Li Tan, Zhang Xiaoyu, Ma Li, Qi Xia, Wang Hongwei, Zhou Qingjun, Sun Xiuli, Wang Fuyan, Zhao Long, Shi Weiyun
State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Eye Institute of Shandong First Medical University, Qingdao 266071, China.
State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Eye Institute of Shandong First Medical University, Qingdao 266071, China; Eye Hospital of Shandong First Medical University (Shandong Eye Hospital), Jinan 250021, China.
Acta Biomater. 2025 Jan 15;192:189-205. doi: 10.1016/j.actbio.2024.12.005. Epub 2024 Dec 4.
Despite significant advancements in hydrogels in recent years, their application in corneal repair remains limited by several challenges, including unfitted curvatures, inferior mechanical properties, and insufficient reactive oxygen species (ROS)-scavenging activities. To address these issues, this study introduces a 3D-printed corneal scaffold with nanocomposite hydrogel consisting of gelatin methacrylate (GelMA), poly (ethylene glycol) diacrylate (PEGDA), Laponite, and dopamine. GelMA and PEGDA act as matrix materials with photo-crosslinking abilities. As a two-dimensional nanoclay, Laponite enhances the rheological properties of the hydrogel, making it suitable for 3D printing. Dopamine self-polymerizes into polydopamine (PDA), providing the hydrogel with ROS-scavenging activity. The incorporation of Laponite and the synergistic effect of PDA endow the hydrogel with good mechanical properties. In vitro investigations demonstrated the cytocompatibility of GelMA-PEGDA-Laponite-dopamine (GPLD) hydrogel and its ROS-scavenging activity. Furthermore, in vivo experiments using a rabbit model of lamellar keratoplasty showed accelerated corneal re-epithelialization and complete stromal repair after the implantation of the 3D-printed scaffold. Overall, due to its high bioactivity and simple preparation, the 3D-printed scaffold using GPLD hydrogel offers an alternative for corneal repair with potential for clinical translation. STATEMENT OF SIGNIFICANCE: The clinical application of hydrogel corneal scaffolds has been constrained by their inadequate mechanical properties and the complex microenvironment created by elevated levels of ROS post-transplantation. In this study, we developed a kind of nanocomposite hydrogel by integrating Laponite and dopamine into GelMA and PEGDA. This advanced hydrogel was utilized to 3D print a corneal scaffold with high mechanical strength and ROS-scavenging abilities. When applied to a rabbit model of lamellar keratoplasty, the 3D-printed scaffold enabled complete re-epithelialization of the cornea within one week. Three months after surgery, the corneal stroma was fully repaired, and regeneration of corneal nerve fibers was also observed. This 3D-printed scaffold demonstrated exceptional efficacy in repairing corneal defects with potential for clinical translation.
尽管近年来水凝胶取得了重大进展，但其在角膜修复中的应用仍受到若干挑战的限制，包括曲率不匹配、机械性能较差以及活性氧（ROS）清除活性不足。为了解决这些问题，本研究引入了一种3D打印角膜支架，其具有由甲基丙烯酸明胶（GelMA）、聚乙二醇二丙烯酸酯（PEGDA）、锂皂石和多巴胺组成的纳米复合水凝胶。GelMA和PEGDA作为具有光交联能力的基质材料。作为二维纳米粘土，锂皂石增强了水凝胶的流变学性能，使其适用于3D打印。多巴胺自聚合成聚多巴胺（PDA），为水凝胶提供ROS清除活性。锂皂石的加入和PDA的协同作用赋予水凝胶良好的机械性能。体外研究证明了GelMA-PEGDA-锂皂石-多巴胺（GPLD）水凝胶的细胞相容性及其ROS清除活性。此外，使用板层角膜移植兔模型的体内实验表明，植入3D打印支架后角膜再上皮化加速且基质完全修复。总体而言，由于其高生物活性和制备简单，使用GPLD水凝胶的3D打印支架为角膜修复提供了一种替代方案，具有临床转化潜力。
水凝胶角膜支架的临床应用受到其机械性能不足以及移植后ROS水平升高所造成的复杂微环境的限制。在本研究中，我们通过将锂皂石和多巴胺整合到GelMA和PEGDA中开发了一种纳米复合水凝胶。这种先进的水凝胶被用于3D打印具有高机械强度和ROS清除能力的角膜支架。当应用于板层角膜移植兔模型时，3D打印支架在一周内实现了角膜的完全再上皮化。手术后三个月，角膜基质完全修复，还观察到了角膜神经纤维的再生。这种3D打印支架在修复角膜缺损方面显示出卓越的疗效，具有临床转化潜力。
