US6176874B1
Expired / Lapsed
US
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Vascularized tissue regeneration matrices formed by solid free form fabrication techniques
Assignee: Boston Children's Hospital
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Filing: 1995-06-07
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Granted: 2001-01-23
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Expires: 2015-06-07
Abstract
Abstract Solid free-form fabrication (SFF) methods are used to manufacture devices for allowing tissue regeneration and for seeding and implanting cells to form organ and structural components, which can additionally provide controlled release of bioactive agents, wherein the matrix is characterized by a network of lumens functionally equivalent to the naturally occurring vasculature of the tissue formed by the implanted cells, and which can be lined with endothelial cells and coupled to blood vessels at the time of implantation to form a vascular network throughout the matrix. The SFF methods can be adapted for use with a variety of polymeric, inorganic and composite materials to create structures with defined compositions, strengths, and densities, using computer aided design (CAD).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).
Inventors
- 👤 Joseph P. Vacanti
- 👤 Linda G. Cima
- 👤 Michael J. Cima
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 20:24
CPC Classifications
A; A61; A61F; A61F2/00; A61F2/02; A61F2/10; A61F2/105; A61F2/022; A61L; A61L27/00; A61L27/36; A61L27/38; A61L27/3804; A61L27/3808; A61L27/40; A61L27/50; A61L27/56; A61L27/60; B; B29; B29C; B29C64/00; B29C64/10; B29C64/106; B29C64/124; B29C64/129; B29C64/135; B29C64/165; B33; B33Y; B33Y10/00; B33Y30/00; A61F2/28; A61F2/30; A61F2/30756; A61F2/3094; A61F2/0077; A61F2002/0086; A61F2002/009; A61F2002/30001; A61F2002/30003; A61F2002/30004; A61F2002/30011; A61F2002/30032; A61F2002/3006; A61F2002/30062; A61F2002/30108; A61F2002/30199; A61F2002/3028; A61F2002/30667; A61F2002/30677; A61F2/30767; A61F2002/3093; A61F2002/30932; A61F2/30942; A61F2002/30962; A61F2210/00; A61F2210/0004; A61F2230/00; A61F2230/0063; A61F2240/00; A61F2240/001; A61F2250/00; A61F2250/0014; A61F2250/0023; A61F2250/003; A61F2250/0031; A61F2250/0058; A61F2250/0067; B29K; B29K2995/00; B29K2995/0037; B29K2995/0063; B29K2995/0064; B33Y80/00; Y; Y10; Y10S; Y10S623/00; Y10S623/901
Claims Analysis
Total Claims: 38
Claim 1
Independent Claim
61 words
A method for making devices for tissue regeneration comprising using a solid free-form fabrication method to sequentially form layers of a biocompatible material into a matrix having (a) interconnected pores extending throughout the matrix wherein the interconnected pores are for seeding with cells, and (b) interconnected lumens within the matrix having openings for connection to ducts within tissue in a patient.
Claim 2
Independent Claim
61 words
A method for making devices for tissue regeneration comprising using a solid free-form fabrication method to sequentially form layers of a biocompatible material into a matrix having (a) interconnected pores extending throughout the matrix wherein the interconnected pores are for seeding with cells, and (b) interconnected lumens within the matrix having openings for connection to ducts within tissue in a patient.
Claim 3
Dependent Claim
19 words
The method of claim 1 comprising forming interconnected lumens within the matrix which can be connected to blood vessels.
Claim 4
Dependent Claim
36 words
The method of claim 1 comprising forming interconnected lumens within the matrix which can be connected to ducts selected from the group consisting of lymph ducts, exocrine function ducts, excretory ducts, and ducts for neural ingrowth.
Claim 5
Dependent Claim
85 words
The method of claim 1 wherein the solid free-form fabrication 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.
Claim 6
Dependent Claim
34 words
The method of claim 1 wherein the solid free-form fabrication method is ballistic particle manufacturing or fusion deposition modeling and polymeric material is applied to a platform in layers to form a polymeric device.
Claim 7
Dependent Claim
33 words
The method of claim 1 wherein the solid free-form fabrication method is selective laser sintering comprising applying polymeric particles to a platform and fusing selected area of the polymeric particles with a laser.
Claim 8
Dependent Claim
25 words
The method of claim 1 wherein the solid free-form fabrication method is stereo-lithography comprising photopolymerizing selected areas of a bath of photopolymerizable prepolymer or monomers.
Claim 9
Dependent Claim
13 words
The method of claim 1 wherein the matrix is formed of biodegradable polymer.
Claim 10
Dependent Claim
28 words
The method of claim 8 wherein structural elements having a longer rate of degradation than the matrix-forming material or which are not biodegradable are incorporated into the matrix.
Claim 11
Dependent Claim
29 words
The method of claim 1 wherein the texture is altered or surface active agents are applied to the device walls to control cell adhesion to and within the device.
Claim 12
Dependent Claim
45 words
The method of claim 10 wherein the matrix is made by three dimensional printing of a binder onto a powder bed where a solution containing surface-active agents is printed into the regions or lines of the powder bed in between where the binder is printed.
Claim 13
Dependent Claim
24 words
The method of claim 10 wherein the outer surface of the matrix is modified with a surface active agent which prevents adhesion of cells.
Claim 14
Dependent Claim
13 words
The method of claim 1 further comprising seeding the device with dissociated cells.
Claim 15
Dependent Claim
31 words
The method of claim 2 further comprising seeding the lumens with dissociated endothelial cells and culturing the device until the cells form a confluent layer on the walls of the lumens.
Claim 16
Dependent Claim
17 words
The method of claim 14 further comprising seeding other regions of the matrix with cells forming tissue.
Claim 17
Dependent Claim
65 words
A medical device for tissue regeneration formed using a solid free-form fabrication method comprising a matrix of successive layers of a biocompatible material, wherein the layers create (a) interconnected pores or lumens extending throughout the matrix wherein the interconnected pores or lumens are for seeding with cells, and (b) interconnected lumens within the matrix having openings for connection to ducts within tissue in a patient.
Claim 18
Dependent Claim
65 words
A medical device for tissue regeneration formed using a solid free-form fabrication method comprising a matrix of successive layers of a biocompatible material, wherein the layers create (a) interconnected pores or lumens extending throughout the matrix wherein the interconnected pores or lumens are for seeding with cells, and (b) interconnected lumens within the matrix having openings for connection to ducts within tissue in a patient.
Claim 19
Dependent Claim
18 words
The device of claim 16 comprising interconnected lumens within the matrix which can be connected to blood vessels.
Claim 20
Dependent Claim
35 words
The device of claim 16 comprising interconnected lumens within the matrix which can be connected to ducts selected from the group consisting of lymph ducts, exocrine function ducts, excretory ducts, and ducts for neural ingrowth.
Claim 21
Dependent Claim
85 words
The device of claim 16 wherein the solid free-form fabrication 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.
Claim 22
Dependent Claim
34 words
The device of claim 16 wherein the solid free-form fabrication method is ballistic particle manufacturing or fusion deposition modeling and polymeric material is applied to a platform in layers to form a polymeric device.
Claim 23
Dependent Claim
33 words
The device of claim 16 wherein the solid free-form fabrication method is selective laser sintering comprising applying polymeric particles to a platform and fusing selected area of the polymeric particles with a laser.
Claim 24
Dependent Claim
25 words
The device of claim 16 wherein the solid free-form fabrication method is stereo-lithography comprising photopolymerizing selected areas of a bath of photopolymerizable prepolymer or monomers.
Claim 25
Dependent Claim
13 words
The device of claim 16 wherein the matrix is formed of biodegradable polymer.
Claim 26
Dependent Claim
25 words
The device of claim 16 wherein structural elements having a longer rate of degradation than the matrix-forming material or which are not biodegradable are incorporated.
Claim 27
Dependent Claim
29 words
The device of claim 16 wherein the texture is altered or surface active agents are applied to the device walls to control cell adhesion to and within the device.
Claim 28
Dependent Claim
45 words
The device of claim 25 wherein the matrix is made by three dimensional printing of a binder onto a powder bed where a solution containing surface-active agents is printed into the regions or lines of the powder bed in between where the binder is printed.
Claim 29
Dependent Claim
24 words
The device of claim 25 wherein the outer surface of the matrix is modified with a surface active agent which prevents adhesion of cells.
Claim 30
Dependent Claim
9 words
The device of claim 16 further comprising bioactive agent.
Claim 31
Dependent Claim
27 words
The device of claim 16 wherein the device is formed by a method that builds a complex three dimensional device as a series of two dimensional layers.
Claim 32
Dependent Claim
17 words
The device of claim 29 wherein the layers are between 2 microns and 1 mm in thickness.
Claim 33
Dependent Claim
19 words
The device of claim 16 wherein the pores or lumens have a diameter of between 150 and 300 microns.
Claim 34
Dependent Claim
13 words
The device of claim 16 further comprising seeding the device with dissociated cells.
Claim 35
Dependent Claim
19 words
The device of claim 17 further comprising dissociated endothelial cells seeded onto the walls of the pores or lumens.
Claim 36
Dependent Claim
17 words
The device of claim 33 further comprising cells forming tissue seeded onto other regions of the matrix.
Claim 37
Dependent Claim
12 words
The device of claim 18 further comprising cells forming tissues seeded therein.
Claim 38
Dependent Claim
13 words
The device of claim 16 wherein the polymeric material includes a bioactive agent.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2004-01-23 | 2004-07-24 | 2005-01-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2008-01-23 | 2008-07-24 | 2009-01-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2012-01-23 | 2012-07-24 | 2013-01-23 | $7700.00 | Window Closed / Lapsed |