Mixed Matrix Membrane with Penetrating Subnanochannels: A Versatile Nanofluidic Platform for Selective Metal Ion Conduction.

Biological ion channels penetrated through cell membrane form unique transport pathways for selective ionic conductance. Replicating the success of ion selectivity with mixed matrix membranes (MMMs) will enable new separation technologies but remains challenging. Herein, we report a soft substrate-assisted solution casting method to develop MMMs with penetrating subnanochannels for selective metal ion conduction. The MMMs are composed of penetrating Prussian white (PW) microcubes with subnanochannels in dense polyimide (PI) matrices, achieving selective monovalent metal ion conduction. The ion selectivity of K+ /Mg2+ is up to 14.0, and the ion conductance of K+ can reach 45.5 µS with the testing diameter of 5 mm, which can be further improved by increasing the testing area. Given the diversity of nanoporous materials and polymer matrices, we expect that the MMMs with penetrating subnanochannels could be developed into a versatile nanofluidic platform for various emerging applications.

In Vivo Measurement of Calcium Ion with Solid-State Ion-Selective Electrode by Using Shelled Hollow Carbon Nanospheres as a Transducing Layer.

In vivo monitoring of extracellular calcium ion (Ca2+) is of great importance due to its significant contributions in different (patho)physiological processes. In this study, we develop a potentiometric method with solid-state ion-selective electrodes (ISEs) for in vivo monitoring of the dynamics of the extracellular Ca2+ by using hollow carbon nanospheres (HCNs) as a transducing layer and solid contact to efficiently promote the ion-to-electron transduction between an ionophore-doped solvated polymeric membrane and a conducting substrate. We find that the use of HCNs essentially improves the stability of the signal response and minimizes the potential drift of the as-prepared ISEs. With three-shelled HCNs (3s-HCNs) as the transducing layer, we fabricate a solid-state Ca2+-selective microelectrode by forming a Ca2+-selective membrane with calcium ionophore II as the recognition unit, 2-nitrophenyl octyl ether as the plasticizer, sodium tetrakis[3,5-bis(trifluoromethyl)phenyl] borate as the ion exchanger, and polyvinyl chloride polymeric as the matrix onto the 3s-HCN-modified carbon fiber electrodes. The as-prepared electrode shows a high stability and a near Nernst response of 28 mV/decade toward Ca2+ over a concentration range from 10-5 to 0.05 M as well as a good selectivity against species endogenously existing in the central nervous system. With these properties, the electrode is used for real-time recording of the dynamics of extracellular Ca2+ during spreading depression induced by electrical stimulation, in which the extracellular Ca2+ in rat cortex is found to decrease by 50.0 ± 7.5% ( n = 5) during spreading depression. This study essentially offers a new platform to develop solid-state ISEs, which is particularly useful for in vivo measurements of metal ions and pH in live rat brain.

Controllable and Reproducible Sheath of Carbon Fibers with Single-Walled Carbon Nanotubes through Electrophoretic Deposition for In Vivo Electrochemical Measurements.

The unique electronic and chemical structures of carbon nanotubes (CNTs) have well enabled their applications in electrochemistry and electroanalytical chemistry; however, the difficulty in reproducibly confining CNTs onto substrate electrodes, particularly onto microelectrodes, still remains to be addressed. In this study, we develop a method to reproducibly confine single-walled carbon nanotubes (SWNTs) onto carbon fiber microelectrodes (CFEs) with electrophoretic deposition (EPD) for in vivo measurement of ascorbate. Under 2.5 V, acid-treated SWNTs are uniformly deposited on CFEs. After thermal treatment at 300 °C followed by electrochemical treatment in 0.5 M H2SO4, the SWNT-sheathed CFEs exhibit good activity to accelerate the electrochemical oxidation of ascorbic acid (i.e., ascorbate, in a neutral solution) at an onset potential of -0.15 V vs Ag/AgCl and could in vivo selectively detect ascorbate. The controllable procedures employed for EPD and pretreatment avoid the deviation in the conventional manual modification methods such as drop casting and hand rolling previously used for confining SWNTs onto an electrode surface. With the electrodes prepared here, we find that level of extracellular ascorbate in the rat cortex increases by 20.4 ± 4.8% ( n = 4), relative to its basal level, within 9 min after infusion of kainic acid into the hippocampus to evoke epilepsy. This study offers a reproducible method to prepare SWNT-sheathed CFEs for in vivo monitoring ascorbate that would largely facilitate future studies on neurochemical processes of ascorbate in various physiological and pathological events.

Mussel-inspired hybrid coating functionalized porous hydroxyapatite scaffolds for bone tissue regeneration.

The scaffold for bone tissue engineering should possess proper porosity, adequate mechanical properties, cell affinity for cell attachment, and the capability to bind bioactive agents to induce cell differentiation. In this study, we successfully prepared a porous hydroxyapatite (HA) scaffold that is functionalized by poly(L-lysine)/polydopamine (PLL/PDA) hybrid coating. The PLL/PDA coating takes advantages of the high protein and cell affinity of PDA, as well as the biodegradability of PLL. Therefore, the coating can anchor bone morphogenic protein-2 (BMP2) to the HA scaffold via catechol chemistry under a mild condition so as to protect the bioactivity of BMP2. Meanwhile, the coating can also release BMP2 in a tunable and sustainable manner as the PLL degrades in the physiological environment. The BMP2-entrapped PLL/PDA coating on the HA scaffold can more efficiently promote osteogenic differentiation of bone marrow stromal cells (BMSCs) in vitro and induce ectopic bone formation to a much greater level in vivo compared with a bare HA scaffold that delivers BMP2 in a burst manner. All of these results suggest that the PDA-mediated catechol modification of the HA scaffold can be an effective strategy to develop sustainable protein delivery system, and that the PLL/PDA-coated HA scaffold could be a promising candidate for bone tissue engineering applications.

Polydopamine mediated assembly of hydroxyapatite nanoparticles and bone morphogenetic protein-2 on magnesium alloys for enhanced corrosion resistance and bone regeneration.

Magnesium alloys have the great potential to be used as orthopedic implants due to their biodegradability and mechanical resemblance to human cortical bone. However, the rapid degradation in physiological environment with the evolution of hydrogen gas release hinders their clinical applications. In this study, we developed a novel functional and biocompatible coating strategy through polydopamine mediated assembly of hydroxyapatite nanoparticles and growth factor, bone morphogenetic protein-2 (BMP-2), onto the surface of AZ31 Mg alloys. Such functional coating has strong bonding with the substrate and can increase surface hydrophilicity of magnesium alloys. In vitro electrochemical corrosion and hydrogen evolution tests demonstrate that the coating can significantly enhance the corrosion resistance and therefore slow down the degradation of AZ31 Mg alloys. In vitro cell culture reveals that immobilization of HA nanoparticles and BMP-2 can obviously promote cell adhesion and proliferation. Furthermore, in vivo implantation tests indicate that with the synergistic effects of HA nanoparticles and BMP-2, the coating does not cause obvious inflammatory response and can significantly reduce the biodegradation rate of the magnesium alloys and induce the new bone formation adjacent to the implants. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2750-2761, 2017.

Mussel-inspired nano-building block assemblies for mimicking extracellular matrix microenvironments with multiple functions.

The assembly of nano-building blocks is an effective way to produce artificial extracellular matrix microenvironments with hierarchical micro/nano structures. However, it is hard to assemble different types of nano-building blocks, to form composite coatings with multiple functions, by traditional layer-by-layer (LbL) self-assembly methods. Inspired by the mussel adhesion mechanism, we developed polydopamine (PDA)-decorated bovine serum albumin microspheres (BSA-MS) and nano-hydroxyapatite (nano-HA), and assembled them to form bioactive coatings with micro/nano structures encapsulating bone morphogenetic protein-2 (BMP-2). First, PDA-decorated nano-HA (nano-pHA) was obtained by oxidative polymerization of dopamine on nano-HA. Second, BMP-2-encapsulated BSA microspheres were prepared through desolvation, and then were also decorated by PDA (pBSA-MS). Finally, the nano-pHA and pBSA-MS were assembled using the adhesive properties of PDA. Bone marrow stromal cell cultures and in vivo implantation, showed that the pHA/pBSA (BMP-2) coatings can promote cell adhesion, proliferation, and benefited for osteoinductivity. PDA decoration was also applied to assemble various functional nanoparticles, such as nano-HA, polystyrene, and Fe3O4 nanoparticles. In summary, this study provides a novel strategy for the assembly of biofunctional nano-building blocks, which surpasses traditional LbL self-assembly of polyelectrolytes, and can find broad applications in bioactive agents delivery or multi-functional coatings.

Bio-inspired two-dimensional nanofluidic generators based on a layered graphene hydrogel membrane.

An electrogenetic layered graphene hydrogel membrane (GHM) possesses ultra-large interlayer spacing of about 10 nm, forming charged 2D nanocapillaries between graphene sheets that selectively permeate counter-ions and exclude co-ions. When an electrolyte flow goes through the GHM, it functions as an integrated 2D nanofluidic generator converting hydraulic motion into electricity. The maximum streaming conductance density approaches 16.8 µA cm(-2) bar(-1) .