The PhD defence will take place in “Sala Multimedia 3.S1.08, Biblioteca Rey Pastor, Universidad Carlos III de Madrid, Campus de Leganés”.

The dissertation is titled “engineering advanced biomaterials for in vitro platforms of lung and skin”.

It has been advised by Jennifer Patterson and Diego Velasco.

Abstract:

This PhD thesis focuses on the design and characterization of innovative biomaterials aimed at recreating complex tissue interfaces in advanced invitro models. In particular, applications in lung-on-a-chip systems and tissue engineering strategies for skin expansion are addressed. To this end,gelatin-based hydrogels produced using different crosslinking strategies, including chemical and photoinduced approaches, as well as flexible polymeric fibrous membranes fabricated by electrospinning, were developed.

In the p ulmonary context, the recreation of the stromal-epithelial interface was investigated using three-dimensional matrices compatible withmicrofluidic environments. Initially, natural gelatin and low-molecular-weight gelatin (LMWG) hydrogels crosslinked with genipin were developed and evaluated in terms of processability, mechanical properties, porous structure, and cytocompatibility. However, these systems exhibited adequate biological performance; the loss of transparency after crosslinking limited their applicability in microfluidic platforms.

To overcome these limitations, photocrosslinkable methacrylated gelatin (GelMA) and low-molecular-weight GelMA (LMWGelMA) hydrogels were explored, demonstrating for the first time the viability of LMWGelMA as a room-temperature processable alternative to conventional GelMA. These hydrogels exhibited tunable mechanical properties within the soft tissue range, appropriate porosity, and high cytocompatibility.

Subsequently, a biomimetic pulmonary stromal-epithelial interface model was developed by encapsulating human fibroblasts within the hydrogels and culturing human epithelial cells on the hydrogel surface. The system was finally integrated into a lung-on-a-chip device, allowing the evaluation of cellular behavior under dynamic flow conditions.

In the field of skin tissue engineering, two complementary strategies were developed. On the one hand, biomimetic electrospun membranes were mechanically and biologically characterized using human dermal fibroblasts. On the other hand, GelMA-based hydrogels were employed to establish dermal-epidermal interface models. Both systems were independently evaluated with skin cells to assess their potential future combination into a more complex three-dimensional skin model integrating both dermis and epidermis.