3D bioprinting and its applications in vascular surgery: in-vitro and in-vivo tests for future 5D personalised nanomedicine

Three-dimensional printing techniques demonstrated the high potentiality of interactive processes applied to medicine and surgery. The current, wide availability of different materials and bio-inks allows the precise control of chemical and physical properties of the printed objects obtained through additive manufacturing technology. In addition, 3D printing may produce far-reaching changes in surgical pre-operative management, thanks to the potential interactions with medical imaging modalities. We developed a method based on rapid freeze prototyping (RFP) 3D printer, reconstruction cutting, nano-dry-formulation, fast-freeze gelation, disinfection and partial processes for the 3D to 5D digital models functionalization. We processed a computed tomography angiography scan of a human femoral artery bifurcation, and we reconstructed the 3D model of the vessel to obtain and verify the additive manufacturing processes. Afterwards, a biocompatible eluting-freeform coating for a drug-eluting balloon selected on the basis of the 3D-printed vessel was created under a biosafety cabinet. The alginate-printed coating contained 40nm fluorescent nanoparticles (NP), and was reconstructed by means of RFP printer, and gelled with ethanol (EtOH 98%). Feasibility and effectiveness of this 3D-printed scaffold was tested in-vivo and in-vitro. In order to test this method in-vivo, the NP-loaded 5D device was deployed in a rat’s vena cava. The coating dissolved in a few minutes releasing NP, which were rapidly absorbed in the vessel’s wall,specifically interstitial tissue and vascular smooth muscle cells (confirmed with two-photon microscopy). NP internalisation was also confirmed in-vitro, on vascular smooth muscle cells, and on human umbilical vein endothelial cell (HUVEC) line. We developed 5D, high-resolution,self-dissolving devices containing NP, which can be applied to the personalised medicine, specifically vascular and endovascular devices (such as coatings for drug-eluting balloons or stents, or vascular graft substitutes). In fact, NP can potentially be loaded with different drugs or molecules, in order to obtain a biological activity, thus clinical applicability.