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PRInted Symbiotic Materials as a dynamic platform for Living Tissues production

Periodic Reporting for period 1 - PRISM-LT (PRInted Symbiotic Materials as a dynamic platform for Living Tissues production)

Periodo di rendicontazione: 2022-11-01 al 2023-10-31

Recent breakthroughs in cell engineering and additive manufacturing have opened new frontiers for developing Engineered Living Materials (ELMs), constructed partially or entirely from living cells. These ELMs, characterized by a hierarchical arrangement of different cell lineages, exhibit multifunctional properties that often surpass those of both natural living materials and traditional non-living materials. However, realizing the full potential of living tissue manufacturing requires overcoming significant challenges, such as achieving controlled printability on a commercially viable scale and speed.

In response to these challenges, the EU-funded PRISM-LT project emerges as a pioneering initiative. Its primary objective is to establish a versatile platform for the 3D bioprinting of living tissues, endowed with dynamic functionalities and predictable shapes. Drawing inspiration from the mechanisms governing natural tissue development, PRISM-LT sets out to engineer heterogeneous 3D printable living materials capable of self-assembly into intricate living tissues. This ambitious endeavor spans scales ranging from sub-millimeters to centimeters.

PRISM-LT will assess the efficacy of its platform through the utilization of two distinct symbiotic materials, each directed towards specific applications: one in the biomedical realm (utilizing organoids as in-vitro models for biomedical research) and the other in the domain of food-related innovations (cultivating marbled cultured meat).
To attain this objective, PRISM-LT is innovating a novel, adjustable bioink that facilitates a synergistic interplay between stem cells and surrounding microorganisms (helper cells), thereby guiding stem cell differentiation towards a specific lineage. In the inaugural year, the consortium has successfully pinpointed operational parameters crucial for the envisioned applications across four key domains: (i) optimizing the biogel for integrating helper cells; (ii) refining the responsive mechanism tied to the microenvironment during stem cell differentiation; (iii) generating relevant molecules to foster localized stem cell differentiation; and (iv) identifying specific strains of helper cells.

Significant headway has been achieved in developing growth factor-secreting helper cells and establishing an inducible promoter system. Simultaneously, progress in devising printing protocols has run in parallel with bioink development, considering the temperature's impact on the final stiffness. Specific compositions have been identified, demonstrating commendable cell viability in preliminary studies and favorable printability during protocol optimization. This advancement is pivotal for upcoming phases involving stem cell differentiation, helper cell integration, and the ultimate objective of producing multiphase bone marrow or meat tissues.
The PRISM-LT project not only addresses the technological hurdles of controlled printability but also aligns with broader societal and scientific needs. By creating a nexus between cutting-edge advancements in biofabrication and tissue engineering, PRISM-LT aims to contribute significantly to the understanding and application of Engineered Living Materials. The envisioned impacts of the project extend beyond the laboratory, holding the promise of transformative applications in various fields, including biofabrication, tissue engineering, and beyond.

While tackling specific biomedical and food applications the platform is very flexible and has several applications. During the project PRISM-Lt will put its platform to the test by developing biomaterials for i) organoids as in vitro models for preclinical research, which could aid in discovering and testing of new drugs or therapies, and ii) synthetic meat that closely mimics its natural counterpart, incorporating typical marbling, texture, nutritional values, and safety.

Identifying these impactful results, the potential for further uptake and success becomes apparent. Areas requiring attention may include additional research to fine-tune and expand the platform's capabilities, demonstrations to showcase its real-world applicability, access to markets and financial support for scaling up production, commercialization efforts to bring these innovations to market, intellectual property rights (IPR) support to protect the project's innovations, internationalization strategies for global reach, and a supportive regulatory and standardization framework to facilitate widespread adoption. These considerations collectively form a roadmap for ensuring the sustained impact, scalability, and success of the PRISM-LT project.
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