Han Yiling, Geng Qiangwang, Dong Aimeng, Jiang Menglu, Ma Jingyi, Song Wulian, Fan Pan, Li Yuanyuan, Gao Jiawen, Zhang Fenghua, Leng Jinsong, Yuan Huiping
Department of Ophthalmology, The Future Medicine Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, People's Republic of China.
Centre for Composite Materials and Structures, Harbin Institute of Technology (HIT), Harbin 150080, People's Republic of China.
Research (Wash D C). 2025 Jan 22;8:0561. doi: 10.34133/research.0561. eCollection 2025.
Excessive fibrosis is the primary factor for the failure of glaucoma drainage device (GDD) implantation. Thus, strategies to suppress scar formation in GDD implantation are crucial. Although it is known that in implanted medical devices, microscale modification of the implant surface can modulate cell behavior and reduce the incidence of fibrosis, in the field of ophthalmic implants, especially the modification and effects of hydrogel micropatterns have rarely been reported. Here, we designed the patterned gelatin/acrylamide double network hydrogel and developed an innovative GDD with micropattern to suppress inflammatory and fibroblast activation after GDD implantation. Pattern topography suppressed F-actin expression and mitigated actin-dependent nuclear migration of myocardin-related transcription factor A (MRTF-A) during the proliferative phase after GDD implantation. Ultimately, the expression of α-smooth muscle actin (α-SMA), a key fibrosis-related gene product, was suppressed. Moreover, the modified GDD effectively controlled intraocular pressure (IOP), mitigated fibrous formation, and remodeled extracellular matrix (ECM) collagen distribution in vivo. Therefore, the novel GDD with surface patterning interventions provides a promising strategy to inhibit scar formation after GDD implantation and raise the efficacy of GDD implantation.
过度纤维化是青光眼引流装置(GDD)植入失败的主要因素。因此,抑制GDD植入过程中瘢痕形成的策略至关重要。尽管已知在植入的医疗设备中,植入物表面的微观尺度修饰可以调节细胞行为并降低纤维化的发生率,但在眼科植入物领域,尤其是水凝胶微图案的修饰及其效果却鲜有报道。在此,我们设计了图案化的明胶/丙烯酰胺双网络水凝胶,并开发了一种带有微图案的创新型GDD,以抑制GDD植入后的炎症和成纤维细胞活化。图案形貌在GDD植入后的增殖期抑制了F-肌动蛋白的表达,并减轻了心肌相关转录因子A(MRTF-A)的肌动蛋白依赖性核迁移。最终,关键的纤维化相关基因产物α-平滑肌肌动蛋白(α-SMA)的表达受到抑制。此外,改良后的GDD在体内有效控制了眼压(IOP),减轻了纤维形成,并重塑了细胞外基质(ECM)胶原蛋白的分布。因此,具有表面图案化干预的新型GDD为抑制GDD植入后的瘢痕形成和提高GDD植入效果提供了一种有前景的策略。