Cartilage Tissue Engineering

Cartilage has limited repair capabilities. Because chondrocytes are bound in lacunae and cannot migrate to damaged areas. Moreover, cartilage is a hyaline tissue with no blood, lymphatic, or nerve supply. Therefore, cartilage damage is difficult to heal. Tissue engineering strategies involving the combination of cells, scaffolding biomaterials and bioactive agents to generate cartilage has emerged as a promising option for the repair and regeneration of damaged articular cartilage (see Fig. 6.6) [71].

Fig. 6.6 Cartilage tissue re-engineering. Schematic presentation of a potential treatment for OA lesions [71] (Copyright permission from Elsevier Science Ltd)

The combination of cells, scaffolds and growth factors could be either directly injected in the lesion or further grown in bioreactors in vitro to form new tissue. Neocartilage would finally be implanted in the lesion [71].

The use of autologous chondrocyte implantation may represent a promising technology for cartilage repair because of avoiding immunogenic response or transferring diseases. MSCs have been regarded as an attractive candidate in the repair and regeneration of cartilage. MSCs can be derived from bone marrow, adipose tissue, trabecular bone, periosteum, synovial membrane, and skeletal muscle, as well as teeth and umbilical cord [72]. In addition, the differentiation of MSCs to obtain hyaline-like structures in vitro, requires seeding and culturing in 3D configurations, which can adopt many forms depending on the geometry and the physicochemical characteristics of the surrounding cells [73]. Besides, cell sheet technology is increasingly considered as a potential way to reconstruct cartilage tissues for its non-use of scaffolds and no destruction of matrix secreted by cultured cells [74].

Building a biomaterial is important in cartilage tissue engineering. This biomaterial needs to repair articular cartilage to reproduce the mechanical properties of the original cartilage and can be integrated into the joint. Fibrin/hyaluronic acid composite hydrogels have been regard as appropriate scaffolds for in vivo artificial cartilage implantation [75]. Polyvinylalcohol/hydroxyapatite cryogel is a potent source of artificial cartilage. Poly vinyl alcohol (PVA) hydrogels are promising implants for cartilage regeneration due to their similar properties for chondrocyte seeding [76].

Although signaling molecules and matrix modifying agents have been used as biochemical stimuli toward cartilage tissue engineering and have led to improvements in the functionality of engineered cartilage, mechanical stimulation is a key factor in articular cartilage generation and maintenance [77]. Bioreactor systems have been designed and built in order to delivery specific types of mechanical stimulation. Using different bioreactors, many researchers have studied the responses of the chondrocytes to well-defined mechanical forces, including compression, shear stress, and hydrostatic pressure. Appropriate mechanical stimulation can lead to increased chondrogenic properties in the bioreactors for articular cartilage tissue engineering [78].

Cartilage is a complex tissue type, therefore it is difficult to reproduce the finely balanced structural interactions of cartilage. OA is a complicated disease, with many factors giving rise to disturbed cartilage homeostasis and joint inflammation. A tissue-engineering approach combining cells, biomaterials, biofactors and disease-modifying OA drugs could be a relevant approach for improving OA treatment [71]. In addition, bioprinting technology may be the ultimate solution to engineer cartilage tissue.

Fig. 6.7 Schematic diagram of the blood vasculature including arterial (arteries, larger arterioles), capillary (smaller arterioles, capillaries), and venous (venules, veins) compartments [79] (Copyright permission from Elsevier Science Ltd)