We achieved ultralow fouling on target surfaces by controlled polymerization of carboxybetaine under ambient conditions. The polymerization process for grafting polymer films onto the surfaces was carried out in air and did not require any deoxygenation step or specialized equipment. This method allows one to conveniently introduce a nonfouling polymer network onto large substrates.

It is highly desirable to develop a universal nonfouling coating via a simple one-step dip-coating method. Developing such a universal coating method for a hydrophilic polymer onto a variety of surfaces with hydrophobic and hydrophilic properties is very challenging. This work demonstrates a versatile and simple method to attach zwitterionic poly(carboxybetaine methacrylate) (PCB), one of the most hydrophilic polymers, onto both hydrophobic and hydrophilic surfaces to render them nonfouling. This is achieved by the coating of a catechol chain end carboxybetaine methacrylate polymer (DOPA-PCB) assisted by dopamine. The coating process was carried out in water. Water miscible solvents such as methanol and tetrahydrofuran (THF) are added to the coatings if surface wettability is an issue, as for certain hydrophobic surfaces. This versatile coating method was applied to several types of surfaces such as polypropylene (PP), polydimethyl siloxane (PDMS), Teflon, polystyrene (PS), polymethylmethacrylate (PMMA), polyvinyl chloride (PVC) and also on metal oxides such as silicon dioxide.

Inhibiting thrombosis without generating bleeding risks is a major challenge in medicine. A promising solution may be the inhibition of coagulation factor XII (FXII), because its knockout or inhibition in animals reduced thrombosis without causing abnormal bleeding. Herein, we have engineered a macrocyclic peptide inhibitor of activated FXII (FXIIa) with subnanomolar activity (K i = 370 ± 40 pM) and a high stability (t 1/2 > 5 days in plasma), allowing for the preclinical evaluation of a first synthetic FXIIa inhibitor. This 1899 Da molecule, termed FXII900, efficiently blocks FXIIa in mice, rabbits, and pigs. We found that it reduces ferricchloride-induced experimental thrombosis in mice and suppresses blood coagulation in an extracorporeal membrane oxygenation (ECMO) setting in rabbits, all without increasing the bleeding risk. This shows that FXIIa activity is controllable in vivo with a synthetic inhibitor, and that the inhibitor FXII900 is a promising candidate for safe thromboprotection in acute medical conditions.

Unlike dialysis, which functions as a bridge to renal transplantation, or a ventricular assist device, which serves as a bridge to cardiac transplantation, no suitable bridge to lung transplantation exists. Our goal is to design and build an ambulatory artificial lung that can be perfused entirely by the right ventricle and completely support the metabolic O2 and CO2 requirements of an adult. Such a device could realize a substantial clinical impact as a bridge to lung transplantation, as a support device immediately post-lung transplant, and as a rescue and/or supplement to mechanical ventilation during the treatment of severe respiratory failure. Research on the artificial lung has focused on the design, mode of attachment to the pulmonary circulation, and intracorporeal versus paracorporeal placement of the device.

No abstract

A thoracic artificial lung (TAL) was designed to treat respiratory insufficiency, acting as a temporary assist device in acute cases or as a bridge to transplant in chronic cases. We developed a computational model of the pulmonary circulatory system with the TAL inserted. The model was employed to investigate the effects of parameter values and flow distributions on power generated by the right ventricle, pulsatility in the pulmonary system, inlet flow to the left atrium, and input impedance. The ratio of right ventricle (RV) power to cardiac output ranges between 0.05 and 0.10 W/(L/min) from implantation configurations of low impedance to those of high impedance, with a control value of 0.04 W/(L/min). Addition of an inlet compliance to the TAL reduces right heart power (RHP) and impedance. A compliant TAL housing reduces flow pulsatility in the fiber bundle, thus affecting oxygen transfer rates. An elevated bundle resistance reduces flow pulsatility in the bundle, but at the expense of increased right heart power. The hybrid implantation mode, with inflow to the TAL from the proximal pulmonary artery (PA), outflow branches to the distal PA and the left atrium (LA), a band around the PA between the two anastomoses, and a band around the outlet graft to the LA, is the best compromise between hemodynamic performance and preservation of some portion of the nonpulmonary functions of the natural lungs.

The functions of anti‐fouling, zwitterionic polycarboxybetaine (pCB) coating, and anti‐platelet nitric oxide (NO) release replicate key anticoagulant properties of the endothelium. The two approaches, only tested separately thus far, are paired on gas permeable polydimethylsiloxane (PDMS) membranes and evaluated for fibrinogen (Fg) and platelet adsorption. Uncoated (control) and pCB‐coated PDMS separate sheep plasma (108 platelets per milliliter) and gas flow chambers within bioreactors used in this study, and either 100 or 0 ppm of NO/N2 flows through the gas chamber so PDMS transfers NO into flowing plasma. Surface‐adsorbed platelets are quantified using a lactate dehydrogenase assay after 8h plasma recirculation. Fg and platelet adsorption on pCB‐coated PDMS are 10.40% ± 3.0% of control (p < 0.01) and 23.3% ± 7.4% (p < 0.01) of control, respectively. NO flux alone limits platelet adsorption to 79.0% ± 5.0% (p < 0.05) of control. Together, NO and pCB reduce platelet adsorption to 6.90% ± 1.30% of control (p < 0.001). The data suggest that pCB coating and NO act in concert to reduce platelet fouling at significantly higher levels than either pCB coating or NO release alone.

No abstract