Electrospun Scaffolds to Model Medulloblastoma Metastasis and Drug Response
Year: 2026
Type: dissertation
Abstract: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite available treatments, such as surgery, craniospinal radiation, and chemotherapy, metastatic dissemination into the leptomeninges remains a major clinical challenge. Between 20% and 30% of MB patients present with metastatic dissemination at diagnosis. Even with treatment, which often results in debilitating long-term side effects, patients can experience metastatic recurrence of the disease. Dissemination of malignant cells occurs through extravasation into the subarachnoid space (SAS), a compartment filled with circulating cerebrospinal fluid and fibrous collagen structures, termed subarachnoid trabeculae. These unique microenvironmental features are thought to facilitate migration of tumor cells throughout the central nervous system, yet current models of MB are limited in their ability to capture cell-microenvironment interactions. To advance therapies targeting MB metastasis, models that accurately reflect the conditions of metastasis and can support reproducible therapeutic testing are needed. Here, we present a scaffold-based metastasis model that recapitulates the MB tumor microenvironment and enables quantification of metastatic behaviors. Poly(caprolactone) random-fiber scaffolds were electrospun to mimic the various architectures of trabeculae observed in vivo. Next, adhesion, proliferation, and migration in HDMB03 and DAOY cells were assessed to investigate metastatic behavior in a fibrous microenvironment. To assess the model’s performance in therapeutic testing, we evaluated dose-response of three small molecule drugs with established in vitro efficacy against MB. With this model, we aim to bridge the gap between 2D culture and in vivo studies, thereby providing a translationally relevant platform for further research into mechanisms of MB metastasis and therapeutic testing.
DOI: 10.7275/58617
Author: Bigelow, Lily
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7223590616