Development of a 3D cell-printed RVO model by advancing a retina-on-a-chip with hybrid retinal dECM bioink and an integrated 3D bioprinting system

Abstract

As the second most prevalent retinal vascular disease leading to vision loss, retinal vein occlusion (RVO) affects approximately 28 million people worldwide, and its prevalence is rising due to high-fat dietary habits. RVO is particularly concerning due to its high recurrence rate and lack of curative treatment strategies. Although various retinal models have been developed to study retinal vascular diseases, replicating tissue-specific microenvironments remains challenging. In particular, incorporating key features, such as the blood–retinal barrier (BRB) and narrow vascular structures, has proven difficult in previous models. To address this issue, we developed a retina-on-a-chip using an integrated 3D bioprinting system that combines multi-nozzle and triple-coaxial printing with a hybrid retinal-derived decellularized extracellular matrix (RdECM) bioink and vascular tissue-derived dECM (VdECM). This platform successfully incorporated BRB compartments and interconnected vascular structures. To simulate RVO, we fabricated an RVO-on-a-chip by perfusing low-density lipoprotein (LDL) and adjusting the vascular printing speed to create a narrowed vasculature. The RVO-on-a-chip successfully recapitulated RVO progression, with pathological changes originating from the blood vessels and propagating through the inner and outer BRB compartments, closely mimicking real RVO lesions. Furthermore, drug treatments applied to the chip demonstrated efficacy comparable to clinical outcomes. Our chip effectively replicated key pathological features of retinal vascular diseases, providing a valuable platform for drug testing and advancing research on retinal vascular pathology. This chip holds promise for improving therapeutic strategies for RVO and related disorders.