What is Platelet-Derived Growth Factor (PDGF)?

What is Platelet-Derived Growth Factor (PDGF)?

Platelet-Derived Growth Factor (PDGF) is a potent mitogen and chemotactic factor for cells of mesenchymal origin—particularly fibroblasts, osteoblasts, and smooth muscle cells—that plays critical roles in wound healing, tissue regeneration, and embryonic development by stimulating cell proliferation, migration, and secretion of other growth factors. 1, 2

Molecular Structure and Isoforms

• PDGF exists as a dimeric molecule composed of two polypeptide chains (A-chain and B-chain) bound together by disulfide bonds, forming at least three isoforms: PDGF-AA, PDGF-AB, and PDGF-BB 2, 3
• A fourth member, PDGF-D (forming PDGF-DD homodimers), has been identified as a specific ligand for the PDGF beta-receptor that requires proteolytic activation 4
• PDGF-BB is the most potent isoform for promoting mitogenic and chemotactic responses of periodontal ligament cells 1
• The recombinant form (becaplermin) is produced through insertion of the gene for the B-chain into yeast (Saccharomyces cerevisiae), resulting in a homodimer with molecular weight of approximately 25 kD 5

Mechanism of Action

• PDGF exerts cellular effects by binding to and activating two structurally related protein tyrosine kinase receptors: the alpha-receptor (PDGFR-α) and beta-receptor (PDGFR-β) 2
• The alpha-receptor binds all PDGF chains (A, B, C), while the beta-receptor binds only PDGF-B and PDGF-D 4, 3
• Upon receptor activation, PDGF stimulates chemotaxis and mitogenicity of neutrophils, monocytes, macrophages, and fibroblasts during the inflammation phase of wound healing 1, 6
• PDGF promotes cell proliferation, migration, secretion of vascular endothelial growth factors, and induces reorganization of the actin filament system 7, 2

Biological Functions in Wound Healing

• Platelets release α-granules containing PDGFs at injury sites, which attract neutrophils and macrophages, inducing chemotaxis and proliferation of mesenchymal stem/progenitor cells 7
• Neutrophils and macrophages serve not only through phagocytic activity but also as a continuous source of PDGFs and other growth factors during the initial steps of wound healing 7
• PDGF appears to transduce its signal through wound macrophages and may trigger positive autocrine feedback loops, enhancing the cascade of tissue repair processes 8
• Exogenously administered PDGF-BB significantly augments inflammatory cell and fibroblast influx, accelerates provisional extracellular matrix deposition and collagen formation, and increases wound breaking strength by 50-70% 8

FDA-Approved Clinical Applications

• Becaplermin (REGRANEX gel 0.01%) is FDA-approved for treatment of lower extremity diabetic neuropathic ulcers that extend into subcutaneous tissue or beyond and have adequate blood supply 5
• The medication is indicated as an adjunct to, not a substitute for, good ulcer care practices 5
• Recombinant human PDGF-BB is FDA-approved in combination with beta-tricalcium phosphate for treating intrabony periodontal defects, furcation defects, and gingival recessions 1
• High-dose rhPDGF-BB with IGF-1 produced mean vertical bone gain of 2.8 mm versus 0.75 mm with open flap debridement alone, with defect fill of 42.3% versus 18.5% 1

Important Limitations and Contraindications

• REGRANEX is contraindicated in patients with known neoplasm(s) at the site(s) of application 5
• The efficacy has not been established for pressure ulcers, venous stasis ulcers, or wounds that close by primary intention 5
• PDGF should not be used in wounds with untreated osteomyelitis, inadequate blood supply, presence of necrotic tissue, or known neoplasms at application sites 1
• The effects on exposed joints, tendons, ligaments, and bone have not been established in humans 5

Role in Pathophysiology

• PDGF synthesis occurs in response to external stimuli such as low oxygen tension, thrombin, or stimulation by other cytokines and growth factors 9
• Overexpression of PDGF has been linked to fibrotic disorders, malignancies, atherosclerosis, and fibroproliferative diseases 9, 2
• The sis oncogene of simian sarcoma virus is related to the B-chain of PDGF, and transformation involves autocrine stimulation by a PDGF-like molecule 2

Clinical Guideline Recommendations

• The International Working Group on the Diabetic Foot (IWGDF) suggests not using growth factor therapy as adjunct treatment for diabetic foot ulcers (conditional recommendation, low quality evidence) 1
• The American College of Cardiology recommends avoiding growth factors unless in specialized research settings, favoring sharp debridement and simple dressings selected for exudate control, comfort, and cost 1, 10
• When considering PDGF therapy, the benefits and risks should be carefully evaluated, particularly in patients with known malignancy 5