Abstract
An implantable and retrievable medical device is provided. The device may be implanted in and extracted from a patient and the device is adapted to house and deliver donor cells or other drugs. The device comprises a hollow core having a volume for receiving cells and a plurality of layers surrounding the core. The layers comprise various materials suitable for enhancing immunoprotection and for promoting vascular growth into the device.
Claims
1. An implantable cell delivery device adapted to be inserted into the tissue of an animal, the device comprising: a shell comprising a core operable to receive and store cells and a first layer provided to enhance immunoprotection and limit fibrosis; a second layer comprising an alginate polyacrylamide layer and having a stiffness; and a third layer comprising a vascularization inducer to promote the growth of new blood vessels to the device.
2. The implantable cell delivery device of claim 1, wherein the vascularization inducer comprises a high-G alginate and VEGF-C.
3. The implantable cell delivery device of claim 1, wherein the device comprises a diameter of approximately 2.0 mm.
4. The implantable cell delivery device of claim 1, wherein the device comprises a length of approximately 12.0 mm.
5. The implantable cell delivery device of claim 1, wherein the core comprises donor cells.
6. The implantable cell delivery device of claim 1, further comprising a plurality of additional cell delivery devices of the same construction and wherein the cell delivery devices are bonded together.
7. The implantable cell delivery device of claim 1, wherein the cell delivery devices are bonded together with alginate-polyacrylamide.
8. An implantable cell delivery device adapted to be inserted into the tissue of an animal, the device comprising: a sheet comprising a plurality of implants bonded together with alginate-polyacrylamide; wherein each of the plurality of implants comprises a core operable to receive and store cells and a first layer provided to enhance immunoprotection and limit fibrosis, a second layer comprising an alginate polyacrylamide layer and having a stiffness; and a third layer comprising a vascularization inducer; and wherein the sheet is operable to be rolled or folded for implantation within an animal.
9. The implantable cell delivery device of claim 8, wherein the vascularization inducer comprises a high-G alginate and VEGF-C.
10. The implantable cell delivery device of claim 8, wherein each of the plurality of implants comprises a diameter of approximately 2.0 mm.
11. The implantable cell delivery device of claim 8, wherein each of the plurality of implants comprises a length of approximately 12.0 mm.
12. The implantable cell delivery device of claim 8, wherein the core of each of the plurality of implants comprises donor cells.
13. The implantable cell delivery device of claim 8, wherein the sheet comprises alginate-polyacrylamide.
14. The implantable cell delivery device of claim 8, wherein at least some of the implants are bonded together with alginate-polyacrylamide.
15. A method of implanting a cell delivery device in an animal, the method comprising: providing an implantable cell delivery device comprising: a shell comprising a core operable to receive and store cells and a first layer provided to enhance immunoprotection and limit fibrosis; a second layer comprising an alginate polyacrylamide layer; and a third layer operable to promote the growth of new blood vessels to the cell delivery device; forming an incision in the dermis of an animal; implanting the cell delivery device within the incision and such that the cell delivery device is provided subcutaneously in the animal; closing the incision and allowing the cell delivery device to remain in the animal, wherein the cell delivery device is operable to promote vascularization induction between the animal and at least one of the first layer, the second layer, and the third layer.
16. The method of claim 15, wherein the animal is a human.
17. The method of claim 15, wherein a plurality of implantable cell delivery devices are provided.
18. The method of claim 17, wherein the plurality of implantable cell delivery devices are provided on a sheet, and further comprising a step of unrolling, unfolding, or spreading the sheet subsequent to inserting the sheet within the incision.
19. The method of claim 15, wherein the third layer comprises a vascularization inducer.
20. The method of claim 15, further comprising the step of removing the cell delivery device from the animal after a predetermined amount of time has elapsed.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate embodiments of the disclosure and together with the general description of the disclosure given above and the detailed description of the drawings given below, serve to explain the principles of the embodiments.
[0032] FIG. 1 is a perspective view of an implant according to one embodiment of the present disclosure, with various features shown in phantom for illustrative purposes.
[0033] FIG. 2 is an illustration of a method of implanting an implant according to various embodiments of the present disclosure.
[0034] FIG. 3 is a side view of a syringe for implanting solid objects according to various embodiments of the present disclosure.
[0035] FIGS. 4A-4C are views of designs for implantation of multiple implants according to embodiments of the present disclosure.
[0036] FIG. 4A is a plan view of an arrangement of multiple implants according to one embodiment of the present disclosure.
[0037] FIG. 4B is a detailed perspective view of an implant for use with the embodiment of FIG. 4A.
[0038] FIG. 4C is a plan view of an arrangement of multiple implants according to one embodiment of the present disclosure.
[0039] FIG. 4D is a detailed perspective view of an implant for use with the embodiment of FIG. 4C.
[0040] FIG. 4E is an exploded perspective view of the arrangement of the embodiment of FIG. 4C.
[0041] FIG. 4F is a plan view of an arrangement of multiple implants according to one embodiment of the present disclosure.
[0042] FIG. 4G is a detailed perspective view of an implant for use with the embodiment of FIG. 4F.
[0043] FIG. 4H is an exploded perspective view of the arrangement of the embodiment of FIG. 4F.
[0044] It should be understood that the drawings are not necessarily to scale. In certain instances, details that are not necessary for an understanding of the disclosure or that render other details difficult to perceive may have been omitted. It should be understood, of course, that the disclosure is not necessarily limited to the particular embodiments illustrated herein.
DETAILED DESCRIPTION
[0045] FIG. 1 is a perspective view of an implant according to one embodiment of the present disclosure, with various features shown in phantom for illustrative purposes. As shown in FIG. 1, the implant 2 comprises a substantially cylindrical shape. The embodiment of FIG. 1 provides a device with an outer surface or shape that comprises a rotationally symmetrical cylinder. It will be recognized, however, that implants 2 of the present disclosure may comprise various shapes, including pill shapes (i.e. cylinders with rounded ends), ovoid shapes, circular shapes, rectilinear shapes, etc. Accordingly, no limitation is provided herewith respect to the outer shape and dimensions of the insert(s). Preferably, the insert 2 comprises outer dimensions including a length L and a width W. In certain embodiments, the length L comprises a distance of between approximately 10.0 millimeters and 15.0 millimeters, and preferably of approximately 12.0 millimeters. In certain embodiments, the width W or diameter of the insert 2 comprises a distance of between approximately 1.0 and 5.0 millimeters, and preferably of approximately 2.0 millimeters. Thus, in preferred embodiments, inserts are provided comprising a length L of approximately 12.0 millimeters and a width W of approximately 2.0 mm. Although various alternative sizes and proportions are contemplated, inserts of preferred embodiments of the disclosure have been determined to provide a suitable interior volume while also being of the appropriate size and dimensions to be accommodated by various insertion and extraction devices.
[0046] The implant 2 of the embodiment of FIG. 1 comprises a hollow core 4. The hollow core 4 is operable to be filled with donor cells that are ultimately to be implanted into a patient. In preferred embodiments, the cells are suspended in partially polymerized high-G alginate and RGD for adhesion. The hollow core 4 is surrounded by a first layer 6, wherein the first layer 6 comprises alginate-polyacrylamide for stiffness, durability, and to promote oxygenation. The first layer 6 is further surrounded by a second layer 8, wherein the second layer 8 comprises a high-G alginate layer for immunoprotection. Additionally, and as shown in the embodiment of FIG. 1, the insert 2 comprises a third layer 10. The third layer 10 comprises a coating of high-G alginate and VEGF-C for vascularization induction and the promotion of a host vascular system receiving and accepting the implant.
[0047] As shown in FIG. 1, an implant 2 is provided comprising a multi-layer construction. The multilayer implant 2 provides greater structural strength to the implant, and provides isolation of at least certain portions of the implant from the immune system. The third layer 10 comprises an alginate shell to reduce the risk of fibrosis, while also promoting vascularization and vascular growth from the host into the implant 2 to facilitate acceptance of donor cells.
[0048] A syringe tip 12 is provided to insert cells into the hollow core 4. Insertion of cells via the syringe 12 occurs at least prior to completion and formation of the third layer 10, and preferably occurs prior to completion of the second and third layers 8, 10.
[0049] FIG. 2 is a perspective view of a method of removal of implants 2 according to various embodiments of the present disclosure. As shown, a plurality of implants 2 is provided within a patient 20. Although five separate implants 2 are provided within the patent 20 in FIG. 2, it will be recognized that removal techniques as shown and described herein may be performed with as few as one implant. The implants 2 are provided subcutaneously in the patient 20, but may be provided as implants in various regions or portions of a patient's anatomy. It is contemplated that implants 2 of the present disclosure may be removed from a patient in approximately one to three minutes. One method of implant removal contemplated by the present disclosure comprises cleansing and/or disinfecting the incision site 14, administering subcutaneous anesthesia, and making an incision that is preferably parallel to the longitudinal axis of an implant 2. The implant is then palpated by a finger 18, and at least a portion of the implant is forced through the incision. A tool 16 (e.g. forceps) is then used to grasp and extract the implant(s) 2. It is contemplated that due to the use and presence of VEGF-C in implants 2 of the present disclosure, extensive vascularization will be present in and around the implantation site. Accordingly, removal methods in accordance with embodiments of the present disclosure contemplate a further step of cutting and/or removing this vasculature before or after implant removal. An anesthetic with epinephrine is preferably provided to promote vasoconstriction and thus reduce bleeding during this method.
[0050] FIG. 3 is a side view of a syringe for implanting solid objects according to various embodiments of the present disclosure. As shown, the syringe 30 comprises a plunger rod 32 within a barrel 34. A synthetic rubber gasket 36 provides a user with the feel of a conventional fluid-injecting hypodermic syringe. The purpose of the gasket 36 is to provide a frictional force that resists the movement of the plunger 32. Since there is no need for a leak-proof seal for a solid-object-implanting syringe, the gasket can 36 be made of a porous material or air channels can be incorporated in the gasket 36 to allow air to pass freely through the gasket, thereby avoiding air pressure build-up in the barrel that might force air through the cannula 38 and the incision in the body during the implantation procedure. An implant 2 in accordance with embodiments of the present disclosure is provided in the cannula 38 and is ready for implantation in the illustration of FIG. 3. Application of force to the plunger rod 32 displaces a push rod 40 which forces the implant 2 out of the syringe 30.
[0051] FIGS. 4A-4C are views of designs for implantation of multiple implants according to embodiments of the present disclosure. In one embodiment, and as shown in FIG. 4A, a plurality of implants 2 are provided on a sheet 50. The sheet 50 comprises twenty-five flat bundles 52 of implants 2 disposed on a flat surface. In the depicted embodiment, the flat surface of the sheet 50 comprises alginate-polyacrylamide providing structural stiffness to hold the implants 2 within the sheet 50. In the depicted embodiment, each bundle 52 comprises six implants. Thus, as depicted in FIGS. 4A-4B, the device comprises 150 of the inner two layers 4, 6 of the implant design as disclosed herein and arranged in flat orientation. These flat bundles of implants 52 are contemplated as being bonded together with alginate-polyacrylamide (for example) for adequate structural stiffness for removing the implant as a whole, while allowing enough flexibility to rest under the skin.
[0052] In further embodiments, and as shown and described herein, multiple layers of flat bundles of implants can be provided. The device may comprise a single layer, two layers, three layers, or more. FIG. 4A depicts the flat bundles of implants 52 oriented in a single layer 50.
[0053] FIG. 4C depicts a plurality of implants provided in a two-layer arrangement, wherein a first sheet 54 and a second sheet 56 are provided. Each of the sheets 54, 56 comprises a plurality of bundles 52 of implants 2, an example of which is shown in the detailed perspective view of FIG. 4D. The first sheet 54 comprises a plurality of spaced-apart gaps or voids 58a, 58b. The second sheet 56 comprises a single void 60 that is operable to and intended to at least partially align with the voids 58a, 58b of the first sheet when the first sheet 54 and the second sheet 56 are stacked or aligned. The voids 58a, 58b, 60 comprise apertures that are devoid of material and allow for transmission of materials including, for example, vasculature and tissue that is to grow in and around the device subsequent to implantation.
[0054] FIG. 4E is a perspective view of the first and second sheets 54, 56, which are intended to be stacked or layered. As shown, the voids 58a, 58b, 60 are positioned such that they at least partially align upon layering the sheets. The larger aperture 60 of the second sheet 56 provides for at least one bundle 62 to be exposed on both sides of the bundle, and the voids generally serve to allow for in-growth of tissue and vasculature subsequent to implantation of the sheet(s). In various embodiments, stacked or layered sheets comprise an alginate-based gel outer coating including vascular endothelial growth factor C (VEGF-C). This outer coating may be used to limit fibrosis and stimulate vascularization.
[0055] FIG. 4F is a top plan view of a plurality of implants provided on sheets. Specifically, a first 64, second 66 and third sheet 68 are provided. Each of the sheets 64, 66, 68 are provided with a plurality of bundles of implants 52, and the sheets are operable to be stacked or layered. At least some of the sheets comprise apertures or void spaces. Specifically, and as shown in the embodiment of FIG. 4F, the second and third sheets 66, 68 comprise first and second apertures 70, 72. The apertures generally comprise areas that are devoid of material and allow for transmission of fluids and tissue. FIG. 4G is a detailed view of an implant 2 that is provided within a bundle 52. The bundles of the depicted embodiment comprise six implants, which comprise implant structure(s) as shown and described herein.
[0056] FIG. 4H is an exploded perspective view of the first, second and third sheets 64, 66, 68 of FIG. 4F. The sheets comprise the same or similar length and width dimensions and are operable to be layered or stacked. The apertures 70, 72 provided in the second and third sheets 66, 68 provide that at least some of the implants of the first sheet 64 are exposed on both sides, even when the sheets are stacked in a three-layer orientation. Although FIG. 4H provides the first, second and third layers in a specific orientation, alternative embodiments are contemplated. For example, the second layer 66 and the first layer 64 may be transposed, such that layers with apertures are provided on the top and bottom and a middle layer is devoid of an aperture. Similar to the embodiment shown in FIG. 4E, this embodiment of stacked or layered first, second and third sheets 64, 66, 68 comprises an alginate-based gel outer coating including vascular endothelial growth factor C (VEGF-C). This outer coating may be used to limit fibrosis and stimulate vascularization.
[0057] In the instance of multiple layers of implant bundles, a gap or void is provided to allow for ingrowth of vasculature. Further, the inner gap can be surrounded as a group by the third layer which is the soft alginate shell containing VEGF-C. Such embodiments provide for a retrievable implant made possible, for example, through a 2 cm incision. In these embodiments of layered implant bundles, the implant bundles in layers are implanted under the animal's skin and subsequently unrolled so that the top layer of implant bundles rests flat under the skin. Removal of the implants can be done through an outpatient procedure.
[0058] In various embodiments, sheets or layers or implants are provided for insertion. No limitation with respect to the number of implants to be inserted within a patient is provided herein. However, in some embodiments, methods and devices are contemplated wherein between approximately 40 and approximately 200 implants as shown and described herein are provided for implantation within a patient.
[0059] While various embodiments of the present disclosure have been described in detail, it is apparent that modifications and alterations of those embodiments will occur to those skilled in the art. It is to be expressly understood that such modifications and alterations are within the scope and spirit of the present disclosure. Further, it is to be understood that the phraseology and terminology used herein is for the purposes of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein are meant to encompass the items listed thereafter and equivalents thereof, as well as, additional items.
