Bioinstructive Layer-by-Layer-Coated Customizable 3D Printed Perfusable Microchannels Embedded in Photocrosslinkable Hydrogels for Vascular Tissue Engineering


The development of complex and large 3D vascularized tissue constructs remains the major goal of tissue engineering and regenerative medicine (TERM). To date, several strategies have been proposed to build functional and perfusable vascular networks in 3D tissue-engineered constructs to ensure the long-term cell survival and the functionality of the assembled tissues after implantation. However, none of them have been entirely successful in attaining a fully functional vascular network. Herein, we report an alternative approach to bioengineer 3D vascularized constructs by embedding bioinstructive 3D multilayered microchannels, developed by combining 3D printing with the layer-by-layer (LbL) assembly technology, in photopolymerizable hydrogels. Alginate (ALG) was chosen as the ink to produce customizable 3D sacrificial microstructures owing to its biocompatibility and structural similarity to the extracellular matrices of native tissues. ALG structures were further LbL coated with bioinstructive chitosan and arginine-glycine-aspartic acid-coupled ALG multilayers, embedded in shear-thinning photocrosslinkable xanthan gum hydrogels and exposed to a calcium-chelating solution to form perfusable multilayered microchannels, mimicking the biological barriers, such as the basement membrane, in which the endothelial cells were seeded, denoting an enhanced cell adhesion. The 3D constructs hold great promise for engineering a wide array of large-scale 3D vascularized tissue constructs for modular TERM strategies.




Biochemistry & Molecular Biology


Sousa, CFV; Saraiva, CA; Correia, TR; Pesqueira, T; Patricio, SG; Rial-Hermida, MI; Borges, J; Mano, JF

nossos autores


This work was funded by the Programa Operacional Regional do Centro -Centro 2020, in the component FEDER, and by national funds (OE) through Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior (FCT/MCTES), in the scope of the project SUPRASORT (PTDC/QUI-OUT/30658/2017, CENTRO-01-0145-FEDER-030658) and by the Programa Operacional Competitividade e Internacionalizacao (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the project MIMETIc (PTDC/BTMMAT/31210/2017). This work was also supported by FCT through the Marine Biotechnology ERA-NET project BLUETEETH (ERA-MBT/0002/2015), as well as by the European Research Council Advanced Grant ATLAS (grant agreement no. ERC-2014-ADG-669858). 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 FCT/MCTES. Cristiana F. V. Sousa, Sonia G. Patricio, and Joao Borges gratefully acknowledge FCT for the individual PhD grant (2020.04408.BD, Cristiana F. V. Sousa) and individual Assistant Researcher contracts (2020.00366.CEECIND, Sonia G. Patricio; 2020.00758.CEECIND, Joao Borges), respectively. Maria Isabel Rial-Hermida acknowledges Xunta de Galicia for her postdoctoral contract (ED481B 2018/009).

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