In-vivo vascular application via ultra-fast bioprinting for future 5D personalised nanomedicine

Abstract

The design of 3D complex structures enables new correlation studies between the engineering parameters and the biological activity. Moreover, additive manufacturing technology could revolutionise the personalised medical pre-operative management due to its possibility to interplay with computer tomography. Here we present a method based on rapid freeze prototyping (RFP) 3D printer, reconstruction cutting, nano dry formulation, fast freeze gelation, disinfection and partial processes for the 5D digital models functionalisation. We elaborated the high-resolution computer tomography scan derived from a complex human peripheral artery and we reconstructed the 3D model of the vessel in order to obtain and verify the additive manufacturing processes. Then, based on the drug-eluting balloon selected for the percutaneous intervention, we reconstructed the biocompatible eluting-freeform coating containing 40 nm fluorescent nanoparticles (NPs) by means of RFP printer and we tested the in-vivo feasibility. We introduced the NPs-loaded 5D device in a rat's vena cava. The coating dissolved in a few minutes releasing NPs which were rapidly absorbed in vascular smooth muscle cell (VSMC) and human umbilical vein endothelial cell (HUVEC) in-vitro. We developed 5D highresolution self-dissolving devices incorporating NPs with the perspective to apply this method to the personalised medicine.Chronic lower extremity peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis, and one of the main causes in loss of walking ability. Two treatments for lower extremity PAD are currently available: surgical (primarily bypass surgery) and endovascular treatment (EVT) mainly through balloon angioplasty. In fact, due to its clear advantages at least in the short-term, EVT represents -at present -the most common treatment for PAD 1 . Drug-Coated Balloons are made up of a semi-compliant or non-compliant balloon catheter covered with an anti-proliferative agent (typically paclitaxel), and an excipient (e.g. urea) to facilitate drug transfer into the vessel wall after balloon inflation 2 . The BASIL (Bypass Versus Angioplasty for Severe Ischemia of the Leg) trial is the only multicentre, randomised and controlled trial (RCT) which compared these two treatments 3 . One of the major limitations of this RCT is that current endovascular technologies have not been included 4 . Important advances developed in endovascular technologies address a great variety of anatomic challenges, while current and future efforts are directed towards improving long-term patency rates.The 3D printing techniques demonstrate the high potentiality of interactive processes applied to medicine and associated toxicity/vitality studies 5,6 . Materials selected for bio-printed scaffolds are predominantly based on both naturally derived polymers (including gelatine, collagen, alginate, chitosan and hyaluronic acid) or synthetic molecules (polyethylene glycol) 7-9 , allowing precise control 10 of chemical and physical properties 11 .

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“…Floor disinfection is performed with 1000 mg/L of chlorine-containing disinfectant every 4 h at least, or when needed. 21 Disinfection sprays must be used carefully because they might infiltrate into the equipment circuits. To facilitate disinfection, it may be useful to cover any electronic part (keyboards, push-button panels, touchscreen monitors) with plastic.…”

“…A low-dose high resolution protocol is strongly advised for detecting COVID-19 16,18,21 due to patient radiation protection concerns, 17 mostly when it comes to patient screening. 16…”

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Bioprinting of Adult Dorsal Root Ganglion (DRG) Neurons Using Laser-Induced Side Transfer (LIST)

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