Multi-layered microfibers and use thereof

Abstract

Multi-layered electrospun microfibers and/or microtubes, comprising cells and/or molecules of interest. The invention is further directed to compositions comprising said microfibers and/or microtubes and methods of use thereof in various applications.

1 . A concentric multi-layered electrospun microfiber comprising an exterior layer, an interior layer, and an intermediate layer residing between the exterior layer and the interior layer, said intermediate layer comprises one or more water soluble polymers, and said interior layer comprises cells and/or molecules of interest. 
     
     
         2 . The concentric multi-layered electrospun microfiber of  claim 1 , wherein interior layer further comprises water soluble polymers or oligomers. 
     
     
         3 . The microfiber of  claim 1  being a triple-layer microfiber. 
     
     
         4 . The microfiber of  claim 1 , wherein said microfiber is hollow. 
     
     
         5 . The microfiber of  claim 1 , wherein said interior layer, intermediate layer and/or interior layer are substantially porous layers. 
     
     
         6 . The microfiber of  claim 1 , wherein said water soluble polymers of said intermediate layer are selected from natural polymers, synthetic polymers or combinations thereof. 
     
     
         7 . The microfiber of  claim 1 , wherein said exterior layer comprises one or more organic soluble polymers. 
     
     
         8 . The microfiber of  claim 7 , wherein said organic soluble polymer of said exterior layer is selected from the group consisting of: poly(vinylidenefluoride), poly (e-caprolactone) (PCL), polyamide, poly(siloxane), poly(silicone), poly(ethylene), poly(2-hydroxy ethylmethacrylate), poly(methyl methacrylate), poly(vinyl acetate), polyacrylamide, poly(ethylene-co-vinyl acetate), poly(methacrylic acid), polylactide, polyglycolide, poly(lactide-co-glycolide), polyanhydride, polyorthoester, poly(carbonate), poly(acrylo nitrile), polyaniline, polyvinyl carbazole, polystyrene, poly(vinyl phenol), polyhydroxyacid, poly(caprolactone), polyanhydride, polyhydroxyalkanoate, polyurethane, collagen, cellulose, and combination/copolymers thereof. 
     
     
         9 . The microfiber of  claim 7 , wherein said organic-soluble polymer is poly(vinylidenefluoride-co-hexafluor-opropylene) (PVDF-HFP). 
     
     
         10 . The microfiber of  claim 1 , wherein said exterior layer comprises any one of water-soluble polymers and antifouling agents. 
     
     
         11 . The microfiber of  claim 10 , wherein said exterior layer comprises water soluble polymers selected from the group consisting of: poly(vinyl pyrrolidone), poly(N-vinyl pyrrolidone), poly(vinyl alcohol), poly(acrylic acid), poly(ethylene glycol), poly(ethylene oxide), albumin, alginate, chitosan, starch, hyaluronic acid, albumin, alginate, chitosan, starch, polypetides and combination/ copolymers thereof. 
     
     
         12 . (canceled) 
     
     
         13 . The microfiber of  claim 1 , wherein said water soluble polymers of said intermediate layer are selected from the group consisting of poly(acrylic acid), poly(vinyl pyrrolidone), poly(N-vinyl pyrrolidone), poly(vinyl alcohol), poly(acrylic acid) poly(ethylene glycol), poly(methacrylic acid), poly(ethylene oxide), polyhydroxyacid, alginate, starch, chitosan, dextran, albumin, chitosan, hyaluronic acid, polyppertides and combination/copolymers thereof. 
     
     
         14 . The microfiber of  claim 2 , wherein said water soluble polymers and/or oligomers of said interior layer are selected from natural and synthetic polymers and/or oligomers, or combinations thereof. 
     
     
         15 . The microfiber of  claim 14 , wherein any one of: (i) said water soluble synthetic polymer is selected from the group consisting of PVA, PVP, PEO, PAA, polystyrene sulfonate and combinations or copolymers thereof, (ii) said water soluble natural polymer is selected from the group consisting of polysaccharides (e.g. alginate), starch, hyaluronic acid, alginate, dextran, chitosan and combinations or copolymers thereof; and (iii) said oligomer is selected from the group consisting of chitosan oligomeric derivatives, and saccharides oligomers. 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . The microfiber of  claim 1 , wherein the cell concentration within said internal layer is at least 10 OD. 
     
     
         19 . The microfiber of  claim 1 , wherein said interior layer further comprises media for maintaining and/or supporting said cell viability and/or activity. 
     
     
         20 . The microfiber of  claim 1 , wherein said molecules of interest are selected from hormones, growth factors, enzymes, nutrients and shock resistance molecules. 
     
     
         21 . The microfiber of  claim 1 , wherein any one of said exterior layer, intermediate layer, or internal layer has a thickness of about 5 nm to 10 micrometer, optionally wherein said interior layer has a diameter of at most 50 micrometer. 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . A method for producing a concentric triple-layered microfiber, the method comprising:
 providing a first polymeric solution for forming an exterior layer of the microfiber, a second polymeric solution for forming an intermediate layer of the microfiber, and a third solution for forming an interior layer or a core of the microfiber, said third solution comprises cells; and   co-electrospinning the first polymeric solution, second polymeric solution and the third solution through a triple-axial capillaries,   thereby producing the concentric triple-layered microfiber.   
     
     
         26 . The method of  claim 25 , wherein any one of (i) the first polymeric solution solidifies faster than the second polymeric solution; (ii) the second polymeric solution solidifies faster than the third solution; (iii) the second polymeric solution and said third solution comprise the same solvent; (iv) the second polymeric solution comprises a solvent which is incapable of dissolving the first polymeric solution; (v) any combination thereof. 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled)