Xiaodong Xu

Hierarchical Polymer Brushes with Dominant Antibacterial Mechanisms Switching from Bactericidal to Bacteria Repellent

Although polycationic surfaces have high antimicrobial efficacies, they suffer from high toxicity to mammalian cells and severe surface accumulation of dead bacteria. For the first time, we propose a surface-initiated photoiniferter-mediated polymerization (SI-PIMP) strategy of constructing a cleaning zwitterionic outer layer on a polycationic bactericidal background layer to physically hinder the availability of polycationic moieties for mammalian cells in aqueous service. In dry conditions, the polycationic layer exerts the contact-active bactericidal property toward the adherent bacteria, as the zwitterionic layer collapses. In aqueous environment, the zwitterionic layer forms a hydration layer to significantly inhibit the attachment of planktonic bacteria and the accumulation of dead bacteria, while the polycationic layer kills bacteria occasionally deposited on the surface, thus preserving the antibacterial capability for a long period. More importantly, the zwitterionic hydrated layer protects the mammalian cells from toxicity induced by the bactericidal background layer, and therefore hierarchical antibacterial surfaces present much better biocompatibility than that of the naked cationic references. The dominant antibacterial mechanism of the hierarchical surfaces can switch from the bactericidal efficacy in dry storage to the bacteria repellent capability in aqueous service, showing great advantages in the infection-resistant applications.

Fabrication of a Detection Platform with Boronic-Acid-Containing Zwitterionic Polymer Brush

Development of technologies for biomedical detection platform is critical to meet the global challenges of various disease diagnoses, especially for point-of-use applications. Because of its natural simplicity, effectiveness, and easy repeatability, random covalent-binding technique is widely adopted in antibody immobilization. However, its antigen-binding capacity is relatively low when compared to site-specific immobilization of antibody. Herein, we report that a detection platform modified with boronic acid (BA)-containing sulfobetaine-based polymer brush. Mainly because of the advantage of oriented immobilization of antibody endowed with BA-containing three-dimensional polymer brush architecture, the platform had a high antigen-binding capacity. Notably, nonspecific protein adsorption was also suppressed by the zwitterionic pendants, thus greatly enhanced signal-to-noise (S/N) values for antigen recognition. Furthermore, antibodies captured by BA pendants could be released in dissociation media. This new platform is promising for potential applications in immunoassays.

Controlled Lecithin Release from a Hierarchical Architecture on Blood-Contacting Surface to Reduce Hemolysis of Stored Red Blood Cells

Hemolysis of red blood cells (RBCs) caused by implant devices in vivo and nonpolyvinyl chloride containers for RBC preservation in vitro has recently gained much attention. To develop blood-contacting biomaterials with long-term antihemolysis capability, we present a facile method to construct a hydrophilic, 3D hierarchical architecture on the surface of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS) with poly(ethylene oxide) (PEO)/lecithin nano/microfibers. The strategy is based on electrospinning of PEO/lecithin fibers onto the surface of poly [poly(ethylene glycol) methyl ether methacrylate] [P(PEGMEMA)]-modified SEBS, which renders SEBS suitable for RBC storage in vitro. We demonstrate that the constructed 3D architecture is composed of hydrophilic micro- and nanofibers, which transforms to hydrogel networks immediately in blood; the controlled release of lecithin is achieved by gradual dissolution of PEO/lecithin hydrogels, and the interaction of lecithin with RBCs maintains the membrane flexibility and normal RBC shape. Thus, the blood-contacting surface reduces both mechanical and oxidative damage to RBC membranes, resulting in low hemolysis of preserved RBCs. This work not only paves new way to fabricate high hemocompatible biomaterials for RBC storage in vitro, but provides basic principles to design and develop antihemolysis biomaterials for implantation in vivo.

Precise patterning of the SEBS surface by UV lithography to evaluate the platelet function through single platelet adhesion

Platelets have exhibited capabilities beyond clotting in recent years. Most of their functions are related to the nature of platelet adhesion. Establishing a facile method to understand the platelet adhesion and assess the platelet function through the mechanism and mechanics of adhesion is highly desired. Here, we report a generally applicable UV lithography technique with a photomask, which performs selective surface functionalization on large substrate areas, for creating stable, physical adhesive sites in the range of 12 μm to 3 μm. Our study demonstrated that the patterned surface facilitated probing of single platelet adhesion in a quantitative manner, and rendered platelets sensitive to adhesive proteins even at a low protein concentration. In addition, the platelet function in the presence of antiplatelet (anticancer) agents on platelets could be accurately estimated based on single platelet adhesion (SPA). This work paves a new way to understand and assess the blood platelet function. The SPA assay methodology has the potential to enable a rapid, accurate point-of-care platform suitable for evaluation of platelet function, detection of dysfunctional platelets, and assay of drug effects on platelets in cancer patients.

Superhydrophobic coating of elastomer on different substrates using a liquid template to construct a biocompatible and antibacterial surface

The construction of biocompatible and antibacterial surfaces is becoming increasingly important. However, most of the existing techniques require multi-step procedures, stringent conditions and specific substrates. We present here a facile method to create a biocompatible and antibacterial surface on virtually any substrate under ambient conditions. The strategy is based on casting a highly adherent elastomer, styrene-b-(ethylene-co-butylene)-b-styrene, from a solvent mixture of xylene and decanol, in which decanol acts as both a polymer precipitator to induce phase separation and a liquid template to stabilize the superhydrophobic structure. The stable and durable superhydrophobic surface shows good biocompatibility and antibacterial properties.

Stimuli-Responsive Polypropylene for the Sustained Delivery of TPGS and Interaction with Erythrocytes

Hemocompatibility and oxidative stress are significant for blood-contacting devices. In this study, N-isopropylacrylamide (NIPAAm) and N-(3-aminopropyl)methacrylamide hydrochloride (APMA) were cografted on polypropylene (PP) membrane using ultraviolet grafting to load antioxidative d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and control the release of TPGS. The immobilization of NIPAAm and APMA onto PP membrane was confirmed by attenuated total reflectance Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. Combined with data from platelet adhesion, red blood cell (RBC) attachment, and hemolysis rate, the hemocompatibility of PP was significantly improved. An in-depth characterization using hemolysis rate test, scanning electron microscopy, atomic force microscopy, and confocal laser scanning microscopy was conducted to confirm that the mechanism of the release of TPGS interacted with RBCs was different at different stages. The release of TPGS from the loading PP membranes affected hemolysis at different stages. At the early stage of release, TPGS maintained the tiny (nanometer-sized) tubers on the membrane surface and enhanced the membrane permeabilization by generating nanosized pores on the cell membranes. Afterward, the incorporated TPGS slowed the lipid peroxidation of erythrocytes and filled in the lipid bilayer of erythrocyte to prevent hemolysis. Thus, the approach implemented to graft NIPAAm and APMA and load TPGS was suitable to develop medical device with excellent hemocompatibility and antioxidative property.

Construction of D-α-tocopheryl polyethylene glycol succinate/PEO core–shell nanofibers on a blood-contacting surface to reduce the hemolysis of preserved erythrocytes

The hemolysis of erythrocytes is a big obstacle to the development of new non-plasticizer polymer containers for erythrocyte preservation. To construct a long-term anti-hemolytic surface of a plasticizer-free polymer, we coaxially electrospin core-shell structured d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)/poly(ethylene oxide) nanofibers on the surface of a styrene-b-(ethylene-co-butylene)-b-styrene (SEBS) elastomer that is covered with grafted poly(ethylene glycol) (PEG) chains. Our strategy is based on the fact that the grafted layers of PEG reduce mechanical damage to red blood cells (RBCs) while the TPGS released from the nanofibers on a blood-contacting surface can act as an antioxidant to protect RBCs from oxidative damage. We demonstrate that TPGS/PEO core-shell structured nanofibers have been well prepared on the surface of PEG modified SEBS; the controlled release of TPGS in distilled water is obtained and the release can last for almost 4 days at 4 °C; during RBC preservation, TPGS acts as the antioxidant to decrease the membrane oxidation and hemolysis of RBCs. Our work paves a new way for the development of non-plasticizer polymers for RBC preservation, which may be helpful for the fabrication of long-term anti-hemolytic biomaterials in vivo.

Construction of 3D Micropatterned Surfaces with Wormlike and Superhydrophilic PEG Brushes To Detect Dysfunctional Cells

Detection of dysfunctional and apoptotic cells plays an important role in clinical diagnosis and therapy. To develop a portable and user-friendly platform for dysfunctional and aging cell detection, we present a facile method to construct 3D patterns on the surface of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS) with poly(ethylene glycol) brushes. Normal red blood cells (RBCs) and lysed RBCs (dysfunctional cells) are used as model cells. The strategy is based on the fact that poly(ethylene glycol) brushes tend to interact with phosphatidylserine, which is in the inner leaflet of normal cell membranes but becomes exposed in abnormal or apoptotic cell membranes. We demonstrate that varied patterned surfaces can be obtained by selectively patterning atom transfer radical polymerization (ATRP) initiators on the SEBS surface via an aqueous-based method and growing PEG brushes through surface-initiated atom transfer radical polymerization. The relatively high initiator density and polymerization temperature facilitate formation of PEG brushes in high density, which gives brushes worm-like morphology and superhydrophilic property; the tendency of dysfunctional cells adhered on the patterned surfaces is completely different from well-defined arrays of normal cells on the patterned surfaces, providing a facile method to detect dysfunctional cells effectively. The PEG-patterned surfaces are also applicable to detect apoptotic HeLa cells. The simplicity and easy handling of the described technique shows the potential application in microdiagnostic devices.

Binary Release of Ascorbic Acid and Lecithin from Core-Shell Nanofibers on Blood-Contacting Surface for Reducing Long-Term Hemolysis of Erythrocyte

There is an urgent need to develop blood-contacting biomaterials with long-term anti-hemolytic capability. To obtain such biomaterials, we coaxially electrospin [ascorbic acid (AA) and lecithin]/poly (ethylene oxide) (PEO) core-shell nanofibers onto the surface of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS) that has been grafted with poly (ethylene glycol) (PEG) chains. Our strategy is based on that the grafted layers of PEG render the surface hydrophilic to reduce the mechanical injure to red blood cells (RBCs) while the AA and lecithin released from nanofibers on blood-contacting surface can actively interact with RBCs to decrease the oxidative damage to RBCs. We demonstrate that (AA and lecithin)/PEO core-shell structured nanofibers have been fabricated on the PEG grafted surface. The binary release of AA and lecithin in the distilled water is in a controlled manner and lasts for almost 5 days; during RBCs preservation, AA acts as an antioxidant and lecithin as a lipid supplier to the membrane of erythrocytes, resulting in low mechanical fragility and hemolysis of RBCs, as well as high deformability of stored RBCs. Our work thus makes a new approach to fabricate blood-contacting biomaterials with the capability of long-term anti-hemolysis.

Effect of surface interactions on adhesion of electrospun meshes on substrates.

Despite the importance of adhesion between electrospun meshes and substrates, the knowledge on adhesion mechanism and the method to improve the adhesion remain limited. Here, we precisely design the model system based on electrospun poly(ethylene oxide) (PEO) meshes and the substrate of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS), and quantitatively measure the adhesion with a weight method. The surfaces of SEBS with different roughness are obtained by casting SEBS solution on the smooth and rough glass slides, respectively. Then, the surfaces of casted SEBS are respectively grafted with PEG oligomers and long PEG chains much larger than the entanglement molecular weight by surface-initiated atom transfer radical polymerization (SI-ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMA). The detached surfaces of SEBS and electrospun fibers after adhesion measurements are analyzed by scanning electron microscopy (SEM). The adhesive force and adhesion energy are found to lie in the range from 68 to 220 mN and from 12 to 46 mJ/m(2), respectively, which are slightly affected by surface roughness of substrate but mainly determined by surface interactions. Just as the chemical cross-linking induces the strong adhesion, the chain entanglements on the interface lead to the higher adhesion than those generated by hydrophilic-hydrophobic interactions and hydrophilic interactions. The long grafted chains and the enhanced temperature facilitate the chain entanglements, resulting in the strong adhesive force. This work sheds new light on the adhesion mechanism at molecular level, which may be helpful to improve the adhesion between the electrospun fibers and substrates in an environmentally friendly manner.