Designing highly customizable human based platforms for cell culture using proteins from the amniotic membrane

abstract

In the past few years researchers have witnessed a paradigm shift in the development of biomaterials for drug discov-ery, tissue engineering, and regenerative medicine. After the great advances resulting from the transition of the 2D to the 3D, the new focus has been to increase the clinical relevance of such systems, as well as avoid the use of animals, by developing platforms that better replicate the human physiology in vitro. In this sense, we envisage the use of human matrices extracted from ethically sourced and readily available tissues as an optimal and promising alternative to cur-rently used approaches. Hereupon, we report for the first time the chemical modification of human ECM proteins from the amniotic membrane (AM) with photoresponsive groups to produce bioinks and hydrogel precursors to engineer customizable platforms that are representative of native tissues and capable of supporting long-term cell culture. Our results demonstrated an efficient decellularization, liquefaction and functionalization of AM-derived ECM with methacryloyl domains (AMMA), with production of stable and versatile hydrogels. Mechanical characterization evi-denced an increased compression strength as a function of methacrylation degree and decellularized ECM concentra-tion. Three-dimensional (3D) stem cell culture in the AMMA hydrogels resulted in viable and proliferative cells up to 7 days; moreover, the mouldable character of the hydrogel precursors permits the processing of patterned hydrogel con-structs allowing the control over cellular alignment and elongation, or microgels with highly tunable shape.

keywords

EXTRACELLULAR-MATRIX; HYDROGEL

subject category

Materials Science

authors

Deus IA, Santos SC, Custódio CA, Mano JF

our authors

acknowledgements

The authors acknowledge the funding from the European Research Council (ERC) for project Amniogel (957585 ERC-2020-PoC) and the Portuguese Foundation for Science and Technology (FCT) for the project BEAT (PTDC/BTM-MAT/30869/2017). Catarina A. Custodio and Sara S. Santos also acknowledge the FCT for the individual contract 2020.01647. CEECIND and doctoral grant SFRH/BD/144520/2019, respectively. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the Portuguese Portuguese Foundation for Science and Technology/MCTES.

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