Advanced in vitro physiological models: Towards real-scale, biomimetic and biohybrid barriers-on-a-chip

Objective

This project is focused on the design, the production, the characterization, and the proposal for future commercialization of the first 1:1 scale 3D-printed realistic model of the brain tumor microenvironment with its associated blood neurovasculature. The proposed biomimetic dynamic 3D system, characterized by microcapillary diameter size and fluid flows similar to the in vivo physiological parameters, represents a drastic innovation with respect to other models well-established in the literature and available on the market, since it will allow to reliably reproduce the physiological environment and to accurately estimate the amount of drugs and/or of nanomaterial-associated compounds delivered through a modular length of the system. At the same time, in vitro 3D models are envisioned, allowing more physiologically-relevant information and predictive data to be obtained. All the artificial components will be fabricated through advanced lithography techniques based on two-photon polymerization (2pp), a disrupting mesoscale manufacturing approach which allows the fast fabrication of low-cost structures with nanometer resolution and great levels of reproducibility/accuracy. The proposed platform can be easily adopted in cell biology laboratories as multi-compartmental scaffold for the development of advanced co-culture systems, the primary biomedical applications of which consist in high-throughput screening of brain drugs and in testing of the efficacy of different anticancer therapies in vitro.

                                  

   SEM image of the fabricated microfluidic BBB          Magnified SEM image of the fabricated microfluidic BBB

Confocal image of the microfluidic BBB (Nuclei: Blue, ZO-1: Green, Actin: Red)

Future goals

NABIS: Towards the commercialization of the 3D real-scale BBB microfluidic system
NAnostructured on-demand 3D-printed BIostructureS (NABIS), is the startup project developed by our group, that proposes a service of 3D microfabrication. The main aim of this project is the commercialization of the 3D real‐scale microfluidic device mimicking the BBB, together with other 3D cell culture devices fabricated by two-photon lithography. 1-4 The fabrication of the microfluidic device using two-photon lithography can be appreciated in the video below.

 References

1. https://www.sciencedirect.com/science/article/pii/S174270611400244X?via%3Dihub 

2. https://pubs.acs.org/doi/10.1021/nn5052426 

3. https://pubs.acs.org/doi/abs/10.1021/acsami.5b08764 

4. https://pubs.acs.org/doi/10.1021/am403895k 

This project is funded by the ERC under the Grant agreement number: 832045

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This webpage was designed by Christos Tapeinos for the ERC project 'SLaMM'