What is Platelet-Derived Growth Factor (PDGF) used for?

Clinical Applications of Platelet-Derived Growth Factor (PDGF)

PDGF is FDA-approved as becaplermin gel (0.01%) for treating lower extremity diabetic neuropathic ulcers that extend into subcutaneous tissue or beyond with adequate blood supply, and is also used off-label in periodontal and oral regenerative procedures. 1

FDA-Approved Indication: Diabetic Foot Ulcers

Becaplermin (REGRANEX) is indicated as an adjunct to good ulcer care practices for diabetic neuropathic ulcers of the lower extremities. 1 The medication works by stimulating chemotaxis and proliferation of inflammatory cells and fibroblasts, accelerating wound closure by approximately 30% in excisional wounds. 2

Application Protocol

• Calculate gel length using the formula: ulcer length × ulcer width × 0.6 (inches) or ÷ 4 (centimeters) for the 15g tube 1
• Apply topically once daily; not for oral, ophthalmic, or intravaginal use 1
• The treatment augments wound breaking strength by 50-70% over the first 3 weeks 2

Important Limitations

• Contraindicated in patients with known neoplasms at application sites 1
• Not established for pressure ulcers or venous stasis ulcers 1
• Effects on exposed joints, tendons, ligaments, and bone are not established 1
• Not intended for wounds closing by primary intention 1

Evidence Quality Considerations

The International Working Group on the Diabetic Foot (IWGDF) 2023 guidelines suggest NOT using growth factor therapy as adjunct treatment for diabetic foot ulcers (Conditional recommendation; Low quality evidence). 3 This recommendation stems from seven studies where only one low-risk-of-bias study showed no difference in healing, though an earlier moderate-risk trial showed benefit. 3 Despite FDA approval, the guideline authors note that most studies were at high risk of bias and none reported sustained healing, amputation, resource utilization, or mortality outcomes. 3

This creates a clinical dilemma: FDA approval exists based on earlier evidence showing 30% acceleration in wound closure 2, but more recent systematic reviews question the strength of this evidence. 3 In practice, consider becaplermin when standard wound care has failed and the patient has adequate perfusion, but recognize the evidence limitations.

Periodontal and Oral Regenerative Applications

Recombinant human PDGF-BB (rhPDGF-BB) is FDA-approved in combination with beta-tricalcium phosphate for treating intrabony periodontal defects, furcation defects, and gingival recessions. 3

Mechanism in Oral Tissues

• PDGF-BB is the most potent isoform for promoting mitogenic and chemotactic responses of periodontal ligament cells 3
• Stimulates formation of new bone, cementum, and periodontal ligament 3
• Acts synergistically with insulin growth factor-1 (IGF-1) on periodontal and bone precursor cells 3

Clinical Outcomes in Periodontal Surgery

Early phase I/II trials demonstrated that high-dose rhPDGF-BB (150 μg/mL) with IGF-1 produced mean vertical bone gain of 2.8 mm versus 0.75 mm with open flap debridement alone at 9 months, with defect fill of 42.3% versus 18.5%. 3

Expanded Uses in Dentistry

Beyond FDA-approved indications, rhPDGF-BB has been utilized with various scaffolds for: 3

• Bone augmentation procedures around dental implants
• Horizontal and vertical ridge augmentation
• Alveolar ridge preservation
• Sinus floor elevation
• Peri-implant bone augmentation

Biological Properties and Mechanism of Action

Cellular Effects

PDGF functions as a potent mitogen for cells of mesenchymal origin, particularly fibroblasts and osteoblasts. 3 The growth factor:

• Stimulates chemotaxis and proliferation of monocytes-macrophages and fibroblasts 2
• Promotes proliferation of pericytes and activation of neutrophils and macrophages 3
• Induces synthesis of endogenous wound PDGF and other growth factors through positive autocrine feedback loops 2

Wound Healing Cascade

According to the American College of Cardiology, PDGF stimulates chemotaxis and mitogenicity of neutrophils, monocytes, macrophages, and fibroblasts during the inflammation phase of wound healing. 4 Macrophages secrete multiple growth factors including PDGF, TGF-β, EGF, FGF-2, and VEGF during this critical phase. 4

Transient Effects

The vulnerary effects of PDGF-BB are transient and fully reversible—PDGF exaggerates but does not alter the normal course of soft tissue repair, with no apparent long-term differences between treated and non-treated wounds. 2

Common Pitfalls and Clinical Caveats

Adverse Effects

• Erythematous rashes occur in 2% of patients treated with becaplermin 1
• Malignancies distant from application sites have been reported in clinical studies and postmarketing surveillance 1
• Benefits and risks must be carefully evaluated before prescribing in patients with known malignancy 1

When NOT to Use PDGF

• Wounds with untreated osteomyelitis 4
• Inadequate blood supply—revascularization must be addressed first 4
• Presence of necrotic tissue—proper debridement is required before application 4
• Known neoplasms at application sites (absolute contraindication) 1

Cost-Effectiveness Concerns

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. 5 This reflects the high resource utilization and limited evidence for routine use beyond FDA-approved indications.

Integration with Standard Wound Care

PDGF is an adjunct to, not a substitute for, good ulcer care practices. 1 Essential components include:

• Sharp debridement to remove inflammatory burden 5
• Adequate blood supply and revascularization when needed 4
• Pressure offloading, particularly in diabetic foot ulcers 4
• Infection control with antibiotics and debridement 4
• Moisture balance and exudate control 5