Three-Dimensional Bioprinted Aneurysm for Intervention Modeling Validation

Project Overview

Aneurysms, localized dilations or "ballooning" of arterial vessel walls, are estimated to affect 4% of Americans, approximately 30,000 of which rupture yearly. While endovascular coil mediated occlusion is now the standard of care, clinicians performing coil embolism are faced with a choice: to treat aggressively and fill the aneurysm dome with a high volume of platinum coil and risk rupture, or treat conservatively with a moderate density of platinum coils and risk incomplete occlusion and reopening of the aneurysm when healing fails to restore normal blood vessel geometry. Engineering an in vitro aneurysm model is desirable to test these next-generation endovascular medical devices for training practitioners how to deploy these devices, to develop accurate computational simulations, and for understanding how effectively treatments induce clotting or lead to a healing response. Current in vitro aneurysm models suffer from a lack of key functional and morphological features of brain vasculature that limit their applicability for these purposes. To advance the field of medical modeling, we have developed the first ever, fully biological, living in vitro aneurysm model to interrogate treatment with an endovascular device. In this work, we demonstrated that not only could print an aneurysm sac with completely confluent endothelium within 7 days of perfusion culture but also that the endothelium formed in this manner prevented indiscriminate thrombogenesis, a critical feature of living vessels. Detachable coils were delivered into the printed aneurysm sac through the vessel using a microcatheter and static blood plasma clotting was monitored inside the aneurysm sac and around the coils. Devices monitored for 8 days post-treatment showed formation of endothelium at the neck of the fully occluded aneurysm which represents the ideal recovery outcome in aneurysm intervention treatments. The platform combines the benefits of both animal and in vitro fluidic models within one device, including controlled geometries, ease of observation, ease of characterization, and meaningful physiological relevance.

Mission Impact

The work generated in this project is a key demonstration of the integration of two technologies, bioprinting and computer simulations, to better understand complex biology with the ultimate goal of creating computational models that predict health risks. This directly supports the institutional initiative on predictive biology through computation and experimentation. In these efforts, we've made instrumental steps with this novel approach to demonstrate the experimental validation of predictive mathematical models for endovascular treatment outcomes with direct applications to computation-based personalized medicine. This is an extension of Lawrence Livermore National Laboratory's ability to combine high-performance computing with experimentation to capabilities beyond predictive drug discovery and evaluation to also include direct physical intervention. Overall, this research advances the science, technology, and engineering competencies that are the foundation of the NNSA mission, as well as the Laboratory's core competency in bioscience and bioengineering. Partnerships with Duke and Texas A&M are anticipated to aid in developing a pipeline of talent in biomedical device/materials engineering and bio-computing.

Publications, Presentations, and Patents

LK Jang, JA Alvarado, M Pepona, EM Wasson, LD Nash, JM Ortega, A Randles, DJ Maitland, ML Moya, and WF Hynes. "Three-Dimensional Bioprinting of Aneurysm-Bearing Tissue Structure for Endovascular Deployment of Embolization Coils," Biofabrication 13(1) 2020.

WF Hynes, LK Jang, JA Alvarado, M Pepona, EM Wasson, LD Nash, JM Ortega, A Randles, DJ Maitland and ML Moya. "Bioprinted Living Aneurysm for Computational Model Validation and Endovascular Intervention Testing." Invited presentation at the BRAIN Conference, London, UK, 7-10^th December 2020.

ML Moya, LK Jang, JA Alvarado, M Pepona, EM Wasson, LD Nash, JM Ortega, A Randles, DJ Maitland and WF Hynes. "Tissue Structure with Deployment of Embolization Coils Three-Dimensional Bioprinting of Aneurysm-Bearing." Oral presentation at Biomedical Engineering Society, 12-15^th October 2020.