3D Bioprinted retina models for drug screening

利用生物打印技术，利用人诱导的多能干细胞，构建了一种含有RPE和三维(3D)血管组织的体外血视网膜屏障工程眼组织。它成功地概括了脉络膜毛细血管的特征和Bruchs膜的成分，包括RPE诱导的血管内皮开窗和细胞外基质的形成。我们进一步证明了HIF-1诱导了组织中RPE的血管生成，并通过贝伐单抗治疗改善了屏障功能而减少了诱导的血管生成。我们还探索了这种3D视网膜组织模型在研究寨卡病毒感染方面的有效性，并展示了组织中的病毒感染和屏障功能的破坏。因此，这种3D血管化的眼组织模型为研究相关疾病的潜在机制和治疗方法的发展提供了广泛的机会。

An engineered ocular tissue of outer blood retina barrier containing RPE and three dimensional (3D) vascularized tissue has been produced using bioprinting techniques with human induced pluripotent stem cells. It successfully recapitulates features of choriocapillaris and components of Bruchs membranes including RPE induced vascular endothelial fenestration and extracellular matrix formation. We have further demonstrated that HIF-1 induced angiogenesis towards RPE in the tissue and the reduction of the induced angiogenesis with improved barrier functions by bevacizumab treatment. We have also explored the usefulness of this 3D retina tissue model to investigate Zika virus infection and demonstrated viral infection in the tissue and disruption of barrier function. This 3D vascularized ocular tissue model therefore provides extensive opportunities to study underlying mechanisms of relevant diseases and the development of therapeutics.