Zhou Hang, Zhang Shaohua, Lei Miao, Cai Yixin, Wang Honglei, Sun Jianguo, Cui Jingyuan, Liu Changsheng, Qu Xue
Key Laboratory for Ultrafine Materials of Ministry of Education, School of Material Science and Engineering, Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, 200237, China.
Eye Institute and Department of Ophthalmology, NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai Key Laboratory of Visual Impairment and Restoration, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.
Bioact Mater. 2023 Jun 28;29:1-15. doi: 10.1016/j.bioactmat.2023.05.008. eCollection 2023 Nov.
Corneal transplantation is a prevailing treatment to repair injured cornea and restore vision but faces the limitation of donor tissue shortage clinically. In addition, suturing-needed transplantation potentially causes postoperative complications. Herein, we design a PEG-Lysozyme injective hydrogel as a suture-free, shape self-adaptive, bioactive implant for corneal stroma defect repair. This implant experiences a sol-gel phase transition via an in situ amidation reaction between 4-arm-PEG-NHS and lysozyme. The physicochemical properties of PEG-Lysozyme can be tuned by the components ratio, which confers the implant mimetic corneal modulus and provides tissue adhesion to endure increased intraocular pressure. In vitro tests prove that the implant is beneficial to Human corneal epithelial cells growth and migration due to the bioactivity of lysozyme. Rabbit lamellar keratoplasty experiment demonstrates that the hydrogel can be filled into defect to form a shape-adaptive implant adhered to native stroma. The implant promotes epithelialization and stroma integrity, recovering the topology of injured cornea to normal. A newly established animal forging behavior test prove a rapid visual restoration of rabbits when use implant in a suture free manner. In general, this work provides a promising preclinical practice by applicating a self-curing, shape self-adaptive and bioactive PEG-Lysozyme implant for suture-free stroma repair.
角膜移植是修复受损角膜和恢复视力的常用治疗方法，但临床上面临供体组织短缺的限制。此外，需要缝合的移植手术可能会导致术后并发症。在此，我们设计了一种聚乙二醇-溶菌酶注射水凝胶，作为一种用于角膜基质缺损修复的免缝合、形状自适应、生物活性植入物。这种植入物通过四臂聚乙二醇-活性酯与溶菌酶之间的原位酰胺化反应经历溶胶-凝胶相变。聚乙二醇-溶菌酶的物理化学性质可以通过组分比例进行调节，这赋予植入物模拟角膜模量并提供组织粘附力以承受增加的眼内压。体外试验证明，由于溶菌酶的生物活性，该植入物有利于人角膜上皮细胞的生长和迁移。兔板层角膜移植实验表明，水凝胶可以填充到缺损处，形成与天然基质粘附的形状自适应植入物。该植入物促进上皮化和基质完整性，使受损角膜的拓扑结构恢复正常。一项新建立的动物锻造行为测试证明，当以免缝合方式使用植入物时，兔子的视力能快速恢复。总的来说，这项工作通过应用一种自固化、形状自适应且具有生物活性的聚乙二醇-溶菌酶植入物进行免缝合基质修复，提供了一种有前景的临床前实践。
