Methods and reagents for tissue engineering of cartilage in vitro

Abstract

The present invention makes available an optimal concentration of a hedgehog polypeptide for modulating growth and / or cartilage production by chondrocytes. The present invention allows for improvements in the culturing of chondrocytes to develop cartilaginous tissue ex vivo suitable for implantation to replace damaged or deteriorated cartilage in a patient.

Description

BACKGROUND OF THE INVENTION [0001] Cartilage is a structural tissue constructed from a variety of hydrated biopolymers. By weight, water comprises 70% to 80% of cartilage. The remaining 20% to 30% comprises extracellular biopolymers such as collagen (primarily type-II) and proteoglycan. The collagen usually accounts for 70% of the dry weight of cartilage (in “Pathology” (1988) Eds. Rubin & Farber, J. B. Lippincott Company, PA. pp. 1369-1371). Proteoglycans are composed of a central protein core from which long chains of polysaccharides extend. These polysaccharides, called glycosaminoglycans, include: chondroitin-4-sulfate; chondroitin-6-sulfate; and keratan sulfate. Chondrocytes are cells responsible for the ordered production and secretion of the cartilagenous polymers. The properties of cartilage are primarily determined by the quantity and quality of the extracellular biopolymers. [0002] Three types of cartilage are present in mammals and include: hyaline cartilage, fibrocartila...

AI Technical Summary

Benefits of technology

This approach leads to increased proteoglycan and collagen production, resulting in more mature and mechanically resistant cartilage constructs, suitable for repairing defects and improving the integration and persistence of the repair tissue.

Problems solved by technology

Since the subchondral bone tissue is both innervated and vascularized, damage to this tissue is often painful.

The repair reaction induced by damage to the subchondral bone usually results in the formation of fibrocartilage at the site of the full-thickness defect.

Fibrocartilage, however, lacks the biomechanical properties of articular cartilage and fails to persist in the joint on a long term basis.

Partial-thickness defects are caused by mechanical arrangements of the joint which in turn induce wearing of the cartilage tissue within the joint.

In the absence of innervation and vasculature, partial-thickness defects do not elicit repair responses and therefore tend not to heal.

Although painless, partial-thickness defects often degenerate into full-thickness defects.

It is believed that chondrocytes transplanted in this manner lose their viability during transplantation and that the procedure may result in the formation of fibrocartilage or islands of cartilage embedded in fibrous tissue at the site of the defect.

The introduction of non-autologous materials into a patient, however, may stimulate an undesirable immune response directed against the implanted material.

Monitoring the formation and development of the resulting synthetic cartilage in situ can be difficult to perform and usually involves an arthroscopic or open joint examination.

Furthermore, implants containing synthetic polymer components may be unsuitable for repairing large cartilage defects since polymer hydrolysis in situ may inhibit the formation of cartilage and / or its integration into the defect.

This approach, however, may have problems similar to those associated with the first approach, herein above.

In vitro tissue engineering of cartilage on a polymer matrix is problematic because the resultant cell-polymer construct often has properties that are unfavorable for successful grafting.

Particularly, the quantity and quality of secreted polymers does not adequately mimic that found in natural cartilage.

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