Tissue regeneration matrices by solid free form fabrication techniques

• US 5,518,680 A
• Filed: 02/23/1994
• Issued: 05/21/1996
• 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): Tentoni, Leo B.
• Application Number:
  US08/200,636
• Time in Patent Office: 818 Days
• Field of Search: 264/22, 264/25, 264/41, 264/255, 264/308, 264/113, 156/62.2, 156/272.8
• US Class Current: 264/401
• 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
• CPC Class Codes: A61F 2002/009 for hindering or preventing attachment of biological tissue
• 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 27/38 : 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 64/165 : 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

Abstract

Solid free-form techniques for making medical devices for implantation and growth of cells from polymers or polymer/inorganic composites using computer aided design are described. 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 devices can incorporate inorganic particles to improve the strength of the walls forming the pores within the matrix and to provide a source of mineral for the regenerating tissue. The devices can contain tissue adhesion peptides, or can be coated with materials which reduce tissue adhesion. 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. A method for making devices for tissue regeneration comprising forming a polymeric matrix using a solid free-form fabrication method to form sequential layers of a biocompatible polymeric matrix having interconnected pores extending throughout the matrix.

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

a) spreading a first dispersion of a biocompatible polymer or composite powder onto a bed,

b) printing a layer comprising a second dispersion of biocompatible polymer or composite powder in a solvent which binds the first biocompatible polymer or composite powder to the second biocompatible polymer or composite powder at locations where it is desired to have walls, and

c) repeating step b until the desired matrix is made.

3. The method of claim 2 wherein the powder is a resorbable powder selected from the group consisting of calcium phosphate, hydroxyapatite, and calcium carbonate.

4. The method of claim 2 wherein the powder size is less than 40 microns in diameter.

5. The method of claim 2 wherein the walls are less than 100 microns thick.

6. The method of claim 2 wherein the binder is a resorbable polymer selected from the group consisting of polyhydroxyacids, polyorthoesters, polyanhydrides, and copolymers and blends thereof.

7. The method of claim 2 further comprising adding a biodegradable latex to the polymer.

8. The method of claim 2 further comprising printing a solution containing surface-active agents into the regions or lines of the powder bed in between where the binder is printed.

9. The method of claim 2 further comprising modifying the surface of the polymer with a surface active agent which prevents adhesion of cells.

10. The method of claim 2, further comprising incorporating an exogenously fabricated device into the matrix by printing layers of binder around the exogenously fabricated device.

11. The method of claim 1 wherein the method is ballistic particle manufacturing or fusion deposition modeling and polymeric material is applied to a platform in layers to form a polymeric device.

12. The method of claim 1 wherein the method is selective laser sintering comprising applying polymeric particles to a platform and fusing selected area of the polymeric particles with a laser.

13. The method of claim 1 wherein the method is stereo-lithography comprising photopolymerizing selected areas of a bath of photopolymerizable prepolymer or monomers.

14. The method of claim 1 further comprising adding a bioactive agent to the polymeric material.

15. The method of claim 14 wherein the bioactive agent is added to the polymeric particles used to form the polymer layers.

16. The method of claim 14 wherein the bioactive agent is added to a solvent or binder for polymeric particles used to form the polymer layers.

17. The method of claim 16 wherein the solvent for the bioactive agent is not a solvent for the polymer, wherein three dimensional printing is used to form discrete regions of bioactive agent within a polymeric matrix.

18. The method of claim 1 further comprising incorporating a non-biodegradable material into the device to form structural elements maintaining the integrity of the device when formed of a biodegradable material.