Cell encapsulation device comprising a porous tube

Abstract

A cell encapsulation device for implantation in a body includes one or more cell encapsulation layers, each of the one or more cell encapsulation layers including at least one membrane and a guide tube. The at least one membrane is semi-permeable. The at least one membrane forms a chamber for encapsulating cells and at least one entry port through the at least one membrane. The guide tube extends from the at least one entry port into the chamber. The guide tube includes a porous wall along at least a portion of its length. The guide tube is capable of guiding movement of a catheter inside the chamber.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 721,063, filed August 22, 2018, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This disclosure relates to implantable medical devices and methods for cell encapsulation. More specifically, this disclosure relates to implantable devices and methods for encapsulating insulin-secreting cells. Background Technology

[0004] Implantable medical devices that utilize the encapsulation of insulin-secreting cells to treat diabetes present several challenges. One issue is the lack of robustness in these devices due to the inability to provide sufficient cellular maintenance substances (such as oxygen and nutrients) to not only keep the insulin-secreting cells alive but also healthy enough to secrete insulin. Other problems include the difficulty, trauma, and inherent risks associated with the surgery required to implant the encapsulated device.

[0005] Improvements are needed in implantable devices used to encapsulate cells, which reduce the risks associated with the surgery required to implant the encapsulation device and enhance the robustness of the device. Summary of the Invention

[0006] Example 1 is a cell encapsulation device for transplantation in the body. The cell encapsulation device includes one or more cell encapsulation layers, each of which includes at least one membrane and a guide tube. The at least one membrane is semi-permeable. The at least one membrane forms a chamber for encapsulating cells and at least one inlet port through the at least one membrane. The guide tube extends from the at least one inlet port into the chamber. The guide tube includes a porous wall along at least a portion of its length. The guide tube is capable of guiding the movement of the catheter within the chamber.

[0007] Example 2 is the cell encapsulation device of Example 1, wherein at least one membrane includes a first membrane and a second membrane. Each layer of one or more cell encapsulation layers further includes a first set of multiple weld lines. The second membrane is attached to the first membrane via the first set of multiple weld lines. The first membrane, the second membrane, and the first set of multiple weld lines define the chamber.

[0008] Example 3 is a cell encapsulation device of either Example 1 or 2, wherein the guide tube is at least partially composed of a metal mesh.

[0009] Example 4 is a cell encapsulation device according to any of Examples 1 to 3, wherein each layer of the cell encapsulation layer further includes a second set of multiple weld lines defining at least two cell channels located inside the chamber, and a third set of multiple weld lines defining a guide tube channel in fluid communication with the at least two cell channels. The guide tube is accommodated inside the guide tube channel.

[0010] Example 5 is a cell encapsulation device according to any of Examples 1 to 4, the device further comprising at least one inlet conduit extending from at least one inlet port in a direction remote from the chamber. The at least one inlet conduit is fluidly connected to a guide tube.

[0011] Example 6 is the cell encapsulation device of Example 5, wherein at least one inlet port includes a first inlet port and a second inlet port. At least one inlet conduit includes a first inlet conduit fluidly connected to the first inlet port and a second inlet conduit fluidly connected to the second inlet port. A guide tube extends from the first inlet port through the chamber to the second inlet port.

[0012] Example 7 is a cell encapsulation device of Example 6, wherein one or more cell encapsulation layers include a first cell encapsulation layer and a second cell encapsulation layer. A second inlet conduit of the first cell encapsulation layer is fluidly connected to a first inlet conduit of the second cell encapsulation layer to fluidly connect the first cell encapsulation layer to the second cell encapsulation layer.

[0013] Example 8 is a cell encapsulation device according to any of Examples 5 to 7, wherein the cell encapsulation device further includes an injection port connected to an end of the inlet catheter opposite to the chamber, the injection port including a port cover, an outer septum, and an inner septum. The port cover forms a port lumen extending through the port cover. The end of the port cover closest to the inlet catheter is in fluid communication with the inlet catheter. The outer septum extends across and seals the port lumen. The inner septum extends across and seals the port lumen. The inner septum is spaced from the outer septum to form a space within the port lumen and between the inner and outer septums. The inner septum is disposed between the outer septum and the inlet catheter. The outer and inner septa are made of an elastic polymer.

[0014] Example 9 is a system for intracorporeal cell transplantation. The system includes a cell encapsulation device according to any of Examples 5 to 8 and a first external catheter capable of passing through at least one inlet catheter into a guide tube to guide movement of the first external catheter within the chamber.

[0015] Example 10 is the system of Example 9, wherein the first external catheter is capable of distributing cells through the porous wall of the guide tube into the chamber as the first external catheter moves through the guide tube.

[0016] Example 11 is the system of Example 9, wherein the first external conduit includes a first inner cavity having a first inner cavity opening and a second inner cavity having a second inner cavity opening. The first inner cavity opening and the second inner cavity opening are spaced apart from each other along a guide tube. The first inner cavity opening is capable of distributing fluid through the porous wall of the guide tube into the chamber. The second inner cavity opening is capable of extracting fluid from the chamber through the porous wall of the guide tube.

[0017] Example 12 is the system of Example 11, wherein the second inner cavity is arranged coaxially with the first inner cavity. The first external conduit further includes a flange disposed between the opening of the first inner cavity and the opening of the second inner cavity. The flange projects outward toward the guide tube to deflect liquid dispensed from the first inner cavity toward the porous wall of the guide tube.

[0018] Example 13 is the system of Example 9, wherein the first external conduit includes a first lumen and is capable of passing through the first inlet conduit into the guide tube. The system further includes a second external conduit having a second lumen. The second external conduit is capable of passing through the second inlet conduit into the guide tube opposite to the first external conduit. The first and second external conduits are spaced apart from each other inside the chamber. The first external conduit is capable of dispensing fluid through the porous wall of the guide tube into the chamber. The second external conduit is capable of removing fluid from the chamber through the porous wall of the guide tube.

[0019] Example 14 is the system of Example 9, wherein at least one inlet port includes a first inlet port and a second inlet port. At least one inlet conduit includes a first inlet conduit fluidly connected to the first inlet port and a second inlet conduit fluidly connected to the second inlet port. A guide tube extends from the first inlet port through the chamber to the second inlet port. A first external conduit is capable of entering the chamber through the first inlet conduit, passing through the guide tube, and exiting the chamber through the second inlet conduit.

[0020] Example 15 is a method for fabricating a cell encapsulation device for transplantation in the body. The method includes: placing a first semipermeable membrane directly onto a second semipermeable membrane; attaching the first semipermeable membrane to the second semipermeable membrane using a first set of multiple weld lines defining a chamber for encapsulating cells, a second set of multiple weld lines defining at least two cell channels within the chamber, and a third set of multiple weld lines defining a guide tube channel in fluid communication with the at least two cell channels; inserting a guide tube into the chamber through the guide tube channel and via an inlet port, the guide tube including a porous wall along at least a portion of its length; and attaching one end of the guide tube to at least one of the first and second semipermeable membranes surrounding the inlet port.

[0021] Example 16 is a cell encapsulation device for transplantation in the body. The cell encapsulation device includes one or more cell encapsulation layers, each layer including a first semi-permeable membrane, a second semi-permeable membrane, a first set of multiple weld lines, and a guide tube. The second membrane is attached to the first membrane via the first set of multiple weld lines. The first membrane, the second membrane, and the first set of multiple weld lines define a chamber for encapsulating cells. The chamber includes at least one inlet port. The guide tube extends from the at least one inlet port into the chamber. The guide tube includes a porous wall along at least a portion of its length. The guide tube is capable of guiding movement of the catheter within the chamber.

[0022] Example 17 is a cell encapsulation device of Example 16, wherein the guide tube includes a metal mesh.

[0023] Example 18 is the cell encapsulation device of Example 17, wherein the metal mesh comprises a metal selected from the group consisting of stainless steel, titanium, platinum, alloys of chromium and cobalt, alloys of nickel and titanium, and alloys of cobalt, chromium, nickel and molybdenum.

[0024] Example 19 is a cell encapsulation of Example 16, wherein each layer of the cell encapsulation layer further includes a second set of multiple weld lines defining at least two cell channels located inside the chamber, and a third set of multiple weld lines defining a guide tube channel in fluid communication with the at least two cell channels. The guide tube is accommodated inside the guide tube channel.

[0025] Example 20 is the cell encapsulation device of Example 16, which further includes at least one inlet conduit extending from at least one inlet port in a direction away from the chamber, and at least one inlet conduit fluidly connected to a guide tube.

[0026] Example 21 is the cell encapsulation device of Example 20, wherein at least one inlet port includes a first inlet port and a second inlet port. At least one inlet conduit includes a first inlet conduit fluidly connected to the first inlet port and a second inlet conduit fluidly connected to the second inlet port. A guide tube extends from the first inlet port through the chamber to the second inlet port.

[0027] Example 22 is a cell encapsulation device of Example 21, wherein one or more cell encapsulation layers include a first cell encapsulation layer and a second cell encapsulation layer. A second inlet conduit of the first cell encapsulation layer is fluidly connected to a first inlet conduit of the second cell encapsulation layer to fluidly connect the first cell encapsulation layer to the second cell encapsulation layer.

[0028] Example 23 is a cell encapsulation device of Example 20, wherein the cell encapsulation device further includes an injection port fluidly connected to at least one end of an inlet catheter opposite to the chamber. The injection port includes a port cover, an outer septum, and an inner septum. The port cover forms a port lumen extending through the port cover. The end of the port cover closest to the inlet catheter is in fluid communication with the inlet catheter. The outer septum extends through and seals the port lumen. The inner septum extends through and seals the port lumen. The inner septum is spaced from the outer septum to form a space within the port lumen and between the inner and outer septums. The inner septum is disposed between the outer septum and the inlet catheter. The outer and inner septa are made of an elastic polymer.

[0029] Example 24 is a system for cell transplantation in the body. The system includes a cell encapsulation device and at least one inlet conduit. The cell encapsulation device includes one or more cell encapsulation layers, each layer including a first semi-permeable membrane, a second semi-permeable membrane, a first set of multiple weld lines, and a guide tube. The second membrane is attached to the first membrane via the first set of multiple weld lines. The first membrane, the second membrane, and the first set of multiple weld lines define a chamber for encapsulating cells. The chamber includes at least one inlet port. The guide tube extends from the at least one inlet port into the chamber. The guide tube includes a porous wall along at least a portion of its length. At least one inlet conduit extends from the at least one inlet port in a direction away from the chamber. The at least one inlet conduit is fluidly connected to the guide tube. A first external conduit is capable of passing through the at least one inlet conduit into the guide tube. The guide tube is capable of guiding movement of the first external conduit within the chamber.

[0030] Example 25 is the system of Example 24, wherein the first external catheter is capable of distributing cells through the porous wall of the guide tube into the chamber as the first external catheter moves through the guide tube.

[0031] Example 26 is the system of Example 24, wherein the first external conduit includes a first inner cavity having a first inner cavity opening and a second inner cavity having a second inner cavity opening. The first inner cavity opening and the second inner cavity opening are spaced apart from each other along a guide tube. The first inner cavity opening is capable of distributing fluid through the porous wall of the guide tube into the chamber. The second inner cavity opening is capable of extracting fluid from the chamber through the porous wall of the guide tube.

[0032] Example 27 is the system of Example 26, wherein the second inner cavity is arranged coaxially with the first inner cavity. The first external conduit further includes a flange disposed between the openings of the first and second inner cavities. The flange projects outward toward the guide tube to deflect liquid dispensed from the first inner cavity toward the porous wall of the guide tube.

[0033] Example 28 is the system of Example 24, further comprising a second external conduit having a second inner cavity. The first external conduit includes a first inner cavity. At least one inlet port includes a first inlet port and a second inlet port. A guide tube extends from the first inlet port through the chamber to the second inlet port. At least one inlet conduit includes a first inlet conduit fluidly connected to the first inlet port and a second inlet conduit fluidly connected to the second inlet port. The first external conduit is capable of passing through the first inlet conduit into the guide tube. The second external conduit is capable of passing through the second inlet conduit in the opposite direction to the first external conduit into the guide tube. The first and second external conduits are spaced apart from each other inside the chamber. The first external conduit is capable of dispensing liquid through the porous wall of the guide tube into the chamber. The second external conduit is capable of removing fluid from the chamber through the porous wall of the guide tube.

[0034] Example 29 is the system of Example 28, further comprising a guidewire extending through a first inner lumen and a second inner lumen. The guidewire includes a flange projecting toward a guide tube between the first and second outer conduits to deflect fluid dispensed from the first outer conduit toward the porous wall of the guide tube.

[0035] Example 30 is the system of Example 24, wherein at least one inlet port includes a first inlet port and a second inlet port. At least one inlet conduit includes a first inlet conduit fluidly connected to the first inlet port and a second inlet conduit fluidly connected to the second inlet port. A guide tube extends from the first inlet port through a chamber to the second inlet port. A first external conduit is capable of entering the chamber, passing through the first inlet conduit, passing through the guide tube, and exiting the chamber through the second inlet conduit.

[0036] Example 31 includes the system of Example 24, wherein the cell encapsulation device further includes an injection port fluidly connected to at least one end of an inlet catheter opposite to the chamber. The injection port includes a port cover, an outer septum, and an inner septum. The port cover forms a port lumen extending through the port cover. The end of the port cover closest to the inlet catheter is in fluid communication with the inlet catheter. The outer septum extends through and seals the port lumen. The inner septum extends through and seals the port lumen. The inner septum is spaced from the outer septum to form a space within the port lumen and between the inner and outer septums. The inner septum is disposed between the outer septum and the inlet catheter. The outer and inner septa are made of an elastic polymer.

[0037] Example 32 is the system of Example 31, further comprising an outer tubular needle and an inner tubular needle. The outer tubular needle is capable of penetrating an outer septum. The outer septum is capable of providing a seal near the outer tubular needle. The inner tubular needle is capable of passing through the outer tubular needle and penetrating the inner septum. The inner septum is capable of providing a seal near the inner tubular needle. A first external conduit is capable of passing through the inner tubular needle, at least one inlet conduit, and entering a guide tube.

[0038] Example 33 is a method for fabricating a cell encapsulation device for transplantation in the body. The method includes: placing a first semipermeable membrane directly onto a second semipermeable membrane; attaching the first semipermeable membrane to the second semipermeable membrane using a first set of multiple welding wires defining a chamber for encapsulating cells; inserting a guide tube into the chamber through a first inlet port, the guide tube including a porous wall along at least a portion of its length; and attaching one end of the guide tube to at least one of the first and second semipermeable membranes surrounding the first inlet port.

[0039] Example 34 is the method of Example 33, wherein a first semipermeable membrane is attached to a second semipermeable membrane using a second set of multiple welding lines defining at least two cell channels inside the chamber and a third set of multiple welding lines defining a guide tube channel in fluid communication with at least two cell channels; and further includes inserting the guide tube into the chamber by inserting the guide tube into the guide tube channel and entering the chamber through a first inlet port.

[0040] Example 35 is the method of Example 33, which further includes attaching an end of a guide tube opposite to the end of a guide tube attached to at least one of the first and second semipermeable membranes surrounding the first inlet port to at least one of the first and second semipermeable membranes surrounding the second inlet port into the chamber.

[0041] While several embodiments have been disclosed, other embodiments of the invention will become apparent to those skilled in the art based on the following detailed description of the illustrative embodiments that disclose and describe the invention. Therefore, the drawings and detailed description are considered to be illustrative in nature rather than limiting. Attached Figure Description

[0042] Figure 1 This is a schematic top view of a cell encapsulation device according to some embodiments of the present disclosure.

[0043] Figure 2 It is based on some implementation schemes disclosed herein. Figure 1 A schematic cross-sectional top view of the cell encapsulation layer of the cell encapsulation device.

[0044] Figure 3 It is based on some implementation schemes disclosed herein. Figure 1A schematic cross-sectional view of the cell encapsulation layer of the cell encapsulation device.

[0045] Figure 4A and Figure 4B This is a schematic cross-sectional top view of a system for cell transplantation according to some embodiments of this disclosure.

[0046] Figure 5 It is based on some implementation schemes disclosed herein. Figure 4A and Figure 4B A schematic side view of a part of the system.

[0047] Figure 6 It is based on yet another implementation scheme of this disclosure. Figure 4A and Figure 4B A schematic side view of a part of the system.

[0048] Figure 7 This is a schematic cross-sectional top view of another system for cell transplantation according to some embodiments of this disclosure.

[0049] Figure 8 This is a schematic side view of a part of yet another system for cell transplantation according to some embodiments of this disclosure.

[0050] Figure 9 This is a side view of another cell encapsulation device according to some embodiments of this disclosure.

[0051] Figure 10 This is a side view of yet another cell encapsulation device according to some embodiments of this disclosure.

[0052] Figure 11 This is a schematic longitudinal sectional view of a portion of a cell encapsulation device including a subcutaneous injection port, according to an embodiment of this disclosure.

[0053] Figures 12A-12D This is a schematic longitudinal cross-sectional view of part of another system for cell encapsulation according to some embodiments of this disclosure.

[0054] While the disclosed subject matter may have various modifications and alternatives, specific embodiments have been shown by way of example in the accompanying drawings and are described in detail below. However, it is not intended to limit this disclosure to the specific embodiments described. Rather, this disclosure is intended to cover all modifications, equivalents, and alternatives that fall within the scope of the disclosed subject matter as defined by the appended claims. Detailed Implementation

[0055] The devices according to this disclosure include implantable instruments for encapsulating cells. These cell encapsulation devices facilitate the flow of oxygen and nutrients to the encapsulated cells while isolating the cells from the patient's immune system. Once implanted, the cell encapsulation devices can be filled with insulin-secreting cells. If, when necessary, the insulin-secreting cells need to be replenished, these cell encapsulation devices can be cleaned and refilled in a minimally invasive manner to reduce trauma to the patient.

[0056] Figure 1 This is a schematic top view of a cell encapsulation device 10 according to some embodiments of this disclosure. (See attached diagram.) Figure 1 As shown, the cell encapsulation device 10 includes at least one cell encapsulation layer 12. The cell encapsulation layer 12 includes a first membrane 14 and a second membrane 16 (shown in...). Figure 2 The first set of multiple welding lines 18 and the first inlet port 20 are included. The first set of multiple welding lines 18 attaches the first membrane 14 to the second membrane 16. The first membrane 14, the second membrane 16, and the first set of multiple welding lines 18 define at least one chamber 22.

[0057] like Figure 1 As shown, the cell encapsulation device 10 may further include a second set of multiple welding lines 24, a third set of multiple welding lines 26, and a first inlet conduit 28. The second set of multiple welding lines 24 attaches a first membrane 14 to a second membrane 16 to define at least two cell channels 30 in the chamber 22. The third set of multiple welding lines 26 attaches the first membrane 14 to the second membrane 16 to define a guide channel 32 within the chamber 22.

[0058] The first inlet conduit 28 is fluidly connected to the guide tube 34 and extends from the first inlet port 20 in a direction away from the chamber 22. The first inlet conduit 28 may be made of a biocompatible polymer (e.g., high-density polyethylene, polyethylene terephthalate, or polytetrafluoroethylene) or a biocompatible metal (e.g., 316VLM stainless steel, nickel-titanium alloy, or Elgiloy nonmagnetic alloy). The tubular structure formed by the first inlet conduit 28 can be attached to the first membrane 14 and / or the second membrane 16, for example, by binding to the first membrane 14 and / or the second membrane 16, or by using a biocompatible adhesive.

[0059] The first membrane 14 and the second membrane 16 are semi-permeable membranes having pores extending through them. The first membrane 14 and the second membrane 16 are semi-permeable because the size of these pores is designed to allow oxygen, nutrients, and waste to pass through but prevent the passage of cells encapsulated by cells or cells of the patient's immune system.

[0060] The first membrane 14 and the second membrane 16 may have an average pore size as small as 2 nanometers (nm), 5 nm, 10 nm, or 20 nm, or 50 nm, or as large as 200 nm, 500 nm, 1,000 nm, 2,000 nm, or 5,000 nm, or within any range defined by any two of the foregoing values. This average pore size may be in the range of 2 nm to 5,000 nm, 5 nm to 2,000 nm, 10 nm to 1,000 nm, 20 nm to 500 nm, or 50 nm to 200 nm. A pore size of 2 nm is sufficient to allow the passage of insulin and glucose through the first membrane 14 and the second membrane 16. A pore size less than 5,000 nm is sufficient to prevent vascularization and immune responses within the cell channel 30.

[0061] The first membrane 14 and the second membrane 16 can be fabric membranes, such as those available from Sefar, 12 Hinterbissaustrasse, 9410 Heiden, Switzerland. Alternatively, the first membrane 14 and the second membrane 16 can be non-woven membranes manufactured by electrospinning.

[0062] Figure 2 yes Figure 1 A schematic cross-sectional top view of the cell encapsulation layer 12, wherein the first membrane 14 is removed to show the second membrane 16. (See diagram) Figure 2 As shown, the cell encapsulation layer 12 further includes a guide tube 34 extending from the first inlet port 20 into the chamber 22. The guide tube 34 includes a porous wall 36 along at least a portion of its length. Figure 2 In the illustrated embodiment, the porous wall 36 of the guide tube 34 extends along the entire length of the guide tube 34. Alternatively, the porous wall 36 may extend only along one or more portions of the guide tube 34. The porous wall 36 allows liquids, gels, and encapsulated liquids to flow easily between the guide tube 34 and the cell channel 30. The guide tube 34 may be accommodated within the guide tube channel 32, thereby holding the guide tube 34 in a position where it is fluidly connected to the cell channel 30.

[0063] The guide tube 34 may include a mesh pattern, such as a braided mesh, or a slitted mesh pattern like that used for implantable stents, to form a porous wall 36. The guide tube 34 may include a metal mesh. This metal mesh may include a metal selected from the group consisting of stainless steel, titanium, platinum, alloys of chromium and cobalt, alloys of nickel and titanium, and alloys of cobalt, chromium, nickel, and molybdenum. The guide tube 34 may include a polymer mesh. This polymer mesh may comprise a polymer selected from the group consisting of polytetrafluoroethylene, polyether block amide, nylon, polyester, polysiloxane, and polycarbonate-type polyurethane.

[0064] The mesh may have holes or openings that pass through the porous wall 36. The holes in the porous wall 36 may have, for example, as small as 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.6 mm, 0.8 mm, or 1.0 mm, or as large as 1.2 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 4 mm, or 5 mm, or within any range defined by any two of the foregoing values, such as an average pore size of 0.1 mm to 5 mm, 0.2 mm to 4 mm, 0.3 mm to 3 mm, 0.4 mm to 2.5 mm, 0.6 mm to 2 mm, 0.8 mm to 1.5 mm, 0.6 mm to 1.0 mm, or 0.8 mm to 1.2 mm.

[0065] Figure 3 It is based on some implementation schemes of this disclosure. Figure 1 A schematic cross-sectional view of the cell encapsulation layer 12. (See attached image.) Figure 3 As shown, the guide tube 34 may have an inner diameter P, for example as small as 0.5 mm, 0.6 mm, 0.8 mm, 1.0 mm, 1.2 mm, 1.4 mm, or 1.6 mm, or as large as 1.8 mm, 2.0 mm, 2.2 mm, 2.4 mm, 2.6 mm, 2.8 mm, or 3.0 mm, or within any range defined by any two of the foregoing values, such as 0.5 mm to 3.0 mm, 0.6 mm to 2.8 mm, 0.8 mm to 2.6 mm, 1.0 mm to 2.4 mm, 1.2 mm to 2.2 mm, 1.4 mm to 2.0 mm, 1.6 mm to 1.8 mm, or 0.8 mm to 1.2 mm.

[0066] Each cell channel 30 may have an average inner diameter D of, for example, as small as 0.01 mm, 0.02 mm, 0.04 mm, 0.06 mm, 0.08 mm, 0.10 mm, 0.12 mm, 0.16 mm, 0.2 mm, 0.4 mm, 0.6 mm, 0.8 mm, 1.0 mm, 1.2 mm, 1.6 mm, 2.0 mm, 2.4 mm, 2.8 mm, 3.2 mm, or 3.6 mm, or within any range defined by any two of the foregoing values, such as 0.01 mm to 3.6 mm, 0.1 mm to 2.0 mm, or 0.01 mm to 1.2 mm.

[0067] When implanted, the cell channels 30 of the cell encapsulation device 10 may be uninflated, meaning they may not be filled with liquid or insulin-secreting cells prior to transplantation to enable a minimally invasive transplantation method, as described in U.S. Patent Application 15 / 922,251 entitled “Cell Encapsulation Device,” filed March 15, 2018, the entire contents of which are incorporated herein by reference. The cell encapsulation device 10 may be implanted in the lower abdomen of a patient, for example, between the transversalis fascia and the parietal peritoneum. Alternatively, the cell encapsulation device 10 may be implanted between the internal oblique muscle and the transversus abdominis muscle.

[0068] Common reference Figures 1-3 For example, a method for fabricating a cell encapsulation device (such as cell encapsulation device 10) according to some embodiments may include: placing a first membrane 14 directly onto a second membrane 16, and then attaching the first membrane 14 to the second membrane 16 using a first set of multiple bonding wires 18 (to define a chamber 22) and a second set of multiple bonding wires 24 (to define at least two cell channels 30 within the chamber 22). A guide tube 34 may be inserted into the chamber 22 through a first inlet port 20, and one end of the guide tube 34 may be attached to the first membrane 14 and / or the second membrane 16 surrounding the first inlet port 20. The second set of multiple bonding wires 24 may be omitted.

[0069] Attaching the first membrane 14 to the second membrane 16 may further include a third set of multiple weld lines 26 defining a guide tube channel 32 in fluid communication with the cell channel 30. The method may further include inserting a guide tube 34 into the guide tube channel 32 through a first inlet port 20. The third set of multiple weld lines 26 may be omitted.

[0070] Figure 4A and Figure 4B This is a schematic cross-sectional top view of a system 38 for cell transplantation, including a cell encapsulation device 10 and a first external conduit 40. For clarity, Figure 4A and Figure 4B The image shows the first membrane 14 being removed to reveal the second membrane 16. Figure 4A and Figure 4B The illustration shows a method, according to some embodiments, of filling the cell encapsulation layer 12 of the cell encapsulation device 10 with a first external catheter 40 after transplantation to inflate the cell channel 30.

[0071] Figure 4A and Figure 4B A cell encapsulation layer 12 is shown, in which a first external catheter 40 passes through a first inlet catheter 28 and a first inlet port 20 to enter a guide tube 34. The first external catheter 40 may be a simple catheter having an opening at its distal end connected to a source (not shown) of fluid or insulin-secreting cells, for example, outside the patient. Figure 4AAs shown, the first external conduit 40 is inserted into one end of the guide tube 34 away from the first inlet port 20, and then the fluid and / or the flow F of insulin-secreting cells can be injected into the chamber 22 and flow through the porous wall 36 of the guide tube 34 into the adjacent cell channel 30, thereby filling the adjacent cell channel 30.

[0072] When the cell channel 30 furthest from the first inlet port 20 is filled, the first external conduit 40 can be retracted toward the first inlet port 20 to continue filling more cell channels 30 closer to the first inlet port 20, such as... Figure 4B As shown in the diagram, the first external conduit 40 can be retracted to the first inlet port 20 to fill the remaining cell channel 30 and complete the filling of the cell encapsulation layer 12 with fluid and / or insulin-secreting cells.

[0073] The guide tube 34 guides the first external conduit 40 through the chamber 22 to help position the first external conduit 40 in a controlled manner at an ideal location for filling the chamber 22, as described above. The guide tube 34 prevents the first external conduit 40 from moving uncontrollably within the chamber 22, which could lead to underfilling or overfilling of parts of the cell channel 30. Additionally, the guide tube 34 prevents the first external conduit 40 from deviating from its entry into the cell channel 30 and from potentially damaging or puncturing the first membrane 14 or the second membrane 16.

[0074] The cell encapsulation device 10 can be implanted and immediately filled with insulin-secreting cells, as described above. Alternatively, the cell encapsulation device 10 can be implanted and immediately filled with liquid to inflate the cell channel 30. The cell encapsulation device 10 can then be maintained in the inflated configuration, allowing blood vessels (not shown) from the patient to grow around the cell encapsulation device 10. Once the blood vessels have grown sufficiently to supply oxygen and nutrients to the cell encapsulation device 10, insulin-secreting cells can be used instead of the inflating fluid. The fluid used to inflate the cell channel 30 may include physiological saline. The fluid used to inflate the cell channel 30 may include a more viscous fluid, such as natural hyaluronic acid. This fluid can remain in the cell channel 30 to maintain the cell encapsulation device 10 in the inflated configuration. The more viscous fluid (such as natural hyaluronic acid) can remain in the cell channel 30 for a longer period of time compared to, for example, saline. This provides additional time for blood vessel growth before the injection of insulin-secreting cells.

[0075] Insulin-secreting cells can be injected into a gel matrix. This gel matrix restricts the movement of the insulin-secreting cells, preventing them from agglomerating. Agglomeration reduces the number of insulin-secreting cells available to receive cellular maintenance substances and secrete insulin. The gel matrix may contain cross-linked hyaluronic acid and / or alginate gel. The gel matrix may further include an emulsion containing an oxygen-containing fluid. The high oxygen solubility of this oxygen-containing fluid allows for cell channels 30 (…). Figure 3 The distance D of the gel matrix is ​​greater than the distance D of the emulsion containing the oxygen-containing fluid. The oxygen-containing fluid can be, for example, a perfluorocarbon liquid of the type known in the art. Examples of such perfluorocarbon liquids may include: perfluorodihexyl ether, perfluorodibutyltetrafluoride, perfluorotriisobutylamine, perfluoro-(N-ethylmorpholine), perfluoro-N,N-dipropylmethylamine, perfluorotriethylamine, perfluoro-N-methylpiperidine, perfluoro-N-methylmorpholine, perfluoro-N,N-dimethyl-N-hexylamine, perfluoro-N-butylmorpholine, perfluoro-4-(N,N-dimethyl-2-aminoethyl)morpholine, and F-tert-butylperfluorocyclohexane, or combinations thereof.

[0076] Periodically, insulin-secreting cells need to be replenished. Figure 5 This is a schematic side view of a part of a system 38 for cell transplantation according to another embodiment. Figure 5 In the embodiment shown, a first external catheter 42 is used instead of Figure 4A and Figure 4B The first external catheter 40, or 42, can be used to replenish insulin-secreting cells while the cell encapsulation device 10 is still implanted inside the patient. The first external catheter 42 may include a first lumen 44 having a first internal opening 46 and a second lumen 48 having a second internal opening 50. The first internal opening 46 and the second internal opening 50 are spaced apart along a guide tube 34. The first lumen 44 may be connected to a source of fluid and / or insulin-secreting cells. The second lumen 48 may be connected to a vacuum source.

[0077] In use, the first external conduit 42 can be inserted into the guide tube 34 at the first inlet port 20. Figure 4A and Figure 4B The contents of the cell channel 30 are then moved through the guide tube 34, along the path through each cell channel 30. At each cell channel 30 along this path, the contents of the cell channel 30 are drawn out by a flow E through the porous wall 36 of the guide tube 34 and into the second inner cavity opening 50 to reach the vacuum source connected to the second inner cavity 48. Once the cell contents have been removed, a flow F of fluid and / or new insulin-secreting cells can be provided from the first inner cavity opening 46, through the porous wall 36 of the guide tube 34, and into the cell channel 30. Figure 4A and Figure 4B ).

[0078] Once the contents of cell channel 30 have been removed, the cell channel 30 can be filled with fluid to clean the interior of the cell channel 30, and then the washing fluid is withdrawn. This removal / filling process can be repeated as needed to clean cell channel 30 before filling with insulin-secreting cells.

[0079] exist Figure 5 In the illustrated embodiment, the second inner lumen 48 is arranged coaxially with the first inner lumen 44, and the first external conduit 42 further includes a flange 52 disposed between the first inner lumen opening 46 and the second inner lumen opening 50. This flange 52 projects outward toward the guide tube 34 to deflect the flow F from the first inner lumen 44 toward the porous wall 36 of the guide tube 34, thereby enhancing the flow F through the guide tube 34 into the cell channel 30.

[0080] Figure 6 This is a schematic side view of a part of a system 38 for cell transplantation according to yet another embodiment. Figure 6 In the embodiment shown, a first external catheter 54 is used instead of Figure 4A and Figure 4B The first external catheter 40, or the first external catheter 54, can be used to replenish insulin-secreting cells while the cell encapsulation device 10 is still implanted inside the patient. The first external catheter 54 may include a first lumen 56 having a first internal opening 58 and a second internal lumen 60 having a second internal opening 62. The first internal opening 58 is spaced from the second internal opening 62 along the guide tube 34. The first internal lumen 56 may be connected to a source of fluid and / or insulin-secreting cells. The second internal lumen 60 may be connected to a vacuum source. The first internal opening 58 and the second internal opening 62 may be tilted toward the guide tube 34 (e.g., ...). Figure 6 As shown in the diagram, this enhances the extraction flow E and flow F of the fluid through the porous wall 36 of the guide tube 34. This can be achieved as described above. Figure 5 The first external catheter 54 shall be used as described for the first external catheter 42.

[0081] Figure 7 This is a schematic cross-sectional top view of a system 64 for cell transplantation, including a cell encapsulation device 66 and a first external conduit 68. Except that the cell encapsulation device 66 may include a second inlet port 70 and a second inlet conduit 72, the cell encapsulation device 66 may be similar to the cell encapsulation device 10 described above. For clarity, Figure 7 The first membrane 14 is removed to reveal the second membrane 16. (See image.) Figure 7As shown, the second inlet conduit 72 is fluidly connected to the second inlet port 70 and extends from the second inlet port 70 in a direction away from the chamber 22. A guide tube 34 extends from the first inlet port 20 through the chamber 22 to the second inlet port 70. The second inlet conduit 72 may be a tubular structure, as described above with respect to the first inlet conduit 28. The first external conduit 68 is able to enter the chamber 22 through the first inlet conduit 28, pass through the guide tube 34, and exit the chamber 22 through the second inlet conduit 72.

[0082] If the vascularization of the cell encapsulation device 66 is insufficient to support the insulin-containing cells within it, then the first external conduit 68 can be a thin-walled silicone tube through which gases (such as oxygen and carbon dioxide) can pass. In use, an oxygenated fluid (such as any perfluorocarbon liquid disclosed above) can flow through the first external conduit 68 to provide an oxygenation circuit for the insulin-secreting cells within the cell channel 30. Oxygen from the oxygenated fluid can diffuse out of the first external conduit 68, pass through the porous wall 36 of the guide tube 34, and enter the cell channel 30, where it can be absorbed by the insulin-secreting cells. Waste from the insulin-secreting cells can flow in the opposite direction and be removed as the oxygenated fluid flows out of the chamber 22 through the first external conduit 68. Alternatively, the oxygenated fluid can be a body fluid that can be collected in the peritoneum and then pumped through the first external conduit 68 to provide oxygen and collect waste from the insulin-secreting cells.

[0083] Alternatively, the first external conduit 68 may be highly elastic, and the flow of oxygenated fluid through the first external conduit 68 may be accomplished by peristalsis, thereby providing a pressure pulse propagating into and through the cell channel 30. This pressure pulse can provide convective flow in the cell channel 30 to enhance the flow of oxygen and waste products to and from the insulin-secreting cells. Once the vascularization of the cell encapsulation device 66 is sufficient to support the internal insulin-containing cells, the first external conduit 68 can be removed from the cell encapsulation device 66.

[0084] Figure 8 This is a schematic side view of a part of a system 74 for cell transplantation according to another embodiment. Besides as described above... Figure 4A and Figure 4B Except that the first external catheter 68 is replaced by the first external catheter 40, system 74 is similar to the above-described system. Figure 7 The described system 64 further includes a guidewire 78 and optionally a second external catheter 80. (As...) Figure 8 As shown, the first external catheter 40 includes a first lumen 82 that is fluidly connected to a source of fluid or insulin-secreting cells, for example, outside the patient, as described above. Figure 4A and Figure 4BAs described. The second external conduit 80 may include a second inner lumen 84 connected to a vacuum source. The guidewire 78 may be a guidewire as known in the art.

[0085] In use, the guidewire 78 can be inserted into the first inlet catheter 28, pass through the guide tube 34, and exit through the second inlet catheter 72. The first external catheter 40 can be screwed onto one end of the guidewire 78 and inserted into the first inlet catheter 28, then enters the guide tube 34 at the first inlet port 20 of the cell encapsulation device 66. Figure 7 The second external catheter 80 can be screwed to the opposite end of the guidewire 78 and inserted into the second inlet catheter 72, and then the guide tube 34 is inserted at the second inlet port 70 opposite to the first external catheter 40. Figure 7 The first external conduit 40 and the second external conduit 80 are spaced apart from each other but can move together through the guide tube 34, passing through each cell channel of the cell channel 30 along this path. At each cell channel of the cell channel 30 along this path, the contents of the cell channel 30 are drawn out by a flow E through the porous wall 36 of the guide tube 34 and into the second inner lumen 84. Once the cell contents have been drawn out, a flow F of fluid and / or fresh insulin-secreting cells can be supplied from the first inner lumen 82, passing through the porous wall 36 of the guide tube 34 and entering the cell channel 30. Figure 4A and Figure 4B ).

[0086] The guidewire 78 may include a flange 86 disposed between the first external conduit 40 and the second external conduit 80. The flange 86 protrudes outward toward the guide tube 34 to deflect the flow F distributed from the first inner lumen 82 toward the porous wall 36 of the guide tube 34, thereby enhancing the flow F entering the cell channel 30 through the guide tube 34.

[0087] For example, when the extraction flow E is not necessary, such as when the cell encapsulation device 66 is filled for the first time to inflate the cell channel 30, the second external conduit 80 can be omitted.

[0088] In the cell encapsulation devices 10 and 66 described above, only a single guide tube 34 is shown inside each cell encapsulation layer 12. However, it will be understood that various embodiments include cell encapsulation devices 10 and 66 having at least one cell encapsulation layer 12, which includes at least two guide tubes 34 extending into the cell encapsulation chamber 22, at least two first inlet ports 20, at least two second inlet ports 70, or any combination thereof. For example, including multiple guide tubes 34 in the single-cell encapsulation layer 12 can improve the speed and efficiency of filling or replenishing the cell encapsulation layer 12 with insulin-secreting cells.

[0089] In the cell encapsulation devices 10 and 66 described above, the guide tube 34 is illustrated as having a generally straight configuration inside the cell encapsulation layer 12. However, it will be understood that various embodiments include cell encapsulation devices 10 and 66 in which the guide tube 34 is bent inside the cell encapsulation layer to accommodate different shapes of the chamber 22 (e.g., U-shaped chamber 22).

[0090] Figure 9 This is a side view of another cell encapsulation device 88 according to some embodiments of the present disclosure. The cell encapsulation device 88 includes two cell encapsulation layers: a first cell encapsulation layer 90 and a second cell encapsulation layer 92. Except that a second inlet conduit 72 of the first cell encapsulation layer 90 and a first inlet conduit 28 of the second cell encapsulation layer 92 are fluidly connected to form an intermediate conduit 94 that fluidly connects the first cell encapsulation layer 90 to the second cell encapsulation layer 92, the first cell encapsulation layer 90 and the second cell encapsulation layer 92 may each be similar to those described above. Figure 7 The described cell encapsulation device 66. A first inlet catheter 28 of the first cell encapsulation layer 90 and a second inlet catheter 72 of the second cell encapsulation layer 92 may each extend to the outside of the patient, or may be connected to a subcutaneous injection port 100 located beneath the patient's skin (below). Figure 11 ).

[0091] Figure 10 This is a side view of another cell encapsulation device 96 according to some embodiments of the present disclosure. The cell encapsulation device 96 is similar to the cell encapsulation device 88 described above, and further includes a multi-guided inlet catheter 98. The multi-guided inlet catheter 98 may be a single catheter that branches to fluidly connect to guide tubes 34 in the first cell encapsulation layer 90 and the second cell encapsulation layer 92. In use, a first external catheter 40 (or any other first or second external catheter described above) may be inserted into the multi-guided inlet catheter 98 and then guided as needed to the guide tubes 34 in the first cell encapsulation layer 90 or the second cell encapsulation layer 92. The multi-guided inlet catheter 98 may extend to the outside of the patient or may be connected to a subcutaneous injection port 100 (below) under the patient's skin. Figure 11 This reduces the number of external or subcutaneous injection ports used in the cell encapsulation device. Limiting the number of external or subcutaneous injection ports reduces the chance of interaction between the insulin-secreting cells in the cell encapsulation device 88 and the patient's immune system.

[0092] Although Figure 9 and Figure 10 Only two cell encapsulation layers 90 and 92 are shown in the illustration, but it is understood that the disclosed structure can be extended to implementations including cell encapsulation devices having as many cell encapsulation layers as needed to provide the amount of insulin-secreting cells required by the patient.

[0093] Figure 11 A schematic longitudinal sectional view of any of the cell encapsulation devices 10, 66, 88, or 96 described above, illustrating a subcutaneous injection port 100 connected to the end of the first inlet catheter 28 opposite to chamber 22 (see, for example...). Figure 1 The subcutaneous injection port 100 may include a port cover 102, an outer septum 104, and an inner septum 106. The port cover 102 may include a port lumen 108. The port lumen 108 extends through the port cover 102, and the end of the port lumen 108 closest to the first inlet catheter 28 is in fluid communication with the first inlet catheter 28. The outer septum 104 extends across and seals the port lumen 108. The inner septum 106 also extends across and seals the port lumen 108. The inner septum 106 is spaced from the outer septum 104 to form a space 110 within the port lumen 108 between the inner septum 106 and the outer septum 104. The inner septum 106 is disposed between the outer septum 104 and the first inlet catheter 28. The outer septum 104 and the inner septum 106 may be made of an elastic polymer capable of being penetrated by a tubular needle and then sealed around the tubular needle. The port cover 102, outer diaphragm 104, and inner diaphragm 106 may be made of, for example, polymers (such as polysiloxane or polycarbonate-type polyurethane).

[0094] although Figure 11 The diagram shows that the subcutaneous injection port 100 is connected to the first inlet catheter 28, but it is understood that some embodiments of the cell encapsulation device have a subcutaneous injection port 100 that is connected to other inlet catheters (such as the second inlet catheter 72 or the multi-guide catheter inlet catheter 98 described above).

[0095] Figures 12A-12D This is a schematic longitudinal sectional view of a portion of another system 112 for cell encapsulation according to some embodiments of this disclosure. In addition to any of the cell encapsulation devices 10, 66, 88, or 96 described above, it further includes as described above regarding... Figure 11 Apart from the described subcutaneous injection port 100, system 112 may be similar to any system described herein, and system 112 may further include, for example, Figures 12A-12D The outer tubular needle 114 shown and as Figure 12C and Figure 12D The inner tubular needle 116 is shown. The outer tubular needle 114 is able to penetrate the outer septum 104 and the outer septum 104 seals around the outer tubular needle 114. The inner tubular needle 116 is able to pass through the outer tubular needle 114 and penetrate the inner septum 106 and the inner septum 106 seals around the inner tubular needle 116.

[0096] like Figure 12A and Figure 12BAs shown, in use, the outer tubular needle 114 can penetrate the patient's skin (not shown) to reach the subcutaneous injection port 100, and then penetrate the outer septum 104 so that one end of the outer tubular needle 114 comes into fluid contact with the space 110 inside the port lumen 108 between the outer septum 104 and the inner septum 106. Upon penetration of the outer septum 104, some bodily fluid may be delivered into the space 110 along with the outer tubular needle 114. The bodily fluid may contain somatic cells, which must remain in contact with the chamber 2 ( Figure 1 The state of isolation of the insulin-secreting cells inside the cell. To maintain this isolation, the other end (not shown) of the outer tubular needle 114 can be fluidly connected to a source (not shown) of the disinfectant S. For example, the disinfectant S can be glutaraldehyde or ethanol. Figure 12B As shown, disinfectant S can be injected into space 110 through outer tubular needle 114 to sterilize the walls of space 110 and the exposed surface of outer tubular needle 114, thereby destroying any somatic cells inside space 110.

[0097] Once space 110 is sterilized, the inner tubular needle 116 can pass through the outer tubular needle 114, through the sterilization space 110, and then through the inner septum 106 so that one end of the inner septum 106 comes into fluid contact with the first inlet conduit 28, such as... Figure 12C As shown in the diagram. The first external catheter 40 can then be inserted into the other end (not shown) of the inner tubular needle 116 and pass through the inner tubular needle 116 into the first access catheter 28 (as shown in the diagram). Figure 12D (as shown in the diagram), and enters guide tube 34, as mentioned above. Figure 4A As described. In this way, insulin-secreting cells can be injected into a cell encapsulation device while maintaining isolation from somatic cells.

[0098] A limiting edge (not shown) may be added to the proximal ends of the outer tubular needle 114 and the inner tubular needle 116 to prevent the outer tubular needle 114 from penetrating the inner diaphragm 106 and to prevent the inner tubular needle 116 from penetrating too far into the first access catheter 28 and the risk of puncturing the first access catheter 28, the guide tube 34, the first membrane 14 or the second membrane 16.

[0099] The first external catheter 40 can be removed while maintaining isolation using a reverse method. The first external catheter 40 can be removed through the inner tubular needle 116, and then the inner tubular needle 116 can be removed from the first inlet catheter 28 through the inner septum 106. The inner septum 106 can be made of a polymer that can seal the hole formed by the inner tubular needle 116 when penetrating the inner septum 106. Alternatively, when the inner tubular needle 116 is removed through the inner septum 106, the hole can be sealed with an alginate gel, siloxane polymer, or another biocompatible adhesive added to the inner tubular needle 116. When the inner tubular needle 116 is removed through the inner septum 106, the insulin-secreting cells can be delivered into the space 110 along with the inner tubular needle 116. To maintain the isolation between insulin-secreting cells and the body, disinfectant S can be injected again into space 110 through the outer tubular needle 114 to sterilize the walls of space 110 and the exposed surface of the outer tubular needle 114, thereby destroying any insulin-secreting cells inside space 110. Figure 12B ).

[0100] Once space 110 is sterilized, the outer tubular needle 114 can be pulled out from space 110 through the outer septum 104. The outer septum 104 may be made of a polymer that can seal the hole formed by the outer tubular needle 114 when it is penetrated. Alternatively, when the outer tubular needle 114 is pulled out through the outer septum 104, the hole can be sealed with an alginate gel, siloxane polymer, or another biocompatible adhesive added through the outer tubular needle 114.

[0101] As used in this article, the phrase “any range between any two of the foregoing values” literally means any range that can be selected from any two values ​​listed preceding the phrase, regardless of whether those values ​​are at the bottom or top of the list. For example, a pair of values ​​can be selected from two lower values, two higher values, or one lower value and one higher value.

[0102] Various modifications and additions may be made to the exemplary embodiments discussed without departing from the scope of this invention. For example, while specific features are mentioned in the above embodiments, the scope of this invention also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Therefore, the scope of this invention is intended to include all such substitutions, modifications, and alterations, together with all their equivalents, that fall within the scope of the claims.

Claims

1. A cell encapsulation device for transplantation into the body, the cell encapsulation device comprising: One or more cell encapsulation layers, each of the one or more cell encapsulation layers comprising: The membrane is at least semi-permeable, the at least one membrane forming a chamber for encapsulating cells and at least one inlet port through the at least one membrane, the at least one inlet port including a first inlet port and a second inlet port; A guide tube extending into the chamber from the at least one inlet port, the guide tube including a porous wall along at least a portion of its length, the guide tube being capable of guiding the movement of the catheter within the chamber, wherein the porous wall is configured to allow flow through insulin-secreting cells; and At least one inlet conduit extending from the at least one inlet port in a direction away from the chamber, the at least one inlet conduit being fluidly connected to the guide tube, wherein the at least one inlet conduit includes a first inlet conduit fluidly connected to the first inlet port and a second inlet conduit fluidly connected to the second inlet port, wherein the guide tube extends from the first inlet port through the chamber to the second inlet port.

2. The cell encapsulation device according to claim 1, wherein, The at least one membrane includes a first membrane and a second membrane, each layer of the one or more cell encapsulation layers further includes a first set of multiple weld lines, the second membrane is attached to the first membrane via the first set of multiple weld lines, and the first membrane, the second membrane and the first set of multiple weld lines define the chamber.

3. The cell encapsulation device according to claim 1 or 2, wherein, The guide tube is at least partially composed of metal mesh.

4. The cell encapsulation device according to any one of claims 1 to 2, wherein, Each layer of the cell encapsulation layer further comprises: A second set of multiple welding lines defining at least two cell channels within the chamber; and A third set of multiple weld lines defines a guide tube channel that is in fluid communication with the at least two cell channels, the guide tube being housed inside the guide tube channel.

5. The cell encapsulation device according to claim 1, wherein, The one or more cell encapsulation layers include a first cell encapsulation layer and a second cell encapsulation layer, wherein the second inlet conduit of the first cell encapsulation layer is fluidly connected to the first inlet conduit of the second cell encapsulation layer, thereby fluidly connecting the first cell encapsulation layer to the second cell encapsulation layer.

6. The cell encapsulation device according to any one of claims 1 to 2, wherein, The cell encapsulation device further includes an injection port connected to the end of the catheter opposite to the chamber, the injection port comprising: A port cover forming a port cavity extending through the port cover, wherein the end of the port cover closest to the inlet catheter is in fluid communication with the inlet catheter; An outer diaphragm extends across and seals the inner cavity of the port; and An inner diaphragm extends across and seals the port cavity, the inner diaphragm being spaced apart from the outer diaphragm to form a space within the port cavity between the inner and outer diaphragms, the inner diaphragm being disposed between the outer diaphragm and the inlet conduit, the outer and inner diaphragms being made of an elastic polymer.

7. A system for intracorporeal cell transplantation, the system comprising: The cell encapsulation device according to any one of claims 1 to 6; as well as A first external conduit is capable of passing through the at least one inlet conduit into the guide tube to guide the movement of the first external conduit within the room.

8. The system according to claim 7, wherein, When the first external catheter moves through the guide tube, the first external catheter is able to distribute cells through the porous wall of the guide tube into the chamber.

9. The system according to claim 7, wherein, The first external conduit includes a first inner cavity having a first inner cavity opening and a second inner cavity having a second inner cavity opening, the first inner cavity opening and the second inner cavity opening being spaced apart from each other along the guide tube, the first inner cavity opening being able to distribute fluid through the porous wall of the guide tube into the chamber, and the second inner cavity opening being able to extract the fluid from the chamber through the porous wall of the guide tube.

10. The system according to claim 9, wherein, The second inner cavity is arranged coaxially with the first inner cavity, and the first external conduit further includes a flange disposed between the opening of the first inner cavity and the opening of the second inner cavity, the flange protruding outward toward the guide tube to deflect fluid distributed from the first inner cavity toward the porous wall of the guide tube.

11. The system according to claim 7, wherein, The first external conduit includes a first lumen and is capable of passing through the first inlet conduit to enter the guide tube. The system further includes a second external conduit having a second lumen and being capable of passing through the second inlet conduit to enter the guide tube, opposite to the first external conduit. The first external conduit and the second external conduit are spaced apart from each other inside the chamber. The first external conduit is capable of dispensing fluid through the porous wall of the guide tube into the chamber, and the second external conduit is capable of extracting the fluid from the chamber through the porous wall of the guide tube.

12. The system according to claim 7, wherein, The at least one inlet port includes a first inlet port and a second inlet port; and the at least one inlet conduit includes a first inlet conduit fluidly connected to the first inlet port and a second inlet conduit fluidly connected to the second inlet port, the guide tube extending from the first inlet port through the chamber to the second inlet port, the first external conduit being able to enter the chamber through the first inlet conduit, through the guide tube, and out of the chamber through the second inlet conduit.

13. A method for fabricating a cell encapsulation device for transplantation into the body, the method comprising: The first semipermeable membrane is placed directly on the second semipermeable membrane; Using a first set of multiple welding lines defining a chamber for encapsulating cells, a second set of multiple welding lines defining at least two cell channels inside the chamber, and a third set of multiple welding lines defining a guide tube channel in fluid communication with the at least two cell channels, the first semipermeable membrane is attached to the second semipermeable membrane to form a first inlet port and a second inlet port. A guide tube is inserted into the guide tube channel through the first inlet port and the second inlet port and enters the chamber. The guide tube includes a porous wall along at least a portion of its length, wherein the porous wall is configured to allow insulin-secreting cells to flow through it. A first inlet conduit is fluidly connected to the first inlet port and a second inlet conduit is fluidly connected to the second inlet port, wherein the guide tube extends from the first inlet port through the chamber to the second inlet port; as well as One end of the guide tube is attached to at least one of the first semi-permeable membrane and the second semi-permeable membrane surrounding the first inlet port and the second inlet port.

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