Crosslinkable macromers

• US 7,547,445 B2
• Filed: 06/27/2006
• Issued: 06/16/2009
• Est. Priority Date: 03/19/1998
• Status: Expired due to Term

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Chudzik, Stephen J., Chinn, Joseph A.
• Primary Examiner(s): Russel; Jeffrey E
• Application Number:
  US11/475,438
• Publication Number:
  US 20060240072A1
• Time in Patent Office: 1,085 Days
• Field of Search: None
• US Class Current: 424/422
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: Y10S 623/92 Method or apparatus for preparing or treating prosthetic
• CPC Class Codes: Y10S 623/926 Synthetic

Abstract

A crosslinkable macromer system and related methods of preparing the system and using the system in the form of a crosslinked matrix between a tissue site and an implant article such as a tissue implant or on the porous surface of a prosthetic device. The macromer system includes two or more polymer-pendent polymerizable groups and one or more multifunctional initiator groups. The polymerizable groups and the initiator group(s), when polymer-pendent, can be pendent on the same or different polymeric backbones. The macromer system provides advantages over the use of polymerizable macromers and separate, low molecular weight initiators, including advantages with respect to such properties as nontoxicity, efficiency, and solubility. A macromer system of the invention can be used as an interface between the tissue site and implant article in a manner sufficient to permit tissue growth through the crosslinked matrix and between the tissue site and implant. In a preferred embodiment, polymers with pendent polymerizable groups, for use in the macromer system, are prepared by reacting a polysaccharide polymer with a reactive moiety in an organic, polar solvent such as formamide.

Claims

1. A method of reducing immediate and chronic adverse reactions to an implanted medical device, comprising:

providing a medical device,

providing a matrix-forming system comprising a multifunctional polymerization initiator and a crosslinikable macromer comprising one or more polymer backbones having pendent polymerizable groups,

implanting the medical device within a tissue site with the matrix-forming system positioned between the medical device and the tissue, and

polymerizing the matrix-forming system to form a crosslinked matrix between the medical device and the tissue,

wherein the multifunctional polymerization initiator is a non-polymer bound initiator and comprises a non-polymeric core with pendent chemical molecules that are capable of initiating a free radical reaction and pendent chemical molecules capable of reducing immediate and chronic adverse reactions to the medical device.

2. The method of claim 1, wherein the backbone comprises polyethylene glycol.

3. The method of claim 1, wherein the polymerizable groups comprise acrylates.

4. The method of claim 1, wherein the chemical molecules that are capable of initiating a free radical reaction are selected from the group consisting of tetrakis (4-benzoylbenzyl ether) of pentaerythritol, 4,5-bis(4-benzoylphenylmethyleneoxy) benzene-1,3-disulfonic acid dipotassium salt (DBDS), and ethylenebis(4-benzoylbenzyldimethylammonium) dibromide (Diphoto-Diquat).

5. The method of claim 1, wherein the chemical molecules that are capable of reducing immediate and chronic adverse reactions to an implanted medical device are selected from the group consisting of fatty acids and salts of organic acids.

6. The method of claim 1, wherein the adverse reactions comprise the adsorbance of undesirable proteins.

13. The method of claim 1, wherein the multifunctional polymerization initiator comprises a photoreactive group and two or more bioactive groups.

14. The method of claim 13, wherein the photoreactive group is selected from the group consisting of acetophenone, benzophenone, anthraquinone, quinone, anthrone, anthrone-like heterocycles and combinations thereof.

15. The method of claim 13, wherein the bioactive groups are selected from the group consisting of cell attachment factors, growth factors, antithrombotic factors, binding receptors, ligands, enzymes, antibiotics, nucleic acids, lysine, and fatty acids.

7. A coated medical device comprising:

a medical device, and

a matrix-forming system positioned upon the medical device including a multifunctional polymerization initiator and a polymer backbone having pendent polymerizable groups wherein the multifunctional polymerization initiator is a non-polymer bound initiator and comprises a non-polymeric core with pendent chemical molecules that are capable of initiating a free radical reaction and pendent chemical molecules capable of reducing immediate and chronic adverse reactions to the medical device.

8. A method of reducing immediate and chronic adverse reactions to an implanted medical device, comprising:

providing an implantable medical device with a surface having sufficient porosity to permit tissue growth in vivo,

providing a matrix-forming system comprising a multifunctional polymerization initiator and a crosslinikable macromer comprising one or more polymer backbones having pendent polymerizable groups,

implanting the medical device within a tissue site with the matrix-forming system positioned between the medical device and the tissue, and

polymerizing the matrix-forming system to form a crosslinked matrix between the medical device and the tissue,

wherein the multifunctional polymerization initiator is a polymer bound initiator that comprises a polymeric core with pendent chemical molecules that are capable of initiating a free radical reaction and pendent bioactive groups and wherein the crosslinked matrix promotes tissue growth between the tissue site and the medical device.

10. The method of claim 8, wherein the adverse reactions comprise absorbance of undesirable proteins.

11. The method of claim 8, wherein the backbone comprises polyethylene glycol.

12. The method of claim 8, wherein the polymerizable groups comprise acrylates.

9. A coated medical device comprising:

an implantable medical device with a surface having sufficient porosity to permit tissue growth in vivo, and

a matrix-forming system positioned upon the medical device and configured to promote tissue growth between a host tissue site and the medical device, wherein the matrix-forming system includes a multifunctional polymerization initiator and a polymer backbone having pendent polymerizable groups wherein the multifunctional polymerization initiator is a polymer bound initiator that comprises a polymeric core with pendent chemical molecules that are capable of initiating a free radical reaction and pendent chemical molecules capable of reducing immediate and chronic adverse reactions to the medical device.