Federico Cantoni: Fabrication advances of microvasculature models on-chip

Abstract

Despite the technological advances of the last decades, drug development remains a lengthy and costly process with uncertainties still associated with the poor predictive power of the in vitro and animal models. To address this limitation, microphysiological systems have been introduced in an attempt to increase the biological relevance of in vitro devices. One of the current challenges in MPS is the integration of a vasculature network to sustain 3D cultures to closely mimic human physiology.  This thesis proposed a new strategy to recreate a more representative vasculature system directly on-chip. As a first step, the 2-photon polymerization was investigated as a 3D printing technique to recreate structures with cell-relevant feature size and resolution. Subsequently, the 2-photon polymerization 3D printing was combined with micromolding to recreate a multi-hydrogel vasculature network integrated on-chip for cell culture. The synergy of the two methods ensured the generation of a high-fidelity multi-hydrogel scaffold for cell co-culture. To preserve the delicate cell culture while still ensuring the sample manipulation for monitoring and analysis, a customized microphysiological system carrier with an integrated heating and perfusion system was also developed. Finally, the possibility of tuning the properties of the 3D-printed hydrogel by controlling the printing parameters was investigated to guide glioblastoma cells to a vascularized compartment. Overall, the thesis not only demonstrated the fabrication versatility of 2 photon polymerization for a vasculature model directly on-chip but also showed the benefits in integrating microphysiological systems on a carrier.