Biocompatible polycaprolactone fumarate formulations
View Patent ↗A polycaprolactone fumarate polymer useful as a matrix material for a biocompatible scaffold for tissue engineering applications is disclosed. The polycaprolactone fumarate polymer can be prepared by reacting caprolactone with an alkane polyol to prepare a polycaprolactone precursor, and then reacting the polycaprolactone precursor with fumaric acid or a salt thereof to prepare the polycaprolactone fumarate polymer. The use of an alkane diol, such as 1,2-propanediol, provides a linear polycaprolactone diol precursor. The use of an alkane triol, such as glycerol, provides a branched polycaprolactone triol precursor. The biocompatible polycaprolactone fumarate formulation releases no diethylene glycol or other undesirable byproducts during degradation.
1. A scaffold for tissue regeneration, the scaffold comprising:
a blend of a polymer having the Formula (I)
H-A 1 -B-A 2 -C-A 1 -B-A 2 -H (I)
wherein
A 1 is
A 2 is
B is —O—X—O— wherein X is selected from the group consisting of ethylene, trimethylene, tetramethylene, pentamethylene, C 1 -C 5 alkylethylene,
C 1 -C 5 alkyltrimethylene, C 1 -C 5 alkyltetramethylene, and C 1 -C 5 alkylpentamethylene;
C is
and geometric isomers thereof;
and n is an integer from 1 to 50, and
a polymer having the Formula (II)
wherein
D 1 is
D 2 is
D 3 is
E is —O—X—O— wherein X is selected from the group consisting of propanetriyl, butanetriyl, pentanetriyl, C 1 -C 5 alkyl propanetriyl,
C 1 -C 5 alkyl butanetriyl, and C 1 -C 5 alkyl pentanetriyl;
F is
and geometric isomers thereof;
and n is an integer from 1 to 50;
wherein the polymer of Formula (I) comprises 20 wt. % to 80 wt % of the scaffold, and the polymer of Formula (II) comprises 20 wt. % to 80 wt % of the scaffold, and
wherein the polymer of Formula (I) is formed using a first initiator such that B is —O—X—O— wherein X is selected from the group consisting of ethylene, trimethylene, tetramethylene, pentamethylene, C 1 -C 5 alkylethylene, C 1 -C 5 alkyltrimethylene, C 1 -C 5 alkyltetramethylene, and C 1 -C 5 alkylpentamethylene, and
wherein the polymer of Formula (II) is formed using a second initiator such that E is —O—X—O— wherein X is selected from the group consisting of propanetriyl, butanetriyl, pentanetriyl, C 1 -C 5 alkyl propanetriyl, C 1 -C 5 alkyl butanetriyl, and C 1 -C 5 alkyl pentanetriyl, and
wherein the first initiator is different from the second initiator.
2. The scaffold of claim 1 wherein:
the polymer of Formula (I) comprises 40 wt. % to 60 wt % of the scaffold, and
the polymer of Formula (II) comprises 40 wt. % to 60 wt % of the scaffold.
3. The scaffold of claim 1 wherein:
in the polymer of Formula (I), X is methylethylene.
4. The scaffold of claim 1 wherein the polymer of Formula (I) has a number average molecular weight in the range of 5,000 to 15,000 g mol −1 .
5. The scaffold of claim 1 wherein:
in the polymer of Formula (II), X is propanetriyl.
6. The scaffold of claim 1 wherein the polymer of Formula (II) has a number average molecular weight in the range of 5,000 to 15,000 g mol −1 .
7. The scaffold of claim 1 wherein:
the scaffold maintains its geometrical structure and dimensions throughout an autoclave sterilization process, and
the scaffold maintains mechanical properties within an order of magnitude during the autoclave sterilization process.
8. The scaffold of claim 1 wherein:
diethylene glycol is not released during hydrolysis of the scaffold.
9. The scaffold of claim 1 wherein:
the scaffold has a fracture stress in a range of 2 to 8 MPa.
10. The scaffold of claim 1 wherein:
the scaffold has a tensile modulus in a range of 20 to 80 MPa.