Injectable Multifunctional Hydrogel with Sustained Release of procyanidin C1 for Selective Senolysis to Remodel Ocular Fundus Neovascularization

The abnormal vascular growth in ocular fundus neovascularization is driven by senescent cells that evade apoptosis. These cells trigger chronic inflammation by overproducing senescence-associated secretory phenotype (SASP) factors. To address this, we developed PCC1/PHCF-Gel, a novel dual-mode hydrogel platform for long-term procyanidin C1 (PCC1) release. Its high-dose localized delivery targets p16INK4a+ senescent cells for ablation (senolysis), while low-dose sustained release inhibits SASP-mediated inflammation. To investigate the alterations in senescent features of oxygen-induced retinopathy (OIR) when treated with PCC1/PHCF-Gel, we carried out bulk RNA sequencing. Subsequently, utilizing senescence-related gene sets, namely SASP_Literature Curated UP, Fridman_Senescence_UP, and Global_Senescence_2020, we conducted a Set Gene Enrichment Analysis (GSEA). The analysis results served to reconfirm the accumulation of senescence in the OIR model. However, in the case of the PCC1/PHCF-Gel group, a significant negative correlation with senescence-related genes was observed. At postnatal day 17 (P17), bulk RNA-seq was performed on the retinas of normoxic mice and OIR mice that had received intravitreal injections of PBS and PCC1/PHCF hydrogel at P15 to conduct a systemic transcriptomic characterization.