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 aim to tackle some of these health problems, advancing the fields of tissue engineering, biomedical devices, and cardiovascular biomechanics.
In the context of tissue engineering, ATOMS Lab is pursuing ground-breaking work in de-cellularization (DC) and subsequent re-cellularization (RC) of donor tissues, as a paradigm with enormous potential for designing tissues and organs for transplantation. Our research foci and specific projects, detailed below, are informed by our close collaboration with Dr. Thomas Waddell and Dr. Shaf Keshavjee, world leaders in lung transplantation, at the Latner Thoracic Research Laboratories, University Health Network.
In DC/RC, the mechanical, biological and chemical environments play a critical role, 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 experiments required to develop DC/RC protocols and bioreactors. 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. However, there is a lack of comprehensive, experimentally validated modelling/simulation methodologies accounting for the most important cell biology behaviours (deposition, attachment, expansion, differentiation, death) and their modulation by the mechano-bio-chemical environment.
Our main research thrust in this area is the development, implementation and experimental validation of efficient computer simulation models for cell removal during de-cellularization processes, and for cell deposition, attachment, and differentiation for perfusion-based re-cellularization. Leveraging the strength of these models, our work progresses in the context of two application-specific projects:
Design of Bioreactors. We are designing bioreactors for DC/RC of trachea and lung scaffolds. Tracheal scaffolds provide an excellent development testbed thanks to their simple cylindrical geometry that allows easy access to every point in the scaffold. Lung scaffolds, our long term target, have complex, branching vascular and airway networks, which increases the complexity and cost of in silico, in vitro and ex vivo models.
RC/DC of Tracheal and Lung Scaffolds. We use simulations to predict how the DC/RC processes are affected by experimental parameters such as flow rate, temperature, pressure, shear stress, and the time, duration and point of injection of biochemical agents. This dramatically reduces the need for costly and time-consuming in vitro and ex vivo experiments, except as needed for model validation.
Cardiovascular Biomechanics and Medical Devices
Cardiovascular disease is one of the leading causes of death in the industrial world. Engineering technologies offer novel solutions to diagnose and treat cardiovascular diseases and improve long-term patient outcomes. Partnering with world-class vascular surgeons, cardiac surgeons, and cardiologists at the Peter Munk Cardiac Centre, University Health Network, and the Labatt Family Heart Centre, Hospital for Sick Children, we aim to use a multidisciplinary approach to solve critical problems related to congenital heart disease and aortic aneurysms.
Surgical Planning and Treatment of Congenital Heart Defects
Congenital heart defects are heart abnormalities at birth that occur in ~1% of the population. The most severe, such as tetralogy of Fallot or single ventricle physiology require one or more surgeries during the first few years of life and monitoring throughout adulthood. Using patient data and computational models, we aim to develop a surgical planning tool to improve long-term outcomes in patients with tetralogy of Fallot and a medical device to bridge patients with failing Fontan circulation (single ventricle physiology) to heart transplants.
Computational Models of Aortic Aneurysm Repairs
Aortic aneurysms are pathological dilations of the body’s main artery than can be treated with either open surgical repair or a minimally invasive medical device called a stent graft. In our lab we are interested in how stent grafts interact with the aorta during and after deployment and we use a combination of computational fluid dynamics and solid mechanics tools to study these interactions. We also use 4D flow magnetic resonance imaging and biaxial tensile test data to understand links between aortic blood flow and aortic wall mechanical properties.