Cell impregnated sleeve for paracrine and other factor production

• US 10,561,830 B2
• Filed: 10/07/2014
• Issued: 02/18/2020
• Est. Priority Date: 10/08/2013
• Status: Active Grant

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Hwang, Chao-Wei, Xia, Zhiyong, Bogdan, Virginia E., Brinker, Jeffrey A., Gerstenblith, Gary, Johnston, Peter V., Schulman, Steven P., Tomaselli, Gordon, Weiss, Robert G.
• Primary Examiner(s): Singh, Satyendra K
• Application Number:
  US15/025,902
• Publication Number:
  US 20160235956A1
• Time in Patent Office: 1,960 Days
• CPC Class Codes: A61F 2/04 Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts A61F2/18, A61F2/20 take precedence; devices, other than stent-grafts, providing patency to, or preventing collapsing of, tubular structures of the body other than stent-grafts, e.g. stents A61F2/82; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95
• CPC Class Codes: A61F 2002/072 Encapsulated stents, e.g. wire or whole stent embedded in lining
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/256 Antibodies, e.g. immunoglobulins, vaccines
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 27/18 obtained otherwise than 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: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/005 Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: A61L 33/08 : Polysaccharides
• CPC Class Codes: A61M 2202/09 : Body tissue
• CPC Class Codes: A61M 2205/04 : implanted
• CPC Class Codes: A61M 37/00 : Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Certain embodiments according to the present invention provide sleeve devices suitable for a wide range of therapeutic uses. In accordance with certain embodiments, the therapeutic sleeve device includes a nanofiber fabric assembly, which defines a plurality of pores, and at least one layer of cells embedded in the nanofiber fabric assembly.

Claims

1. A therapeutic sleeve device configured to be wrapped around an object and inserted into a subject, the therapeutic sleeve device comprising:

(a) a nonwoven fiber fabric assembly defining a plurality of pores, wherein said nonwoven fiber fabric assembly comprises a nanofiber fabric assembly comprising at least one of poly(lactic acid), poly(L-lactic acid), poly(lactic-co- glycolic acid) copolymer, polycaprolactone, or polyethylene terephthalate; and

(b) a plurality of stem cells, each stem cell of the plurality of stem cells embedded in one of the plurality of pores of the nonwoven fiber fabric assembly,

wherein each stem cell of the plurality of stem cells is configured to emit paracrine factors, the paracrine factors being configured to promote healing of a tissue, organ, or wound of the subject,

wherein each stem cell of the plurality of stem cells has a cell diameter,

wherein each pore of the plurality of pores has a maximal pore size of less than 10 microns in diameter,

wherein the maximal pore size of each pore is less than the cell diameter to form a cage inside which any of the plurality of stem cells is embedded and retained thereby configuring the cage to prevent interaction between cells of the subject and the plurality of stem cells in response to the therapeutic sleeve device being inserted into the subject, and

wherein the maximal pore size is larger than a diameter of the paracrine factors emitted by each stem cell of the plurality of stem cells to allow for the paracrine factors to be emitted through the cage while the cage prevents washout and dilution of the plurality of stem cells from the therapeutic sleeve.

2. The therapeutic sleeve device according to claim 1, wherein the nonwoven fiber fabric assembly comprises a first nonwoven fiber fabric layer and a second nonwoven fiber fabric layer and the plurality of stem cells are embedded between the first nonwoven fiber fabric layer and the second nonwoven fiber fabric layer.

3. The therapeutic sleeve device according to claim 1, wherein the stem cells are mesenchymal stem cells.

4. The therapeutic sleeve device according to claim 1, wherein the maximal pore size is less than cell diameters of the cells of the subject.

5. The therapeutic sleeve device according to claim 4, wherein the cells of the subject comprise host immune cells.

6. The therapeutic sleeve device according to claim 1, wherein an average pore size is greater than embedded cell product, nutrient, or waste diameters.

7. The therapeutic sleeve device according to claim 6, wherein the average pore size is greater than about 100 nanometers, the cell diameter is about 20 microns, and paracrine factor diameters are less than 100 nanometers.

8. The therapeutic sleeve device according to claim 6, wherein the average pore size is greater than about 300 nanometers, the cell diameter is about 20 microns, and exosome diameters are about 300 nanometers.

9. The therapeutic sleeve device according to claim 1, wherein the nanofiber fabric assembly further comprises at least one of collagen, peptides, proteins, nucleic acids, fatty acids, gelatin, chitosan, or hyaluronic acid.

10. The therapeutic sleeve device according to claim 1, further comprising at least one layer of adhesion molecules.

11. The therapeutic sleeve device according to claim 10, wherein the adhesion molecules comprise at least one of fibronectin, fibrinogen, laminins, collagen, vitronectin, proteoglycans, arginyl-glycyl-aspartic (RGD) acid peptides, or cell specific antibodies.

12. The therapeutic sleeve device according to claim 11, wherein the cell specific antibodies comprise anti-CD29 antibody.

13. The therapeutic sleeve device according to claim 1, further comprising at least one layer of an antithrombotic material.

14. The therapeutic sleeve device according to claim 13, wherein the antithrombotic material comprises at least one of an anticoagulant or an anti-platelet agent.