Regenerative Medicine
and
Tissue Engineering
Research Areas
The research of my group is aimed at furthering our understanding of the mechanical behavior of the respiratory system to improve the diagnosis and treatment of respiratory diseases. We use basic and translational approaches in a multidisciplinary framework involving close cooperation with clinical research groups working in the field of respiratory medicine. We study respiratory mechanics with a multiscale approach extending from organ to molecule. At the organ level, we study the mechanical properties of the airways and lung tissues and the alterations of the mechanical function associated with respiratory diseases. Our work is focused on four main areas:
Area 1: Physiopathology of Obstructive Sleep Apnea and its Consequences.
Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder among adult population and is characterized by an increased collapsability of the upper airway promoting recurrent occlusions during sleep hours leading to intermittent hypoxia (IH) and sleep fragmentation (SF). The most common risk factors of OSA are age, male gender and obesity.
My group has a tight translational collaboration with Dr. Josep Maria Montserrat at Hospital Clinic of Barcelona and participates in the Spanish Sleep Network. During the last years and we have started an active and proliferative collaboration with Dr. Gozal at the University of Minessota. Our expertise in bioengineering allowed the development of new in vitro and in vivo translational models to better understand the phatophysiology of obstructive sleep apnea. These models have been crucial to study in more detail the effects of sleep fragmentation, intermittent hypoxia and hypercapnia in the cardiovascular, cognitive, metabolic and recently cancer adverse outcomes observed in OSA patients.
Intermittent hypoxia has been associated to increased neuronal apoptosis and expression of Alzheimer Disease markers. We found that a reduction in brain stiffness, measured by atomic force microscopy, in AD could be explained by neuronal demyelination.
Study of the cardiovascular consequences of IH and SF. The images show the aortic remodeling induced by chronic intermittent hypoxia (CIH) in a murine model of OSA
Development and characterization of in vitro and in vivo systems to understand the physiophatology of respiratory diseases
Area 2: Cancer and hypoxia
In 2012, our lab showed for the first time that intermittent hypoxia similar to that suffered by OSA patients is able to promote tumor growth, invasiveness and metastasis. This work posed a new challenge in the field of OSA, opening a new perspective unexplored to date. Those findings served as proof of concept of the epidemiological studies published later on, revealing an independent association between OSA and cancer.
Intermittent hypoxia mimicking OSA enhances melanoma growth and metastatic potential
Lab-on-a-chip to mimic the gradient of oxygen between blood vessels and tumor insterticium
(From Roser Colina's project)
Micropatterned surfaces: Techniques and applications in cell biophysics
Engineering microchannels for guided cell migration in a gradient of oxygen (From Aina Laguarta's project).
Area 3: Tissue engineering and regenerative medicine
We are currently investigating the development of natural scaffolds from decellularized lungs to better understand the role of the extracellular matrix in the development of respiratory diseases such as fibrosis, lung cancer and emphysema. These models will provide a more realistic environment to understand all the mechanisms involved in these respiratory diseases. Novel lung-derived hydrogels will be used to understand the role of the mechanical stimuli in the lungs to differentiate and improve the therapeutic potential of stem cells after acute lung injury. In this regard, I have developed a new lab-on-a-chip capable to reproduce the cyclic stretch that occurs during spontaneous breathing in lung scaffolds and a pulsatile shear stress biorreactor.
