Osteogenic peptides in bone regeneration

Due to their short half-life and diffusion away from the site of regeneration, osteogenic proteins, used in regenerative medicine, require high doses leading to undesirable side effects. An exciting approach is to utilize peptides derived from the active domains of soluble and insoluble components of the bone extracellular matrix (ECM) to initiate the cascade of osteogenesis, vasculogenesis, mineralization, and bone formation. Osteogenic peptides derived from bone morphogenetic proteins, integrin-binding and heparin-binding peptides, collagen-derived peptides, peptides derived from bone sialoprotein and enamel matrix proteins, vasoconstrictive peptides, peptides derived from the histone proteins involved in the structure of chromatin and those derived from receptor-binding domain of human thrombin, peptides that abolish the expression of tumor necrosis factor-α, and neuropeptides have been discovered. In this work, anabolic effects of osteogenic peptides in particular with respect to cell adhesion, differentiation, and mineralization are discussed. These peptides show significantly higher biological activity in vitro and in vivo, in small animal models, when immobilized in a matrix by conjugation or grafting, most likely due to the peptide mobility and its diffusion away from the site of regeneration. Combination of osteogenic and integrin- binding peptides synergistically enhances cell adhesion and mineralization. Functionalization of orthopedic implants with osteogenic peptides can improve cell adhesion, mineralization, and overall integration of the implant with the surrounding tissue, which in turn reduces implant loosening and failure. The use of osteogenic peptides as an alternative growth factor in orthopedic applications rests on future in vivo studies that evaluate these peptides in primates and humans.