Additive manufacturing of patient-specific intracranial aneurysm cell culture models

Abstract

Intracranial aneurysms (IAs) are present in 2-6% of the global population. While rare, rupture results in mortality rates of 30-50% and lifelong disabilities in survivors. While treatment of unruptured IAs carries its own risk of mortality, there are no rigid guidelines indicating which IA presentation is at greater risk of rupture. We develop and evaluate the suitability of various additive manufacturing processes to fabricate patient-specific IA culture models for understanding IA pathophysiology and thereby support future development of a rupture risk prediction tool. Material compatibility of several 3D printed resins, polydimethylsiloxane (PDMS) and collagen gel with immortalised human brain endothelial cells (HBECs) were investigated. Patient angiograms were segmented to produce in vitro models via two fabrication approaches: stereolithography (SLA) 3D printing versus chocolate injection moulding of a sacrificial core embedded in PDMS. These 3D arterial models were then cellularised with HBECs, and geometric accuracy and distension properties evaluated. PDMS, collagen gel and the elastic50A resin materials supported cellularisation on material surfaces with high cell viability and proliferation. Both the 3D printed resin and injection moulding techniques successfully fabricated patient-specific basilar artery IA models with a Dice-Sorensen coefficient of over 90%. However, only PDMS models offered complete cell coverage in 3D geometries. This exceeds current benchmarks on IA fabrication accuracy. Through controlling IA model wall thickness, we demonstrate the ability to create localised distension under pressure in the context of thin- and thick-walled aneurysms. In vitro IA models present a promising platform for investigating IA pathophysiology and rupture risk. The novel chocolate sacrificial core technique offers a biocompatible, support-free fabrication method suitable for 3D cultures. Given the independent effects of fluid dynamics and mechanical strain on cell behaviour, it is essential to characterise distension under pressure and ensure accurate fabrication for reliable analysis into cell behaviour.