STRATEGY FOR TISSUE ENGINEERING OF OSTEOCHONDRAL CONSTRUCTS

摘要

Damage to articular cartilage is a common condition affecting the joints of millions of people. This is a major problem considering the poor regenerative capacity of adult articular cartilage and the disability and pain that accompanies these injuries. There exists a range of options that have been applied in clinical practice, with variable degrees of success, for repair of focal lesions and damage of the articular surface, including tissue adhesives, enzymatic treatments and laser solder welding, autograft cell/tissue transfer via osteoperiosteal grafts, osteochondral grafts (mosaicplasty)and Carticel. The poor healing capacity of articular cartilage, potential for donor site pain and morbidity in autograft procedures, risk of disease transmission in allograft procedures, and the limited longevity of arthroplasty systems (i.e., ～15 years for a total knee arthroplasty), has generated considerable research efforts to develop cell-based therapies for articular cartilage repair and replacement. Our laboratory has been applying physiologic loading to chondrocyte-seeded agarose hydrogel constructs in an effort to engineer a tissue possessing functional properties capable of withstanding the harsh joint loading environment. It is well known that partial-thickness defects in articular cartilage do not heal spontaneously, whereas injuries that penetrate the subchondral bone undergo some repair. With the aim to promote the greatest possible graft-host tissue integration in vivo, we have begun to consider the development (and subsequent physiologic loading) of a stratified agarose construct consisting of chondrocytes and bone cells that mimics the normal articular cartilage-bone interface (schematically presented in Fig. 1). There is limited information in the literature regarding the behavior of bone cells cultured in a three dimensional agarose hydrogel culture To this end, we have cultured osteoblast-like cells in three-dimensional agarose (free-swelling) constructs in order to characterize their phenotypic stability and biosynthetic behavior.