Mineralization and biological modification of biomaterial surfaces

• US 9,072,813 B2
• Filed: 04/30/2009
• Issued: 07/07/2015
• Est. Priority Date: 03/19/1999
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Murphy, William L., Peters, Martin C., Mooney, David J., Kohn, David H.
• Primary Examiner(s): EPPS -SMITH, JANET L
• Application Number:
  US12/433,518
• Publication Number:
  US 20090226602A1
• Time in Patent Office: 2,259 Days
• Field of Search: 427/2.26, 514/44.R, 424/93.2, 424/93.21, 424/484, 424/486, 521/51
• US Class Current: 1/1
• 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 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/00 Materials for grafts or prostheses or for coating grafts or prostheses dental prostheses A61C13/00; shape or structure of prostheses A61F2/00; use of preparations for artificial teeth A61K6/80; artificial kidneys A61M1/14
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/306 Other specific inorganic materials not covered by A61L27/303 - A61L27/32
• CPC Class Codes: A61L 27/44 having a macromolecular matrix
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Disclosed are advantageous methods for patterning and/or mineralizing biomaterial surfaces. The techniques described are particularly useful for generating three-dimensional or contoured bioimplant materials with patterned surfaces or patterned, mineralized surfaces. Also provided are various methods of using the mineralized and/or patterned biomaterials in tissue engineering, such as bone tissue engineering, providing more control over ongoing biological processes, such as mineralization, growth factor release, cellular attachment and tissue growth.

Claims

1. A method for controlling mineralization of a biomaterial surface, comprising

functionalizing at least a first surface of a biomaterial by at least one of:

chemical hydrolysis, electrolysis, or electromagnetic radiation; and

contacting the functionalized biomaterial surface with an amount of a mineral-containing solution effective to form a mineralized biomaterial that comprises an extended, mineral coating at the functionalized biomaterial surface;

said biomaterial comprising at least a first porous, biodegradable polymer portion that has an interconnected pore structure and that is degradable over a controllable time scale,

wherein the polymer portion of the biomaterial is a poly(alpha-hydroxy acid),

wherein the poly(alpha-hydroxy acid) is a polylactic acid polymer, a polyglycolic acid polymer or a polylactic-co-glycolic acid copolymer, and

wherein the functionalization provides for specific control over the mineral coating on the biomaterial surface.

2. The method of claim 1 wherein the functionalizing step creates a plurality of polar oxygen groups on the biomaterial surface.

3. The method of claim 1 wherein said mineral coating is osteoconductive.

4. The method of claim 1 wherein the biomaterial is associated with a biologically effective amount of at least a first bioactive substance or biological cell.

5. The method of claim 1, wherein the first surface is homogeneously functionalized.

6. The method of claim 1, wherein the first surface is functionalized in a pattern.

7. The method of claim 6, wherein the first surface is functionalized using pre-patterned electromagnetic irradiation.

8. The method of claim 7, wherein the pre-patterned electromagnetic irradiation is constructively and destructively interfering irradiation.

9. The method of claim 8, wherein the constructively and destructively interfering irradiation is formed using diffraction lithography.

10. The method of claim 1, wherein the first surface is functionalized by electron beam irradiation.

11. The method of claim 1, wherein the first surface is functionalized by UV irradiation.

12. The method of claim 1, wherein the first surface is functionalized by NaOH treatment.

13. The method of claim 1, wherein the biomaterial is a flat, two-dimensional biomaterial.

14. The method of claim 1, wherein the biomaterial is a three-dimensional biomaterial.

15. The method of claim 1, wherein the mineral-containing solution is a synthetic medium comprising calcium and phosphate that mimics a body fluid.

16. The method of claim 1, wherein the mineral coating comprises hydroxyapatite.

17. The method of claim 4, wherein the biomaterial is associated with a biologically effective amount of growth hormone, parathyroid hormone, a bone morphogenic protein, a transforming growth factor, a fibroblast growth factor, a granulocyte/macrophage colony stimulating factor, an epidermal growth factor, a platelet derived growth factor, an insulin-like growth factor, a scatter factor/hepatocyte growth factor, fibrin, collagen, fibronectin, vitronectin, hyaluronic acid, an RGD-containing peptide or polypeptide, an angiopoietin, or a vascular endothelial cell growth factor (VEGF).

18. The method of claim 17, wherein the biomaterial is associated with a biologically effective amount of VEGF.

19. The method of claim 4, wherein the biomaterial is associated with a biologically effective amount of a bone progenitor cell, a fibroblast or an endothelial cell.