Double network laminarin-boronic/alginate dynamic bioink for 3D bioprinting cell-laden constructs


The design of dynamically crosslinked hydrogel bioinks for three-dimensional (3D) bioprinting is emerging as a valuable strategy to advance the fabrication of mechanically tuneable cell-laden constructs for 3D in vitro disease modelling and tissue engineering applications. Herein, a dynamic bioink comprising boronic acid-functionalised laminarin and alginate is explored for bioprinting 3D constructs under physiologically relevant conditions. The formulated bioink takes advantage of a double crosslinked network that combines covalent but reversible boronate ester bonds and ionic gelation via divalent cations. Moreover, it exhibits suitable rheological properties and improved mechanical features owing to its modular crosslinking chemistry, yielding stable constructs with user-programmable architecture. We explored such dynamic bioink as a supporting matrix for different cell classes, namely osteoblast precursors, fibroblasts and breast cancer cells. The resulting cell-laden bioprinted hydrogels display a homogeneous cell distribution post-printing and exceptional cell viability (>90%) that can be maintained for prolonged time periods in culture (14 days) for all cell lines. This simple and chemically versatile approach is envisaged to accelerate the development of multifunctional bioinks and contribute towards the fabrication of biomimetic 3D scaffolds with applicability in a wide range of predictive or exploratory biomedical platforms.




Engineering, Biomedical; Materials Science, Biomaterials


Amaral, AJR; Gaspar, VM; Lavrador, P; Mano, JF

nossos autores


The authors acknowledge the financial support of the European Research Council grant agreement ERC-2014-ADG-669858 for project ATLAS, and CICECO-Aveiro Institute of Materials, UIDB/50011/2020 and UIDP/50011/2020 (financed by national funds through the Portuguese FCT/MCTES). This work was also supported by Fundo Azul/Portugal Blue within the aim of the project BLUEGLUE (FA_05_2017_031), and by Programa Operacional Competitividade e InternacionalizacAo (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES in the scope of the project MARGEL (PTDC/BTM-MAT/31498/2017) and project PANGEIA (PTDC/BTM-SAL/30503/2017). The NMR spectrometer is part of the National NMR Network (PTNMR) and partially supported by Infrastructure Project No. 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL, and FCT through PIDDAC). Image acquisition was performed in the LiM facility of iBiMED, a node of PPBI (Portuguese Platform of BioImaging) with grant agreement POCI-01-0145-FEDER-022122. PL acknowledges the Portuguese Foundation for Science and Technology (FCT) for his individual PhD fellowship (SFRH/BD/141834/2018). VMG and AJRA acknowledge an individual Junior Researcher contract by FCT (CEECIND/01410/2018 and POCI-01-0145-FEDER-030770, respectively). We also thank Prof. Dmitry Evtyugin for his help with the SEC analysis.

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