Considering the complexity in terms of design that characterizes the different tissues of the human body, it is necessary to study and develop more precise therapies. In this sense, this article presents the possibility of fabricating photocurable thermosensitive hydrogels with free geometry and based on N-Vinyl Caprolactam (VCL) with the aim of modulating the adhesion of non-planar cell cultures. The fabrication process is based on the use as a mold of two-layer thick water-soluble polyvinyl alcohol (PVA) previously printed by Extrusion Material (MatEx). From this technology it has been possible to obtain hydrogels with different 3D geometries and different crosslinking percentages (2, 4 and 6 mol%). Studies have shown that networks reduce their thermosensitivity not only when the percentage of crosslinking in the formulation increases, but also when the thickness of the hydrogel obtained increases. Based on this reduction in thermosensitivity, the less crosslinked (2 mol%) hydrogels have been evaluated to carry out a novel direct application in which hydrogels with curved geometry have allowed cell adhesion and proliferation at 37 °C with the endothelial cell line C166-GFP; likewise, non-aggressive cell detachment was observed when the hydrogel temperature was reduced to values of 20 °C. Therefore, the present manuscript shows a novel application for the synthesis of free-form thermosensitive hydrogels that allows modulation of non-planar cell cultures.

Thoracic Aortic Aneurysms are life-threatening vascular conditions linked to inherited disorders such as Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, and Familial Thoracic Aortic Aneurysms and Dissections. While traditionally associated with extracellular matrix and contractile defects in vascular smooth muscle cells, emerging evidence suggests a key role for mitochondrial dysfunction. Here, we show that overexpression of ACTA2R179H and TGFBR2G357W in murine aortic VSMCs reduces Mitochondrial Transcription Factor A (Tfam) expression, decreases mitochondrial DNA (mtDNA) content, and impairs oxidative phosphorylation, shifting metabolism toward glycolysis. Notably, nicotinamide riboside, a NAD+ precursor, restores mitochondrial respiration, increases Tfam and mtDNA levels, and promotes a contractile phenotype by enhancing actin polymerization and reducing matrix metalloproteinase activity. These findings identify mitochondrial dysfunction as a shared feature in hereditary Thoracic Aortic Aneurysm, not only in Marfan syndrome but also in other genetic forms and highlight mitochondrial boosters as a potential therapeutic strategies.