Two-component implantable therapeutic delivery device

Abstract

An implantable therapeutic delivery device comprising a porous pouch and a cell encapsulation device configured to be housed in the porous pouch. The porous pouch can comprise a bioabsorbable material and / or a vascularization promoter, and the porous pouch can be packaged separately from the cell encapsulation device.

Description

TECHNICAL FIELD

[0001] The present invention relates to the field of medical devices and, in particular, to implantable devices for delivering biological therapies to a patient. BACKGROUND

[0002] Biological therapies are increasingly viable methods of treating peripheral arterial disease, aneurysms, heart disease, Alzheimer's and Parkinson's disease, autism, blindness, diabetes, and other maladies.

[0003] With respect to biological therapies in general, cells, viruses, viral vectors, bacteria, proteins, antibodies, and other biologically active moieties are introduced into a patient through surgical or interventional methods that place the biologically active moieties in the tissue bed of the patient. Typically, the biologically active moieties are first placed in a device, which is then inserted into the patient. Alternatively, the device can be first inserted into the patient, and the biologically active moieties are subsequently added.

[0004] Devices for encapsulating biological moieties typically include a selectively permeable membrane for containing a therapeutic agent while maintaining the permeability of nutrients for feeding the therapeutic agent; waste products from the therapeutic agent and therapeutic products produced by the therapeutic agent. The typical biological response to the introduction of these therapeutic devices is the formation of a fibrotic capsule around the device, which can cause the encapsulated cells to lose the ability to exchange life-sustaining nutrients and waste products with the patient's tissue, thereby limiting the performance of the device. This result is typically fatal to the encapsulated cells. In addition, the fibrotic capsule that surrounds the therapeutic device typically makes it difficult to surgically remove the device.

[0005] To avoid the formation of this fibrotic capsule, some implantable devices include an outer layer that can support vascularization, i.e., the growth of the patient's vascular tissue into direct contact or near direct contact with the device. This is desirable because the therapeutic products of the device can then be delivered directly to the patient's circulation through the vascular tissue in contact with the device. A significant drawback of this vascularization is that the removal of the device requires surgical dissection of the tissue to expose the device for removal. The surgical dissection of vascular tissue, particularly capillary tissue, is typically a difficult and painful process.

[0006] The implantation causes a certain amount of trauma to the patient and a healing period before the therapy provided by the device can be effective. Therefore, there remains a need for devices that allow for the implantation of cells and other biological moieties to provide biological therapies, where the devices can be quickly integrated into the tissue bed with minimal trauma and without disturbing the tissue bed beyond what is necessary. There is also a need to avoid damaging the implanted device or harming the biological moieties during implantation or after implantation. SUMMARY

[0007] The terms "application," "the application," "this application" and "the present application" used herein are intended to refer broadly to all of the subject matter of this patent application, under any and all possible theories of prosecution. Statements containing these terms should be understood not to limit the claimed subject matter to a single application, and these statements should not be interpreted to have any other limiting effect. This summary is intended to provide a brief overview of some concepts related to the various aspects of the application described below in the detailed description section. This summary does not identify key or essential features of the claimed subject matter and shall not be used to interpret the scope or essential features of the claimed subject matter. The subject matter should be understood by reference to the entire specification of the application, all drawings and any claims.

[0008] The present application relates to an implantable assembly for providing a biological therapy in a tissue bed for a patient. The implantable assembly includes a porous pocket for housing a cell encapsulation device. The porous pocket has properties that promote vascularization and / or incorporation of the device into the tissue bed. For example, the porous pocket can include a bioabsorbable material and / or a vascularization promoting agent. The cell encapsulation device includes a plurality of cells in a cell maintenance medium. The cell encapsulation device can be stored in the cell maintenance medium, or processed (grown, matured) in the cell maintenance medium. Certain elements of the porous pocket (e.g., the bioabsorbable material and the vascularization promoting agent) are not compatible with the cell maintenance medium. Advantageously, to provide separate environments prior to implantation, the implantable assembly is maintained as two separate elements in two separate environments. During implantation, the separate elements can form one implantable assembly.

[0009] As described herein, a kit includes a cell encapsulation device contained within a first cell maintenance environment, and a porous pocket contained within a second environment, wherein the second environment is different than the first environment, and the cell encapsulation device is configured to fit within the porous pocket. The cell maintenance environment can include a medium that facilitates survival of the plurality of cells. In some embodiments, the cell maintenance medium can be an aqueous medium. In some embodiments, the cell maintenance medium can include at least one cell nutrient.

[0010] In some embodiments, the porous pouch described herein comprises a bioabsorbable material. The bioabsorbable material can be, for example, polyglycolide:trimethylene carbonate (PGA:TMC), poly alpha-hydroxy acids, such as, for example, polylactic acid, polyglycolic acid polyglycolide, and poly(propylene-co-caprolactone), polycaprolactone polycarbonates, polydioxanones, polyhydroxybutyrates, polyhydroxyvalerates, poly(hydroxybutyrate-co-valerate), and copolymers and blends thereof. In some embodiments, the cell maintenance environment is hostile to the bioabsorbable material. In some embodiments, the bioabsorbable material is configured to degrade upon contact with moisture. Also, the bioabsorbable material can be temperature dependent, for example, more flexible at warmer environments (e.g., body temperature) and less flexible at cooler environments (e.g., room temperature). Thus, in some embodiments, the second environment is a dry environment and / or a temperature controlled environment. The dry environment can include a desiccant for maintaining a reduced level of moisture in the environment.

[0011] In some embodiments, the porous pouch comprises a polymer selected from the group consisting of alginate, cellulose acetate, polyalkylene glycols, such as, for example, polyethylene glycol and polypropylene glycol, panvinyl polymers, such as, for example, polyvinyl alcohol, chitosan, polyacrylates, such as, for example, polyhydroxyethyl methacrylate, agarose, hydrolyzed polyacrylonitrile, polyacrylonitrile copolymers, polyvinyl acrylates, such as, for example, polyethylene-co-acrylic acid, porous polytetrafluoroethylene, modified polytetrafluoroethylene polymers, tetrafluoroethylene (TFE) copolymers, porous polyalkylenes, such as, for example, porous polypropylene and porous polyethylene, porous polyvinylidene fluoride, porous polyester sulfone, porous polyurethane, porous polyester, and copolymers and combinations thereof. In exemplary embodiments, the polymer is porous polytetrafluoroethylene, porous polypropylene, porous polyethylene, porous polyvinylidene fluoride, and combinations thereof. In some embodiments, a porous material other than a bioabsorbable material can be included.

[0012] In some embodiments, the porous pouch comprises a plurality of pores sized to permit vascular tissue from the patient to grow within the plurality of pores. In addition, the porous pouch can include a second layer comprising a plurality of pores sized to restrict or prevent vascular tissue from the patient from growing. Inclusion of a non-vascular forming layer can help preserve space within the porous pouch so that the cell encapsulation device can be removed and reinserted one or more times. The porous pouch can also comprise a vascularization promoting agent. The vascularization promoting agent can be water soluble.

[0013] In some embodiments, the porous pouch is configured to hold the cell encapsulation device within the porous pouch. The porous pouch and / or the cell encapsulation device can be configured to allow insertion of the cell encapsulation device into the pouch and to allow subsequent removal of the cell encapsulation device from the pouch. In some embodiments, the porous pouch is configured to attach to the cell encapsulation device.

[0014] Also described herein is an implantable device comprising: a porous pouch comprising a bioabsorbable material and a cell encapsulation device within the porous pouch. The cell encapsulation device is configured to fit within the porous pouch. In some embodiments, the bioabsorbable material can have the ability to generate different levels of reactive oxygen species (ROS) in vivo.

[0015] In some embodiments, the porous pouch comprises a bioabsorbable material, which can be: polyglycolide:trimethylene carbonate (PGA:TMC), poly alpha-hydroxy acids, such as, for example, polylactic acid, polyglycolic acid polyglycolide, and poly(lactide-co-caprolactone), polycaprolactone, polycarbonates, polydioxanones, polyhydroxybutyrate, polyhydroxyvalerate, poly(hydroxybutyrate-co-valerate), and copolymers and blends thereof. The bioabsorbable material can be configured to degrade upon contact with moisture.

[0016] In some embodiments, in addition to the bioabsorbable material, the porous pouch can comprise a polymer selected from the group consisting of: polyethylene glycol and polypropylene glycol, panvinyl polymers, such as, for example, polyvinyl alcohol, chitosan, polyacrylates, such as, for example, polyhydroxyethyl methacrylate, agarose, hydrolyzed polyacrylonitrile, polyacrylonitrile copolymers, polyvinyl acrylates, such as, for example, polyethylene-co-acrylic acid, porous polytetrafluoroethylene (PTFE), modified polytetrafluoroethylene polymers, tetrafluoroethylene (TFE) copolymers, porous polyalkylenes, such as, for example, porous polypropylene and porous polyethylene, porous polyvinylidene fluoride, porous polyesther sulfone, porous polyurethane, porous polyesters, and copolymers and combinations thereof.

[0017] In some embodiments, the porous pouch contains a plurality of pores sized to allow vascular tissue from a patient to grow within the plurality of pores. The porous pouch can also comprise a vascularization promoting agent. The vascularization promoting agent can be water soluble.

[0018] In some embodiments, the porous pouch and / or the cell encapsulation device are configured to allow insertion of the cell encapsulation device into the pouch and to allow subsequent removal of the cell encapsulation device from the pouch. The porous pouch can be configured to attach to the cell encapsulation device. In some embodiments, the porous pouch can be opened to allow insertion or access of the cell encapsulation device. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 is a top view of an implantable assembly of the embodiments described herein, comprising a porous pocket and a cell encapsulation device;

[0020] Figure 2 is a top view of a porous pocket of the embodiments described herein;

[0021] Figure 3 is a partial cross-sectional view of one embodiment of an assembly comprising a vascularization promoting agent distributed within a porous pocket of the embodiments described herein;

[0022] Figure 4 is a partial cross-sectional view of one embodiment of an assembly comprising a vascularization promoting agent on the outer surface of a porous pocket of the embodiments described herein;

[0023] Figure 5 is a partial cross-sectional view of one embodiment of an assembly comprising a vascularization promoting agent on the inner surface of a porous pocket of the embodiments described herein;

[0024] Figure 6 is a perspective view of one embodiment of a porous pocket comprising a mesh of bioabsorbable material of the embodiments described herein;

[0025] Figure 7 is a perspective view of one embodiment of a porous pocket comprising a bioabsorbable ridge of the embodiments described herein;

[0026] Figure 8 is a perspective view of one embodiment of a porous pocket shaped as three adjacent and connected tubes for receiving a cylindrical cell encapsulation device and comprising a bioabsorbable material of the embodiments described herein;

[0027] Figure 9 is a perspective view of one embodiment of a porous pocket having a sharp edge according to the embodiments described herein to aid implantation;

[0028] Figure 10 is a perspective view of one embodiment of a porous pocket having a sharp tip at one end according to the embodiments described herein to aid implantation. DETAILED DESCRIPTION

[0029] Implantable assemblies for delivering a biological therapy to a patient are described herein. The assemblies include a porous pouch and a cell encapsulation device configured to fit within the porous pouch such that the combination of the porous pouch and the cell encapsulation device can be implanted into a patient (simultaneously or sequentially), e.g., into a tissue bed, to provide the biological therapy to the patient. The porous pouch can include a bioabsorbable material and / or a vascularization promoter, and the porous pouch can be packaged separately from the cell encapsulation device.

[0030] The cell encapsulation device is designed to include a living biological component that will provide a biological therapy to a patient once implanted. Biological components suitable for encapsulation and implantation using the devices described herein include cells, viruses, viral vectors, bacteria, proteins, antibodies, and other biologically active components. In short, the biological component herein refers to a cell, but nothing in this specification limits the biological component to a cell or any particular type of cell, and the description that follows applies to non-cellular biological components as well. As used herein, the term "cell encapsulation device" refers to an implantable device that can contain cells and any other biological component that can provide a biological therapy to a patient.

[0031] Various types of prokaryotic and eukaryotic cells can be used with the cell encapsulation devices described herein. In some embodiments, the cells secrete a therapeutically useful substance. The substance includes a hormone, a growth factor, a trophic factor, a neurotransmitter, a lymphokine, an antibody, or other cellular product that provides a therapeutic benefit to the recipient of the device. Examples of such therapeutic cellular products include, but are not limited to, insulin, a growth factor, an interleukin, parathyroid hormone, erythropoietin, transferrin, and factor VIII. Non-limiting examples of suitable growth factors include vascular endothelial growth factor, platelet-derived growth factor, platelet-activating factor, transforming growth factor, bone morphogenic protein, activin, inhibin, fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, glial cell line-derived neurotrophic factor, growth differentiation factor-9, epidermal growth factor, and combinations thereof.

[0032] Once the cells are introduced into the cell encapsulation device, the cell encapsulation device is maintained in a cell-maintaining environment until implantation to allow the cells to survive and remain capable of producing the therapeutic agent to be delivered to the patient. A cell-maintaining environment as used herein is intended to mean any environment that has conditions that maintain the cells in a condition such that they can provide the desired therapeutic agent to the patient once implanted. It should be noted that in some embodiments, the cells can be microencapsulated (i.e., individually coated).

[0033] The implantable assembly also includes a porous pocket for receiving and retaining the cell encapsulation device in the tissue bed. The porous pocket has an internal cavity region for the cell encapsulation device. The porous pocket has properties that promote vascularization and / or incorporate the pocket into the tissue bed. For example, the porous pocket can include a bioabsorbable material and / or a vascularization promoting agent. However, certain elements (e.g., bioabsorbable materials and vascularization promoting agents) are not compatible with the cell maintenance environment. For example, a bioabsorbable material can begin to degrade in the presence of water. In this case, exposing the porous pocket to the cell maintenance environment can cause the bioabsorbable material in the porous pocket to degrade prematurely (e.g., prematurely degrade before insertion into the patient) if the cell maintenance environment includes water. If the cell maintenance medium required by the cell encapsulation device is not compatible with the porous pocket, then the porous pocket and the cell maintenance medium must be separated until implantation or until an acceptable time before implantation.

[0034] As described herein, a kit includes a cell encapsulation device contained within a first cell maintenance environment, and a porous pocket contained within a second environment, wherein the second environment is different from the first environment, and the cell encapsulation device is configured to fit within the porous pocket.

[0035] The cell maintenance environment can include a medium that facilitates the survival of the plurality of cells. The optimal environment can vary depending on the characteristics of the cells, the length of time the device can be stored before implantation, the desire to promote or delay maturation of the cells, the sensitivity of the components in the porous pocket to the cell maintenance environment or the surrounding environment, and other factors known to those skilled in the art. The cell maintenance medium can maintain the cells for a period of time before and / or after implantation, such that the cells are still able to provide a therapeutic agent to the patient after implantation. The cell maintenance medium can also promote cell growth. In some embodiments, the cell maintenance medium can be an aqueous medium. In some embodiments, the cell maintenance medium can include at least one cell nutrient. For example, the cell maintenance medium can include one or more amino acids, vitamins, sugars, and / or inorganic ions (e.g., sodium, potassium, calcium, copper, and / or zinc). In some embodiments, the medium must be maintained at or above or below a certain temperature.

[0036] The kits described herein also include a porous pocket configured to receive and retain the cell encapsulation device in the patient tissue bed. In the kit, the porous pocket can be contained in a second environment different from the first cell maintenance environment. In some embodiments, the porous pocket described herein comprises a bioabsorbable material. Upon placement of the porous pocket in the body, the bioabsorbable material degrades and resorbs into the body. There should be little to no degradation prior to implantation. In some embodiments, only a portion of the porous pocket is formed from the bioabsorbable material, such that when the bioabsorbable material ablates, the porous pocket still maintains some structure to contain the cell encapsulation device. In some embodiments, the bioabsorbable material constitutes all, or nearly all, of the porous pocket, such that upon ablation of the bioabsorbable material, the porous pocket structure is no longer maintained.

[0037] The bioabsorbable material can ablate quickly and completely (e.g., within just a few days or just a few months), or can take significantly longer (e.g., years) to ablate completely. The rate of ablation of the bioabsorbable material will depend on the properties of the material and the biological environment, and can be selected by one of skill in the art as desired. The bioabsorbable material can be: polyglycolide:trimethylene carbonate (PGA:TMC), a poly-alpha-hydroxy acid, e.g., polylactic acid, polyglycolic acid, or a copolymer or blend thereof. The bioabsorbable material can be formed as a solid (molded, extruded, or crystalline), a coating (e.g., on the porous pocket), a self-adhesive web, a raised ribbon, or a mesh. Advantageously, certain bioabsorbable materials provide a slow bioabsorption profile that can be used to direct vascularization and other tissue ingrowth into various components of the implantable porous pocket, to secure the porous pocket in the implant site. For example, the bioabsorption profile can be slower than the rate of vascularization. In addition, a slow degradation profile can allow for transplantation / extraction of the porous pocket.

[0038] In some embodiments, the bioabsorbable material can have the ability to generate different levels of reactive oxygen species (ROS) in the body. ROS have been shown to promote various cellular responses in the body, including but not limited to: inhibition or promotion of cell proliferation, differentiation, migration, apoptosis, and angiogenesis. ROS-generating materials can be prepared according to the teachings set forth, for example, in U.S. Patent No. 9,259,435 to Brown et al.

[0039] In some embodiments, the cell maintenance environment is hostile to the bioabsorbable material. Thus, the second environment is different from the first cell maintenance environment. In some embodiments, the bioabsorbable material is configured to degrade upon contact with moisture. The dry environment need only be dry enough to prevent the bioabsorbable material from degrading adversely prior to implantation. In some embodiments, the dry environment has a reduced level of moisture than the surrounding environment. The dry environment can include a desiccant for maintaining the reduced level of moisture in the dry environment. Also, the bioabsorbable material can be temperature dependent, e.g., softer in a warmer environment (e.g., body temperature) and less soft in a cooler environment (e.g., room temperature). Thus, in some embodiments, the second environment can be a dry environment and / or a temperature controlled environment.

[0040] In some embodiments, the porous pouch comprises a polymeric material. The polymeric material can be selected from the group consisting of alginate, cellulose acetate, polyalkylene glycol, such as polyethylene glycol and polypropylene glycol, panvinyl polymers, such as polyvinyl alcohol, chitosan, polyacrylate, such as polyhydroxyethyl methacrylate, agarose, hydrolyzed polyacrylonitrile, polyacrylonitrile copolymer, polyvinyl acrylate, such as polyethylene-co-acrylic acid, porous polytetrafluoroethylene, modified polytetrafluoroethylene polymers, tetrafluoroethylene (TFE) copolymers, porous polyalkylenes, such as porous polypropylene and porous polyethylene, porous polyvinylidene fluoride, porous polyesther sulfone, porous polyurethane, porous polyester, porous polyvinylidene fluoride, and copolymers and combinations thereof. The polymeric material can be selected from the group consisting of porous polytetrafluoroethylene (PTFE) or expanded PTFE (ePTFE), porous polypropylene, porous polyethylene, porous polyvinylidene fluoride, and combinations thereof. In some embodiments, the polymer can be expanded PTFE (ePTFE), expanded polypropylene, expanded polyethylene, or combinations thereof.

[0041] Useful ePTFE materials can have a microstructure comprising nodes, fibrils, and voids between the nodes and fibrils. In addition to the bioabsorbable material, PTFE, polypropylene, polyethylene, and / or polyvinylidene fluoride can be included. For example, the bioabsorbable material can be copolymerized or blended with the polymer. In some embodiments, the bioabsorbable material can be present in the ePTFE or other polymeric material (e.g., as a powder). In some embodiments, the bioabsorbable material can be a coating on the polymer.

[0042] In some embodiments, the porous pouch contains a plurality of pores sized sufficiently to allow vascular tissue from the patient to grow within the plurality of pores. In some non-limiting examples, the porous pouch has a pore size greater than about 5.0 microns as measured by porometry. The ingrowth of vascular tissue through the porous pouch facilitates the transfer of nutrients from the body to the cells enclosed in the cell encapsulation device, and the material of the porous pouch is sometimes referred to herein as a vascularization material. In one embodiment, the porous pouch can include two layers, i.e., one layer having a pore size sufficient to allow ingrowth of vascular tissue (e.g., a vascularization layer), and one layer having a pore size sufficient to limit ingrowth of vascular tissue (e.g., a non-vascularization layer). The presence of a non-vascularization layer can help to preserve the space within the porous pouch so that the cell encapsulation device can be removed and reinserted one or more times.

[0043] The porous pouch can also contain a vascularization promoter to promote angiogenesis or vascularization within the porous pouch. Useful vascularization promoters are known to those skilled in the art and include, but are not limited to, vascular endothelial growth factor (VEG-F), fibroblast growth factor (FGF), matrix metalloproteinases (MMPs), angiopoietins (e.g., Angl and Ang2), delta-like ligand 4 (DII4), and class 3 semaphorins (SEMA3).

[0044] The vascularization promoter can be water soluble. In embodiments where the vascularization promoter is water soluble, storing the porous pouch in an aqueous cell maintenance environment can cause the vascularization promoter to leach from the porous pouch and, once implanted, reduce the amount and effectiveness of the vascularization promoter. Accordingly, in some embodiments, the porous pouch containing the vascularization promoter is stored in an environment different from the cell maintenance environment in which the cell encapsulation device is stored. In some embodiments, the porous pouch containing the vascularization promoter is stored in a dry environment. The dry environment need only be dry enough to prevent the vascularization promoter from leaching detrimentally from the porous pouch prior to implantation. In some embodiments, the dry environment has a reduced level of moisture than the surrounding environment. The dry environment can include a desiccant for dryly maintaining the reduced level of moisture in the environment.

[0045] The shape of the porous pocket is not limited, but in some embodiments, the shape of the porous pocket is consistent with the shape of the cell encapsulation device that is to be inserted into and contained by the porous pocket. However, at different times, one porous pocket can contain different cell encapsulation devices, and at times can contain one or more dummy devices. For example, when a porous pocket is initially implanted, it can include a dummy device to simulate the presence of a cell encapsulation device without containing living cells. Once vascularization has occurred and nutrients are available from the body, the dummy device can be replaced with a cell encapsulation device containing cells. This dummy device can be useful in situations where cells are not expected to survive the initial phase of implantation prior to vascularization of the porous pocket. Furthermore, in some embodiments, different cell encapsulation devices can be inserted into a single porous pocket to provide different therapies simultaneously or sequentially. Thus, the porous pocket should have a shape that accommodates and retains any cell encapsulation device intended for use by the clinician.

[0046] In some embodiments, the porous pocket can include an edge or tip along a portion of the porous pocket to facilitate implantation. The edge or tip can be a solid (i.e., non-porous) material and / or a denser material than the material that makes up the rest of the porous pocket. The edge or tip can be tapered to aid in implanting the porous pocket into a tissue bed. In some embodiments, the edge or tip is completely absorbable.

[0047] In some embodiments, the porous pocket is configured to hold a cell encapsulation device within the porous pocket. In some embodiments, the porous pocket is configured to attach to a cell encapsulation device. The porous pocket and / or the cell encapsulation device can be configured to allow insertion of the cell encapsulation device into the porous pocket and to allow subsequent removal of the cell encapsulation device from the porous pocket. Thus, in some embodiments, the porous pocket includes one or more openings through which a cell encapsulation device can be placed into the porous pocket, retrieved from the porous pocket, and replaced in the porous pocket. The openings can be resealable.

[0048] In some embodiments, a resealable port is affixed to an opening of the porous pocket. The resealable port can have any shape suitable for facilitating the placement, retrieval, and replacement of a cell encapsulation device in the porous pocket. In some embodiments, a commercially available fitting (e.g., a luer connector) can be used as the resealable port in the container apparatus described herein. In some embodiments, the resealable port is a hollow cylindrical fitting having a first portion that fits snugly within an end of the porous pocket and a second portion that extends outside of the porous pocket. In some embodiments, the resealable port is an opening in the porous pocket and has one or more flexible pieces or sheets of porous polymeric material positioned to cover and seal the opening. The sheets can be formed as part of the apparatus or can be attached to the apparatus after its initial construction.

[0049] In some embodiments, the resealable opening can be repeatedly opened and closed with a seal. Useful seals include, but are not limited to, caps, plugs, clamps, compression rings, and valves. In some embodiments, a cap can be used to close the opening in the porous pouch. The seal can be attached to the resealable opening by friction, by clamping, or with any other sealing means known to those skilled in the art. Depending on the intended use of the device, the resealable opening can be sealed to form a hermetic seal, a fluid-tight seal, or a non-fluid-tight seal. In some embodiments, a cell encapsulation device for permanent or long-term implantation in a patient can be sealed with a hermetic seal or a fluid-tight seal.

[0050] Cell encapsulation devices suitable for use in the embodiments described herein are not limited, but include any device useful for containing a plurality of cells or other biological moieties that can provide a therapeutic agent to a patient when implanted in the patient. In some embodiments, cell encapsulation devices suitable for use in the disclosed assemblies include any device for maintaining cells or other biological moieties in discrete space while allowing cell nutrients and waste to pass into and out of the device.

[0051] Figure 1 is one embodiment of an implantable assembly 100 described herein that includes a porous pouch 110 and a cell encapsulation device 120. The cell encapsulation device 120 is shown with a fill needle 130 for injecting cells (not shown) into the encapsulation device. Prior to insertion into the porous pouch 110, the encapsulation device 120 is sealed at a sealing region 140 and the needle 130 is removed. Additionally, the encapsulation device can be trimmed at a trimming region 150 outside the sealing region to remove extraneous material. The porous pouch 110 includes an open end 112 that is molded for engagement with a cap (not shown). In some embodiments, the molding for engagement with the cap can be a thermoplastic or thermoset plastic attached to or molded onto the porous pouch. In other embodiments, the porous pouch can be formed as a solid structure for engagement with the cap.

[0052] Figure 2 One embodiment of a porous pouch 210 described herein is shown. The porous pouch includes an open, molded end 212 for engagement with a cap (not shown) and a sealed end 214.

[0053] Figure 3 is a cross-sectional side view of one embodiment of an assembly 300 described herein. A porous pouch 310 surrounds a cell encapsulation device 320. The porous pouch 310 contains a vascularization promoting agent 330 distributed in the material forming the porous pouch 310.

[0054] Figure 4is a cross-sectional side view of one embodiment of an assembly 400 described herein. A porous pouch 410 surrounds a cell encapsulation device 420. The porous pouch 410 contains a vascularization promoter 430 distributed on the outer surface of the porous pouch 410.

[0055] Figure 5 is a cross-sectional side view of one embodiment of an assembly 500 described herein. A porous pouch 510 surrounds a cell encapsulation device 520. The porous pouch 510 contains a vascularization promoter 530 distributed on the inner surface of the porous pouch 510.

[0056] Figure 6 is a perspective view of one embodiment of a porous pouch 610 described herein. The porous pouch 610 has a molded end 612 for engaging a cap (not shown). The porous pouch 610 includes an opening 614 for receiving a cell encapsulation device (not shown). The porous pouch also has a lattice of bioabsorbable material 630.

[0057] Figure 7 is a perspective view of one embodiment of a porous pouch 710 described herein. The porous pouch 710 has an open end 714 for receiving a cell encapsulation device (not shown). The porous pouch also has a bioabsorbable ridge 730 to increase rigidity during implantation.

[0058] Figure 8 is a perspective view of one embodiment of a porous pouch 810 described herein. The porous pouch 810 has an opening 814 for receiving one or more cell encapsulation devices (not shown). In the embodiment shown, the porous pouch 810 is in the shape of three adjacent and connected tubes 820 for receiving cylindrical cell encapsulation devices (not shown). Between the tubes 820 is bioabsorbable material 830. The bioabsorbable material 830 is connected to the tubes 820 and provides rigidity to the porous pouch 810 during implantation. Figure 8

[0059] Figure 9 is a perspective view of one embodiment of a porous pouch 910 described herein. The porous pouch 910 has a sharp edge 916 to aid in implantation. The sharp edge 916 can be formed of bioabsorbable material. The porous pouch 910 has an opening 914 for receiving a cell encapsulation device (not shown).

[0060] Figure 10 is a perspective view of one embodiment of a porous pouch 1010 described herein. The porous pouch 1010 has a sharp tip 1016 at one end 1018 to aid in implantation. The sharp tip 1016 can be formed of bioabsorbable material. The porous pouch 1010 has an opening 1014 at the other end 1012 for receiving a cell encapsulation device (not shown).

[0061] ​The porous pouch and the cell delivery device can be inserted into the tissue bed together or separately. Non-limiting examples of tissue beds in which the assembly can be implanted include: subcutaneous tissue, adipose tissue, long bone, and central nervous system. As non-limiting examples, the tissue can be liver, skin, brain, thymus, pancreas, spleen, testes, kidney, portal vein, muscle, or heart. In some embodiments, the porous pouch can be inserted into the tissue bed first, followed by insertion of the cell encapsulation device into the porous pouch. In some embodiments, the cell encapsulation device can be subsequently removed from the porous pouch and a different cell encapsulation device inserted to provide continued therapy using the same or different cell populations. In some embodiments, a dummy device (containing no living cells) can be inserted into the porous pouch.

[0062] The present invention can be illustrated by the following:

[0063] 1. A kit comprising:

[0064] a cell encapsulation device housed in a first environment, wherein the first environment is a cell maintenance environment; and

[0065] a porous pouch housed in a second environment, wherein the second environment is different than the first environment,

[0066] wherein the cell encapsulation device is configured to fit within the porous pouch.

[0067] 2. The kit of claim 1, wherein the cell maintenance environment comprises a medium that facilitates survival of a plurality of cells.

[0068] 3. The kit of claim 1 or 2, wherein the medium is an aqueous medium.

[0069] 4. The kit of claim 1 or 2, wherein the medium comprises at least one cell nutrient.

[0070] 5. The kit of any of the preceding claims, further comprising: a plurality of cells in the cell maintenance environment.

[0071] 6. The kit of any of the preceding claims, wherein the cells are microencapsulated.

[0072] 7. The kit of any of the preceding claims, wherein the second environment is at least one member selected from the group consisting of a dry environment and a temperature controlled environment.

[0073] 8. The kit of any of the preceding claims, wherein the dry environment comprises a desiccant.

[0074] 9. The kit of any of the preceding claims, wherein the porous pouch comprises a bioabsorbable material.

[0075] 10. The kit of any of the preceding claims, wherein the bioabsorbable material is configured to degrade upon contact with moisture.

[0076] 11. The kit of any of the preceding claims, wherein the porous pocket has a sharp edge or a sharp tip to assist in implanting into a tissue bed.

[0077] 12. The kit of any of the preceding claims, wherein the porous pocket contains a plurality of pores sized to allow vascular tissue from a patient to grow within the plurality of pores.

[0078] 13. The kit of any of the preceding claims, wherein the porous pocket further comprises a non-vascularization layer containing a plurality of pores sized to limit ingrowth of vascular tissue into the plurality of pores.

[0079] 14. The kit of any of the preceding claims, wherein the porous pocket comprises a vascularization promoter.

[0080] 15. The kit of any of the preceding claims, wherein the porous pocket holds a cell encapsulation device within the porous pocket.

[0081] 16. The kit of any of the preceding claims, wherein the bioabsorbable material produces reactive oxygen species.

[0082] 17. The kit of any of the preceding claims, wherein the porous pocket is attachable to a cell encapsulation device.

[0083] 18. An implantable device, the implantable device comprising:

[0084] a porous pocket of bioabsorbable material;

[0085] a cell encapsulation device within the porous pocket;

[0086] wherein the cell encapsulation device is configured to fit within the porous pocket.

[0087] 19. The implantable device of claim 18, further comprising a plurality of cells.

[0088] 20. The implantable device of claim 18 or 19, wherein the cells are microencapsulated.

[0089] 21. The implantable device of any of claims 18, 19, or 20, wherein the bioabsorbable material is configured to degrade upon contact with moisture.

[0090] 22. The implantable device of any of the preceding claims, wherein the porous pocket comprises a plurality of pores sized to permit vascular tissue from the patient to grow within the plurality of pores.

[0091] 23. The implantable device of any of the preceding claims, wherein the porous pocket further comprises a water-soluble vascularization promoter.

[0092] 24. The implantable device of any of the preceding claims, wherein the porous pocket and / or the cell encapsulation device are configured to permit insertion of the cell encapsulation device into the porous pocket and removal of the cell encapsulation device from the porous pocket.

[0093] 25. The implantable device of any of the preceding claims, wherein the porous pocket is configured to be attached to the cell encapsulation device.

[0094] 26. The implantable device of any of the preceding claims, wherein the porous pocket has a sharp edge or a sharp tip to assist in implanting into a tissue bed.

[0095] The scope of the compositions and methods of the appended claims is not limited to the specific compositions described herein, which are intended as illustrations of some aspects of the claims. Any compositions and methods functionally equivalent to those described herein are within the scope of the present disclosure. Various modifications of the compositions and methods described herein are intended to fall within the scope of the appended claims. Furthermore, although only certain representative combinations of compositions, methods and aspects are specifically described herein, other combinations of compositions, methods and aspects are intended to fall within the scope of the appended claims. Thus, to the extent that steps, elements, components, or ingredients are expressly listed herein as part of the composition or method, and equivalents thereof are specifically recited, even if not expressly stated, are expressly included.

Claims

1. A kit for providing intra-tissue bed biotherapy to a patient, the kit comprising: A cell encapsulation device contained in a first environment, wherein... The first environment is the cell-maintaining environment; as well as A porous bag containing a bioabsorbable material is contained in a second environment, wherein the second environment is different from the first environment. The encapsulation device is configured to be fitted into the porous bag. The cell maintenance environment includes media that contribute to the survival of multiple cells. The medium is an aqueous medium. The bioabsorbable material is configured to degrade upon contact with moisture. The porous bag has multiple pores, the size of which is sufficient to allow vascular tissue from the patient to grow within the pores. The porous bag also includes a non-vascularization layer containing multiple pores, the size of which restricts vascular tissue from growing inward into the multiple pores.

2. The kit according to claim 1, wherein, The medium contains at least one cell nutrient.

3. The kit of claim 1, further comprising: a plurality of cells in the cell maintenance environment.

4. The kit according to claim 3, wherein, The cells are microencapsulated.

5. The kit according to claim 1, wherein, The second environment is at least one of a dry environment or a temperature-controlled environment.

6. The kit according to claim 5, wherein, The drying environment includes a desiccant.

7. The kit according to claim 1, wherein, The porous bag contains bio-absorbable material.

8. The kit according to claim 1, wherein, The porous bag has sharp edges or sharp tips to aid in implantation into the tissue bed.

9. The kit according to claim 1, wherein, The porous bag contains an angiogenesis promoter.

10. The kit according to claim 1, wherein, The porous bag is configured to hold the cell encapsulation device within the porous bag.

11. The kit according to claim 1, wherein, The bioabsorbable material generates reactive oxygen species.

12. The kit according to claim 1, wherein, The porous bag can be attached to the cell encapsulation device.

13. An implantable device for providing intra-tissue bed biotherapy to a patient, the implantable device comprising: Porous bags containing bioabsorbable materials; and Cell encapsulation device in a cell maintenance environment within a porous bag; The cell encapsulation device is configured to be placed inside a porous bag. The cell maintenance environment includes media that contribute to the survival of multiple cells. The medium is an aqueous medium. The bioabsorbable material is configured to degrade upon contact with moisture. The porous bag has multiple pores, the size of which is sufficient to allow vascular tissue from the patient to grow within the pores. The porous bag also includes a non-vascularization layer containing multiple pores, the size of which restricts vascular tissue from growing inward into the multiple pores.

14. The implantable device of claim 13, wherein the implantable device further comprises a plurality of cells.

15. The implantable device of claim 14, wherein, The cells are microencapsulated.

16. The implantable device of claim 13, wherein, The porous bag also contains a water-soluble angiogenesis promoter.

17. The implantable device of claim 13, wherein, The porous bag and / or the cell encapsulation device are configured to allow the cell encapsulation device to be inserted into the porous bag or removed from the porous bag.

18. The implantable device of claim 13, wherein, The porous bag is configured to be attached to the cell encapsulation device.

19. The implantable device of claim 13, wherein, The porous bag has sharp edges or sharp tips to aid in implantation into the tissue bed.

20. The kit according to claim 1, wherein, The cell encapsulation device has a sealing region that seals the cells injected into the cell encapsulation device.

21. The implantable device of claim 13, wherein, The cell encapsulation device has a sealing region that seals the cells injected into the cell encapsulation device.

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