{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:40:49Z","timestamp":1789594849685,"version":"build-2803163510"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Small incision lenticule extraction (SMILE)-derived lenticules have been repurposed as biocompatible scaffolds to incorporate and release therapeutic substances for ocular therapeutics. We aim to investigate the <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> release profiles of recombinant human nerve growth factor (rhNGF) from bioengineered human stromal lenticules prepared with microparticles incorporated with rhNGF (rhNGF-MPs) for up to 1 and 4\u00a0weeks, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Upon bioengineered lenticule implantation, slit lamp, Anterior Segment Optical Coherence Tomography, and <jats:italic>In Vivo<\/jats:italic> Confocal Microscopy were performed to assess corneal biocompatibility, central corneal thickness (CCT), corneal nerve -fiber density (CNFD), -branch density, and -fiber length. Rabbit cornea, tears and aqueous humour were collected to quantify rhNGF release <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A rapid <jats:italic>in vitro<\/jats:italic> release of rhNGF was detected until day 2, and with sustained release over 7\u00a0days. The pattern remains comparable even with the presence of antibiotic-antimycotic, trypan blue or fluorescein. Throughout the <jats:italic>in vivo<\/jats:italic> follow-up, no signs of corneal haze, edema, infiltration, or pathological increase in CCT were observed. A significant increase in CNFD (p = 0.001) at week 4 was reported in rhNGF-MPs than in Blank-MPs group. Finally, significantly higher NGF content in rabbit cornea and tear was found in rhNGF-MPs group compared to the endogenous NC group (p = 0.035 and p = 0.043, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Bioengineered lenticules exhibit sustained rhNGF release for at least 7\u00a0days <jats:italic>in vitro<\/jats:italic> and up to 1\u00a0month <jats:italic>in vivo<\/jats:italic>. These results, together with absence of adverse effects, and significant increase in CNFD at 4\u00a0weeks after lenticule implantation suggest its promising potential for clinical use.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fbioe.2025.1588629","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T13:14:49Z","timestamp":1758287689000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of in vitro and in vivo release of recombinant human nerve growth factor from bioengineered human stromal lenticule"],"prefix":"10.3389","volume":"13","author":[{"given":"Molly Tzu-Yu","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle Xin Yu","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domitilla","family":"Mandatori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Detta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Ying Evelina","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Pelusi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Mastropasqua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Nubile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Cattani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Romeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Allegretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assunta","family":"Pandolfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harminder S.","family":"Dua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodhbir S.","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"108451","DOI":"10.1016\/j.exer.2021.108451","article-title":"Safety of grafting acellular human corneal lenticule seeded with Wharton's Jelly-Derived Mesenchymal Stem Cells in an experimental animal model","volume":"205","author":"Aghamollaei","year":"2021","journal-title":"Exp. 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