{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:04:44Z","timestamp":1791223484078,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"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":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hyaluronic acid (HA) fillers are widely used in aesthetic medicine, but their in\u00a0vivo behavior and long\u2010term effects are not fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To review the decomposition and changes occurring in the body following HA filler injections, focusing on crosslinking agents, degradation processes, and tissue responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review analyzed oxidative and enzymatic degradation processes of HA fillers, evaluated the impact of 1,4\u2010Butanediol Diglycidyl Ether (BDDE) crosslinking, and examined histological changes post\u2010injection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Uncrosslinked HA degrades rapidly due to endogenous hyaluronidase, while crosslinked HA undergoes slower degradation via free radicals and hyaluronidase. Complete cross\u2010linking (C\u2010MoD) showed better durability compared to partially cross\u2010linked BDDE (P\u2010MoD). The concept of modification efficiency (MoE) was proposed to optimize filler safety and viscoelastic properties. Histological analysis revealed collagen capsule formation and autologous tissue replacement, affecting long\u2010term outcomes. The degree of chemical modification (MoD) influences filler durability and safety, with concerns raised about potential delayed immune reactions from accumulated pendent BDDE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Clinicians should consider injection site, tissue conditions, and filler properties for safe and effective HA filler use. Emphasizing thorough BDDE removal and optimal crosslinking can enhance treatment safety and efficacy. The balance between achieving desired viscoelastic properties and minimizing potential risks is crucial. Future studies should include diverse ethnic groups to validate findings and further explore long\u2010term tissue responses to HA fillers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jocd.16652","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T14:16:42Z","timestamp":1730125002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Decomposition and Changes in In\u00a0Vivo Post\u2010\n                    <scp>HA<\/scp>\n                    Filler Injection: A Review"],"prefix":"10.1111","volume":"24","author":[{"given":"Gi\u2010Woong","family":"Hong","sequence":"first","affiliation":[{"name":"Samskin Plastic Surgery Clinic  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovian","family":"Wan","sequence":"additional","affiliation":[{"name":"Asia Pacific Aesthetic Academy  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Chang","sequence":"additional","affiliation":[{"name":"Harmony Aesthetic Clinic  Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngjin","family":"Park","sequence":"additional","affiliation":[{"name":"Obliv Clinic  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5572-1364","authenticated-orcid":false,"given":"Kyu\u2010Ho","family":"Yi","sequence":"additional","affiliation":[{"name":"Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project Yonsei University College of Dentistry  Seoul Korea"},{"name":"Maylin Clinic (Apgujeong)  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14764172.2017.1293825"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/146.5_Pt_2.S37"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.prs.0000234900.26676.0b"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-016-0201-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/asj\/sjae009"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2007.07.001"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470513774.ch4"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1078\/0171-9335-00392"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1090820X13484492"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2007.02354.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-013-0043-7"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/archfaci.7.4.231"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/DSS.0000000000000562"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsc.2015.07.006"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0000000000002184"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181cb4620"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00266-011-9803-z"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-012-2305-7"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.5999\/aps.2015.42.2.232"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-33-6212-3_2"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/GOX.0000000000001154"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.prs.0000234672.69287.77"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/2049-632X.12139"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00101"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181ead122"},{"issue":"4","key":"e_1_2_10_27_1","first-page":"359","article-title":"Evaluation of Injectable CaHA for the Treatment of Mid\u2010Face Volume Loss","volume":"7","author":"Beer K.","year":"2008","journal-title":"Journal of Drugs in Dermatology"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/DSS.0000000000000418"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e31816b1234"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-4725.2009.01335.x"},{"issue":"5","key":"e_1_2_10_31_1","first-page":"486","article-title":"Cosmetic Complications: Rare and Serious Events Following Botulinum Toxin and Soft Tissue Filler Administration","volume":"14","author":"Sorensen E. 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