Roles of the calcified cartilage layer and its tissue engineering reconstruction in osteoarthritis treatment

Abstract

Sandwiched between articular cartilage and subchondral bone, the calcified cartilage layer (CCL) takes on both biomechanical and biochemical functions in joint development and ordinary activities. The formation of CCL is not only unique in articular cartilage but can also be found in the chondro-osseous junction adjacent to the growth plate during adolescence. The formation of CCL is an active process under both cellular regulation and intercellular communication. Abnormal alterations of CCL can be indications of degenerative diseases including osteoarthritis. Owing to the limited self-repair capability of articular cartilage and core status of CCL in microenvironment maintenance, tissue engineering reconstruction of CCL in damaged cartilage can be of great significance. This review focuses on possible tissue engineering reconstruction methods targeting CCL for further OA treatment.

Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts

“…The articulating ends of the bones are enveloped in a smooth, hyaline cartilage layer designed to minimize friction and offer cushioning, thus giving rise to a synovial cavity encapsulated by a sturdy capsule, serving to stabilize it [75]. At the interface between the bone and the hyaline cartilage, a chondro-osseous junction is present in the form of mineralized cartilage, bound to the bone by a lower cement line and, by the upper tidemark, to the articular soft cartilage [76,77]. The capsule comprises an outer layer of densely packed connective tissue, which is sparsely vascularized but richly innervated, firmly attached around the entire circumference of each bone articular end.…”

“…The discovery that these vesicles are enriched with microRNAs hints at a greater complexity underlying the process than previously understood [123]. From the bone marrow, new vessels and sensitive nervous terminations start to grow through the new fissures in the osteochondral junction, surrounded by novel bone [76]. This phenomenon also arises from the migration and excessive proliferation of new chondrocytes, which commence depositing new layers of type X collagen.…”

“…surrounded by novel bone [76]. This phenomenon also arises from the migration and excessive proliferation of new chondrocytes, which commence depositing new layers of type X collagen.…”

Recent development in multizonal scaffolds for osteochondral regeneration

“…To address this issue, cell-based approaches have been attempted using chondrocytes to form a CCL by secreting type II collagen and a mineral phase, but the degree of control of this technique remains low [ 101 ]. On the other hand, scaffold-based strategies have been made with their structure, composition, and mechanical and biological properties exquisitely tailored through various chemical modifications such as by incorporating inorganic bioceramics or bioglasses [ 102 , 103 ]. More importantly, a CCL barrier allowing the transportations of oxygen and nutrition while minimizing cell passage can be obtained by both densifying the layer and reducing the pore size [ 98 ].Recent studies on trilayered scaffolds with an intermediate dense layer exhibited not only superior regeneration of hyaline-like cartilage and subchondral bone tissue in vivo [ [104] , [105] , [106] ], but also improved mechanical properties of the neo-formed tissues compared to bilayered scaffolds [ 64 , 104 ].…”

High Hopes for the Biofabrication of Articular Cartilage—What Lies beyond the Horizon of Tissue Engineering and 3D Bioprinting?

“…In the transition zone, collagen fibres are randomly oriented, while in the deep zone, they appear to be parallel to each other and perpendicular to the superficial zone. In the calcified zone, there is less collagen (~20%) and more ossification [ 5 ]. This unique arrangement of cells and ECM components (mainly different types of collagens, proteoglycans, and 65–80% water) provides the required mechanical load-bearing properties of this type of connective tissue [ 6 , 7 ].…”