Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Implantable prosthesis – Bone
Reexamination Certificate
1995-06-05
2003-03-11
Prebilic, Paul B. (Department: 3738)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Implantable prosthesis
Bone
C623S023570, C623S023610, C623S901000
Reexamination Certificate
active
06530958
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention is in the area of methods for formulating devices for tissue regeneration, which uses computer-aided design (CAD) in combination with solid free-form fabrication technology.
Strategies for regenerating tissue are being developed in response to a range of clinical needs, including replacement of damaged or genetically absent metabolic function from tissues such as liver, pancreas and pituitary tissue, and repair or restructuring of damaged or malformed connective tissues such as bone, cartilage and skin. Unlike blood or bone marrow tissues which can be regenerated by intravenous injection of cells, regeneration of most tissues requires a template to guide their growth.
New therapies for tissue regeneration include approaches in which cells are transplanted into a patient along with a device, and approaches in which a device is implanted next to normal tissue and guides the growth of that tissue into a new region. An example of the latter is a bone regeneration device placed into a fracture site, which guides growth of bone tissue into the fracture.
A number of approaches have been described for fabricating tissue regeneration devices for either in vitro or in vivo growth of cells. Polymeric devices have been described for replacing organ function or providing structural support. Such methods have been reported by Vacanti, et al.,
Arch. Surg
. 123, 545-549 (1988), U.S. Pat. No. 4,060,081 to Yannas, et al., U.S. Pat. No. 4,485,097 to Bell, and U.S. Pat. No. 4,520,821 to Schmidt, et al. In general, however, the methods used by Vacanti, et al., and Schmidt, et al., can be practiced by selecting and adapting existing polymer fiber compositions for implantation and seeding with cells, while the methods of Yannas and Bell produce very specific modified collagen sponge-like structures.
Various materials are used to fabricate inorganic or inorganic/polymer matrices for bone regeneration. These include the coralline replaniform hydroxyapatite, which is essentially an adapted coral as described by Martin, R. B., et al., “Bone ingrowth and mechanical properties of coralline hydroxyapatite one year after implantation,”
Biomaterials
, 14:341-348 (1993), and devices which incorporate a cellular component, as described by U.S. Pat. Nos. 4,620,327, 4,609,551, 5,226,914 and 5,197,985 to Arnold Caplan. Composite materials have also been described; however, they have been used primarily for fixation devices, and not bone ingrowth. See, for example, Boeree, N. R., et al., “Development of a degradable composite for orthopedic use: mechanical evaluation of an hydroxyapatite-polyhydroxybutyrate composite material,”
Biomaterials
, 14:793-796 (1993).
Tissue regeneration devices must be porous with interconnected pores to allow cell and tissue penetration. Factors such as pore size, shape and tortuosity can all affect tissue ingrowth but are difficult to control using standard processing techniques.
It would be advantageous to construct specific structures from biocompatible synthetic or natural polymers, inorganic materials, or composites of inorganic materials with polymers, where the resulting structure has defined pore sizes, shapes and orientations, particularly different pore sizes and orientations within the same device, with more than one surface chemistry or texture at different specified sites within the device.
It is therefore an object of the present invention to provide methods and compositions for the preparation of complex, temporal and spatial patterns for use in tissue regeneration.
It is another object of the present invention to provide methods and compositions for making complex medical devices of bioerodible or non-bioerodible materials or composites for either cell transplantation or matrix-guided tissue regeneration.
It is a further object of the present invention to provide methods that operate with high precision and reproducibility to produce medical devices.
It is a still further object of the present invention to produce devices which can selectively encourage the growth of one tissue type over another at specific sites within the matrix by virtue of control of surface chemistry and texture or growth factor release at that region of the matrix.
SUMMARY OF THE INVENTION
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. 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). In a preferred embodiment, 3DP is used to precisely create channels and pores within a matrix to control subsequent cell growth and proliferation in the matrix. For example, 3DP can be used to create a porous bioerodible matrix having interconnected pores or channels, typically between 0.15 and 0.5 mm, which are separated by walls approximately 30 to 100 microns thick, which have an average pore size of approximately 5 to 40 microns.
The macrostructure and porosity of the device can be manipulated by controlling printing parameters, the type of polymer and particle size, as well as the solvent and/or binder. Porosity of the matrix walls, as well as the matrix per se, can be manipulated using SFF methods, especially 3DP. Structural elements that maintain the integrity of the devices during erosion can also be incorporated. For example, to provide support, the walls of the device can be filled with resorbable inorganic material, which can further provide a source of mineral for the regenerating tissue. Most importantly, these features can be designed and tailored using computer assisted design (CAD) for individual patients to individualize the fit of the device.
DETAILED DESCRIPTION OF THE INVENTION
Solid free-form fabrication methods offer several advantages for constructing medical devices for tissue engineering. Devices for tissue regeneration can be constructed to fit the individual patient, individual cell type or organ structure. The device can include a specified bioactive agent composition gradient and structure to deliver drugs to the site of regeneration, and can be tailored to the needs of individual patients. SFF methods can be used to selectively control the composition within the build plane by varying the composition of printed material. Unconventional microstructures, such as those with complicated porous networks or unusual composition gradients, can be designed at a CAD terminal and built through an SFF process such as 3DP. Complex resorbable or erodible medical devices can be built which incorporate structural elements to insure the structural integrity of the device during erosion.
EXAMPLES OF USEFUL SFF PROCESSES
Three Dimensional Printing (3DP)
3DP is described by Sachs, et al., “CAD-Casting: Direct Fabrication of Ceramic Shells and Cores by Three Dimensional Printing”
Manufacturing Review
5(2), 117-126 (1992) and U.S. Pat. No. 5,204,055 to Sachs, et al., the teachings of which are incorporated herein. Suitable devices include both those with a continuous jet stream print head and a drop-on-demand stream print head. A high speed printer of the continuous type, for example, is the Dijit printer made and sold by Diconix, Inc., of Dayton, Ohio, which has a line printing bar containing approximately 1,500 jets which can deliver up to 60 million droplets per second in a continuous fashion and can print at speeds up to 900 feet per minute. Both raster and vector apparatuses can be used. A raster apparatus is where the printhead goes back and forth across the bed with the jet turning on and off. This can have problems when the material is likely to clog the jet upon settling. A vector ap
Cima Linda G.
Cima Michael J.
Holland & Knight LLP
Massachusetts Institute of Technology
Prebilic Paul B.
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