Retinal degenerative diseases such as age-related macular degeneration (AMD) represent a leading cause of blindness, resulting in permanent damage to retinal cells that are essential for maintaining normal vision. Around 12% of people over the age of 65 have some form of retinal degenerative disease. Whilst antibody-based drugs have revolutionised treatment of neovascular AMD, they are only effective at an early stage and cannot prevent eventual progression or allow recovery of previously lost vision. Hence, there is a clear unmet need to find innovative treatment strategies to develop a long-term cure. The replacement of damaged retinal cells is thought to be the best therapeutic strategy for the treatment of patients with retinal degeneration. Advanced therapy medicinal products (ATMPs) are a group of innovative and complex biological products including cell therapy medicinal products, gene therapy medicinal products, and tissue engineered products. Development of ATMPs for the treatment of retinal degeneration diseases has become a fast-growing field of research because it offers the potential to replace damaged retinal cells for long-term treatment of AMD. While gene therapy has shown encouraging results, its effectiveness for treatment of retinal disease may be hampered by the body’s response and problems associated with inflammation in the eye. In this mini-review, we focus on describing ATMP approaches including cell- and gene-based therapies for treatment of AMD along with their applications. We also aim to provide a brief overview of biological substitutes, also known as scaffolds, that can be used for delivery of cells to the target tissue and describe biomechanical properties required for optimal delivery. We describe different fabrication methods for preparing cell-scaffolds and explain how the use of artificial intelligence (AI) can aid with the process. We predict that combining AI with 3D bioprinting for 3D cell-scaffold fabrication could potentially revolutionise retinal tissue engineering and open up new opportunities for developing innovative platforms to deliver therapeutic agents to the target tissues.

Modelling human cortical microcircuitry in vitro requires platforms that recapitulate both the compositional complexity and spatial architecture of developing neural tissue. Current organoid and assembloid models often rely on the bulk fusion of pre-differentiated, region-specific cells, lacking the capacity for emergent spatial co-differentiation and microenvironment-driven multiscale organisation. There is also a lack of neural and neuronal-glial models with photo-architectured network geometries. To address these limitations, we present a volumetric in situ differentiation system using a triculture of precision reprogrammed human iPSC-derived glutamatergic neurons, GABAergic neurons and astrocytes embedded throughout ultra-soft photocrosslinkable hydrogel microenvironments. The deterministic and spatially controlled method allows us to engineer macro-scale, interconnected human neural networks directly onto functional microelectrode array interfaces using projection photopatterning for high-throughput screening. Unlike fusion-based organoids and assembloids, our platform enables simultaneous, spatially distributed lineage differentiation and maturation, and extensive topography-guided neurite outgrowth bridging localised cellular hubs to recapitulate various aspects of neurodevelopmental patterning and synaptic integration in 3D. The model enables topographic patterning of neuronal-glial networks as well as 3D cell-embedded bioprinting with the developed triculture system. Both modes of cellular growth are studied and demonstrated here. Longitudinal electrophysiological tracking over a month of culture reveals a transition from immature, quiescent states to asynchronous, information-dense microcircuits characterised by an expanded state-space manifold and physiological excitatory-inhibitory balance. By replicating the mechanics of native brain parenchyma, the model presents a highly reproducible, scalable and flexible platform for the study of cortical microcircuitry development, neurodegenerative decline, and inter-regional network assembly.