Current in vitro and in vivo tests applied to assess the safety of medical devices retain several limitations, such as an incomplete ability to faithfully recapitulate human features, and to predict the response of human tissues together with non-trivial ethical aspects. We here challenged a new hybrid biofabrication technique that combines bioprinting and Fast Diffusion-induced Gelation strategy to generate a vessel-like structure with the attempt to spatially organize fibroblasts, smooth-muscle cells, and endothelial cells. The introduction of Fast Diffusion-induced Gelation minimizes the endothelial cell mortality during biofabrication and produce a thin endothelial layer with tunable thickness. Cell viability, Von Willebrand factor, and CD31 expression were evaluated on biofabricated tissues, showing how bioprinting and Fast Diffusion-induced Gelation can replicate human vessels architecture and complexity. We then applied biofabricated tissue to study the cytotoxicity of a carbothane catheter under static condition, and to better recapitulate the effect of blood flow, a novel bioreactor named CuBiBox (Customized Biological Box) was developed and introduced in a dynamic modality. Collectively, we propose a novel bioprinted platform for human in vitro biocompatibility testing, predicting the impact of medical devices and their materials on vascular systems, reducing animal experimentation and, ultimately, accelerating time to market.
Keywords: 3D bioprinting; biocompatibility; cytotoxicity assay; fast diffusion-induced gelation; in vitro models; medical device; three-layered artificial blood vessel.
Our study provides an innovative convergence of 3D biofabrication technologies to realize multi-cellularized vessel-like models, as a new tool for in vitro biocompatibility testing of medical devices, minimizing animal experimentation.
© 2024 The Author(s). Published by National Institute for Materials Science in partnership with Taylor & Francis Group.