Engineering tissues with a perfusable vessel-like network using endothelialized alginate hydrogel fiber and spheroid-enclosing microcapsules

Abstract

Development of the technique for constructing an internal perfusable vascular network is a challenging issue in fabrication of dense three-dimensional tissues in vitro. Here, we report a method for realizing it. We assembled small tissue (about 200 μm in diameter)-enclosing hydrogel microcapsules and a single hydrogel fiber, both covered with human vascular endothelial cells in a collagen gel. The microcapsules and fiber were made from alginate and gelatin derivatives, and had cell adhesive surfaces. The endothelial cells on the hydrogel constructs sprouted and spontaneously formed a network connecting the hydrogel constructs with each other in the collagen gel. Perfusable vascular network-like structure formation after degrading the alginate-based hydrogel constructs by alginate lyase was confirmed by introducing solution containing tracer particles of about 3 μm in diameter into the lumen templated by the alginate hydrogel fiber. The introduced solution flowed into the spontaneously formed capillary branches and passed around the individual spherical tissues.

Horseradish Peroxidase Catalyzed Hydrogelation for Biomedical, Biopharmaceutical, and Biofabrication Applications

“…The usefulness of these cell‐laden hydrogel constructs obtained through HRP‐mediated cross‐linking as building blocks of large 3D tissues was recently reported . A 3D tissue with a perfusable microvascular‐like network was obtained by assembling cell‐laden hydrogel constructs in a collagen gel after coating the surfaces with HUVECs and degrading the hydrogels by using non‐proteolytic degrading enzymes (Figure ) …”

Fiber‐based fluorescence lifetime imaging of recellularization processes on vascular tissue constructs

“…Bovine pericardium (BP), mainly composed of collagen (∼70% of their dry weight), is a natural biomaterial widely utilized clinically as a vascular scaffold, although current generations of BP require glutaraldehyde fixation to overcome recipient graft‐specific immune response. In arterial patches, glutaraldehyde‐fixed BP is used as surgical closures, since it supports limited arterial remodeling by endothelialization of the luminal surface . Recent efforts to generate antigen removed BP provide unfixed scaffolds with suppressed antigenicity and maintained structure and function, enhancing its regenerative potential .…”

Vascularized microfluidic organ-chips for drug screening, disease models and tissue engineering

“…Liu et al created a high cell density liver model using an aggregation of many spheroids coated with endothelial cells. They demonstrated perfusion of culture medium into this dense hepatic tissue using an endothelialized alginate hydrogel fiber in vitro [49].…”