Abstract
Growth factors hold great promise for the treatment of various musculoskeletal conditions. Growth factors are small proteins that serve as signaling agents for cells. The discovery of these substances revolutionized the field of cell biology by revealing the mechanism of regulation of cell activities. Growth factors are present in plasma or tissues at concentrations measured in billionths of a gram yet they are the principal effector of such critical cellular functions such as cell division, matrix synthesis and tissue differentiation.
Several growth promoting substances have been identified in bone matrix and at the site of healing fractures. Among these are the transforming growth factor beta’s, bone morphogenetic proteins, fibroblast growth factors, insulin like growth factors and platelet derived growth factor. These growth factors are mainly produced by osteoblasts and incorporated into the extracellular matrix during bone formation. Small amounts of the growth factors can also be trapped systemically from serum and be incorporated into matrix. The present hypothesis is that growth factors are located within the matrix until remodeling or trauma causes solubilization and release of the proteins.
The discovery of growth factors and their study in in vitro cultures has allowed an understanding of the mechanism of the regulation of a broad range of cell activities. However, their presence in plasma and tissues in minute quantities limited their evaluation in vivo and precluded clinical application of the natural purified products. Advances in recombinant DNA methodology have allowed sufficient quantities of these materials to be produced and many are in various stage of in vivo pre-clinical and clinical evaluation.
Extensive efforts have been made to find methods by which growth factors can be used to stimulate local bone healing and bone formation in a variety of clinical models. The growth factors TGF-α, BMP and basic FGF are the only growth factors that have been demonstrated to possess substantial in vivo bone stimulatory capacity. The growth factors BMP-2 and BMP-7, also known as osteogenic protein-1, are in the final stages of pivotal human trials.
There are many challenges to the clinical application of growth factors. It is unlikely that cell signaling molecules act independently of each other or are present in isolation from each other at their sites of action. The therapeutic application of growth factors must also accommodate the fact that most factors have a widespread and varied distribution of target cells. A growth factor administered to elicit a desired response from one cell type may also influence other cell types possible in unintended or undesirable ways. Finally, in the current era of cost consciousness in health care, a growth factor treatment must demonstrate cost effectiveness along with clinical efficacy.
The abstracts were prepared by Professor Jegan Krishnan. Correspondence should be addressed to him at the Flinders Medical Centre, Bedford Park 5047, Australia.
