Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Implantable prosthesis
Reexamination Certificate
1998-03-17
2001-01-30
Zirker, Daniel (Department: 1771)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Implantable prosthesis
C623S016110, C530S354000, C530S356000, C442S123000, C428S304400
Reexamination Certificate
active
06179872
ABSTRACT:
BACKGROUND OF THE INVENTION
Collagen scaffolds have been used in tissue repair and tissue reconstruction. The scaffolds are usually crosslinked to provide the degree of wet strength and measured resistance to dissolution needed for these applications. In general, the crosslinking of collagen sponges or foams reduces or degrades the normal binding sites to which cells and certain molecules secreted by cells attach. Furthermore, collagen sponges, gelatin sponges or collagen gels, while biologically active, lack biological activity typically present in the extracellular matrix environment due to the lack of non-collagen components and thus information which binds to collagen or to non-collagen components themselves. Because of their deficiencies, collagen scaffolds crosslinked by known methods induce little regeneration in vivo or serve poorly as histiotypic and organotypic models in vitro.
A need exists, therefore, for an improved biopolymer form that overcomes or minimizes the above-mentioned problems and preserves the natural structure of the collagen.
SUMMARY OF THE INVENTION
The invention features biopolymer scaffolds in the form of biopolymer matt or biopolymer matt composites, e.g., resorbable biopolymer matt, for membranous or thick tissue applications, or as a filler material for tissue repair and tissue reconstruction which has a high strength to unit volume even before crosslinking. The invention also features biopolymer matt compositions comprising biopolymer matt and various layers of biopolymer foams, biocompatible constructs comprising biopolymer matt and extracellular matrix macromolecules, and methods for making and using the biopolymer matt, biopolymer matt composites, biopolymer matt compositions, and biocompatible matt constructs.
The biopolymer matt and biopolymer matt compositions can be used in vitro, for example, as model systems for research, or in vivo as prostheses or implants to replace damaged or diseased tissues or to provide scaffolds which, when occupied by cells, e.g., host cells, are remodeled to become functional tissues. In either case, the matt, matt composites, and matt compositions can be seeded with cells, e.g., mammalian cells, e.g., human cells, of the same type as those of the tissue which the matt, matt composites, or matt compositions is used to repair, reconstruct, or replace. Examples of tissues which can be repaired and/or reconstructed using the matt, matt composites, and matt compositions described herein include nervous tissue, skin, vascular tissue, cardiac tissue, pericardial tissue, muscle tissue, ocular tissue, periodontal tissue, connective tissue such as bone, cartilage, tendon, and ligament, organ tissue such as kidney tissue, and liver tissue, glandular tissue such as pancreatic tissue, mammary tissue, and adrenal tissue, urological tissue such as bladder tissue and ureter tissue, and digestive tissue such as intestinal tissues.
In one aspect of the invention, the matt, matt composites, and matt compositions seeded with tissue specific cells are introduced into a recipient, e.g., a mammal, e.g., a human. Alternatively, the seeded cells which have had an opportunity to organize into a tissue in vitro and to secrete tissue specific biosynthetic products such as extracellular matrix proteins and/or growth factors which bond to the matt and matt compositions are removed prior to implantation of the matt or matt compositions into a recipient.
Accordingly, the invention pertains to biopolymer matts having selected characteristics. In another aspect of the invention, the biopolymer matt comprises a densely packed random array of biopolymer fibrils and has a high strength to unit volume and preserves the native structure of the biopolymer fibrils. Examples of molecules which can form biopolymer fibrils which can be used in the biopolymer matt include collagen, laminin, elastin, fibronectin, fibrinogen, thrombospondin, gelatin, polysaccharides, poly-
1
-amino acids and combinations of biopolymers. A preferred molecule for biopolymer production is collagen, e.g., porcine fetal collagen. In other embodiments, the biopolymer matt can include macromolecules necessary for cell growth, morphogenesis, differentiation, or tissue building and combinations thereof, extracellular matrix particulates and/or cells.
Biopolymer matt of the invention can be prepared by forming a biopolymer solution in which fibril formation occurs, e.g., collagen fibril formation, pouring the solution over a porous structure which traps and/or embeds the fibrils and forms a semisolid fibril-gel structure which can be dried to a thin, dense fibrillar membrane, e.g., a matt. In another embodiment, the addition of sodium chloride in the neutralization buffer diminishes the gel component resulting in a higher concentration of fibrils.
In another aspect of the invention, matt composites can be formed by collecting sequential layers of fibril slurry on the porous support.
In yet another aspect of the invention, the porosity of the matt can be manipulated by various physical or chemical methods. In still another aspect of the invention, the strength of the biopolymer matt can be manipulated by various physical or chemical methods.
In yet an additional aspect of the invention, the biopolymer matt, matt composite, or matt composition can further be conditioned with cells prior to use in vitro or in vivo. Cell conditioning is an application-specific method used to speed integration of the matt, matt composite, or matt composition into its new function, to speed recovery of repair tissue and to direct authentic replacement of the damaged or missing tissue. Biopolymer matt, biopolymer matt composites, or biopolymer matt compositions can be used as a substrate for the growth of cells appropriate for the site of use. For example, for a biopolymer matt, biopolymer matt composite, or biopolymer matt composition used to repair bone defects as a periosteum, the conditioning cells would include, e.g., osteoblasts. For a biopolymer matt, biopolymer matt composite, or biopolymer matt composition used as pericardial membrane, the conditioning cells would include, e.g., mesothelial cells. For a biopolymer matt, biopolymer matt composite, or biopolymer matt composition used in the abdomen, the conditioning cells would include, e.g., mesothelial cells.
During conditioning, cells residing on biopolymer matt, biopolymer matt composite, or biopolymer matt composition deposit onto the matt, matt composite, or matt composition, macromolecules, such as protein products recognizable by the cells neighboring the defect at the site of matt, matt composite, or matt composition placement. The cell choice and thus the protein products can direct two things. They can direct the migration of the neighboring cells onto the matt, matt composite, or matt composition and the remodeling of the matt, matt composite, or matt composition material to replace the matt, matt composite, or matt composition with authentic covering tissue or the cell products will stimulate the regrowth of the tissue desired beneath the matt, matt composite, or matt composition while other cells remodel the matt, matt composite, or matt composition from the opposite side. After a period of time for the conditioning cells to deposit sufficient signaling and extracellular matrix molecules onto the matt, matt composite, or matt composition, the matt, matt composite, or matt compositions can be used as living implants to serve as living tissue equivalents or model tissue systems. Alternatively, cells of the matt, matt composite, or matt compositions can be killed by freezing or freeze drying the construct. Freeze drying eliminates living material, but leaves the deposited proteins in their natural states.
The biopolymer matt can be used alone, e.g., as a collagenous membrane for a periodontal barrier, or as a periosteal barrier to aid in bone repair. The biopolymer matt can also be used as a biopolymer composite by collecting sequential layers of different fibril slurry on the porous support and fusing these layers to each other. The
Begley Michael J.
Bell Eugene
Sioussat Tracy M.
Lahive & Cockfield LLP
Tissue Engineering
Zirker Daniel
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