Polymer fibers as contact guidance to orient microvascularization in a 3D environment

We describe an in vitro culture process that uses 100-microm diameter poly(ethylene terephthalate) monofilaments as contact guidance of human umbilical vein endothelial cells (HUVECs) to orient the development of microvessels in a 3D environment. Untreated fibers, distanced either by 0.05, 0.1, 0.15, or 0.2 mm were first covered with HUVECs and then sandwiched between two layers of fibrin gel containing HUVECs. After 2 and 4 days of culture, cell connections and microvessels were evaluated. Cell connections formed massively along and in between adjacent fibers that were distanced by 0.05 and 0.1 mm, whereas with fibers separated by larger distances, connections were rare. After 4 days of culture, the optimum fiber-to-fiber distance to form microvessels was 0.1 mm. This study reveals that polymer fibers embedded in gel can be used as guides to direct the microvascularization process, with potential applications in cancer and cardiovascular research and tissue engineering.