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3D in-vitro mechanobiology and disease treatment models

unleashing the potential of two-photon polymerization

Dr. Angelo Accardo, Associate Professor,

Two-photon polymerization (2PP) is a high-resolution 3D printing method enabling the creation of 3D engineered cell microenvironments featuring (sub-)micrometric structures and unlimited design freedom. These properties cover a crucial role to provide topographical and mechanical cues to cells, while mimicking at the same time geometries characteristic of the natural tissue. In such context, understanding the functioning of cells in health and disease, plays a fundamental role for future tissue engineering and disease treatments applications. However, most of the current cell biology protocols are still limited to 2D cultures, which, although inexpensive and easy to handle, do not reproduce the complexity of real tissues. In this talk, I will show how to surpass these conventional approaches by realizing polymeric 3D microenvironments [1,2] for both fundamental cell mechanobiology and in-vitro disease/treatment modelling. I will in particular focus on the creation of biomimetic microenvironments for two types of tissue: brain and brain cancer. Concerning the first type, I will show how 3D nanostructures are able to guide the fate of primary microglia [3,4] (part of the brain immune defense system) isolated from the brain of rhesus macaque, towards a physiological ramified phenotype. Concerning brain cancer (glioblastoma) on the other hand, 3D engineered microenvironments, mimicking brain micro-vessels, are employed as a reliable benchmark tool for proton radiobiology [5,6] and for unveiling patient-derived glioblastoma mechanobiology [7]. Finally, I will give a short overview of recent results on neuronal growth cone mechanisms guided by 3D nanostructures and bone tissue engineering metamaterials [8,9].

[1] D. Fan, U. Staufer, A. Accardo, Bioengineering 2019, 6, 113.

[2] L. Castillo Ransanz, P. F. J. Van Altena, V. M. Heine, A. Accardo, Front. Bioeng. Biotechnol. 2022, 10:1096054.

[3] A. Sharaf, B. Roos, R. Timmerman, G.-J. Kremers, J. J. Bajramovic, A. Accardo, Front. Bioeng. Biotechnol. 2022, 10, 1105.

[4] A. Sharaf, R. Timmerman, J. Bajramovic, A. Accardo, Neural Regen. Res. 2022, 18, 1709.

[5] Q. Akolawala, M. Rovituso, H. H. Versteeg, A. M. R. Rondon, A. Accardo, ACS Appl. Mater. Interfaces 2022, 14, 20778.

[6] Q. Akolawala, F. Keuning, M. Rovituso, W. van Burik, E. van der Wal, H. H. Versteeg, A. M. R. Rondon, A. Accardo, Adv. Healthc. Mater. 2024, 13, 2302988.

[7] N. Barin, H. E. Balcioglu, I. de Heer, M. de Wit, M. L. M. Lamfers, M. E. van Royen, P. J. French, A. Accardo, Small 2022, 18, 2204485.

[8] E. Yarali, A. A. Zadpoor, U. Staufer, A. Accardo, M. J. Mirzaali, ACS Appl. Bio Mater. 2023, 6, 2562.

[9] E. Yarali, M. Klimopoulou, K. David, P.E. Boukany, U. Staufer, L.E. Fratila-Apachitei, A.A. Zadpoor, A. Accardo, M.J. Mirzaali, Acta Biomater. 2024, 177, 228–242.