Thermal and Reactive Oxygen Species Dual-Responsive OEGylated Polysulfides with Oxidation-Tunable Lower Critical Solution Temperatures.

In this work, two monomethoxy oligo(ethylene glycol) (OEG)-substituted episulfides are prepared and a series of polysulfides are synthesized with subsequent ring-opening polymerization. The OEGylated polysulfides exhibit thermal and reactive oxygen species (ROS) dual-responsive behavior. Their lower critical solution temperatures (LCSTs) are close to human body temperature and depend on the degree of polymerization and OEG length. Notably, the LCST of the polysulfide increases linearly with the oxidation degree by H2 O2 , showing a highly tunable change regulated by the ratio between hydrophobic sulfide and hydrophilic sulfoxide/sulfone in the backbone. Further, the OEGylated polysulfide can act as a ROS scavenger to protect red blood cells (RBCs) from oxidative damage in an RBCs aging model in vitro. This work paves a facile way to synthesize LCST-tunable polysulfides, which hold great promise in biological applications.

Do electrospun polymer fibers stick?

Adhesion between electrospun polycaprolactone (PCL) fibers was directly measured in a cross-cylinder geometry using a nanoforce tensile tester. The surface roughness of fibers was determined by an atomic force microscope (AFM), and the structural factors were characterized by differential scanning calorimeter (DSC) and wide-angle X-ray diffraction (WAXD). "Pull-off" force was found to be in the order of 10(-6) N, and the adhesion energy was 190 +/- 7 mJ/m(2). Adhesion increases with decreasing fiber radius. The experimental data are analyzed by the classical Johnson-Kendall-Roberts (JKR) contact mechanics model. The study provides fruitful insights into future development of bio-inspired adhesives and devices.

Morphological and X-ray diffraction studies of crystalline hydroxyapatite-reinforced polycaprolactone.

Morphological and mechanical properties of hydroxyapatite (HAP)-reinforced polycaprolactone (PCL) were studied. The objective was to examine how morphological features alter the bulk mechanical properties in our laboratory-synthesized HAP-reinforced PCL. HAP crystals were synthesized by hydrolysis of mixtures of calcium and phosphate salts in the laboratory with wet chemical methods. The properties of the commercially available hydroxyapatite (HAP(1)) are compared with that of laboratory-synthesized hydroxyapatite (HAP(2)). The HAP crystals and composition were characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectrometry (FTIR). The HAP(1) and HAP(2) crystals were dispersed into polymers to examine the mechanical behavior of bioactive composites, and the interfacial interactions between the polymer and HAP crystals are addressed. The FTIR results confirmed that the two forms of HAP crystals are consistent in terms of the functional chemical groups. The wide angle X-ray diffraction study was performed to determine the crystallinity of the bioactive composites. It was observed that the crystallinty of HAP-filled PCL steadily increased as the filler concentration increased. Generally, HAP(2) has a particle size considerably smaller than HAP(1) and the composite derived had higher modulus than conventional HAP-filled polymers. This increase in modulus is attributed to better interfacial interaction. Bioresorbability tests performed on HAP particles found that the synthesized HAP had higher resorption rates. It is clear that the mechanical properties are influenced by the particle size and therefore by the processing method used.

Bioinspired Antioxidant Defense System Constructed by Antioxidants-Eluting Electrospun F127-Based Fibers.

Cells were continuously exposed to oxidative damage by overproduction of reactive oxygen species (ROS) when they contacted implanted biomaterials. The strategy to prevent cells from oxidative injures remains a challenge. Inspired by the antioxidant defense system of cells, we constructed a biocompatible and ROS-responsive architecture on the substrate of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS). The strategy was based on fabrication of architectures through reactive electrospinning of mixture including SEBS, acylated Pluronic F127, copolymer of poly(ethylene glycol) diacrylate and 1,2-ethanedithiol (PEGDA-EDT), and antioxidants (AA-2G) and ROS-triggered release of AA-2G from microfibers to detoxify the excess ROS. We demonstrated that the stable and hydrophilic architecture was constructed by phase separation of SEBS/F127 components and cross-linking between polymer chains during electrospinning; the ROS-responsive fibers controlled the release of AA-2G and the interaction of AA-2G with ROS reduced the oxidative damage to cells. The bioinspired architecture not only reduced mechanical and oxidative damage to cells but also maintained normal ROS level for physiological hemostasis. This work provides basic principles to design and develop antioxidative biomaterials for implantation in vivo.

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.

A novel hydrophilic polymer-brush pattern for site-specific capture of blood cells from whole blood.

A novel hydrophilic PAMPS-PAAm brush pattern is fabricated to selectively capture blood cells from whole blood. PAMPS brushes provide antifouling surfaces to resist protein and cell adhesion while PAAm brushes effectively entrap targeted proteins for site-specific and cell-type dependent capture of blood cells.

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.

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.

Fracture strength and adhesive strength of hydroxyapatite-filled polycaprolactone.

Fracture toughness and tear strength of hydroxyapatite (HAP)-filled poly(epsilon-caprolactone) (PCL) with increasing HAP concentration were studied. The toughness was assessed in terms of essential work of fracture (EWF). Adhesive strength between HAP and PCL interfaces was evaluated using T-peel testing. The adhesion between the two components was found to be relatively strong. Double edge notched tension (DENT) and trousers test specimens were used for the EWF tests. The effect of HAP phase in PCL on the fracture and tearing toughness was investigated. The results obtained from the EWF tests for the HAP-filled PCL complied with the validity criteria of the EWF concept, namely, (1) geometric similarity for all ligament lengths; (2) fully yielded ligament and (3) plane-stress fracture condition. Values for specific essential work of fracture (w ( e )) and specific plastic work of fracture (betaw ( p )) were found to decrease with increase in HAP concentration. The testing procedure showed promise in quantifying the tearing resistance and rising R-curve behavior common in natural materials and it can be extended to other biomaterials that exhibit post-yield deformation. A quantitative assessment based on fracture mechanics of the adhesive strength between the bioactive interfaces plays an important role for continued development of tissue replacement and tissue regeneration materials.