Recombinant Human Platelet-Derived Growth Factor: Biology and Clinical Applications

Abstract

The abilities of bone to remodel, fractures to repair, and bone grafts to incorporate are all fundamental reflections of the bone remodeling cycle. This process is characterized by the recruitment and differentiation of osteoblastic and osteoclastic cell populations, whose cellular activities are coordinated and regulated by an elaborate system of growth factors and cytokines. One of the crucial biological factors responsible for reparative osseous activity is platelet-derived growth factor (PDGF). The potent stimulatory effects of PDGF as a chemoattractant and mitogen for mesenchymal cells (including osteogenic cells), along with its ability to promote angiogenesis, have been demonstrated in a variety of preclinical models predicting maxillofacial, spine and appendicular skeletal, and soft-tissue applications. The biological profile of PDGF, including its ability to recruit osteoprogenitor cells, makes it particularly suited to address the skeletal defects that are seen with comorbid conditions such as osteoporosis, diabetes, and the effects of smoking. The clinical success and safety that have been demonstrated with use of recombinant human PDGF (rhPDGF) in the repair of periodontal defects have led to U.S. Food and Drug Administration (FDA) approval of rhPDGF for this indication. Ongoing pilot and pivotal trials in the United States and internationally will continue to clarify the promising role of PDGF in the treatment of challenging skeletal disorders.

TNF-α promotes fracture repair by augmenting the recruitment and differentiation of muscle-derived stromal cells

“…In contrast, IL-1β did not influence migration of MDSC within the dose range tested. PDGF is an established chemoattractant factor for cells of stromal origin (33). Moreover, chemokines including CCL-2 (MCP-1), CXCL-8 (IL-8), and CXCL-12 (SDF-1) have been implicated in stromal cell migration (34)(35)(36).…”

Adsorbed Fibrinogen Enhances Production of Bone- and Angiogenic-Related Factors by Monocytes/Macrophages

“…70 Moreover, it has been implicated in the formation of new bone in several in vivo studies. [71][72][73][74][75][76] Interestingly, fully differentiated macrophages cultured on Fg also evidenced enhanced secretion of angiogenic-associated proteins. This suggests that when triggered by Fg, macrophages influence different key steps, are able to modulate the inflammatory response, and also contribute to new bone formation and angiogenesis, both of which were stimulated with Fg-adsorbed Ch scaffolds in vivo.…”

Updates in biological therapies for knee injuries: bone

“…Platelet Derived Growth Factor (PDGF) is involved not only on angiogenesis but also on osteoblast proliferation [35,36]. Thus, it enhances bone healing through improvement of vascularity and increase of osteogenesis.…”

“…Platelet-rich plasma (PRP) is also a method of delivering angiogenic growth factors to fracture sites. Laboratory data on the use of PRP advocates that it promotes cell proliferation and increases the extracellular matrix [35]. Clinical data is still controversial and based on case series where PRP is used either alone or associated with bone grafts or bone substitutes [37,38].…”