Pulp regeneration compositions and methods of forming and using the same

Patent metadata

Field	Value
Publication number	US-11278474-B2
Application number	US-201715777304-A
Country	US
Kind code	B2
Filing date	Dec 1, 2017
Priority date	Dec 1, 2016
Publication date	Mar 22, 2022
Grant date	Mar 22, 2022

Abstract

A dental tissue regenerative composition. The composition includes a combination of (1) human dental pulp stem cells and (2) at least one of human umbilical vein endothelial cells or vascular endothelial growth factor. The combination is encapsulated in a light-activated gelatin methacrylate hydrogel.

First claim

What is claimed is:

1. A dental tissue regenerative composition comprising a combination of (1) human dental pulp stem cells and (2) at least one of human umbilical vein endothelial cells or vascular endothelial growth factor, wherein the combination is encapsulated in a light-activated gelatin methacrylate hydrogel.

2. The composition of claim 1 , further comprising a photo-initiator.

3. The composition of claim 2 , wherein the photo-initiator is present at a concentration of about 0.05% to about 0.5% (w/v).

4. The composition of claim 2 , wherein the photo-initiator is selected from the group consisting of: 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one, azobisisobutyronitrile, benzoyl peroxide, di-tert-butyl peroxide, 2,2-dimethoxy-2-phenylacetophenone, Eosin Y, and any combination thereof.

5. The composition of claim 1 , wherein the methacrylate hydrogel is present at a concentration of about 3% to about 5% (w/v).

6. The composition of claim 1 , wherein the human dental pulp stem cells have been isolated from dental pulp.

7. The composition of claim 6 , wherein the dental pulp is from a mature tooth.

8. The composition of claim 7 , wherein the mature tooth is a wisdom tooth.

9. The composition of claim 7 , wherein the mature tooth is a cryopreserved tooth.

10. The composition of claim 1 , wherein the composition is used for pulpal revascularization, to replace infected pulpal tissues in pulpotomy, or as a temporary intra canal medicament.

11. The composition of claim 1 , wherein the composition is used for regenerating pulp-like tissues in tooth root segments.

12. The composition of claim 1 , wherein the ratio of human dental pulp stem cells to the at least one of the human umbilical vein endothelial cells or vascular endothelial growth factor in the composition is about 1:1.

13. A method of regenerating pulp-like tissues in a tooth root segment of a tooth, the method comprising:
injecting a composition into the tooth root segment, the composition including gelatin methacrylate hydrogel and a photo-initiator;
combining the composition with (1) human dental pulp stem cells and (2) at least one of human umbilical vein endothelial cells or vascular endothelial growth factor; and
cross-linking the gelatin methacrylate hydrogel with the human dental pulp stem cells and the at least one of human umbilical vein endothelial cells or vascular endothelial growth factor by exposure to a UV or visible light.

14. The method of claim 13 , wherein the duration of the exposure is from about 18 seconds to about 30 seconds.

15. The method of claim 13 , wherein the photo-initiator is present in the composition at a concentration of about 0.05% to about 0.5% (w/v).

16. The method of claim 13 , wherein the photo-initiator is selected from the group consisting of: 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one, azobisisobutyronitrile, benzoyl peroxide, di-tert-butyl peroxide, 2,2-dimethoxy-2-phenylacetophenone, Eosin Y, and any combination thereof.

17. The method of claim 13 , wherein the methacrylate hydrogel is present in the composition at a concentration of about 3% to about 5% (w/v).

18. The method of claim 13 , further comprising inducing bleeding near the apex of the tooth to obtain the human dental pulp stem cells.

19. The method of claim 13 , wherein the human dental pulp stem cells have been isolated from dental pulp.

20. The method of claim 19 , wherein the dental pulp is from a mature tooth.

21. The method of claim 20 , wherein the mature tooth is a wisdom tooth.

22. The method of claim 20 , wherein the mature tooth is a cryopreserved tooth.

23. The method of claim 13 , wherein the ratio of human dental pulp stem cells to the at least one of the human umbilical vein endothelial cells or vascular endothelial growth factor in the composition is about 1:1.

24. The method of claim 13 , wherein the composition is combined with the human dental pulp stem cells and the at least one of human umbilical vein endothelial cells or vascular endothelial growth factor prior to being injected into the tooth root segment.

25. A method of forming a dental tissue regenerative composition, the method comprising:
combining human dental pulp stem cells, at least one of human umbilical vein endothelial cells or vascular endothelial growth factor, a gelatin methacrylate hydrogel, and a photo-initiator; and
cross-linking the gelatin methacrylate hydrogel with the human dental pulp stem cells and the at least one of human umbilical vein endothelial cells or vascular endothelial growth factor by exposure to a UV or visible light.

26. The method of claim 25 , wherein the photo-initiator is present at a concentration of about 0.05% to about 0.5% (w/v).

27. The method of claim 25 , wherein the photo-initiator is selected from the group consisting of: 1-[-4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one, azobisisobutyronitrile, benzoyl peroxide, di-tert-butyl peroxide, 2,2-dimethoxy-2-phenylacetophenone, Eosin Y, and any combination thereof.

28. The method of claim 25 , wherein the methacrylate hydrogel is present at a concentration of about 3% to about 5% (w/v).

29. The method of claim 25 , wherein the human dental pulp stem cells have been isolated from dental pulp.

30. The method of claim 29 , wherein the dental pulp is from a mature tooth.

31. The method of claim 30 , wherein the mature tooth is a wisdom tooth.

32. The method of claim 30 , wherein the mature tooth is a cryopreserved tooth.

33. The method of claim 25 , wherein the composition is used for pulpal revascularization, to replace infected pulpal tissues in pulpotomy, or as a temporary intra canal medicament.

34. The method of claim 25 , wherein the composition is used for regenerating pulp-like tissues in tooth root segments.

35. The method of claim 25 , wherein the ratio of human dental pulp stem cells to the at least one of the human umbilical vein endothelial cells or vascular endothelial growth factor in the composition is about 1:1.

Assignees

• Tufts College
• Brigham & Womens Hospital Inc

Inventors

• Yelick Pamela C
• Khademhosseini Ali

Classifications

• A61K6/56

  Apical treatment · CPC title

• A61K6/69

  Medicaments · CPC title

• A61K6/62 Primary

  Photochemical radical initiators · CPC title

• A61C5/40

  Implements for surgical treatment of the roots or nerves of the teeth; Nerve needles; Methods or instruments for medication of the roots · CPC title

• A61L2400/06

  Flowable or injectable implant compositions · CPC title