Polydopamine and related polycatecholamines can be easily deposited onto almost any surface from mild, aqueous solution. This results in durable, nanoscale coatings that exhibit high biocompatibility and have useful chemical and electronic properties. Additionally, these materials can be readily chemically and physically modified, and consequently, they are used extensively for surface modification. This review investigates the formation and modification of polycatecholamines; how they adhere to surfaces; and the chemical, physical, and electronic properties of the resultant materials. There is also an exploration of the extraordinary array of applications in which these fascinating materials are employed.

Versatile Surface Modification Using Polydopamine and Related Polycatecholamines: Chemistry, Structure, and Applications

Devices that function in contact with blood are ubiquitous in clinical medicine and biotechnology. These devices include vascular grafts, coronary stents, heart valves, catheters, hemodialysers, heart-lung bypass systems and many others. Blood contact generally leads to thrombosis (among other adverse outcomes), and no material has yet been developed which remains thrombus-free indefinitely and in all situations: extracorporeally, in the venous circulation and in the arterial circulation. In this article knowledge on blood–material interactions and “thromboresistant” materials is reviewed. Current approaches to the development of thromboresistant materials are discussed including surface passivation; incorporation and/or release of anticoagulants, antiplatelet agents and thrombolytic agents; and mimicry of the vascular endothelium.

Blood compatible materials: state of the art

肝・胆道疾患の Thrombelastography

Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called "organ-on-a-chip" technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field.

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Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering.

Microfluidic or microchannel artificial lungs promise to enable a new class of truly portable, therapeutic artificial lungs through feature sizes and blood channel designs that closely mimic those found in their natural counterpart. These new artificial lungs could potentially: 1) have surface areas and priming volumes that are a fraction of current technologies thereby decreasing device size and reducing the foreign body response; 2) contain blood flow networks in which cells and platelets experience pressures, shear stresses, and branching angles that copy those in the human lung thereby improving biocompatibility; 3) operate efficiently with room air, eliminating the need for gas cylinders and complications associated with hyperoxemia; 4) exhibit biomimetic hydraulic resistances, enabling operation with natural pressures and eliminating the need for blood pumps; and, 5) provide increased gas exchange capacity enabling respiratory support for active patients. This manuscript reviews recent research efforts in microfluidic artificial lungs targeted at achieving the advantages above, investigates the ultimate performance and scaling limits of these devices using a proven mathematical model, and discusses the future challenges that must be overcome in order for microfluidic artificial lungs to be applied in the clinic. If all of these promising advantages are realized and the remaining challenges are met, microfluidic artificial lungs could revolutionize the field of pulmonary rehabilitation.

The promise of microfluidic artificial lungs

A miniaturized oxygenator device that is perfused like an artificial placenta via the umbilical vessels may have significant potential to save the lives of newborns with respiratory insufficiency. Recently we presented the concept of an integrated modular lung assist device (LAD) that consists of stacked microfluidic single oxygenator units (SOUs) and demonstrated the technical details and operation of SOU prototypes. In this article, we present a LAD prototype that is designed to accommodate the different needs of term and preterm infants by permitting changing of the number of parallel-stacked microfluidic SOUs according to the actual body weight. The SOUs are made of polydimethylsiloxane, arranged in parallel, and connected though 3D-printed polymeric interconnects to form the LAD. The flow characteristics and the gas exchange properties were tested in vitro using human blood. We found that the pressure drop of the LAD increased linearly with flow rate. Gas exchange rates of 2.4-3.8 μL/min/cm(2) (0.3-0.5 mL/kg/min) and 6.4-10.1 μL/min/cm(2) (0.8-1.3 mL/kg/min) for O2 and CO2 , respectively, were achieved. We also investigated protein adsorption to provide preliminary information on the need for application of anticoagulant coating of LAD materials. Albumin adsorption, as measured by gold staining, showed that surface uptake was evenly distributed and occurred at the monolayer level (>0.2 μg/cm(2) ). Finally, we also tested the LAD under in vivo conditions using a newborn piglet model (body weight 1.65-2.0 kg). First, the effect of an arteriovenous bypass via a carotid artery-to-jugular vein shortcut on heart rate and blood pressure was investigated. Heart rate and mean arterial blood pressure remained stable for extracorporeal flow rates of up to 61 mL/kg/min (101 mL/min). Next, the LAD was connected to umbilical vessels (maximum flow rate of 24 mL/min [10.4 mL/kg/min]), and O2 gas exchange was measured under hypoxic conditions (Fi O2  = 0.15) and was found to be 3.0 μL/min/cm(2) . These results are encouraging and support the feasibility of an artificial placental design for an LAD.

An integrated array of microfluidic oxygenators as a neonatal lung assist device: in vitro characterization and in vivo demonstration.

A modified poly(dimethyl siloxane) (PDMS) material is under development for use in an extracorporeal microfluidic blood oxygenator designed as an artificial placenta to treat newborn infants suffering from severe respiratory insufficiency. To prevent thrombosis triggered by blood-material contact, an antithrombin–heparin (ATH) covalent complex was coated on PDMS surface using polydopamine (PDA) as a “bioglue”. Experiments using radiolabelled ATH showed that the ATH coating on PDA-modified PDMS remained substantially intact after incubation in plasma, 2% SDS solution, or whole blood over a three day period. The anticoagulant activity of the ATH-modified surfaces was also demonstrated: in contact with plasma the ATH-coated PDMS was shown to bind antithrombin (AT) selectively from plasma and to inhibit clotting factor Xa. It is concluded that modification of PDMS with polydopamine and ATH shows promise as a means of improving the blood compatibility of PDMS and hence of the oxygenator device.

Surface modification of poly(dimethylsiloxane) with a covalent antithrombin-heparin complex for the prevention of thrombosis: use of polydopamine as bonding agent.

To prevent coagulation in contact with blood, polydimethylsiloxane (PDMS) was modified with an antithrombin–heparin (ATH) covalent complex using polyethylene glycol (PEG) as a linker/spacer. Using NHS chemistry, ATH was attached covalently to the distal chain end of the immobilized PEG linker. Surfaces were characterized by contact angle and X-ray photoelectron spectroscopy; attachment was confirmed by decrease in contact angles and an increase in nitrogen content as determined by X-ray photoelectron spectroscopy. Protein interactions in plasma were investigated using radiolabeled proteins added to plasma as tracers, and by immunoblotting of eluted proteins. Modification of PDMS with PEG alone was effective in reducing non-specific protein adsorption; attachment of ATH at the distal end of the PEG chains did not significantly affect protein resistance. It was shown that surfaces modified with ATH bound antithrombin selectively from plasma through the pentasaccharide sequence on the heparin moiety of ATH, ...

Jennifer M. Leung

Papers

An integrated array of microfluidic oxygenators as a neonatal lung assist device: in vitro characterization and in vivo demonstration.

Surface modification of poly(dimethylsiloxane) with a covalent antithrombin-heparin complex for the prevention of thrombosis: use of polydopamine as bonding agent.

Surface modification of polydimethylsiloxane with a covalent antithrombin-heparin complex to prevent thrombosis.