The field of lung regenerative medicine is still in its infancy, and it largely overlooks the potential role of biomaterial-based microenvironments in promoting lung regeneration in emphysema in COPD. In this study, we aimed at understanding the interactions between primary human lung mesenchymal cells (MCs) and an elastin-like (EL) scaffold that mimics the extracellular matrix, which may be used to trigger regenerative pathways in host MCs in vivo.

As a first step, we have evaluated the cytocompatibility and the morphology of the MCs when seeded inside the scaffold in 3D, in comparison to regular 2D cultures on plastic surfaces. To this end, the MCs were embedded in the EL scaffolds homogeneously, and the cytocompatibility was assessed in terms of cell viability (LIVE/DEAD) and cell metabolic activity (resazurin reduction) at 0, 1, 3 and 7 days of culture. The MCs remained alive similarly to the 2D control, showing excellent cell viability (approx. 98%). The metabolic activity showed a slower increase in 3D than in 2D, with stable levels after 1 day. This is considered more physiological, given that cells expand fast in 2D, which does not reflect the in vivo situation. A similar conclusion could be drawn from the morphological evaluation of the cells by actin (Phalloidin iFluor-555) and nuclei (DAPI) staining. The MCs seeded in 3D were found spread anisotropically in branches, which suggests a more physiological phenotype than the cells grown in 2D.

Altogether, this work sets the ground for further investigations on the interaction of EL scaffolds with lung cells, as a first step to study the potential induction of the regeneration of emphysema in COPD.