Abstract
BACKGROUND: Recombinant human platelet-derived growth factor-BB (rhPDGF-BB or pure PDGF) has been extensively studied in medicine, resulting in four FDA approvals for products based on pure PDGF for tissue regeneration applications, including stimulation of the healing of skin wounds in diabetic patients, stimulation of healing of intra-oral tissue defects, and stimulation of bone and tissue regeneration following foot and ankle arthrodesis surgery. More recently, pure PDGF has also been introduced for esthetic and cosmetic applications. OBJECTIVE: Here, we review the extensive nonclinical and clinical pharmacokinetic and safety studies performed on rhPDGF-BB across diverse administration routes, including topical, injection, and surgical implantation to establish a large margin of safety. RESULTS: Pharmacokinetic studies confirmed that systemic exposure to rhPDGF-BB is negligible following repeated topical application, injection, or implantation, minimizing any potential for systemic risks. Biocompatibility and toxicology studies demonstrated that rhPDGF-BB applied topically to skin, implanted, or injected subcutaneously, intradermally, intramuscularly, intraperitoneally, or intravenously, one time, or repeatedly, is noncytotoxic, nonirritating, nonsensitizing, nonmutagenic, nonclastogenic, noncarcinogenic, and nontoxic. No risk of cancer incidence or cancer mortality was detected following injection, implantation, or repeated, daily topical application of rhPDGF-BB onto partial or full thickness skin wounds for up to 20 weeks, that is, 140 doses. CONCLUSION: The totality of the data demonstrates that the use of rhPDGF-BB for regeneration and rejuvenation of skin and other tissues has an excellent safety profile, a finding further affirmed by its record of safe and effective use in multiple medical indications for over 25 years.