US-12618031-B2 - Delivery devices

Abstract

The present disclosure is directed to devices used for transplanting or recruiting cells, in addition to methods for making said devices and for using said devices in the treatment of medical disorders.

Inventors

• Ying Xuan Chua
• Alessandro Grattoni
• Jesus Paez Mayorga
• Simone Capuani

Assignees

• THE METHODIST HOSPITAL SYSTEM

Dates

Publication Date

20260505

Application Date

20210624

Claims (20)

1. 1 . A device comprising: a housing comprising a perimeter wall defining a cavity; and a support structure separating the cavity into a cell chamber and a reservoir chamber, the support structure comprises a nanoporous membrane for fluid communication between the cell chamber and the reservoir chamber; wherein the cell chamber has an outside surface that comprises at least one mesh layer; and wherein the outside surface of the cell chamber comprises at least 50% of the total outside surface of the device.
2. 2 . The device of claim 1 , wherein each mesh layer comprises a plurality of openings with an average opening size that facilitates the growth of vascular tissue into the cell chamber.
3. 3 . The device of claim 1 , wherein the outside surface of the cell chamber comprises a top surface and a bottom surface, and wherein each of the top surface and the bottom surface comprises one or more mesh layers.
4. 4 . The device of claim 3 , wherein each of the one or more mesh layers has a plurality of openings.
5. 5 . The device of claim 4 , wherein the plurality of openings for the first mesh layer has an average opening size of about 100 microns.
6. 6 . The device of claim 1 , wherein the cell chamber comprises a cell population.
7. 7 . The device of claim 6 , where the cell population comprises pancreatic islet cells, Leydig cells, follicular cells, stem cells, dendritic cells, stem cell-derived b-cells, genetically engineered cells, or combinations thereof.
8. 8 . The device of claim 1 , wherein the reservoir chamber contains one or more bioactive agents.
9. 9 . The device of claim 8 , wherein the one or more bioactive agents comprise one or more growth factors.
10. 10 . The device of claim 8 , wherein the one or more bioactive agents comprise one or more cytokines.
11. 11 . The device of claim 8 , wherein the one or more bioactive agents comprise one or more immunomodulators.
12. 12 . The device of claim 1 , wherein the reservoir chamber comprises one or more immune adjuvants.
13. 13 . A method of treating diabetes in a subject, comprising: a. implanting a device according to claim 1 in the subject, b. incubating the device until the device is infiltrated with vascular tissues; and c. injecting insulin producing cells into the cell chamber of the devices.
14. 14 . The method of claim 13 , further comprising injecting an immunosuppressant into the reservoir chamber of the device.
15. 15 . A method of treating cancer in a tumor in a subject, comprising: a. implanting a device according to claim 1 in the subject; and b. injecting a cell lysate from a population of cells from the cancer into the cell chamber of the device.
16. 16 . The method of claim 15 , further comprising injecting an immune adjuvant into the reservoir chamber of the device.
17. 17 . The device of claim 1 , wherein the nanoporous membrane has a porosity ranging from about 2.5 nm to about 1000 nm.
18. 18 . A device comprising: a housing comprising a perimeter wall defining a cavity; and a support structure separating the cavity into a cell chamber and a reservoir chamber; wherein the cell chamber comprises a cell population and vascularized tissue; wherein the reservoir chamber comprises one or more trophic factors; wherein the support structure comprises a membrane configured to homogenously deliver the one or more trophic factors to the cell population in the cell chamber; wherein the cell chamber has an outside surface that comprises at least one mesh layer; and wherein the outside surface of the cell chamber comprises at least 50% of the total outside surface of the device.
19. 19 . A device comprising: a housing comprising a perimeter wall defining a cavity; and a support structure separating the cavity into a cell chamber and a reservoir chamber; wherein the cell chamber comprises a cell population, one or more antigens, and vascularized tissue; wherein the reservoir chamber comprises one or more immune adjuvants; wherein the support structure comprises a membrane configured to homogenously deliver the one or more immune adjuvants to the cell population; wherein the cell chamber has an outside surface that comprises at least one mesh layer; and wherein the outside surface of the cell chamber comprises at least 50% of the total outside surface of the device.
20. 20 . The device of claim 19 , wherein the cell population comprises an immune cell population.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 63/043,439 filed Jun. 24, 2020, the disclosure of which is incorporated herein by reference in its entirety. BACKGROUND Cell therapy is a promising strategy for treatment of chronic diseases in which living, functional cells produce therapeutic factors in lieu of exogenous drug administration. To promote successful engraftment, survival, and functionality, cells require an optimal and protected environment that provides oxygen, nutrients, and cell-specific trophic factors such as growth factors, cytokines, hormones, and/or immune modulators. Importantly, long term cell survival may require that the trophic factors vary and remain confined throughout the lifespan of the graft. A promising approach to consolidate all these components into one environment is through cell encapsulation. However, cell encapsulation still faces the challenge of providing sufficient support for oxygen and nutrient transfer while maintaining versatile long-term administration of trophic factors. Therapeutic vaccines have shown promise in the clinic for a variety of indications including cancer and autoimmune disease management. However, poor localization due to bolus injection leads to low and transient vaccine levels, which reduces the duration of antigen presentation and thus limits efficacy. As such, repeated administration is required to maintain a robust immune response over time. Numerous technologies are under development to WDVAX developed by Mooney and colleagues and licensed by Novartis for commercial use, are currently under clinical investigation to deliver vaccine components in melanoma patients. However, once implanted, vaccine components in these biomaterial-based scaffolds cannot be retrieved, modified or tuned according to a patient's response. The present disclosure, including materials, devices and methods disclosed herein, address this and other needs. SUMMARY In accordance with the purposes of the disclosed devices, systems and methods as embodied and broadly described herein, the disclosed subject matter related to devices and systems, methods of making said devices and systems, and methods of using said devices and systems. More specifically, a device is provided comprising: a housing comprising a perimeter wall defining a cavity; and a support structure separating the cavity into a cell chamber and a reservoir chamber, the support structure comprises a porous membrane for fluid communication between the cell chamber and the reservoir chamber; wherein the cell chamber has an outside surface that comprises at least one mesh layer; and wherein the outside surface of the cell chamber comprises at least 50% of the total outside surface of the device. In some embodiments, each mesh layer comprises a plurality of openings. In some embodiments, the plurality of openings has an average opening size that facilitates the growth of vascular tissue into the cell chamber. In some embodiments, the plurality of openings has an average opening size that prevents infiltration of immune cells into the cell chamber. In some embodiments, the plurality of openings has an average opening size that allows infiltration of immune cells into the cell chamber. In some embodiments, the plurality of openings has an average opening size ranging from about 50 microns to about 500 microns. In some embodiments, the outside surface of the of the cell chamber comprises one mesh layer. In some embodiments, the outside surface of the cell chamber comprises a first mesh layer and a second mesh layer. In some embodiments, each of the first mesh layer and the second mesh layer has a plurality of openings. In some embodiments the plurality of openings for the first mesh layer has an average opening size of about 100 microns. In some embodiments, the plurality of openings for the second mesh layer has an average opening size of about 300 microns. In some embodiments, the at least one mesh layer is derived from a polymeric material, for example nylon. In some embodiments, the porous membrane comprises a nanoporous membrane. In some embodiments, the nanoporous membrane has a porosity ranging from about 2 nm to about 1000 nm. In some embodiments, the porous membrane comprises a nano-channel membrane having nano-channels with an average diameter ranging from about 2 nm to about 1000 nm. In some embodiments, the housing is derived from a polymeric material, for example nylon. In some embodiments, the cell chamber comprises a cell population, for example pancreatic islet cells, Leydig cells, follicular cells, stem cells, dendritic cells, stem cell-derived β-cells, genetically engineered cells, or combinations thereof. In some embodiments, the cell chamber comprises a cell lysate, for example a tumor cell lysate. In some embodiments, the cell chamber comprises one or more antigens. In some embodiments, the reservoir chamber comp