Ionic rectifying effect is a unique ion transport phenomenon observed in certain types of nanofluidic devices and cannot be implemented in microfluidics. Analogous to a diode in solid-state electronics, these diode-like nanofluidic devices can be used to turn the ionic flow on and off depending on the polarity of the applied electric-field. In this tutorial review, we summarize recent advances in the experimental and theoretical studies of ion current rectification in several types of nanofluidic devices. We also present a unified model to elucidate the physical mechanism behind the asymmetric ion transport behavior in nanofluidics.

We investigate the ionic rectifying effect through 4 and 20 nm thick silica nanochannels placed between two ionic solutions of different concentrations. The effect was observed when only a single side of the channel has electric double-layer overlap. The calculation based on Poisson-Nernst-Planck (PNP) theory and a simplified model suggests that the phenomenon result from the accumulation and depletion of both cations and anions in the nanochannels responding to different bias polarities. The model also elucidates that the basis of the rectifying effects in the nanofluidic devices reported to date is due to the asymmetric cation/anion ratios or equivalently built-in potentials on the two sides of the nanochannels. The study benefits the design of nanofluidic devices for attoliter-scale chemical delivery.

We investigate several ion transport behaviors in sub-20 nm nanofluidic channels consisting of heterogeneous oxide materials. By utilizing distinct isoelectric points of SiO2 and Al2O3 surfaces and photolithography to define the charge distribution, nanofluidic channels containing positively and negatively charged surfaces are created to form an abrupt junction. This method provides much more robust surface charges than previous approaches by surface chemical treatment. The fabricated nanofluidic diodes exhibit high rectification of ion current and achieve record-high rectification factors (ratio of forward current to reverse current) of over 300. The current-voltage property of the device follows the theoretical model quantitatively, except that at low ion concentrations the forward current degrades and the reverse current is greater than theoretical prediction, which can be attributed to access resistance and breakdown of water molecules. The breakdown effect characterized by a negative conductance followed by a rapid increase of current is observed in a double junction diode. The occurrence of the breakdown is found to be enhanced by the abruptness of the junction between the heterogeneous nanochannels. Finally, we demonstrate ionic switching in a three-terminal nanofluidic triode in which the ionic flow can be electrically regulated between different channel branches. The study provides insight into the ion transport behavior in nanofluidic devices containing heterogeneous surfaces.

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Modular tissue engineering holds great potential in regenerating natural complex tissues by engineering three-dimensional modular scaffolds with predefined geometry and biological characters. In modular tissue-like construction, a scaffold with an appropriate mechanical rigidity for assembling fabrication and high biocompatibility for cell survival is the key to the successful bioconstruction. In this work, a series of composite hydrogels (GH0, GH1, GH2, and GH3) based on a combination of methacrylated gelatin (GelMA) and hydroxyapatite (HA) was exploited to enhance hydrogel mechanical rigidity and promote cell functional expression for osteon biofabrication. These composite hydrogels presented a lower swelling ratio, higher mechanical moduli, and better biocompatibility when compared to the pure GelMA hydrogel. Furthermore, on the basis of the composite hydrogel and photolithograph technology, we successfully constructed an osteon-like concentric double-ring structure in which the inner ring encapsulating human umbilical vascular endothelial cells (HUVECs) was designed to imitate blood vessel tubule while the outer ring encapsulating human osteoblast-like cells (MG63s) acts as part of bone. During the coculture period, MG63s and HUVECs exhibited not only satisfying growth status but also the enhanced genic expression of osteogenesis-related and angiogenesis-related differentiations. These results demonstrate this GelMA-HA composite hydrogel system is promising for modular tissue engineering.

Inflexible hydrophilic AlgMA was introduced into a bioactive GelMA hydrogel to enhance stiffness and hydrophilicity, thus improving surface tension driven assembly of modular constructs with spatial organized cell distribution and biofunctions.

It is controversial whether a biomaterial itself, rather than addition of any exogenous growth factor, could induce mesenchymal stem cells (MSCs) to differentiate into chondrogenic lineage, further to regenerate cartilage. Previous studies have shown that collagen-based hydrogel could induce MSCs to differentiate into chondrocytes in vivo but the in vitro studies only have a few reports. The evidence that biomaterials could induce chondrogenesis is not adequate. In this study, we tried to address whether type I collagen hydrogel has chondro-inductive capability in vitro and how this scaffold induces MSCs to generate cartilage tissue without exogenous growth factors in the culture medium. We encapsulated neonatal rabbit bone marrow mesenchymal stem cells (BMSCs) in type I collagen hydrogel homogeneously or implanted cell aggregates in hydrogel, and cultured them in nonchondrogenic inductive media. After at least 28 days culture, cells in the homogeneous group were tending to chondrogenic differentiation while cell density was high, and cells in the aggregate group have almost gone through chondrogenesis and formed neo-cartilage tissue with abundant specific extracellular matrix (ECM) deposition. These results indicate collagen hydrogel has inherent inductivity for the chondrogenic differentiation of BMSCs, and the optimum specification and tissue formation were accompanied with local high cell density. This research suggests a feasible strategy to induce the chondro differentiation of BMSCs independent of exogenous growth factors, which may greatly contribute to clinical cartilage regeneration.

Microenvironments, composed of many kinds of cytokines and growth factors plus extracellular matrices with diverse electrostatic properties, play key roles in controlling cell functions in vivo. In this study, three kinds of water-soluble polymers, positively charged poly(L-lysine) (PLL), negatively charged poly(acrylic acid) (PAAc) and neutral poly(ethylene glycol) (PEG), were compared based on their effects on the adhesion, spread, proliferation and chondrogenic differentiation of human mesenchymal stem cells (MSCs). The MSCs were seeded and cultured in the presence of polymers of different concentrations applied by methods using coating, mixing or covering. The effects of the water-soluble polymers depended on their electrostatic properties and method of application. The methods were in the order of coating, mixing and covering in terms of high to low influence. A low concentration of PLL promoted MSC adhesion, spread, proliferation and chondrogenic differentiation, while a high concentration of PLL was toxic. The PEG-coated surface facilitated cell aggregation and spheroid formation by inhibiting cell adhesion. A high concentration of mixed PEG (10 microg/ml) promoted cell proliferation in serum-free medium. PAAc showed no obvious effects on MSC adhesion, spread, proliferation, or chondrogenic differentiation.