BIODEGRADABLE SIDE CHAIN LIQUID CRYSTAL ELASTOMERS: SMART RESPONSIVE SCAFFOLDS (SRS) FOR TISSUE REGENERATION

• US 20160046761A1
• Filed: 04/14/2014
• Published: 02/18/2016
• Est. Priority Date: 04/15/2013
• Status: Active Grant

• Current Assignee: Kent State University
• Original Assignee: Kent State University
• Inventors: HEGMANN, Elda, HEGMANN, Torsten, SHARMA, Anshul, NESHAT, Abdollah
• Granted Patent: US 9,815,935 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: C08G 63/08 Lactones or lactides
• CPC Class Codes: C08G 63/916 Dicarboxylic acids and dihydroxy compounds
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C09K 19/3866 containing steroid groups

Abstract

Controlled biodegradable smart responsive scaffold (SRS) materials enhance attachment and viability of cells, i.e. actively guiding their expansion, proliferation and in some cases differentiation, while increasing their biomechanical functionality is an important key issue for tissue regeneration. Chemically build-in functionality in these biodegradable SRS materials is achieved by varying structural functionalization with biocompatible liquid crystal motifs and general polymer composition allowing for regulation and alteration of tensile strength, surface ordering, bioadhesion and biodegradability, bulk liquid crystal phase behavior, porosity, and cell response to external stimuli. Liquid crystal modification of such polymeric scaffolds is an ideal tool to induce macroscopic ordering events through external stimuli. None of these approaches have been demonstrated in prior art, and the use of biocompatible scaffolds that respond to a variety of external stimuli resulting in a macroscopic ordering event is a novel aspect of the present invention.

Claims

1. A star block copolymer having pendant liquid crystal side chains, comprising:

a core derived from a polyol; and

a plurality of random block polymers comprising;

a polymer block derived from halide substituted lactone monomers;

a polymer block derived from lactone monomers or isomers thereof; and

a polymer block derived from lactide monomers;

said halide containing block polymer having a plurality of non-toxic, biocompatible liquid crystal chains pendant therefrom that are substituted for or added at said halide site.

2. The star block copolymer of claim 1, wherein the porosity of said copolymer is from about 5 micron to about 700 micron in the dry state.

3. The star block copolymer of claim 2, wherein said polyol core is derived from a polyol having from 2 to 8 hydroxy groups;

wherein said substituted halide is a chlorine atom or a bromine atom.

4. The star block copolymer of claim 3, wherein said liquid crystal is a cholesterol-based chiral nematic liquid crystal or derivative thereof, a cholesteryl liquid crystal or a derivative thereof, or a 3,4-difluoropentyl-bicyclohexyl-base nematic liquid crystal or a derivative thereof;

wherein said polyol comprises glycerol, pentaerythirol, or dipentaerythirol;

wherein said lactone is ε

-caprolactone, α

-caprolactone, β

-caprolactone, γ

-caprolactone, or δ

-caprolactone; and

wherein said lactide is D-Lactide, L-Lactide, or D,L-Lactide.

5. The star block copolymer of claim 4, wherein said halide substituted lactone monomer is α

-chloro-ε

-caprolactone or γ

-bromo-ε

-caprolactone, wherein said lactone monomer is ε

-polycaprolactone, and wherein said lactide is D,L-lactide; and

wherein said liquid crystal is cholesteryl-5 hexynoate.

6. The star block copolymer of claim 5, wherein said porosity of said star block copolymer is from about 10 micron to about 500 micron.

7. The star block copolymer of claim 2, wherein “

x”

is the number of mass moles of said halide substituted lactone of said substituted lactone, wherein “

y”

is the number of mass moles of said lactone, and wherein “

z”

is the number of mass moles of said lactide,

wherein “

x”

is from about 1 to about 99% based upon the total mass moles of said “

x” and

said “

y”

;

wherein “

x+y”

is from about 1 to about 90% based upon the total mass moles of said “

x”

, said “

y”

, and said “

z”

mass moles; and

wherein the amount of said core polyol is from about 0.001 to about 50 mass moles based upon the total of said “

x”

, said “

y”

, and said “

z”

mass moles.

8. The star block copolymer of claim 6, wherein “

x”

is the number of mass moles of said halide substituted lactone, wherein “

y”

is the number of mass moles of said lactone, and wherein “

z”

is the number of mass moles of said lactide,

wherein “

x”

is from about 5 to about 70% based upon the total mass moles of said “

x” and

said “

y”

;

wherein “

x+y”

is from about 2 to about 80% based upon the total mass moles of said “

x”

, said “

y”

, and said “

z”

mass moles; and

wherein the amount of said core polyol is from about 0.01 to about 40 mass moles based upon the total of said “

x”

, said “

y”

, and said “

z”

mass moles.

9. The star block copolymer of claim 8, wherein “

x”

is the number of mass moles of said halide substituted lactone, wherein “

y”

is the number of mass moles of said lactone, and wherein “

z”

is the number of mass moles of said lactide,

wherein “

x”

is from about 40 to about 60% based upon the total mass moles of said “

x” and

said “

y”

;

wherein “

x+y”

is from about 5 to about 40% based upon the total mass moles of said “

x”

, said “

y”

, and said “

z”

mass moles; and

wherein the amount of said core polyol is from about 0.1 to about 30 mass moles based upon the total of said “

x”

, said “

y”

, and said “

z”

mass moles.

10. The star block copolymer of claim 1, wherein said star block copolymer is crosslinked by a crosslinking agent to form a thermoset elastomer.

11. The star block copolymer of claim 4, wherein said star block copolymer is crosslinked by a crosslinking agent to form a thermoset elastomer, wherein said crosslinking agent is a compound that is biocompatible and biodegradable with said star block copolymer.

12. The star block copolymer of claim 6, wherein said star block copolymer is crosslinked by a crosslinking agent to form a thermoset elastomer wherein said crosslinking agent is 2,2-Bis(1-caprolactone-4-yl) propane (BCP) and derivatives thereof, or Bis-caprolactone with oligoethylene glycol spacer and derivatives thereof.

13. The star block copolymer of claim 7, wherein said star block copolymer is crosslinked by a crosslinking agent to form a thermoset elastomer wherein said crosslinking agent is 2,2-Bis(1-caprolactone-4-yl) propane (BCP) and derivatives thereof, or Bis-caprolactone with oligoethylene glycol spacer, and derivatives thereof.

14. The star block copolymer of claim 9, wherein said star block copolymer is crosslinked by a crosslinking agent to form a thermoset elastomer wherein said crosslinking agent is 2,2-Bis(1-caprolactone-4-yl) propane (BCP).

15. The star block copolymer of claim 10, wherein said elastomer is adaptable for use in:

a drug delivery patch for skin, internal tissues, or tumors, medical implants, and in the treatment of neurological, skin, tissue, organ, or bone disorders;

or any combination thereof.

16. The star block copolymer of claim 11, wherein said elastomer is adaptable for use in:

a drug delivery patch for skin, internal tissues, or tumors, medical implants, and in the treatment of neurological, skin, tissue, organ, or bone disorders;

or any combination thereof.

17. The star block copolymer of claim 14, wherein said elastomer is adaptable for use in:

a drug delivery patch for skin, internal tissues, or tumors, medical implants, and in the treatment of neurological, skin, tissue, organ, or bone disorders;

or any combination thereof.

18. A process for forming a star block copolymer having pendant liquid crystal side chains, comprising the steps of:

forming a random star block copolymer by reacting a core polyol with halide substituted lactone monomers, with lactone monomers or isomers thereof, and with lactide monomers; and

subsequently reacting said star block copolymer with an azide compound or an ester compound that is substituted for or added to said star block copolymer at said halide site.

19. The process according to claim 18, including adding a biocompatible and biodegradable liquid crystal to said star block copolymer.

20. The process according to claim 19, wherein said liquid crystal is a cholesterol-based chiral nematic liquid crystal or derivative thereof, a cholesteryl liquid crystal or a derivative thereof, or a 3,4-difluoropentyl-bicyclohexyl-base nematic liquid crystal or a derivative thereof.