Self-Assembled Microframeworks for Spatially Controlled Growth of Vascularised Brain Organoids

Brain research still relies heavily on animal models, which raise ethical concerns and often do not fully recapitulate human physiology. Brain organoids (BOs), derived from pluripotent stem cells, have recently emerged as promising in vitro models that reproduce key human-specific features of brain. However, current BO protocols offer little control over the tissue microarchitecture, which is essential for guiding tissue structure and function. Here, scaffold-based approaches show promise, but still remain limited. An ideal scaffold for BOs should support cell adhesion, allow dynamic remodelling, and be porous to enable vascularisation. BRAINFRAME aims to fill this gap by developing a self-assembling microparticle framework that serves as a structural scaffold for BO growth and differentiation. Cell-adhesive microparticles engineered with supramolecular functionality will be fabricated by two-photon polymerisation and designed to self-assemble into porous three-dimensional frameworks. Through reversible noncovalent interactions, these microframeworks provide structural support, enable remodelling during growth, and impart a “living” characteristic that allows incorporation of additional microparticles at later stages. The intrinsic porosity of framework enables nutrient and oxygen perfusion for BO growth. The “living” quality and porosity will be further exploited to promote vascularisation of BOs. Thus, by combining microfabrication, supramolecular chemistry, and organoid technology, BRAINFRAME will establish dynamic and perfusable microstructural scaffolds for next-generation organoid models. These outcomes will have direct impact on fundamental neuroscience and drug discovery while reducing reliance on animal models. This fellowship will allow me to integrate my expertise in organic and supramolecular chemistry with bioengineering while gaining interdisciplinary skills in microfabrication and organoid culture to achieve innovative in vitro models for the future.