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Third Strategy in Tissue Engineering – Functional microfabricated multicellular spheroid carriers for tissue engineering and regeneration

Periodic Reporting for period 3 - THIRST (Third Strategy in Tissue Engineering – Functional microfabricated multicellular spheroid carriers for tissue engineering and regeneration)

Periodo di rendicontazione: 2021-05-01 al 2022-10-31

Tissue engineering is a highly interdisciplinary research field with the long-term goal to restore and/or replace defective tissues. Taking into account increases in life expectancy and ageing population, this research field is more relevant than ever. Despite the enormous amount of new knowledge and undisputable progress achieved during the last few decades, current clinical advances in TE are largely represented by fragmented solutions restricted to a particular disease or tissue type. This situation is partially conditioned by the technical limitations of available methods and the inability to apply them universally for treatment of different target tissues and / or organs.
The overarching aim of the project is to develop a new technological platform sufficiently versatile to potentially address a wide range of current TE challenges. The concept of this third tissue engineering strategy (THIRST) relies on a directed tissue assembly from multicellular spheroids encaged within robust 3D printed microscaffolds. In contrast to the two most widespread approaches, namely scaffold-based and a scaffold-free approach, this project aims to develop a radically new strategy combining the advantages of the two approaches.
The main aims of the first reporting period were to develop the means for a drastic upscaling of microscaffold production and their handling. In addition, the microscaffold design / geometry and the biodegradable material, suitable for high resolution 3D printing of scaffolds by means of two-photon polymerization (2PP), were established. The systematic studies allowed to develop material formulations uniquely suitable for high-resolution 2PP of highly porous microscaffolds envisioned in THIRST. Thorough characterization of these materials, including biocompatibility evaluation using extract protocols, in accordance to ISO 10993-5 standard, along with in vitro degradation study and 2PP-processing results, served as a basis for a manuscript accepted to publication to a highly cited Elsevier journal Materials Today.
The project developments on the 2PP-microfabrication side, along with the materials, enabled a fewfold increase in the throughput of the scaffold production. Furthermore, it was demonstrated the new biodegradable material concept allows to overcome limitations associated with the 2PP-based high-resolution printing. By the end of the project we expect to demonstrate the feasibility of this novel tissue engineering strategy in repairing tissue.
SEM image of microscaffolds (A), agarose micro-well mold for cell seeding (B), illustration of the u