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

a technology of synovial-derived tissue or cells and compositions, applied in the direction of skeletal/connective tissue cells, prostheses, peptide/protein ingredients, etc., can solve the problems of severe pain, full thickness defects and superficial defects, extent of physical damage to the cartilage, etc., to induce cartilage lesions and effective therapeutic compositions and methods, the effect of promoting healing

Inactive Publication Date: 2008-02-14
ORTHOGENE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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

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

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example i

Use of Synovial Membranes to Cover Articular Cartilage Defects In Vivo

[0115] In order to test the effectiveness of using a synovial membrane to cover articular cartilage defects, defects 5 mm wide, 10 mm long and 0.7 mm deep were created with a planing instrument in mature goats. The new defects were filled with a fibrin matrix containing free proliferation agent (IGF-1) at a concentration of 40 ng / ml and a liposome-encapsulated transforming growth factor (BMP-2) at a concentration of 1.0 μg / ml. The defect was then covered with a synovial membrane that was excised from the joint wall, of the same dimensions, and sutured to the defect borders by vycril 7.0 suture material by using single interrupted sutures. After closure of the joint the animals were kept with the joint immobilized in a soft cast over 4 weeks (n=6 animals). Following euthanasia and histological analysis, it was found that the synovial membrane was well incorporated into the surrounding cartilage tissue border, and ...

example ii

B. Partial Devitalization of Synovial Tissue Prior to Transplantation

[0117] The experiment in II. A. (above) was modified such that the transplanted synovial covering membrane was frozen a single time and immediately thawed. This was also done with the synovial tissue bits in order to reduce the number of macrophages present in the synovial tissue. By adding this step, a more homogenous transformation of cartilage tissue was achieved.

example iii

Use of Stacks of Synovial Membranes To Repair Articular Cartilage Defects In Vivo

[0118] The experiment described in Example I. (above) was modified such that the defect was filled with stacks of synovial membranes of the approximate dimensions of the defect itself. Prior to placement in the defect, each of the synovial membranes was soaked in a BMP-2 solution at a concentration of 4.4 mg / ml, to induce transformation into cartilage tissue. Additionally, between the layers of synovial membranes, a small amount of fibrin matrix or microspheres containing transforming factors (BMP-2, 4.4 mg / ml) was deposited to allow for the controlled release of the transforming factor. Macroscopic results showed transformation of the synovial tissue into cartilage-like tissue.

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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 ...

Claims

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Application Information

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IPC IPC(8): A61K35/12A61F2/00A61K45/00A61L27/00A61F2/02A61F2/28A61F2/30A61F2/46A61K35/32A61L27/36A61L27/38
CPCC12N5/0655A61L27/3852C12N2533/56A61L27/3817A61L27/3804A61L27/3683A61L27/3654A61L27/3612A61F2002/2817A61F2002/30062A61F2002/30677A61F2002/30761A61F2002/4635A61F2210/0004A61K35/12A61K35/32A61K38/1841A61K38/1875A61K38/51A61L27/3604A61K2300/00A61P19/00A61P19/02A61P19/04A61K38/18
Inventor HUNZIKER, ERNST B.
Owner ORTHOGENE
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