Optically transparent silk hydrogels

Patent metadata

Field	Value
Publication number	US-2016237128-A1
Application number	US-201415025034-A
Country	US
Kind code	A1
Filing date	Sep 26, 2014
Priority date	Sep 27, 2013
Publication date	Aug 18, 2016
Grant date	—

Abstract

The present application relates to silk fibroin-based hydrogels, methods for making and using the same.

First claim

What is claimed is:

1 . A silk fibroin-based hydrogel, having at least 60% transmittance in a visible spectrum.

2 . The silk fibroin-based hydrogel of claim 1 , having at least 70% transmittance in the visible spectrum.

3 . The silk fibroin-based hydrogel of claim 1 , having at least 75% transmittance in the visible spectrum.

4 . The silk fibroin-based hydrogel of claim 1 , having at least 80% transmittance in the visible spectrum.

5 . The silk fibroin-based hydrogel of claim 1 , having at least 85% transmittance in the visible spectrum.

6 . The silk fibroin-based hydrogel of claim 1 , having at least 90% transmittance in the visible spectrum.

7 . The silk fibroin-based hydrogel of claim 1 , having at least 95% transmittance in the visible spectrum.

8 . The silk fibroin-based hydrogel of any one of claims 1 - 7 , comprising a plurality of crystalized silk fibroin spheres.

9 . The silk fibroin-based hydrogel of claim 8 , wherein the crystalized silk fibroin spheres have an average diameter ranging between about 10 nm and about 150 nm.

10 . The silk fibroin-based hydrogel of any one of claims 1 - 8 , having a compressive modulus ranging between about 2 and about 20 kPa when measured with a crosshead speed of about 2.0 mm/hr.

11 . The silk fibroin-based hydrogel of any one of claims 1 - 9 , wherein the silk fibroin is crosslinked.

12 . The silk fibroin-based hydrogel of claim 11 , wherein the silk fibroin is crosslinked with a crosslinking agent.

13 . The silk fibroin-based hydrogel of claim 12 , wherein the crosslinking agent is an amine-to-amine crosslinker, amine-to-sulfhydryl crosslinker, carboxyl-to-amine crosslinker, photoreactive crosslinker, sulfhydryl-to-carbohydrate crosslinker, sulfhydryl-to-hydroxyl crosslinker, sulfhydryl-to-sulfhydryl crosslinker, or any combination thereof.

14 . The silk fibroin-based hydrogel of claim 12 , wherein the crosslinking agent is EDTA.

15 . The silk fibroin-based hydrogel of any one of claims 1 - 14 , having a porosity of between about 0% and 50%.

16 . The silk fibroin-based hydrogel of any one of claims 1 - 15 , wherein the silk fibroin-based hydrogel comprises silk fibroin polypeptides having an average molecular weight of between about 3.5 kDa and about 350 kDa.

17 . The silk fibroin-based hydrogel of claim 16 , wherein the silk fibroin polypeptides have an average molecular weight of between about 3.5 kDa and about 200 kDa.

18 . The silk fibroin-based hydrogel of claim 16 , wherein the silk fibroin polypeptides have an average molecular weight of between about 3.5 kDa and about 200 kDa.

19 . The silk fibroin-based hydrogel of claim 16 , wherein the silk fibroin polypeptides have an average molecular weight of between about 3.5 kDa and about 120 kDa.

20 . The silk fibroin-based hydrogel of claim 16 , wherein the silk fibroin polypeptides have an average molecular weight of between about 25 kDa and about 200 kDa.

21 . The silk fibroin-based hydrogel of any one of claims 1 - 20 , wherein the silk fibroin-based hydrogel is a three-dimensional (3D) structure, wherein at least one dimension of the 3D structure is at least than 10 micrometer.

22 . The silk fibroin-based hydrogel of claim 21 , wherein the 3D structure comprises a predetermined microstructure fabricated therein.

23 . The silk fibroin-based hydrogel of claim 22 , wherein the predetermined microstructure is a void.

24 . The silk fibroin-based hydrogel of claim 23 , wherein the void is or comprises a hole, a channel, a cavity, or any combination thereof.

25 . A method comprising steps of:
providing silk fibroin polypeptides; contacting the silk fibroin polypeptides with an organic solvent so as to induce beta-sheet formation in the silk fibroin polypeptides; flashing off the organic solvent so as to induce formation of the silk fibroin-based hydrogel of any one of claims 1 - 21 .

26 . The method of claim 25 , further comprising a step of crosslinking.

27 . The method of claim 26 , wherein the step of crosslinking is achieved with a crosslinking agent.

28 . The method of claim 27 , wherein the crosslinking agent is EDTA.

29 . The method of any one of claims 25 - 28 , wherein the organic solvent is acetone.

30 . A method comprising steps of:
providing the silk fibroin-based hydrogel of any one of claims 1 - 21 ; machining a predetermined microstructure in and/or on the silk fibroin-based hydrogel.

31 . The method of claim 30 , wherein the step of machining is performed with a laser.

32 . A silk fibroin-based hydrogel, comprising:
silk fibroin polypeptides that have an average molecular weight in a range of about 3.5 kDa and about; and nanosized crystalline particles are in a range of about 10 nm and about 150 nm, wherein the hydrogel is characterized by an optical transmittance in the visible spectrum between at least 40% and at least 99%.

33 . The silk fibroin-based hydrogel of claim 32 , wherein the hydrogel is characterized as having a compressive modulus in a range between about 2 kPa and about 20 kPa when measured with a crosshead speed of about 0.200 mm/min.

34 . The silk fibroin-based hydrogel of claim 32 , wherein the hydrogel is formed from a silk fibroin solution having a silk fibroin concentration between about 0.1 mg/ML and about 15 mg/ML.

34 . The silk fibroin-based hydrogel of claim 32 , wherein the hydrogel is formed from a silk fibroin solution having a silk fibroing concentration between about 0.1 mg/ML and about 15 mg/ML.

35 . The silk fibroin-based hydrogel of claim 32 , wherein the hydrogel is characterized by an optical transmittance in the visible spectrum between at least 50% and at least 99%.

36 . The silk fibroin-based hydrogel of claim 32 , wherein the hydrogel is characterized by an optical transmittance in the visible spectrum between at least 60% and at least 99%.

37 . The silk fibroin-based hydrogel of claim 32 , wherein the hydrogel is characterized by an optical transmittance in the visible spectrum between at least 70% and at least 99%.

38 . The silk fibroin-based hydrogel of claim 32 , wherein the hydrogel is characterized by an optical transmittance in the visible spectrum between at least 80% and at least 99%.

39 . The silk fibroin-based hydrogel of claim 32 , wherein the hydrogel is characterized by an optical transmittance in the visible spectrum between at least 90% and at least 99%.

40 . The silk fibroin-based hydrogel of claim 32 , wherein the hydrogel is characterized by an optical transmittance in the visible spectrum between at least 95% and at least 99%.

41 . The silk fibroin-based hydrogel of claim 32 , wherein the hydrogel is configured to support incorporation of functional moieties.

42 . The silk fibroin-based hydrogel of claim 41 , wherein the functional moieties are or comprise cells.

43 . The silk fibroin-based hydrogel of claim 42 , wherein the cells are human cornea epithelial cells (HCECs).

44 . The silk fibroin-based hydrogel of claim 32 , wherein the hydrogel degrades rele

Assignees

• Univ Tufts

Inventors

• Omenetto Fiorenzo G
• Kaplan David L
• Marelli Benedetto
• Mitropoulos Alexander Nicholas

Classifications

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · CPC title

• B23K26/402

  involving non-metallic material, e.g. isolators · CPC title

• B23K2203/32

  Operations & Transport · mapped topic

• C12N2537/10

  Cross-linking · CPC title

• C12N5/0075

  using microcarriers · CPC title