In Vivo Anastomosis and Perfusion of a Three-Dimensionally-Printed Construct Containing Microchannel Networks

Abstract

The field of tissue engineering has advanced the development of increasingly biocompatible materials to mimic the extracellular matrix of vascularized tissue. However, a majority of studies instead rely on a multiday inosculation between engineered vessels and host vasculature rather than the direct connection of engineered microvascular networks with host vasculature. We have previously demonstrated that the rapid casting of three-dimensionally-printed (3D) sacrificial carbohydrate glass is an expeditious and a reliable method of creating scaffolds with 3D microvessel networks. Here, we describe a new surgical technique to directly connect host femoral arteries to patterned microvessel networks. Vessel networks were connected in vivo in a rat femoral artery graft model. We utilized laser Doppler imaging to monitor hind limb ischemia for several hours after implantation and thus measured the vascular patency of implants that were anastomosed to the femoral artery. This study may provide a method to overcome the challenge of rapid oxygen and nutrient delivery to engineered vascularized tissues implanted in vivo.

A Facile Strategy for Fabricating Tissue Engineering Scaffolds with Sophisticated Prevascularized Networks for Bulk Tissue Regeneration

“…For the main channel, different scale main channels can be formed by combining different sizes of copper wire (according to Section 5.2). Furthermore, as the field progresses to engineer thicker and more complex cellularized tissues such as the myocardium, liver, or lung, it is indispensable to fabricate more complex vascular architecture channel to ensure sufficient diffusion of oxygen and nutrients to the cells . More complex channel networks were fabricated in this way (Figure ); however, it is very difficult to fabricate for many previous researches of hydrogel vascularization scaffold .…”

3D Bioprinting for Vascularized Tissue Fabrication

“…72, 107 Miller and others extruded a dextran-incorporated sucrose-glucose solution to form a 3D carbohydrate glass lattice skeleton. This lattice skeleton was then embedded in cell-loaded matrices (e.g., fibrin, Matrigel, alginate).…”

“…94 Engineering approaches to extend beyond the diffusional limit of nutrients/oxygen have explored a variety of strategies, including improving tissue/scaffold perfusion and culture (e.g., scaffold porosity, bioreactor) 7, 18, 33, 34, 41, 67, 75, 88, 90, 118 , incorporating oxygen delivery mechanisms 59, 85, 95, 97, 109 , and constructing biomimetic vessel structures, with or without cells. 5, 24, 95, 107 In addition, advances in the biomaterials (e.g., hydrogel) and vascular cell biology have been leveraged to recreate the natural vasculogenic (i.e., de novo vessel formation) and angiogenic (i.e., new vessel forms from pre-existing vessel) environment to form organized vessel sizes from micron to millimeter dimensions. 21, 25, 36, 38, 43, 110, 114 The overarching goal of the vascularization of tissue-engineered constructs (in vitro or after transplantation) is to provide a cell-based, long-term (i.e., stable) solution for supply of oxygen and nutrients to the tissue.…”

Multiscale technologies for treatment of ischemic cardiomyopathy

“…Therefore, more attention should be given to tissue-engineering approaches, in combination with recently evolved 3D bioprinting technologies, for fabricating heart muscle or even whole hearts 148 . One key challenge in bioprinting cardiac tissue grafts is the incorporation of a functional, mechanically integrated vascular network into the bioengineering myocardium that can be perfused in vivo 149 . Access to physiologically relevant cell types and densities, clinically relevant cardiac patch size and architecture, and more bioactive inks to maintain the phenotype, function and maturation of cardiac cells are other confounding factors 150 .…”