Compositions and methods for the treatment and repair of defects or lesions in articular cartilage using synovial-derived tissue or cells

Abstract

Compositions and methods are provided for treatment of cartilage defects in animals and humans. The compositions of the invention include synovial tissue, synovial cells and matrices containing synovial (or cambium) tissue or cells for use in filling a cartilage defect. The matrix and synovial tissue or cell preparations may also contain a proliferation agent, transforming factor or other active agents to promote healing. A controlled-release delivery system may be used to administer the transforming factor. The compositions of the invention also include a synovial covering membrane or devitalized fascial sheet for covering the cartilage defect. The methods of this invention are those in which a minimally invasive surgical intervention is performed to remove a small portion of synovial membrane from a joint. Portions of the synovial membrane, or cells expanded in vitro, are implanted alone or within a matrix, into the defect site, where they produce new cartilage tissue and repair the defect. Alternatively, partially transformed synovial-derived tissue may be formed in situ and implanted into the defect site.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional of U.S. application Ser. No. 10 / 060,009, filed on Jan. 30, 2002, which claims the benefit of U.S. Provisional Application Ser. Nos. 60 / 265,053 and 60 / 265,064, both filed on Jan. 30, 2001, the contents of each of which are incorporated herein by reference in their entirety.TECHNICAL FIELD OF THE INVENTION [0002] This invention relates to the treatment and repair of defects or lesions (used interchangeably herein) in cartilage. The compositions of the invention include matrices and synovial tissue or cells for use in filling a cartilage defect. Cambium cells may also be used. The matrices and synovial tissue or cell preparations may also contain a proliferation agent and / or transforming factor to facilitate, respectively, expansion of synovial cells and differentiation of synovial cells into chondrocytes, leading to the formation of cartilage tissue. The compositions of the invention also include synovial ...

AI Technical Summary

Benefits of technology

[0020] The present invention provides effective therapeutic compositions and methods to induce the repair of lesions in cartilage of humans and other animals. Use of the compositions and methods of this invention also promotes the healing of traumatic lesions and forms of osteoarthritis that would otherwise lead to loss of effective joint function leading to probable resection and replacement of the joint with a metal and / or plastic artificial joint.

Problems solved by technology

These are full-thickness defects and superficial defects.

These defects differ not only in the extent of physical damage to the cartilage, but also in the nature of the repair response each type of lesion can elicit.

Full-thickness defects can cause severe pain because the bone plate contains sensory nerve endings.

Such defects are notorious because they generally do not heal and show no propensity for repair reactions.

Superficial defects may have no known cause, but often they are the result of mechanical derangements that lead to a wearing down of the cartilaginous tissue.

However, although painless, superficial defects generally do not heal, and often degenerate into full-thickness defects.

It is theorized that chondrocytes in cartilaginous tissue are normally not exposed to sufficient amounts of repair-stimulating agents such as growth factors and fibrin clots typically present in damaged vascularized tissue.

Unfortunately, the repair response of the tissue to such surgical trauma is usually comparable to that observed to take place naturally in full-thickness defects that cause bleeding, viz., formation of a fibrous type of cartilage that exhibits insufficient biomechanical properties and that does not persist on a long-term basis [Buckwalter et al.

Nevertheless, despite claims of various methods to elicit a repair response in damaged cartilage, none of these treatments has received substantial application [Buckwalter et al.

And such treatments have generally provided only temporary relief.

However, such agents have not been shown to promote repair of lesions or defects in cartilage tissue.

This approach suffers from the disadvantages of being more invasive than the instant invention, and creating additional cartilage defects by removing mature cartilage.

The use of articular chondrocytes to repair defects is also disadvantaged because articular chondrocytes have a more limited potential for proliferation as compared to synovial cells.

These covering membranes or other artificial covering membranes have the significant disadvantage that the covering membrane itself does not transform into cartilage tissue, or does so to only a limited extent.

Moreover, the degradation of fibrous types of covering membranes is extremely slow.

In addition, these covering membranes do not integrate with the native tissue along the defect lesion borders.

Such covering membrane tissue may contain fibroblasts, which will not transform into chondrocytes but instead result in undesirable scar-like tissue.

Thus, in certain prior art covering membranes, fibroblasts may migrate out into the repair space, contaminate it and lead to unwanted scar tissue formation.