Scaffold for tissue growth and repair

• US 10,420,856 B2
• Filed: 08/22/2016
• Issued: 09/24/2019
• 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:
  US15/242,711
• Publication Number:
  US 20160354515A1
• Time in Patent Office: 1,128 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 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• 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 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: C08L 27/12 containing fluorine atoms
• CPC Class Codes: C08L 27/16 Homopolymers or copolymers or vinylidene fluoride
• 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 5/0618 Cells of the nervous system
• CPC Class Codes: C12N 5/0668 Mesenchymal stem cells from other natural sources

Abstract

Provided is an electroactive structure and method 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 and differentiating a differentiable cell comprising a three dimensional matrix of electro spun fibers;

wherein

the electro spun fibers are formed by electrospinning a biocompatible synthetic piezoelectric polymer at an electric potential of between about 15 kV and about 30 kV;

wherein the electro spun fibers comprise a higher β

phase content than electro spun fibers formed by electrospinning the biocompatible synthetic piezoelectric polymer at an electric potential of less than about 15 kV;

wherein the electro spun fibers are annealed, wherein annealing of the electro spun fibers further increases the β

phase content and enhances piezoelectric characteristics;

wherein the matrix of electro spun fibers forms a scaffold for supporting cell growth and differentiation; and

wherein the scaffold conditions are sufficient to induce differentiation of a mesenchymal stem cell into a cell with either an osteogenic or chondrogenic phenotype.

2. The electroactive structure according to claim 1, wherein the biocompatible synthetic piezoelectric polymer is a homopolymer, a copolymer or combination thereof.

3. The electroactive structure according to claim 2, wherein the homopolymer is a polyvinylidene fluoride (PVDF) homopolymer or a trifluoroethylene homopolymer (TrFE).

4. The electroactive structure according to claim 2, wherein the copolymer is a poly(vinylidene fluoride trifluoroethylene) (PVDF-TrFE) copolymer.

5. The electroactive structure of claim 1, wherein the matrix of electrospun fibers further comprises a growth factor capable of further promoting the differentiation of the mesenchymal stem cell into a cell with osteogenic or chondrogenic phenotype.

6. The electroactive structure of claim 5, wherein the growth factor is associated with the matrix of electrospun 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 of electrospun fibers is forms a non-woven mesh of nanofibers, microfibers or a combination of both.

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

9. The electroactive structure according to claim 1, wherein the fibers are thermally or chemically annealed.

10. The electroactive structure according to claim 1, wherein the osteogenic or chondrogenic phenotype is demonstrated by at least one of increased collagen expression, growth or a combination thereof.

11. The electro active structure according to claim 1, wherein the fibers are formed by electrospinning a biocompatible synthetic piezoelectric polymer at an electric potential of about 25 kV.

12. The electro active structure according to claim 1 further comprising a mesenchymal stem cell.

13. The electro active structure according to claim 1 further comprising a cell with osteogenic or chondrogenic phenotype, wherein the cell has differentiated from a mesenchymal stem cell.

14. An electro active structure for growing and differentiating a differentiable cell comprising a three dimensional matrix of electro spun fibers;

wherein

the electro spun fibers are formed by electrospinning a biocompatible synthetic piezoelectric polymer selected from the group consisting of a polyvinylidene fluoride (PVDF) homopolymer, a trifluoroethylene homopolymer (TrFE) and a poly(vinylidene fluoride trifluoroethylene) (PVDF-TrFE) copolymer at an electric potential of between about 15 kV and about 30 kV;

wherein the electro spun fibers comprise a higher β

phase content than electro spun fibers formed by electrospinning the biocompatible synthetic piezoelectric polymer at an electric potential of less than about 15 kV;

wherein the electro spun fibers are annealed, wherein annealing of the electro spun fibers further increases the β

phase content and enhances piezoelectric characteristics;

wherein the matrix of electro spun fibers forms a scaffold for supporting cell growth and differentiation; and

wherein the scaffold conditions are sufficient to induce differentiation of a mesenchymal stem cell into either an osteogenic or chondrogenic phenotype.