Biodegradable Silicon MICROMATRIX for Controllable RETINOIC Acid Supplement in NEUROAL Differentiation

Abstract

Human induced pluripotent stem cells (hiPSCs) offer the potential to generate motor neurons, providing a valuable platform for studying neuro-muscular diseases. However, current methodologies for deriving motor neurons from hiPSCs face limitations in replicating the diversity and maturity of native motor neurons, primarily due to the challenge of mimicking the spatiotemporal gradient of morphogens. Among these morphogens, retinoic acid (RA) plays a crucial role in spinal cord development. We address current limitations in deriving motor neurons from hiPSCs by employing biodegradable porous silicon microparticles. Overcoming the challenge of replicating the diversity and maturity of native motor neurons, we strategically utilize a biodegradable porous silicon microparticles to enable sustained release of the crucial morphoge. While RA plays a pivotal role in spinal cord development, its short half-life in physiological environments hampers efficient neural differentiation. Our approach involves loading hydrophobic RA molecules into the porous silicon microparticles, transforming it into a reservoir for controlled and prolonged release of RA. Through a systematic exploration of structural parameters such as pore size, particle size, and RA-sealing chemistry, we precisely manipulate RA concentration in culture conditions. Our results demonstrate a continuous and secure release of RA, maintaining its activity over an extended period, offering a novel methodology to enhance motor neuron differentiation from hiPSCs.