Morphogenesis and Tissue Engineering of Bone and Cartilage: Inductive Signals, Stem Cells, and Biomimetic Biomaterials

Abstract

Morphogenesis is the developmental cascade of pattern formation, body plan establishment, and the architecture of mirror-image bilateral symmetry of many 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 molecular developmental biology and morphogenesis governed by bioengineering. The three key ingredients for both morphogenesis and tissue engineering are inductive signals, responding stem cells, and the extracellular matrix. Among the many tissues in the human body, bone has considerable powers for regeneration and is a prototype model for tissue engineering based on morphogenesis. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. This model mimics sequential limb morphogenesis and permitted the isolation of bone morphogens. Although it is traditional to study morphogenetic signals in embryos, bone morphogenetic proteins (BMPs), the inductive signals for bone, were isolated from demineralized bone matrix from adults. BMPs and related cartilage-derived morphogenetic proteins (CDMPs) initiate, promote, and maintain chondrogenesis and osteogenesis and have actions beyond bone. The symbiosis of bone inductive and conductive strategies are critical for tissue engineering, and is in turn governed by the context and biomechanics. The context is the microenvironment, consisting of extracellular matrix, which can be duplicated by biomimetic biomaterials 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 morphogenesis, and thus may be universal for all tissues, including bones and joints.

The chondrogenic differentiation of mesenchymal stem cells on an extracellular matrix scaffold derived from porcine chondrocytes

“…The design principles of scaffolds have recently been focused on ECM molecules, because they can play a key role in cell attachment, proliferation, and differentiation [8,9]. The ECM contains many macromolecules such as proteoglycans, collagens, laminins, fibronectin and sequestered growth factors that are favorable for cell Table 2 Quantitative analysis of the chondrogenic and calcified areas in the specimens retrieved from the in vivo experiment.…”

“…In addition to supporting the structural integrity of engineered tissues, ECM materials can have diverse physiological functions by acting as a reservoir of cytokines and growth factors, transmitting specific signals through interactions with cell surface receptors, and providing specific microenvironments similar to natural tissues [7,8]. The composition and structure of ECM materials can affect the cell phenotype, attachment, migration and proliferation of cells [9].…”

Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization

“…(3) Recent evidence indicates that many of the bone extracellular matrix and signaling molecules, such as osteopontin, SPARC, fibronectin, collagens, and BMPs, are pleiotropic in nature and serve multiple functions ranging from pattern formation, osteoinduction, and osteoclastogenesis to the control of cell proliferation, cell differentiation, and cell adhesion. (4)(5)(6)(7)(8) In the present study, we focus on the role of a characteristically pleiotropic extracellular matrix molecule, the secretory calcium-binding phosphoprotein (SCPP) family member ameloblastin (AMBN).…”

Potential of bone scaffolds containing vancomycin and bone morphogenetic protein-2 in a rat model of osteomyelitis

“…In addition, bone morphogenetic protein-2 (BMP-2) has been clinically applied for fractures and nonunions because it is the most potent osteoinductive factor [8]. For effective treatment of open fractures and osteomyelitis by diminishing the systemic toxicity of the antibiotic, problems relating to protein instability, and rapid clearance after in vivo bolus administration, it is necessary to develop advanced vehicles for the sustained local release of antibiotics.…”