We aim to further the field’s understanding of the anatomical structures within the subarachnoid space (SAS) as it relates to leptomeningeal disease (LMD), i.e., cancer metastasis to the meninges, which is a devastating complication of many systemic cancers.

The three meningeal layers, called the dura, arachnoid, and pia, enclose the central nervous system. The subarachnoid space is a cerebrospinal fluid (CSF)-filled compartment that contains dense networks of collagen-rich fibers known as trabeculae, which support leptomeningeal cells. Although studies have discussed the role of trabeculae in CSF exchange and clearance, little has been done to characterize trabeculae patterns within different CNS regions or to examine how this may influence LMD.

We first engaged in detailed neuroanatomical characterization of trabeculae samples obtained from human cadavers, nonhuman primates, pigs, guinea pigs, rabbits, and mice. SEM imaging revealed significant variation in fiber diameter, density, and arrangement as a function of location within the CNS. After characterization, we developed a library of poly(caprolactone) (PCL) electrospun scaffolds bearing remarkable similarity to trabeculae ultrastructure with biomechanical properties that mimic innate CNS tissues. Cell culture studies using medulloblastoma lines on these scaffolds were performed to evaluate how trabecular fiber organization influences tumor cell behavior within the subarachnoid microenvironment.

The studies revealed that trabeculae fiber ultrastructure plays a role in cell attachment and infiltration into tissue mimics. Quantitative analysis revealed that more open, porous fiber architectures promoted greater medulloblastoma cell infiltration and radial migration, underscoring the role of trabecular morphology in guiding metastatic behavior.

Our findings demonstrate that recreating native trabecular ultrastructure in vitro provides a powerful platform for investigating how meningeal microenvironments influence CNS metastasis and for developing new therapeutic strategies.