THREE-DIMENSIONAL PRINTING WITH SUPRAMOLECULAR TEMPLATED HYDROGELS

• US 20200131383A1
• Filed: 04/27/2018
• Published: 04/30/2020
• Est. Priority Date: 04/27/2017
• Status: Active Grant

• Current Assignee: The Trustees of Dartmounth College (Dartmouth College)
• Original Assignee: The Trustees of Dartmounth College (Dartmouth College)
• Inventors: Ke, Chenfeng, Zhang, Pengfei, Li, Longyu, Lin, Qianming
• Granted Patent: US 11,814,527 B2
• Time in Patent Office: Days
• CPC Class Codes: B29C 64/106 using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
• CPC Class Codes: B29C 64/314 Preparation
• CPC Class Codes: B29K 2105/0061 Gel or sol
• CPC Class Codes: B33Y 10/00 Processes of additive manufacturing
• CPC Class Codes: B33Y 40/10 Pre-treatment
• CPC Class Codes: B33Y 70/00 Materials specially adapted for additive manufacturing
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C09D 11/04 based on proteins
• CPC Class Codes: C09D 11/101 Inks specially adapted for printing processes involving curing by wave energy or particle radiation, e.g. with UV-curing following the printing
• CPC Class Codes: C09D 11/102 containing macromolecular compounds obtained by reactions other than those only involving unsaturated carbon-to-carbon bonds

Abstract

The invention provides a supramolecular polymer composition capable of co-assembly to maintain a three dimensional (3-D) macrostructural form after 3-D printing, made of a solvent, a template molecule; and a reactive component. The reactive component can be at least one monomer that is capable of hydrogen bonding with the template molecule to form a 1D supramolecular structure. The template may be an amphiphilic polymer. The monomer has at least two pendant groups capable of covalent crosslinking. The invention also includes a 3-D structure formed by crosslinking a 3-D printed supramolecular polymer composition, which optionally has a mesoporous structure. Also included is a method of manufacturing a 3-D structure by delivering a supramolecular polymer composition onto a surface of a substrate to form the 3-D structure.

Claims

1. A supramolecular polymer composition capable of co-assembly to maintain a three dimensional (3-D) macrostructural form after 3-D printing, comprising:

i) a solvent;

ii) a template molecule comprising an at least partially linear amphiphilic or hydrophilic polymer; and

iii) a reactive component comprising at least one monomer, wherein the at least one monomer is capable of hydrogen bonding with the template molecule to form a 1 D supramolecular structure, and wherein the monomer comprises least two pendant groups capable of covalent crosslinking;

wherein the supramolecular polymer composition has a suitable viscoelastic property which allows for 3-D printing of the hydrogel to form a 3-D structure, and is capable of co-assembly after 3-D printing to maintain the printed three dimensional (3-D) macrostructural form; and

wherein the template molecule is removable after a chemical crosslinking step.

2. The supramolecular polymer composition of claim 1, wherein the template-monomer co-assembled hydrogel structure comprises a second crosslinking monomer having at least one crosslinkable group.

3. The supramolecular polymer composition of claim 1, wherein at least a portion of the groups capable of covalent crosslinking are crosslinked to form a crosslinked monomer.

4. The supramolecular polymer composition of claim 1, wherein the crosslinking is achieved by UV treatment, or by heating, or by removal of the solvent.

5. The supramolecular polymer composition of claim 1 or 2, wherein the template-monomer co-assembled supramolecular polymer structure is formed by at least partial removal of solvent.

6. The supramolecular polymer composition of claim 1 or 2, wherein the composition is capable of maintaining the shape and dimensional stability in a 3-D pattern after 3-D printing.

7. The supramolecular polymer composition of claim 3, wherein the monomer is crosslinked and the template molecule is removable from the crosslinked composition.

8. The supramolecular polymer composition of claim 3, wherein the composition is capable of substantially isotropic expansion or substantially isotropic contraction after 3D printing.

9. The supramolecular polymer composition of claim 8, wherein the substantially isotropic expansion or contraction occurs via, respectively, addition of or removal of a monomer capable of hydrogen bonding with the crosslinked monomer.

10. The supramolecular polymer composition of claim 3, wherein the composition is capable of contraction after 3D printing via a polycondensation reaction.

11. The supramolecular polymer composition of claim 10, wherein the contraction occurs substantially isotropically due to template-monomer co-assembly.

12. The supramolecular polymer composition of claim 1 or 2, wherein the at least partially linear amphiphilic or hydrophilic polymer is ionic or non-ionic.

13. The supramolecular polymer composition of claim 1, wherein the amphiphilic or hydrophilic at least partially linear polymer is a nonionic amphiphilic polymer.

14. The supramolecular polymer composition of claim 13, wherein the nonionic amphiphilic polymer is present at a concentration above its critical micellular concentration (cmc).

15. The supramolecular polymer composition of claim 13, wherein the nonionic amphiphilic polymer is a copolymer comprising at least one block of lesser hydrophilicity and at least one hydrophilic block.

16. The supramolecular polymer composition of claim 13, wherein the nonionic amphiphilic polymer is a copolymer comprising at least one hydrophilic central block and at least two terminal hydrophilic blocks of comparatively lesser hydrophilicity.

17. The supramolecular polymer composition of claim 13, wherein the at least partially linear polymer is a nonionic polymer wherein the hydrophilic blocks are selected from the group consisting of polyethylene oxide (PEO), polyethylene imide, and polyvinyl alcohol, and the block of lesser hydrophilicity (and/or hydrophobic block) is selected from the group consisting of polypropylene oxide (PPO), polydimethylsiloxane (PDMS), polystyrene, and polycaprolactone (PCL).

18. The supramolecular polymer composition of claim 13, wherein the nonionic amphiphilic polymer is a biocompatible polymer.

19. The supramolecular polymer composition of claim 13, wherein the nonionic amphiphilic polymer is a copolymer comprising poly(ethylene oxide) and poly(propylene oxide).

20. The supramolecular polymer composition of claim 13, wherein the amphiphilic polymer is a PPO-PEO-PPO triblock copolymer.

21. The supramolecular polymer composition of claim 1, wherein the at least partially linear polymer is a nonionic hydrophilic polymer.

22. The supramolecular polymer composition of claim 21, wherein the nonionic hydrophilic polymer is a biocompatible polymer.

23. The supramolecular polymer composition of claim 22, wherein the nonionic hydrophilic polymer is a polymer or copolymer comprising poly(ethylene oxide).

24. The supramolecular polymer composition of claim 1 or 2, wherein the solvent is an aqueous solvent.

25. The supramolecular polymer composition of claim 24, wherein the solvent comprises ethanol and water, or the solvent comprises ethanol, water, and tetrahydrofuran (THF).

26. The supramolecular polymer composition of claim 1, wherein the monomer is a hydrolysable organosilicate compound.

27. The supramolecular polymer composition of claim 26, wherein the monomer is selected from tetraethyl orthosilicate (TEOS) or a compound represented by Formula 1

28. The supramolecular polymer composition of claim 27, wherein the monomer is selected from a compound represented by Formula 2:

29. The supramolecular polymer composition of claim 28, wherein the monomer is a compound represented by Formula 2 or Formula 3:

30. The supramolecular polymer composition of claim 1, wherein the at least one monomer comprises aryl linked to the at least two crosslinking groups through a linker comprising at least one hydrogen bonding group.

31. The supramolecular polymer composition of claim 29, wherein the at least one monomer is a compound represented by Formula 3:

32. The supramolecular polymer composition of claim 31, wherein X is selected from the group consisting of:

33. The supramolecular polymer composition of claim 31, wherein Y is selected from the group consisting of:

34. The supramolecular polymer composition of claim 1, wherein L is a hydrogen bonding group and is selected from the following:

35. The supramolecular polymer composition of claim 1, wherein at least one monomer comprises two monomers wherein the two monomers independently comprise a charge donor and a charge acceptor capable of forming a charge donor/charge acceptor complex.

36. The supramolecular polymer composition of claim 35, wherein the charge donor comprises a compound selected from the group consisting of:

37. The supramolecular polymer composition of claim 35, wherein the charge acceptor comprises a compound selected from the group consisting of:

38. The supramolecular polymer composition of claim 31, wherein the hydrogen bonding group is a urea, carboxamide group and the aryl group is substituted or unsubstituted C₅-C₂₀ arylene, or substituted or unsubstituted C₅-C₂₀ heteroarylene.

39. The supramolecular polymer composition of claim 30, wherein the monomer comprises

40. The supramolecular polymer composition of claim 2, wherein the second crosslinking monomer comprises a crosslinking moiety capable of crosslinking with a crosslinkable group on the at least one monomer.

41. The supramolecular polymer composition of claim 40, wherein the second monomer comprises a crosslinking group selected from a thiol group or an azide group.

42. The supramolecular polymer composition of claim 41, wherein the second monomer is

43. The supramolecular polymer composition of claim 1, wherein the monomer comprises an oligopeptide comprising at least three peptide residues linked to least two crosslinkable groups.

44. The supramolecular polymer composition of claim 43, wherein the oligopeptide comprises at least one cysteine residue and at least two cysteine-reactive crosslinkable groups, or wherein the oligopeptide comprises at least two cysteine residues and at least one cysteine-reactive crosslinkable groups.

45. The supramolecular polymer composition of claim 44, wherein the oligopeptide is a compound of Formula 4:

46. The supramolecular polymer composition of claim 45, wherein R¹¹ is H₂NR¹²—

, H₂NCOR¹²—

, HSR¹²—

, HO₂R¹²—

, or R¹³R¹²—

,

wherein R¹² is substituted or unsubstituted C₁-C₂₀ alkylene, substituted or unsubstituted C₁-C₂₀ alkenylene and R¹³ is imidazoline, pyrazolidine, pyrrolidine, triazoline, pyridine, diazine, or triazine.

47. The supramolecular polymer composition of claim 46, wherein at least one R¹¹ is HSR¹²—

, and at least one R¹¹ is selected from H₂NR¹²—

, H₂NCOR¹²—

, or R¹³R¹²—

, and Z is —

NR¹⁴N—

, wherein R¹⁴ is substituted or unsubstituted C¹-C²⁰ alkylene, substituted or unsubstituted C¹-C²⁰ alkenylene. In embodiments, R¹⁴ is substituted with carbamate or carboxyl.

48. The supramolecular polymer composition of claim 1, wherein the monomer is a hydrolysable organosilicate compound and wherein the template-monomer co-assembled supramolecular polymer structure has a molar ratio of about 150:

1 monomer to template molecule in the template-monomer co-assembled supramolecular polymer structure.

49. The supramolecular polymer composition of claim 48, wherein the solvent further comprises a water-soluble acidic compound.

50. The supramolecular polymer composition of claim 49, wherein the acid is acetic acid and is present in the composition at a ratio of about 1:

1 with the template molecule.

51. The supramolecular polymer composition of claim 1, wherein the monomer is present in the template-monomer co-assembled supramolecular polymer structure in a molar ratio of about 1:

1 monomer;

template.

52. The supramolecular polymer composition of claim 51, wherein the template-monomer co-assembled supramolecular polymer structure comprises a second crosslinking monomer in an amount of about 1:

3.8 monomer;

second crosslinking monomer.

53. The supramolecular polymer composition of claim 2, wherein the monomer is

54. The supramolecular polymer composition of claim 1 or 2, wherein the storage modulus is at least about 1 kPa.

55. The supramolecular polymer composition of claim 1 or 2, wherein the storage modulus is between about 1-100 kPa.

56. The supramolecular polymer composition of claim 1 or 2, wherein the viscosity at a shear rate of 1 s⁻

1 and 25°

C. is between 5-5000 Pa·

s.

57. The supramolecular polymer composition of claim 3 or 4, wherein the covalent crosslinking is a free radical reaction, cycloaddition, or a condensation reaction.

58. The supramolecular polymer composition of claim 56, wherein the covalent crosslinking is a photo-initiated free radical reaction.

59. A 3-D structure comprising

(i) a crosslinked polymer network comprising a crosslinked monomer;

wherein the crosslinked polymer network has a mesoporous structure;

wherein the 3-D structure comprises internal cavities or voids that are interconnected in one, two or three dimensions within the structure.

60. The 3-D structure of claim 59, wherein the mesoporous structure is formed by removal of a template molecule.

61. The 3-D structure of claim 59, wherein the 3-D structure is a shaped implantable tissue graft scaffold, an implantable cellular matrix, a drug release reservoir, a model tissue, an implantable gel, a wound dressing, a sensing device, a wearable device, a porous ceramic scaffold for catalyst loading, a porous device for molecular sieving, a porous device for gas separation, or a sorption device.

62. A method of manufacturing a supramolecular polymer composition capable of co-assembly to maintain a 3-D macrostructural form after 3-D printing, comprising:

(a) providing a solvent;

(b) providing a template molecule comprising an at least partially linear amphiphilic or hydrophilic polymer;

(c) providing at least one reactive component comprising at least one monomer, wherein the at least one monomer is capable of hydrogen bonding with the template molecule to form a 1D supramolecular structure, and wherein the at least one monomer comprises least two groups capable of covalent crosslinking;

(d) providing conditions wherein the template molecule and the reactive component form a template-monomer co-assembled supramolecular polymer structure;

wherein the supramolecular polymer composition has a viscosity which allows for 3-D printing of the supramolecular polymer composition to form a 3-D structure, and is capable of co-assembly after 3-D printing to maintain the printed three dimensional (3-D) macrostructural form.

63. The method of claim 62, wherein the conditions comprise allowing an at least partial evaporation of the solvent.

64. The method of claim 63, wherein the method further comprises the step of polymerizing the monomer.

65. The method of claim 64, wherein the method further comprises the step of removing the template molecule, and wherein the step of removing the template molecule causes the formation of a mesoporous structure.

66. A method of manufacturing a 3-D structure, the method comprising:

(a) delivering one or more supramolecular polymer compositions onto a surface of a substrate to form the 3-D structure, wherein the 3-D structure comprises internal cavities or voids that are interconnected in one, two or three dimensions within the structure;

wherein the supramolecular polymer composition comprises a template-monomer co-assembled supramolecular polymer structure comprising;

i) a solvent;

ii) a template molecule comprising an at least partially linear amphiphilic or hydrophilic polymer;

iii) a reactive component comprising a monomer, wherein the monomer is capable of hydrogen bonding with the template molecule to form a 1 D supramolecular structure, and wherein the monomer comprises least two groups capable of covalent crosslinking;

wherein the supramolecular polymer composition has a suitable viscoelastic property which allows for 3-D printing of the supramolecular polymer composition to form a 3-D structure, and is capable of re-co-assembly after 3-D printing to maintain the printed three dimensional (3-D) macrostructural form.

67. The method of claim 66, wherein the method further comprises the step of providing conditions for polymerization for the delivered composition.

68. The method of claim 66, wherein the method of delivering comprises additive manufacturing or 3-D printing.

69. The method of claim 66, wherein the template-monomer co-assembled supramolecular structure is retained during an at least partial evaporation of the solvent.

70. The method of claim 67, wherein the method further comprises the step of removing the template molecule.

71. The method of claim 70, wherein the step of removing the template molecule causes the formation of a mesoporous structure.

72. An article comprising a structure prepared by the method of claim 66.

73. The article of claim 72, wherein the article is a shaped implantable tissue graft scaffold, an implantable cellular matrix, a drug release reservoir, a model tissue, an implantable gel, a wound dressing, or a sorption device.