Page 18 - Improved endothelialization by silicone surface modification and fluid hydrodynamics modulation- Implications for oxygenator biocompatibility Nasim

GENERAL INTRODUCTION
From an engineering perspective, the lung is a paradigm of design efficiency. A gas transfer surface area of approximately 70 m2 accomplishes efficient oxygen and carbon dioxide transfer [1, 2]. In mammals, oxygen is transferred via diffusion through pulmonary alveoli which is then distributed to different tissues by red blood cells. On the other hand, carbon dioxide produced by living cells is absorbed by the blood flow and is transferred to the pulmonary capillaries from where it penetrates into the alveoli and is finally discharged through the airways [1-3]. A membrane of 0.4-2 μm thickness separates air-carrying alveoli from the pulmonary capillaries (Figure 1).
There has been modest success in decellularization and recellularization of rat lung and also in organizing cells into small-scale structures to mimic pulmonary tissue, but scale-up and creating effective connect between such structures require further research [3]. There is a prominent need to develop new and more effective therapies for cardiopulmonary support or treatment of end-stage lung failure due to different lung-related diseases, e.g. acute respiratory distress syndrome [4, 5], chronic obstructive pulmonary disease [6], pulmonary fibrosis, pulmonary hypertension, and cystic fibrosis, mostly involving people in developing countries and mainly resulting from increasing rates of tobacco smoking and pollutants of urbanization [6].
Current treatment options to provide respiratory support (chronic aid) during cardiac surgery or for patients with end-stage pulmonary failure are mainly limited to extracorporeal membrane oxygenation (ECMO) [5, 6]. An ECMO device can only give partial respiratory support because of the low blood volumes that can be bypassed externally. This treatment can avert the death of the patient, but is generally used only temporarily until lung transplantation is possible [4, 6]. ECMO devices utilize an external circuit consisting of a blood pump, an oxygenator, a heat exchanger, and several feet of tubing. The membrane oxygenator component of ECMO devices, also called artificial lung, typically takes the form of a bundle of microporous hollow fibres fabricated from different synthetic polymers such as polypropylene, silicone, etc (Figure 1). Blood flows around the outside of the hollow fibers and oxygen flows through the lumen of the hollow fibers. ECMO circuits are primarily designed for open-heart surgical procedures (4–8 h), and require high levels of anticoagulation [5]. The limits of the current technology are found at the interface of the gas and blood sides of synthetic hollow fibers. Long term usage of hollow fibers is limited by plasma-wetting, and biocompatibility issues associated with thrombosis and/or bleeding [1, 5]. Plasma-wetting is the penetration of liquid into the fiber pores, which inhibits gas exchange. The plasma-wetting problem can be solved by using non-porous membrane hollow fibers or diffusive capillary-form hollow spheres [5, 7]. However, the poor biocompatibility of hollow fibers is still a
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