Implantable cell device with supportive and radial diffusive scaffolding

Abstract

The Invention features an implantable cell device that includes a membrane defining and enclosing a chamber; a distance body within the chamber for reducing the diffusion distance for a biological active factor to or across the membrane; and a support scaffold within the chamber for increasing the cell support surface area per unit volume of the chamber for distributing cells.

1 . An implantable cell device comprising:
 a membrane defining and enclosing a chamber;   a distance means, within the chamber, for reducing diffusion distance for a biologically active factor to/across the membrane; and   a support means, within the chamber, for increasing cell support surface area per unit volume of the chamber for distributing cells.   
     
     
         2 . The device according to  claim 1 , wherein the cells are capable of secreting a biologically active factor or providing a biological function to a recipient. 
     
     
         3 . The device according to any of the preceding claims, wherein the biologically active factor is selected from a group consisting of neuropeptides, neurotransmitters, hormones, cytokines, lymphokines, enzymes, biological response modifiers, growth factors, antibodies and trophic factors. 
     
     
         4 . The device according to any of the preceding claims, wherein the membrane is connected to a chamber top at one end and a chamber bottom at the other end. 
     
     
         5 . The device of  claim 4 , wherein the ends comprise a plug. 
     
     
         6 . The device of  claim 5 , wherein the plug comprises glue. 
     
     
         7 . The device according to any of the preceding claims, wherein the membrane comprises at least one biocompatible semi-permeable layer across which the biologically active factor is passed through from the chamber into surroundings such as a central nervous system. 
     
     
         8 . The device according to any of the preceding claims, wherein the membrane is made up of a material selected from a group consisting of polyacrylates including acrylic copolymers, polyvinylidenes, polyvinyl chloride copolymers, polyurethanes, polystyrenes, polyamides, cellulose acetates, cellulose nitrates, polysulfones including polyether sulfones, polyphosphazenes, polyacrylonitriles, poly(acrylonitrile/covinyl chloride), polytetrafluoroethylene, and derivatives, copolymers and mixtures thereof. 
     
     
         9 . The device according to any of the preceding claims, wherein the distance means comprises a body such as a rod, which extends longitudinally from close to a first end of the chamber. 
     
     
         10 . The device according to any of the preceding claims, wherein the distance means comprises a body such as a rod, which extends longitudinally from close to the first end of the chamber to close to a second end of the chamber. 
     
     
         11 . The device according to any of the preceding claims, wherein the distance means extends through one end of the chamber. 
     
     
         12 . The device according to any of the preceding claims, wherein the diffusion distance is defined by relative dimensions of a cross-section of the distance means with respect to a cross-section of the chamber. 
     
     
         13 . The device according to any of the preceding claims, wherein the diffusion distance in a particular radial direction is defined by relative dimensions of the cross-section of the distance means with respect to the cross-section of the chamber and positioning of the distance means within the chamber. 
     
     
         14 . The device according to any of the preceding claims, wherein the cross-section of the distance means includes a shape selected from a group consisting of a regular shape, an irregular shape, a symmetrical shape, an asymmetrical shape and a combination thereof. 
     
     
         15 . The device according to any of the preceding claims, wherein the distance means is made up of a material selected from a group consisting of a metal, an alloy, a polymer and a combination thereof. 
     
     
         16 . The device according to  15 , wherein:
 the metal includes a medical grade titanium or stainless steel;   the alloy includes a medical grade titanium or stainless steel; and   the polymer includes acrylic, polyester, polyethylene, polypropylene, polyacetonitrile, polyethylene terephthalate, nylon, polyamides, polyurethanes, polybutester, silk, cotton, chitin, carbon and biocompatible metals.   
     
     
         17 . The device according to  claim 16 , wherein the distance means comprises a twisted wire. 
     
     
         18 . The device according to any of the preceding claims, wherein the distance means is made up of a material, which is substantially non-toxic to cells. 
     
     
         19 . The device according to any of the preceding claims, wherein the distance means is placed such that:
 at least one end of the distance means is at a centre of the cross-section of the chamber; or   the ends of the distance means are off-centre to the cross-sectional centres of the chamber.   
     
     
         20 . The device according to any of the preceding claims, wherein the distance means is placed at an angle to a longitudinal axis of the chamber. 
     
     
         21 . The device according to any of the preceding claims, wherein the support means comprises a plurality of bristles secured to the distance means at at least one end of the plurality of bristles, the plurality of bristles being spread around and along at least a part of a length of the distance means. 
     
     
         22 . The device according to any of the preceding claims, wherein the support means comprises a plurality of bristles intertwined into a twisted wire to constitute a brush scaffold. 
     
     
         23 . The device according to any of the preceding claims, wherein the support means comprises a plurality of plates secured to the distance means, the plurality of plates being spread around and along at least a part of a length of the distance means. 
     
     
         24 . The device according to any of the preceding claims, wherein the support means comprises a plurality of filaments with a first end of the plurality of filaments secured close to a first end and a second end of the plurality of filaments close to a second end of the distance means, the plurality of filaments being spread around and along a length of the distance means. 
     
     
         25 . The device according to any of the preceding claims, wherein the support means comprises a plurality of filaments, wherein a first end and a second end of the plurality of the filaments are secured to the distance means at different locations along a length of the distance means. 
     
     
         26 . The device according to any of the  claims 24 - 25 , wherein the filament is selected from a group consisting of twisted yarns and woven mesh tubes. 
     
     
         27 . The device according to any of the preceding claims, wherein the support means comprises a coating of a cell-adhesive agent or cell viability enhancing substance. 
     
     
         28 . The device according to any of the preceding claims, wherein the support means includes a cell-adhesive agent or cell viability enhancing substance co-extruded with the distance means. 
     
     
         29 . The device according to any of the preceding claims, wherein the support means divides the chamber into a plurality of compartments defining sub-volumes within the chamber. 
     
     
         30 . The device according to any of the preceding claims, wherein the support means comprises a combination of any of the features of  claims 21 - 29 . 
     
     
         31 . The device according to any of the preceding claims, wherein the support means is made up of a biocompatible, substantially non-degradable material. 
     
     
         32 . The device according to any of the preceding claims, wherein the support means is made up of a material selected from a group consisting of acrylic, polyester, polyethylene, polypropylene, polyacetonitrile, polyethylene terephthalate, nylon, polyamides, polyurethanes, polybutester, silk, cotton, chitin, carbon and biocompatible metals. 
     
     
         33 . The device according to any of the preceding claims, further comprising a plurality of distance means. 
     
     
         34 . The device according to  claim 33 , wherein the plurality of distance means are placed within the chamber in a regular pattern or an irregular pattern. 
     
     
         35 . The device according to any of the  claims 33 - 34 , wherein at least one of the plurality of distance means comprises the support means. 
     
     
         36 . The device according to any of the preceding claims, further comprising a connecting means for connecting the device with a distal end of an elongated tether. 
     
     
         37 . The device according to any of the preceding claims, wherein ratio of diameter of the distance means having circular cross-section relative to diameter of the chamber having circular cross section is in the range of approximately 1:5 to close to 1:1. 
     
     
         38 . The device according to any of the preceding claims, wherein the distance means includes a circular cross-section having a diameter in the range of approximately 50-1000 μm. 
     
     
         39 . The device according to any of the preceding claims, wherein the chamber includes a circular cross-section having a diameter in the range of approximately 250-1500 μm. 
     
     
         40 . The device according to any of the preceding claims wherein the diffusion distance is in the range of approximately 100-500 μm. 
     
     
         41 . The device according to any of the preceding claims, wherein thickness of the membrane is in the range of approximately 50-200 μm. 
     
     
         42 . The device according to any of the preceding claims, wherein the device is an elongated cylindrical capsule with a plug in each end. 
     
     
         43 . The device according to  claim 42 , wherein the diameter of the cylinder is in the range of approximately 350-2000 μm and length of the elongated capsule is in the range of approximately 5-50 mm. 
     
     
         44 . A method for manufacturing an implantable cell device, the method comprising:
 forming a chamber enclosed by a membrane, the chamber comprising a distance means for reducing diffusion distance for a biologically active factor to/across the membrane and a support means for increasing cell support surface area per unit volume of the chamber for distributing cells;   loading the chamber with a population of cells, the cells being capable of secreting a biologically active factor or providing a biological function to a recipient; and   sealing the chamber.   
     
     
         45 . The method according to  claim 44 , further comprising placing the distance means in the chamber such that the distance means is secured to close to a first end of the chamber. 
     
     
         46 . The method according to any of the preceding  claims 44 - 45 , further comprising placing the distance means in the chamber such that a first end of the distance means is secured close to a first end of the chamber and a second end of the distance means is secured close to a second end of the chamber. 
     
     
         47 . The method according to any of the preceding  claims 44 - 46 , further comprising placing the distance means such that:
 at least one end of the distance means is at a centre of the cross-section of the chamber; or   the ends of the distance means are off-centre to the cross-sectional centres of the chamber.   
     
     
         48 . The method according to any of the preceding  claims 44 - 47 , further comprising placing the distance means at an angle to a longitudinal axis of the chamber. 
     
     
         49 . The method according to any of the preceding  claims 44 - 48 , further comprising:
 securing the support means comprising a plurality of bristles to the distance means at at least one end of the plurality of bristles; and   spreading the plurality of bristles around and along at least a part of a length of the distance means.   
     
     
         50 . The method according to any of the preceding  claims 44 - 49 , further comprising:
 securing the support means comprising a plurality of plates to the distance means; and   spreading the plurality of plates around and along at least a part of a length of the distance means.   
     
     
         51 . The method according to any of the preceding  claims 44 - 50 , further comprising:
 securing the support means comprising a plurality of filaments with a first end of the plurality of filaments close to a first end and a second end of the plurality of filaments close to a second end of the distance means; and   spreading the plurality of filaments around and along a length of the distance means.   
     
     
         52 . The method according to any of the preceding  claims 44 - 51 , further comprising securing the support means comprising a plurality of filaments to the distance means such that a first end and the second end of the plurality of the filaments are secured at different locations along a length of the distance means. 
     
     
         53 . The method according to any of the preceding  claims 44 - 52 , further comprising coating the support means with a cell-adhesive agent or cell viability enhancing substance. 
     
     
         54 . The method according to any of the preceding  claims 44 - 53 , further comprising co-extruding the support means comprising a cell-adhesive agent or cell viability enhancing substance co-extruded with the distance means. 
     
     
         55 . The method according to any of the preceding  claims 44 - 54 , further comprising placing a plurality of distance means within the chamber in a regular pattern or an irregular pattern, wherein at least one of the plurality of the distance means comprises the support means. 
     
     
         56 . The method according to any of the preceding  claims 44 - 55 , further comprising providing the device with a connecting means for connecting with a distal end of an elongated tether. 
     
     
         57 . The method according to  claim 44 - 56 , wherein the device includes features claimed in any of the  claims 1 - 43 .