Oxygen Delivery Strategies in Tissue-Engineering Constructs

The supply of nutrients and the removal of waste products play a major role in tissue engineering. From all the nutrients necessary for cells seeded on scaffolds for tissue regeneration, oxygen is the limiting component due to its low solubility in culture media while cells consume five to six moles of oxygen for every mole of monosaccharide. The aim of the present work was to develop different strategies to improve the supply of oxygen to human coronary artery smooth muscle cells (HCASMC) seeded on three dimensional (3D) porous biostable polyurethane scaffolds. As a springboard for the study, the measured value of oxygen diffusivity through porous polyurethane scaffolds, fabricated by using pressure differential/particulate leaching technique, was used to screen the best polymer concentration. Scaffolds fabricated form 15 wt% polymer concentration not only had higher oxygen diffusivity but also have better pore interconnectivity as shown by SEM image analysis. Moreover a convective mass transfer approach showed an improvement in the infiltration of HCASMCs into the 3D scaffolds. An oxygen carrier molecule, perfluorodecalin (PFD), was found to improve dissolved oxygen concentration in culture media. PFD was shown to be not only non-toxic to HCASMC but also have no significant effect on the morphology of the HCASMCs. Therefore, higher cell density and infiltration depth into the polyurethane scaffolds were observed when HCASMCs were cultured in a media containing PFD. The final stage of this work was to introduce an oxygen vector into the skeleton of polyurethane scaffolds. For this reason, inert Zeolite Y particles were fluorinated and shown to enhance the amount of dissolved oxygen when suspended in culture media. Fluorinated Zeolite (FZ) particles were then embedded into polyurethane scaffolds without modifying the porosity and morphology of the 3D structures. Subsequently, higher cell density and infiltration depths were observed when HCASMCs were cultured on FZ particles embedded polyurethane scaffolds in contrast to bare polyurethane scaffolds. Taken together, these data show three different but equally advantageous strategies of improving the supply of oxygen to HCASMC seeded into the interstices of 3D polyurethane scaffolds