Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Implantable prosthesis – Tissue
Reexamination Certificate
1998-12-03
2001-12-11
Willse, David H. (Department: 3738)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Implantable prosthesis
Tissue
C623S023760, C623S023580
Reexamination Certificate
active
06328765
ABSTRACT:
FIELD OF THE INVENTION
This invention relates generally to tissue regeneration in a living host. More particularly, the invention relates to tissue regeneration using porous polymeric materials in combination with tissue stimulatory substances.
BACKGROUND OF THE INVENTION
Surgical options to treat tissue surplus are generally successful in achieving the desired goals of reduced tissue mass and restoration of normal tissue geometry. Procedures of this nature include ostectomy, mastectomy, partial and complete hepatectomy. However, when tissue deficiencies are present and there is a need or desire to increase tissue mass, therapeutic options become more involved, and less certain in outcome. Options to increase tissue mass include the use of autografts, allografts, xenografts and alloplastic materials. Autografts involve the transfer of tissue from one part of the patient to another (either as a vascularized graft or as a non-vascularized graft). The main drawbacks of autograft therapies are; the limited amount of tissue that is available for transfer, donor site morbidity and, in some cases, the complete lack of available or appropriate donor sites. In addition, in the case of non-vascularized bone grafts, resorption of the transferred tissue can result in decreased tissue mass and inadequate function and/or aesthetic outcome.
When autograft tissue is not available, allografts may often be used. Allografting involves the transfer of tissue between two individuals of the same species. Such procedures are not without problems however. Associated problems with this technique may include lack of donors, immunological response of the host, the need for immunosuppression to prevent immune rejection of the transferred tissue, revitalization of the grafted material by the host, and the possibility of disease transfer from donor tissue to the recipient. Xenograft therapies (transplantations from one species to another) circumvents the tissue supply problems associated with allografts, however the problem of xenograft immune rejection has yet to be solved. Immuno-isolation techniques involving encapsulation of xenograft cells show promise in some applications, especially those related to metabolic tissues, but have yet to reach clinical efficacy.
Much attention has been paid to the possibilities of generating or regenerating tissues. In the case of tissues which have some potential for self-regeneration (such as bone, cartilage and nerve), porous matrices, which are usually biodegradable, have been used to direct tissue formation. However, these regenerative processes are dependent on, and limited by, both device design and the regenerative potential inherent in the biological processes of the individual. This dependence may affect rate of formation, quantity and architecture of the resulting tissue. In the case of bone, porous materials, such as coralline hydroxyapatite and certain preparations of allograft bone, have been used as scaffolds to facilitate tissue growth into bony defects. This approach has been successful in instances associated with small defects but lacks the desired predictability of outcome in many clinically relevant large defects. Interaction of the host cells, e.g. the so called foreign body reaction, with the porous matrix also may limit the rate, quantity and architecture of the tissue formed within the device.
Recent research has also focused on the use of bioactive molecules or transplanted cells that have the potential to stimulate tissue formation. The local administration of cells or bioactive molecules alone is insufficient and does not result in predictable regeneration of tissue masses (Bessho 1996). Research efforts have therefore focused on the use of carriers to deliver bioactive molecules or act as scaffolds for transplanted cells. In addition the carriers act as scaffolds to direct cell growth and tissue formation. Such carriers usually take the form of space filling devices, such as three-dimensional porous networks, gels, microspheres or granular materials. Membranes which create and maintain a space for tissue regeneration have also been used as carriers for bioactive molecules.
Space filling devices have been used extensively in the field of bone regeneration to act as carriers for bioactive molecules known to stimulate bone formation (Wolfe and Cook, 1994). The materials used to fill a space where bone formation is required vary widely in their structural geometry and mechanical properties and include porous hydroxyapatite, allograft bone, collagen sponge and degradable polymer foams, scaffolds (Brekke, U.S. Pat. No. 5,683,459) and microspheres. These various approaches to bone regeneration each suffer one or more drawbacks.
For example, relatively strong and rigid materials, such as porous coralline hydroxyapatite, can withstand the forces created by surrounding soft tissue, wound contracture and local load induced stresses. These materials have the capacity to resist collapse of the geometric form defined by the material and thus maintain the original shape of the space occupied by the porous matrix. However, these materials also take up a significant proportion of the space which could otherwise be occupied by newly formed bone. As a consequence, such materials interfere with bone formation and also result in a potentially detrimental interface between bone and the biomaterial. The presence of a biomaterial interposed within bone can interfere with normal bone remodeling processes and can ultimately result in bone resorption or stress fractures (Spector 1991). In addition, with scaffolds or carriers constructed from synthetic degradable polymers, such as poly(a-hydroxyesters), a relatively large volume of material resulting in lower porosity, is required to produce a structure with sufficient strength. Consequently, there is less space available for bone formation and significantly greater quantities of degradation products. These degradation products can interfere with bone formation and can also result in bone resorption (Bostman 1992).
Many of these problems may be circumvented through the use of carriers such as collagen sponges which do not appear to significantly interfere with tissue formation or remodeling even during the degradation phase of the material. For example, Ksander et al. (U.S. Pat. No. 4,950,483), Chu et al. (U.S. Pat. No. 5,024,841) and Chu et al. (U.S. Pat. No. 5,219,576) describe a space filling collagen sponge with pores greater than 35 microns which may be used in conjunction with bioactive agents to promote wound healing. However, collagen sponges, especially those with suitable degradation time frames, are generally not able to withstand the above-listed in vivo stresses and consequently are unable to maintain the size and shape of the filled space. As a result, the newly created tissue assumes an ill-defined geometry which is not the same as the original shape of the sponge and which is often not of adequate or optimal functional or therapeutic benefit. Such an outcome is reported by Oppermann et al. (U.S. Pat. No. 5,354,557) who describes the use of a collagen sponge combined with osteogenic proteins for bone regeneration. Wolfe and Cook (1994) have also recognized the difficulty of controlling the geometry of bone formed using osteogenic proteins and state that “the osteoinductive effect of the protein can be difficult to confine to a limited anatomic area, especially using semi-solid carrier vehicles.” This same phenomenon can be seen with degradable synthetic polymer structures that, although they can be designed with appropriate mechanical stresses at the time of implantation, gradually lose their ability to withstand in vivo stresses and collapse at some point during degradation.
Kuboki et al. (1995) used bioactive molecules in conjunction with a flat, space-filling, unwoven glass fibril membrane to study bone formation. In this case, the majority of the tissue formed was cartilage that was located within the microstructure of the membrane. The desired bone tissue was therefore not formed and the cartilage
Cleek Robert L.
Cook Alonzo D.
Hardwick William R.
Mane Shrikant M.
Thomson Robert C.
Gore Enterprise Holdings Inc.
Sheets Eric J
Stewart Alvin
Willse David H.
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