Three-dimensional tissue engineering and organoid technologies for retinal regeneration and therapy

The human eye, a masterpiece of evolution, orchestrates the intricate process of vision. The retina is a tissue with a layered structure that plays a critical role in converting light signals into neural impulses interpretable by the brain. Various eye conditions such as glaucoma, retinitis pigmentosa, age-related macular degeneration, and other retinopathies are characterized by damage or degeneration in the retina. Recent strides in organoid cultivation and advanced three-dimensional (3D) bioengineering technologies offer promising avenues for potential therapeutic interventions. Compared to traditional two-dimensional cell culture models, which are non-natural and limited in accuracy, 3D models, including organoids, electrospinning constructs, microfabrication-based scaffolds, and hydrogel systems, are more delicate, especially in recapitulating tissue architecture, offering spatial patterning, and enabling vascularization. Retinal organoids are 3D multicellular structures derived from stem cells that can mimic the retina's layered architecture and functionality. However, their inherent complexity, including the presence of multiple differentiated cell types, may not be necessary for all disease modeling applications. In contrast, engineered 3D technologies can be tailored to specific retinal diseases by incorporating only the most relevant cell types, matrix stiffness, and spatial arrangements, offering greater experimental control and reproducibility in targeted therapeutic testing. In the following paper, we will discuss organoid generation in detail. Besides retinal organoids, bioprinting is another promising avenue for regenerative medicines. We further review a suite of 3D fabrication strategies, including inkjet and laser-assisted bioprinting, electrospun scaffolds, and hydrogel systems, and evaluate their current and potential applications in modeling retinal diseases and developing translational therapies. We will also delve into the contemporary advancements in retinal therapies, particularly emphasizing the roles and prospects of organoid and engineered 3D technologies.