Piezoelectric scaffold for nerve growth and repair

• US 9,771,557 B2
• Filed: 04/21/2016
• Issued: 09/26/2017
• Est. Priority Date: 03/12/2009
• Status: Active Grant

• Current Assignee: New Jersey Institute of Technology
• Original Assignee: New Jersey Institute of Technology
• Inventors: Arinzeh, Treena, Collins, George, Lee, Yee-Shuan
• Primary Examiner(s): Lankford, Blaine
• Application Number:
  US15/134,639
• Publication Number:
  US 20170051251A1
• Time in Patent Office: 523 Days
• Field of Search: None
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 2430/32 for nerve reconstruction
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/3675 Nerve tissue, e.g. brain, spinal cord, nerves, dura mater
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C08L 27/16 Homopolymers or copolymers or vinylidene fluoride
• CPC Class Codes: C12N 2501/13 Nerve growth factor [NGF]; Brain-derived neurotrophic factor [BDNF]; Cilliary neurotrophic factor [CNTF]; Glial-derived neurotrophic factor [GDNF]; Neurotrophins [NT]; Neuregulins
• CPC Class Codes: C12N 2513/00 3D culture
• CPC Class Codes: C12N 2529/00 Culture process characterised by the use of electromagnetic stimulation
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0619 Neurons

Abstract

Provided is an electroactive structure for growing isolated differentiable cells comprising a three dimensional matrix of fibers formed of a biocompatible synthetic piezoelectric polymeric material, wherein the matrix of fibers is seeded with the isolated differentiable cells and forms a supporting scaffold for growing the isolated differentiable cells, and wherein the matrix of fibers stimulates differentiation of the isolated differentiable cells into a mature cell phenotype on the structure.

Claims

1. An electroactive structure for growing an isolated differentiable cell comprising

a three-dimensional matrix of electrospun fibers comprising a biocompatible synthetic permanently piezoelectric polymeric material, wherein the fibers are annealed, either thermally or chemically, and demonstrate enhanced piezoelectric characteristics, crystal organization or a combination of both, wherein the matrix forms a supporting scaffold for growing the differentiable cell, and

at least one isolated differentiable neural progenitor cell seeded in the matrix.

2. The electroactive structure according to claim 1, wherein the matrix of fibers stimulates differentiation of the isolated differentiable neural cell into a mature neural cell phenotype on the structure.

3. The electroactive structure according to claim 1, wherein the biocompatible synthetic permanently piezoelectric polymeric material is poly(vinylidene fluoride trifluoroethylene) copolymer.

4. The electroactive structure of claim 2, wherein the matrix of fibers further comprises a growth factor capable of further promoting the differentiation of the isolated differentiable neural cell into a mature neural cell phenotype.

5. The electroactive structure of claim 4, wherein the growth factor is at least one of NGF, BDNF or a combination of both.

6. The electroactive structure of claim 5, wherein the growth factor is associated with the matrix of fibers through at least one of a covalent interaction, a non-covalent interaction or a combination of both.

7. The electroactive structure according to claim 1, wherein the matrix fibers is a non-woven mesh of nanofibers, microfibers or a combination of both.

8. The electroactive structure according to claim 1, wherein matrix fibers are arranged in the matrix randomly, substantially aligned or a combination of both.

9. The electroactive structure according to claim 4, wherein the mature neural cell phenotype is demonstrated by at least one of increased tubulin expression, reduced expression of nestin, neurite growth or a combination thereof.

10. The electroactive structure according to claim 1, wherein the fibers have an average fiber diameter of from about 500 nm to about 5 μ

m.