Creation of Perfusable Tissue Engineering Constructs through Biological Assembly

Abstract

One of the biggest barriers in creating large tissues is the lack of oxygen and nutrient transport required for cell growth and tissue development in the interior region. The post-implantation cell survival in large tissue engineering constructs can be assisted by prevascularization. In this work we used a bottom-up approach to prepare large, prevascularized tissue constructs through perfusion culture of porous, cell-laden hydrogel constructs biologically assembled from smaller gel modules. The small gel modules had a controlled shape and were laden with HUVECs and hMSCs. They were packed in a bioreactor for perfusion culture, during which capillary formation inside and between individual gel modules led to the assembly of the small modules into a nearly centimeter sized porous construct. Viable cells and hollow lumen-like structures were observed throughout the porous construct, while in a nonporous control construct with similar dimensions viable cells were only observed in a peripheral layer several hundred micron thick. This modular assembly approach allows for creation of prevascularized large tissue constructs through the biological assembly of gels, which was difficult previously.