Liu Xin, Li Jiale, Liu Shuyu, Long Yan, Kang Ching, Zhao Chen, Wei Ling, Huang Shaoqi, Luo Yi, Dai Bo, Zhu Xiangjia
Cataract and Lens Refractive Surgery Group, Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai 200031, People's Republic of China.
NHC Key Laboratory of Myopia, Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Fudan University, Shanghai 200031, People's Republic of China.
Regen Biomater. 2024 Mar 1;11:rbae020. doi: 10.1093/rb/rbae020. eCollection 2024.
Posterior capsule opacification (PCO) remains the predominant complication following cataract surgery, significantly impairing visual function restoration. In this study, we developed a PCO model that closely mimics the anatomical structure of the crystalline lens capsule post-surgery. The model incorporated a threaded structure for accurate positioning and observation, allowing for opening and closing. Utilizing 3D printing technology, a stable external support system was created using resin material consisting of a rigid, hollow base and cover. To replicate the lens capsule structure, a thin hydrogel coating was applied to the resin scaffold. The biocompatibility and impact on cellular functionality of various hydrogel compositions were assessed through an array of staining techniques, including calcein-AM/PI staining, rhodamine staining, BODIPY-C11 staining and EdU staining in conjunction with transwell assays. Additionally, the PCO model was utilized to investigate the effects of eight drugs with anti-inflammatory and anti-proliferative properties, including 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), THZ1, sorbinil, 4-octyl itaconate (4-OI), xanthohumol, zebularine, rapamycin and caffeic acid phenethyl ester, on human lens epithelial cells (HLECs). Confocal microscopy facilitated comprehensive imaging of the PCO model. The results demonstrated that the GelMA 60 5% + PLMA 2% composite hydrogel exhibited superior biocompatibility and minimal lipid peroxidation levels among the tested hydrogels. Moreover, compared to using hydrogel as the material for 3D printing the entire model, applying surface hydrogel spin coating with parameters of 2000 rpm × 2 on the resin-based 3D printed base yielded a more uniform cell distribution and reduced apoptosis. Furthermore, rapamycin, 4-OI and AICAR demonstrated potent antiproliferative effects in the drug intervention study. Confocal microscopy imaging revealed a uniform distribution of HLECs along the anatomical structure of the crystalline lens capsule within the PCO model, showcasing robust cell viability and regular morphology. In conclusion, the PCO model provides a valuable experimental platform for studying PCO pathogenesis and exploring potential therapeutic interventions.
后囊膜混浊(PCO)仍然是白内障手术后的主要并发症,严重损害视力功能恢复。在本研究中,我们开发了一种PCO模型,该模型紧密模拟了手术后晶状体囊膜的解剖结构。该模型采用螺纹结构进行精确的定位和观察,并可实现开合。利用3D打印技术,使用由刚性空心底座和盖子组成的树脂材料创建了一个稳定的外部支撑系统。为了复制晶状体囊膜结构,在树脂支架上涂覆了一层薄水凝胶涂层。通过一系列染色技术,包括钙黄绿素-AM/PI染色、罗丹明染色、BODIPY-C11染色以及与Transwell分析相结合的EdU染色,评估了各种水凝胶组合物的生物相容性及其对细胞功能的影响。此外,利用PCO模型研究了八种具有抗炎和抗增殖特性的药物,包括5-氨基咪唑-4-甲酰胺核苷酸(AICAR)、THZ1、索比尼尔、4-辛基衣康酸酯(4-OI)、黄腐酚、泽布勒林、雷帕霉素和咖啡酸苯乙酯,对人晶状体上皮细胞(HLEC)的影响。共聚焦显微镜有助于对PCO模型进行全面成像。结果表明,在测试的水凝胶中,GelMA 60 5% + PLMA 2%复合水凝胶表现出优异的生物相容性和最低的脂质过氧化水平。此外,与使用水凝胶作为3D打印整个模型的材料相比,在基于树脂的3D打印底座上以2000 rpm×2的参数进行表面水凝胶旋涂,可产生更均匀的细胞分布并减少细胞凋亡。此外,在药物干预研究中,雷帕霉素、4-OI和AICAR表现出强大的抗增殖作用。共聚焦显微镜成像显示,PCO模型内的HLEC沿晶状体囊膜的解剖结构均匀分布,显示出强大的细胞活力和规则的形态。总之,PCO模型为研究PCO发病机制和探索潜在治疗干预措施提供了一个有价值的实验平台。