{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T23:53:13Z","timestamp":1781913193502,"version":"3.54.5"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recombinant human platelet\u2010derived growth factor\u2010BB (rhPDGF\u2010BB 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\u2010oral 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Here, we review the extensive nonclinical and clinical pharmacokinetic and safety studies performed on rhPDGF\u2010BB across diverse administration routes, including topical, injection, and surgical implantation to establish a large margin of safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pharmacokinetic studies confirmed that systemic exposure to rhPDGF\u2010BB is negligible following repeated topical application, injection, or implantation, minimizing any potential for systemic risks. Biocompatibility and toxicology studies demonstrated that rhPDGF\u2010BB 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\u2010BB onto partial or full thickness skin wounds for up to 20\u2009weeks, that is, 140 doses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The totality of the data demonstrates that the use of rhPDGF\u2010BB 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\u2009years.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jocd.70636","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T07:02:11Z","timestamp":1767164531000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Safety of Exogenous Recombinant Human Platelet\u2010Derived Growth Factor\u2010\n                    <scp>BB<\/scp>\n                    (\n                    <scp>rhPDGF<\/scp>\n                    \u2010\n                    <scp>BB<\/scp>\n                    ) for Medical and Cosmetic Applications: A Review"],"prefix":"10.1111","volume":"25","author":[{"given":"Christopher K.","family":"Hee","sequence":"first","affiliation":[{"name":"Lynch Regenerative Medicine  Franklin Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0550-8757","authenticated-orcid":false,"given":"Herbert B.","family":"Slade","sequence":"additional","affiliation":[{"name":"Chisholm Clinical Research Services, LLC  Ft. Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9342-9414","authenticated-orcid":false,"given":"Samuel E.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Lynch Regenerative Medicine  Franklin Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.21.7696"},{"key":"e_1_2_11_3_1","volume-title":"Tissue Engineering: Applications in Maxillofacial Surgery and Periodontics","author":"Lynch S. E.","year":"1999"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.G.01231"},{"key":"e_1_2_11_5_1","unstructured":"S.Nephew \u201cREGRANEX \u201dPrescribing Information (1997) https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/103691s5138lbl.pdf."},{"key":"e_1_2_11_6_1","unstructured":"Lynch \u201cGEM 21S. 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