Polyesters, methods of making polyesters and uses therefor
Polyester compositions and functionalized polyester compositions are provided along with methods of making the compositions as well as methods of using the compositions, for example as a tissue engineering bioscaffold and as a drug-delivery vehicle.
1. A polymer composition comprising at least one moiety selected from the following:
(a) [—OC(O)—CH(NHY)—CH 2 —C(O)O—CH 2 —CH(O—R1)—CH 2 —O—CH 2 —CH 2 —O—CH 2 —CH(O—R2)—CH 2 —] n ,
(b) [—OC(O)—CH 2 —CH(NHY)—C(O)O—CH 2 —CH(O—R1)—CH 2 —O—CH 2 —CH 2 —O—CH 2 —CH(O—R2)—CH 2 ] n ,
(c) [—OC(O)—CH(NHY)—CH 2 —CH 2 —C(O)O—CH2—CH(O—R1)—CH 2 —O—CH 2 —CH 2 —O—CH 2 —CH(O—R2)—CH 2 ] n , and/or
(d) [—OC(O)—CH 2 —CH 2 —CH(NHY)—C(O)O—CH2—CH(O—R1)—CH 2 —O—CH 2 —CH 2 —O—CH 2 —CH(O—R2)—CH 2 —] n ,
wherein Y is —C(O)—CH(NH 3 + )—(CH 2 ) 3 —NH—C(NH 2 ) 2 + or —C(O)—CH(NH 3 + )—(CH 2 ) 4 —(NH 3 ) + , and R1 and R2 are the same or different and are independently selected from the group consisting of hydrogen,
a carboxy-containing group, an α, β unsaturated carboxylic acid, a cinnamic acid containing group, a p-coumaric acid containing group, a ferulic acid containing group, a caffeic acid containing group, an amine-containing group, a quaternary ammonium containing group, maleic acid, a peptide, maleate, succinate, a phosphate-containing group, and a halo-containing group.
2. The composition of claim 1 having a polydispersity index of less than 3.0.
3. The composition of claim 1 having a polydispersity index of less than 2.0.
4. The composition of claim 1 in which one or both of R1 and R2 are charged.
5. The composition of claim 1 in which one or both of R1 and R2 are a phosphate-containing group.
6. The composition of claim 1 , attached non-covalently to a calcium phosphate selected from the group consisting of hydroxyapatite, apatite, tricalcium phosphate, octacalcium phosphate, calcium hydrogen phosphate, and calcium dihydrogen phosphate.
7. The composition of claim 1 , in which R1 and R2 are selected from the group consisting of Ile-Lys-Val-Ala-Val (IKVAV) (SEQ ID NO: 1), Arg-Gly-Asp (RGD), Arg-Gly-Asp-Ser (RGDS) (SEQ ID NO: 2), Ala-Gly-Asp (AGD), Lys-Gln-Ala-Gly-Asp-Val (KQAGDV) (SEQ ID NO: 3), Val-Ala-Pro-Gly-Val-Gly (VAPGVG) (SEQ ID NO: 4), APGVGV (SEQ ID NO: 5), PGVGVA (SEQ ID NO: 6), VAP, GVGVA (SEQ ID NO: 7), VAPG (SEQ ID NO: 8), VGVAPG (SEQ ID NO: 9), VGVA (SEQ ID NO: 10), VAPGV (SEQ ID NO: 11) and GVAPGV (SEQ ID NO: 12)).
8. The composition of claim 1 , complexed with heparin or heparan sulfate.
9. The composition of claim 8 , further complexed with a growth factor.
10. The composition of claim 1 in which one or both of R1 and R2 are maleate or phosphate.
11. The composition of claim 1 wherein the at least one polymer is selected from formulae (a) or (b).
12. The composition of claim 11 , wherein Y is —C(O)—CH(NH 3 + )—(CH 2 ) 4 —(NH 3 ) + .
13. The composition of claim 11 , wherein Y is —C(O)—CH(NH 3 30 )—(CH 2 ) 3 —NH—C(NH 2 ) 2 ± .
14. The composition of claim 1 , wherein Y is —C(O)—CH(NH 3 + )—(CH 2 ) 4 —(NH 3 ) + .
15. The composition of claim 1 , wherein Y is —C(O)—CH(NH 3 + )—(CH 2 ) 3 —NH—C(NH 2 ) 2 ± .
16. The composition of claim 1 in which one or both of R1 and R2 are
17. The composition of claim 12 in which R1 is hydrogen.
18. The composition of claim 13 in which R1 is hydrogen.
19. The composition of claim 1 wherein the at least one polymer is selected from formulae (c) or (d).
20. The composition of claim 19 , wherein Y is —C(O)—CH(NH 3 + )—(CH 2 ) 3 —NH—C(NH 2 ) 2 ± .
21. The composition of claim 20 in which R1 is hydrogen.
22. The composition of claim 19 , wherein Y is —C(O)—CH(NH 3 + )—(CH 2 ) 4—(NH 3 ) + .
23. The composition of claim 22 in which R1 is hydrogen.
24. The composition of claim 19 in which one or both of R1 and R2 is
25. The composition of claim 19 in which one or both of R1 and R2 are charged.
26. The composition of claim 25 in which one or both of R1 and R2 are maleate or phosphate.
27. The composition of claim 19 in which one or both of R1 and R2 are a phosphate-containing group.
28. The composition of claim 19 , attached non-covalently to a calcium phosphate selected from the group consisting of hydroxyapatite, apatite, tricalcium phoshate, octacalcium phosphate, calcium hydrogen phosphate, and calcium dihydrogen phosphate.
29. The composition of claim 19 , in which R1 and R2 are selected from the group consisting of Ile-Lys-Val-Ala-Val (IKVAV) (SEQ ID NO: 1), Arg-Gly-Asp (RGD), Arg-Gly-Asp-Ser (RGDS) (SEQ ID NO: 2), Ala-Gly-Asp (AGD), Lys-Gln-Ala-Gly-Asp-Val (KQAGDV) (SEQ ID NO: 3), Val-Ala-Pro-Gly-Val-Gly (VAPGVG) (SEQ ID NO: 4), APGVGV (SEQ ID NO: 5), PGVGVA (SEQ ID NO: 6), VAP, GVGVA (SEQ ID NO: 7), VAPG (SEQ ID NO: 8), VGVAPG (SEQ ID NO: 9), VGVA (SEQ ID NO: 10), VAPGV (SEQ ID NO: 11) and GVAPGV (SEQ ID NO: 12)).
30. The composition of claim 19 , complexed with heparin or heparan sulfate.
31. The composition of claim 30 , further complexed with a growth factor.
32. The composition of claim 19 having a polydispersity index of less than 3.0.
33. The composition of claim 19 having a polydispersity index of less than 2.0.
34. The composition of claim 11 in which one or both of R1 and R2 are
35. The composition of claim 11 in which one or both of R1 and R2 are charged.
36. The composition of claim 35 in which one or both of R1 and R2 are maleate or phosphate.
37. The composition of claim 11 in which one or both of R1 and R2 are a phosphate-containing group.
38. The composition of claim 11 , attached non-covalently to a calcium phosphate selected from the group consisting of hydroxyapatite, apatite, tricalcium phosphate, octacalcium phosphate, calcium hydrogen phosphate, and calcium dihydrogen phosphate.
39. The composition of claim 11 , in which R1 and R2 are selected from the group consisting of Ile-Lys-Val-Ala-Val (IKVAV) (SEQ ID NO: 1), Arg-Gly-Asp (RGD), Arg-Gly-Asp-Ser (RGDS) (SEQ ID NO: 2), Ala-Gly-Asp (AGD), Lys-Gln-Ala-Gly-Asp-Val (KQAGDV) (SEQ ID NO: 3), Val-Ala-Pro-Gly-Val-Gly (VAPGVG) (SEQ ID NO: 4), APGVGV (SEQ ID NO: 5), PGVGVA (SEQ ID NO: 6), VAP, GVGVA (SEQ ID NO: 7), VAPG (SEQ ID NO: 8), VGVAPG (SEQ ID NO: 9), VGVA (SEQ ID NO: 10), VAPGV (SEQ ID NO: 11) and GVAPGV (SEQ ID NO: 12)).
40. The composition of claim 11 , complexed with heparin or heparan sulfate.
41. The composition of claim 40 , further complexed with a growth factor.
42. The composition of claim 11 having a polydispersity index of less than 3.0.
43. The composition of claim 11 having a polydispersity index of less than 2.0.
44. The composition of claim 18 , further complexed with heparin or heparin sulfate to produce a vehicle.
45. The composition of claim 44 , further comprising an active agent complexed with the vehicle.
46. The composition of claim 45 , wherein the active agent is a growth factor.
47. The composition of claim 46 , wherein the growth factor is one or more of a FGF, an EGF and VEGF.
48. A biological scaffold comprising a polymer composition according to claim 1 .
49. A drug delivery vehicle comprising a polymer composition according to claim 1 .
50. A biological scaffold comprising a polymer composition according to claim 19 .
51. A drug delivery vehicle comprising a polymer composition according to claim 19 .
52. A biological scaffold comprising a polymer composition according to claim 11 .
53. A drug delivery vehicle comprising a polymer composition according to claim 11 .
54. A method of growing cells, comprising culturing cells on the scaffold of claim 48 .
55. A method of inducing neurite formation in a neuron comprising contacting a neuron with a composition according to claim 16 .
56. A method of growing cells, comprising culturing cells on the scaffold of claim 50 .
57. A method of inducing neurite formation in a neuron comprising contacting a neuron with a composition according to claim 24 .
58. A method of growing cells, comprising culturing cells on the scaffold of claim 52 .
59. A method of inducing neurite formation in a neuron comprising contacting a neuron with a composition according to claim 34 .