Preparation of medical devices by solid free-form fabrication methods

• US 5,869,170 A
• Filed: 06/05/1995
• Issued: 02/09/1999
• Est. Priority Date: 10/18/1993
• Status: Expired due to Term

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Cima, Michael J., Cima, Linda G.
• Primary Examiner(s): Yamnitzky, Marie
• Application Number:
  US08/464,593
• Time in Patent Office: 1,345 Days
• Field of Search: 424/422, 424/423, 424/424, 424/425, 424/426, 523/113, 523/114, 523/115, 428/212, 428/304.4, 428/305.5, 428/313.3, 428/316.6, 428/317.1, 428/317.9, 428/320.2, 428/322.2, 428/322.7, 428/397, 428/398, 428/411.1 , 428/315.5
• US Class Current: 428/304.4
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• CPC Class Codes: A61F 2/105 Skin implants, e.g. artificial skin
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2002/0086 for preferentially controlling or promoting the growth of specific types of cells or tissues of bone tissue onto implantable joints A61F2002/3093
• CPC Class Codes: A61F 2002/009 for hindering or preventing attachment of biological tissue of bone tissue onto implantable joints A61F2002/30932
• CPC Class Codes: A61F 2002/30011 differing in porosity
• CPC Class Codes: A61F 2002/30032 differing in absorbability or resorbability, i.e. in absorption or resorption time
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/3028 polyhedral different from parallelepipedal and pyramidal
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/3093 for promoting ingrowth of bone tissue
• CPC Class Codes: A61F 2002/30932 for retarding or preventing ingrowth of bone tissue
• CPC Class Codes: A61F 2002/30962 using stereolithography
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2230/0063 Three-dimensional shapes
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61F 2250/0023 differing in porosity
• CPC Class Codes: A61F 2250/003 : differing in adsorbability or resorbability, i.e. in adsorption or resorption time
• CPC Class Codes: A61F 2250/0031 : made from both resorbable and non-resorbable prosthetic parts, e.g. adjacent parts
• CPC Class Codes: A61F 2250/0067 : Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2310/00359 : Bone or bony tissue
• CPC Class Codes: A61K 9/0024 : Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0097 : Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips intradermal microneedle arrays A61K9/0021; MEMS in general B81B7/02
• CPC Class Codes: A61K 9/1647 : Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1694 : resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61L 27/34 : Macromolecular materials
• CPC Class Codes: A61L 27/38 : containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3808 : Endothelial cells
• CPC Class Codes: A61L 27/40 : Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: A61L 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/60 : Materials for use in artificial skin
• CPC Class Codes: B29C 64/00 : Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
• CPC Class Codes: B29C 64/165 : using a combination of solid and fluid materials, e.g. a powder selectively bound by a liquid binder, catalyst, inhibitor or energy absorber
• CPC Class Codes: B29K 2995/0064 : Non-uniform density
• CPC Class Codes: B33Y 10/00 : Processes of additive manufacturing
• CPC Class Codes: B33Y 70/00 : Materials specially adapted for additive manufacturing
• CPC Class Codes: B33Y 70/10 : Composites of different types of material, e.g. mixtures of ceramics and polymers or mixtures of metals and biomaterials
• CPC Class Codes: B33Y 80/00 : Products made by additive manufacturing
• CPC Class Codes: Y10S 623/901 : Method of manufacturing prosthetic device
• CPC Class Codes: Y10T 428/249953 : Composite having voids in a component [e.g., porous, cellular, etc.]
• CPC Class Codes: Y10T 428/249954 : With chemically effective material or specified gas other than air, N, or carbon dioxide in void-containing component
• CPC Class Codes: Y10T 428/249961 : With gradual property change within a component
• CPC Class Codes: Y10T 428/249978 : Voids specified as micro
• CPC Class Codes: Y10T 428/249986 : Void-containing component contains also a solid fiber or solid particle
• CPC Class Codes: Y10T 428/249994 : Composite having a component wherein a constituent is liquid or is contained within preformed walls [e.g., impregnant-filled, previously void containing component, etc.]
• CPC Class Codes: Y10T 428/249999 : Differentially filled foam, filled plural layers, or filled layer with coat of filling material

Abstract

Solid free-form techniques for making medical devices for controlled release of bioactive agent and implantation and growth of cells are described using computer aided design. Examples of SFF methods include stereo-lithography (SLA), selective laser sintering (SLS), ballistic particle manufacturing (BPM), fusion deposition modeling (FDM), and three dimensional printing (3DP). The macrostructure and porosity of the device can be manipulated by controlling printing parameters. Most importantly, these features can be designed and tailored using computer assisted design (CAD) for individual patients to optimize therapy.

Claims

1. An implantable medical device for controlled release of a bioactive agent made using a solid free-form fabrication method to form successive layers of a biocompatible material into a matrix with a defined macroscopic shape and a defined microstructure comprising

porous or solid walls, and

a bioactive agent selectively distributed within or between the walls of the microstructure to provide constant rate or pulsed controlled release of the bioactive agent, and/or to form a concentration gradient within the matrix.

2. The device of claim 1 wherein the method is ballistic particle manufacturing or fusion deposition modeling comprising

applying particulate biocompatible material to a platform and bonding the particles to each other to form a layer with a defined pattern, and

repeating the method to form successive layers into a matrix having a desired macroscopic shape and microstructure.

3. The device of claim 1 wherein the method is three dimensional printing, comprising

preparing a dispersion of particles formed of a biocompatible material on a platform;

and

applying a binder or solvent for the particles to the dispersion of particles to form a layer of solidified material with a defined pattern, and

repeating the method to form layers into a matrix having a desired macroscopic shape and microstructure.

4. The device of claim 1 wherein the method is selective laser sintering comprising

applying particles to a platform and fusing selected areas of the particles with a laser to form a layer of solidified material with a defined pattern, and

repeating the method to form sequential layers into a matrix with a desired macroscopic shape and microstructure.

5. The device of claim 1 wherein the method is stereo-lithography and the biocompatible material is photopolymerizable prepolymer or monomers comprising

photopolymerizing selected areas of a bath of photopolymerizable prepolymer or monomers to form a layer of photopolymerized polymer with a defined pattern, and

repeating the process to form successive layers into a matrix having a desired macroscopic shape and microstructure.

6. The device of claim 1 wherein the bioactive agent is added to particles used to form the layers of the matrix and is thereby dispersed throughout the matrix.

7. The device of claim 1 wherein the method comprises using a solvent for the bioactive agent that is not a solvent for the biocompatible material, wherein three dimensional printing is used to form discrete regions of bioactive agent within the matrix.

8. The device of claim 1 wherein the biocompatible material used in the solid free-form fabrication method is in the form of particles.

9. The device of claim 1 wherein the biocompatible material is biodegradable polymer.

10. The device of claim 1 wherein the biocompatible material is a non-degradable polymer and forms a porous matrix through which bioactive agent can diffuse out of the device.

11. The device of claim 1 wherein the bioactive agent is present in different areas of the matrix in different concentrations.

12. The device of claim 1 wherein the bioactive agent is incorporated into the matrix so as to result in pulsed release.