Augmented Fluorescence Signaling on a Single BaTiO3 Microbead Optical Booster toward High-Sensitive Biosensing.

In this work, we report a new generation of single microbead bioassay that employs a single BaTiO3 microbead as an optical booster for target biomarker enrichment and optical enhancement toward protein and nucleic acid analysis. The single BaTiO3 microbead can not only concentrate the target molecules by nearly 104-fold but also act as an optical booster to prominently enhance the target-induced fluorescence signal by the whispering gallery mode for improving the excitation efficiency and the microlens effect for promoting the signal collecting efficiency, respectively. Compared with using a conventional single microbead, this optical booster exhibits nearly 2 orders of magnitude higher sensitivity without the assistance of any signal amplification techniques or costly instruments. Moreover, this single microbead optical booster is capable of detecting different kinds of protein and nucleic acid biomarkers in a simple mix-and-read manner, holding great potential for early clinical diagnosis.

Construction of BaTiO3-TiO2 hollow sphere heterojunctions for enhanced microwave dynamic therapy in cancer treatment.

Cancer is one of the primary health concerns among humans due to its high incidence rate and lack of effective treatment. Currently, medical techniques to achieve the precise elimination of local cancer lesions with negligible damage to normal tissues are still intensely desired. Herein, we synthesized BaTiO3-TiO2 hollow spheres (BTHSs) for use in microwave dynamic therapy (MWDT) for cancer. Under UV irradiation, BTHSs can mediate the production of multiple reactive oxygen species (ROS), mainly 1O2, which results in a rapid photocatalytic degradation rate (97%), 1.6-fold that of commercial P25. Importantly, the ROS production process can be triggered by microwaves to effectively execute MWDT for cancer. Under microwave irradiation, BTHSs exhibit a remarkable therapeutic effect and slight cytotoxicity. In terms of mechanism, the enhanced ROS production efficiency of BTHSs can be attributed to their unique hollow structure and the formation of a type-II heterojunction by the incorporation of BaTiO3. The hollow structure increases the availability of active sites and enhances light scattering, while the BaTiO3-TiO2 heterojunction enhances the photocatalytic activity of TiO2 through charge transfer and electron-hole separation. Overall, this study provides important insights into the design and optimization of sensitizers for MWDT applications.

Deep insight into physical properties of carboxymethyl cellulose-barium oxide nanocomposites.

Nanocomposites, blending the unique properties of inorganic nanoparticles with polymers, are gaining momentum in various industries. This study delves into the synthesis and characterization of barium oxide (BaO)-doped carboxymethyl cellulose (CMC) nanocomposites, focusing on their structural, optical, electrical, and dielectric properties. Using an in-situ polymerization method, CMC films were doped with 5 % and 10 % BaO nanoparticles. X-ray diffraction analysis revealed that the doped samples exhibited enhanced crystallinity compared to pure CMC, with crystallinity percentages measured at 37.95 % and 28.86 % for 5 % and 10 % BaO, respectively, indicating the successful incorporation of BaO. Scanning electron microscopy illustrated the distribution of BaO nanoparticles, showing spherical agglomerations on the film surface. SEM analysis reveals emergence of spherical agglomerations and bright spots on nanocomposite film surface upon BaO introduction, indicating BaO nanoparticles presence. Further, the BaO nanoparticles act as catalytic and nucleating agents, influencing crystalline structure nucleation and growth, potentially enhancing film homogeneity and structural integrity. In addition, UV-visible spectroscopy elucidated the optical properties, indicating a shift in the bandgap from indirect to direct with BaO addition. The bandgap values decrease upon the addition of BaO, indicating a transition from an amorphous to a nanocrystalline structure, with respective reduction percentages of 22.73 % and 10.71 % for the 5%BaO/CMC and 10 %BaO/CMC samples compared to CMC. Electrical conductivity measurements showed enhanced conductivity in 10 % BaO/CMC due to improved charge carrier mobility, supported by dielectric studies demonstrating increased dielectric. The introduction of 5 % and 10 % BaO resulted in reductions of approximately 62.06 % and 65.77 %, respectively, compared to the pure CMC sample. This decrease in dielectric loss indicates an enhancement in the electrical properties of the nanocomposites. This comprehensive investigation could give further insights into the different properties of BaO-doped CMC nanocomposites, offering insights into their potential applications in various fields such as electronics, energy storage, and optoelectronics.

Biophysical stimulation for bone regeneration using a chitosan/barium titanate ferroelectric composite.

Herein we report the synthesis of a ferroelectric composed of chitosan (C)/barium titanate (BT) nanoparticles (NPs) with enhanced biocompatibility, non-toxicity, and piezoelectric behavior that can be advantageously used in biomedical applications. FTIR and SEM measurements were performed to assess the mechanism of interaction between the C matrix and BT NPs and their correlation with the biological responses. The dielectric measurements of the as-prepared composites reveal that incorporation of 50% BT NPs in the chitosan matrix leads to a steady increase of the dielectric constant as compared with neat chitosan films. The ferroelectric behavior of the sample was confirmed by the values of the loss factor (0.21-0.003) in the analyzed frequency range (10-1-106 Hz). This behavior suggests that ferroelectric C/BT nanocomposites can act as an active material that promotes accelerated bone regeneration.

Confinement Enrichment Effect in HoMS-BaTiO3 Microwave Gas Sensors for the Detection of 10 ppb-0.55 v/v% Ammonia at Room Temperature.

The construction of ammonia gas sensors with wide detection ranges is important for exhalation diagnosis and environmental pollution monitoring. To achieve a wide detection range, sensitive materials must possess excellent spatial confinement and large active surfaces to enhance gas adsorption. In this study, an ammonia microwave gas sensor with a wide detection range of 10 ppb-0.55 v/v% at room temperature was fabricated by incorporating hollow multishelled-structured BaTiO3 (HoMS-BaTiO3). The effect of the number of shells and the quantity of the sensitive material on the gas-sensing performance was investigated, and two-layered HoMS-BaTiO3 demonstrated the best response at high concentrations (0.15-0.55 v/v%). Conversely, single-layered HoMS-BaTiO3 displayed outstanding performance at low concentrations (10 ppb-0.15 v/v%). The lower the quantity of the sensitive material, the higher the response. This study offers a method for preparing room-temperature ammonia sensors with a wide detection range and reveals the link between the structure and quantity of sensitive materials and gas-sensing performance.

A Comprehensive Review on Barium Titanate Nanoparticles as a Persuasive Piezoelectric Material for Biomedical Applications: Prospects and Challenges.

Stimulation of cells with electrical cues is an imperative approach to interact with biological systems and has been exploited in clinical practices over a wide range of pathological ailments. This bioelectric interface has been extensively explored with the help of piezoelectric materials, leading to remarkable advancement in the past two decades. Among other members of this fraternity, colloidal perovskite barium titanate (BaTiO3 ) has gained substantial interest due to its noteworthy properties which includes high dielectric constant and excellent ferroelectric properties along with acceptable biocompatibility. Significant progression is witnessed for BaTiO3 nanoparticles (BaTiO3 NPs) as potent candidates for biomedical applications and in wearable bioelectronics, making them a promising personal healthcare platform. The current review highlights the nanostructured piezoelectric bio interface of BaTiO3 NPs in applications comprising drug delivery, tissue engineering, bioimaging, bioelectronics, and wearable devices. Particular attention has been dedicated toward the fabrication routes of BaTiO3 NPs along with different approaches for its surface modifications. This review offers a comprehensive discussion on the utility of BaTiO3 NPs as active devices rather than passive structural unit behaving as carriers for biomolecules. The employment of BaTiO3 NPs presents new scenarios and opportunity in the vast field of nanomedicines for biomedical applications.

Performance and mechanism of a novel S-scheme heterojunction sonocatalyst CuS/BaWO4 for degradation of bisphenol A by ultrasonic activation.

A novel CuS/BaWO4 heterojunction catalyst was prepared and characterized. Taking bisphenol A as the target pollutant for catalytic degradation, the sonocatalytic activity of CuS/BaWO4 composite was evaluated, and the combination with persulfate improved the sonocatalytic degradation of bisphenol A. The results showed that CuS/BaWO4 composite had good sonocatalytic degradation activity for bisphenol A, and the degradation rate was 70.99% ± 1.46%. After combined with persulfate, the degradation rate was further increased to 95.34% ± 0.10%, and the reaction time was relatively shortened. The results of the trapping experiment and calculated energy band positions showed that the formation of S-scheme heterojunction and the formation of hydroxyl radicals and holes were the key to the catalytic degradation of bisphenol A by CuS/BaWO4 composite. In this study, a new CuS/BaWO4 heterojunction sonocatalyst was synthesized. The catalyst can efficiently remove bisphenol A from the water environment and can be used as a potential solution for endocrine disruptor pollution in the water environment.

Tip-Induced In-Plane Ferroelectric Superstructure in Zigzag-Wrinkled BaTiO3 Thin Films.

The complex micro-/nanoscale wrinkle morphology primarily fabricated by elastic polymers is usually designed to realize unique functionalities in physiological, biochemical, bioelectric, and optoelectronic systems. In this work, we fabricated inorganic freestanding BaTiO3 ferroelectric thin films with zigzag wrinkle morphology and successfully modulated the ferroelectric domains to form an in-plane (IP) superstructure with periodic surface charge distribution. Our piezoresponse force microscopy (PFM) measurements and phase-field simulation demonstrate that the self-organized strain/stress field in the zigzag-wrinkled BaTiO3 film generates a corresponding pristine domain structure. These domains can be switched by tip-induced strain gradient (flexoelectricity) and naturally form a robust and unique "braided" in-plane domain pattern, which enables us to offer an effective and convenient way to create a microscopic ferroelectric superstructure. The corresponding periodic surface potential distribution provides an extra degree of freedom in addition to the morphology that could regulate cells or polar molecules in physiological and bioelectric applications.

3-Aminopyrazolo[3,4-b]pyridine: Effective Precursor for Barium Hydroxide-Mediated Three Components Synthesis of New Mono- and Bis(pyrimidines) with Potential Cytotoxic Activity.

In this study, an efficient one-pot procedure for preparing a new series of pyrazolo[3,4-b]pyridine-fused pyrimidines was described. The target hybrids were developed through a three-component reaction of 3-amino-1H-pyrazolo[3,4-b]pyridine, benzaldehydes, and acetophenones (molar ratio 1 : 1 : 1). The best conditions for the previous reaction were 2.5 equivalents of barium hydroxide in DMF at 150 °C for 6 h. New bis(pyrimidines) were synthesized in high yields using a similar one-pot reaction protocol with some modifications. Thus, two equivalents of each of the appropriate acetophenones and 3-aminopyrazolopyridine were reacted with one equivalent of the appropriate bis(aldehydes). The reaction was carried out at 150 °C for 8 h using 4.5 equivalents of barium hydroxide in DMF. Repeating the previous reaction with the appropriate bis(acetyl) derivatives and benzaldehydes resulted in good yields of the target bis(pyrimidines). The in vitro cytotoxic activity of new pyrimidines against the MCF-7, HEPG2, and Caco2 cell lines was evaluated using the reference doxorubicin (IC50 values of 4.34-6.97 µM). Hybrid 6h had the best activity against Caco2 and MCF-7 cell lines, IC50 values of 12.62 and 14.50 µM, respectively. The IC50 values for hybrids 6c, 6e, and 6f against MCF-7 and Caco2 cell lines were 23.99-41.69 and 33.14-43.33 µM, respectively. Furthermore, hybrid 6e displayed IC50 value of 20.06 µM HEPG2 cell lines, while the hybrids 6c, 6f and 6h exhibited IC50 values ranging between 26.29-50.51 µM. Furthermore, hybrid 6e had an IC50 value of 20.06 µM for the HEPG2 cell lines, whereas hybrids 6c, 6f, and 6h had IC50 values ranging from 26.29 to 50.51 µM.

Highly Flexible Freestanding BaTiO3 -CoFe2 O4 Heteroepitaxial Nanostructure Self-Assembled with Room-Temperature Multiferroicity.

Multiferroics with simultaneous electric and magnetic orderings are highly desirable for sensing, actuation, data storage, and bio-inspired systems, yet developing flexible materials with robust multiferroic properties at room temperature is a long-term challenge. Utilizing water-soluble Sr3 Al2 O6 as a sacrificial layer, the authors have successfully self-assembled a freestanding BaTiO3 -CoFe2 O4 heteroepitaxial nanostructure via pulse laser deposition, and confirmed its epitaxial growth in both out-of-plane and in-plane directions, with highly ordered CoFe2 O4 nanopillars embedded in a single crystalline BaTiO3 matrix free of substrate constraint. The freestanding nanostructure enjoys super flexibility and mechanical integrity, not only capable of spontaneously curving into a roll, but can also be bent with a radius as small as 4.23 µm. Moreover, piezoelectricity and ferromagnetism are demonstrated at both microscopic and macroscopic scales, confirming its robust multiferroicity at room temperature. This work establishes an effective route for flexible multiferroic materials, which have the potential for various practical applications.

In Vitro Study on the Piezodynamic Therapy with a BaTiO3-Coating Titanium Scaffold under Low-Intensity Pulsed Ultrasound Stimulation.

To solve the poor sustainability of electroactive stimulation in clinical therapy, a strategy of combining a piezoelectric BaTiO3-coated Ti6Al4V scaffold and low-intensity pulsed ultrasound (LIPUS) was unveiled and named here as piezodynamic therapy. Thus, cell behavior could be regulated phenomenally by force and electricity simultaneously. First, BaTiO3 was deposited uniformly on the surface of the three-dimensional (3D) printed porous Ti6Al4V scaffold, which endowed the scaffold with excellent force-electricity responsiveness under pulsed ultrasound exposure. The results of live/dead staining, cell scanning electron microscopy, and F-actin staining showed that cells had better viability, better pseudo-foot adhesion, and more muscular actin bundles when they underwent the piezodynamic effect of ultrasound and piezoelectric coating. This piezodynamic therapy activated more mitochondria at the initial stage that intervened in the cell cycle by promoting cells' proliferation and weakened the apoptotic damage. The quantitative real-time polymerase chain reaction data further confirmed that the costimulation of the ultrasound and the piezoelectric scaffolds could trigger adequate current to upregulated the expression of osteogenic-related genes. The continuous electric cues could be generated by the BaTiO3-coated scaffold and intermittent LIPUS stimulation; thereon, more efficient bone healing would be promoted by piezodynamic therapy in future treatment.

Multifunctional Dental Composite with Piezoelectric Nanofillers for Combined Antibacterial and Mineralization Effects.

After nearly seven decades of development, dental composite restorations continue to show limited clinical service. The triggering point for restoration failure is the degradation of the bond at the tooth-biomaterial interface from chemical, biological, and mechanical sources. Oral biofilms form at the bonded interfaces, producing enzymes and acids that demineralize hard tissues and damage the composite. Removing bacteria from bonded interfaces and remineralizing marginal gaps will increase restorations' clinical service. To address this need, we propose for the first time the use of piezoelectric nanoparticles of barium titanate (BaTiO3) as a multifunctional bioactive filler in dental resin composites, offering combined antibacterial and (re)mineralization effects. In this work, we developed and characterized the properties of dental piezoelectric resin composites, including the degree of conversion and mechanical and physical properties, for restorative applications. Moreover, we evaluated the antibacterial and mineralization responses of piezoelectric composites in vitro. We observed a significant reduction in biofilm growth (up to 90%) and the formation of thick and dense layers of calcium phosphate minerals in piezoelectric composites compared to control groups. The antibacterial mechanism was also revealed. Additionally, we developed a unique approach evaluating the bond strength of dentin-adhesive-composite interfaces subjected to simultaneous attacks from bacteria and cyclic mechanical loading operating in synergy. Our innovative bioactive multifunctional composite provides an ideal technology for restorative applications using a single filler with combined long-lasting nonrechargeable antibacterial/remineralization effects.

Bimodal Nanocomposite Platform with Antibiofilm and Self-Powering Functionalities for Biomedical Applications.

Advances in microelectronics and nanofabrication have led to the development of various implantable biomaterials. However, biofilm-associated infection on medical devices still remains a major hurdle that substantially undermines the clinical applicability and advancement of biomaterial systems. Given their attractive piezoelectric behavior, barium titanate (BTO)-based materials have also been used in biological applications. Despite its versatility, the feasibility of BTO-embedded biomaterials as anti-infectious implantable medical devices in the human body has not been explored yet. Here, the first demonstration of clinically viable BTO-nanocomposites is presented. It demonstrates potent antibiofilm properties against Streptococcus mutans without bactericidal effect while retaining their piezoelectric and mechanical behaviors. This antiadhesive effect led to ∼10-fold reduction in colony-forming units in vitro. To elucidate the underlying mechanism for this effect, data depicting unfavorable interaction energy profiles between BTO-nanocomposites and S. mutans using the classical and extended Derjaguin, Landau, Verwey, and Overbeek theories is presented. Direct cell-to-surface binding force data using atomic force microscopy also corroborate reduced adhesion between BTO-nanocomposites and S. mutans. Interestingly, the poling process on BTO-nanocomposites resulted in asymmetrical surface charge density on each side, which may help tackle two major issues in prosthetics-bacterial contamination and tissue integration. Finally, BTO-nanocomposites exhibit superior biocompatibility toward human gingival fibroblasts and keratinocytes. Overall, BTO-embedded composites exhibit broad-scale potential to be used in biological settings as energy-harvestable antibiofilm surfaces.

Sensitivity enhancement of the SPR biosensor for Pseudomonas bacterial detection employing a silicon-barium titanate structure.

A novel, to the best of our knowledge, surface plasmon resonance (SPR) sensor, employing a silicon-barium titanate structure for Pseudomonas bacterial detection, is designed. Three bacterial attachments operate as a protective layer for the detection process with refractive indices (RI) of 1.437, 1.49368, and 1.5265. Performance analysis shows a sensitivity (S) of 155, 168, and 370°/RIU at RI of 1.5265 for Structures 1, 2, and 3, respectively. Additionally, the proposed sensor (Structure 3) accomplishes a magnified figure of merit (FOM) of 86.43 and quality factor of 86.65 at the RI of 1.5265. Finally, the proposed sensor's performance is compared with that of the existing sensors, thus demonstrating a heightened S and FOM.

"Green" Flexible Electronics: Biodegradable and Mechanically Strong Soy Protein-Based Nanocomposite Films for Human Motion Monitoring.

Soy protein isolate (SPI) is envisioned as a promising alternative to fabricate "green" flexible electronics, showing great potential in the field of flexible wearable electronics. However, it is challenging to simultaneously achieve conductive film-based human motion-monitoring strain sensors with reliable fatigue resistance, robust mechanical property, environmental degradability, and sensing capability of human motions. Herein, we prepared a series of SPI-based nanocomposite films by embedding a surface-hydroxylated high-dielectric constant inorganic filler, BaTiO3, (HBT) as interspersed nanoparticles into a biodegradable SPI substrate. In particular, the fabricated film comprising 0.5 wt % HBT and glycerin (GL), namely, SPI-HBT0.5-GL0.5, presents multifunctional properties, including a combination of excellent toughness, tensile strength, conductivity, translucence, recyclability, and excellent thermal stability. Meanwhile, this multifunctional film could be simply degraded in phosphate buffered saline solution and does not cause any pollution to the environment. Attractively, wearable sensors prepared with this particular material (SPI-HBT0.5-GL0.5) displayed excellent biocompatibility, prevented the occurrence of an immune response, and could accurately monitor various types of human joint motions and successfully remain operable after 10,000 cycles. These properties make the developed SPI-based film a great candidate in formulating biobased and multifunctional wearable electronics.

Toughening and polymerization stress control in composites using thiourethane-treated fillers.

Filler particle functionalization with thiourethane oligomers has been shown to increase fracture toughness and decrease polymerization stress in dental composites, though the mechanism is poorly understood. The aim of this study was to systematically characterize the effect of the type of filler surface functionalization on the physicochemical properties of experimental resin composites containing fillers of different size and volume fraction. Barium glass fillers (1, 3 and 10 µm) were functionalized with 2 wt% thiourethane-silane (TU-Sil) synthesized de novo and characterized by thermogravimetric analysis. Fillers treated with 3-(Trimethoxysilyl)propyl methacrylate (MA-Sil) and with no surface treatment (No-Sil) served as controls. Fillers (50, 60 and 70 wt%) were incorporated into BisGMA-UDMA-TEGDMA (5:3:2) containing camphorquinone/ethyl-4-dimethylaminobenzoate (0.2/0.8 wt%) and 0.2 wt% di-tert-butyl hydroxytoluene. The functionalized particles were characterized by thermogravimetric analysis and a representative group was tagged with methacrylated rhodamine B and analyzed by confocal laser scanning microscopy. Polymerization kinetics were assessed by near-IR spectroscopy. Polymerization stress was tested in a cantilever system, and fracture toughness was assessed with single edge-notched beams. Fracture surfaces were characterized by SEM. Data were analyzed with ANOVA/Tukey's test (α = 0.05). The grafting of thiourethane oligomer onto the surface of the filler particles led to reductions in polymerization stress ranging between 41 and 54%, without affecting the viscosity of the composite. Fracture toughness increased on average by 35% for composites with the experimental fillers compared with the traditional methacrylate-silanized groups. SEM and confocal analyses demonstrate that the coverage of the filler surface was not homogeneous and varied with the size of the filler. The average silane layer for the 1 µm particle functionalized with the thiourethane was 206 nm, much thicker than reported for traditional silanes. In summary, this study systematically characterized the silane layer and established structure-property relationships for methacrylate and thiourethane silane-containing materials. The results demonstrate that significant stress reductions and fracture toughness increases are obtained by judiciously tailoring the organic-inorganic interface in dental composites.

Hard magnetic membrane based on bacterial cellulose - Barium ferrite nanocomposites.

Magnetic membranes based on bacterial cellulose (BC) nanocomposites have been extensively researched. However, most magnetic nanoparticles (NPs) incorporated in the BC matrix were focused on soft magnetic phases, which limited the extensive use of magnetic BC membranes. Therefore, this work proposes a method to fabricate hard magnetic membrane based on the BC matrix and magnetically hard phase barium ferrite (BFO) NPs. The nanocomposites showed the peaked tensile strength and modulus at the low concentration of BFO whereas the magnetization increased drastically with the BFO content. They also demonstrate the high flexibility up on bending and the sensitivity to external magnetic fields. Furthermore, unlike other magnetic BC membranes, the BC/BFO nanocomposites exhibited the hard magnetic properties, i.e. they could retain their magnetic attraction after being magnetized by a permanent magnet. These properties open the possibility to employ these materials in various fields, such as information storage, anti-couterfeit or electromagnetic shieldings.

Unique Noncontact Monitoring of Human Respiration and Sweat Evaporation Using a CsPb2Br5-Based Sensor.

Respiration monitoring and human sweat sensing have promising application prospects in personal healthcare data collection, disease diagnostics, and the effective prevention of human-to-human transmission of fatal viruses. Here, we have introduced a unique respiration monitoring and touchless sensing system based on a CsPb2Br5/BaTiO3 humidity-sensing layer operated by water-induced interfacial polarization and prepared using a facile aerosol deposition process. Based on the relationship between sensing ability and layer thickness, the sensing device with a 1.0 µm thick layer was found to exhibit optimal sensing performance, a result of its ideal microstructure. This sensor also exhibits the highest electrical signal variation at 0.5 kHz due to a substantial polarizability difference between high and low humidity. As a result, the CsPb2Br5/BaTiO3 sensing device shows the best signal variation of all types of breath-monitoring devices reported to date when used to monitor sudden changes in respiratory rates in diverse situations. Furthermore, the sensor can effectively detect sweat evaporation when placed 1 cm from the skin, including subtle changes in capacitance caused by finger area and motion, skin moisture, and contact time. This ultrasensitive sensor, with its fast response, provides a potential new sensing platform for the long-term daily monitoring of respiration and sweat evaporation.

Tunable Substrate Functionalities Direct Stem Cell Fate toward Electrophysiologically Distinguishable Neuron-like and Glial-like Cells.

Engineering cellular microenvironment on a functional platform using various biophysical cues to modulate stem cell fate has been the central theme in regenerative engineering. Among the various biophysical cues to direct stem cell differentiation, the critical role of physiologically relevant electric field (EF) stimulation was established in the recent past. The present study is the first to report the strategy to switch EF-mediated differentiation of human mesenchymal stem cells (hMSCs) between neuronal and glial pathways, using tailored functional properties of the biomaterial substrate. We have examined the combinatorial effect of substrate functionalities (conductivity, electroactivity, and topography) on the EF-mediated stem cell differentiation on polyvinylidene-difluoride (PVDF) nanocomposites in vitro, without any biochemical inducers. The functionalities of PVDF have been tailored using conducting nanofiller (multiwall-carbon nanotube, MWNT) and piezoceramic (BaTiO3, BT) by an optimized processing approach (melt mixing-compression molding-rolling). The DC conductivity of PVDF nanocomposites was tuned from ∼10-11 to ∼10-4 S/cm and the dielectric constant from ∼10 to ∼300. The phenotypical changes and genotypical expression of hMSCs revealed the signatures of early differentiation toward neuronal pathway on rolled-PVDF/MWNT and late differentiation toward glial lineage on rolled-PVDF/BT/MWNT. Moreover, we were able to distinguish the physiological properties of differentiated neuron-like and glial-like cells using membrane depolarization and mechanical stimulation. The excitability of the EF-stimulated hMSCs was also determined using whole-cell patch-clamp recordings. Mechanistically, the roles of intracellular reactive oxygen species (ROS), Ca2+ oscillations, and synaptic and gap junction proteins in directing the cellular fate have been established. Therefore, the present work critically unveils complex yet synergistic interaction of substrate functional properties to direct EF-mediated differentiation toward neuron-like and glial-like cells, with distinguishable electrophysiological responses.

Biological Effects of a Three-Dimensionally Printed Ti6Al4V Scaffold Coated with Piezoelectric BaTiO3 Nanoparticles on Bone Formation.

Bone defect repair at load-bearing sites is a challenging clinical problem for orthopedists. Defect reconstruction with implants is the most common treatment; however, it requires the implant to have good mechanical properties and the capacity to promote bone formation. In recent years, the piezoelectric effect, in which electrical activity can be generated due to mechanical deformation, of native bone, which promotes bone formation, has been increasingly valued. Therefore, implants with piezoelectric effects have also attracted great attention from orthopedists. In this study, we developed a bioactive composite scaffold consisting of BaTiO3, a piezoelectric ceramic material, coated on porous Ti6Al4V. This composite scaffold showed not only appropriate mechanical properties, sufficient bone and blood vessel ingrowth space, and a suitable material surface topography but also a reconstructed electromagnetic microenvironment. The osteoconductive and osteoinductive properties of the scaffold were reflected by the proliferation, migration, and osteogenic differentiation of mesenchymal stem cells. The ability of the scaffold to support vascularization was reflected by the proliferation and migration of human umbilical vein endothelial cells and their secretion of VEGF and PDGF-BB. A well-established sheep spinal fusion model was used to evaluate bony fusion in vivo. Sheep underwent implantation with different scaffolds, and X-ray, micro-computed tomography, van Gieson staining, and elemental energy-dispersive spectroscopy were used to analyze bone formation. Isolated cervical angiography and visualization analysis were used to assess angiogenesis at 4 and 8 months after transplantation. The results of cellular and animal studies showed that the piezoelectric effect could significantly reinforce osteogenesis and angiogenesis. Furthermore, we also discuss the molecular mechanism by which the piezoelectric effect promotes osteogenic differentiation and vascularization. In summary, Ti6Al4V scaffold coated with BaTiO3 is a promising composite biomaterial for repairing bone defects, especially at load-bearing sites, that may have great clinical translation potential.