BIO-INSPIRED MORPHOGENS AND BIOMIMETIC BIOMATERIALS FOR REGENERATIVE MEDICINE

摘要

Regenerative medicine is the science of design and manufacture of parts for functional restoration of damaged tissues due to cancer, disease and trauma. Morphogenesis is the developmental cascade of pattern formation, body plan establishment and differentiation of tissues culminating in adult form. Regeneration in general, recapitulates in parts, embryonic morphogenesis. Thus, the principles of morphogenesis can be applied to tissue engineering for regenerative medicine and surgery. The three-key ingredients for tissue engineering and regenerative medicine are inductive morphogens, responding stem cells, and extracellular matrix materials. Therefore bioactive morphogens can be integrated into materials for functional restoration by tissue engineering. A morphogen is a morphogenetic protein signal that acts on responding stem cells. Bone morphogenesis is induced by bone morphogenetic proteins (BMPs). BMPs play a role in pattern formation, cell differentiation, maintenance and regeneration of tissues. BMPs are pleiotropic and act on chemotaxis, mitosis and differentiation of progenitor stem cells. There are nearly twenty BMPs in the human genome. BMPs have actions beyond bone in development of teeth, heart, kidney, eye, skin, and brain. Thus, BMPs may be called body morphogenetic proteins. Stem cells are primordial cells with unlimited replicative potential and can be programmed by morphogens such as BMPs. Extracellular matrix is the native scaffolding material that can be used to deliver morphogens such as BMPs for tissue engineering of bone. Biomimetic materials are typically synthetic, polymeric structures that mimic extracellular matrix scaffolding by presenting the cellular binding sites found within collagens, fibronectin, proteoglycans and glycoproteins. Materials that mimic extracellular matrix scaffolding such as BMPs bind to collagens I&IV, heparan sulfate and heparin. BMPs bound to collagen acts as a composite biomaterial to initiate bone formation and the shape can be molded by an appropriate template. In addition to including BMPs in a carrier matrix, the geometry of the carrier matrix is critical for optimal tissue engineering. For example: collagen particles smaller than 44 μm are feeble in bone induction compared to the coarse (420μm) particles. Gene therapy approaches using genes for morphogenesis such as BMPs allows a sustained, prolonged secretion of gene products. Thus, morphogens integrated into biomaterials may be useful in regenerative medicine.