关键词: AF127, Aldehyded Pluronic F127 AS-OCT, Anterior Segment Optical Coherence Tomography Bioadhesives CCK-8, Cell Counting Kit-8 COL I, Collagen Type I CXL CXL, Corneal Cross-linking Corneal patch DLS, Dynamic Light Scattering DMEM, Dulbecco's Modified Eagle's Medium ECM, Extracellular Matrix F127DA, Pluronic F127 diacrylate FBS, Fetal Bovine Serum GelMA, Methacryloylated Gelatin H&E, Hematoxylin and Eosin IHC, Immunohistochemistry IOP, Intraocular Pressure PBS, Phosphate-buffered Saline RF, Riboflavin-5-phosphate ROS, Reactive Oxygen Species SD, Standard Deviation Sutureless repair TEM, Transmission Electron Microscopy Tough hydrogel UV, Ultraviolet α-SMA, Alpha Smooth Muscle Actin

来  源:   DOI:10.1016/j.bioactmat.2023.02.006   PDF(Pubmed)

Abstract:
Corneal transplantation is an effective clinical treatment for corneal diseases, which, however, is limited by donor corneas. It is of great clinical value to develop bioadhesive corneal patches with functions of \"Transparency\" and \"Epithelium & Stroma generation\", as well as \"Suturelessness\" and \"Toughness\". To simultaneously meet the \"T.E.S.T.\" requirements, a light-curable hydrogel is designed based on methacryloylated gelatin (GelMA), Pluronic F127 diacrylate (F127DA) & Aldehyded Pluronic F127 (AF127) co-assembled bi-functional micelles and collagen type I (COL I), combined with clinically applied corneal cross-linking (CXL) technology for repairing damaged cornea. The patch formed after 5 min of ultraviolet irradiation possesses transparent, highly tough, and strongly bio-adhesive performance. Multiple cross-linking makes the patch withstand deformation near 600% and exhibit a burst pressure larger than 400 mmHg, significantly higher than normal intraocular pressure (10-21 mmHg). Besides, the slower degradation than GelMA-F127DA&AF127 hydrogel without COL I makes hydrogel patch stable on stromal beds in vivo, supporting the regrowth of corneal epithelium and stroma. The hydrogel patch can replace deep corneal stromal defects and well bio-integrate into the corneal tissue in rabbit models within 4 weeks, showing great potential in surgeries for keratoconus and other corneal diseases by combining with CXL.
摘要:
角膜移植术是临床治疗角膜疾病的有效方法,which,然而,受到供体角膜的限制。开发具有“透明”和“上皮和基质生成”功能的生物粘附性角膜补片具有重要的临床价值,以及“无情”和“坚韧”。同时满足\"T.E.S.T.“要求,基于甲基丙烯酰化明胶(GelMA)设计了一种光固化水凝胶,PluronicF127二丙烯酸酯(F127DA)和醛化PluronicF127(AF127)共组装双功能胶束和I型胶原蛋白(COLI),结合临床应用的角膜交联(CXL)技术修复受损角膜。紫外线照射5分钟后形成的贴片具有透明,非常艰难,和强大的生物粘合性能。多次交联使贴片承受近600%的变形,并表现出大于400mmHg的爆裂压力,显著高于正常眼压(10-21mmHg)。此外,与无COLI的GelMA-F127DA和AF127水凝胶相比,降解速度较慢,使水凝胶贴片在体内基质床上稳定,支持角膜上皮和基质的再生。水凝胶贴剂可在4周内替代角膜深层基质缺损,并能很好地生物整合到兔模型的角膜组织中,联合CXL在圆锥角膜和其他角膜疾病的手术中显示出巨大的潜力。
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