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

The 5D printing design and the related correlation study between the engineering parameters and the biological activity could support the surgical training and the syntetic organ fabrication.

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The 3D printed object assures the adherence to the real model; the implementation of 4D bio-composite materials permits the biological devices performances improvement, and finally the 5D customisation enables the in-vitro/in-vivo interaction studies.

In detail, modifying the composite biomaterial and the manufacturing methods, the interaction of the transplanted structures with the biological substrate can be varied accordingly to experimental needs.

Thus, the implemented FANNAM (Formulation and Analysis for Nanoparticle Additive Manufacturing) method permits the continuous improvement, the functionalisation and the customisation of the additive manufacturing using nanoparticles (NPs).

We digitally reconstructed the 3D model derived from a complex human peripheral artery, directly from computer tomography. Then, we printed the biocompatible eluting-freeform coating containing 40nm fluorescent nanoparticles. The bioprinted device was dehydrated becoming an aerogel scaffold.

The aerogel 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. Finally, to test the final 5D object we inserted it in rat vena cava, observing the internalisation of nanoparticles into both the interstitial tissue and the vascular cells with two-photon microscopy imaging.

The high variability in biological application requires rigorous standards for analysis and we identified a good scheduling for the 5D processes and parameters digitalisation with the aim to support the synthetic organ development and the digital bio-library improvement. Our method showed that is possible to develop nano-laden 5D devices for training, pharmacological tests and in-vivo applications, improving the typical drug eluting balloon therapy merging patient morphology with the high resolution of rapid freeze prototyping technology.

The complete operative processes were scheduled from 3D to 5D, giving the basis for the bio-based smart bioprinting (6D) through the realisation of digital bio-library related to the pathology (containing the functional customisation data, supporting the study for syntetic organ development), based on bionics and the related human mimicry and autonomous regeneration.

https://www.nature.com/articles/s41598-020-60196-y#Sec3

Ruben Foresti

PhD, University of Parma

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