Adithya Pillai
BME MS Thesis Defense Presentation
Date: 2026-03-27
Time: 12:00 PM - 1:00 PM
Location / Meeting Link: https://teams.microsoft.com/meet/26447873151173?p=U9ZAYoBxOcQZtYt18v

Committee Members:
Dr. Hananeh Fonoudi, Dr. Scott Hollister, Dr. Lakshmi Prasad Dasi


Title: Integration of 3D bioprinting, perfusion bioreactors, and cell spheroids for tissue engineering of the neuroblastoma tumor microenvironment

Abstract:
Neuroblastoma is the most common solid pediatric extracranial tumor, almost always occurring before age 5, mostly diagnosed around 1-2 years of age. High risk neuroblastomas are characterized by high tumor heterogeneity and poor prognosis. While advancements in the treatment have resulted in the improved survival rates of low- and intermediate-risk neuroblastoma patients, the prognosis for high-risk neuroblastoma cases has not increased correspondingly. This indicates a need for further study and treatment development for high-risk patients. Various TME properties are known to promote cancer survival and limit therapeutic efficacy. In vitro models are critical for understanding neuroblastoma tumor progression and therapeutic resistance, yet available systems fail to mimic the complex tumor microenvironment (TME) accurately. This study employs 3D bioprinting and perfusion bioreactor technologies to develop tunable in vitro solid tumor models, using neuroblastoma cells as a representative system. Models including a vascular channel and a central NB housing were developed through embedded extrusion and Digital Light Processing (DLP) bioprinting using methacrylated gelatin (GelMA) as bioink. Print fidelity, mechanical properties, and porosity of the constructs were evaluated. Human umbilical vein endothelial cells (HUVECs) were seeded in the vascular channels (1×10^7 million/mL), and IMR-5 NB cell spheroids were cultured and seeded in the housing. Models were cultured under static and dynamic perfusion conditions at a 100 µL/min flow rate. Models were then analyzed using brightfield microscopy, live/dead imaging, and immunohistochemistry. Bioprinted constructs displayed a high print/design fidelity and tunable mechanical properties. Seeded HUVECs formed a uniform channel lining in both DLP and extrusion bioprinted constructs. Both the HUVECs and NBs maintained a high viability and physiological ratio under static and dynamic perfusion conditions. The results allowed modeling of various TME mechanical and cellular elements and replicating natural drug responses. This study develops a perfusable in vitro model of NB suitable to study disease progression and therapy resistance. Future steps will focus on modeling various biomechanical cues affecting NB therapy and assessing advanced therapeutic options like immunotherapy.