Morphogenesis and Morphogenetic Proteins for Articular Cartilage Regeneration

Morphogenesis is the developmental cascade of pattern formation, establishment of body plan and the architecture of mirror-image bilateral symmetry of musculoskeletal structures culminating in the adult form. Regenerative medicine is the emerging discipline of the science of design and manufacture of spare parts for the human body including the skeleton to restore function of lost parts due to cancer diseases and trauma. Regenerative medicine and surgery are based on rational principles of molecular developmental biology and morphogenesis and is further governed by principles of bioengineering and biomechanics.

The three key elements for regenerative medicine and surgery are inductive morphogenetic signals, responding stem cells, and the extracellular matrix (ECM) scaffolding. Recent advances in molecular cell biology of morphogens will aid in the design principles and architecture for regenerative medicine and sur­gery. Regeneration recapitulates in part embryonic development and morphogenesis.

Among many tissues in the human body, bone has considerable powers for regeneration and therefore is a prototype model for tissue engineering. On the other hand, cartilage is feeble in its prowess for regeneration. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. The sequential cascade of bone morphogenesis mimics sequential skeletal morphogenesis in limbs and permitted the isolation of bone morphogens.

Although it is traditional to study morphogenetic signals in embryos, bone morphogenetic proteins (BMPs), the primordial inductive signals for bone were isolated from demineralized bone matrix from adults. BMPs initiate, promote, and maintain chondrogenesis and osteogenesis and have actions beyond bone. The cartilage-derived morphogenetic proteins (CDMPs) are critical for cartilage and joint morphogen­esis.

The symbiosis of bone inductive and conductive strategies is critical for regenerative medicine, and is in turn governed by the context and biomechanics. The context in bone is the microenvironment, consisting of ECM scaffolding and can be duplicated by biomimetic biomaterials such as collagens, hydroxyapatite, proteo-glycans, and cell adhesion proteins including fibronectins and laminins. The rules of architecture for regener­ative medicine and surgery are an imitation and adaptation of the laws of developmental biology and morphogenesis, and thus may be universal for all tissues, including musculoskeletal tissues and a variety of other tissues in the human body.

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