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

Cristiana F V Sousa,Tiago R Correia,Maria Isabel Rial-Hermida,João Borges,Sónia G Patrício,Catarina A Saraiva,João F Mano,Tamagno Pesqueira

doi:10.3390/biom11060863

Cristiana F V Sousa, Tiago R Correia + Show 6 more

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https://doi.org/10.3390/biom11060863

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Journal: Biomolecules	Publication Date: Jun 10, 2021
Citations: 25	License type: CC BY 4.0

Affiliation: University of Aveiro

Abstract

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.

Highlights

Introduction iationsThe ability to bioengineer biomimetic 3D tissue-like biofunctional vascular constructs to accurately recreate living tissue-specific vascular architectures and their physicochemical, biomechanical and biological functions is the major and long-standing goal of bottom-up tissue engineering and regenerative medicine (TERM), aiming to replace, restore and/or regenerate damaged tissues and organs [1,2,3,4,5,6]
human umbilical vein endothelial cells (HUVECs) were seeded onto the microchannels aiming to colonize them and form8 ofprevascular networks (Figure 1)
We have successfully developed 3D constructs encompassing bioinstructive LbL-coated customizable 3D printed perfusable microchannels embedded in photocrosslinkable hydrogels for vascular tissue engineering

Summary

Introduction

Introduction iationsThe ability to bioengineer biomimetic 3D tissue-like biofunctional vascular constructs to accurately recreate living tissue-specific vascular architectures and their physicochemical, biomechanical and biological functions is the major and long-standing goal of bottom-up tissue engineering and regenerative medicine (TERM), aiming to replace, restore and/or regenerate damaged tissues and organs [1,2,3,4,5,6]. Biomolecules 2021, 11, 863 the clinical practice by resorting to hydrogel-based constructs [11,12,13,14]. Their effectiveness in sustaining cell viability is limited to microsized systems. 200 μm) denote an inhomogeneous cell distribution and poor long-term and controlled diffusion of oxygen, nutrients, and metabolic waste removal due to their inability to build spatially organized perfusable vascular networks, leading to cell apoptosis and the formation of necrotic cores that dictate their failure upon implantation and prevent their clinical translation [15]. As such, engineering complex and large vascularized functional tissue constructs remains elusive, being essential to maintain tissue health

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