3D bioprinting microgels to construct implantable vascular tissue

Abstract

Engineered implantable functional thick tissues require hierarchical vasculatures within cell-laden hydrogel that can mechanically withstand the shear stress from perfusion and facilitate angiogenesis for nutrient transfer. Yet current extrusion-based 3D printing strategies are unable to recapitulate hierarchical networks, highlighting the need for bioinks with tunable properties. Here, we introduce an approach whereby crosslinkable microgels enhance mechanical stability and induce spontaneous microvascular networks comprised of human umbilical cord vein endothelial cells (HUVECs) in a soft gelatin methacryoyl (GelMA)-based bioink. Furthermore, we successfully implanted the 3D printed multi-branched tissue, being connected from the rat carotid artery to the jugular vein direct surgical anastomosis. The work represents a significant step toward in the field of large vascularized tissue fabrication and may have implications for the treatment of organ failure in the future. | INTRODUCTIONTissue engineering has shown tremendous potential for generating large functional tissue constructs as an alternative therapy for repairing or replacing damaged tissues and organs. [1][2][3][4][5] Although advances in organoid technologies or organ-on-a-chip have been made, the scale and complexity of bionic tissue still pose challenges that limit the applications. [6][7][8][9] In order to assure and promote the functions of the large engineered tissues, the fabrication of 3D vascular networks within the tissue constructs plays a critical role.To date, only a few groups have attempted to bioprint the vessellike channels and capillary-like structures in cell-laden hydrogels. [10][11][12] However, the mechanical strength of these hydrogels is typically insufficient to bear the shear stress of blood flow in vivo. While direct surgical anastomosis with immediate blood perfusion of vascularized tissues has been demonstrated using vascular stents or biodegradable scaffolds (e.g., POMAC), these approaches have limitations such as poor integration and potential biocompatibility issues. [13][14][15] Xinhuan Wang & Xin Liu contributed equally to this work.

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