Cell selective implant surface with controlled release of bioactive agents

• US 20070190107A1
• Filed: 01/11/2007
• Published: 08/16/2007
• Est. Priority Date: 01/11/2006
• Status: Abandoned Application

• Current Assignee: Eidgenossiche Technische Hochschule Zurich, ETH Zurich
• Original Assignee: Straumann Holding AG
• Inventors: Tosatti, Samuele, De Wild, Michael, Schuler, Martin, Trentin, Diana
• Application Number:
  US11/652,168
• Publication Number:
  US 20070190107A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/426 Immunomodulating agents, i.e. cytokines, interleukins, interferons
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites

Abstract

The present invention relates to an implant (1) with at least partially a roughened surface (2), which is at least partially covered by an organic or polymeric intermediate layer (3) and attached thereto a top layer (4). The top layer (4) provides for a controlled release of at least one bioactive agent. A kit for preparing such an implant is also described.

Claims

1. A metal implant having at least partially a roughened surface, which is at least partially covered by an organic or polymeric intermediate layer and attached thereto a top layer with at least one bioactive agent and said top layer providing for a controlled release of the bioactive agent(s).

2. The implant according to claim 1 wherein the surface is at least partially hydroxylated.

3. The implant of claim 1, wherein the metal implant comprises titanium, zirconium, niobium, tantalum, hafnium or compositions thereof.

4. The implant of claim 1, wherein the roughened surface comprises a macro-roughness with a pit size greater than 10 μ

m.

5. The implant of claim 1, wherein the roughened surface comprises a micro-roughness with a pit size of 4 μ

m or less.

6. The implant of claim 1, wherein the implant is completely covered by an organic or polymeric intermediate layer.

7. The implant of claim 1, wherein the intermediate layer is a graft copolymer.

8. The implant of claim 6, wherein the intermediate layer is DOPA-PEG.

9. The implant of claim 7, wherein the graft copolymer is poly(L-lysine)-graft-poly(ethylene glycol).

10. The implant of claim 1, wherein the top layer is non-covalently bound to the intermediate layer.

11. The implant of claim 1, wherein the top layer is covalently bound to the intermediate layer.

12. The implant of claim 1, wherein the top layer is attached to the intermediate layer by a linker selected from the group consisting of nucleic acids, PNA, peptides, proteins, glycosylated proteins and carbohydrates.

13. The implant of claim 12, wherein the linker is selected from the group consisting of the peptides RGD, KRSR, (KRSR)₃ and FHRIKKA, SY(SO₃)DY(SO₃), heparin and chopped heparin.

14. The implant of claim 12, wherein the linker is selected from the group consisting of nucleic acids and PNA.

15. The implant of claim 1, wherein the top layer comprises at least one carrier which is selected from the group consisting of lipid vesicles, polyelectrolyte stabilized vesicles, micro-spheres and nano-particles.

16. The implant of claim 15, wherein the carrier comprises poly(lactic acid) or a poly(lactic-co-glycolide acid) micro-spheres.

17. The implant of claim 1, wherein the bioactive agent is selected from the group consisting of systemic hormones, cytokines, growth factors, enamel matrix derivatives (EMD) and anti-inflammatory drugs.

18. The implant of claim 17, wherein the bioactive agent is selected from the group consisting of parathyroid hormones, VEGF and the bone morphogenetic proteins.

19. The implant of claim 18, wherein the bioactive agent is selected from the bone morphogenetic proteins.

20. The implant of claim 18, wherein the bioactive agent is selected from the parathyroid hormones.

21. The implant of claim 17, wherein the bioactive agent is selected from the enamel matrix derivatives (EMD).

22. A kit for preparing the implant of claim 1 comprising (i) an individually stored implant having at least partially a roughened surface, (ii) at least one individually stored component for forming an intermediate layer and (iii) at least one individually stored component comprising a carriers with at least one bioactive agent.

23. A kit of claim 22 wherein the individually stored implant (i) has at least partially a hydroxylated surface.

24. The kit of claim 22, wherein the components (ii) and (iii) are individually stored in containers.

25. The use of an implant of claim 1 comprising a dental implant.

27. The implant of claim 25, wherein the implant has at least partially a hydroxylated surface.

28. The implant of claim 4, wherein the macro-roughness pit size is greater than 20 μ

m.

29. The implant of claim 5, wherein the micro-roughness pit size is 2 μ

m or less.

26. A method of preparing an implant wherein a component (ii), comprising at least one individually stored component for forming an intermediate layer, and a component (iii), comprising at least one individually stored component comprising a carriers with at least one bioactive agent, are applied to coat an implant having at least partially a roughened surface.