{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T19:17:28Z","timestamp":1787685448381,"version":"build-2784847793"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although manufacturers of 1,4\u2010butanediol diglycidyl ether (BDDE)\u2010cross\u2010linked hyaluronic acid (HA) fillers assert effective removal of unreacted BDDE, the hydrolyzed derivative 3,3\u2032\u2010(butane\u20101,4\u2010diyl)bis(oxy)bis(propane\u20101,2\u2010diol) (BDPE) is routinely monitored, despite possessing structural features associated with sensitization potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To quantify free BDPE content across commercially available HA dermal fillers and assess potential safety implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials\/Methods<\/jats:title>\n                    <jats:p>\n                      A validated liquid chromatography\u2013tandem mass spectrometry method was developed to quantify BDPE levels in 38 commercial HA filler products from seven major manufacturers.\n                      <jats:italic>In silico<\/jats:italic>\n                      prediction models were used to evaluate the skin sensitization and irritation potential of BDPE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BDDE levels were non\u2010detectable in all analyzed products. By contrast, free BDPE content varied markedly, with over 1000\u2010fold differences observed between products, indicating substantial variability in purification efficiency across manufacturing processes. Considerable variability was also identified among Food and Drug Administration\u2013approved products, with some containing BDPE concentrations exceeding 100\u2009ppm. Conversely, several products exhibited low BDPE levels ranging from 0.1 to 2.5\u2009ppm, further highlighting inconsistencies in manufacturing control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Industry claims regarding complete cross\u2010linker removal may fail to account for the persistence of BDPE species. The substantial inter\u2010product variability observed in this study suggests inadequate process control among manufacturers. Given the structural similarity of BDPE to known sensitizers and the direct dermal injection route that circumvents the skin barrier, free BDPE should be designated a critical quality attribute with defined acceptance limits. These findings suggest that BDPE can be reduced to concentrations below 2.5\u2009ppm, supporting the need for stricter manufacturing standards.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jocd.70790","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T09:56:08Z","timestamp":1773136568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comprehensive Analysis of Free\n                    <scp>BDPE<\/scp>\n                    Content in Commercial Hyaluronic Acid Fillers: Implications for Safety Assessment and Regulatory Standards"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8495-0321","authenticated-orcid":false,"given":"Cheol Joo","family":"Kim","sequence":"first","affiliation":[{"name":"R&amp;D Department Across Co. Ltd.  Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1157-6769","authenticated-orcid":false,"given":"Mirou","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs Hugel Inc.  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9227-2982","authenticated-orcid":false,"given":"Hyeongtaek","family":"Park","sequence":"additional","affiliation":[{"name":"R&amp;D Department Across Co. Ltd.  Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeyoung","family":"Jo","sequence":"additional","affiliation":[{"name":"R&amp;D Department Across Co. Ltd.  Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyolim","family":"Lee","sequence":"additional","affiliation":[{"name":"R&amp;D Department Across Co. Ltd.  Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pius J.","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs Hugel Inc.  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6893-2455","authenticated-orcid":false,"given":"Seung Jun","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs Hugel Inc.  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1595-5285","authenticated-orcid":false,"given":"Chulho","family":"Shin","sequence":"additional","affiliation":[{"name":"R&amp;D Department Across Co. Ltd.  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