Tortuosity Engineering for Improved Charge Storage Kinetics in High-Areal-Capacity Battery Electrodes.

The increasing demands of electronic devices and electric transportation necessitate lithium-ion batteries with simultaneous high energy and power capabilities. However, rate capabilities are often limited in high-loading electrodes due to the lengthy and tortuous ion transport paths with their electrochemical behaviors governed by complicated electrode architectures still elusive. Here, we report the electrode-level tortuosity engineering design enabling improved charge storage kinetics in high-energy electrodes. Both high areal capacity and high-rate capability can be achieved beyond the practical level of mass loadings in electrodes with vertically oriented architectures. The electrochemical properties in electrodes with various architectures were quantitatively investigated through correlating the characteristic time with tortuosity. The lithium-ion transport kinetics regulated by electrode architectures was further studied via combining the three-dimensional electrode architecture visualization and simulation. The tortuosity-controlled charge storage kinetics revealed in this study can be extended to general electrode systems and provide useful design consideration for next-generation high-energy/power batteries.

The influence of roughness on stem cell differentiation using 3D printed polylactic acid scaffolds.

With the increase in popularity of 3D printing, an important question arises as to the equivalence between devices manufactured by standard methods vs. those presenting with identical bulk specifications, but manufactured via fused deposition modeling (FDM) printing. Using thermal imaging in conjunction with electron and atomic force microscopy, we demonstrate that large thermal gradients, whose distribution is difficult to predict, are associated with FDM printing and result in incomplete fusion and sharkskin of the printing filament. Even though these features are micro or submicron scale, and hence may not interfere with the intended function of the device, they can have a profound influence if the device comes in contact with living tissue. Dental pulp stem cells were cultured on substrates of identical dimensions, which were either printed or molded from the same PLA stock material. The cultures exhibited significant differences in plating efficiency, migration trajectory, and morphology at early times stemming from attempts by the cells to minimize cytoplasm deformation as they attempt to adhere on the printed surfaces. Even though biomineralization without dexamethasone induction was observed in all cultures at later times, different gene expression patterns were observed on the two surfaces. (Osteogenic markers were upregulated on molded substrates, while odontogenic markers were upregulated on the FDM printed surfaces.) Our results clearly indicate that the method of manufacturing is an important consideration in comparing devices, which come in contact with living tissues.

Design of a molecular imprinting biosensor with multi-scale roughness for detection across a broad spectrum of biomolecules.

The molecular imprinting technique has tremendous applications in artificial enzymes, bioseparation, and sensor devices. In this study, a novel molecular imprinting (MI) biosensor platform was developed for the detection of a broad range of biomolecules with different sizes. Previously this method has been applied to 2D molecular imprinting, where the height of the self-assembled monolayer (SAM) of around 2 nm limited the maximum dimensions of the molecule that can be imprinted to create template-shaped cavities. In order to match the size of the imprinted molecules with the height of the SAM, we propose a model for 3D molecular imprinting where the analyte is sequestered within a niche created by the surface roughness. The SAM is assembled on the walls of the niche, forming a 3D pattern of the analyte uniquely molded to its contour. Surfaces with multi-scale roughness were prepared by evaporation of gold onto electropolished (smooth) and unpolished (rough) Si wafers, where the native roughness was found to have a normal distribution centered around 5 and 90 nm respectively. Our studies using molecules with size ranging on a nanometer scale, from proteins of a few nanometers to bacteria of hundreds of nanometers, showed that when the size of the analyte matched the roughness range of the gold surface, the molecular imprinting process was optimized for the best biosensing performance. After optimization, the MI biosensor platform enabled the identification and quantification of a broad range of biomolecules with great discrimination abilities. Hemoglobin under different pH values and several mutated fibrinogen molecules can also be well differentiated through the test.

Quantitative real-time detection of carcinoembryonic antigen (CEA) from pancreatic cyst fluid using 3-D surface molecular imprinting.

In this study, a sensitive, yet robust, biosensing system with real-time electrochemical readout was developed. The biosensor system was applied to the detection of carcinoembryonic antigen (CEA), which is a common marker for many cancers such as pancreatic, breast, and colon cancer. Real time detection of CEA during a medical procedure can be used to make critical decisions regarding further surgical intervention. CEA was templated on gold surface (RMS roughness ∼3-4 nm) coated with a hydrophilic self-assembled monolayer (SAM) on the working electrode of an open circuit potentiometric network. The subsequent removal of template CEA makes the biosensor capable of CEA detection based on its specific structure and conformation. The molecular imprinting (MI) biosensor was further calibrated using the potentiometric responses in solutions with known CEA concentrations and a detection limit of 0.5 ng ml(-1) was achieved. Potentiometric sensing was then applied to pancreatic cyst fluid samples obtained from 18 patients when the cyst fluid was also evaluated using ELISA in a certified pathology laboratory. Excellent agreement was obtained between the quantitation of CEA obtained by both the ELISA and MI biosensor detection for CEA. A 3-D MI model, using the natural rms roughness of PVD gold layers, is presented to explain the high degree of sensitivity and linearity observed in those experiments.

TiO2 nanoparticles synergize with substrate mechanics to improve dental pulp stem cells proliferation and differentiation.

Multiple studies exist on the influence of TiO2 nanoparticle uptake on cell behavior. Yet little is known about the lingering influence of nanoparticles accumulation within the external environment which is particularly important to stem cell differentiation. Herein, dental pulp stem cells were cultured on hard and soft polybutadiene substrates, where 0.1 mg/mL rutile TiO2 nanoparticles were introduced once, 24 h after plating. In the absence of TiO2, the doubling time on soft substrate is significantly longer, while addition of TiO2 decreases it to the same level as on the hard substrate. FACS analysis indicates particle uptake initially at 25% is reduced to 2.5% after 14 days. In the absence of TiO2, no biomineralization on the soft and snowflake-like hydroxyapatite deposits on the hard substrate are shown at week 4. With the addition of TiO2, SEM/EDAX reveals copious mineral deposition templated on large banded collagen fibers on both substrates. The mineral-to-matrix ratios analyzed by Raman spectroscopy are unremarkable in the absence of TiO2. However, with addition of TiO2, the ratios are consistent with native bone on the hard and dentin on the soft substrates. This is further confirmed by RT-PCR, which showed upregulation of markers consistent with osteogenesis and odontogenesis, respectively.

Combination of 3D Printing and ALD for Dentin Fabrication from Dental Pulp Stem Cell Culture.

A combination of fused deposition modeling printing with atomic layer deposition (ALD) of titania was designed to achieve templated biomineralization and terminal odontogenic differentiation of dental pulp stem cells on three-dimensional (3D) printed polylactic acid (PLA) scaffolds. In the absence of the ALD-deposited titania coating, we had previously shown that both plating efficiency and differentiation are adversely impacted when scaffolds are produced by 3D printing rather than traditional polymer molding. These differences were removed when both printed and molded structures were coated with ALD of titania, which improved the outcomes regardless of the manufacturing method. In this case, on all titania-coated substrates, the plating efficiency increased, copious mineral deposition was observed, and RT-PCR indicated a significant upregulation of osteocalcin, a gene associated with mineral deposition. The influence of additional coatings of collagen, gelatin, or fibronectin on the ALD titania-coated and uncoated PLA-printed and molded scaffolds was also investigated. Upregulation of the odontogenic late-stage differentiation sibling protein, dentin sialoprotein, was observed on the collagen ALD-titania-coated scaffolds and to a lesser extent on the gelatin ALD-titania-coated scaffolds.

Regulating substrate mechanics to achieve odontogenic differentiation for dental pulp stem cells on TiO2 filled and unfilled polyisoprene.

We have shown that materials other than hydrogels commonly used in tissue engineering can be effective in enabling differentiation of dental pulp stem cells (DPSC). Here we demonstrate that a hydrophobic elastomer, polyisoprene (PI), a component of Gutta-percha, normally used to obturate the tooth canal, can also be used to initiate differentiation of the pulp. We showed that PI substrates without additional coating promote cell adhesion and differentiation, while their moduli can be easily adjusted either by varying the coating thickness or incorporation of inorganic particles. DPSC plated on those PI substrates were shown, using SPM and hysitron indentation, to adjust their moduli to conform to differentially small changes in the substrate modulus. In addition, optical tweezers were used to separately measure the membrane and cytoplasm moduli of DPSC, with and without Rho kinase inhibitor. The results indicated that the changes in modulus were attributed predominantly to changes within the cytoplasm, rather than the cell membrane. CLSM was used to identify cell morphology. Differentiation, as determined by qRT-PCR, of the upregulation of OCN, and COL1α1 as well as biomineralization, characterized by SEM/EDAX, was observed on hard PI substrates in the absence of induction factors, i.e. dexamethasone, with moduli 3-4 MPa, regardless of preparation. SEM showed that even though biomineralization was deposited on both spun cast thin PI and filled thick PI substrates, the minerals were aggregated into large clusters on thin PI, and uniformly distributed on filled thick PI, where it was templated within banded collagen fibers. STATEMENT OF SIGNIFICANCE: This manuscript demonstrates the potential of polyisoprene (PI), an elastomeric polymer, for use in tissue engineering. We show how dental pulp stem cells adjust their moduli continuously to match infinitesimally small changes in substrate mechanics, till a critical threshold is reached when they will differentiate. The lineage of differentiation then becomes a sensitive function of both mechanics and morphology for a given chemical composition. Since PI is a major component of Gutta-percha, the FDA approved material commonly used for obturating the root canal, this work suggests that it can easily be adapted for in vivo use in dental regeneration.

Effect of Graphene on Differentiation and Mineralization of Dental Pulp Stem Cells in Poly(4-vinylpyridine) Matrix in Vitro.

We have investigated the influence of graphene nanoplatelet scaffolds for dental pulp cells (DPSCs) made from poly(4-vinylpyridine) (P4VP) either via spin-casting flat films or electrospinning nano- and microscale fibers. We found that graphene predominated over other factors in promoting differentiation of DPSCs. In the absence of graphene, real-time-polymerase chain reaction (RT-PCR) and energy dispersive X-ray (EDX) analyses indicated that the DPSCs differentiated along odontogenic lineages only on the nano- and microelectrospun scaffolds. Closer scanning electron microscopy (SEM) imaging revealed formation of banded collagen structures, which nucleated on the electrospun fibers in the absence of graphene. Biomineral deposition was templated on these fibers, with mineral to protein ratios similar to dentin. In the microfibers, the graphene was completely encapsulated and appeared to hinder biomineralization. Previously minimal biomineralization and banded collagen were observed on flat spun cast substrates. Addition of graphene appeared to induce nucleation of banded collagen fibers and template biomineral deposition. Addition of graphene did not affect the outcome of the DPSCs cultured on the nanofibers, which biomineralized regardless of graphene inclusion. Based on these results, we hypothesize that direct contact with graphene is the primary factor determining differentiation of the DPSCs. On the flat surface and nanoscale electrospun fibers, the graphene protrudes from the sample enabling direct contact with the extracellular matrix (ECM) and cells, while on the microfibers, the graphene is fully encapsulated within the matrix. TUNA imaging with scanning force microscopy showed enhanced conductivity on fibers with encapsulated graphene, which we hypothesize may change the conformation of adsorbed ECM proteins, affecting DPSCs differentiation.

Sulfoethylated nanofibrillated cellulose: Production and properties.

Sulfoethylated nanofibrillated cellulose (NFCSulf) was produced by an industrially relevant process. The properties of the NFCSulf were compared with those of carboxymethylated nanofibrillated cellulose (NFCCarb), which has been identified as an attractive NFC for several industrial applications. The investigations revealed that NFCSulf is characterized by a higher degree of fibrillation and has superior redispersion properties. Furthermore, NFCSulf displays higher stability in varying pH values as compared to NFCCarb. Hence, NFCSulf may be a more attractive alternative than NFCCarb in applications such as rheological modifiers or adsorbing components in personal care products, in which the performance of NFC must remain unaffected in varying ambient conditions. The superior properties of NFCSulf compared to NFCCarb were proposed to be due to the combination of the unique chemical characteristics of the sulfoethylated reagent, and the larger size of the sulfonate group compared to the carboxymethyl group.

Correction: Manipulation of cell adhesion and dynamics using RGD functionalized polymers.

Correction for 'Manipulation of cell adhesion and dynamics using RGD functionalized polymers' by Juyi Li et al., J. Mater. Chem. B, 2017, DOI: .

Manipulation of cell adhesion and dynamics using RGD functionalized polymers.

We have successfully synthesized an ABA tri-block co-polymer of poly(methacrylic acid)-block-poly(2-hydroxyethyl methacrylate)-block-poly(methacrylic acid), having Mw = 100k and 272k where we were able to insert RDG or RGD peptide sequences using thiol-acrylate Michael addition. A soft silicone stamp was then used to imprint a 0.4-micron wide grating of the copolymer with a period of 10 microns. The samples were then examined with atomic force microscopy after application of an external electric field and the pattern was observed to stretch by a factor of five. Cells plated onto these substrates showed clear preference for the striped patterns formed under the influence of the external field, and no preferential attachment to the patterns formed in the absence of the field. Cell migration experiments, using the agarose droplet method, performed on spun cast copolymer films showed minimal migration and adhesion on the substrates without peptides or those with only with the RDG peptide, while good adhesion and significant outward migration was observed for cells plated on the copolymers with the RGD sequence. Taken together these results confirmed our hypothesis that a smart biomimetic polymer substrate could be constructed where functional domains could be revealed selectively allowing us to mimic the natural design of engineered tissue constructs.

Differentiation of Dental Pulp Stem Cells on Gutta-Percha Scaffolds.

Advances in treatment of tooth injury have shown that tooth regeneration from the pulp was a viable alternative of root canal therapy. In this study, we demonstrated that Gutta-percha, nanocomposites primarily used for obturation of the canal, are not cytotoxic and can induce differentiation of dental pulp stem cells (DPSC) in the absence of soluble mediators. Flat scaffolds were obtained by spin coating Si wafers with three Gutta-percha compounds: GuttaCore™, ProTaper™, and Lexicon™. The images of annealed surfaces showed that the nanoparticles were encapsulated, forming surfaces with root mean square (RMS) roughness of 136⁻211 nm. Then, by culturing DPSC on these substrates we found that after some initial difficulty in adhesion, confluent tissues were formed after 21 days. Imaging of the polyisoprene (PI) surfaces showed that biomineral deposition only occurred when dexamethasone was present in the media. Spectra obtained from the minerals was consistent with that of hydroxyapatite (HA). In contrast, HA deposition was observed on all Gutta-percha scaffolds regardless of the presence or absence of dexamethasone, implying that surface roughness may be an enabling factor in the differentiation process. These results indicate that Gutta-percha nanocomposites may be good candidates for pulp regeneration therapy.

Enhancing the Mechanical Properties of Biodegradable Polymer Blends Using Tubular Nanoparticle Stitching of the Interfaces.

"Green" polymer nanocomposites were made by melt blending biodegradable poly(lactic acid) (PLA) and poly(butylene adipate-co-butylene terephthalate) (PBAT) with either montmorillonite clays (Cloisite Na(+)), halloysite nanotubes (HNTs), the resorcinol diphenyl phosphate (RDP)-coated Cloisite Na(+), and coated HNTs. A technique for measuring the work of adhesion (Wa) between nanoparticles and their matrixes was used to determine the dispersion preference of the nanoparticles in the PLA/PBAT blend system. Transmission electron microscopy (TEM) images of thin sections indicated that even though both RDP-coated nanotubes and clay platelets segregated to the interfacial regions between the two immiscible polymers, only the platelets, having the larger specific surface area, were able to reduce the PBAT domain sizes. The ability of clay platelets to partially compatibilize the blend was further confirmed by the dynamic mechanical analysis (DMA) which showed that the glass transition temperatures of two polymers tended to shift closer. No shift was observed with either coated or uncoated HNTs samples. Izod impact testing demonstrated that the rubbery PBAT phase greatly increased the impact strength of the unfilled blend, but addition of only 5% of treated clay decreased the impact strength by nearly 50%. On the other hand, an increase of 9% relative to the unfilled blend sample was observed with the addition of 5% treated nanotubes. TEM cross-section analysis confirmed that the RDP-coated clay platelets covered most of the interfacial area. On one hand, this enabled them to reduce the interfacial tension effectively; on the other hand, it prevented chain entanglements across the phase boundary and increased the overall brittleness, which was confirmed by rheology measurements. In contrast, the RDP-coated HNTs were observed to lie perpendicular to the interface, which made them less effective in reducing interfacial tension but encouraged interfacial entanglements across the interface, resulting in "stitching" of the interface and an increase in the Izod impact of the blend.