Selective Promotion of Retinal Organoid Attachment and Differentiation by Amine‐ and Hydroxyl‐Modified Surfaces

The clinical success of organoid‐based therapies depends critically on understanding and controlling how biomaterial surfaces influence organoid behavior and integration. Retinal organoids (ROs) are emerging as advanced in vitro models with potential for transplantation, yet the molecular underpinnings of their interactions with engineered biomaterials remain largely unexplored. Here, this study systematically examines the effects of surface chemical modifications: amine (NH 2 ), hydroxyl (OH), phenyl (Ph), and methyl (CH 3 ) groups presented via alkyl‐based self‐assembled monolayers, on RO attachment, migration, and differentiation at key developmental stages. This study's' findings reveal that surface chemistry is a major determinant of organoid response: Hydrophilic surfaces (OH and NH 2 ) markedly enhance RO migration and retinal ganglion cell differentiation, while less wettable surfaces (Ph and CH 3 ) restrict initial attachment. These results shed new light on the pivotal role of the biomaterial interface in directing 3D organoid development, offering actionable insights for the optimization of organoid delivery, integration, and function in regenerative medicine. A deeper understanding of these interactions will enable the rational design of biomaterial platforms and accelerate the translation of organoid models to clinical therapies.