IP Library Granted Patent US 12,383,652
Granted Patent B2
US 12,383,652 · App. 17/413,147 · Granted Aug 12, 2025

Nanofiber structures and methods of manufacture and use thereof

Inventors: Jingwei Xie (Omaha, NE); Shixuan Chen (Omaha, NE)
Assignee: BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA
A61L27/18A61P19/00C12N5/0656D01D5/0007A61L2430/02B82Y40/00C12N2513/00C12N2533/30C12N2535/00D10B2331/041
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Quick Facts
Patent No.
US 12,383,652
App. No.
17/413,147
Granted
Aug 12, 2025
Kind
B2
Abstract

Nanofiber structures are provided as well as methods of use thereof and methods of making.

Claims (55)

1. An expanded nanofiber or microfiber structure,

wherein said expanded nanofiber or microfiber structure is an expanded nanofiber or microfiber mat having only one fixed side or a portion thereof.

2. The expanded nanofiber or microfiber structure of claim 1 , wherein said nanofiber or microfiber mat comprises electrospun fibers.

3. The expanded nanofiber or microfiber structure of claim 1 , wherein said nanofiber or microfiber mat comprises a plurality of uniaxially-aligned nanofibers or microfibers, random nanofibers or microfibers, and/or entangled nanofibers or microfibers.

4. The expanded nanofiber or microfiber structure of claim 1 , wherein said nanofiber or microfiber mat comprises polycaprolactone (PCL).

5. The expanded nanofiber or microfiber structure of claim 1 , wherein said nanofiber or microfiber mat comprises a poloxamer.

6. The expanded nanofiber or microfiber structure of claim 5 , wherein said poloxamer is poloxamer 407.

7. The expanded nanofiber or microfiber structure of claim 1 , wherein said fixed side or a portion thereof is thermally fixed.

8. The expanded nanofiber or microfiber structure of claim 1 , wherein said fixed side or a portion thereof is chemically fixed.

9. The expanded nanofiber or microfiber structure of claim 1 , wherein an entire side of said nanofiber or microfiber mat is fixed.

10. The expanded nanofiber or microfiber structure of claim 1 , wherein said expanded nanofiber or microfiber structure is a cylinder, sphere, tube, or hollow sphere.

11. The expanded nanofiber or microfiber structure of claim 1 , wherein said expanded nanofiber or microfiber structure comprises an active agent.

12. The expanded nanofiber or microfiber structure of claim 11 , wherein said active agent is selected from the group consisting of a therapeutic agent, a growth factor, a signaling molecule, a cytokine, a hemostatic agent, an antimicrobial, and an antibiotic.

13. The expanded nanofiber or microfiber structure of claim 1 , wherein said expanded nanofiber or microfiber structure comprises holes or wells.

14. The expanded nanofiber or microfiber structure of claim 1 , wherein said expanded nanofiber or microfiber structure is crosslinked.

15. The expanded nanofiber or microfiber structure of claim 1 , wherein said expanded nanofiber or microfiber structure further comprises a material selected from the group consisting of gelatin, chitosan, starch, pectin, cellulose, methylcellulose, sodium polyacrylate, and starch-acrylonitrile co-polymers.

16. The expanded nanofiber or microfiber structure of claim 1 , wherein at least one side of the expanded nanofiber or microfiber structure is blocked with a nanofiber mat or membrane.

17. The expanded nanofiber or microfiber structure of claim 1 , wherein said nanofiber or microfiber mat is expanded by exposing the nanofiber or microfiber mat to gas bubbles.

18. The expanded nanofiber or microfiber structure of claim 1 , wherein said nanofiber or microfiber mat has only one melted side or a portion thereof.

19. The expanded nanofiber or microfiber structure of claim 1 , wherein said nanofiber or microfiber mat has only one melted side.

20. The expanded nanofiber or microfiber structure of claim 1 , wherein said nanofiber or microfiber mat has only one chemically crosslinked side or a portion thereof.

21. The expanded nanofiber or microfiber structure of claim 1 , wherein said nanofiber or microfiber mat has only one chemically crosslinked side.

22. The expanded nanofiber or microfiber structure of claim 1 , wherein said nanofiber or microfiber mat has only one fixed side.

23. An expanded nanofiber or microfiber structure,

wherein said expanded nanofiber or microfiber structure is an expanded nanofiber or microfiber mat having only one melted side,

wherein said expanded nanofiber or microfiber structure is a cylinder.

24. A method for producing the expanded nanofiber or microfiber structure of claim 1 , said method comprising:

a) fixing only one side or a portion thereof of a nanofiber or microfiber mat, and

b) expanding the nanofiber or microfiber mat after step a) by exposing the nanofiber or microfiber mat to gas bubbles,

thereby producing said nanofiber or microfiber structure.

25. The method of claim 24 , wherein step b) comprises exposing the nanofiber or microfiber mat to a subcritical fluid and depressurizing.

26. The method of claim 25 , wherein said subcritical fluid comprises CO 2 , N 2 , N 2 O, hydrocarbons, or fluorocarbons.

27. The method of claim 25 , wherein said subcritical fluid is subcritical CO 2 .

28. The method of claim 25 , wherein said exposure comprises immersing said nanofiber or microfiber mat in said subcritical fluid.

29. The method of claim 24 , wherein said nanofiber or microfiber mat comprises electrospun fibers.

30. The method of claim 24 , wherein said nanofiber or microfiber mat comprises a plurality of uniaxially-aligned nanofibers or microfibers, random nanofibers or microfibers, and/or entangled nanofibers or microfibers.

31. The method of claim 24 , further comprising synthesizing said nanofiber or microfiber mat by electrospinning prior to step a).

32. The method of claim 24 , further comprising cutting said nanofiber or microfiber mat prior to step a).

33. The method of claim 24 , wherein said nanofiber or microfiber mat comprises polycaprolactone (PCL).

34. The method of claim 24 , wherein said nanofiber or microfiber mat comprises a poloxamer.

35. The method of claim 34 , wherein said poloxamer is poloxamer 407.

36. The method of claim 24 , wherein step a) comprises thermally fixing only one side or a portion thereof of said nanofiber or microfiber mat.

37. The method of claim 24 , wherein step a) comprises chemically fixing only one side or a portion thereof of said nanofiber or microfiber mat.

38. The method of claim 24 , wherein step a) comprises fixing an entire side of said nanofiber or microfiber mat.

39. The method of claim 24 , wherein said nanofiber or microfiber structure is a cylinder, sphere, tube, or hollow sphere.

40. The method of claim 24 , wherein said nanofiber or microfiber structure comprises an active agent.

41. The method of claim 40 , wherein said active agent is selected from the group consisting of a therapeutic agent, a growth factor, a signaling molecule, a cytokine, a hemostatic agent, an antimicrobial, and an antibiotic.

42. The method of claim 24 , wherein said nanofiber or microfiber structure comprises holes or wells.

43. The method of claim 24 , further comprising crosslinking the nanofiber or microfiber structure.

44. The method of claim 24 , wherein said nanofiber or microfiber structure further comprise a material selected from the group consisting of gelatin, chitosan, starch, pectin, cellulose, methylcellulose, sodium polyacrylate, and starch-acrylonitrile co-polymers.

45. The method of claim 24 , further comprising blocking at least one side of the nanofiber or microfiber structure with a nanofiber mat or membrane.

46. A method for producing the nanofiber or microfiber structure of claim 1 , said method comprising:

a) thermally fixing only one side or a portion thereof of a nanofiber or microfiber mat, wherein said nanofiber or microfiber mat comprises polycaprolactone (PCL) and a poloxamer, wherein said nanofiber or microfiber mat comprises electrospun fibers, and

b) expanding the nanofiber or microfiber mat after step a) by exposing the nanofiber or microfiber mat to subcritical fluid CO 2 and depressurizing,

thereby producing said nanofiber or microfiber structure.

Assignments (2)
CONFIRMATORY LICENSE Recorded Dec 6, 2023
From: UNIVERSITY OF NEBRASKA MEDICAL CENTER
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065790/0756 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 15, 2021
From: XIE, JINGWEI; CHEN, SHIXUAN
To: BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA
Reel/Frame 056592/0566 →
Continuity (2)
Provisional Application 62779564 · Dec 14, 2018
Related Publication 20220023496A1 · Jan 27, 2022
References Cited (121)
US 3674540A · Pergaminos · 1972 [cited by applicant]
US 6653005B1 · Muradov · 2003 [cited by applicant]
US 7465784B2 · Wang · 2008 [cited by applicant]
US 7704740B2 · Schindler et al. · 2010 [cited by applicant]
US 9403958B2 · Lindner et al. · 2016 [cited by applicant]
US 9580472B2 · Wang · 2017 [cited by applicant]
US 9655995B2 · Xie · 2017 [cited by applicant]
US 9913862B2 · Collins et al. · 2018 [cited by applicant]
US 10144767B2 · Wang · 2018 [cited by applicant]
US 10799620B2 · Xie et al. · 2020 [cited by applicant]
US 11033659B2 · Xie et al. · 2021 [cited by applicant]
US 11318224B2 · Xie et al. · 2022 [cited by applicant]
US 11427936B2 · Xie · 2022 [cited by applicant]
US 20050084532A1 · Howdle et al. · 2005 [cited by applicant]
US 20050187330A1 · Gulari et al. · 2005 [cited by applicant]
US 20060002978A1 · Shea et al. · 2006 [cited by applicant]
US 20070077272A1 · Li et al. · 2007 [cited by applicant]
US 20080112998A1 · Wang · 2008 [cited by applicant]
US 20090156499A1 · Wang · 2009 [cited by applicant]
US 20100183699A1 · Wan et al. · 2010 [cited by applicant]
US 20110070151A1 · Braithwaite et al. · 2011 [cited by applicant]
US 20110195123A1 · Shemi · 2011 [cited by applicant]
US 20110293685A1 · Kuo et al. · 2011 [cited by applicant]
US 20120040581A1 · Kim · 2012 [cited by applicant]
US 20120226295A1 · Jabbari · 2012 [cited by applicant]
US 20130095167A1 · Warnke · 2013 [cited by applicant]
US 20130112625A1 · Bahukudumbi et al. · 2013 [cited by applicant]
US 20140024760A1 · Kwon et al. · 2014 [cited by applicant]
US 20140051169A1 · Ganey et al. · 2014 [cited by applicant]
US 20140303069A1 · Wang et al. · 2014 [cited by applicant]
US 20150259382A1 · Wang · 2015 [cited by applicant]
US 20160015792A1 · Hendricus van Pinxteren et al. · 2016 [cited by applicant]
US 20160015952A1 · Omachi et al. · 2016 [cited by applicant]
US 20160106548A1 · Li et al. · 2016 [cited by applicant]
US 20160176714A1 · Do et al. · 2016 [cited by applicant]
US 20170296703A1 · Xie et al. · 2017 [cited by applicant]
US 20180028317A1 · Schlachter · 2018 [cited by applicant]
US 20190209732A1 · Xie et al. · 2019 [cited by applicant]
US 20200164107A1 · Xie et al. · 2020 [cited by applicant]
US 20200277711A1 · Xie · 2020 [cited by applicant]
US 20210268154A1 · Xie et al. · 2021 [cited by applicant]
US 20220226537A1 · Xie et al. · 2022 [cited by applicant]
CN 102068716A · 2011 [cited by applicant]
CN 102071485A · 2011 [cited by applicant]
CN 102703996A · 2012 [cited by applicant]
CN 103382625A · 2013 [cited by applicant]
CN 104464712A · 2015 [cited by applicant]
CN 106421898A · 2017 [cited by applicant]
CN 106492289A · 2017 [cited by applicant]
CN 106563172A · 2017 [cited by applicant]
CN 106620881A · 2017 [cited by applicant]
CN 105012991B · 2018 [cited by applicant]
EP 1611877A1 · 2006 [cited by applicant]
EP 2813212A1 · 2014 [cited by applicant]
JP 2006169497A · 2006 [cited by applicant]
JP 2007160691A · 2007 [cited by applicant]
JP 2007222477A · 2007 [cited by applicant]
JP 4656320B2 · 2011 [cited by applicant]
KR 101493444B1 · 2015 [cited by applicant]
WO 0050104A1 · 2000 [cited by applicant]
WO 2006019600A2 · 2006 [cited by applicant]
WO 2018227078A1 · 2008 [cited by applicant]
WO 2009011658A1 · 2009 [cited by applicant]
WO 2009088777A1 · 2009 [cited by applicant]
WO 2014037651A1 · 2014 [cited by applicant]
WO 2014191739A1 · 2014 [cited by applicant]
WO 2015051042A2 · 2015 [cited by applicant]
WO WO2016053988A1 · 2016 [cited by examiner]
WO 2018064281A1 · 2018 [cited by applicant]
WO 2019060393A1 · 2019 [cited by applicant]
WO 2019209762A1 · 2019 [cited by applicant]
WO 2020076381A1 · 2020 [cited by applicant]
WO 2020159946A1 · 2020 [cited by applicant]
Jiang, J. et al., Expanded 3D nanofiber scaffolds: cell penetration, neovascularization, and host response, Advanced Healthcare Materials, 2016, vol. 5, 2993-3003 (Year: 2016). [cited by examiner]
Pan, J.F. et al., Preparation and characterization of electrospun PLCL/Poloxamer nanofibers and dextran/gelatin hydrogels for skin tissue engineering, PLOS One, Nov. 18, 2014, vol. 9, 12 pages (Year: 2014). [cited by examiner]
Dumortier, G. et al., A review of poloxamer 407 pharmaceutical and pharmacological characteristics, Pharmaceutical Research, Nov. 11, 2006, vol. 23, 2709-2728 (Year: 2006). [cited by examiner]
Xie, J. et al., Putting electrospun nanofibers to work for biomedical research, Macromolecular Rapid Communications, 2008, vol. 29 , 1775-1792 (Year: 2008). [cited by examiner]
Sun, B. et al., Development of nanofiber spondges-containing nerve guidance conduit for peripheral nerve regeneration in vivo, ACS Applied Materials & Interfaces, Jul. 18, 2017, vol. 9, 26684-26696 (Year: 2017). [cited by examiner]
Chen, S.-H et al., Prevention of peritendinous adhesions with electrospun chitosan-grafted polycaprolactone nanofibrous membranes, Acta Biomaterialia, Sep. 2, 2014, vol. 10, 4971-4982 (Year: 2014). [cited by examiner]
Chen, et al., “Three-Dimensional Objects Consisting of Hierarchically Assembled Nanofibers with Controlled Alignments for Regenerative Medicine” Nano Lett. (2019) 19(3):2059-2065. [cited by applicant]
Kang, et al., “Chitosan-coated poly(vinyl alcohol) nanofibers for wound dressings” J. Biomed. Mater. Res. B Appl. Biomater. (2010) 92(2):568-76. [cited by applicant]
Chen, et al., “Fabrication of Injectable and Superelastic Nanofiber Rectangle Matrices (“Peanuts”) and Their Potential Applications in Hemostasis” Biomaterials (2018) 179:46-59. [cited by applicant]
Liu, Y., et al., “HB-EGF embedded in PGA/PLLA scaffolds via subcritical CO2 augments the production of tissue engineered intestine” Biomaterials (2016) 103:150-159. [cited by applicant]
Geiger, B.C., et al., “Dual Drug Release from CO2-Infused Nanofibers via Hydrophobic and Hydrophilic Interactions” J. Appld. Polymer Sci. (2015) 132(38):42571. [cited by applicant]
Ayodeji, O., et al., “Carbon dioxide impregnation of electrospun polycaprolactone fibers” J. Supercritical Fluids (2007) 41:173-178. [cited by applicant]
Jiang, J., et al., “CO2-Expanded Nanofiber Scaffolds Maintain Activity of Encapsulated Bioactive Materials and Promote Cellular Infiltration and Positive Host Response” Acta Biomater. (2018) 68: 237-248. [cited by applicant]
Nazarov, R., et al., “Porous 3-D scaffolds from regenerated silk fibroin” Biomacromolecules (2004) 5(3):718-26. [cited by applicant]
Joshi, M.K., et al., “Multi-layered macroporous three-dimensional nanofibrous scaffold via a novel gas foaming technique” Chem. Engr. J. (2015) 275:79-88. [cited by applicant]
Bencherif, S.A., et al., “Advances in the design of macroporous polymer scaffolds for potential applications in dentistry” J. Periodontal Implant Sci. (2013) 43(6):251-61. [cited by applicant]
Xie, J., et al., “Putting Electrospun Nanofibers to Work for Biomedical Research” Macromol. Rapid Commun. (2008) 29:1775-1792. [cited by applicant]
Jiang, J., et al., “Expanding Two-Dimensional Electrospun Nanofiber Membranes in the Third Dimension By a Modified Gas-Foaming Technique” ACS Biomater. Sci. Eng. (2015) 1(10):991-1001. [cited by applicant]
Liu, W., et al., “Electrospun nanofibers for regenerative medicine” Adv. Healthc. Mater. (2012) 1(1):10-25. [cited by applicant]
Nam, Y.S., et al., “A Novel Fabrication Method of Macroporous Biodegradable Polymer Scaffolds Using Gas Foaming Salt as a Porogen Additive” J. Biomed. Mater. Res. (2000) 53(1):1-7. [cited by applicant]
Lee, Y.H., et al., “Electrospun dual-porosity structure and biodegradation morphology of Montmorillonite reinforced PLLA nanocomposite scaffolds” Biomaterials (2005) 26:3165-3172. [cited by applicant]
Jiang, J., et al., “Local Sustained Delivery of 25-Hydroxyvitamin D3 for Production of Antimicrobial Peptides” Pharm. Res. (2015) 32(9): 2851-2862. [cited by applicant]
Ma, B., et al., “Rational design of nanofiber scaffolds for orthopedic tissue repair and regeneration” Nanomedicine (2013) 8(9):1459-81. [cited by applicant]
Dehghani, et al., “Engineering porous scaffolds using gas-based techniques” Current Opinion in Biotechnology (2011) 22:661-666. [cited by applicant]
Mulmi, et al., “Fabrication of Air Freshening Spongy Three Dimensional Electrospun Membrane” Journal of the Institute of Engineering (2018) 14(1):14-21. [cited by applicant]
Keit, et al., “Expansion of Two-dimension Electrospun Nanofiber Mats into Three-dimension Scaffolds” J. Vis. Exp. (2018):e58918. [cited by applicant]
Liu, Y., et al., “Composite vascular scaffold combining electrospun fibers and physically-crosslinked hydrogel with copper wire-induced grooves structure” J. Mech. Behav. Biomed. Mater. (2016) 61:12-25. [cited by applicant]
Zhao, Y., et al., “Preparation of Nanofibers with Renewable Polymers and Their Application in Wound Dressing” Intl. J. Polmer Sci. (2016) 2016:4672839. [cited by applicant]
Pok, S., et al., “A multilayered scaffold of a chitosan and gelatin hydrogel supported by a PCL core for cardiac tissue engineering” Acta Biomater. (2013) 9(3):5630-5642. [cited by applicant]
Xie, J, et al., “Controlled biomineralization of electrospun poly(ε-caprolactone) fibers for enhancing their mechanical properties” Acta Biomaterialia (2013) 9(3):5698-5707. [cited by applicant]
Xie, J., et al., “The differentiation of embryonic stem cells seeded on electrospun nanofibers into neural lineages” Biomaterials (2009) 30(3):354-362. [cited by applicant]
Chen, S., et al., “Recent advances in electrospun nanofibers for wound healing” Nanomedicine (Lond.) (2017) 12 (11):1335-1352. [cited by applicant]
Electrospin Tech, “Post-electrospinning expansion of 2D membrane to 3D scaffold using gas foaming” (Oct. 27, 2015) available at: http://electrospintech.com/gasfoam3d.html#.X5bnPC9h0kg. [cited by applicant]
Borjigin, M., et al., “Proliferation of Genetically Modified Human Cells on Electrospun Nanofiber Scaffolds” Mol. Ther.-Nuc. Acids (2012) 1:e59. [cited by applicant]
Lee, S.J., et al., “The use of thermal treatments to enhance the mechanical properties of electrospun poly(E-caprolactone) scaffolds” Biomaterials (2008) 29:1422-1430. [cited by applicant]
Xie, J., et al., “Electrospray in the dripping mode for cell microencapsulation” J. Colloid Interface Sci. (2007) 312:247-255. [cited by applicant]
Cai, H., et al., “Aerogel Microspheres from Natural Cellulose Nanofibrils and Their Application as Cell Culture Scaffold” Biomacromolecules (2014) 15:2540-2547. [cited by applicant]
Hiwang, P.T.J., et al., “Poly(ε-caprolactone)/gelatin composite electrospun scaffolds with porous crater-like structures for tissue engineering” J Biomed Mater Res A. (2016) 104(4):1017-1029. [cited by applicant]
Wang, W., et al., “Dentin regeneration by stem cells of apical papilla on injectable nanofibrous microspheres and stimulated by controlled BMP-2 release” Acta Biomater. (2016) 36:63-72. [cited by applicant]
Gu, B.K., et al., “Fabrication of sonicated chitosan nanofiber mat with enlarged porosity for use as hemostatic materials” Carbohydr. Polym. (2013) 97(1):65-73. [cited by applicant]
Jiang, J., et al., “Expanded Three-dimensional Nanofiber Scaffolds: Cell Penetration, Neovascularization, and Host Response” Adv. Healthc. Mater. (2016) 5(23): 2993-3003. [cited by applicant]
Gao, Q., et al., “Fabrication of electrospun nanofibrous scaffolds with 3D controllable geometric shapes” Mater. Design (2018) 157:159-169. [cited by applicant]
Boda, S.K., et al., “Electrospraying Electrospun Nanofiber Segments into Injectable Microspheres for Potential Cell Delivery” ACS Appl. Mater. Interfaces (2018) 10:25069-25079. [cited by applicant]
Boda, S.K., et al., “Mineralized nanofiber segments coupled with calcium-binding BMP-2 peptides for alveolar bone regeneration” Acta Biomater. (2019) 85:282-293. [cited by applicant]
Fu, L., et al., “Three-dimensional nanofiber scaffolds with arrayed holes for engineering skin tissue constructs” MRS Communications (2017) 7:361-366. [cited by applicant]
Wei, et al., “The multifunctional wound dressing with core-shell structured fibers prepared by coaxial electrospinning” Front. Mater. Sci. (2016) 10(2):113-121. [cited by applicant]
Su, et al., “Nanofiber Dressings Topically Delivering Molecularly Engineered Human Cathelicidin Peptides for the Treatment of Biofilms in Chronic Wounds” Mol. Pharmaceutics (2019) 16:2011-2020. [cited by applicant]
Su, et al., “Dissolvable Microneedles Coupled with Nanofiber Dressings Eradicate Biofilms via Effectively Delivering a Database-Designed Antimicrobial Peptide” ACS Nano (2020) 14(9):11775-11786. [cited by applicant]