Assembly of thin-walled, cell-laden hydrogel conduits inflated with perfluorocarbon

Abstract

Autologous vessel grafts are considered the best option for coronary artery bypass surgery. However, their restricted availability and the poor patency of allografts as well as synthetic polymer grafts, make the development of biofunctional, small-calibre blood vessel substitutes of great interest. We propose a novel free-form manufacturing technique for the extrusion of cell-laden hydrogel tubes with adjustable wall thickness. Alginate and an alginate–fibrinogen blend were coextruded with high-density perfluorocarbon, which served as a liquid-supporting core. Hydrogel conduits measuring several centimetres in length and 2 mm in diameter were fabricated. By varying the volume flow ratio of gel and perfluorocarbon the wall thickness could be adjusted precisely in a range from 0.2 to 0.3 mm. In order to adjust the operating parameters of the technique, a theoretical model of the bioextrusion process based on the gelling kinetics of alginate was developed. Experimental validation revealed a high level of accordance with this model (90–100%). Burst-pressure tests indicated high mechanical stability of the extruded conduits (>100 kPa). Fibroblasts encapsulated in the hydrogel tubes were cultured for 7 days and exhibited a high degree of cell viability (>90%) and proliferation over the first week of culture. The proposed technique holds great promise for the fully automated manufacturing of cell-laden hydrogel conduits to be used for tissue engineering purposes or as tubing in bio-artificial, medical devices such as dialysers or liver support systems, in the future.