Figure 2. The phases of self-assembly and cartilage development.

Self-assembling articular cartilage forms in a manner reminiscent of cartilage morphogenesis. In the first phase of self-assembly (a), a high-density cell solution is seeded in a non-adherent well. During phase two (b), minimization of free energy occurs as cells bind to one another via cell-adhesion receptors like N-cadherin. In phase three (c), extracellular matrix synthesis is up-regulated. Finally, the engineered tissue matures as distinct regions develop and native tissue-like functional properties are approached (d). Similarly, the process of long bone formation is mediated first by mesenchymal condensation (e). Robust matrix deposition begins as cells differentiate (f), following chemotactic agents to elongate the bone in opposite directions (g). Over time, the core forms a site for vascularization to become bone (h).