Scaffold-free approaches for the fabrication of engineered articular cartilage tissue

Tissue engineered cartilaginous constructs have meet great advances in the past decades as a treatment for osteoarthritis, a degenerative disease affecting people all over the world as the population ages. Scaffold-free tissue engineered constructs are designed and developed in recent years with only cells and cell-derived matrix involved. Scaffold-free tissue constructs do not require cell adherence on exogenous materials and are superior to scaffold-based constructs in (a) relying on only cells to produce matrix, (b) not interfering cell-cell signaling, cell migration or small molecules diffusion after implantation and (c) introducing no exogenous impurities. In this review, three main scaffold-free methodologies for cartilage tissue engineering, the cell sheet technology, the phase transfer cell culture-living hyaline cartilage graft system and the cell aggregate-based (bottom-up) methods, were reviewed, covering mold fabrication, decellularization and 3D bioprinting. The recent advances, medical applications, superiority and drawbacks were elaborated in detail.