Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Implantable prosthesis
Reexamination Certificate
2002-10-08
2004-02-10
Isabella, David J. (Department: 3738)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Implantable prosthesis
C623S023740
Reexamination Certificate
active
06689166
ABSTRACT:
FIELD OF THE INVENTION
It has now been found that the components in biocompatible scaffolds or matrices of nanometer diameter provide favorable environments for cell adhesion, cell proliferation and directional growth. Fibrous and fibrillar organic and inorganic biocompatible materials of nanometer diameter can be integrated into nonwoven three-dimensional matrices conducive for cell seeding and proliferation. These three-dimensional scaffolds or matrices can then be fabricated into appropriate shapes to simulate the hierarchical micro- and macro-geometry of tissues and/or organs to be repaired or replaced.
BACKGROUND OF THE INVENTION
The unique combination of light weight, flexibility, permeability, strength and toughness of linear, 2-dimensional and 3-dimensional textile structures renders them useful in a variety of ways beyond traditional apparel. Various fiber structures are disclosed by Ko, F. K. in
Textile Structural Composites
, Chou, T. W., and Ko, F. K., eds., Elsevier, 1989, and
Bull. Am. Cer. Soc. February
1989. An important element dictating the physical characteristics of a textile structure and its usefulness in various applications is the fineness as determined by diameter and linear density of the fibers. In general the range of fiber fineness expressed in terms of fiber diameter has been well above 2 &mgr;M. Also important is the organization and orientation of these fibers.
Many of the applications for these structures including, but not limited to, medical devices and chemical separation and/or protection apparatus require broad ranges of fiber architecture, packing density, surface texture, porosity, total reactive surface areas and fiber tortuosity. Accordingly, it would be of great advantage in the art in many of these uses, if fibers of smaller diameter with greater strength could be prepared. For example, trauma, pathological degeneration, or congenital deformity of tissues can result in the need for surgical reconstruction or replacement. Reconstructive surgery is based upon the principle of replacing these types of defective tissues with viable, functioning alternatives. In skeletal applications, surgeons have historically used bone grafts. The two main types of bone grafts currently used are autografts and allografts. An autograft is a section of bone taken from the patient's own body, while an allograft is taken from a cadaver. This method of grafting provides the defect site with structural stability and natural osteogenic behavior. However, both types of grafts are limited by certain uncontrollable factors. For autografts, the key limitation is donor site morbidity where the remaining tissue at the harvest site is damaged by removal of the graft. Other considerations include the limited amount of bone available for harvesting, and unpredictable resorption characteristics of the graft. The main limitation of allografts has been the immunologic response to the foreign tissue of the graft. The tissue is often rejected by the body and is subject to the inflammatory response. Allografts are also capable of transmitting disease. Although a thorough screening process eliminates most of the disease carrying tissue, this method is not 100% effective.
Conventional orthopedic implants such as screws, plates, pins and rods serve as loadbearing replacements for damaged bone and are usually composed of a metal or alloy. Although these implants are capable of providing rigid fixation and stabilization of the bone, they cause improper bone remodeling of the implant site due to the large difference in the modulus between bone and metal.
These limitations have initiated the search for a dependable synthetic bone graft substitute. However, in order for an implant to be used as a replacement for bone, it must be capable of both osteointegration and osteoconduction. Osteointegration refers to direct chemical bonding of a biomaterial to the surface of bone without an intervening layer of fibrous tissue. This bonding is referred to as the implant-bone interface. A primary problem with skeletal implants is mobility. Motion of the implant not only limits its function, but also predisposes the implant site to infection and bone resorption. With a strong implant-bone interface, however, mobility is eliminated, thus allowing for proper healing to occur. Osteoconduction refers to the ability of a biomaterial to sustain cell growth and proliferation over its surface while maintaining the cellular phenotype. For osteoblasts, the phenotype includes mineralization, collagen production, and protein synthesis. Normal osteoblast function is particularly important for porous implants that require bone ingrowth for proper strength and adequate surface area for bone bonding. In addition, implants should be both biocompatible and biodegradable.
Three-dimensional polymer matrix systems have shown considerable promise for tissue regeneration because of their increased surface area for cell growth, pathways for cellular migration and channels for transport of nutrients and effector molecules to cells (Eggli et al.
Clin. Orthop.
1987 232:127-138; Allcock et al.
Macromolecules
1977 10:824-830). Porous, three-dimensional matrices comprising biodegradable, biocompatible polymers or copolymers such as poly(lactic acid-glycolic acid), referred to herein as PLAGA, and its homopolymer derivatives, PLA and PGA, have been demonstrated to be useful in skeletal repair and regeneration (Coombes, A. D. and Heckman, J. D.
Biomaterials
1992 13:217-224; Mikos et al.
Polymer
1994 35:1068-1077; Robinson et al.
Otolaryngol. Head and Neck Surg.
1995 112:707-713; Thomson et al.
J. Biomater. Sci. Polymer Edn.
1995 7:23-38; Devin et al.
J. Biomateri. Sci. Polymer Edn.
1996 7:661-669). Pores of these structures are believed to aid in the polymer resorption-graft incorporation cycle by increasing pathways through which cells can migrate, increasing the surface area for cell attachment, providing pathways by which nutrients may reach the cells, and increasing the polymer surface exposed to the degradation medium (Attawia et al.
Biochem. and Biophys. Res. Commun.
1995 213(2):639-644). Accordingly, much of the research concerning production of polymeric matrices for tissue engineering has focused upon formation of matrices of adequate pore size which maintain the compressive strength required for a bone replacement device. Due to the size of osteoblasts, studies have established 100 &mgr;M as the minimum pore diameter required for the successful ingrowth of bone cells to these scaffolds (Friedlander, G.
Bone and Cartilage Allografts
, AAOS, Park Ridge, Ill., 1991).
It has now been found, however, that tissue engineered devices with enhanced properties of cell adhesion, cell proliferation and directional growth can be prepared from matrices comprising biocompatible fibers of a diameter which is an order of magnitude smaller than the cells. Accordingly, the present invention relates to fibers of nanometer diameter, referred to herein as nanofibrils, with adequate strength for use in textile processing processes and methods of producing these nanofibrils. Tissue engineering devices are also provided which are prepared from scaffolds or matrices comprising nonwoven nanofibrils.
SUMMARY OF THE INVENTION
An object of the present invention is to provide fibers of nanometer diameter and adequate strength to be useful in textile processing processes. These fibers of the present invention are referred to herein as “nanofibrils.”
Another object of the present invention is to provide a method of making nanofibrils for use in nanofibril matrices.
Yet another object of the present invention is to provide a tissue engineered device with enhanced properties of cell adhesion, cell proliferation and directional growth which comprises a nonwoven nanofibril matrix.
REFERENCES:
patent: 4970298 (1990-11-01), Silver et al.
patent: 6106913 (2000-08-01), Scardino et al.
Ko Frank K.
Laurencin Cato T.
Drexel University
Isabella David J.
Licata & Tyrrell P.C.
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