Engineering technologies are key to solving the world’s complex health problems. Partnering with renowned surgeons and clinicians at the University Health Network, researchers in the ATOMS lab advance the fields of tissue engineering, biomedical devices, and cardiovascular biomechanics.

Tissue Engineering

In the context of tissue engineering, the ATOMS Lab is pursuing ground-breaking work in the production of airway and cardiac tissues. Our research foci and specific projects, detailed below, are informed by our close collaboration with Dr. Thomas Waddell and Dr. Shaf Keshavjee, Latner Thoracic Research Laboratories, and Dr. Michael Laflamme, McEwen Stem Cell Institute, University Health Network.

The mechanical, biological and chemical environments play a critical role in the successful development of tissues, and several research groups are working towards developing devices and experimental protocols to characterize, predict and control these environments. However, the pace of progress is hindered by the costly, time-consuming nature of the required in vitro, ex vivo and in vivo experiments. Computer simulations, referred to as in silico experiments in the bioengineering and biomedical literature, have been identified as key for accelerated discovery across many bioengineering/biomedical domains. Yet, a comprehensive, experimentally validated modelling/simulation methodology, accounting for how the most important cell biology behaviours (deposition, attachment, expansion, differentiation, death) are modulated by the mechano-bio-chemical environment, is still unavailable.

Our main research trust in this area is the development and experimental validation of efficient computer simulation models for cell deposition, attachment, proliferation and differentiation in both perfusion-based and static in vitro processes. We have developed a comprehensive methodology to formulate, select, calibrate, validate and analyze these in silico models (figure below). These simulation models combine traditional Computational Fluid Dynamics (CFD) methods for advection-diffusion-reaction systems, as well as cell population models based on system of ordinary differential equations. Using these models, we can inform the design of bioreactors for decellularization and recellularization of tissue scaffolds, and for de novo production of cells, micro-tissues, organoids and artificial organs. Furthermore, since our models consider both mechanical and biochemical cues and their effect on cell population, we can leverage these models to optimize the associated experimental protocols (e.g., frequency of media replenishment, required mixing levels) to maximize cell yield, minimize production costs, and minimize variability.

Methodology for development, calibration and validation of cell population models.

Computational Modelling of Artificial Placenta System

Preterm births, before 37 weeks of gestation, is a major global health problem, affecting 15 million deliveries per year. Morbidity and mortality are particularly high in extremely premature (22 – 28 weeks of gestation) deliveries. At this stage, the maternal placenta provides oxygen transfer to the fetus, and the lungs are not fully developed. The purpose of Artificial Placenta (AP) systems, depicted in the picture, is to mimic the placenta’s function of oxygen distribution while maintaining blood circulation when the fetus is transferred from the maternal womb to a synthetic bag connected to a closed-loop system that provides circulatory and gas-exchange support. With the collaboration between our lab and the SickKids Research Institute, we aim to create an accurate computational model for the AP system hemodynamics that can enable us to determine how changing certain AP circuit parameters can help optimize the fetus’ hemodynamics to improve survival.

Schematic (left) and flow circuit (right) of an Artificial Placenta (AP) system for fetal pigs.

CFD Study of Hemodynamics in Pulmonary Vein Stenosis

Pulmonary vein stenosis (PVS) is a progressive vascular disease characterized by narrowing of the blood vessels that transport oxygenated blood from the lungs to the heart. Treatment of PVS is challenging, and rates of restenosis remain high. The goal of our research is to provide insight into the role that blood flow conditions have on the initiation and progression of PVS to inform the future development of novel treatment strategies. This research is in collaboration with Dr. Rachel Vanderlaan at the Hospital for Sick Children.

Distribution of time-averaged wall shear stress in pulmonary veins. Red regions near the heart atria indicate increased shear stress caused by stenosis.

Hemodynamics of Ascending Thoracic Aortic Aneurysms (ATAAs)

Ascending thoracic aortic aneurysms (ATAA) pose a significant risk of aortic dissection and death. Valve-sparing root replacement (VSRR) is a common treatment for aneurysms affecting the root, but complications still occur, especially in the descending aorta of Marfan syndrome patients. Our research explores a potential correlation between post-VSRR geometric changes and late complications in the descending aorta, based on altered blood flow patterns and hemodynamic parameters. The long-term objective of our research is to inform the development of personalized treatment plans for patients undergoing VSRR.  

Distribution of time-averaged walls shear stress on the descending aorta. The aortic wall has been unrolled into a rectangular region for ease of visualization.