Cardiovascular diseases are increasingly becoming the main cause of death all over the world, leading to an increase in the economical and social burden. Vascular tissue engineering (VTE) is paving its routes toward challenging applications, focused mainly on substitutions of small-diameter blood vessels (<6 mm). Native collagen, a natural biological material which possesses extraordinary properties in terms of biocompatibility, has been extensively investigated as a scaffold for VTE. However, collagen is mainly extracted from collagen-rich native natural tissues by different harsh chemical and physical treatments, resulting in a solution susceptible to be processed for the fabrication of supports. These treatments imply the destruction of the native organization of the collagen microstructure, thus resulting in a collagen-based support less resistant in terms of mechanical properties than the native one. Therefore, different approaches have been investigated to increase these mechanical properties. Although UV irradiation present a strong potential for efficient crosslinking collagen macromolecules, the undesirable effects of UV on cell activity still remain the main challenge to be overpassed. The aim of this study was to investigate the potential of UV radiation and glycation for the crosslinking of collagen gels, with particular concern to the cells and capacity of the cells to remodel the collagen structure.