{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:46:21Z","timestamp":1790178381107,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bioengineering &amp;amp; Transla Med"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We employed the mechanical effect from 40\u2009kHz ultrasound (US) to improve the delivery of riboflavin into corneal stroma for collagen crosslinking, which can benefit the treatment of keratoconus and other corneal ectasias. Experiments were conducted, first with porcine corneas ex vivo and then with New Zealand white rabbits in vivo, at varying mechanical index (MI) and sonication time. Results showed that 15\u2009min of US applied on the cornea at MI\u00a0=\u00a00.8 in the presence of 0.5% of riboflavin solution enabled its delivery to deeper corneal stroma. Excessive heat was removed by a cooling setup to negate the thermal effect. The corneal absorption amount and penetration of riboflavin through cornea as detected by fluorotron, as well as the enhancement of corneal stiffness as measured by Young's modulus, were comparable to the conventional approach that requires complete corneal epithelium debridement. Histological analysis revealed minor exfoliation of superficial cell layers of corneal epithelium and loss of ZO\u20101 tight junctions immediately after US. Full recovery of the corneal epithelium and restoration of tight junctions occurred in 3\u20134\u2009days. The study shows that low\u2010intensity low\u2010frequency ultrasound (LILF US) is a less invasive alternative to the conventional epithelium\u2010off method for delivering riboflavin into the corneal stroma.<\/jats:p>","DOI":"10.1002\/btm2.10442","type":"journal-article","created":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T02:13:10Z","timestamp":1669428790000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>Low\u2010intensity low\u2010frequency<\/scp>\n                    ultrasound mediates riboflavin delivery during corneal crosslinking"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3279-7176","authenticated-orcid":false,"given":"Zhe","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Chemical and Biological Engineering The Hong Kong University of Science and Technology  Hong Kong SAR 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