Controllable implantable encapsulation device for reinjectable injection of single or multiple cell line

Abstract

In the systems and methods herein, an encapsulation device useful for cell line delivery is provided, the device having a multi-compartment design; a plurality of injection ports; encapsulating the cell line by using the device; porous; and maintaining cell function of different cell lines within the same device.

Description

Technical Field

[0001] The utility model relates to an encapsulation device. More particularly, the encapsulation device of the utility model can be used for stem cell therapy, delivering one or more cell lines to improve treatment effects, and regulating cell growth curves in an implanted subject. Background Art

[0002] Existing implantable devices may often encounter the following problems in actual use: (1) attempts to avoid immune attacks on stem cells, which limits the migration of stem cells after implantation; (2) the inability to repeat the injection of cells; (3) the inability to control the function of the encapsulated cells; and (4) the inability to carry more than one type of cell line, as reflected in patent publications US20230256137A1, US20200100921A1, CN110167485B, AU2021204321B2 and US20200281987A1. Utility Model Content

[0003] In order to solve the above-mentioned problems, the present invention provides a reusable, controllable, implantable encapsulation device for single or multiple cell lines. The implantable encapsulation device is made of biocompatible materials and includes:

[0004] a plurality of compartments, the plurality of compartments comprising at least a first compartment and a second compartment;

[0005] an interior compartment wall operably connected to the first compartment and the second compartment such that the interior compartment wall separates the first compartment from the second compartment, wherein the interior compartment wall includes a pair of control units, wherein the pair of control units are configured to control access to the first compartment and the second compartment;

[0006] a first set of two injection ports in the first compartment for receiving or expelling a first cell line, wherein the first cell line is thereby encapsulated in the first compartment;

[0007] a second set of two injection ports in the second compartment for receiving or expelling a second cell line, wherein the second cell line is thereby encapsulated in the second compartment;

[0008] a membrane surrounding the first compartment, the second compartment, and the inner compartment wall;

[0009] pores in the membrane and the inner compartment wall, wherein the pores are configured to facilitate transport of oxygen and secretions from the first cell line and the second cell line through the pores and to block transport of oxygen and secretions from the first cell line and the second cell line through the pores; and

[0010] The encapsulated second cell line is kept separate from the encapsulated first cell line to maintain the corresponding cell functions.

[0011] The encapsulation device provided by the present utility model solves the aforementioned technical problems and achieves the following technical effects: (1) The cell line can be repeatedly injected without removing the device from the implantation site; (2) The cell line can be washed without removing the device from the implantation site; (3) The function of the cell line, such as the secretion function, can be controlled through the device; and (4) Single or multiple cell lines are allowed to coexist with each other in the device. Description of the Drawings

[0012] According to one or more different embodiments, the present utility model will be described in detail with reference to the following drawings. The drawings are provided for illustrative purposes only and depict typical or exemplary embodiments of the present utility model. These drawings are provided to facilitate the reader's understanding of the present utility model and should not be construed as limiting the breadth, scope, or applicability of the present utility model. It should be noted that these drawings are not necessarily drawn to scale for clarity and convenience of illustration.

[0013] Some of the drawings included herein show various embodiments of the present utility model from different perspectives. Although the accompanying descriptive text may refer to these views as "top view", "bottom view", or "side view", these references are merely descriptive and do not imply or require the present utility model to be implemented or used in a specific spatial orientation, unless otherwise expressly stated.

[0014] Figure 1 A repeatable injection, controllable, and implantable encapsulation device is depicted, which can support two or more cell lines such that each corresponding cell line maintains its respective corresponding function. Among them, Figure 1 The pore size is 2 - 5 μm, the device length is 2 - 4 cm, the width is 1 - 1.5 cm, and the height is 2 - 4 cm. The injection port is a silicone-sealed injection port that can be identified subcutaneously, and the internal pipe structure for accommodating cells is not shown here. Circle A represents the first cell injection port 11 and the second cell injection port 12 in the first compartment, circle B represents the third cell injection port 13 and the fourth cell injection port 14 in the second compartment, and circle C represents the first control port 21 and the second control port 22 in the compartment wall 3.

[0015] Figure 2 A repeatable injection, controllable, and implantable encapsulation device is depicted, which can support two or more cell lines such that each corresponding cell line maintains its respective corresponding function, and can also be implanted into the skin layer S. Among them, the first cell injection port 11 is an injection port, the second cell injection port 12 is a discharge port, and the syringe needle is used to repeatedly inject or wash the cell contents or control materials through different ports. Detailed Description of the Embodiment

[0016] In this document, the present utility model is often described in accordance with exemplary environments. The descriptions of these environments are provided to permit the portrayal of the various features and embodiments of the present utility model in the context of exemplary applications. After reading this specification, it will become apparent to those of ordinary skill in the art how to implement the present utility model in different and alternative environments.

[0017] The present utility model provides a technical solution to the foregoing technical problems in the form of a device that can: (1) come into contact with a site via implantation at a certain location; (2) encapsulate a cell line (i.e., a large entity); and (3) selectively facilitate the transport of proteins, hormones, and small molecules (i.e., small entities) secreted from the encapsulated cell line while blocking the transport of large entities.

[0018] Thus, the device comes into contact with the implantation site, which produces the following technical advantages: (1) the cell line can be repeatedly injected without removing the device from the implantation site; (2) the cell line can be washed without removing the device from the implantation site; (3) the functions of the cell line, such as the secretion function, can be controlled through the device; and (4) allows single or multiple cell lines to coexist with each other in the device.

[0019] The device of the present utility model is an implantable device that can carry any type of human cell line, including stem cell lines for cell therapy purposes, such as carrying pancreatic β cell lines in diabetic patients to replace insulin, or any other disease with impaired function, such as hypothyroidism.

[0020] The device of the present utility model can be incorporated into a remotely wireless controllable system to automatically or manually control the functions of the stem cell line, or incorporated into a continuous glucose monitoring system for real-time feedback regulation purposes.

[0021] The device of the present utility model can be made of biocompatible materials, thereby achieving a permanent or semi-permanent state depending on the materials used in manufacturing (i.e., the length of time the device can remain in the body after implantation). Devices made of highly biocompatible materials can reduce the body's reaction when foreign objects are placed in the body. Due to its highly biocompatible and rigid design, the device is expected to last at least several months or even years at the implantation site without side effects. By manufacturing the device with different biocompatible materials, the lifespan of the device can be controlled, ranging from several months to several years.

[0022] The device of the present utility model can encapsulate two or more cell lines, such that each cell line, i.e., the load encapsulated by the device, can maintain its corresponding functions and properties. The load within the encapsulation device of the present utility model can be located in two or more different compartments, and each of the two or more different compartments contains a corresponding cell line. The encapsulation performed by the device of the present utility model enables controlled and selective transport while maintaining the corresponding functions and properties of each encapsulated cell line. The encapsulated cell lines of the present utility model can be characterized by Feature 1, Feature 2, and Feature 3. Features 1 - 3 are contrasted with encapsulation, which can lead to property changes such as: (i) the over-forceful release of the load from the encapsulation system, resulting in the uncontrolled and non-selective transport of the load from the encapsulation system; and (ii) the over-elastic accommodation of the load within the encapsulation system, resulting in the complete blockage of the transport of the load from the encapsulation system.

[0023] Regarding Feature 1 of the present utility model, the biocompatible material of the moldable device can be used to produce a polygonal device that contains multiple pores on the surface wall and the internal compartment walls (if required) to allow oxygen and cell secretions (such as insulin) to be permeable, and to avoid immune attack by restricting the migration of cells through the pores by size (i.e., the application of size exclusion). Thus, the device of the present utility model can be configured to encapsulate cell lines, and the encapsulated cell lines can avoid detection by the immune cells of the host organism into which the device is implanted. The pores can apply size exclusion. Oxygen and small entity secretions from cells (e.g., secreted small molecules or proteins) are small enough, so oxygen and small entity secretions from cells can pass through the pores (i.e., can be transported through the pores). Cells are too large, so cells can be blocked from passing through the pores (i.e., cannot be transported through the pores).

[0024] Regarding Feature 1 of the present utility model, the device can include a first group of encapsulated cell lines that can be located in a first compartment and a second group of encapsulated cell lines that can be located in a second compartment, where the first compartment and the second compartment are separated by an internal compartment wall. The outer surface wall can form a membrane around the ends of the first compartment, the second compartment, and the internal compartment wall. The outer surface wall and the internal compartment wall have pores, and these pores can apply size exclusion to achieve selective permeability. In other embodiments, more than one internal compartment wall can be placed between two or more compartments.

[0025] Regarding Feature 2 of the present utility model, the device of the present utility model may have multiple injection ports, with silicone seals and an internal piping structure to allow cell lines and control materials to be injected subcutaneously without removing the device. Each compartment may have a corresponding pair of injectable ports for transporting the cell line. For example, the first compartment may include a first cell injection port 11 and a second cell injection port 12; and the second compartment may include a third cell injection port 13 and a fourth cell injection port 14. The first compartment and the second compartment may each be operably connected to an internal compartment wall containing a first control port 21 and a second control port 22, wherein the internal compartment wall 3 may impose a physical barrier between the first compartment and the second compartment, and wherein the first control port 21 and the second control port 22 may control access to the first compartment and the second compartment. Thus, the device is configured to allow repeated injection or washing through different injection ports.

[0026] Regarding Feature 3 of the present utility model, the device of the present utility model may include an internal piping and compartment structure for accommodating cells to keep them alive and functional. If there is more than one cell line in the device of the present utility model, one or more cell lines may be injected into the device and encapsulated by the device in separate compartments or chambers. By locating the corresponding cell lines in compartments separate from other cell lines, one or more cell lines will not interfere with each other's functions. For example, the internal compartment wall 3 in the device of the present utility model may block chemical communication and physical contact between the encapsulated cell lines, as the wall imposes a physical barrier within the device. Each cell line in one or more cell lines may be expected to maintain all its functions. Thus, the device may be configured to manually or automatically confer controllable cell functions through control ports (the first control port 21 and the second control port 22).

[0027] Regarding Feature 3 of the present utility model, the device may have a multi-compartment design, i.e., the compartmentalization of the device of the present utility model may allow different cell lines to be introduced without coming into contact with each other. This may avoid the possibility of disrupted functions due to incompatibilities between different cell lines. The compartmentalization of the device of the present utility model may allow oxygen-generating materials to be introduced into the first compartment and ensure sufficient oxygen supply for the cells in the second compartment. Thus, the device may be configured to allow multiple cell lines to exist without adversely affecting the functions of the corresponding cell lines within the device.

[0028] In response to device insertion and subsequent device loading steps, cell lines may be delivered via the device of the present utility model.

[0029] Device Insertion: The implantable device may be inserted subcutaneously into a human subject, such as the dorsal side of the upper arm. This may be done in any doctor's clinic with appropriate sterile preparations.

[0030] Device Loading: Viable cells, such as stem cells or other cell lines, can be loaded either before or after the device is inserted. If loading a cell line after the device is inserted, simply touch the device from the skin surface, feel the front / back orientation of the button, identify the correct port, and use two syringes with needles, one for injection and one for releasing air / fluid pressure. Wash the cells or materials in the same manner.

[0031] Device Delivery of Cell Lines: The cell line can be contained within the device such that it is encapsulated by the device for the entire time the cell line is within the device. The encapsulated cells are not released outside the device. Instead, the encapsulated cells release small entities, such as therapeutic proteins or insulin, which are small enough to pass through the pores of the device of the present utility model and enter the surrounding tissue and blood vessels. The rigidity of the device of the present utility model can be maintained by the duration of implantation and the pore size of the pores, which are carefully selected such that size exclusion can be applied. Smaller entities (such as oxygen and secretions) released by the encapsulated cells can pass freely through the membrane, while larger entities (such as the encapsulated cells and immune cells) are prevented from coming into contact with each other because the pore size is not large enough to allow the encapsulated cells and immune cells to pass through the pores. The cell line can be retained in the device of the present utility model, and the secretions from the cell line can deliver a therapeutic effect by contacting, for example, the implantation area of a human subject through the pores.

[0032] Exemplary aspects of the device of the present utility model can include: a multi-compartment design; a plurality of dual injection ports; a plurality of pores and a plurality of control ports.

[0033] The multi-compartment design can be used to encapsulate corresponding cell lines, where the corresponding cell lines are located within the compartments due to encapsulation while maintaining the corresponding functions of each cell line and not interacting with each other due to the encapsulation and the internal walls separating the compartments.

[0034] The plurality of dual injection ports are operably connected to the multi-compartment design such that each compartment can have a dual injection port that allows for the washing, entry, re-entry, and discharge of the cell line;

[0035] The plurality of pores within the multi-compartment design can use size exclusion to allow the transport of oxygen and cell secretions and block the transport of cells, where the pores are located in the membrane and the internal walls; and

[0036] The plurality of control ports are operably connected to the internal walls, which allows for access to the compartments separated by the internal walls (i.e., inter-compartment access).

Claims

1. A reusable, controllable implantable encapsulation device for single or multiple cell lines, said implantable encapsulation device being composed of a biocompatible material, said implantable encapsulation device comprising: A plurality of compartments, said plurality of compartments including at least a first compartment and a second compartment; An internal compartment wall operatively connected to said first compartment and said second compartment such that said internal compartment wall separates said first compartment from said second compartment, wherein said internal compartment wall includes a pair of control units, wherein said pair of control units is configured to control access to said first compartment and said second compartment; A first set of two injection ports (11, 12) in said first compartment for receiving or discharging a first cell line, wherein said first cell line is thereby encapsulated in said first compartment; A second set of two injection ports (13, 14) in said second compartment for receiving or discharging a second cell line, wherein said second cell line is thereby encapsulated in said second compartment; A membrane surrounding said first compartment, said second compartment and said internal compartment wall; Pores in said membrane and said internal compartment wall, wherein said pores are configured to facilitate the transport of oxygen and secretions from said first cell line and said second cell line through said pores, and to block the transport of said first cell line and said second cell line through said pores; And Wherein the encapsulated second cell line remains separate from the encapsulated first cell line to maintain the respective cell functions.

2. The device according to claim 1, wherein said biocompatible material is configured to reduce the body's reaction when a foreign object is placed in the body.

3. The device according to claim 1, wherein said first set of injection ports (11, 12) and said second set of injection ports (13, 14) are configured to: (i) allow the re-entry of said first cell line and said second cell line, and (ii) wash said first cell line and said second cell line.

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