Methods for stepwise deposition of silk fibroin coatings
The invention provides a method for the controlled assembly of layered silk fibroin coatings using aqueous silk fibroin material. The methods described herein can be used to coat substrates of any material, shape, or size. Importantly, the described methods enable control of the biomaterial surface chemistry, thickness, morphology and structure using layered thin film coatings, or bulk coatings. Furthermore, the methods can be performed in all water and do not require intensive chemical processing enabling controlled entrapment of labile molecules such as, drugs, cytokines, and even cells or viruses to generate functional coatings that can be used in a variety of applications.
1. A substrate which is coated with a ultrathin silk fibroin biomaterial coating ranging from about 1 to about 12 nm in thickness, wherein the substrate is a mesh, and wherein the silk fibroin biomaterial coating comprises a bioactive agent, wherein the bioactive agent is a therapeutic agent, and wherein the silk fibroin biomaterial coating has a uniform distribution of a granule morphology.
2. The substrate of claim 1 , further comprising a silk fibroin biomaterial coating over the silk fibroin biomaterial coating containing the bioactive agent.
3. The substrate of claim 1 , wherein the bioactive agent is mixed with an aqueous solution that is used to make the silk fibroin biomaterial coating containing the bioactive material.
4. The substrate of claim 1 , wherein the bioactive agent is loaded onto the silk fibroin biomaterial coating.
5. The substrate of claim 1 , wherein the bioactive agent is a therapeutic agent.
6. The substrate of claim 5 , wherein the therapeutic agent is selected from the group consisting of a protein, a peptide, a nucleic acid, a peptide nucleic acid, an aptamer, an antibody and a small molecule.
7. The substrate of claim 1 , wherein the bioactive agent is selected from the group consisting of an antiproliferative agent, an antineoplastic agent, an antiinflammatory agent, an antiplatelet agent, an anticoagulant agent, an antifibrin agent, an antithrombin agent, an antimitotic agent, an antibiotic agent, or an antioxidant.
8. The substrate of claim 1 , wherein the agent is an antiproliferative agent.
9. The substrate of claim 1 , wherein the silk biomaterial coating is prepared by:
(a) contacting a substrate with an aqueous silk fibroin solution such that the solution forms a layer upon the substrate; and
(b) dehydrating said layer by exposure of the layer to a flow of a dehydrating gas.
10. The substrate of claim 9 , wherein the silk fibroin solution further comprises a bioactive agent.
11. The substrate of claim 10 , wherein the bioactive agent is a therapeutic agent.
12. The substrate of claim 11 , wherein the therapeutic agent is selected from the group consisting of a protein, a peptide, a nucleic acid, a peptide nucleic acid, an aptamer, an antibody and a small molecule.
13. The substrate of claim 10 , wherein the bioactive agent is an antiproliferative agent.
14. The substrate of claim 10 , wherein the bioactive agent is selected from the group consisting of an antiproliferative agent, an antineoplastic agent, an antiinflammatory agent, an antiplatelet agent, an anticoagulant agent, an antifibrin agent, an antithrombin agent, an antimitotic agent, an antibiotic agent, or an antioxidant.
15. A substrate comprising a layered silk fibroin biomaterial coating comprising a plurality of silk fibroin layers, wherein each layer is of about 1 to about 12 nm in thickness and wherein the substrate is a mesh, and wherein the silk fibroin biomaterial coating comprises a bioactive agent, wherein the bioactive agent is a therapeutic agent, and wherein the silk fibroin biomaterial coating has a uniform distribution of a granule morphology.
16. The substrate of claim 15 , further comprising a silk fibroin biomaterial coating over at least one layer of the silk fibroin biomaterial coating containing the bioactive agent.
17. The substrate of claim 15 , wherein the bioactive agent is mixed with an aqueous solution that is used to make the layered silk fibroin biomaterial coating containing the bioactive agent.
18. The substrate of claim 15 , wherein the bioactive agent is loaded onto the layered silk fibroin biomaterial coating.
19. The substrate of claim 15 , wherein the therapeutic agent is selected from the group consisting of a protein, a peptide, a nucleic acid, a peptide nucleic acid, an aptamer, an antibody and a small molecule.
20. The substrate of claim 15 , wherein the bioactive agent is selected from the group consisting of an antiproliferative agent, an antineoplastic agent, an antiinflammatory agent, an antiplatelet agent, an anticoagulant agent, an antifibrin agent, an antithrombin agent, an antimitotic agent, an antibiotic agent, or an antioxidant.
21. The substrate of claim 15 , wherein the bioactive agent is an antiproliferative agent.
22. The substrate of claim 15 , wherein the silk fibroin biomaterial coating is prepared by:
(a) contacting a substrate with an aqueous silk fibroin solution such that the solution forms a first layer upon the substrate;
(b) dehydrating said first layer by exposure of the layer to a flow of a dehydrating gas;
(c) contacting the dehydrated first layer with a silk fibroin solution such that the solution forms a second layer upon the dehydrated first layer;
(d) dehydrating said second layer by exposure of the second layer to a flow of dehydrating gas; and
(e) repeating steps (c) and (d) until the desired numbers of layers are deposited upon the substrate resulting in a layered coating on said substrate.
23. The substrate of claim 22 , wherein the silk fibroin solution further comprises a bioactive agent.
24. The substrate of claim 23 , wherein the bioactive agent is a therapeutic agent.
25. The substrate of claim 24 , wherein the therapeutic agent is selected from the group consisting of a protein, a peptide, a nucleic acid, a peptide nucleic acid, an aptamer, an antibody and a small molecule.
26. The substrate of claim 23 , wherein the bioactive agent is selected from the group consisting of an antiproliferative agent, an antineoplastic agent, an antiinflammatory agent, an antiplatelet agent, an anticoagulant agent, an antifibrin agent, an antithrombin agent, an antimitotic agent, an antibiotic agent, or an antioxidant.
27. The substrate of claim 23 , wherein the bioactive agent is an antiproliferative agent.
28. A substrate which is coated with a silk fibroin biomaterial coating ranging from about 50 nm to about 5000 nm, wherein the silk fibroin biomaterial coating comprises a bioactive material agent, and wherein the bioactive agent is a cell, a virus, a metal, or a therapeutic agent, and wherein the silk fibroin biomaterial coating has a uniform distribution of a granule morphology.
29. The substrate of claim 28 , wherein the substrate is a biomedical device, a biomaterial, a biosensor, or a tissue engineering scaffold.
30. The substrate of claim 29 , further comprising a silk fibroin biomaterial coating over the layer containing the bioactive agent.
31. The substrate of claim 28 , wherein the substrate is a stent, a suture, a mesh, a plate, a screw, a catheter, a tubing, a gel, a 3D porous scaffold or a tissue engineering scaffold.
32. The substrate of claim 28 , wherein the therapeutic agent is selected from the group consisting of a protein, a peptide, a nucleic acid, a peptide nucleic acid, an aptamer, an antibody, and a small molecule.
33. The substrate of claim 28 , wherein the therapeutic agent is selected from the group consisting of an antiproliferative agent, an antineoplastic agent, an antiinflammatory agent, an antiplatelet agent, an anticoagulant agent, an antifibrin agent, an antithrombin agent, an antimitotic agent, an antibiotic agent, or an antioxidant.
34. A substrate which is coated with a layered silk fibroin biomaterial coating comprising a plurality of silk fibroin layers, wherein thickness of at least one layer is from about 50 nm to about 5,000 nm, wherein said silk fibroin biomaterial coating has a uniform distribution of a granule morphology.
35. The substrate of claim 34 , wherein the substrate is a biomedical device, a biomaterial, a biosensor, or a tissue engineering scaffold.
36. The substrate of claim 35 , wherein the substrate is a stent, a suture, a mesh, a plate, a screw, a catheter, a tubing, a gel, a 3D porous scaffold or a tissue engineering scaffold.
37. The substrate of claim 34 , wherein the coating further comprises a bioactive agent.
38. The substrate of claim 37 , wherein the bioactive agent is a cell, a virus, a metal, or a therapeutic agent.
39. The substrate of claim 38 , wherein the therapeutic agent is selected from the group consisting of a protein, a peptide, a nucleic acid, a peptide nucleic acid, an aptamer, an antibody, and a small molecule.
40. The substrate of claim 37 , wherein the bioactive agent is selected from the group consisting of an antiproliferative agent, an antineoplastic agent, an antiinflammatory agent, an antiplatelet agent, an anticoagulant agent, an antifibrin agent, an antithrombin agent, an antimitotic agent, an antibiotic agent, or an antioxidant.
41. The substrate of claim 37 , further comprising a silk fibroin biomaterial coating over the layer containing the bioactive agent.