymer having a second polymer concentration that is different than the first polymer concentration.

20. The method of claim 2, wherein the second solution comprises the first photoinitiator having a second photoinitiator concentration that is different than the first photoinitiator concentration.

21. The method of claim 1 further comprising cleaning the hydrogel construct.

22. The method of claim 1 further comprising curing/drying the hydrogel construct.

23. The method of claim 1 further comprising incorporating an additive into the first solution.

24. The method of claim 23, wherein the additive is selected from the group consisting of color altering, thermal property altering, electrical property altering, optical property altering, mechanical property altering, strength altering, function altering, biofunction altering additives and any combination thereof.

25. The method of claim 23, wherein the additive is selected from the group consisting of imbedded devices and imbedded materials, bioactive ingredients and cells, and any combination thereof.