{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:15:06Z","timestamp":1780586106413,"version":"3.54.1"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"24","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Aesth Plast Surg"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study examined the clinical efficacy of botulinum toxin type A (BTX-A) combined with non-cross-linked bovine collagen in improving periorbital wrinkles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty participants with periorbital wrinkles were recruited from the Plastic Surgery and Aesthetic Department of the Central Hospital Affiliated to Dalian University of Technology in China between November 2021 and August 2022. Participants were randomly assigned to either an observation group or a control group, with each group comprising 20\u00a0participants. The control group received BTX-A injection alone, whereas the observation group received combined injections of BTX-A and collagen filler.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Standardized photographic images were taken at baseline and at 1-week, 1-month, 3-month, and 6-month follow-ups after the injection. The rejuvenation effect was evaluated using the 5-grade Wrinkle Severity Rating Scale, whereas patient satisfaction was assessed using the Global Aesthetic Improvement Scale. Both groups achieved a total effective rate of 100%. However, the markedly effective rate was significantly higher in the observation group (90%) than in the control group (40%;\n                      <jats:italic>p\u2009<\/jats:italic>\n                      &lt;\u20090.01). Moreover, 95% patients in the observation group reported great satisfaction, and the percentage was significantly higher than that in the control group (20%;\n                      <jats:italic>p\u2009<\/jats:italic>\n                      &lt;\u20090.01). No adverse events were reported during the study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BTX-A injections combined with non-cross-linked bovine collagen filler provide a highly effective and safe therapy for improving periorbital wrinkles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence II<\/jats:title>\n                    <jats:p>\n                      This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors \u00a0\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.springer.com\/00266\" ext-link-type=\"uri\">www.springer.com\/00266<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00266-025-04906-9","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T18:20:02Z","timestamp":1755109202000},"page":"6932-6941","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Randomized Controlled Trial of Botulinum Toxin Combined with Non-Cross-Linked Bovine Collagen for Improving Periorbital Wrinkles"],"prefix":"10.1007","volume":"49","author":[{"given":"Yao","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"4906_CR1","first-page":"198","volume":"31","author":"H Li","year":"2022","unstructured":"Li H, Chen D, Peng Q, Chen X, Chen X. Research progress of periorbital aging grading. Chin J Aesthet Med. 2022;31:198\u2013202.","journal-title":"Chin J Aesthet Med"},{"key":"4906_CR2","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/1749-8546-9-26","volume":"9","author":"Q Zhang","year":"2019","unstructured":"Zhang Q. Clinical management of the combined treatment plan for eye rejuvenation. Chin Med Cosmet. 2019;9:26\u20138.","journal-title":"Chin Med Cosmet"},{"key":"4906_CR3","first-page":"21","volume":"31","author":"Du Xue","year":"2022","unstructured":"Xue Du, Zhang P, Zhen L. Clinical application of Peninsula gold microneedles combined with FIMAN Fillderm medical collagen filler in facial acne depression scar. Med Aesthet Cosmet. 2022;31:21\u20134.","journal-title":"Med Aesthet Cosmet"},{"key":"4906_CR4","doi-asserted-by":"publisher","first-page":"49","DOI":"10.2165\/00128071-200405010-00007","volume":"5","author":"DJ Day","year":"2004","unstructured":"Day DJ, Littler CM, Swift RW, Gottlieb S. The wrinkle severity rating scale: a validation study. Am J Clin Dermatol. 2004;5:49\u201352.","journal-title":"Am J Clin Dermatol"},{"issue":"5","key":"4906_CR5","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.clindermatol.2019.07.010","volume":"37","author":"V Gupta","year":"2019","unstructured":"Gupta V, Sharma VK. Skin typing: Fitzpatrick grading and others. Clin Dermatol. 2019;37(5):430\u20136.","journal-title":"Clin Dermatol"},{"key":"4906_CR6","doi-asserted-by":"publisher","unstructured":"Hua W, Fan L-M, Dai R et al. Comparison of two series of non-invasive instruments used for the skin physiological properties measurements: the DermaLab (\u00ae) from Cortex Technology vs the series of detectors from Courage & Khazaka. Skin Res Technol. 2017;23(1):70\u201378. https:\/\/doi.org\/10.1111\/srt.12303.","DOI":"10.1111\/srt.12303"},{"key":"4906_CR7","unstructured":"China Dermatologist Association Aesthetic Injection Group. Consensus recommendations on aesthetic use of botulinum toxin. Chin J Aesthet Med 2017;26:3\u20138."},{"issue":"4","key":"4906_CR8","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/BF01570645","volume":"6","author":"FV Nicolle","year":"1982","unstructured":"Nicolle FV. Use of Zyderm in the aging face. Aesthet Plast Surg. 1982;6(4):193\u20135. https:\/\/doi.org\/10.1007\/BF01570645.","journal-title":"Aesthet Plast Surg"},{"key":"4906_CR9","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202202042","author":"M Zheng","year":"2023","unstructured":"Zheng M, Wang X, Chen Y, Yue O, Bai Z, Cui B, Jiang H, Liu X. A review of recent progress on collagen-based biomaterials. Adv Healthc Mater. 2023. https:\/\/doi.org\/10.1002\/adhm.202202042.","journal-title":"Adv Healthc Mater"},{"key":"4906_CR10","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1111\/j.1468-3083.2010.03963.x","volume":"25","author":"E Kohl","year":"2011","unstructured":"Kohl E, Steinbauer J, Landthaler M, Szeimies RM. Skin ageing. J Eur Acad Dermatol Venereol. 2011;25:873\u201384.","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"4906_CR11","first-page":"133","volume":"14","author":"Y Zhu","year":"2023","unstructured":"Zhu Y, Chandran SP. Clinical efficacy and safety of combined treatment with hyaluronic acid and botulinum toxin type A for reducing facial wrinkles and increases rejuvenation. 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Food Sci Hum Wellnes. 2022;11:218\u201329.","journal-title":"Food Sci Hum Wellnes"}],"container-title":["Aesthetic Plastic Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00266-025-04906-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00266-025-04906-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00266-025-04906-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T19:05:14Z","timestamp":1769713514000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00266-025-04906-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,13]]},"references-count":17,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["4906"],"URL":"https:\/\/doi.org\/10.1007\/s00266-025-04906-9","relation":{},"ISSN":["0364-216X","1432-5241"],"issn-type":[{"value":"0364-216X","type":"print"},{"value":"1432-5241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,13]]},"assertion":[{"value":"2 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was conducted in accordance with the ethical principles stated in the \u201cDeclaration of Helsinki\u201d and approved by Ethics Committee of the Central Hospital affiliated to Dalian University of Technology (YN2022-082-01).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Written informed consent was obtained from all participants prior to performance of any study-related procedure.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}}]}}