Morphogenesis and tissue engineering of bone and cartilage: Inductive signals, stem cells, and biomimetic biomaterials

Morphogenesis is the developmental cascade of pattern formation, body plan establishment, and the architecture of mirror-image bilateral symmetry of m any structures and asymmetry of some, culminating in the adult form. Tissue engineering is the emerging discipline of design and construction of spare parts for the human body to restore function based on principles of molecu lar developmental biology and morphogenesis governed by bioengineering. The three key ingredients for both morphogenesis and tissue engineering are in ductive signals, responding stem cells, and the extracellular matrix. Among the many tissues in the human body, bone has considerable powers for regen eration and is a prototype model for tissue engineering based on morphogene sis. Implantation of demineralized bone matrix into subcutaneous sites resu lts in local bone induction. This model mimics sequential limb morphogenesi s and permitted the isolation of bone morphogens. Although it is traditiona l to study morphogenetic signals in embryos, bone morphogenetic proteins (B MPs), the inductive signals for bone, were isolated from demineralized bone matrix from adults. BMPs and related cartilage-derived morphogenetic prote ins (CDMPs) initiate, promote, and maintain chondrogenesis and osteogenesis and have actions beyond bone. The symbiosis of bone inductive and conducti ve strategies are critical for tissue engineering, and is in turn governed by the context and biomechanics. The context is the microenvironment, consi sting of extracellular matrix, which can be duplicated by biomimetic biomat erials such as collagens, hydroxyapatite, proteoglycans, and cell adhesion proteins including fibronectins. Thus, the rules of architecture for tissue engineering are an imitation of the laws of developmental biology and morp hogenesis, and thus may be universal for all tissues, including bones and j oints.