System and method for transplanting and transporting macroencapsulation devices

Abstract

This paper describes a macroencapsulation implantation device, a container for storing a macroencapsulation device disposed within a receptacle of the macroencapsulation implantation device, and related methods. In some embodiments, the macroencapsulation implantation device may include a handle configured to selectively engage with a receptacle containing a recess in which the macroencapsulation device may be disposed. In some embodiments, the container may be configured to hold the receptacle of the macroencapsulation implantation device and the macroencapsulation device disposed within it in a desired orientation within the internal volume of the container.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority to U.S. Provisional Patent Application No. 63 / 515,018, filed on July 21, 2023, entitled "MACROENCAPSULATION DEVICE IMPLANTATION AND TRANSPORT SYSTEM AND METHODS" under 35 U.S.C. § 119(e), the entire disclosure of which is incorporated herein by reference for all purposes.

[0002] The disclosed embodiments relate to macroencapsulation devices and their associated implantation devices.

Background Art

[0003] Therapeutic devices for delivering biological products can be used to treat metabolic disorders such as diabetes. These therapeutic devices can be implantable to provide biological products such as insulin over a long period of time. Some of these devices include macroencapsulation devices that can be used to house cells therein to produce the desired biological products.

Summary of the Invention

Means for Solving the Problems

[0004] In some embodiments, the macroencapsulation implantation device may include a receptacle that includes an internal channel that passes at least partially through and extends along the longitudinal axis of the receptacle. A recess may be formed in the distal portion of the receptacle, and the recess may form the distal opening of the internal channel. The recess may be sized and shaped to receive the macroencapsulation device placed therein. The macroencapsulation implantation device may also include a first portion of a lock formed on the proximal portion of the receptacle. The macroencapsulation implantation device may also include a handle having a second portion of the lock configured to selectively engage with the first portion of the lock for connecting the handle to the receptacle. The macroencapsulation implantation device may also include a pusher configured to be inserted into the internal channel of the receptacle when the handle is connected to the receptacle, and the receptacle may be configured to be displaced proximal to the pusher to displace the macroencapsulation device out of the distal opening of the internal channel.

[0005] In some embodiments, a method for implanting a macroencapsulation device is provided. The method may include inserting a handle pusher into an internal channel of the receptacle and connecting the handle to the receptacle with a lock. The method may also include displacing the receptacle proximal to the pusher and handle to displace the macroencapsulation device, which is located in a recess formed in the distal portion of the receptacle, out of the distal opening of the internal channel.

[0006] In some embodiments, the macroencapsulation implantation device may include a receptacle that includes an internal channel that passes at least partially through and extends along the longitudinal axis of the receptacle. The macroencapsulation implantation device may also include a recess formed in the distal portion of the receptacle, which may form the distal opening of the internal channel. The recess may be sized and shaped to receive the macroencapsulation device placed therein. The macroencapsulation implantation device may also include a plurality of slots formed in the distal portion of the receptacle and extending substantially parallel to the longitudinal axis of the receptacle. The plurality of slots may be configured to allow fluid communication between the recess and the surrounding environment.

[0007] In some embodiments, a method for storing a macroencapsulation device is provided. The method may include transferring nutrients and waste between the macroencapsulation device and the surrounding medium through a plurality of slots formed in the distal portion of the receptacle in which the macroencapsulation device is located.

[0008] In some embodiments, a container system for storing a macroencapsulation device is provided. The container system may include a body including an internal volume and an opening, and a pair of rails positioned on opposite sides of the longitudinal axis of the internal volume and extending into the internal volume. The container system may also include a pair of opposing grooves formed in and extending along at least a portion of the longitudinal length of the pair of rails, the pair of rails may be configured to hold receptacles of corresponding size and shape engaged with the pair of opposing grooves in a predetermined position within the internal volume.

[0009] In some embodiments, a method for storing a macroencapsulation device is provided. The method may include inserting a receptacle into a pair of opposing grooves formed in and extending along at least a portion of the longitudinal length of a pair of rails positioned on opposite sides of the longitudinal axis of the internal volume of a container. The macroencapsulation device may be placed in a recess formed within the distal portion of the receptacle. The method may also include supporting the receptacle in a predetermined orientation within the internal volume of the container by the pair of opposing grooves.

[0010] Naturally, the concepts described above, and the additional concepts discussed below, may be arranged in any suitable combination, as this disclosure is not limited thereto. Furthermore, other advantages and novel features of this disclosure will become apparent from the following detailed description of various non-limiting embodiments, when considered in conjunction with the accompanying drawings.

[0011] Brief explanation of the drawing The attached drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component illustrated in various figures may be represented by similar numbers. For clarity, not all components may be labeled in all drawings. In the drawings, this is as follows: [Brief explanation of the drawing]

[0012] [Figure 1A] Figure 1A is a top view of the handle of a macroencapsulation implantation device according to one embodiment. [Figure 1B] Figure 1B is a bottom view of the handle of a macroencapsulation implantation device according to one embodiment. [Figure 1C] Figure 1C is a perspective view of the handle of a macroencapsulation implantation device according to one embodiment. [Figure 2] Figure 2 is a top view of a pusher in a macroencapsulation implantation device according to one embodiment. [Figure 3A] Figure 3A is a perspective view of the distal portion of the pusher of a macroencapsulation device according to one embodiment. [Figure 3B] Figure 3B is a second perspective view of the distal portion of the pusher of Figure 3A, according to one embodiment. [Figure 4A] Figure 4A is a bottom view of the elongated shaft of a macroencapsulation implantation device, according to one embodiment. [Figure 4B] Figure 4B is a perspective view showing a first side of the elongated shaft of a macroencapsulation implantation device, according to one embodiment. <QQ000072>Figure 4C is a perspective view showing a second side of the elongated shaft of a macroencapsulation implantation device, according to one embodiment. [Figure 4D] Figure 4D is a perspective view of a first section of the elongated shaft of a macroencapsulation implantation device, according to one embodiment. [Figure 4E] Figure 4E is a perspective view showing a second section of the elongated shaft of a macroencapsulation implantation device, according to one embodiment. <000Q0078>Figure 5 is a top view of a macroencapsulation implantation device, according to one embodiment. [Figure 6A] Figure 6A is a perspective view of a container configured to hold a macroencapsulation implantation device, according to one embodiment. [Figure 6B] Figure 6B is an exploded perspective view of the components of a macroencapsulation implantation device within a container, according to one embodiment. [Figure 6C] [[ID=QQ29]]Figure 6C is an exploded perspective view of a container configured to hold a macroencapsulation implantation device in a predetermined orientation, according to one embodiment. [Figure 6D] Figure 6D is a front cross-sectional view of a container configured to hold a macroencapsulation implantation device in a predetermined orientation, according to one embodiment. [Figure 7] Figure 7 is a perspective view of a cover, according to one embodiment. [Figure 8] Figure 8 is a perspective view of an intermediate support configured to engage with a macroencapsulation implantation device, according to one embodiment. [Figure 9A]FIG. 9A is a perspective view of a cap of a container configured to engage a proximal end portion of a macroencapsulation implantation device, according to one embodiment. [Figure 9B] FIG. 9B is a second perspective view of a cap of a container configured to engage a proximal end portion of a macroencapsulation implantation device, according to one embodiment. [Figure 10A] FIG. 10A is a top view of a macroencapsulation device, according to one embodiment. [Figure 10B] FIG. 10B is a cross-sectional side view of an embodiment of a portion of the membrane of a macroencapsulation device in a non-filled configuration. [Figure 10C] FIG. 10C is a cross-sectional side view of an embodiment of a portion of the membrane of a macroencapsulation device in a filled configuration.

DETAILED DESCRIPTION OF THE INVENTION

[0013] Detailed Description The increasing need to deliver biological products to treat various disorders such as diabetes has led to the design of different types of implantable therapeutic devices. However, such devices, which may include macroencapsulation devices, are often difficult to transport, move, and / or implant within a subject (e.g., human and / or animal subjects). For example, macroencapsulation devices may contain fragile membranes that can be damaged when sufficiently large forces and / or pressures are applied, potentially causing damage and / or contamination of the entire macroencapsulation device. Depending on the therapeutic purpose of the macroencapsulation device, any damage and / or contamination may prevent the macroencapsulation device from being suitable for implantation within the subject. In addition, depending on the type and magnitude of the force applied to the macroencapsulation device, one or more cell populations present within the macroencapsulation device may be adversely affected (e.g., by the application of large shear forces that can cause cytotoxicity or death). However, the inventors have recognized that many conventional methods and systems used to handle implantable devices during transport and implantation typically do not protect the device from the application of forces that could damage the macroencapsulation device and / or the potential cell populations contained within it, as described above.

[0014] Considering the above, the inventors recognized the benefits associated with implantation devices for surgical implantation of macroencapsulation devices, which may help minimize the forces and / or pressures applied to the macroencapsulation devices during transport, manipulation, and / or implantation of the macroencapsulation devices. Specifically, the inventors recognized the benefits associated with storing the macroencapsulation devices in recesses formed in the elongated channels of the macroencapsulation implantation device prior to implantation. This may include storage and / or transport of the macroencapsulation devices within the elongated shaft. However, in some embodiments, since one or more cell populations are contained within the macroencapsulation devices, it may be desirable to store the elongated shaft and the macroencapsulation devices placed therein in a suitable medium to provide nutrients to one or more cell populations and remove waste from one or more cell populations. This transport of nutrients and waste may occur between the medium surrounding the elongated shaft of the macroencapsulation implantation device and the macroencapsulation devices, through one or more membranes of the macroencapsulation devices.

[0015] While it may be desirable to house the macroencapsulation device within a recess in the elongated shaft of the macroencapsulation implantation device before implantation, it may not be practical to store the macroencapsulation device together with the entire macroencapsulation implantation device while keeping the macroencapsulation device immersed in the desired medium. Therefore, in some embodiments, the macroencapsulation implantation device may include an elongated shaft configured to be selectively detached from and attached to an associated handle. The elongated shaft, which may include a recess sized and shaped to receive the macroencapsulation device when detached from the handle, may be sized and shaped to be placed within the internal volume of a container containing a suitable medium in which it is placed. To help avoid blocking exposed portions of the macroencapsulation device and / or applying undesirable forces to the macroencapsulation device while it is stored within the elongated shaft in the container, the container may be configured to support the elongated shaft in a desired orientation within its internal volume. Various types of supports may be used, including but not limited to rails, stoppers, spacers, covers, grips, or other types of supports that can engage with the elongated shaft and be configured to maintain the elongated shaft and the macroencapsulation device placed within it in a desired orientation. In some embodiments, the desired orientation may correspond to the orientation of an elongated shaft that is at least partially located within the internal volume of the container and oriented substantially parallel to the longitudinal axis of the internal volume of the container.

[0016] To facilitate the aforementioned storage of the elongated shaft of the macroencapsulation implantation device within the internal volume of the container, the macroencapsulation implantation device may include both a handle and an elongated shaft. The handle may include a pusher, which may extend distally away from a portion of the handle configured to be grasped by the user and / or a robotic surgical system, or otherwise engaged. The pusher may be configured to be inserted into an internal channel extending along the length of the elongated shaft. If the pusher is located within the internal channel of the elongated shaft, the handle may be selectively attached to the elongated shaft using a lock. The first portion of the lock may be formed on the proximal portion of the elongated shaft, and the second portion of the lock may be formed on the handle. Thus, the elongated shaft and the handle may be selectively attached to and / or detached from each other using the lock. Therefore, the entire elongated shaft can be attached to or detached from the handle, which may allow the elongated shaft to be stored within the aforementioned container having an internal volume at least partially filled with the desired medium.

[0017] In some embodiments, it may be desirable to use a lock to selectively allow or prevent relative movement of the elongated shaft and handle of the macroencapsulation implantation device. For example, as will be further detailed below with reference to the figures, when the handle's pusher is inserted into the internal channel of the elongated shaft, the lock may be moved between a first unlocked configuration and a second locked configuration. This may selectively allow the elongated shaft to be held on or removed from the handle. In addition, in some embodiments, when attached to the handle and the lock is in the second locked configuration, the elongated shaft may be configured to displace proximal to the handle's pusher. However, when the lock is in the first unlocked configuration, proximal movement of the elongated shaft relative to the pusher beyond the initial insertion of the pusher into the internal channel of the elongated shaft may be prevented. A safety device configured to prevent movement of the elongated shaft relative to the handle may also be used in some embodiments. Both of these features may help prevent unintended and / or partial deployment of the macroencapsulation device in operation.

[0018] As described above, macroencapsulation devices can be exposed to a desired medium during storage in a container containing the medium. However, when a non-porous elongated shaft is used, the diffusion of the medium into the macroencapsulation device may be hindered. Therefore, in some embodiments, the inventors have recognized the advantages associated with using one or more slots formed in a portion of an elongated shaft into which a recess configured to house a macroencapsulation device is formed. One or more slots formed in an elongated shaft can allow the recess, and therefore the macroencapsulation device placed therein, to be fluid communication with the surrounding environment of the elongated shaft. In some embodiments, one or more slots are a plurality of slots, including one or more slots formed on opposite sides of the elongated shaft. For example, a first group of slots may be formed on a first surface of the distal portion of the elongated shaft containing the recess, and a second group of slots may be formed on a second surface of the elongated shaft opposite the first surface. In any case, one or more slots may be sized and shaped to allow sufficient diffusion of nutrients and waste between the internal volume of the macroencapsulation device and the surrounding environment through one or more slots in order to maintain the viability of one or more cell populations contained within the macroencapsulation device. In some examples, the multiple slots may be elongated slots extending parallel to the longitudinal axis of the elongated shaft, which may help avoid scraping of the target tissue while inserting the elongated shaft into the target surgical site. In some embodiments, each of the multiple slots may be a linear slot, but other suitable shapes including, but not limited to, elliptical, circular, square, and / or other non-linear shapes may also be used, and the disclosure is not so limited.

[0019] In various embodiments disclosed herein, the multiple slots may have a total area (in a plane parallel to the surface of the macroencapsulation device) that is 30%, 40%, 50%, 60%, or other appropriate percentage or more of the corresponding total surface area of ​​the macroencapsulation device and / or recess. Therefore, in some embodiments, the multiple slots may have a total area of ​​30% or more of the corresponding total surface area of ​​the macroencapsulation device and / or recess. In some embodiments, the multiple slots may have a total area of ​​40% or more of the corresponding total surface area of ​​the macroencapsulation device and / or recess. In some embodiments, the multiple slots may have a total area of ​​50% or more of the corresponding total surface area of ​​the macroencapsulation device and / or recess. In some embodiments, the multiple slots may have a total area of ​​60% or more of the corresponding total surface area of ​​the macroencapsulation device and / or recess. The total area of ​​the multiple slots may also be 80%, 70%, 60%, 50%, 40%, or other appropriate percentage of the corresponding total surface area of ​​the macroencapsulation device and / or recess. Therefore, in some embodiments, the total area of ​​the multiple slots may be 80% or less of the corresponding total surface area of ​​the macroencapsulation device. In some embodiments, the total area of ​​the multiple slots may be 70% or less of the corresponding total surface area of ​​the macroencapsulation device. In some embodiments, the total area of ​​the multiple slots may be 60% or less of the corresponding total surface area of ​​the macroencapsulation device. In some embodiments, the total area of ​​the multiple slots may be 50% or less of the corresponding total surface area of ​​the macroencapsulation device. In some embodiments, the total area of ​​the multiple slots may be 40% or less of the corresponding total surface area of ​​the macroencapsulation device. Combinations of the above ranges are intended to include, for example, a total area of ​​multiple slots that is 30% to 80% of the corresponding total surface area of ​​the macroencapsulation device and / or recess.

[0020] The term “elongated shaft” is frequently used herein to describe a portion of the implantation device that facilitates the storage, transport, and / or deployment of the macroencapsulation device; however, the macroencapsulation device may, alternatively, be stored, transported, and / or deployed from within another type of receptacle configured to selectively engage with the handle of the implantation device described herein (e.g., using a lock or other arrangement). The receptacle may include an internal channel configured to receive the pusher of the handle described herein, a recess sized and shaped to receive the macroencapsulation device described herein, and / or a distal opening formed by the recess described herein. The receptacle may be formed in any suitable geometric shape, including the elongated shaft described herein and / or any other suitable geometric shape.

[0021] The use of elongated shafts or other receptacles for both delivering and storing macroencapsulation devices can offer several advantages. For example, reduced handling of macroencapsulation devices can help minimize the potential for contamination and / or damage to them, both pre- and during implantation. For example, storage within a recess of an elongated shaft / receptacle and delivery from there can help protect the macroencapsulation devices from inadvertently applied potentially damaging forces and / or contact, while eliminating the need for physicians to manipulate the macroencapsulation devices before implantation. Naturally, this disclosure should be understood to be not limited to these advantages, and other advantages different from those described above are also possible.

[0022] Suitable materials for use with any one of the embodiments of the macroencapsulation implantation device and / or associated container disclosed herein may include, but are not limited to, biocompatible plastics, metals, ceramics, and / or combinations thereof that can be used in the applications disclosed herein. For example, suitable materials may include, but are not limited to, aluminum, titanium, stainless steel, alumina, silicone, polycarbonate, polyvinyl chloride (PVC), polypropylene (PP), polyetheretherketone (PEEK), polyurethane (PU), and polyethylene (PE). In some embodiments, components of the macroencapsulation implantation device and / or associated container may also be treated and / or coated to modify material properties such as chemical resistance and / or color. For example, components of the macroencapsulation implantation device and / or associated container that are at least partially constructed from aluminum may include an anodized coating. Naturally, since this disclosure is not limited to being made from any particular material, various components of the macroencapsulation implantation device and associated container may be made from any suitable combination of materials.

[0023] In some embodiments, the macroencapsulation implantation device and / or associated container is sterile. The macroencapsulation implantation device and / or associated container may be configured as a single-use sterile device or as a reusable, sterilizable device. A reusable device may be used multiple times on the same subject and / or may be sterilized between each use, particularly between different uses on different subjects. In some embodiments, only a portion of the macroencapsulation implantation device, such as the handle, may be reusable and sterilizable, while other components, such as the elongated shaft and pusher, may be single-use. In addition, some components of the macroencapsulation implantation device, such as the handle, may, in some embodiments, not have to be in direct contact with the biological material and may be detachably attached to a pusher and / or elongated shaft that can be in direct contact with the biological material. The inventors have recognized that in some applications, such detachable couplings between these components may allow the use of separate sterile components with a single handle.

[0024] For any reusable components that can be sterilized, the components may be made from any suitable material for the desired type of sterilization. Possible sterilization methods may include, but are not limited to, thermal sterilization, chemical sterilization, and / or radiation sterilization, and specific examples include moist heat (autoclave), dry heat, flash steam, performic acid, peracetic acid, formaldehyde, carbon dioxide, ethylene oxide, ozone, plasma, and ultraviolet light.

[0025] As used herein, the user of a macroencapsulation implantation device may refer to an individual who can store, move, implant, and / or otherwise manipulate the macroencapsulation device before or during a surgical procedure. In some embodiments, the user may refer to a surgeon and / or physician, and the macroencapsulation implantation device may be used during surgery and / or other medical procedures.

[0026] A macroencapsulation device may include multiple layers of membranes. At least one outer membrane of these multiple layers of membranes may be semipermeable. However, embodiments are also intended in which each of the membranes is semipermeable, or at least one of the membranes in the device is substantially impermeable. Furthermore, the device may include two stacked membranes, three stacked membranes, and / or any other suitable number of membranes, as the disclosure is not limited to this form. For example, in one embodiment including two membranes, one membrane may be semipermeable and the other impermeable, or both may be semipermeable. It should be understood that the disclosure is not limited to any particular combination of membranes in a stacked structure. Examples of macroencapsulation devices include, for example, those described in WO2018232180, WO2019068059, WO2020206150, WO2020206157, and WO2023023006, each of which is incorporated as a whole by reference.

[0027] In some embodiments, the macroencapsulation device may include at least one population of cells located within the internal volume of the device. For example, the cell population may be located within an internal volume formed between two or more opposing layers of one or more outer membranes of the device, and the outer edge of the internal volume may be defined by one or more bindings that extend at least partially, in some examples, around the perimeter of the membrane or other suitable portion of the membrane, and extend throughout it. In such embodiments, at least the outer membrane of the device may be configured to block the passage of one or more cell populations from the device. Thus, one or more cell populations can be retained within the internal volume of the device. While the use of two outer membranes forming a single internal volume is primarily described, the use of multiple intermembranes positioned between the outer membranes of the device and / or multiple unconnected internal volumes within the device is also intended. In addition, examples are considered in which a single membrane is folded and bound to itself to provide two opposing membranes to form an internal volume.

[0028] While stretched polytetrafluoroethylene (ePTFE) may be used as the membrane material, the membrane of the macroencapsulation device may be formed from any suitable biocompatible material. The biocompatible material may be substantially inert to the cells contained within the macroencapsulation device and the surrounding tissue. The biocompatible material may include synthetic polymers or natural polymers. In some embodiments, the polymer may also be linear polymers, crosslinked polymers, network polymers, addition polymers, condensation polymers, elastomers, fibrous polymers, thermoplastic polymers, non-degradable polymers, combinations of the foregoing, and / or any other suitable type of polymer, as this disclosure is not limited in this way. As described above, in one embodiment, the polymer may include stretched polytetrafluoroethylene (ePTFE). Appropriate types of polymers may also include polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP), polymethyl methacrylate (PMMA), polystyrene (PS), polytetrafluoroethylene (PTFE), ePTFE, polyurethane (PU), polyamide (nylon), polyethylene terephthalate (PET), polyethersulfone (PES), polyetherimide (PEI), polyvinylidene difluoride (PVDF), polycaprolactone (PCL), poly(lactic acid-co-glycolic acid) (PLGA), poly-L-lactide (PLLA), polyacrylonitrile (PAN), electrospun PAN / PVC, any combination of the above, and / or any other suitable polymer material. In some embodiments, the membrane used in any of the embodiments disclosed herein may include PVDF. In some embodiments, the membrane used in any of the embodiments disclosed herein may include electrospun PAN PVC. In some embodiments, the membrane used in any of the embodiments disclosed herein may include PES. In some embodiments, the film used in any of the embodiments disclosed herein may include PS. In some embodiments, the film used in any of the embodiments disclosed herein may include PAN. In some embodiments, the film used in any of the embodiments disclosed herein may include polycarbonate.In some embodiments, the film used in any of the embodiments disclosed herein may include polypropylene. In some embodiments, the film used in any one of the embodiments disclosed herein may include PVC. In some embodiments, the film used in any one of the embodiments disclosed herein may include PU. In some embodiments, the film used in any one of the embodiments disclosed herein may include PET. In some embodiments, the film used in any one of the embodiments disclosed herein may include PCL. In some embodiments, the film used in any one of the embodiments disclosed herein may include PLGA. In some embodiments, the film used in any one of the embodiments disclosed herein may include PLLA. In some embodiments, the film used in any one of the embodiments disclosed herein may include PMMA. In some embodiments, the film used in any one of the embodiments disclosed herein may include PEI. In some embodiments, the film used in any one of the embodiments disclosed herein may include nylon. In some embodiments, the film used in any one of the embodiments disclosed herein may include PTFE. In some embodiments, the film used in any one of the embodiments disclosed herein may include PE. The synthesis methods used to form one or more porous films from the polymer materials described above may include, but are not limited to, expansion, solvent casting, immersion precipitation and phase separation, electrospinning, methods for generating isodivisional networks, methods for generating fibrous networks, or any other suitable methods for forming porous polymer films.

[0029] Sintering of a film can be used to alter its porosity and magnetic flux properties. For example, sintering can increase the porosity of a film while maintaining its porous structure. Sintering can also improve the mechanical stability and diffusion flux of a film. In some cases, sintered films may have a lower melting temperature than unsintered films of the same type. Furthermore, sintered films may exhibit different energy release during differential scanning calorimetry scans, showing a looser structure in addition to the thick, porous network found in sintered materials.

[0030] Considering the above, sintering may be used to alter the porosity and / or mechanical properties of the film, which can then be used to adjust the porosity and magnetic flux properties of the macroencapsulation device. Thus, in some embodiments, any desired combination of sintered and / or unsintered films or film layers may be used. For example, the two outer film layers of the device may be joined together in one way, either by combining a sintered film and an unsintered film, two sintered films, or two unsintered films. Furthermore, any number of intermediate films positioned between these outer films may be used, provided that these intermediate films are sintered or unsintered.

[0031] The membranes of the macroencapsulation devices described herein may be made from porous membrane materials configured to allow the transport of materials such as biological products having molecular weights of approximately 3000 kDa, 2000 kDa, 1000 kDa, 500 kDa, 400 kDa, 300 kDa, 200 kDa, 100 kDa, 50 kDa, 40 kDa, 30 kDa, 20 kDa, 10 kDa, 6 kDa, 5 kDa, 4 kDa, 3 kDa, 2 kDa, less than 1 kDa and / or any other suitable range of molecular weights depending on the desired application. The membranes of the macroencapsulation devices described herein may be made from porous membrane materials configured to allow the transport of materials such as biological products through the membrane, within molecular weight ranges of 1 to 3000 kDa, 1 to 2000 kDa, 1 to 1000 kDa, 1 to 500 kDa, 1 to 400 kDa, 1 to 30 kDa, 1 to 200 kDa, 1 to 100 kDa, 1 to 50 kDa, 1 to 40 kDa, 1 to 30 kDa, 1 to 20 kDa, 1 to 10 kDa, 1 to 6 kDa, 1 to 5 kDa, 1 to 4 kDa, 1 to 3 kDa, or 1 to 2 kDa. For example, one or more membranes of the macroencapsulation device may be configured to allow the flow of insulin through a membrane having a molecular weight of about 5.8 kDa. In some embodiments, one or more membranes of the macroencapsulation device may be configured to allow the flow of materials such as biological products within the range of 1 to 10 kDa. In some embodiments, one or more membranes of the macroencapsulation device may be configured to allow the flow of material, such as biological products, within the range of 1 to 6 kDa. In some embodiments, one or more membranes of the macroencapsulation device may be configured to allow the flow of material, such as biological products, within the range of 1 to 5 kDa. In some embodiments, one or more membranes of the macroencapsulation device may be configured to allow the flow of material, such as biological products, within the range of 1 to 4 kDa. In some embodiments, one or more membranes of the macroencapsulation device may be configured to allow the flow of material, such as biological products, within the range of 1 to 3 kDa. In some embodiments, one or more membranes of the macroencapsulation device may be configured to allow the flow of material, such as biological products, within the range of 1 to 2 kDa.

[0032] To provide desirable selectivity, the porous membranes used in the macroencapsulation devices disclosed herein may have an open porous structure (i.e., a structure containing multiple interconnected pores) with an average pore size of approximately 1 nm, 5 nm, 10 nm, 15 nm, 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 200 nm, 300 nm or more, and / or any other suitable size range. Accordingly, the average pore sizes of the various films described herein may have average pore sizes of 2500 nm, 2000 nm, 1700 nm, 1500 nm, 1400 nm, 1300 nm, 1200 nm, 1100 nm, 1000 nm, 900 nm, 800 nm, 700 nm, 600 nm, 500 nm, 400 nm, 300 nm, 200 nm, 100 nm, 90 nm, 80 nm, 70 nm, 60 nm, 50 nm, 40 nm, 30 nm, 20 nm or less, and / or any other suitable size range. The aforementioned combinations are intended to include, for example, average pore sizes between or equal to 1 nm and 20 nm, 1 nm and 2500 nm, 50 nm and 1200 nm, and / or any other suitable combination. In some embodiments, the average pore size of the various films described herein is 25 nm to 1500 nm. In some embodiments, the average pore size of the various films described herein is 50 nm to 1200 nm. In some embodiments, the average pore size of the various films described herein is 50 nm to 1000 nm. In some embodiments, the average pore size has an upper limit of 1500 nm. In some embodiments, the average pore size has an upper limit of 1200 nm. In some embodiments, the average pore size has a lower limit of 25 nm. In some embodiments, the average pore size has a lower limit of approximately 50 nm. While specific average pore sizes are described above, naturally, any suitable average pore size, including both larger and smaller average pore sizes than those described above, can be used for the various films described herein.

[0033] In some embodiments, the cell population contained within a compartment of the macroencapsulation device may be an insulin-secreting cell population. In some embodiments, the cell population contained within a compartment of the macroencapsulation device includes a heterogeneous cell population. In some embodiments, the cell population includes at least one cell derived from stem cells. In some embodiments, at least one cell is a genetically modified cell. In some cases, at least one cell is genetically engineered to reduce the immune response in the subject upon implantation of the device compared to an equivalent ungenetically engineered cell. In some embodiments, the cell population is stem cell-derived cells capable of glucose-stimulated insulin secretion (GSIS). For example, a suitable cell population may include pancreatic progenitor cells, endocrine cells, beta cells, a matrix including one or more of the aforementioned, or any combination thereof. Furthermore, the matrix may include isolated islet cells, cells isolated from the pancreas, cells isolated from tissue, stem cells, stem cell-derived cells (e.g., stem cell-derived islet cells), induced pluripotent cells, differentiated cells, transformed cells, or expression systems capable of synthesizing one or more biological products. In some embodiments, the macroencapsulation device includes a population of stem cell-derived islet cells. In some embodiments, stem cell-derived islet cells include stem cell-derived beta cells, stem cell-derived alpha cells, and / or stem cell-derived delta cells.

[0034] To provide the macroencapsulation device with sufficient strength and / or rigidity, various membranes and frames may be made from materials rigid enough to maintain the desired shape of the macroencapsulation device during use. The desired rigidity can be provided through a suitable combination of the material's Young's modulus (also called elastic modulus), thickness, and the overall structure that can be balanced with the desired permeability of the device. A suitable Young's modulus for the various membranes and frames described herein is at least 10 5 Pa, 10 6 Pa, 10 7 Pa, 10 8 Pa, 10 9 Pa, and / or 10 10It may be Pa. Other suitable Young's moduli for the various films and frames described herein may be used, including both Young's moduli greater than and less than these ranges. The range between the aforementioned Young's moduli is intended, for example, Young's moduli about 10 6 Pa~10 10 It is Pa.

[0035] The frame of the macroencapsulation device may be formed from any suitable biocompatible thermoplastic material. As mentioned above, in some embodiments, suitable materials for the frame may include polyetheretherketone (PEEK). Suitable materials for the frame may also include, but are not limited to, polycarbonate, polyurethane, polyetheretherketone (PEEK), polyvinyl chloride (PVC), poly(oxymethylene), poly(methyl methacrylate) (PMMA), thermoplastic polymer composites, polypropylene, fluorinated ethylene propylene (FEP), low-density polyethylene (LDPE), high-density polyethylene (HDPE), ultra-high-density polyethylene (UHDPE), polycaprolactone, polylactic acid, poly(glycolic acid), polylactic acid-co-glycolide, ethylene vinyl acetate copolymer, polyamide, poly(butylene) terephthalate, combinations of the above, and / or any other suitable thermoplastic material. In addition to the use of thermoplastic materials in frames, the disclosure is not limited to frames made entirely from thermoplastic materials, and embodiments are envisioned in which the frame includes a thermoplastic portion and another non-thermoplastic portion configured to be bonded to a film. In some embodiments, suitable materials for frames include polypropylene. In some embodiments, suitable materials for frames include fluorinated ethylene propylene (FEP). In some embodiments, suitable materials for frames include ultra-high density polyethylene (UHDPE). In some embodiments, suitable materials for frames include polycarbonate. In some embodiments, suitable materials for frames include polyurethane. In some embodiments, suitable materials for frames include PVC. In some embodiments, suitable materials for frames include poly(oxymethylene). In some embodiments, suitable materials for frames include poly(methyl methacrylate (PMMA)). In some embodiments, suitable materials for frames include thermoplastic polymer composite materials. In some embodiments, suitable materials for frames include polypropylene. In some embodiments, suitable materials for frames include LDPE. In some embodiments, suitable materials for frames include HDPE. In some embodiments, suitable materials for frames include polycaprolactone.In some embodiments, the frame material includes polylactic acid. In some embodiments, the frame material includes poly(glycolic acid). In some embodiments, the frame material includes polylactic acid-co-glycolide. In some embodiments, the frame material includes ethylene vinyl acetate copolymer. In some embodiments, the frame material includes polyamide. In some embodiments, the frame material includes poly(butylene) terephthalate. In other embodiments, the frame material or a portion of the frame may include titanium, graphene, stainless steel, or other suitable biocompatible material that exhibits sufficient rigidity to function as the frame of a macroencapsulation device.

[0036] As used herein, attitude can refer to a combination of the position (i.e., three-dimensional position) and orientation (i.e., angular orientation) of an object. For example, the attitude of an elongated shaft placed within the internal volume of a container can correspond to both the position and orientation of the elongated shaft within the internal volume of the container. In one such embodiment, as will be further detailed below, the attitude of the elongated shaft can correspond to the elongated shaft being located at least partially within the internal volume and being oriented such that its longitudinal axis extends substantially parallel to the longitudinal axis of the container.

[0037] Naturally, the above-mentioned materials, parameter ranges, and general descriptions of the construction and / or operation of the various components can be used individually or in combination with any one of the embodiments of macroencapsulation implantation devices and / or containers disclosed herein.

[0038] Referring to the figures, certain non-limiting embodiments are described in further detail. Naturally, the various systems, components, features, and methods described in connection with these embodiments can be used individually and / or in any desired combination, as this disclosure is not limited to the specific embodiments described herein.

[0039] Figures 1A–1C show one embodiment of the first part of a macroencapsulation implantation device, including a handle 100 and a pusher 110 extending distally away from the handle. As further detailed below, the pusher 110 may be sized and shaped to be inserted into an internal channel of a receptacle / elongated shaft, such that the distal portion 114 of the pusher opposite to the portion of the handle grasped by the user can be positioned to contact the macroencapsulation device located within a recess of the elongated shaft / receptacle. The handle 110 and the elongated shaft may be selectively coupled together by a lock 102. As shown in the figure, the lock may include a knob or other user-operable feature (e.g., a latch, switch, button, stopper, or other structure) that can be selectively moved between a first configuration 104, a second configuration 106, and / or a third configuration 108. In some embodiments, the lock 102 may include a first portion of the lock located on the elongated shaft / receptacle and a second portion of the lock located on the handle (e.g., the illustrated knob and corresponding lock structure). During operation, the handle 100 may be coupled to an elongated shaft by engaging a first part of the lock and a second part of the lock together. The lock 102 may transition from a first unlock configuration 104 to a second lock configuration 106. When the lock 102 is in the second lock configuration 104, the lock 102 or other suitable trigger may be configured to displace the engaged elongated shaft proximal to the handle, as indicated by the arrows and a third configuration 108. In the first configuration 104, the elongated shaft may be disengaged from the handle 100. To disengage the elongated shaft from the handle 100, the lock 102 or other trigger may be moved to displace the elongated shaft distally to its initial position relative to the handle 100, or the lock 102 may be moved from the second lock configuration to the first unlock configuration. The elongated shaft may then be disengaged from the associated handle 100, including the pusher 110.In some embodiments, switching the lock between different configurations may provide tactile feedback to the user so that the user receives an indication that a configuration change has occurred in the lock via an audible and / or tactile click. Various embodiments may include any suitable type of lock for selectively coupling / uncoupling the receptacle (i.e., the elongated shaft) and the handle.

[0040] In some embodiments, the macroencapsulation implantation device may also include a safety device to prevent unintended or partial deployment from the macroencapsulation implantation device. In some such embodiments, the safety device may, in a first configuration, prevent relative movement of the elongated shaft / receptacle and the handle of the macroencapsulation implantation device, and in a second configuration, allow relative movement of the elongated shaft and the handle. The safety device may correspond to any suitable structure that can selectively allow or prevent relative movement of the elongated shaft, and may include, but is not limited to, switches, clips, pins, and any other components that can selectively block or allow movement of structures associated with the movement of the elongated shaft relative to the handle. For example, Figures 1A-1C illustrate the use of a safety device 112 in the form of a clip positioned in a slot through which the knob of the lock 102 passes during the movement of the elongated shaft (see, for example, the elongated opening 206 formed in the pusher 200 in Figure 2). The presence of the clip in this elongated opening physically prevents the movement of the lock 102, and thus prevents the movement of the elongated shaft relative to the handle 100. Once the safety device moves to the second configuration (i.e., is removed from the elongated opening in this embodiment), the elongated shaft can be moved relative to the handle using the lock 102 or other trigger.

[0041] In consideration of the above, in some embodiments, the safety device may be selectively attachable to the handle and may be configured to selectively prevent the elongated shaft / receptacle from moving relative to the handle by preventing the lock from being displaced distally while in the second configuration. For example, the safety device may block the path of the lock's displacement in the second configuration. Thus, the lock and the connected elongated shaft cannot be displaced until the safety device is removed or moved by the user from a position that otherwise blocks the lock's path.

[0042] In some embodiments, it may be desirable to indicate the proper orientation of the elongated shaft / receptacle relative to the handle. This can be done using indicators such as the illustrated indicator arrow 116, which may be formed on the handle 100 and include a keyed shape and / or a corresponding indicator. These indicators may be aligned by the user to help connect the elongated shaft to the handle 100 in the correct orientation (see, for example, the corresponding indicator 420 formed on the elongated shaft in Figure 4C).

[0043] In the embodiments described above, the movement of the lock 102 between the first and second configurations, and the movement from the second to the third configuration, are shown as proximal displacement along a path blocked by the safety device 112, following the rotation of the knob. However, naturally, the lock can be moved between the first unlocked configuration and the second locked configuration using any desired combination of movements. In addition, although the proximal displacement of the lock is illustrated, other methods may be used to displace the lock and the associated elongated shaft. For example, the change between the locked and unlocked configurations may be caused by pressing a button, the path between the second and third configurations may be curved, or, since this disclosure is not limited to how the components are specifically selectively locked or displaced together, other suitable methods may be used to lock and / or displace these components.

[0044] Figure 2 shows one embodiment of a pusher 200 that can be attached to a portion of a handle configured to be grasped by a user. For example, the proximal portion 204 of the pusher may be configured to be attached to a first portion of the handle (e.g., the handle in Figure 1). The pusher may be attached to a portion of the handle using fasteners, adhesives, welding, brazing, or other suitable types of connections. Alternatively, the pusher may be formed integrally with the entire handle. The pusher may include an elongated straight portion including a distal end portion 202 of the pusher configured to be fixed relative to the macroencapsulation device during use. The pusher 200 may also have an elongated opening 206 formed along at least a portion of the length of the pusher 200. The elongated opening may engage with a portion of the lock to guide and restrict the lock and the movement of the connected elongated shaft relative to the other portion of the handle during proximal and distal movement of the elongated shaft.

[0045] Figures 3A-3B show perspective views of one embodiment of the distal portion 300 of a pusher that may be used in the embodiments described above. In some embodiments, the distal portion 300 may be sized and shaped to complement the shape of a corresponding portion of a macroencapsulation device located in a recess of an elongated shaft with which the pusher is in contact. By complementing the shape of the macroencapsulation device with the distal portion of the pusher, the contact area between the pusher and the macroencapsulation device can be maximized while helping to avoid stress concentration. This can help to distribute stress more uniformly across the engagement area of ​​the macroencapsulation device. For example, the distal portion 300 shown in Figures 3A-3B may be curved in multiple directions, and / or one or more edges (or any edges that may come into contact with the macroencapsulation device) may be chamfered. In the illustrated embodiment, the distal portion is curved to complement a circular macroencapsulation device and includes rounded edges. The width 302 of the distal portion 300 may have a radius of curvature that can at least partially match the radius of curvature of the macroencapsulation device. The thickness 304 of the distal portion 300 may also have a radius of curvature that can at least partially conform to the rounded and / or chamfered edges of the macroencapsulation device. An example of a macroencapsulation device that can be used with the pusher 300 is described below in further detail with reference to Figures 10A-10C. Depending on the embodiment, the curvature of the pusher in the width direction may differ from the curvature of the pusher in the thickness direction. In addition, as shown below in further detail with reference to Figures 4A-4E, the width of the pusher may be less than the width of the cross-section of the recess (not shown in Figures 3A-3B).

[0046] Figures 4A–4E show an elongated shaft 400 that can be detachably attached to a handle using a second portion of the lock 412. Figure 4A shows a first side view of the elongated shaft 400 having a proximal end portion 402 and a distal end portion 404, where at least a portion of the proximal end portion 402 can engage with the handle. Specifically, in the illustrated embodiment, the second portion of the lock 412 is a molded slot including a neck and an associated internal opening having a width greater than the corresponding width of the neck. This forms the second portion of the cam lock, and the first portion of the lock rotates into a second configuration where the dimensions of the first portion of the lock are too large to pass through the neck of the slot, thus locking the handle and the elongated shaft together, although other types of locks may also be used. The distal end portion 404 of the elongated shaft may include a recess 424 formed therein, which is configured to hold a macroencapsulation device placed within the recess. The macroencapsulation device can enter and exit the recess 424 through a distal opening 426 formed in the distal end portion of the elongated shaft. The distal opening may have a cross-section perpendicular to the longitudinal axis of the elongated shaft, which is sized and shaped to accommodate passage through the corresponding cross-section of the macroencapsulation device. For example, in the illustrated embodiment, the width and thickness of the cross-section of the distal opening may be greater than the corresponding width and thickness of the macroencapsulation device. In some embodiments, the distal portion of the elongated shaft / receptacle may be shaped to complement the shape of the macroencapsulation, for example, the distal end portion 404 of the elongated shaft 400 has an end shaped as a semicircle to fit a circular macroencapsulation device housed in a circular recess. However, such fit is not essential, and the distal portion may have any suitable geometric shape as long as the elongated shaft / receptacle can hold the macroencapsulation device in a recess formed in the distal end portion of the elongated shaft.

[0047] The elongated shaft 400 may include an internal channel 422 extending from the proximal end portion of the elongated shaft, which includes an opening through which an associated pusher is inserted, up to a recess 424 formed in the distal end portion of the elongated shaft. The internal channel may extend parallel to and, in some examples, along the longitudinal axis of the elongated shaft. In this case as well, the recess may form a distal opening of the internal channel in the distal end portion of the elongated shaft. In some embodiments, the maximum width of the cross-section of the recess and / or associated opening in a first direction perpendicular to the longitudinal axis of the elongated shaft may be greater than the thickness of the cross-section of the recess in a second direction perpendicular to the longitudinal axis and the first direction. In addition, in some embodiments, the width of the internal channel 422 and the corresponding pusher configured to be placed therein may be less than the corresponding maximum width of the recess and / or distal opening of the elongated shaft. During use, when the handle and the elongated shaft are connected together, the handle's pusher may be inserted through the internal channel 422 of the elongated shaft 400, and the width and thickness of the pusher may be sufficiently smaller than the width and thickness of the internal channel of the elongated shaft to allow for a slip-fit ​​of the pusher within the internal channel.

[0048] In the illustrated embodiment, the internal channel 422 of the elongated shaft 400 has a rectangular cross-sectional shape perpendicular to the longitudinal axis of the elongated shaft. However, the disclosure is not so limited, and other shapes may be used, including squares, rounded rectangles, elongated ellipses, and / or any other shapes through which a pusher can pass for engagement with a corresponding macroencapsulation device. Also, although a circular macroencapsulation device is illustrated, the disclosure is not limited to the shapes of the macroencapsulation device, the recess through which it is received, or the opening through which the macroencapsulation device is deployed, and other macroencapsulation devices having other cross-sectional shapes such as squares, rectangles, ellipses, or other suitable shapes may be used. The illustrated recess and macroencapsulation device have a width significantly greater than their thickness, so that the illustrated recess and macroencapsulation device configured to be received therein may have a flat, plate-like geometric shape in some embodiments. In any case, the size and shape of the recess formed in the distal end portion of the elongated shaft / receptacle may be sized and shaped to at least partially complement the size and shape of the macroencapsulation device placed within the recess.

[0049] In some embodiments, the elongated shaft / receptacle may be a two-piece structure. This may include a first section 416 and a second section 418 of an elongated shaft 400 which can be connected along their length at a connector 410. For example, the male connector 410a of the first section 416 may be connected to the female connector 410b of the second section 418 by heat riveting, threaded fasteners, friction fit, rivets, adhesives, brazing, or other suitable methods. During heat riveting, the male connector may melt and / or deform after being inserted through the female connector to permanently join the two sections, but other types of connections may also be used as described above. In some embodiments, the edges and / or seams of the elongated shaft may be rounded and / or chamfered to help prevent tissue damage during insertion into and removal from the object. In addition, in some embodiments, the elongated shaft / receptacle may be fabricated from a single piece of material using casting, injection molding, machining, a combination of the foregoing, and / or any other suitable manufacturing method, as the present disclosure is not limited thereto.

[0050] As described above, multiple slots 406 may be formed in the distal end portions 404 of both the first section 416 and the second section 418 of the elongated shaft 400. Thus, the multiple slots may include a first group of slots formed on the first surface of the distal portion of the elongated shaft 400 and a second group of slots formed on the second surface of the distal portion of the elongated shaft 400 opposite to the first surface. These slots may be aligned with and formed within a portion of the elongated shaft containing the recess 424. The slots may be elongated linear slots or other appropriately shaped slots, as described above. Thus, the slots may provide fluid communication between the recess 424 and the external environment surrounding the elongated shaft 400. This may expose a macroencapsulation device placed within the recess 424 to the environment surrounding the elongated shaft 400 through multiple slots that may be formed on at least one or two opposing sides of the recess. In some examples, the slots may be positioned within the outer periphery of the shape of the recess. For example, as best shown in Figure 4D, the slot 406 is formed in a portion of an elongated shape that forms a recess and is housed within the circular cross-section of the recess; however, other geometric shapes may also be used. As mentioned above, in some embodiments, the slot may extend in a direction substantially aligned with the longitudinal axis of the elongated shaft / receptacle to help minimize engagement with and / or tissue abrasion during insertion of the elongated shaft / receptacle into the target surgical site (e.g., within 5°, or more preferably within 1°). In some embodiments, it may be desirable for the slot to include rounded corners to help minimize abrasion with tissue that moves across it during the implantation procedure.

[0051] In some embodiments, the elongated shaft / receptacle may be configured with features that can improve the user's convenience and ease of use associated with the operation and use of the macroencapsulation device. For example, the elongated shaft 400 may include length indicators 408 (e.g., distance markings) positioned along the length of the elongated shaft on the outer surface of the elongated shaft. In such an embodiment, these length indicators 408 may be positioned on the outer surfaces of a first section 416 and / or a second section 418 on two large opposing surfaces of the elongated shaft. The length indicators 408 can assist the user in estimating the implantation depth of the macroencapsulation device during operation. In some embodiments, the length indicators may be provided at increments of any desired length measurement. Furthermore, at least one outer surface of a section of the elongated shaft 400 may have an orientation indicator 420 corresponding to the orientation indicator formed on the handle as described above. By aligning these indicators, it may be possible to properly orient the elongated shaft 400 with respect to the handle of the macroencapsulation implantation device.

[0052] Figure 5 shows a macroencapsulation implantation device in which an elongated shaft 400 is connected to a handle 100 by a lock 102 that has already moved from a first unlocking configuration 104 to a second locking configuration 106. In this configuration, the proximal end portion 402 may be partially located within the handle 100, and a pusher (not shown) is inserted into and located within an internal channel of the corresponding shape of the elongated shaft 400. As previously mentioned, orientation indicators 116 and 420 located on the handle 100 and the elongated shaft 400 can be aligned with each other to indicate that these components are positioned in the correct orientation relative to each other. If a macroencapsulation device is present, it may be located within a recess formed within the distal end portion 404 of the elongated shaft, as described above. In addition, the elongated shaft 400 is connected to the handle 100, and before the relative displacement of the elongated shaft 400 and the handle 100 when the lock 102 is first moved to the second lock configuration, the distal end portion of the pusher may be positioned adjacent to, and optionally in contact with, the macroencapsulation device in the recess of the elongated shaft 400.

[0053] If it is desired to displace the macroencapsulation device out of the distal opening of the elongated shaft / receptacle, the illustrated safety device 112 may be removed or otherwise moved to an unlock configuration to allow the lock 102 to move proximal to the handle. Thus, the lock 102 may be displaced from the second configuration 110 to the third configuration 108, and the elongated shaft 400 may be moved proximal to the handle 100 in the corresponding direction. In one embodiment, the lock may be displaced along a predetermined path in a direction substantially parallel to the longitudinal axis of the handle as the lock moves from the second configuration to the third configuration. For example, while the pusher is held fixed relative to the rest of the handle 100, the lock may be displaced within the elongated opening 206 formed in the pusher (see Figure 2). Thus, while the handle 100 and pusher are held fixed relative to the coordinate system of the user and / or robotic surgical system interacting with the macroencapsulation implantation device, the elongated shaft 400 may be moved proximal to the handle 100 and pusher.

[0054] When the elongated shaft 400 is displaced proximal to the handle 100 and the associated pusher is positioned within the internal channel of the elongated shaft, the distal end portion of the stationary pusher can exert force on the associated macroencapsulation device, which is located in the recess, to hold the macroencapsulation device in a fixed position relative to the handle. Thus, as the elongated shaft 400 moves proximal from an expanded configuration to a contracted configuration, the fixed macroencapsulation device can be displaced outward through the distal opening 426 formed in the distal end portion 404 of the elongated shaft. In some embodiments, the fully contracted configuration of the elongated shaft 400 and the lock 102 may correspond to a third configuration of the lock 102.

[0055] After the macroencapsulation device is deployed from the distal opening 426 of the elongated shaft 400, the macroencapsulation implantation device may be removed from the deployment site within the object. Optionally, the lock 102 may be moved back from the third configuration 108 to the second configuration 106 to return the elongated shaft 400 from a retracted configuration to an extended configuration relative to the handle 100. The lock may then be moved from the second lock configuration 106 to the first unlock configuration 104. The elongated shaft 400 may then be disengaged and removed from the handle 100. With the elongated shaft 400 released from the handle 100, the handle 100 may optionally be used to engage and deploy another macroencapsulation device located in another elongated shaft.

[0056] Figures 6A–6D show various diagrams of one embodiment of a container 600 that may be used to store a macroencapsulation device 614 positioned within the internal channels and / or recesses of the elongated shaft 616 of the macroencapsulation implantation device. This includes diagrams of different internal components of the container 600 that may be configured to support the elongated shaft 616 and associated macroencapsulation device in a predetermined orientation within the internal volume 602a of the container 600. In this case as well, this may serve both to protect the macroencapsulation device when it is stored in the container before use and to provide appropriate exposure to the surrounding medium.

[0057] The body 602 of the container 600 may include an internal volume 602a extending into the body from an opening 624 of the body. The internal volume 602a may be appropriately sized and shaped to at least partially accommodate an elongated shaft 616 of the macroencapsulation implantation device, and other internal components of the container 600 that may be configured to support the elongated shaft 616 and the macroencapsulation device 614 positioned within it in a predetermined orientation. When the elongated shaft 616 is appropriately positioned within the internal volume 602a of the container 600, the macroencapsulation device 614 may be in fluid communication with the medium contained within the internal volume 602 of the body through a plurality of slots on the elongated shaft 616, as described above.

[0058] The container 600 may include any number and / or types of supports to maintain the elongated shaft 616 in a predetermined position. For example, as is best seen in Figures 6C and 6D, opposing portions of the elongated shaft 616 (e.g., opposing thin sides extending between the larger flat surfaces of the illustrated elongated shaft) may be formed within at least a portion of the length of a pair of rails 618 and slidably engaged with opposing grooves extending along them. The pair of rails 618 may extend within the internal volume 602a of the container 600 and may be positioned on both sides of the longitudinal axis of the internal volume 602a of the body 602 of the container 600. The grooves 618a may extend along at least a portion of the longitudinal length of each rail of the pair of rails. Thus, the elongated shaft 616 may engage with a pair of opposing grooves so that it engages with the grooves 618a between the two opposing rails 618 in a desired predetermined position within the internal volume and is held within the grooves 618a. In some embodiments, the pair of rails 618 and associated grooves may be configured such that the gap between the pair of rails is larger near the opening 624 of the internal volume 102a compared to the distal portions of the pair of rails 618 away from the opening 624. For example, the rails and associated grooves may have a shape that conforms to the corresponding size and shape of an elongated shaft and may curve inward as they extend along the longitudinal axis, as shown in the figure. For example, the distal inner portions of the rails 618 and grooves 618a located opposite the opening 624 may be optionally sized and shaped to partially surround the distal end portion of the elongated shaft, which can help maintain the elongated shaft at a desired distance from the bottom surface of the internal volume located opposite the opening.

[0059] Naturally, the rail 618 of the container may be formed on any suitable part of the container. In the illustrated embodiment, the rail is formed as part of an intermediate support 620. The intermediate support includes a first part configured to be attached to a part of the container adjacent to the opening 624 or to another part of the container, such that the rail 618 is supported and can extend from the first part of the intermediate support into the interior volume 602a in a predetermined orientation. In some examples, the intermediate support may be a plate-like structure positioned on a support surface of the body 602 and configured to slide rotatably. However, the use of a non-rotatable support and / or other types of attachments is intended, and includes integral formation of the intermediate support 620 and the rail 618 with the body 602, and / or attachment of the intermediate support 620 to the body 602 using connectors such as threaded fasteners, welds, adhesives, mechanical interlocking features, and / or any other suitable method of connection for supporting the intermediate support 620 and the rail 618 with respect to the interior volume 602a of the container 600. In some embodiments, a pair of rails and (optionally) their respective grooves may be joined at their distal ends so that the pair of rails can form a single continuous structure (however, each rail may be formed as a separate component and joined to form a single continuous structure). For example, in some embodiments, a pair of rails 618 may be optionally joined by a rail connector 618a. In some embodiments, the rail connector 618a may additionally connect the grooves of the rails 618, but in other embodiments, the rail connector may comprise one or more flat walls that connect only the outer surfaces of each rail 618.

[0060] In some examples, it may be desirable to prevent leakage between the intermediate support 620 and the opening 624 of the body 602 of the container 600. In such embodiments, a seal 622 may be positioned between a portion of the intermediate support and another portion of the container 600, such as the corresponding cap 608 and / or the body 602 of the container. For example, in some embodiments, the seal 622 may be located between the outer rim of the intermediate support 620 and the cap 608 of the container. The seal 624 may help to seal the internal volume to the surrounding environment, which can help prevent contaminants from entering the container and / or prevent the medium and / or fluid inside the container from leaking out of the container. The seal 624 may be at least one of O-rings, flange seals, extruded profiles, static radial seals, axial face axial seals, and any other suitable type of seal. Suitable materials for the seal may include silicone, rubber, and / or any other suitable elastic material.

[0061] To facilitate the operation and engagement of the elongated shaft with the corresponding handle, in some embodiments, it may be desirable for the proximal portion of the elongated shaft 616 to extend proximal to the opening 624 of the container 600. For example, having a portion of the elongated shaft 616 that extends proximal to the opening 624 when the elongated shaft 616 is positioned within the container 600 can facilitate the operation and engagement of the proximal portion of the elongated shaft 616 with the handle of the macroencapsulation implantation device. Thus, the rail 618 and / or other supports may be configured to support the elongated shaft 616 in a position where the proximal portion of the elongated shaft 616 extends from the opening. In such embodiments, it may be desirable to have a cap 608 configured to engage with the elongated shaft 616 and help maintain it in the desired position. For example, the container may include a cap 608 that, when the cap 608 is attached to the body 602 of the container 600, includes a projection 608a that extends outward in a direction away from the body 602 and the opening 624 of the container 600, for example, along the longitudinal axis of the internal volume 602a. The projection 608a of the cap may include a cavity that is oriented toward the internal volume 602a when attached to the container body 602. The cavity of the projection may be sized and shaped to receive the proximal end portion of an elongated shaft 616 positioned therein when the cap is positioned on the container body 602. This can help hold the elongated shaft / receptacle in a desired position within the internal volume 602a of the container by holding the elongated body between the projection 608a of the cap 608 and the rail 618.

[0062] In some applications, it may be desirable to sample the medium contained within the container. Therefore, in some embodiments, the cap may include a sampling port 610 that can be used to sample the medium contained within the body 602. In some embodiments, the sampling port 610 may be a Luer port that prevents undesirable exchange of fluid from the external environment of the container 600 and from the internal volume 602a of the container 600. Therefore, in some embodiments, the container cap includes the sampling port 610. In some embodiments, the container cap does not include the sampling port 610. In some embodiments, the sampling port may be used to exchange the medium inside the container.

[0063] The cap 608 may be releasably coupled to the body 602 of the container 600 using any suitable type of releasable attachment, including but not limited to mating threads, threaded fasteners, clamps, interlocking fits, mechanical interlocking features, and / or any other suitable type of releasable attachment formed on the cap 608 and the container body 602. In some applications, it may be desirable to keep the elongated shaft / receptacle fixed to the container body during opening. In such embodiments, the rotary clamp 604 may include threads that engage with corresponding threads formed on the body 602, so that the rotary clamp can compress the cap 608 against the container body 602. During use, the projection of the cap 608 may be gripped by the user to hold the cap and container body fixed to each other. The cap may then be removed by rotating the rotary clamp 604 against the cap and container body 602. This may help to keep the elongated shaft 616 fixed during opening the container and avoid movement and / or application of force to the macroencapsulation device.

[0064] During use, the cap 604 may be disengaged from its engagement with the body 602. After the cap 604 is removed, the handle, with the lock in the first configuration, can engage with the proximal portion of the elongated shaft 616 extending from the opening 624 of the container. Since the elongated shaft 616 can protrude from the opening 624 of the body 602, the user can easily engage the handle and the elongated shaft 616 together. After the two parts are connected, the lock on the handle is selectively moved to the second configuration, so that the elongated shaft 616 and the handle can be connected as described above. The handle and elongated shaft assembly can then be removed from the container as a single assembly whenever the user is ready to implant the macroencapsulation device positioned in the recess of the elongated shaft.

[0065] As previously mentioned, the internal volume 602a of the container 600 may be designed to facilitate the diffusion of oxygen, nutrients, and waste between the medium contained in the internal volume and the macroencapsulation device 614 positioned within the elongated shaft 616. Therefore, in some embodiments, the container 600 may be configured with dimensions and / or geometric shape suitable for immersing at least the distal end portion of the elongated shaft / receptacle in a suitable volume of medium. The volume of the medium, and the gap between the wall of the internal volume 602a and the elongated shaft, may be sufficiently large to ensure adequate diffusion of waste and nutrients between the medium in the internal volume and the macroencapsulation device. For example, the body 602 may be an elongated cylinder having a body 602 and an opening 624 sized and shaped to receive the elongated shaft 616 therein. However, the use of an elongated cylinder can result in an unstable container that cannot easily maintain its orientation on a support surface during use. Therefore, the container 600 may include a base 606 connected to the bottom portion of the container body 602a, configured to support the container 600 on a support surface. To improve the stability of the container 600, the base may have a larger cross-sectional area than the cross-sectional area of ​​the container body 602. Therefore, the base may be appropriately sized to help provide stability for maintaining the container 600 in a desired position on the support surface. In addition, in some embodiments, a support or other reinforcing feature may extend between the outer surface of the body 602a and the base 606 to improve the stability and rigidity of the container 600.

[0066] In addition to supporting the elongated shaft 616 and the macroencapsulation device placed therein in a desired position within the container 600, it may be desirable to help prevent unintended movement of the macroencapsulation device from exiting the distal opening of the elongated shaft while it is placed within the container 600. Therefore, as best shown in Figure 6B, the cover 612 may be configured to selectively engage with and cover at least a portion, or all, of the distal opening of the elongated shaft 616 while it is placed within the container 600. By blocking the distal opening of the elongated shaft / receptacle, it may be possible to prevent the macroencapsulation device from unintentionally moving out of the recess and distal opening. The cover may be selectively attached to and detached from the distal portion of the elongated shaft 616 using any suitable type of connector. For example, the retainers 414 located on either side of the distal portion 404 of the elongated shaft on either side of the distal opening 426 (see Figures 4A-4E) may selectively engage with corresponding retainers 704 located on the corresponding portion of the cover 612 (see Figure 7). However, in some embodiments, the retainers may be located on different portions of the cover and / or the elongated shaft / receptacle. In addition, other selectively attachable and detachable connections may be used between the cover and the elongated shaft / receptacle, including, for example, friction fits, magnetic connectors, clamps, mechanical interlocking features, threaded fasteners, and / or any other suitable type of detachable connection.

[0067] Figure 7 shows the cover 612 in more detail. The cover 612 may be made of an elastically deformable material so that the cover 700 can be elastically deformed until the projection of the retaining arm 704 engages with the retaining arm on the elongated shaft. In some embodiments, the cover 612 may additionally include one or more projections 706 configured to extend at least partially into the distal opening of the elongated shaft when the cover is positioned on the distal portion of the elongated shaft. In the illustrated embodiments, these one or more projections extend proximal away from the elongated shaft and the surface of the cover oriented toward the distal opening when the cover is mounted on the elongated shaft such that one or more projections extend into the opening. The projections may help maintain the macroencapsulation device in a desired position within the recess of the elongated shaft. The one or more projections 706 may also be configured to restrict the movement of the macroencapsulation device positioned within the elongated shaft, while helping to minimize the forces and / or pressures applied to the macroencapsulation device by complementing and / or conforming to the dimensions and / or geometric shape of the macroencapsulation device.

[0068] While the rails of the container may help maintain the elongated shaft / receptacle in a desired position within the container, it may be desirable to include additional supports to maintain the desired positioning of the elongated shaft / receptacle relative to the bottom surface of the container. For example, as shown in Figures 6B, 6D, and 7, in some embodiments, a cover 612 selectively engageable with the distal portion of the elongated shaft 616 may include a support shaft 702 to help the elongated shaft maintain its position within the container. The support shaft may extend distally away from the cover, oriented toward the bottom surface of the internal volume 602a of the container, so that it moves away from the elongated body 616 when the cover 612 and the elongated shaft are positioned within the internal volume 602a. Thus, the support shaft may extend distally away from the distal portion of the elongated shaft when the cover is positioned on the elongated shaft. The length of the support shaft may be selected to maintain a desired distance between the distal portion of the elongated shaft and the bottom surface of the internal volume 602a of the container opposite the opening 624. In some embodiments, the support shaft 702 may be in contact with the bottom surface of the internal volume 602a of the container. In addition, during the user's operation and use of the macroencapsulation implantation device and associated container, the support shaft 702 may serve as a visual reminder to remove the cover 612 before any attempt to implant the macroencapsulation device.

[0069] Figure 8 shows an intermediate support 800 and a pair of associated rails 802 extending away from the intermediate support 800. As previously mentioned, the pair of rails 802 and the grooves 804 within each rail may be positioned on opposing portions of the intermediate support 800 such that the grooves 804 formed within the rails 802 can be oriented toward each side of the longitudinal axis of the intermediate support 800. In addition, the intermediate support 800 may include coupling holes 806 or other types of connectors formed within the body of the intermediate support 800, which can mate with corresponding connectors formed on the cap of the container, as shown in Figure 9B below. For example, the holes 806 may be sized and shaped to receive a projection 608b extending from the inner surface of the cap 608. The resulting coupling between the intermediate support 800 and the cap 608 of the container can prevent rotation between the cap and the intermediate support, as well as rotation of the elongated shaft engaged in the grooves 804 of the intermediate support 800. This may help avoid the application of undesirable rotational forces to the elongated shaft and macroencapsulation device when the cap 608 is removed from the container.

[0070] Figures 9A-9B show a cap 608 of the container, which may be removably coupled to the body of the container as described above. The cap 608 may again include a threaded swivel clamp 604 that can fasten the cap to the body of the container. The swivel clamp 604 may include a threaded connection, which may be coupled to a corresponding threaded connection on the opening of the container. In Figure 9B, the cap 608 is illustrated without the outer swivel clamp 604. As seen in this figure, the cap 608 may include one or more couplings configured to engage with an intermediate support of the container in the form of one or more protrusions 608b, which may be configured to selectively engage with and detach from a coupling hole 806 of the intermediate support shown in Figure 8 or other types of selectively detachable connections as described above.

[0071] Figures 10A–10C show embodiments of a macroencapsulation apparatus 1000 that may be used in any one of the embodiments of macroencapsulation implantation apparatus and / or container systems disclosed herein. As shown in the figures, the macroencapsulation apparatus may comprise a first membrane layer 1002 and a second membrane layer 1004. In some embodiments, the first and / or second membrane layers may comprise a polymer material such as ePTFE. In various embodiments, each of the first membrane layer 1002 and the second membrane layer 1004 may be sintered or unsintered. Each of the first and second membrane layers may also comprise a single layer or multiple layers.

[0072] The first membrane layer 1002 and the second membrane layer 1004 may be joined together at a joined periphery 1022 and a joining portion 1024 located within the joined periphery. In Figure 10A, the upper surface of the second membrane layer 1004 is shown together with the joined periphery 1022 of the membrane extending around the periphery of the membrane (e.g., where the first and second membrane layers are joined). The joined periphery 1022 may form an internal volume located between the first and second membrane layers, configured to encapsulate a cell population. In some embodiments, the joined periphery 1022 may extend around the entire periphery of the membrane, but as shown in Figure 10A, the joined periphery may have an unjointed portion 1035 to accommodate, for example, a filling port through which a cell population can be introduced into the internal volume of the device, and / or to cooperate with it. As understood, the dimensions of the joined periphery 1022 may at least partially define the size of the internal volume. For example, in embodiments in which the membrane(s) and / or apparatus have a generally circular shape, the joined peripheral portion 1022 may have a diameter 1028 that can at least partially define the size of the internal volume between the first membrane layer and the second membrane layer.

[0073] In some embodiments, the internal volume between the first and second film layers may include a network of continuous interconnected volumes formed by and / or between various junctions of the film. For example, as shown in Figure 10C, the internal volume between the first film layer 1002 and the second film layer 1004 may include a network of interconnected volumes (e.g., channels 1026) formed between junctions 1024. In some embodiments, the internal volume may have a volumetric thickness 1036, which may be the maximum distance between the first and second film layers in the direction perpendicular to the maximum transverse dimension of the apparatus. As understood, the overall thickness of the film (e.g., overall thickness 1040) may depend at least in part on the internal volumetric thickness 1036, as well as the film layer thickness 1038 for each film layer. As described herein, the thickness may be measured in the direction perpendicular to the maximum transverse dimension of the apparatus.

[0074] As shown in the figure, the bonded periphery may be located radially inward from the outer periphery 1050 of the membrane. The bonded portions 1024 may take the form of bonded dots distributed across the surface area of ​​the hexagonal array membrane. However, any suitable shape, arrangement, configuration, and / or spacing of these bonded regions may also be used. For example, as shown in Figure 10C, the bonded spacing 1042 may be the distance between adjacent bonded portions 1024. In addition, in some embodiments, one or more bonded portions 1024 may include through holes 1032 formed therein. Each through hole may have a through hole diameter 1044. Due to the presence of these bonded regions located radially inward from the bonded periphery of the membrane, the internal volume formed between the membranes may take the form of multiple interconnected channels 1026 corresponding to the unbonded regions of the membrane extending between these bonded portions when the configuration is filled (for example, as shown in Figure 10C).

[0075] In some embodiments, the membrane layer is connected to a frame 1100 that extends at least partially, and in some embodiments, entirely, around the bonded periphery 1022 of the membrane. The unbonded portion 1035 of the membrane may be positioned around the filling port 1110 of the frame and sealed so that the filling port remains in fluid communication with the internal volume. In some embodiments, the filling port 1110 may be contained within the frame 1100 to allow fluid communication in at least one direction between the external environment and the internal volume of the device. For example, the filling port 1110 may be configured to allow the introduction of a cell population into the volume between the first membrane layer 1002 and the second membrane layer 1004. The filling port 1110 may include a through-hole (not shown) extending through the filling port into the internal volume of the macroencapsulation device 1000 formed by the first membrane layer 1002 and the second membrane layer 1004, as shown in Figures 10A-10C.

[0076] In various embodiments, the frame 1100 may be formed in any suitable shape, including any suitable circular, elongated, linear, polygonal (e.g., pentagonal, hexagonal, octagonal, etc.), and / or any other suitable regular or irregular shape. For example, in the shown embodiment, the frame 1100 may be formed in a substantially circular shape. The frame thickness may be the maximum thickness between any two opposing surfaces or points in the cross-section of the frame. In some embodiments, the frame thickness may be measured in a direction perpendicular to the maximum transverse dimension of the frame 1100 and / or the device 1000.

[0077] While the above embodiments of the macroencapsulation apparatus may be used in either a macroencapsulation implantation apparatus and / or a container, it should be understood that the various embodiments disclosed herein are not limited to use in such apparatuses. Rather, the various embodiments of the macroencapsulation implantation apparatus and / or container disclosed herein may be used in any suitable type of macroencapsulation apparatus, as this disclosure is not limited to this form.

[0078] While this instruction has been described in conjunction with various embodiments and examples, it is not intended to limit this instruction to such embodiments or examples. On the contrary, this instruction includes various substitutes, modifications, and equivalents, as will be understood by those skilled in the art. Accordingly, the foregoing description and drawings are for illustrative purposes only.

Claims

1. A receptacle comprising an internal channel that passes through and extends along the longitudinal axis of the receptacle, A recess formed in the distal portion of the receptacle, wherein the recess forms the distal opening of the internal channel, and the recess is sized and shaped to receive a macroencapsulation device disposed therein, The first part of the lock formed on the receptacle, It is a handle, A second part of the lock is configured to selectively engage with the first part of the lock to connect the handle to the receptacle, A handle comprising: a pusher configured to be inserted into the internal channel of the receptacle when the handle is connected to the receptacle, wherein the receptacle is configured to be displaced proximal to the pusher, thereby displacing the macroencapsulation device out of the distal opening of the internal channel; A macroencapsulation implantation device equipped with the following features.

2. The macroencapsulation implantation apparatus according to claim 1, wherein the receptacle comprises an elongated shaft, and the internal channel passes at least partially through and extends along the longitudinal axis of the elongated shaft.

3. The macroencapsulation implantation apparatus according to claim 1 or 2, wherein the lock is configured to move selectively between at least a first configuration and a second configuration, in the first configuration the lock is disengaged, and in the second configuration the first portion of the lock and the second portion of the lock engage to hold the receptacle on the handle.

4. The macroencapsulation implantation apparatus according to claim 3, wherein the lock is configured to provide at least one of a tactile click or an audible click in response to a transition from the first configuration to the second configuration.

5. The macroencapsulation implantation apparatus according to any one of claims 1 to 4, wherein the lock is configured to displace when the lock is in the second configuration, thereby displacing the receptacle relative to the pusher.

6. The macroencapsulation implantation apparatus according to claim 5, further comprising a safety device configured to selectively prevent the lock from being displaced and displacing the receptacle relative to the handle.

7. The macroencapsulation implantation apparatus according to claim 6, wherein the safety device is removable in order to allow the lock to be displaced.

8. The macroencapsulation implantation apparatus according to any one of claims 1 to 7, wherein the width of the cross-section of the recess in a first direction perpendicular to the longitudinal axis of the receptacle is greater than the thickness of the cross-section of the recess in a second direction perpendicular to the longitudinal axis and the first direction.

9. The macroencapsulation implantation apparatus according to claim 8, wherein the width of the cross-section of the recess is less than or equal to the width of the receptacle.

10. The macroencapsulation implantation apparatus according to any one of claims 1 to 9, wherein the width of the pusher is smaller than the width of the cross-section of the recess.

11. The macroencapsulation implantation apparatus according to any one of claims 1 to 10, wherein the distal portion of the pusher is curved to complement the shape of the proximal portion of the macroencapsulation apparatus.

12. The macroencapsulation implantation apparatus according to claim 11, wherein the curvature of the distal portion of the pusher in the thickness direction of the pusher is different from the curvature of the distal portion of the pusher in the width direction of the pusher.

13. The macroencapsulation implantation apparatus according to any one of claims 1 to 12, further comprising a cover configured to be selectively held on the distal portion of the receptacle, wherein the cover is configured to at least partially cover the distal opening of the receptacle when positioned on the distal portion of the receptacle.

14. The macroencapsulation implantation apparatus according to claim 13, wherein the cover includes a support shaft configured to extend distally from the distal portion of the receptacle when the cover is positioned on the receptacle.

15. The macroencapsulation implantation apparatus according to claim 13 or 14, further comprising one or more return stoppers configured to selectively hold the cover on the distal portion of the receptacle.

16. The macroencapsulation transplantation apparatus according to any one of claims 1 to 15, further comprising the macroencapsulation device disposed within the recessed area.

17. The macroencapsulation implantation apparatus according to any one of claims 1 to 16, further comprising a plurality of length indicators arranged at intervals along the length of the apparatus, wherein the plurality of length indicators are configured to indicate the depth of insertion during an implantation procedure.

18. A method for implanting a macroencapsulation device, Insert the handle pusher into the internal channel of the receptacle, The handle is connected to the receptacle with a lock, A method comprising displacing the receptacle proximal to the pusher and handle, thereby displacing a macroencapsulation device, positioned within a recess formed in the distal portion of the receptacle, outward from the distal opening of the internal channel.

19. The method according to claim 18, further comprising moving the lock to a first configuration to selectively disengage the lock, and moving the lock to a second configuration to lock and hold the receptacle on the handle.

20. The method according to claim 19, wherein moving the lock to the second configuration provides at least one of a tactile click or an audible click.

21. The method according to any one of claims 18 to 20, wherein displacing the receptacle proximal to the handle and pusher includes displacing the lock when the lock is in the second configuration.

22. The method according to claim 21, further comprising selectively preventing the displacement of the lock in the second configuration with a safety device.

23. The method according to claim 22, further comprising removing the safety device to allow the lock to be displaced in the second configuration.

24. The method according to any one of claims 18 to 23, further comprising selectively holding a cover on the distal portion of the receptacle, wherein the cover is configured to at least partially cover the distal opening of the receptacle when positioned on the distal portion of the receptacle.

25. The method according to claim 24, further comprising removing the cover before displacing the receptacle proximal to the pusher.

26. A receptacle comprising an internal channel that passes through and extends along the longitudinal axis of the receptacle, A recess formed in the distal portion of the receptacle, wherein the recess forms the distal opening of the internal channel, and the recess is sized and shaped to receive a macroencapsulation device disposed therein, A plurality of slots formed in the distal portion of the receptacle and extending in a direction substantially parallel to the longitudinal axis of the receptacle, wherein the recessed portion is configured to be in fluid communication with the surrounding environment, A macroencapsulation implantation device equipped with the following features.

27. The macroencapsulation implantation apparatus according to claim 26, wherein the plurality of slots are a plurality of linear slots.

28. The macroencapsulation implantation apparatus according to any one of claims 26 to 27, wherein each of the plurality of slots includes a rounded corner.

29. The macroencapsulation implantation apparatus according to any one of claims 26 to 28, wherein the plurality of slots include a first group of slots formed on a first surface of the distal portion of the receptacle and a second group of slots formed on a second surface of the distal portion of the receptacle opposite to the first surface.

30. The macroencapsulation implantation device according to any one of claims 26 to 29, wherein the plurality of slots are formed in a portion of the distal portion of the receptacle in which the recess is formed.

31. The macroencapsulation implantation apparatus according to any one of claims 26 to 30, wherein the total area of ​​the slots is 30% to 80% of the cross-sectional area of ​​the recess.

32. The macroencapsulation implantation apparatus according to any one of claims 26 to 31, wherein the width of the cross-section of the recess in a first direction perpendicular to the longitudinal axis of the receptacle is greater than the thickness of the cross-section of the recess in a second direction perpendicular to the longitudinal axis and the first direction.

33. The macroencapsulation implantation apparatus according to claim 32, wherein the width of the cross-section of the recess is less than or equal to the width of the receptacle.

34. A method for storing a macroencapsulation device, A method comprising transferring nutrients and waste between a macroencapsulation device and a surrounding medium through a plurality of slots formed in the distal portion of a receptacle in which the macroencapsulation device is located.

35. The method according to claim 34, further comprising inserting the receptacle into a container, wherein the macroencapsulation device is in fluid communication with a medium placed within the internal volume of the container.

36. The method according to any one of claims 34 to 35, further comprising removing the macroencapsulation device from the container.

37. The method according to any one of claims 34 to 36, wherein the distal opening of the receptacle is formed by a recess in an internal channel of the receptacle, and the macroencapsulation device is disposed within the recess.

38. Inserting the handle pusher into the internal channel of the receptacle, The handle is connected to the receptacle with a lock, Displacing the receptacle proximal to the pusher and the handle, thereby displacing the macroencapsulation device located outside the recess and the distal opening of the internal channel, The method according to claim 37, further comprising:

39. The method according to any one of claims 37 to 38, further comprising selectively holding a cover on the distal portion of the receptacle to prevent the macroencapsulation device from moving out of the distal opening.

40. The method according to claim 39, further comprising removing the cover before displacing the macroencapsulation device by displacing the receptacle proximal to the pusher and the handle.

41. A container system for storing a macroencapsulation device, wherein the container is The main body, including the internal volume and openings, A pair of rails positioned on both sides of the longitudinal axis of the internal volume and extending within the internal volume, A container system comprising: a pair of opposing grooves formed in at least a portion of the longitudinal length of the pair of rails and extending thereto, wherein the pair of rails are configured to hold receptacles of corresponding size and shape engaged with the pair of opposing grooves in a predetermined position within the internal volume.

42. The container system according to claim 41, further comprising rail connectors for attaching the pair of rails at their distal ends.

43. The container system according to claim 41 or 42, wherein the gap between the pair of rails is larger near the opening than the distal portions of the pair of rails away from the opening.

44. The container system according to any one of claims 41 to 43, further comprising the receptacle and the macroencapsulation device, wherein the receptacle is positioned within the internal volume between the pair of rails and engages with the pair of opposing grooves, and the macroencapsulation device is positioned within a recess formed in the distal portion of the receptacle.

45. The container system according to claim 44, wherein the distal portion of the receptacle is spaced apart from the bottom surface opposite to the opening.

46. The container system according to claim 44 or claim 45, wherein the proximal portion of the receptacle extends proximal to the opening.

47. The container system according to any one of claims 44 to 46, further comprising a plurality of slots formed in the distal portion of the receptacle and extending in a direction substantially parallel to the longitudinal axis of the receptacle, wherein the plurality of slots are configured to allow the recess to be in fluid communication with the surrounding environment.

48. The container system according to any one of claims 45 to 47, further comprising a cover configured to be selectively held on the distal portion of the receptacle, wherein the cover is configured to at least partially cover the distal opening of the receptacle.

49. The container system according to claim 48, wherein the cover is provided with a support shaft extending distally from the cover when the cover is attached to the distal portion of the receptacle.

50. The container system according to claim 49, wherein the support shaft is configured to maintain a distance between the distal portion of the receptacle and the bottom surface of the internal volume of the container.

51. The container system according to any one of claims 48 to 50, further comprising one or more return stoppers configured to selectively hold the cover on the distal portion of the receptacle.

52. The container system according to any one of claims 41 to 51, further comprising a cap attached to the main body and configured to cover the opening.

53. The container system according to claim 52, wherein the cap includes a projection that extends proximal to the opening of the container when the cap is attached to the body, the receptacle is positioned within the internal volume, and when the cap is attached to the body, a cavity formed in the projection is configured to receive the proximal portion of the receptacle within it.

54. The container system according to claim 52, wherein the cap is configured to be removed while maintaining the receptacle fixed to the main body.

55. The container system according to any one of claims 41 to 54, further comprising an intermediate support coupled to the proximal portions of the pair of rails, wherein the intermediate support engages with the main body to support the pair of rails within the internal volume of the main body.

56. The container system according to any one of claims 41 to 55, further comprising a medium disposed within the internal volume.

57. A method for storing a macroencapsulation device, Inserting a receptacle into a pair of opposing grooves formed in and extending along the longitudinal length of a pair of rails located on both sides of the longitudinal axis of the internal volume of a container, wherein the macroencapsulation device is positioned in a recess formed in the distal portion of the receptacle. A method comprising supporting the receptacle in a predetermined position within the internal volume of the container by a pair of opposing grooves.

58. The method according to claim 57, further comprising positioning the macroencapsulation device in a recess formed in the distal portion of the receptacle before inserting the receptacle into the pair of opposing grooves.

59. The method according to any one of claims 57 to 58, further comprising immersing a portion of the receptacle, including the macroencapsulation device, in a medium.

60. The method according to claim 59, further comprising transferring nutrients and waste between the macroencapsulation device and the medium through a plurality of slots formed in the receptacle.

61. The method according to any one of claims 57 to 60, further comprising maintaining the distance of the receptacle from the bottom surface of the container.

62. The method according to any one of claims 57 to 61, further comprising attaching a cover to the distal portion of the receptacle to at least partially cover the distal opening of the receptacle.

63. The method according to claim 62, further comprising removing the cover from the distal portion of the receptacle.

64. The method according to any one of claims 57 to 63, further comprising maintaining the receptacle in a fixed state relative to the body of the container when removing the cap from the container.

65. A receptacle comprising an internal channel that passes through and extends along the longitudinal axis of the receptacle, A recess formed in the distal portion of the receptacle, wherein the recess forms the distal opening of the internal channel, and the recess is sized and shaped to receive a macroencapsulation device disposed therein, A pusher configured such that when the handle is connected to the receptacle, it is inserted into the internal channel of the receptacle, wherein the receptacle is configured to be displaced proximal to the pusher, thereby displacing the macroencapsulation device out of the distal opening of the internal channel; A plurality of length indicators arranged at intervals along the length of the device, configured to indicate the depth of insertion during the implantation procedure, A macroencapsulation implantation device equipped with the following features.

66. The macroencapsulation implantation apparatus according to claim 65, wherein the plurality of length indicators are arranged on the outer surface of the receptacle along the length of the receptacle.

67. The macroencapsulation implantation apparatus according to claim 65 or claim 66, wherein the receptacle comprises an elongated shaft, the internal channel passing at least partially through and extending along the longitudinal axis of the elongated shaft, and the plurality of length indicators arranged on the outer surface of the elongated shaft.

68. The macroencapsulation implantation apparatus according to any one of claims 65 to 67, wherein the pusher includes a portion of the handle of the apparatus, and the apparatus further comprises a lock configured to selectively engage the handle and the receptacle.

69. The macroencapsulation implantation apparatus according to claim 68, wherein the lock is configured to move selectively between at least a first configuration and a second configuration, in the first configuration the lock is disengaged, and in the second configuration the first portion of the lock and the second portion of the lock engage to hold the receptacle on the handle.

70. The macroencapsulation implantation apparatus according to claim 69, wherein the lock is configured to provide at least one of a tactile click or an audible click in response to a transition from the first configuration to the second configuration.

71. The macroencapsulation implantation apparatus according to any one of claims 68 to 70, wherein the lock is configured to displace when the lock is in the second configuration, thereby displacing the receptacle relative to the pusher.

72. The macroencapsulation implantation apparatus according to any one of claims 68 to 71, further comprising a safety device configured to selectively prevent the lock from being displaced and displacing the receptacle relative to the handle.

73. The macroencapsulation implantation apparatus according to claim 71, wherein the safety device is removable in order to allow the lock to be displaced.

74. The macroencapsulation implantation apparatus according to any one of claims 65 to 73, wherein the width of the cross-section of the recess in a first direction perpendicular to the longitudinal axis of the receptacle is greater than the thickness of the cross-section of the recess in a second direction perpendicular to the longitudinal axis and the first direction.

75. The macroencapsulation implantation apparatus according to claim 74, wherein the width of the cross-section of the recess is less than or equal to the width of the receptacle.

76. The macroencapsulation implantation apparatus according to any one of claims 65 to 75, wherein the width of the pusher is smaller than the width of the cross-section of the recess.

77. The macroencapsulation implantation apparatus according to any one of claims 65 to 76, wherein the distal portion of the pusher is curved to complement the shape of the proximal portion of the macroencapsulation apparatus.

78. The macroencapsulation implantation apparatus according to claim 77, wherein the curvature of the distal portion of the pusher in the thickness direction of the pusher is different from the curvature of the distal portion of the pusher in the width direction of the pusher.

79. The macroencapsulation implantation apparatus according to any one of claims 65 to 78, further comprising a cover configured to be selectively held on the distal portion of the receptacle, wherein the cover is configured to at least partially cover the distal opening of the receptacle when positioned on the distal portion of the receptacle.

80. The macroencapsulation implantation apparatus according to claim 79, wherein the cover includes a support shaft configured to extend distally from the distal portion of the receptacle when the cover is positioned on the receptacle.

81. The macroencapsulation implantation apparatus according to claim 79 or 80, further comprising one or more return stoppers configured to selectively hold the cover on the distal portion of the receptacle.

82. The macroencapsulation transplantation apparatus according to any one of claims 65 to 81, further comprising the macroencapsulation device disposed within the recessed area.

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