專題討論5:尖端科技與未來醫療

S5-2
Cartilage Tissue Engineering Turning Research into Products
田英俊院長
高雄醫學大學醫學院

  Due to the lack of vascularity and the paucity of undifferentiated cells, articular cartilage has an extremely limited self-healing potential, If a focal cartilage lesion is left untreated, it almost progress to more extensive defect and later ultimately require joint replacement surgery. Thus, reparative approaches have been designed to replace the damaged cartilage.
Microfracture procedures provide access to biological healing molecules and mesenchymal stem cells from bone marrow by drilling through subchondral bone into the bone marrow. This allows the bone marrow stem cells to differentiate into chondrocyte-like cells, developing a cartilage layer of tissue at the defect site. However, this approach often results in fibrocartilage formation which is mechanically inferior to articular hyaline cartilage.
Autologous chondrocyte implantation (ACI) uses healthy cartilage harvested from the patient for autologous chondrocyte isolation and their ex vivo expansion. The chondrocytes are then seeded onto the defect site and localized with a periosteal flap or synthetic membrane. Long term postoperative analysis of the defect site has shown varying results, with much of the site being filled with fibrocartilage and Collagen I.
Tissue engineering involving specialized scaffolds that can support bone and cartilage layer regeneration along with the development of native-like bone cartilage interface. The three principal components of tissue engineering are scaffolds, cells, and bioactivators.
1.Scaffolds: The optimal scaffold, in addition to being able to support cell attachment, proliferation and in-growth, the scaffold must also withstand functional site loading and must also be able to regenerate tissue that is similar to that of the native tissue. Hybrid materials are now most accepted for building scaffold, which contain natural origin materials to provide the niche for cartilage regeneration and synthetic material to provide mechanical support. On the architectural arrangement, the scaffold had been designed with monophasic, bi-phasic, tri-phasic, gradient configurations.
2.Cells:  Articular chondrocytes have been extensively used in the past years for autologous chondrocyte transplantation. However, the use of articular chondrocytes is limited by morbidity at the harvest site, the requirement of a second surgical procedure, and cell dedifferentiation due to in vitro expansion.
Substantial clinical information shows the suitability of adult stem cells for cartilage tissue engineering. These stem cells had been isolated from several tissues: bone marrow, synovium, adipose tissue, periosteum, peripheral blood, and umbilical cord blood, as well as from the inner part of cartilage of the knee.
3.Bioactivators: Both chondrocytes and mesenchymal stem cells are troubled with fibroblastic de-differentiation and terminal differentiation to a hypertrophic phenotype in vivo. It is therefore likely that these cell types will require some degree of modulation to be applied successfully. This may be provided by the addition of growth factors such as Transforming growth factor-β (TGF-β), Bone morphogenetic proteins (BMP), Insulin-like growth factor-1 (IGF-I), Fibroblast growth factor, Platelet-derived growth factor, and Vascular endothelial growth factor.
 Right now, there are 33 ongoing clinical trials or interventional studies are pursued for the investigation of new approaches in the field of chondral and osteochondral repair studies. Although tissue engineering has already shown tremendous progress, a long and difficult road in the regulatory and legal path has to be travelled in order to transform new therapeutic approaches into a clinical reality.