| 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. |
