Light-controlled microenvironment for Advanced organoids with Neural tube and somite Tissues Engineered with Responsive Nanoparticles

Objective

Neural tube (NT) defects, such as spina bifida and encephalocele, affect over 300000 births worldwide each year and originate from alterations in the earliest stages of embryogenesis. Understanding their causes remains challenging because human NT development is inaccessible to direct investigation. To overcome this limitation, LANTERN aims to create a dynamic and shape-controlled reproducible in vitro model of human NT development using hiPSC-derived Neural tube and Somites Advanced Organoids (NSAO). The main objective is to reproduce, with unprecedented precision, the spatial and temporal signals that drive NT patterning, thereby providing a reliable platform to study NT defects. The project integrates complementary innovations: (i) a biomimetic hydrogel niche, engineered from extracellular matrix-like biopolymers and dynamically reshaped through multiphoton microscopy; (ii) nanoparticle-mediated morphogen delivery, exploiting photosensitive gold nanorods to establish adaptive gradients of morphogens; (iii) advanced organoid culture, where NSAO grow under controlled mechanical constraints and are exposed to tunable morphogen sources. Together, these technologies will yield reproducible tissue architecture and accurate dorsal-ventral axis regionalization, validated through advanced imaging and RNA sequencing. By integrating bioengineering, nanotechnology, and stem cell biology, LANTERN goes beyond the state of the art in organoid systems, scaffolds, and morphogen delivery strategies. The outcomes will provide a robust model to identify the molecular and mechanical causes of NT defects, reduce reliance on animal studies, and establish a platform with translational potential for drug screening. Aligned with the MSCA work programme, the fellowship will foster interdisciplinary training, enhance the researcher’s independence and employability, and contribute to Europe’s leadership in innovative and ethically responsible biomedical research.