Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Implantable prosthesis – Tissue
Reexamination Certificate
2001-03-05
2002-09-17
Smith, Jeffrey A. (Department: 3732)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Implantable prosthesis
Tissue
Reexamination Certificate
active
06451060
ABSTRACT:
The present invention relates to the method of production of cartilage tissue for surgical implantation into human joints for the purpose of filling defects of the articular cartilage or replacing damaged or degenerated cartilage.
BACKGROUND OF THE INVENTION
Cartilage Injury and Repair
Human joint surfaces are covered by articular cartilage, a low friction, durable material that distributes mechanical forces and protects the underlying bone. Injuries to articular cartilage are common, especially in the knee. Data from the Center for Disease Control (CDC) and clinical studies have suggested that approximately 100,000 articular cartilage injuries occur per year in the United States. Such injuries occur most commonly in young active people and result in pain, swelling, and loss of joint motion. Damaged articular cartilage does not heal. Typically, degeneration of the surrounding uninjured cartilage occurs over time resulting in chronic pain and disability. Cartilage injuries therefore frequently lead to significant loss of productive work years and have enormous impact on patients' recreation and lifestyle.
Joint surface injuries may be limited to the cartilage layer or may extend into the subchondral bone. The natural histories of these types of injuries differ. Cartilage injuries which do not penetrate the subchondral bone have limited capacity for healing (1). This is due to properties inherent to the tissue. Nearly 95 percent of articular cartilage is extracellular matrix (ECM) that is produced and maintained by the chondrocytes dispersed throughout it. The ECM provides the mechanical integrity of the tissue. The limited number of chondrocytes in the surrounding tissue are unable to replace ECM lost to trauma. A brief overproduction of matrix components by local chondrocytes has been observed (2); however, the response is inadequate for the repair of clinically relevant defects. Cellular migration from the vascular system does not occur with pure chondral injury and extrinsic repair is clinically insignificant.
Osteochondral injuries, in which the subchondral bone plate is penetrated, can undergo healing due to the influx of reparative cells from the bone marrow (1). Numerous studies have shown, however, that the complex molecular arrangement of the ECM necessary for normal cartilage function is not recapitulated. The repair response is characterized by formation of fibrocartilage, a mixture of hyaline cartilage and fibrous tissue. Fibrocartilage lacks the durability of articular cartilage and eventually undergoes degradation during normal joint use Many osteochondral injuries become clinically asymptomatic for a period of a few to several years before secondary degeneration occurs. However, like isolated chondral injuries, these injuries ultimately result in poor joint function, pain, and disability.
Molecular Organization of the ECM
The physical properties of articular cartilage are tightly tied to the molecular structures of type II collagen and aggrecan. Other molecules such as hyaluronan and type IX collagen play important roles in matrix organization. Type II collagen forms a 3-dimensional network or mesh that provides the tissue with high tensile and shear strength (3). Aggrecan is a large, hydrophilic molecule, which is able to aggregate into complexes of up to 200 to 300×10
6
Daltons (4)]. Aggrecan molecules contain glycosaminoglycan chains that contain large numbers of sulfate and carboxylate groups. At physiological pH, the glycosaminoglycan chains are thus highly negatively charged (5). In cartilage, aggrecan complexes are entrapped within the collagen network. A Donnan equilibrium is established in which small cations are retained by electrical forces created by the sulfate and carboxylate groups (6). Water is in turn retained by the osmotic force produced by large numbers of small cations in the tissue.
When the joint is mechanically loaded, movement of water results in perturbation of the electrochemical equilibrium. When the load is removed, the Donnan equilibrium is reestablished and the tissue returns to its pre-loaded state (7). The physical properties of articular cartilage are tightly tied to the molecular structures of type II collagen and aggrecan. Other matrix molecules, such as hyaluronan (8) and type IX collagen (9), play important roles in matrix organization. Failure to restore the normal molecular arrangement of the ECM leads to failure of the repair tissue over time, as demonstrated by the poor long-term performance of fibrocartilage as a repair tissue (10).
Distinct compartments have been demonstrated within the ECM. These differ with respect to the composition and turnover of matrix macromolecules. Immediately surrounding each chondrocyte is a thin shell of ECM characterized by a relatively rapid turnover of matrix components (11). This region is termed the pericellular matrix (11). Surrounding the pericellular matrix is the territorial matrix. Further from the cells is the interterritorial matrix (11). Turnover of matrix macromolecules is slower in the interterritorial matrix than in the pericellular and territorial matrices (11). The role that these various compartments play in the function of the tissue as a whole is unclear. From the perspective of articular cartilage repair, however, they represent a higher level of matrix organization that must be considered in the restoration of injured tissue.
Surgical Treatment of Articular Cartilage Injury
Current methods of surgical restoration of articular cartilage fall into three categories: (1) stimulation of fibrocartilaginous repair; (2) osteochondral grafting; and (3) autologous chondrocyte implantation. Fibrocartilage, despite its relatively poor mechanical properties, can provide temporary symptomatic relief in articular injuries. Several surgical techniques have been developed to promote the formation of fibrocartilage in areas of cartilage damage. These include subchondral drilling, abrasion, and microfracture. The concept of these procedures is that penetration of the subchondral bone allows chondroprogenitor cells from the marrow to migrate into the defect and effect repair. The clinical success rate of this type of treatment is difficult to assess. In published series, success rates as high as 70% are reported at 2 years; however, the results deteriorate with time. At five years post-treatment, the majority of patients are symptomatic.
In osteochondral grafting, articular cartilage is harvested with a layer of subchondral bone and implanted into the articular defect. Fixation of the graft to the host is accomplished through healing of the graft bone to the host bone. The major advantage of this technique is that the transplanted cartilage has the mechanical properties of normal articular cartilage and therefore can withstand cyclical loading. The major disadvantages are donor-site morbidity (in the case of autograft) and risk of disease transmission (in the case of allograft). Additionally, tissue rejection can occur with allografts which compromises the surgical result. Osteochondral autografting (mosaicplasty) has demonstrated short-term clinical success. The long-term effectiveness is unknown. Osteochondral allografts are successful in approximately 65% of cases when assessed at 10 years post-implantation, but are generally reserved for larger areas of damage extending deep into the subchondral bone.
Autologous chondrocyte implantation is a method of cartilage repair that uses isolated chondrocytes. Clinically, this is a two-step treatment in which a cartilage biopsy is first obtained and then, after a period of ex vivo processing, cultured chondrocytes are introduced into the defect (12). During the ex vivo processing, the ECM is removed and the chondrocytes are cultured under conditions that promote cell division. Once a suitable number of cells are produced, they are implanted into the articular defect. Containment is provided by a patch of periosteum which is sutured to the surrounding host cartilage. The cells attach to the defect walls and produce the extracel
Hejna Michael
Masuda Koichi
Thomar Eugene J-M. A.
Foley & Lardner
Rush-Presbyterian-St. Luke's Medical Center
Smith Jeffrey A.
LandOfFree
Cartilage matrix and in vitro production of transplantable... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Cartilage matrix and in vitro production of transplantable..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cartilage matrix and in vitro production of transplantable... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2884499