Data-driven bioengineering of the extracellular matrix to promote tissue homeostasis and repair

The dysregulation of the extracellular matrix (ECM) is related to several diseases, like cancer or pulmonary disorders. Thus, an opportunity arises in targeting the restoration of the physiological ECM signalling.

However, current methodologies to build ECM equivalents are limited in recapitulating the main features of the native matrix.

This is partially due to the lack of information about specific changes in the ECM, an issue that can be addressed with the use of advanced mass spectrometry (MS) methods.

Herein, I will develop a data-driven strategy to bioengineer ECM equivalents (bioECM) that can be employed to promote tissue homeostasis and repair.

As a first approach, I will focus on emphysema, one of the main aspects of chronic obstructive pulmonary disease (COPD) that implies the breakdown of the ECM in the alveolar spaces where oxygen diffuses from the air to the blood.

In this project, 1) I will identify ECM components lost in emphysema using MS on human lung biopsies from COPD patients, 2) I will develop a Lung-bioECM made of a biomaterial hydrogel and the identified lost components bioconjugated through ‘click chemistry’, 3) I will study the interaction of the Lung-bioECM with human COPD fibroblasts in vitro, and 4) I will confirm the repair potential with a pre-clinical model of emphysema.

My vision is to define a data-driven workflow for the development of tissue- and disease-specific bioECM as therapeutic alternatives with broad clinical impact.