Engineered nascent living human tissues with unit programmability

abstract

Leveraging human cells as materials precursors is a promising approach for fabricating living materials with tissue-like functionalities and cellular programmability. Here we describe a set of cellular units with metabolically engineered glycoproteins that allow cells to tether together to function as macrotissue building blocks and bioeffectors. The generated human living materials, termed as Cellgels, can be rapidly assembled in a wide variety of programmable three-dimensional configurations with physiologically relevant cell densities (up to 108 cells per cm3), tunable mechanical properties and handleability. Cellgels inherit the ability of living cells to sense and respond to their environment, showing autonomous tissue-integrative behaviour, mechanical maturation, biological self-healing, biospecific adhesion and capacity to promote wound healing. These living features also enable the modular bottom-up assembly of multiscale constructs, which are reminiscent of human tissue interfaces with heterogeneous composition. This technology can potentially be extended to any human cell type, unlocking the possibility for fabricating living materials that harness the intrinsic biofunctionalities of biological systems. Glycoengineered cells containing bioorthogonal tethers function as building blocks for the programmable fabrication of human living materials with distinct structures and tissue functionalities.

keywords

MODEL

subject category

Chemistry; Materials Science; Physics

authors

Lavrador, P; Moura, BS; Almeida-Pinto, J; Gaspar, VM; Mano, JF

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

Full human-based multi-scale constructs with jammed regenerative pockets for bone engineering. (REBORN)

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

Collaboratory for Emerging Technologies, CoLab (EMERGING TECHNOLOGIES)

acknowledgements

This work was financed by the European Research Council Advanced Grant REBORN (grant agreement number H2020-ERC-AdG-883370) and within the scope of project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 and LA/P/0006/2020, financed by national funds through FCT/MEC (PIDDAC). P.L., B.S.M. and J.A.-P. acknowledge individual PhD fellowships from the Portuguese Foundation for Science and Technology (FCT) (SFRH/BD/141834/2018 (P.L.), 2021.08331.BD (B.S.M.) and 2023.04716.BD (J.A.-P.). V.M.G. acknowledges FCT for an assistant researcher contract (CEECIN/02106/2022). Transcriptomics library preparation and sequencing was conducted in IGC Genomic Facility, partially supported by LISBOA-01-0246-FEDER-000037 - Single cell HUB co-funded by Programa Operacional Regional Lisboa 2020. We acknowledge i3S Proteomics platform for conducting sample processing and mass spectrometry. We acknowledge i3S Animal facility for providing laboratory animal care and conducting the in vivo study.