Aerogel library with varying porous structures and mechanics regulates motor neuron progenitor differentiation for spinal cord injury repair

The properties of external environment have been acknowledged as important factors influencing cell differentiation. Although efforts have been spared to study the influence of properties on cell differentiation, it is still unknown about how porous structure and mechanics of materials regulate the differentiation of motor neuron progenitors (MNPs) for spinal cord repair. Aerogel library with varying pore sizes and moduli fabricated by methacrylated gelatin and various sacrificial biomaterials according to binary cooperative complementary have been built to study the regulation on differentiation of induced pluripotent stem cells-derived motor neuron progenitors. After cell implantation via gas-liquid technique, MNPs are more likely to differentiate into motor neuron in materials of smaller pore sizes and lower moduli within the proper range (0-100 μm and 0-3 kPa). The experiments for spinal cord injury model revealed that cell-loaded aerogels with pore size of 20 μm and modulus of 0.4 kPa possessed best repair effects. The research provides a promising strategy for fabrication of structurally multiscale composites and clarified the rules of influences of pore sizes and mechanics on the differentiation of motor progenitors, offering theoretical support for manufacture of neural scaffold materials in clinic.