Poly(thioketal-urethane) scaffolds and methods of use

Patent metadata

Field	Value
Publication number	US-10046086-B2
Application number	US-201615290875-A
Country	US
Kind code	B2
Filing date	Oct 11, 2016
Priority date	Sep 21, 2012
Publication date	Aug 14, 2018
Grant date	Aug 14, 2018

Abstract

A biodegradable scaffold, a low-molecular weight thioketal, and a method of forming a biodegradable scaffold are provided. The biodegradable scaffold includes a thioketal and an isocyanate, where the thioketal is linked to the isocyanate to form the scaffold. The low-molecular weight thioketal includes 2,2-dimethoxypropane and thioglycolic acid, wherein the thioketal includes at least two hydroxyl terminal groups. The method of forming the biodegradable scaffold includes blending a thioketal with an excess isocyanate, forming a quasi-prepolymer, mixing the thioketal, the quasi-prepolymer, and a ceramic, and then adding a catalyst to form the biodegradable scaffold. The thioketal is a low-molecular weight thioketal having at least two hydroxyl terminal groups.

First claim

What is claimed is:

1. A thioketal of formula I:

wherein R 1 and R 2 are independently selected from the group consisting of CH 2 C(O)OH and CH 2 CH 2 OH;
wherein R 3 is selected from the group consisting of CH 3 and CH 2 CH 2 CH 2 CH 3 ;
wherein R 4 is selected from the group consisting of CH 3 , SCH 2 C(O)OH, and SCH 2 CH 2 OH; and
wherein when R 3 and R 4 are both CH 3 at least one of R 1 and R 2 is CH 2 CH 2 OH.

2. The thioketal of claim 1 , wherein R 1 and R 2 are both CH 2 CH 2 OH.

3. The thioketal of claim 2 , wherein R 4 is CH 3 .

4. The thioketal of claim 2 , wherein R 4 is SCH 2 CH 2 OH.

5. The thioketal of claim 1 , wherein R 1 and R 2 are both CH 2 C(O)OH.

6. The thioketal of claim 5 , wherein R 4 is SCH 2 C(O)OH.

7. The thioketal of claim 1 , wherein the low molecular weight thioketal comprises an equivalent weight of at least 95 grams/equivalent.

8. The thioketal of claim 1 , wherein the low molecular weight thioketal comprises an equivalent weight of about 100 grams/equivalent.

9. A biodegradable scaffold, comprising:
the thioketal of claim 1 ; and
an isocyanate, where the thioketal is linked to the isocyanate to form the scaffold.

10. The scaffold of claim 9 , wherein the scaffold further comprises a catalyst.

11. The scaffold of claim 10 , wherein the catalyst comprises an amine.

12. The scaffold of claim 11 , wherein the catalyst is a solution of triethylene diamine in dipropyleneglycol.

13. The scaffold of claim 9 , further comprising a ceramic selected from the group consisting of β-tricalcium phosphate (β-TCP), hydroxyapatite, and combinations thereof.

14. The scaffold of claim 9 , wherein the isocyanate comprises lysine triisocyanate (LTI).

15. The scaffHold of claim 9 , wherein the thioketal provides a crosslinker that is selectively degraded by reactive oxygen species (ROS) to permit cell-mediated degradation of the scaffold.

16. The scaffold of claim 12 , wherein the solution of triethylamine diamine in dipropyleneglycol comprises 33% triethylenediamine in 67% dipropyleneglycol.

17. A method of forming a biodegradable scaffold, the method comprising:
blending the thioketal of claim 1 with an isocyanate, forming a prepolymer;
mixing the thioketal, the prepolymer, and a ceramic; and then
adding a catalyst to form the biodegradable scaffold;
wherein the thioketal is a low-molecular weight thioketal having at least two hydroxyl terminal groups.

Assignees

• Univ Vanderbilt

Inventors

• Guelcher Scott A
• Mcgough Madison
• Gupta Mukesh K
• Duvall Craig L
• Martin John
• Page Jon

Classifications

• C08G18/5072

  containing sulfur · CPC title

• A61L2400/06

  Flowable or injectable implant compositions · CPC title

• A61L27/58

  Materials at least partially resorbable by the body · CPC title

• A61L27/425

  of phosphorus containing material, e.g. apatite · CPC title

• C08G18/3868

  the sulfur atom belonging to a sulfide group · CPC title