Artificial tissue systems and uses thereof

• US 8,916,184 B2
• Filed: 11/05/2004
• Issued: 12/23/2014
• Est. Priority Date: 11/07/2003
• Status: Active Grant

• Current Assignee: University of Connecticut (State of Connecticut)
• Original Assignee: University of Connecticut (State of Connecticut)
• Inventors: Klueh, Ulrike W., Dorsky, David I., Kreutzer, Donald L.
• Primary Examiner(s): Schultz, Doug
• Application Number:
  US10/578,171
• Publication Number:
  US 20070077265A1
• Time in Patent Office: 3,700 Days
• US Class Current: 424/423
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: C12N 5/0062 General methods for three-dimensional culture

Abstract

An implant system and a method for controlling the natural and artificial microenvironments surrounding an implanted device using an artificial tissue system (ATS) and includes methods of diagnostic and testing related thereto. The ATS, among other things, induce better integration, function, and extended lifespan of the devices at the site of implantation. The ATS includes cells, such as naturally occurring, engineered, and/or artificial cells; matrices such as natural, engineered, artificial and/or hybrid matrices; tissue response modifiers (TRM); and/or cell response modifiers (CRM). The specific composition of the ATS is based on the nature of the tissue in which ATS-device combination is implanted and the nature of the implant device, as well as the required function and lifespan of the implanted device. Additionally, the ATS, as well as ATSdevice combinations can be utilized in vitro to aid in the design of improved ATS, devices and ATS-device combinations for in \>ivo uses.

Claims

1. An implant system, comprising:

(a) a sensor having an outer surface including an analyte permeable coating,

(b) a biological matrix comprising a cell culture derived basement membrane exterior to the sensor and in contact with the analyte permeable coating on the outer surface of the sensor and with biological tissue, and

(c) a plurality of cells supported by the biological matrix, the plurality of cells comprising cells expressing vascular endothelial growth factor and extending sensor functionality by promoting a biological interaction between the sensor and the biological tissue.

2. The implant system of claim 1, wherein said cells expressing vascular endothelial growth factor include at least one member selected from the group consisting of biological cells, engineered cells, support cells, stem cells, artificial cells and hybrid cells.

3. The implant system of claim 1, wherein said biological tissue comprises mammalian tissue.

4. The implant system of claim 1, wherein said sensor is an amperometric glucose sensor.

5. The implant system of claim 1, wherein said sensor is a glucose sensor.

6. The implant system of claim 1, wherein said biological matrix at least partially embeds said sensor.

7. The implant system of claim 1, wherein the plurality of cells comprise cells that are configured to suppress deleterious reactions between said sensor and said biological tissue and/or said biological matrix.

12. The implant system of claim 1, wherein the system is configured to test the effectiveness of the sensor.

14. The implant system of claim 1, wherein said plurality of cells comprise cells that induce the growth of new tissue exterior to the sensor.

15. The implant system of claim 14, wherein said new tissue comprises vascular structures.

21. The implant system of claim 14, wherein the new tissue comprises capillaries.

22. The implant system of claim 1, wherein the cells comprise at least one member selected from the group consisting of cells that inhibit inflammation and cells that inhibit fibrosis.

8. An implant system comprising:

(a) an implantable sensor having an outer surface including an analyte permeable coating,

(b) a biological matrix comprising cell culture derived basement membrane, the biological matrix being positioned exterior to the sensor and in contact with the analyte permeable coating on the outer surface of the sensor, and

(c) a plurality of cells supported by said biological matrix, the plurality of cells comprising cells expressing vascular endothelial growth factor and being configured to extend sensor functionality when the sensor and matrix are implanted in biological tissue by promoting neovascularization of the biological tissue.

13. The implant system of claim 8, wherein the sensor comprises a glucose sensor.

16. The implant system of claim 8, wherein said implant system further comprises at least one genetic element supported by said matrix.

17. The implant system of claim 8, wherein said system further comprises at least one response modifier supported by said matrix.

23. The implant system of claim 8, wherein the cells comprise at least one member selected from the group consisting of cells that inhibit inflammation and cells that inhibit fibrosis.

9. An implant system in biological contact with biological tissue comprising:

(a) a cellular component, said cellular component includes at least one cellular community comprising cells expressing vascular endothelial growth factor;

(b) a biological matrix material comprising a cell culture derived basement membrane in contact with the biological tissue, said biological matrix material being associated with a portion of the cellular community; and

(c) a sensor having an outer surface including an analyte permeable coating in contact with the biological matrix material, at least one of the biological matrix material and the cellular community extending sensor functionality by promoting neovascularization of the biological tissue,

wherein the biological matrix is exterior to the sensor.

10. The implant system in biological contact with the biological tissue of claim 9, wherein the biological tissue is mammalian tissue.

11. The implant system of claim 9, wherein the cellular component comprises a cellular community that inhibits at least one of inflammation and fibrosis.

18. The implant system in biological contact with the biological tissue of claim 9 wherein the cellular component includes at least one member selected from the group consisting of normal vascular stem cells;

a combination of normal vascular stem cells and engineered support cells; and

a combination of normal vascular stem cells and engineered stem cells.

19. The implant system in biological contact with the biological tissue of claim 18, wherein the basement membrane has at least one of cytokines and growth factors bound thereto.

20. The implant system in biological contact with the biological tissue of claim 9, wherein at least a portion of the cellular community is bound to the biological matrix.