Thin Film Cell Encapsulation Devices

Abstract

Thin film devices, e.g., multilayer thin film devices, that encapsulate cells for transplantation into a subject are provided. Also provided are methods of using and methods of preparing the subject devices. The thin film devices include a first porous polymer layer and a second porous polymer layer that define a lumen therebetween and encapsulate a population of cells within the lumen. The thin film devices can promote vascularization into the lumen of the device via the pores in the first polymer layer and/or second polymer layer; limit foreign body response to the device; limit ingress of cells, immunoglobulins, and cytokines into the lumen via the first and the second polymer layers; and release from the first polymer layer and/or the second polymer layer molecules secreted by the population of cells.

1 . A method for transplanting cells in a subject, the method comprising:
 (a) providing a thin film device comprising:   (i) a first nanoporous or microporous polymer layer;   (ii) a second nanoporous or microporous polymer layer, wherein the first and second layers define a lumen between the first and second layers; and   (iii) a population of cells disposed in the lumen between the first and second layers, wherein first and second polymer layers are less than 15 μm thick, and the device has a surface area of 1 cm 2  to 5 cm 2 ,   (b) transplanting the device into a subject, wherein one or more of: (i) vascularization into the lumen of the device via the pores in the first polymer layer and/or second polymer layer; (ii) a limited foreign body response to the device; (iii) a limited ingress of cells, immunoglobulins, and cytokines into the lumen via the first and the second polymer layers, is observed.   
     
     
         2 . The method of  claim 1 , further comprising releasing from the first polymer layer and/or the second polymer layer molecules secreted by the population of cells. 
     
     
         3 . The method of  claim 1 , wherein the population of cells survives for at least one month after the transplanting. 
     
     
         4 . The method of  claim 1 , wherein the population of cells comprises pancreatic islet cells and wherein the pancreatic islet cells respond to glucose level of the subject by secreting insulin. 
     
     
         5 . The method of  claim 1 , wherein the subject has or is predisposed to developing diabetes. 
     
     
         6 . The method of  claim 1 , wherein the first and second polymer layers are nanoporous polymer layers. 
     
     
         7 . The method of  claim 1 , wherein the first and second polymer layers are microporous polymer layers. 
     
     
         8 . The method of  claim 1 , wherein the first polymer layer is a nanoporous polymer layer and the second polymer layer is a microporous polymer layer. 
     
     
         9 . The method of  claim 1 , wherein first and second polymer layers comprise poly-caprolactone (PCL). 
     
     
         10 . The method of  claim 1 , wherein the first and second polymer layers are sealed along the entire periphery of the device thereby providing a closed lumen. 
     
     
         11 . The method of  claim 1 , wherein the lumen comprises an opening at which the first and second polymer layers are not sealed to each other. 
     
     
         12 . The method of  claim 1 , wherein the lumen comprises an opening at which the first and second layers are not in contact with each other, the device further comprising a tubing comprising a first end and a second end distal to the first end, wherein the first end of the tubing is positioned in the opening and the second end is configured to introduce the population of cells into the lumen. 
     
     
         13 . The method of  claim 1 , wherein the lumen comprises a first opening and a second opening at which the first and second layers are not in contact with each other, the device further comprising a first tubing and a second tubing, each of the first and second tubing comprising a first end and a second end distal to the first end, wherein the first end of the first tubing is positioned in the first opening and the first end of the second tubing is positioned in the second opening, and wherein the second end of each tubing is used for ingress or egress of fluids from the lumen. 
     
     
         14 . The method of  claim 13 , wherein the method comprises after the transplanting, attaching the second ends of the first and second tubing to a fill port. 
     
     
         15 . The method of  claim 14 , wherein the fill port comprises a first chamber in fluid communication at the fill port with the second end of the first tubing; and a second chamber in fluid communication at the fill port with the second end of the second tubing. 
     
     
         16 . A thin film device for transplanting cells in a subject, the device comprising:
 a first nanoporous or microporous polymer layer;   a second nanoporous or microporous polymer layer, wherein the first and second polymer layers define a lumen between the first and second polymer layers; and   a population of cells disposed in the lumen between the first and second polymer layers,   wherein first and second layers are less than 15 μm thick, and the device has a surface area of 1 cm 2  to 5 cm 2 , and wherein (a) the pores in the first and second polymer layers limit ingress of cells, immunoglobulins, and cytokines into the lumen via the first and the second layers, (b) the pores are sized to promote vascularization into the lumen of the device, (c) the device is configured to limit foreign body response to the transplanted device, and (d)   the pores are sized to release molecules secreted by the population of cells.   
     
     
         17 . The device of  claim 16 , wherein the first and second polymer layers are nanoporous layers. 
     
     
         18 . The device of  claim 16 , wherein the first and second polymer layers are microporous layers. 
     
     
         19 . The device of  claim 16 , wherein the first polymer layer is a nanoporous polymer layer and the second polymer layer is a microporous polymer layer. 
     
     
         20 .- 27 . (canceled) 
     
     
         28 . A method for making a device of  claim 16 , the method comprising:
 placing a first nanoporous or microporous polymer layer over a second nanoporous or microporous polymer layer, wherein the first and second polymer layers are similarly dimensioned;   sealing the first and the second polymer layers along the periphery of the polymer layers leaving an unsealed area at a location along the periphery to provide an opening for access to a lumen defined between the first and second layers and the periphery of the polymer layers at which the polymer layers are sealed together,   placing a population of cells into the lumen through the opening; and   sealing the opening.   
     
     
         29 .- 33 . (canceled)