Controlled local/global and micro/macro-porous 3D plastic, polymer and ceramic/cement composite scaffold fabrication and applications thereof

• US 7,087,200 B2
• Filed: 06/24/2002
• Issued: 08/08/2006
• Est. Priority Date: 06/22/2001
• Status: Active Grant

• 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: Chu, Tien-Min Gabriel, Taboas, Juan, Maddox, Rachel D, Hollister, Scott J, Krebsbach, Paul H
• Primary Examiner(s): Kuhns, Allan R.
• Application Number:
  US10/178,292
• Publication Number:
  US 20030006534A1
• Time in Patent Office: 1,506 Days
• Field of Search: 164/47, 264/49, 264/51, 264/219, 264/220, 264/222, 264/255, 264/317, 264/212, 264/232, 264/299, 264/328.1
• US Class Current: 264/49
• CPC Class Codes: A61F 2/062 Apparatus for the production of blood vessels made from natural tissue or with layers of living cells prostheses made from natural tissue or living cells A61L27/507
• CPC Class Codes: A61F 2/08 Muscles; Tendons; Ligaments sutures A61B17/04
• CPC Class Codes: A61F 2/0811 Fixation devices for tendons or ligaments
• 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 2/30942 for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques
• CPC Class Codes: A61F 2002/0086 for preferentially controlling or promoting the growth of specific types of cells or tissues
• CPC Class Codes: A61F 2002/0894 Muscles
• CPC Class Codes: A61F 2002/30199 Three-dimensional shapes
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/30766 Scaffolds for cartilage ingrowth and regeneration
• CPC Class Codes: A61F 2002/3092 having an open-celled or open-pored structure
• CPC Class Codes: A61F 2002/3093 for promoting ingrowth of bone tissue
• CPC Class Codes: A61F 2002/30948 using computerized tomography, i.e. CT scans
• CPC Class Codes: A61F 2002/30952 using CAD-CAM techniques or NC-techniques
• CPC Class Codes: A61F 2002/30957 using a positive or a negative model, e.g. moulds
• CPC Class Codes: A61F 2230/0063 Three-dimensional shapes
• CPC Class Codes: A61F 2240/002 Designing or making customized prostheses
• CPC Class Codes: A61F 2240/004 Using a positive or negative model, e.g. moulds
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: B22C 9/00 : Moulds or cores uniquely adapted to particular casting processes B22D; Moulding processes
• CPC Class Codes: B29C 2791/001 : Shaping in several steps
• CPC Class Codes: B29C 33/3835 : Designing moulds, e.g. using CAD-CAM
• CPC Class Codes: B29C 33/3842 : Manufacturing moulds, e.g. shaping the mould surface by machining
• CPC Class Codes: B29C 33/52 : soluble or fusible in particular used in injection moulding B29C45/4457
• CPC Class Codes: B29C 39/021 : by casting in several steps
• CPC Class Codes: B29C 43/006 : Pressing and sintering powders, granules or fibres
• 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: B29C 64/40 : Structures for supporting 3D objects during manufacture and intended to be sacrificed after completion thereof
• CPC Class Codes: B29K 2105/04 : cellular or porous
• CPC Class Codes: B29K 2995/0094 : Geometrical properties
• CPC Class Codes: B29L 2031/7532 : Artificial members, protheses
• CPC Class Codes: B33Y 70/00 : Materials specially adapted for additive manufacturing
• CPC Class Codes: B33Y 80/00 : Products made by additive manufacturing
• CPC Class Codes: C04B 35/447 : based on phosphates , e.g. hydroxyapatite
• CPC Class Codes: C04B 35/6264 : Mixing media, e.g. organic solvents
• CPC Class Codes: C04B 35/63 : using additives specially adapted for forming the products , e.g.. binder binders
• CPC Class Codes: C04B 35/632 : Organic additives
• CPC Class Codes: C04B 35/634 : Polymers C04B35/636 takes precedence
• CPC Class Codes: G05B 19/4099 : Surface or curve machining, making 3D objects, e.g. desktop manufacturing
• CPC Class Codes: G05B 2219/45204 : Die, mould making

Abstract

An indirect solid free form scaffold manufacturing technique is provided. More particularly, the present invention provides a set of molds, casting methods, mold removals, and surface modification techniques that are compatible with image-based design methods and with solvent, melt, and slurry casting of polymers and ceramics.

Claims

1. A method of indirectly fabricating a desired structure comprising:

computationally designing the desired structure;

fabricating a three dimensional mold for indirectly producing the desired structure;

casting a material in the mold to form the desired structure;

removing the mold from the desired structure; and

imparting a desired surface property to the desired structure in vitro, where said surface property comprises at least one of chemically active and biologically active.

2. The method of claim 1 wherein said step of computationally designing the desired structure further comprises at least one of computer aided design techniques or image based design techniques.

3. The method of claim 2 wherein said imaged based design technique further maps the computationally designed desired structure to a 3D image scan.

4. The method of claim 3 wherein the mold is fabricated directly using said image based design.

5. The method of claim 1 wherein said step of fabricating a mold for indirectly producing the desired structure further comprises at least one of 3D printing, fused deposition, selective laser sintering, stereolithography, layered object manufacturing, and direct material deposition.

6. The method of claim 1 wherein the mold is formed of at least one of wax, plastic, polymer, sugar, ceramic, cement, and metal.

7. The method of claim 1 further comprising producing smaller feature sizes in the structure by at least one of shrinking said mold prior to said casting step and shrinking said desired structure after said casting step.

8. The method of claim 1 wherein said step of casting a material in the mold further comprises at least one of:

solvent casting in wax;

solvent casting in plastic;

solvent casting in polymer

solvent casting in ceramic;

solvent casting in cement;

solvent casting in metal;

uncured material casting in wax;

uncured material casting in plastic;

uncured material casting in polymer;

uncured material casting in ceramic;

uncured material casting in cement;

uncured material casting in metal;

melt casting in plastic

melt casting in polymer

melt casting in ceramics;

melt casting in cements;

melt casting in metals

injection molding in ceramics;

injection molding in cements; and

composite material casting.

9. The method of claim 1 wherein said step of removing the mold from the desired structure further comprises at least one of fracturing, melting, and dissolving.

10. The method of claim 9 wherein said step of dissolving further comprises dissolving at least one of a ceramic and a cement mold using a buffered acid solution.

11. The method of claim 1 wherein said desired surface property further comprises at least one of activation, derivitization, and functionalization of the desired structure surface.

12. The method of claim 1 wherein said step of computationally designing the desired structure further comprises designing a global porous architecture for the desired structure.

13. The method of claim 12 wherein said global porous architecture is selected to promote at least one of tissue ingrowth, media perfusion and angiogenesis.

14. The method of claim 12 wherein said local porous architecture is selected to promote at least one of tissue growth, cell seeding, cell delivery, and biofactor delivery.

15. The method of claim 12 wherein said global porous architecture includes branching global channels.

16. The method of claim 15 wherein said channels are interconnected in three dimensional space.

17. The method of claim 15 wherein said channels interpenetrate an interior of said desired structure but remain exclusive of said local porous architecture.

18. A method of indirectly fabricating a desired structure comprising:

computationally designing the desired structure;

fabricating a three dimensional mold for indirectly producing the desired structure;

casting a material in the mold to form the desired structure

removing the mold from the desired structure, and

imparting a desired surface property to the desired structure in vitro, where said surface property comprises at least one of chemically active and biologically active;

wherein said step of casting the material in the mold further comprises production of a local porous structure via the casting step and a global porous structure via the mold shape to impart the desired structure with two levels of internal architecture scale.

19. The method of claim 18 wherein said step of casting the material in the mold further comprises forming a local porous architecture in the desired structure.

20. The method of claim 18 where said casting step further comprises casting a local porous structure within the mold that defines global pores for the cast structure.

21. The method of claim 18 further comprising casting using at lest one local pore fabrication technique selected from:

porogen leaching;

emulsion freeze dry;

phase separation;

emulsion solvent diffusion;

supercritical fluid; and

gas foaming.

22. A method of indirectly fabricating a desired structure comprising:

computationally designing the desired structure;

fabricating a three dimensional mold for indirectly producing the desired structure;

casting a material in the mold to form the desired structure; and

removing the mold from the desired structure,

wherein said casting step further comprises a primary casting step wherein a first material is cast into the mold to yield a global porous structure and a secondary casting step wherein a second material is cast within global pores of the global porous structure to create a local porous structure within the global porous structure.

23. A method of indirectly fabricating a desired structure comprising:

computationally designing the desired structure;

fabricating a three dimensional mold for indirectly producing the desired structure;

casting a material in the mold to form the desired structure;

removing the mold from the desired structure; and

functionalizing a surface of the desired structure with a desired ligand.

24. The method of claim 23 further comprising coating the mold with a material to impart a pre-selected characteristic to the desired structure.

25. The method of claim 24 further comprising coating the mold with a derivitizing agent prior to casting the desired structure.

26. The method of claim 23 further comprising incorporating a derivitizing agent into an uncured material and then casting the uncured material in said casting step.

27. The method of claim 23 further comprising activation and derivitization of the desired structure by way of plasma activation.

28. The method of claim 23 further comprising covalently linking a desired ligand to the derivitizing agent.

29. The method of claim 28 wherein a stable functionalization is achieved by using a ligand with multiple functional groups that links to multiple derivitizing agents on the structure.

30. The method of claim 23 wherein a stable functionalization is achieved by stabilizing the ligand after said step of functionalizing the desired structure by covalently coupling functional groups of said ligand using a primary cross-linker.

31. The method of claim 23 further comprising orienting the desired ligand.

32. A method of indirectly fabricating a desired structure comprising:

computationally designing the desired structure;

fabricating a three dimensional mold for indirectly producing the desired structure;

casting a material in the mold to form the desired structure; and

removing the mold from the desired structure;

wherein said step of casting the material in the mold further comprises production of a local porous structure via the casting step and a global porous structure via the mold shape to impart the desired structure with two levels of internal architecture scale, and wherein said step of computationally designing the desired structure and mold for casting said structure further comprises designing a biomimetic scaffold using imaged based design techniques.

33. A method of indirectly fabricating a desired structure comprising:

computationally designing the desired structure;

fabricating a three dimensional mold for indirectly producing the desired structure;

casting a material in the mold to form the desired structure;

removing the mold from the desired structure; and

seeding cells that produce a desired biofactor onto the desired structure.

34. A method of indirectly fabricating a desired structure comprising:

computationally designing the desired structure;

fabricating a three dimensional mold for indirectly producing the desired structure;

casting a material in the mold to form the desired structure; and

removing the mold from the desired structure,

wherein said material comprises a low-viscosity ceramic slurry including tricalcium phosphate powder, acrylates, dispersants, and initiators.

35. The method of claim 34 wherein:

a particle size of the powder is less than 100 microns;

a viscosity of the acrylates is less than 100 mPa·

S; and

the dispersants are at least one of anionic and cationic.

36. The method of claim 34 wherein said material further comprises:

40 volume percent tricalcium phosphate powder, a particle size of the powder being about 1 micron in diameter;

a balancing reactive medium in a 50;

50 mixture of isobornyl acrylate and propoxylated neopentylglycol diacylate;

a 2.5% cationic dispersant and 2.5% antionic dispersant; and

a thermal initiator.

37. The method of claim 34 further comprising an accelerator to allow a curing reaction at room temperature.

38. The method of claim 37 wherein said accelerator further comprises N,N-dimethyl p-toludine.

39. A method of designing a desired structure comprising:

computationally designing the desired structure to support a tissue interface that includes interfaces between soft tissues and interfaces between bone and soft tissue;

fabricating a three dimensional mold of the desired structure;

casting a material in the mold to form the desired structure, said casting step including;

casting first material base with a macro-porous architecture and external geometry selected to promote angiogenesis, bone ingrowth, and anchoring of the structure into bone;

casting a second material interface region on the base, the interface region being anchored in the base through an interconnected network; and

casting a third material block on the interface region, the block including longitudinal fibers interconnected in an off axis lattice network;

removing the mold from the desired structure.

40. The method of claim 39 wherein the interface region further comprises ellipsoidal channels interconnected with orthogonal links.

41. The method of claim 39 wherein the block includes locally porous material between the longitudinal fibers.

42. The method of claim 39 wherein the interconnecting lattice network further comprises a non-linear strain providing structure.

43. The method of claim 39 wherein a lattice network is formed orthogonal to a long axis of the desired structure.

44. The method of claim 39 wherein the lattice network includes individual struts interconnecting the fibers at acute angles.