Osteogenic molecules for clinical applications: improving the BMP-collagen system

Abstract

Among the osteogenic growth factors used for bone tissue engineering, bone morphogenetic proteins (BMPs) are the most extensively studied for use in orthopaedic surgery. BMP-2 and BMP-7 have been widely investigated for developing therapeutic strategies and are the only two approved for use in several clinical applications. Due to the chemical and biological characteristics of these molecules, their authorised uses are always in combination with a carrier based on collagen type I. Although the use of these growth factors is considered safe in the short term, the very high doses needed to obtain signifi cant osteoinduction make these treatments expensive and their longterm safety uncertain, since they are highly pleiotropic and have the capacity to induce ectopic ossifi cation in the surrounding tissues. Therefore it is necessary to improve the currently used BMP-collagen system in terms of effi ciency, biosecurity and costs. There are several strategies to increase the clinical eff ectiveness of these treatments. In this review we summarize the most promising results and our related work focused on this fi eld through two diff erent approaches: i) the development of recombinant BMPs with additional features, and ii) complementing these systems with other growth factors or molecules to enhance or accelerate osteogenesis.

Combining bone morphogenetic proteins‐2 and ‐6 has additive effects on osteoblastic differentiation in vitro and accelerates bone formation in vivo

“…This led the FDA to issue a Public Health Notification of complications associated with rhBMP‐2, after which a tendency toward reducing the use of BMPs in spinal fusions was noticed . Since then, important efforts have been made to search for alternative ways to administer BMPs at lower doses without affecting the outcome of the treatments . In this line, the co‐administration of different BMPs might be a suitable alternative to improve osteogenesis by combining the features of both individual growth factors while reducing the pressure of each single BMP on the immune system of the patient and on the local environment.…”

TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation

“…54 BMP has sites for N and O glycosylation, which increases the stability and half-life of the protein, in addition to determining the specificity of receptor coupling. 55 Nevertheless, only BMP2 and 4 possess a potential secondary cleavage site. BMP2 is a multifunctional growth factor and a homodimer of two 114 peptides subunits, and two receptor-binding motifs have been identified in the BMP2 ligand.…”

Ovariectomized Rats with Established Osteopenia have Diminished Mesenchymal Stem Cells in the Bone Marrow and Impaired Homing, Osteoinduction and Bone Regeneration at the Fracture Site

“…Currently, recombinant human bone morphogenetic protein-2 (BMP-2) and BMP-7 are approved for spinal fusion surgery and treatment of recalcitrant tibial fractures, respectively [5]. Recently, recombinant platelet-derived growth factor-BB has obtained U.S. FDA approval for the treatment of accelerated periodontal regeneration [6].…”