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3D Printed Vascular Model-on-Chip Platform with Automated Customization

Periodic Reporting for period 1 - 3DPRINT-VASCU-CHIP (3D Printed Vascular Model-on-Chip Platform with Automated Customization)

Reporting period: 2018-05-01 to 2020-04-30

Cardiovascular diseases cause over 14 million deaths worldwide each year, particularly in the form of heart attacks and strokes. Such diseases have been commonly studied by employing in vitro and in vivo models that do not completely recapitulate the human physiology/disease, therefore undermining the search for efficient new treatments. High resolution 3D printing has the potential to revolutionize the study of cardiovascular diseases by means of organ-on-chip approaches. Unlike conventional 2D wafer-based microfabrication techniques, 3D printing can generate truly 3D, organically shaped, and highly accurate microfluidic replicas of blood vessels. These replicas can further be lined with cells and perfused with blood, disease-like events can be studied in detail, and therapeutic molecules can be tested.
In this project, the overall objectives were to explore the potential of such methodology by developing a software tool that enables automated application-specific customization of the on-chip study platform and to utilize more complex and biologically relevant materials in the devices' fabrication. Other goals were to demonstrate the added value of the devices by comparison with well-established protocols/methods in the study of angiogenesis in high throughput screening settings, to assess the commercial viability of such an approach, and to pursue translation to the market.
This project enabled the development of a parametric design online platform (BIOFABICS TOOLBOX) that empowers users to easily, quickly and in a visual manner develop microfluidic systems by defining multiple parameters. Various microfluidic system designs were subsequently manufactured via high-resolution 3D printing and tested in a variety of proof-of-concept studies:
- In collaboration with the University of Santiago de Compostela (Spain), various gel formulations, forming inner vessel-like architectures, were characterized in terms of their mechanical properties, while contained into microfluidic devices designed and manufactured by employing the BIOFABICS TOOLBOX. This enabled to screen and identify various suitable gel formulations which would be able to be employed in further biological studies within the developed microfluidic devices.
- In collaboration with University of Minho (Portugal), 3D biomodels were designed and manufactured employing the BIOFABICS TOOLBOX in order to generate physical replicas of blood vessels with varying degrees of stenosis. This enabled to study and compare the results from physical experimental tests with results from numerical (in silico) tests. Both visually and numerically, it was possible to assess in detail how the degree of stenosis affects fluid behavior properties of blood within stenotic vessels, such as flow turbulence, velocity fields, among others. This work originated two research articles. One was published in the journal Micromachines and the other one is currently under peer review.
- In collaboration with Stanford University (USA), the BIOFABICS TOOLBOX was also employed to design and manufacture devices which, in combination with hydrogel 3D bioprinting technology, were able to generate and maintain over time living functional 3D models of the blood-brain barrier. This work originated one research article which was published in the journal Frontiers in Bioengineering and Biotechnology.
Beyond the scientific activities, this project also allowed the researcher to further develop his skills and know-how regarding product/service development, translation of technology to market and management by attending highly reputed training programs and business acceleration programs. Furthermore, this project also enabled the generation of intellectual property which was duly registered for protection by official bodies.
Promotion of BIOFABICS’ technology has been achieved regularly via publication of scientific articles (both review articles and experimental articles), attendance and presentation in various conferences and meetings and interviews to various media outlets. The exposure provided by such dissemination and exploitation activities allowed the researcher and the company to be invited to take part in various initiatives. For example, the researcher became invited editor in the journal “Micromachines” and an expert evaluator for the European Commission as well as established new partnerships with multiple companies and academic/research institutions, which in turn resulted in the participation of BIOFABICS in various other EU projects.
As a result of the project, the BIOFABICS TOOLBOX, which allows researchers to easily create devices according to their own precise requirements, has been launched on the company website (www.biofabics.com/toolbox). These devices can now be manufactured using biocompatible, autoclavable, and transparent materials and shipped to researchers across the world. Devices manufactured by BIOFABICS were used in collaboration with researchers at Stanford University (USA) to create tissue models and with researchers at University of Minho (Portugal) to create stenotic vessel models. The results of these studies were disseminated by means of joint open access publications. It is likely that other researchers in the scientific community will start to use such devices for the applications described in this project as well as for other new applications. Additionally, this project has allowed for the career development of the researcher, who is the founder and CEO/CTO of BIOFABICS, by means of publication of several open access review articles and participation in communication activities to the broader public, including newspaper, radio and TV interviews.
Summary Image BIOFABICS TOOLBOX