Biointerface membranes incorporating bioactive agents

• US 7,875,293 B2
• Filed: 05/10/2004
• Issued: 01/25/2011
• Est. Priority Date: 05/21/2003
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Brauker, James H., Tapsak, Mark, Carr-Brendel, Victoria, Markovic, Dubravka, Shults, Mark
• Primary Examiner(s): Tate; Christopher R
• Assistant Examiner(s): Kosar; Aaron J
• Application Number:
  US10/842,716
• Publication Number:
  US 20050031689A1
• Time in Patent Office: 2,451 Days
• Field of Search: None
• US Class Current: 424/473
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 2400/08 Methods for forming porous structures using a negative form which is filled and then removed by pyrolysis or dissolution
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: G01N 33/48707 by electrical means G01N33/49, G01N33/493 take precedence

Abstract

A biointerface membrane for an implantable device including a nonresorbable solid portion with a plurality of interconnected cavities therein adapted to support tissue ingrowth in vivo, and a bioactive agent incorporated into the biointerface membrane and adapted to modify the tissue response is provided. The bioactive agents can be chosen to induce vascularization and/or prevent barrier cell layer formation in vivo, and are advantageous when used with implantable devices wherein solutes are transported across the device-tissue interface.

Claims

1. An implantable glucose sensor having a biointerface membrane comprising:

a first domain comprising a nonresorbable solid portion comprising a plurality of interconnected cavities having a pore size greater than about 30 μ

m, as determined by a bubble point test measurement, wherein the solid portion is adapted to support a tissue ingrowth in vivo;

a second domain located adjacent to the first domain, wherein the second domain is impermeable to cells or cell processes and is configured to allow a passage of glucose therethrough; and

a bioactive agent incorporated into the biointerface membrane, wherein the bioactive agent is capable of modifying a tissue response in such a way that sleep period effects on the implantable glucose sensor are reduced, wherein the bioactive agent is configured to be released from the first domain and/or the second domain.

2. The implantable glucose sensor according to claim 1, wherein the interconnected cavities and the solid portion are configured to redirect a fibrous tissue contracture in vivo, thereby interfering with formation of a barrier cell layer within or around the membrane.

3. The implantable glucose sensor according to claim 2, wherein the membrane comprises a micro-architecture situated within at least some of the cavities of a macro-architecture, wherein the macro-architecture comprises a frame comprising a plurality of elongated strands of a material, wherein the strands are less than about 6 μ

m in all but the longest dimension.

4. The implantable glucose sensor according to claim 1, wherein the solid portion is selected from the group consisting of silicone, polytetrafluoroethylene, expanded polytetrafluoroethylene, polyethylene-co-tetrafluoroethylene, polyolefin, polyester, polycarbonate, biostable polytetrafluoroethylene, homopolymers, copolymers, terpolymers of polyurethanes, polypropylene, polyvinyl alcohol, polyvinylchloride, polyvinylidene fluoride, polybutylene terephthalate, polymethylmethacrylate, polyether ether ketone, polyurethanes, cellulosic polymers, polysulfones, block copolymers thereof, and combinations or mixtures thereof.

5. The implantable glucose sensor according to claim 1, wherein the solid portion comprises silicone.

6. The implantable glucose sensor according to claim 1, wherein the bioactive agent is selected from the group consisting of inflammatory agents, growth factors, angiogenic factors, cytotoxic agents, and combinations or mixtures thereof.

7. The implantable glucose sensor according to claim 1, wherein the bioactive agent comprises a vascularization agent.

8. The implantable glucose sensor according to claim 7, wherein the vascularization agent comprises an angiogenic agent configured for stimulating a neovascularization.

9. The implantable glucose sensor according to claim 7, wherein the vascularization agent comprises sphingosine-1-phosphate.

10. The implantable glucose sensor according to claim 7, wherein the vascularization agent comprises monobutyrin.

11. The implantable glucose sensor according to claim 7, wherein the vascularization agent comprises an anti-sense molecule.

12. The implantable glucose sensor according to claim 7, wherein the vascularization agent comprises a pro-inflammatory agent configured for promoting an inflammation response or an immune response.

13. The implantable glucose sensor according to claim 12, wherein the pro-inflammatory agent comprises a xenogenic carrier.

14. The implantable glucose sensor according to claim 12, wherein the pro-inflammatory agent comprises a lipopolysaccharide (LPS).

15. The implantable glucose sensor according to claim 12, wherein the pro-inflammatory agent comprises a protein.

16. The implantable glucose sensor according to claim 7, wherein the vascularization agent is selected from the group consisting of basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), vascular endothelial growth factor (VEGF), platelet derived endothelial cell growth factor BB (PDECGF-BB), transforming growth factor beta (TGF-β

), tumor necrosis factor alpha (TNF-α

), and combinations or mixtures thereof.

17. The implantable glucose sensor according to claim 1, wherein the bioactive agent is incorporated into the biointerface membrane via a carrier matrix.

18. The implantable glucose sensor according to claim 17, wherein the carrier matrix is selected from the group consisting of collagen, a particulate matrix, a non-resorbable matrix, resorbable matrix, a controlled-release matrix, a gel, and combinations or mixtures thereof.

19. The implantable glucose sensor according to claim 1, wherein the bioactive agent is cross-linked with a material that forms the biointerface membrane.

20. The implantable glucose sensor according to claim 1, wherein the bioactive agent is sorbed into the biointerface membrane by a process selected from the group consisting of absorption, adsorption, imbibing, and combinations thereof.

21. The implantable glucose sensor according to claim 1, wherein the bioactive agent is configured to be released for a time period of from about one day to about one year.

22. The implantable glucose sensor according to claim 1, wherein the bioactive agent is configured to be released for a time period of from about one week to about four weeks.

23. The implantable glucose sensor according to claim 1, wherein the substantial number of each of the interconnected cavities are from about 30 μ

m to about 1000 μ

m in at least one dimension.

24. The implantable glucose sensor according to claim 1, wherein the bioactive agent is capable of modify the tissue response in such a way that maturation of a vascularized tissue bed is accelerated.

25. An implantable glucose sensor having a biointerface membrane comprising:

a first domain comprising a nonresorbable solid portion comprising a plurality of interconnected cavities having a pore size greater than about 30 μ

m, as determined by a bubble point test measurement, wherein the solid portion is adapted to support a tissue ingrowth in vivo;

a second domain located adjacent to the first domain, wherein the second domain is impermeable to cells or cell processes and is configured to allow a passage of glucose therethrough; and

a pro-inflammatory agent incorporated into the biointerface membrane, wherein the pro-inflammatory agent is capable of modifying a tissue response in such a way that sleep period effects on the implantable glucose sensor are reduced, wherein the pro-inflammatory agent is configured to be released from the first domain and/or the second domain.