Biomimetic biomaterial scaffolds for bone and cartilage regeneration

Regeneration is in part recapitulation of embryonic development and morphogenesis. Morphogenesis is the developmental cascade of pattern formation, body plan establishment and differentiation of tissues including bone and cartilage. Regenerative medicine is the science of design of tissues for functional restoration of damaged tissues. The three key elements of regenerative medicine are morphogens, stem cells and scaffolds of biomaterials. Biomaterials that mimic the tissue of interest will be most optimal for regeneration. Bone has considerable potential for regeneration. Yet, cartilage on adjacent tissue is feeble in the regenerative capacity. We have systematically investigated bone and cartilage regeneration with special focus on biomaterial properties including morphogens. Morphogens direct the lineage and final fate of responding stem cells. Morphogens include bone morphogenetic proteins (BMPs), hedgehogs, fibroblast growth factors (FGFs) and members of Wnts family. BMPs are the premier signals for bone and cartilage differentiation. The BMP family includes BMPs, cartilage derived morphogenetic proteins (BMPs) and growth/differentiation factors (GDFs). CDMPs 1-3 are also known as GDFs 5-7, and they play critical role in joint formation. Morphogens bind to biomaterials of the extracellular matrix such as collagens, proteoglycans and glycosaminoglycans. BMPs bind to collagens I and IV and heparin. BMPs bound to collagen is a bioactive biomaterial scaffold that can induce bone and cartilage. BMPs were purified from extracellular matrix of demineralized bone. The dissociative extraction and reconstitution of BMPs from collagens in 1981 established the basic concept of the biomimetic biomaterial scaffold and its role in regeneration and tissue engineering. The optimal scaffolds for bone regeneration are collagens and hydroxyapatite. The ideal scaffold for cartilage is materials with viscoelastic and hydrodynamic properties that mimic extracellular matrix of cartilage. The integration of morphogens in the optimal biomaterial scaffold to permit optimal rate of release is the key challenge for cartilage regeneration.