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3D and 4D Bioprinting: Additive Manufacturing of Smart Biodegradable Hydrogels

Periodic Reporting for period 2 - 4D-Biogel (3D and 4D Bioprinting: Additive Manufacturing of Smart Biodegradable Hydrogels)

Periodo di rendicontazione: 2021-06-01 al 2022-05-31

Bio-based plastics that can supplant petroleum-derived materials are necessary to meet the future demands of sustainability in the life cycle of plastic materials. Furthermore, the association of biosourced and biodegradable polymers with additive manufacturing could enable the fabrication of objects that can be recycled back into feedstock or degraded into nontoxic products after they have served their function. In this context, 4D-BIOGEL is a European funded Marie Skłodowska-Curie Action that aims to create biodegradable plastics from sustainable sources for 4D printing, so that a 3D printed construct can undergo spatiotemporal changes (with time as the 4th dimension) in response to an external stimulus, as in plants (e.g. Mimosa and Venus flytraps). The fundamental knowledge generated by 4D-BIOGEL will help to make a “greener” additive manufacturing based on the use of renewable feedstock, as well as pathways for innovative shape transformations inspired by nature.
The fellow developed reproducible protocols for the synthesis of water-based resins for vat photopolymerization 3D printing, based on an simple in-situ functionalization of proteins. The procedures allow to control the printability of the inks, the mechanical properties, as well as the biodegradability. She selected the best performing resins for studies of shape transformation and mechanical behavior using an array of structural and thermal characterization techniques.

An innovative strategy for shape transformation based on the unfolding and refolding ability of proteins has been discovered using two different stimuli: heat and hydration. Once the best resin formulation was determined, she 3D printed different stent prototypes to evaluate their performance, as well as their shape recovery after deformation. Furthermore, the fellow could achieve a remote-shape transformation using a near-infrared laser (NIR) through the incorporation of gold nanorods (AuNRs) to the resin formulation before 3D-printing. She printed these natural macromolecules by using different vat photopolymerization techniques that utilize patterned light to initiate the chemical cross-linking of a resin, because this layer by layer manufacturing process enables the rapid fabrication of innumerable 3D geometries that cannot be easily produced by other means with a high resolution. Thus, this additive manufacturing technology is particularly interesting for the medical sector where highly personalized products are required.

The results of 4D-Biogel were disseminated through publications in peer reviewed international journals, as well as contributions to international conferences and symposiums. The fellow has been the leading author of 2 and co-author of 4 publications at the end of the fellowship in high-level scientific journals, e.g. Advanced Materials (32.1) ACS Applied Materials & Interfaces (9.2) or Chemistry of Materials (9.4). The highly interdisciplinary aspects of the actions ensured a broad audience among the scientific community, increasingly interested in 4D-printing. During the fellowship timeframe, Dr. Eva Sanchez attended and participated giving presentations in 6 conferences including international meetings such as those organized by the ACS, the Society for Biomaterials, and Materials Research Society in the US. The action is active in various social channels: https://twitter.com/EvaRexach https://alshakim1.wixsite.com/website https://haritzsardonlab.com

The results with commercial potential were protected through the filing of 2 international patents.
The fellow created bio-sourced protein-based resins for vat photopolymerization through a simple "in situ" functionalization to make proteins printable. In addition, she developed a universal method to determine the printability of resins for vat photopolymerization 3D printing within MSCA-4D BIOGEL by using rheometry. She took advantage of the native conformation of proteins to create natural bioplastics with mechanical properties comparable to commercial plastics. Likewise, she used the natural conformation of these macromolecules that are an essential part of all living organisms, for shape transformation purpose. Additionally, new engineered proteins with designed functionalities were used to prepare a second generation of bio- sourced inks for 4D-printing. The rapid shape recovery behavior of the bioplastics of MSCA-4D BIOGEL, which can occur in a matter of seconds, can be useful for the production of medical devices such as scaffolds, implants, or stents.

The main impact of the MSCA-4D BIOGEL action is to enhance the future career prospects of the researcher, as well as her employability after the fellowship, to become a leading independent researcher in the field of biomaterials. It is a fact that the topic of the proposal is highly relevant from both the scientific and socio-economic perspective, and that after 3 years and amid the pandemic, the field of additive manufacturing is even more relevant that at the beginning of the fellowship. Furthermore, the fellow’s research work is contributing to a greener additive manufacturing by combining biosourced and biodegradable polymers with 3D printing to enable the fabrication of objects that can be recycled back into feedstock or degraded into nontoxic products after they have served their function. This fellowship provided her with multidisciplinary research experiences and training activities that allowed her to develop new inks for new applications within fields such as aerospace, robotics, and healthcare. Undoubtedly, 4D-BIOGEL project has allowed the fellow to strengthen collaborations between the hosting institutions and collaborators, enlarging her international network and becoming a nexus between the world leaders in 3D printing and the European researchers.

The fellow was awarded an appointment to the General Atomics (GA) Postgraduate Research Participation Program in recognition of her achievements starting in June 2022 in San Diego, California. She will perform research in the Inertial Fusion Technology Division on smart materials development, along with 2PP 3D-printing and photolithography for different nanofabrication applications. The 4D-BIOGEL project has allowed the fellow to obtain this position as a researcher in a professional environment, and she will contribute to the progress of science from there.

She contributed as patent inventor where the under-representation of women researchers is more apparent, as she has a patent from the research work carried out in this project. Moreover, she covered two of the 17 UN sustainable development goals to transform our world, since the fellow investigated towards a more sustainable additive manufacturing by using renewable natural sources that reduce the environmental footprint, and she also developed medical devices to promote the well-being for all at all ages.

The accomplishment of this innovative project allowed the fellow to employ her knowledge for the development of a modern, green and ethic investigation in line with the sustainability claimed in Horizon 2020. Moreover, the combination of laser-based 4D printing with biobased feedstocks offers great potential for the creation of sophisticated dynamic structures with high resolution that could find application not only in regenerative medicine or drug-delivery, but also in robotics or bioelectronics.
General scheme of the 4D-Biogel project