Mechanobiology &
Soft Materials
Laboratory
Research Projects
At the MSML (aka Balalab), our area of research is in the development of organ-chip technologies to study cell and tissue mechanobiology – The understanding of how organ/cell structure, function and biology are modulated by mechanical forces, in health and disease. This is a line of inquiry that seeks to understand the role of an organ’s environment, and not just innate genetics, in the initiation and progression of disease, and using this knowledge to develop novel therapeutic strategies. The study of cell function and disease in the context of mechanobiology is especially significant in organs and tissues that are in continuous dynamic motion during their function (e.g. the heart, heart valves, blood vessels and bone). Within this theme, we have focused on the following areas of research:
To ensure the maintenance of the delicate homeostasis of the brain, the surrounding vasculature is specialized to prevent most substances from freely reaching it. The highly selective interface between the brain and its blood vessels is known as the blood-brain barrier (BBB) and is formed by the complex interplay between 5 major cell types: brain microvascular endothelial cells (BMECs), brain pericytes, astrocytes, neurons, and microglia. As BBB structure and function are uncovered in the cellular and molecular level, there is increasing evidence pointing to the role of BBB disruption in the pathophysiology of several neuropathologies and injury outcomes. A key challenge in this field is the lack of physiologically relevant models to enable a deep understanding of the healthy and diseased BBB. Our lab has been working on the development of a multicellular BBB-on-chip device that mimics the neurovasculature organization and microenvironment while being compatible with experimental traumatic brain injuries (TBIs). The platform that started housing primary rat BMECs and astrocytes, now has been further developed to include isogenic co-cultures of human induced pluripotent stem cells (hiPSCs) derived neurovascular cell types. Our current focus is to apply this technology to understand the role of BBB dysfunction in primary and secondary injury mechanisms in the context of repetitive TBIs, as commonly sustained in the context of intimate partner violence, combat, and sports.
Coco Chip is a groundbreaking heart muscle-on-chip platform designed to transform the way we study and treat heart diseases. This patented innovative technology, short for "Co-cultured Cardiomyocytes-on-a-Chip," allows scientists to non-invasively track the contractility (or beating) of heart muscle cells. By mimicking the natural environment of heart tissue on a benchtop device, Coco Chip opens new doors for drug screening, evaluating cardiac treatments like pacemakers, and studying the progression of heart diseases in individuals from varying genetic backgrounds. These applications can lead to personalized treatment strategies and a better understanding of heart diseases in diverse groups.
Our lab is dedicated to understanding the underlying mechanisms of heart valve physiology and disease, particularly calcific aortic valve disease (CAVD), which poses a significant socio-economic burden due to its prevalence and the aging population. Currently, surgical valve replacement is the only treatment strategy as early diagnostic, mitigation, and drug strategies remain underdeveloped. To address this, we design and engineer novel microphysiological or organ-chip systems to mimic the aortic valve using microfabrication techniques like 3D printing, photolithography and soft lithography. We also engineer physiologically relevant biomaterials like extracellular matrices for disease modeling and scaffolds for heart valve prosthetics using centrifugal jet spinning to create biopolymeric scaffolds. We use porcine- and human-derived cells to study the interplay between the mechanical environment (e.g. cell shape modeled through microcontact printing and cyclic strain modeled through a custom biostretcher), cell signaling (Local renin-angiotensin system, fibroblast growth factor and PI3K, Akt pathway) and biological processes (endoplasmic reticulum stress and proteostasis). We also use multiphoton imaging in collaboration with the metabolic core in the university to track disease progression and altered cell metabolism in diseased cells. Our work aims to provide insights into how the valve responds to pathological stimuli and identify therapeutic targets for valvular disease treatment.
The human nasal airway is the first line of defense against airborne pathogens, and it is often the site of debilitating disorders such as asthma and rhinitis. Physiologically relevant models of the nasal airway are essential to understanding how these diseases develop, but many current models lack important dynamic conditions (such as breathing) which affect cellular function. Our lab is focused on developing a nasal airway-on-chip platform which can mimic the breathing airway. Using this dynamic platform, we can study how airflow affects cell behavior and investigate how healthy and diseased nasal airways are impacted by airborne particulates.
