Hemocompatibility Assessment of Carbonic Anhydrase Modified Hollow Fiber Membranes for Artificial Lungs

Artificial lungs composed of bundles of micro-porous hollow fiber membranes (HFMs), which are made from polymeric materials such as poly (methylpentene) and poly(propylene), are routinely employed to both oxygenate blood and remove carbon dioxide (CO2) in an extraluminal blood flow format. The efficiency of CO2 and oxygen (O2) gas exchange in the current artificial lung model, which is based on passive diffusion, is limited by the fiber surface area to blood volume ratio with devices requiring approximately 1–2 m2 of HFM surface to provide adequate gas exchange (1,2). Such large blood-contacting surfaces present significant challenges to hemocompatibility, necessitating aggressive anticoagulation and stimulating research into devices with improved efficiency (i.e., smaller) and hemocompatibility. A wide variety of surface modification techniques have been evaluated to reduce the thrombogenicity of blood-contacting biomaterials, although there have been relatively few reports specifically focused on the HFMs utilized in artificial lung applications. Siloxane-grafted HFMs prepared by a plasma polymerization process with 1,3,3,7-tetramethyhydrocyclosiloxane (TMCTS)-coated fibers have shown reduced thrombogenesis relative to unmodified fibers (3). Plasma polymerization techniques have a number of advantages with regard to surface modification including: facile preparation of a thin, conformal, and pinhole-free coating; amenability to a wide variety of substrates; achievement of good adhesion between coating and substrate; and the ability to generate coatings that present excellent thermal and chemical resistance (4,5). Another approach to improving artificial lung biocompatibility is to effectively reduce the required HFM surface area by increasing the gas exchange rate of HFM-based devices. Increasing the efficiency of CO2 removal is especially important because the natural concentration gradient for CO2 diffusion is much smaller than that for O2 addition. Furthermore, in many patients with respiratory failure, the need for CO2 removal is more important clinically, as oxygenation can be provided by nasal cannula or lung-protective ventilation (1,6–8). In a previous study, we reported the development of a bioactive HFM that could improve CO2 removal rates in lung failure patients (9). Carbonic anhydrase (CA) was covalently immobilized to the surface of a conventional HFM, and by catalyzing the dehydration of bicarbonate in blood was shown to facilitate diffusion of CO2 toward the fiber membranes, essentially mimicking the function of the enzyme on lung capillary surfaces. Results indicated that CO2 exchange rates from buffer were increased by as much as 75% in the model device. In this brief report, we addressed whether the attachment of CA onto a HFM surface increased fiber thrombogenicity, which would negate the biocompatibility benefits associated with a smaller device. A commercial poly(propylene) HFM (Celgard, Charlotte, NC,USA) was used as the base material and for control purposes. Fibers representing the intermediate modification steps of siloxane coating and amine grafting on siloxane (Alung Technologies, Pittsburgh, PA, USA) as well as the final CA-modified fiber were evaluated. A second control of a commercial poly (methyl pentene) HFM (Oxyplus, Membrana, Wuppertal, Germany) was also included.