IP Library › Granted Patent US 12,331,429
Granted Patent B2
US 12,331,429 · App. 17/309,005 · Granted Jun 17, 2025

Compression and heat-assisted production of silk-based materials

Inventors: David L. Kaplan (Concord, MA); Fiorenzo G. Omenetto (Lexington, MA); Chunmei Li (Stoneham, MA); Chengchen Guo (Wakefield, MA)
Assignee: Trustees of Tufts College
D01F4/02C08L89/00B82Y40/00D10B2211/04D10B2211/22
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,331,429
App. No.
17/309,005
Granted
Jun 17, 2025
Kind
B2
Abstract

In some embodiments, the present disclosure provides methods including the steps of (i) providing silk fibroin material comprising substantially amorphous structure, and (ii) applying at least one of elevated temperature and elevated pressure to the silk fibroin material to form a silk fibroin article, wherein the applying induces fusion between at least a portion of the silk fibroin and structural change of fibroin in the silk fibroin material. In some embodiments, the present disclosure also provides silk fibroin articles made in accordance with the methods disclosed herein.

Claims (16)

1. A silk fibroin article comprising semi-crystalline silk fibroin, wherein the silk fibroin article has a glass transition temperature between about 40° C. to 120° C., wherein a flexural strength of the silk fibroin article is at least 5 MPa and density of the entire silk fibroin article is at least 1.20 g/cm 3 .

2. The silk fibroin article of claim 1 , wherein the silk fibroin article is homogenous.

3. The silk fibroin article of claim 1 , wherein the silk fibroin article is transparent.

4. The silk fibroin article of claim 1 , wherein the silk fibroin article is at least one of macro-patterned, micro-patterned, or nano-patterned.

5. The silk fibroin article of claim 1 , wherein the silk fibroin article comprises at least one additive to form a composite silk article.

6. The silk fibroin article of claim 5 , wherein the at least one additive comprises at least one of small organic or inorganic molecules, an organic macromolecule, an inorganic macromolecule, a biological macromolecule; an electrically conductive material, a carbon-based material, antibodies and antigen-binding fragments thereof; an antigen; a nucleic acid; nucleic acid analogs and derivatives; a sugar; an immunogen; natural compounds and extraction from biological systems, cells, bacterias, or tissues; a synthetic material; a metallic material; an alloy; a hydrophobic material; a hydrophilic material; or a nanomaterial.

7. The silk fibroin article of claim 6 , wherein the at least one additive is the organic macromolecule, and wherein the organic macromolecule is or comprises at least one enzyme.

8. The silk fibroin article of claim 7 , wherein the at least one enzyme comprises at least one of Protease XIV, Proteinase K, a-chymotrypsin, collagenase, matrix metalloproteinase-1 (MMP-1) or MMP-2.

9. The silk fibroin article of claim 7 , wherein an activity of the at least one enzyme is stabilized by silk at elevated temperature and pressure.

10. The silk fibroin article of claim 6 , wherein the at least one additive is the electrically conductive material, wherein the electrically conductive material comprises at least one of an inorganic conductive material, an organic conductive material, a metal, an alloy, a semiconductor material, or a conjugated polymer.

11. The silk fibroin article of claim 5 , wherein the at least one additive is mixed with the semi-crystalline silk fibroin at a ratio between 0.001 wt % and 95.0 wt %.

12. The silk fibroin article of claim 1 , wherein the silk fibroin article degrades at least 1 wt % after 30 days of exposure to an aqueous environment at 37° C.

13. The silk fibroin article of claim 1 , wherein the silk fibroin article is bioresorbable.

14. The silk fibroin article of claim 1 , wherein the silk fibroin article has thermal forming properties and can be reformed to desirable shapes at elevated temperatures or elevated pressures.

15. The silk fibroin article of claim 1 , wherein the silk fibroin article is or comprises a packaging material.

16. The silk fibroin article of claim 15 , wherein the packaging material is suitable for use in fabricating electronic devices, drug delivery system, patterning, molding, and any combination thereof.

Assignments (2)
SECURITY INTEREST Recorded Apr 6, 2022
From: PAVMED INC.; VERIS HEALTH INC.
To: ALTO OPPORTUNITY MASTER FUND, SPC - SEGREGATED MASTER PORTFOLIO B
Reel/Frame 059620/0086 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 12, 2021
From: KAPLAN, DAVID L.; OMENETTO, FIORENZO G.; LI, CHUNMEI; GUO, CHENGCHEN
To: TRUSTEES OF TUFTS COLLEGE
Reel/Frame 055894/0024 →
Continuity (2)
Provisional Application 62743975 · Oct 10, 2018
Related Publication 20210381129A1 · Dec 9, 2021
References Cited (50)
US 20140093902A1 · Omenetto · 2014 [cited by examiner]
US 20150283298A1 · Kaplan · 2015 [cited by applicant]
US 20160046679A1 · Kluge · 2016 [cited by examiner]
US 20160089854A1 · Omenetto · 2016 [cited by applicant]
US 20160237128A1 · Omenetto · 2016 [cited by examiner]
US 20160263228A1 · Kluge · 2016 [cited by applicant]
JP H0310019A · 1991 [cited by applicant]
JP 2007277481A · 2007 [cited by applicant]
WO 2005012606A2 · 2005 [cited by applicant]
WO WO2005103158 · 2008 [cited by examiner]
WO 2014125505A4 · 2014 [cited by applicant]
WO 2017047503A1 · 2017 [cited by applicant]
WO 2020117368A2 · 2020 [cited by applicant]
Daijirou Akiyama et al., “Effect of Preparation Method of Powdered Silk on the Mechanical Properties of Moulded Silk”, 2355-2358 (1993). [cited by applicant]
Yongzhen Tao et al., “Structure and Properties of Composites Compression-molded from Silk Fibroin Powder and Waterborne Polyurethane”, 639-644 (2011). [cited by applicant]
Altman, G. H. et al. Silk-based Biomaterials. Biomaterials 24, 401-416 (2003). [cited by applicant]
Cebe, P. et al. Beating the Heat—Fast Scanning Melts Silk Beta Sheet Crystals. Sci. Rep. 3, 741-7 (2013). [cited by applicant]
Cheng, G., et al. Differences in regenerated silk fibroin prepared with different solvent systems: From structures to conformational changes. Journal of Applied Polymer Science 132.22 (2015). [cited by applicant]
Ha, S.-W., et al. Dissolution of Bombyx mori silk fibroin in the calcium nitrate tetrahydrate-methanol system and aspects of wet spinning of fibroin solution. Biomacromolecules 4, 488-496 (2003). [cited by applicant]
Ha, S.-W., et al. Structural studies of Bombyx mori silk fibroin during regeneration from solutions and wet fiber spinning. Biomacromolecules 6, 1722-1731 (2005). [cited by applicant]
Hu, X., et al. “Dynamic protein-water relationships during ß-sheet formation.” Macromolecules 41.11 (2008): 3939-3948. [cited by applicant]
Hu, X., et al. “Effect of water on the thermal properties of silk fibroin.” Thermochimica Acta 461.1-2 (2007): 137-144. [cited by applicant]
Hu, X., et al. Determining Beta-Sheet Crystallinity in Fibrous Proteins by Thermal Analysis and Infrared Spectroscopy. Macromolecules 39, 6161-6170 (2006). [cited by applicant]
International Searching Authority. International Search Report and Written Opinion for application PCT/US2019/055736. Mailed on May 28, 2020. 10 pages. [cited by applicant]
Kluge, J. A., et al. Optimizing molecular weight of lyophilized silk as a shelf-stable source material. ACS Biomater. Sci. Eng. 2, 595-605 (2016). [cited by applicant]
Koebley, S. R. et al. Silk Reconstitution Disrupts Fibroin Self-Assembly. Biomacromolecules 16, 2796-2804 (2015). [cited by applicant]
Koh, L.-D. et al. Structures, mechanical properties and applications of silk fibroin materials. Prog. Polym. Sci. 46, 86-110 (2015). [cited by applicant]
Krywka, C., et al. Determination of silkworm silk fibroin compressibility using high hydrostatic pressure with in situ X-ray microdiffraction. Macromolecules 47, 7187-7193 (2014). [cited by applicant]
Kundu, B., et al. Silk fibroin biomaterials for tissue regenerations. Advanced Drug Delivery Reviews 65, 457-470 (2013). [cited by applicant]
Lee, K. H. “Silk sericin retards the crystallization of silk fibroin.” Macromolecular rapid communications 25.20 (2004): 1792-1796. [cited by applicant]
Lefevre, T., et al. Protein Secondary Structure and Orientation in Silk as Revealed by Raman Spectromicroscopy. Biophys. J. 92, 2885-2895 (2007). [cited by applicant]
Li, C. et al. Regenerated silk materials for functionalized silk orthopedic devices by mimicking natural processing. Biomaterials 110, 24-33 (2016). [cited by applicant]
Lu, Q. et al. Silk Self-Assembly Mechanisms and Control From Thermodynamics to Kinetics. Biomacromolecules 13, 826-832 (2012). [cited by applicant]
Marelli, B. et al. Programming function into mechanical forms by directed assembly of silk bulk materials. Proc. Natl. Acad. Sci. USA 114, 451-456 (2017). [cited by applicant]
Marsh, R. E., et al. An Investigation of the Structure of Silk Fibroin. Biochim. Biophys. Acta 16, 1-34 (1955). [cited by applicant]
Pauling, L. et al. Configurations of Polypeptide Chains with Favored Orientations Around Single Bonds: Two New Pleated Sheets. Proc. Natl. Acad. Sci. U.S.A. 37, 729-740 (1951). [cited by applicant]
Perrone, G. S. et al. The use of silk-based devices for fracture fixation. Nat. Commun. 5, 1-9 (2014). [cited by applicant]
Qiao, X., et al. “Effect of electron beam irradiation on the crystallization of silk fibroin fiber-reinforced poly (e-caprolactone) biocomposites.” Polymer international 59.4 (2010): 447-455. [cited by applicant]
Rockwood, D. N. et al. Materials fabrication from Bombyx mori silk fibroin. Nat. Protoc. 6, 1612-1631 (2011). [cited by applicant]
Sidhu, M. S., et al. The processing and heterostructuring of silk with light. Nat. Mater. 16, 938-945 (2017). [cited by applicant]
Trabbic, K. A. et al. Comparative structural characterization of naturally- and synthetically-spun fibers of Bombyx mori fibroin. Macromolecules 31, 462-471 (1998). [cited by applicant]
Um, I. C., et al. Structural characteristics and properties of the regenerated silk fibroin prepared from formic acid. Int. J. Biol. Macromol. 29, 91-97 (2001). [cited by applicant]
Vepari, C. et al. Silk as a biomaterial. Prog. Polym. Sci. 32, 991-1007 (2007). [cited by applicant]
Wray, L. S. et al. Effect of processing on silk-based biomaterials: reproducibility and biocompatibility. J. Biomed. Mater. Res. Part B Appl. Biomater. 99, 89-101 (2011). [cited by applicant]
Yamaguchi, K. et al. Primary Structure of the Silk Fibroin Light Chain Determined by cDNA Sequencing and Peptide analysis. J. Mol. Biol. 210, 127-139 (1989). [cited by applicant]
Zhou, C. et al. Silk Fibroin: Structural Implications of a Remarkable Amino Acid Sequence. Proteins: Struct., Funct., Genet. 44, 119-122 (2001). [cited by applicant]
19893001.8 , “European Application Serial No. 19893001.8, Extended European Search Report mailed Jun. 21, 2022”, Tufts University, 4 pages. [cited by applicant]
Akiyama, Daijirou , “Effect of preparation method of powdered silk on the mechanical properties of moulded silk”, Polymer, vol. 35, 1994, pp. 2355-2358. [cited by applicant]
Guo, Chengchen , et al., “Thermoplastic moulding of regenerated silk”, Nature Materials, Nature Publishing Group UK, London, vol. 19, No. 1, Dec. 16, 2019, pp. 102-108. [cited by applicant]
PCT/US2019/055736 , “International Application Serial No. PCT/US2019/055736, International Preliminary Report on Patentability mailed Apr. 8, 2021”, Tufts University, 7 pages. [cited by applicant]