Cell behavior is not only guided by chemical signals, but by the mechanical properties of the cells and their environment their microenvironment. Thus, is of high importance to fabricate models that incorporate the physical stimuli to which cells are exposed to, specially in cardiovascular and lung models where breathing and heart beating forces are predominant. In this regard, the concept of 4 dimensional (4D) in vitro modelling has emerged, which accounts for responses to a given stimuli in the context of a 3D model setup, resulting in a change over time, thereby representing a fourth dimension.

Cardiovascular models

We are focused on the fabrication of multilayered vascular models. We are working on the production of an artery model with cyclic expansive properties, capable of mimicking the different physical forces and stress factors that cells experience in physiological conditions. For that we develop hybrid multifunctional formulations that include a stimuli-responsive and thermosensitive polymeric ink, and extracellular matrixes-derived bioinks for the more internal artery wall layers. Cyclic expansion can be induced thanks to the inclusion of photo-responsive plasmonic NPs embedded within the thermoresponsive ink composition, resulting in changes in the thermoresponsive polymer hydration state and hence volume, in a stimulated on–off manner. The direct effect of cyclic expansion and contraction on the overlying cell layers by analyzing transcriptional changes in mechanoresponsivemesenchymal genes associated with such microenvironmental physical cues.

Pulmonary models

The lung, specifically, the air-liquid interface (ALI) of the alveolar region where breathing occurs is a complex tissue where its mechanical properties, ALI arrangement and breathing dynamism are crucial for the correct tissue maturation and functioning. Thus, when developing 3D alveolar models as tissue analogues that represent the in vivo environment, it is highly important to mimic the ALI both structurally and mechanically, including the expansion-contraction motions that occur during breathing. In this sense we are focused on the fabrication of dinalic ALI models including all the different layers. We also include NPs as stimuli actuator that can help mimiching such breathing forces. We also design lung extracellular matrixes that can support the representative cells of the alveoli.

Breast cancer lung metastatic Models

Breast cancer (BC) remains the leading cause of cancer related mortality in women worldwide, primarily as a result of metastatic outgrowth in distant organs including lungs. In order to advance therapeutic strategies and patient prognosis, it is imperative to gain insight into metastatic events within the target site. This requires biomimetic materials which recapitulate lung tissue composition and mechanics, compatible with conventional as well as novel technologies such as microfluidics and 3D printing. Thus, we are focused on designing tunable BC lung metastatic niches within in vitro models to investigate the role of extracellular matrix (ECM) stiffness during metastatic outgrowth. We are also focused on vascularization of such models