Materials for flexible bioelectronic systems as chronic neural interfaces.

Engineered systems that can serve as chronically stable, high-performance electronic recording and stimulation interfaces to the brain and other parts of the nervous system, with cellular-level resolution across macroscopic areas, are of broad interest to the neuroscience and biomedical communities. Challenges remain in the development of biocompatible materials and the design of flexible implants for these purposes, where ulimate goals are for performance attributes approaching those of conventional wafer-based technologies and for operational timescales reaching the human lifespan. This Review summarizes recent advances in this field, with emphasis on active and passive constituent materials, design architectures and integration methods that support necessary levels of biocompatibility, electronic functionality, long-term stable operation in biofluids and reliability for use in vivo. Bioelectronic systems that enable multiplexed electrophysiological mapping across large areas at high spatiotemporal resolution are surveyed, with a particular focus on those with proven chronic stability in live animal models and scalability to thousands of channels over human-brain-scale dimensions. Research in materials science will continue to underpin progress in this field of study.

Recent progress in the development of upconversion nanomaterials in bioimaging and disease treatment.

Multifunctional lanthanide-based upconversion nanoparticles (UCNPs), which feature efficiently convert low-energy photons into high-energy photons, have attracted considerable attention in the domain of materials science and biomedical applications. Due to their unique photophysical properties, including light-emitting stability, excellent upconversion luminescence efficiency, low autofluorescence, and high detection sensitivity, and high penetration depth in samples, UCNPs have been widely applied in biomedical applications, such as biosensing, imaging and theranostics. In this review, we briefly introduced the major components of UCNPs and the luminescence mechanism. Then, we compared several common design synthesis strategies and presented their advantages and disadvantages. Several examples of the functionalization of UCNPs were given. Next, we detailed their biological applications in bioimaging and disease treatment, particularly drug delivery and photodynamic therapy, including antibacterial photodynamic therapy. Finally, the future practical applications in materials science and biomedical fields, as well as the remaining challenges to UCNPs application, were described. This review provides useful practical information and insights for the research on and application of UCNPs in the field of cancer.

Halogenated Organic Pollutant Residuals in Human Bared and Clothing-Covered Skin Areas: Source Differentiation and Comprehensive Health Risk Assessment.

To comprehensively clarify human exposure to halogenated flame retardants (HFRs) and polychlorinated biphenyls (PCBs) through dermal uptake and hand-to-mouth intake, skin wipe samples from four typical skin locations from 30 volunteers were collected. The total concentration of the target chemicals (24 HFRs and 16 PCBs) ranged from 203 to 4470 ng/m2. BDE-209 and DBDPE accounted for about 37 and 40% of ∑24HFRs, respectively, and PCB-41 and PCB-110 were the dominant PCB congeners, with proportion of 24 and 10%, respectively. Although exhibiting relatively lower concentrations of contaminants than bared skin locations, clothing-covered skin areas were also detected with considerable levels of HFRs and PCBs, indicating clothing to be a potentially significant exposure source. Significant differences in HFR and PCB levels and profiles were also observed between males and females, with more lower-volatility chemicals in male-bared skin locations and more higher-volatility compounds in clothing-covered skin locations of female participants. The mean estimated whole-body dermal absorption doses of ∑8HFRs and ∑16PCBs (2.9 × 10-4 and 6.7 × 10-6 mg/kg·d) were 1-2 orders of magnitude higher than ingestion doses via hand-to-mouth contact (6.6 × 10-7 and 3.1 × 10-7 mg/kg·d). The total noncarcinogenic health risk resulted from whole-body dermal absorption and oral ingestion to ∑7HFRs and ∑16PCBs were 5.2 and 0.35, respectively.

Theoretical Explanation for How SO3H-Functionalized Ionic Liquids Promote the Conversion of Cellulose to Glucose.

While the catalytic transformation of cellulose to glucose by functionalized ionic liquids (ILs) has been achieved successfully under mild conditions, insight into the fundamental molecular mechanism is still lacking. The present work presents the first attempt to address the fundamental reaction chemistry of the catalytic transformation. An enzyme-like catalytic mechanism of ILs, in which glycosidic bond hydrolysis proceeds through a retaining mechanism and/or an inverting mechanism, is proposed. DFT calculations show that both mechanisms involve moderate barriers (<30 kcal mol(-1)), which is consistent with the catalytic performance of the ILs under mild conditions (<100 °C). The "biomimetic" mechanism model proposed herein is expected to be viable for understanding the unique catalytic activity of ILs under mild conditions.

Multifunctional Fe2O3@PPy-PEG nanocomposite for combination cancer therapy with MR imaging.

In recent years, magnetic hyperthermia nanoparticles have drawn great attention for cancer therapy because they have no limitation of tissue penetration during the therapy process. In this study, cubic nanoporous Fe2O3 nanoparticles derived from cubic Prussian blue nanoparticles were used as magnetic cores to generate heat by alternating the current magnetic field (AMF) for killing cancer cells. In addition, polypyrrole (PPy) was coated on the surfaces of the cubic Fe2O3 nanoparticles to load doxorubicin hydrochloride (DOX). The PEG component was then physically adsorbed onto the surfaces of the nanoparticles, resulting in a Fe2O3@PPy-DOX-PEG nanocomposite. The nanocomposite was triggered by acid stimulus and AMF to release DOX, resulting in a remarkable combination therapeutic effect via chemotherapy and magnetic hyperthermia. Furthermore, the nanocomposite could realize magnetic resonance imaging (MRI) due to the magnetic core structure. The study provides an alternative for the development of new nanocomposites for combination cancer therapy with MR imaging in vivo.

Recyclable heparin and chitosan conjugated magnetic nanocomposites for selective removal of low-density lipoprotein from plasma.

A new fabrication protocol is described to obtain heparin and chitosan conjugated magnetic nanocomposite as a blood purification material for removal of low-density lipoprotein (LDL) from blood plasma. The adsorbent could be easily separated with an external magnet for recyclable use since it had a magnetic core. The LDL level of plasma decreased by 67.3 % after hemoperfusion for 2 h. Moreover, the adsorbent could be recycled simply washing with NaCl solution. After eight cycles, the removal efficiency of the adsorbent was still above 50 %. The recyclable magnetic adsorbent had good blood compatibility due to the conjugation of heparin to the chitosan-coated magnetic nanocomposites. The fabricated magnetic adsorbent could be applied for LDL apheresis without side effects.

Injectable Polyzwitterionic Lubricant for Complete Prevention of Cardiac Adhesion.

After cardiac surgery, tissue damage to the heart may cause adhesion between heart and its surrounding tissues. Post-operative cardiac adhesion may lead to limited normal cardiac function, decreased quality of cardiac surgery, and increased risk of major bleeding during reoperation. Therefore, it is necessary to develop an effective anti-adhesion therapy to overcome cardiac adhesion. An injectable polyzwitterionic lubricant is developed to prevent adhesion between the heart and surrounding tissues and to maintain normal pumping function of the heart. This lubricant is evaluated in a rat heart adhesion model. Poly (2-methacryloyloxyethyl phosphorylcholine) (i.e., PMPC) polymers are successfully prepared via free radical polymerization of monomer MPC, and the optimal lubricating performance, biocompatibility both in vitro and in vivo is demonstrated. Besides, a rat heart adhesion model is conducted to evaluate the bio-functionality of lubricated PMPC. The results prove that PMPC is a promising lubricant for complete adhesion-prevention. The injectable polyzwitterionic lubricant shows excellent lubricating properties and biocompatibility and can effectively prevent cardiac adhesion.

Environmentally adaptive polysaccharide-based hydrogels and their applications in extreme conditions: A review.

Polysaccharide hydrogels are one of the most promising hydrogel materials due to their inherent characteristics, including biocompatibility, biodegradability, renewability, and easy modification, and their structure and functional designs have been widely researched to adapt to different application scenarios as well as to broaden their application fields. As typical wet-soft materials, the high water content and water-absorbing ability of polysaccharide-based hydrogels (PHs) are conducive to their wide biomedical applications, such as wound healing, tissue repair, and drug delivery. In addition, along with technological progress, PHs have shown potential application prospects in some high-tech fields, including human-computer interaction, intelligent driving, smart dressing, flexible sensors, etc. However, in practical applications, due to the poor ability of PHs to resist freezing below zero, dehydration at high temperature, and acid-base/swelling-induced deformation in a solution environment, they are prone to lose their wet-soft peculiarities, including structural integrity, injectability, flexibility, transparency, conductivity and other inherent characteristics, which greatly limit their high-tech applications. Hence, reducing their freezing point, enhancing their high-temperature dehydration resistance, and improving their extreme solution tolerance are powerful approaches to endow PHs with multienvironmental adaptability, broadening their application areas. This report systematically reviews the study advances of environmentally adaptive polysaccharide-based hydrogels (EAPHs), comprising anti-icing hydrogels, high temperature/dehydration resistant hydrogels, and acid/base/swelling deformation resistant hydrogels in recent years. First, the construction methods of EAPHs are presented, and the mechanisms and properties of freeze-resistant, high temperature/dehydration-resistant, and acid/base/swelling deformation-resistant adaptations are simply demonstrated. Meanwhile, the features of different strategies to prepare EAPHs as well as the strategies of simultaneously attaining multienvironmental adaptability are reviewed. Then, the applications of extreme EAPHs are summarized, and some meaningful works are well introduced. Finally, the issues and future outlooks of PH environment adaptation research are elucidated.

Simultaneous measurement of two biological signals using a multi-layered polyvinylidene fluoride sensor.

Cardiovascular and deep breathing diseases can be detected by measuring human signals such as heart rate, respiration, and blood pressure, which are important physiological parameters for accessing the state of the body. However, conventionally, heart and respiration rates are monitored using different sensors, which is cumbersome and can further increase the psychological burden on patients. To address these issues, this report proposes a sensor consisting of two stacked elements that can simultaneously measure heart and respiration rates. The two signals received can be expressed separately as heart and respiration rates after signal processing. The two stacked elements are composed of polyvinylidene fluoride thin film bonded to a polydimethylsiloxane substrate. One element (element 1) measures movement related to the heart, and the other (element 2) measures movement related to breathing. Elements 1 and 2 were experimentally observed to have sensitivities of 0.163 V/N and 0.209 V/N, respectively. In addition, the proposed system was compared with a commercial digital heart rate and respiration rate measurement instrument and was verified to be effective for simultaneous measurement of human vital signals with multiple sensors. In addition, the proposed system is flexible, lightweight, and inexpensive, making it convenient and economical.

Highly stretchable, self-healing elastomer hydrogel with universal adhesion driven by reversible cross-links and protein enhancement.

Engineered hydrogels with excellent mechanical properties and multi-functionality have great potential as soft electronic skins, tissue substitutes and flexible robotic joints. However, it has been a challenge to construct multifunctional hydrogels, especially when integrating high stretchability, toughness and strength, low hysteresis, good self-healing and adhesion abilities into a hydrogel system simultaneously. Here, we successfully developed a structural hydrogel composed of a reversible covalently cross-link-based poly-N-(2-hydroxyethyl)acrylamide (PHEMAA) network and available plastically deformable casein micelles. Such a design enabled the reversible covalent cross-links and casein micelles to enhance energy dissipation and toughen the PHEMAA/casein hybrid hydrogel synergistically. More importantly, the hydrogel could respond to the imposed strains reversibly by cross-link and micelle deformation induced-network reconstitution, which led to low hysteresis of the hydrogels. The recoverable gel networks still exhibited their effects on energy dissipation at the stress-focused area, endowing the hydrogels with fatigue resistance. As a result, the hydrogels exhibited a compressive strength of 36.5 MPa, high stretchability (1460%), high toughness (∼5.98 MJ m-3), low hysteresis (<30%) and fatigue resistance with almost completely overlapped hysteresis curves during 10 loading cycles. In addition, the introduction of casein micelles and reversible covalent bonding endowed the elastomer hydrogels with high adhesivity, self-healing abilities and biocompatibility.

Conjugation of organic-metallic hybrid polymers and calf-thymus DNA.

Strong electrostatic interaction between metallo-supramolecular polymers and DNA was confirmed by UV-vis and CD spectral measurements during titration, and cyclic voltammetry. The stable conjugation structure based on groove binding was revealed by using QM/MM computational methodology and supported by AFM.

Coaxially electrospun 5-fluorouracil-loaded PLGA/PVP fibrous membrane for skin tumor treatment.

As a biocompatible and biodegradable polymer, poly(lactide-co-glycolide) (PLGA) has been widely used as a carrier to achieve controlled drug delivery in various forms. Focusing on skin tumor treatment, herein 5-fluorouracil (5-FU) was embedded into the core of coaxially electrospun PLGA fibers to get a drug-loaded core-shell fibrous membrane. In the coaxial electrospinning, poly(vinylpyrrolidone) was applied in the inner flow to facilitate the formation of the core-shell structured fibers. The morphology and micro-structure of the fibers were characterized by scanning electron microscope and transmission electron microscope. The influences of the molecular weights and chemical compositions of PLGA copolymers on the release behaviors were studied. The cytotoxicity of the fibers was characterized by cell proliferation and living-dead cell staining experiments. The results showed that faster release rates would be obtained if the copolymers were of lower molecular weights and higher fraction of glycidyl unit. All the prepared 5-FU loaded fibrous membranes were non-cytotoxic, suggesting their potential applications in skin tumor treatment.

Cu-loaded Brushite bone cements with good antibacterial activity and operability.

Bone defect-related surgical procedures are traumatic processes carrying potential inflammation and infection risks in the clinic, which are associated with prolonged antibiotic therapy that promotes bacterial antibiotic-resistance. In the present study, Cu-loaded brushite bone cements were designed, and the properties of the bone cements were evaluated. The setting time of the cement was prolonged from 12 to 50 min as the copper content increased. All cements were anti-washout, and the injectable coefficient of the cements was approximately 88%. Scanning electron microscopy results revealed that the crystal grains grew larger and thicker as the copper content in the cement increased, and brushite was determined to be the dominant crystalline phase for all the cements. However, a small amount of newly formed calcium copper phosphate was observed in the cement. Simultaneously, band shifts were observed in the Fourier transform infrared spectroscopy results at a Cu content of 5%. Moreover, the addition of Cu improved the compressive strength of brushite cements, and all cements were degradable. Furthermore, the Cu-loaded brushite bone cements performed well in inhibiting the growth and proliferation of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, and the diameter of the inhibition zone increased with increasing copper content. The study revealed that the Cu-loaded brushite bone cements possessed good cellular affinity to mouse bone marrow stem cells when a lower dose of copper was added in vitro. These results support the great potential of injectable antibacterial brushite bone cement specifically for bone tissue defect-related repair and regeneration.

Specific Anti-biofilm Activity of Carbon Quantum Dots by Destroying P. gingivalis Biofilm Related Genes.

INTRODUCTION: Biofilms protect bacteria from antibiotics and this can produce drug-resistant strains, especially the main pathogen of periodontitis, Porphyromonas gingivalis. Carbon quantum dots with various biomedical properties are considered to have great application potential in antibacterial and anti-biofilm treatment. METHODS: Tinidazole carbon quantum dots (TCDs) and metronidazole carbon quantum dots (MCDs) were prepared by a hydrothermal method with the clinical antibacterial drugs tinidazole and metronidazole, respectively. Then, TCDs and MCDs were characterized by transmission electron microscopy, UV-visible spectroscopy, infrared spectroscopy and energy-dispersive spectrometry. The antibacterial effects were also investigated under different conditions. RESULTS: The TCDs and MCDs had uniform sizes. The results of UV-visible and energy-dispersive spectrometry confirmed their important carbon polymerization structures and the activity of the nitro group, which had an evident inhibitory effect on P. gingivalis, but almost no effect on other bacteria, including Escherichia coli, Staphylococcus aureus and Prevotella nigrescens. Importantly, the TCDs could penetrate the biofilms to further effectively inhibit the growth of P. gingivalis under the biofilms. Furthermore, it was found that the antibacterial effect of TCDs lies in its ability to impair toxicity by inhibiting the major virulence factors and related genes involved in the biofilm formation of P. gingivalis, thus affecting the self-assembly of biofilm-related proteins. CONCLUSION: The findings demonstrate a promising new method for improving the efficiency of periodontitis treatment by penetrating the P. gingivalis biofilm with preparations of nano-level antibacterial drugs.

Recent Advances in Materials, Devices, and Systems for Neural Interfaces.

Technologies capable of establishing intimate, long-lived optical/electrical interfaces to neural systems will play critical roles in neuroscience research and in the development of nonpharmacological treatments for neurological disorders. The development of high-density interfaces to 3D populations of neurons across entire tissue systems in living animals, including human subjects, represents a grand challenge for the field, where advanced biocompatible materials and engineered structures for electrodes and light emitters will be essential. This review summarizes recent progress in these directions, with an emphasis on the most promising demonstrated concepts, materials, devices, and systems. The article begins with an overview of electrode materials with enhanced electrical and/or mechanical performance, in forms ranging from planar films, to micro/nanostructured surfaces, to 3D porous frameworks and soft composites. Subsequent sections highlight integration with active materials and components for multiplexed addressing, local amplification, wireless data transmission, and power harvesting, with multimodal operation in soft, shape-conformal systems. These advances establish the foundations for scalable architectures in optical/electrical neural interfaces of the future, where a blurring of the lines between biotic and abiotic systems will catalyze profound progress in neuroscience research and in human health/well-being.

Polyethyleneimine-coated quantum dots for miRNA delivery and its enhanced suppression in HepG2 cells.

Quantum dots (QDs) have been intensively investigated for bioimaging, drug delivery, and labeling probes because of their unique optical properties. In this study, CdSe/ZnS QDs-based nonviral vectors with the dual functions of delivering miR-26a plasmid and bioimaging were formulated by capping the surface of CdSe/ZnS QDs with polyethyleneimine (PEI). The PEI-coated QDs were capable of condensing miR-26a expression vector into nanocomplexes that can emit strong red luminescence when loaded with CdSe/ZnS QDs. Further results showed that PEI-modified nanoparticles (NPs) could transfect miR-26a plasmid into HepG2 cells in vitro. Meanwhile, imaging of living cells could be achieved based on the CdSe/ZnS QDs. Further study suggested that miR-26a transfection up-regulated miR-26a expression, induced cycle arrest, and triggered proliferation inhibition in HepG2 cells. The results indicated that PEI-coated QD NPs possess the capability of bioimaging and gene delivery and could be a promising vehicle with the engineering of QD NPs for gene therapy in the future.

Membrane cartridges for endotoxin removal from interferon preparations.

The suitability of membrane cartridges for the removal of endotoxin from both distilled water and interferon preparations was examined. The endotoxin concentrations were reduced to 4.0 and 7.3 EU/ml, respectively, when about 4000 ml of distilled water with 20 and 28 EU/ml were passed through the deoxycholate and chitosan immobilized membrane cartridges. When 200 ml of interferon preparation with endotoxin concentration more than 80 EU/ml and pH 3.9 were applied to a deoxycholate immobilized membrane cartridge at a flow-rate of 9 ml/min, the endotoxin concentration was reduced to less than 10 EU/ml. However, if an interferon preparation of 450 ml, with more than 80 EU/ml of endotoxin and pH 3.9 was applied to the chitosan immobilized membrane cartridge at a flow-rate of 18 ml/min, the endotoxin concentration was reduced to less than 10 EU/ml.

Effects of mesoporous SiO2 , Fe3 O4 , and TiO2 nanoparticles on the biological functions of endothelial cells in vitro.

To comparatively investigate the cytotoxicities of nanomaterials in circulation, in this study, three different types of nanoparticles (NPs; mesoporous SiO2, Fe3O4, and TiO2) with diameters of around 100 nm were synthesized. The morphologies, crystalline phases, and zeta potentials of those NPs were characterized by scanning electron microscopy, X-ray diffraction and zeta potential measurement, respectively. Then, we investigated the influences of different NPs on the biological functions of endothelial cells, in particular of the organelle of cells. The results indicated that different types of NPs had cytotoxic effects in a dose- and time-dependent manner, and there was no significant difference in cytotoxicity between SiO2 and Fe3O4 at concentrations <0.20 mg/mL. The shape and surface charges of NPs greatly affected cellular internalization. We found that cytoskeleton and integrity of cells were destroyed by different NPs. Additionally, the production of reactive oxygen species damaged the mitochondria of cells, in turn leading to cells apoptosis and death.

Hydrazone-bearing PMMA-functionalized magnetic nanocubes as pH-responsive drug carriers for remotely targeted cancer therapy in vitro and in vivo.

To develop vehicles for efficient chemotherapeutic cancer therapy, we report a remotely triggered drug delivery system based on magnetic nanocubes. The synthesized magnetic nanocubes with average edge length of around 30 nm acted as cores, whereas poly(methyl methacrylate) (PMMA) was employed as an intermediate coating layer. Hydrazide was then tailored onto PMMA both for doxorubicin (DOX) loading and pH responsive drug delivery via the breakage of hydrazine bonds. The successful fabrication of the pH responsive drug carrier was confirmed by transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and magnetic hysteresis loops, respectively. The carrier was stable at neutral environment and doxorubicin released at pH of 5.0. Cell viability assay and confocal laser scanning microscopy observations demonstrated that the loaded DOX could be efficiently released after cellular endocytosis and induced cancer cells apoptosis thereby. More importantly, the carrier could be guided to the tumor tissue site with an external magnetic field and led to efficient tumor inhibition with low side effects, which were reflected by magnetic resonance imaging (MRI), change of tumor size, TUNEL staining, and H&E staining assays, respectively. All results suggest that hydrazide-tailoring PMMA-coated magnetic nanocube would be a promising pH-responsive drug carrier for remotely targeted cancer therapy in vitro and in vivo.

Regulation of the biological functions of osteoblasts and bone formation by Zn-incorporated coating on microrough titanium.

To improve the biological performance of titanium implant, a series of Zn-incorporated coatings were fabricated on the microrough titanium (Micro-Ti) via sol-gel method by spin-coating technique. The successful fabrication of the coating was verified by combined techniques of scanning electron microscopy, surface profiler, X-ray diffraction, X-ray photoelectron spectroscopy, and water contact angle measurements. The incorporated zinc existed as ZnO, which released Zn ions in a sustained manner. The Zn-incorporated samples (Ti-Zn0.08, Ti-Zn0.16, and Ti-Zn0.24) efficiently inhibited the adhesion of both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria. The in vitro evaluations including cell activity, alkaline phosphatase (ALP), mineralization, osteogenic genes expressions (Runx2, ALP, OPG, Col I, OPN, and OC), and tartrate-resistant acid phosphatase, confirmed that Ti-Zn0.16 sample was the optimal one to regulate the proliferation or differentiation for both osteoblasts and osteoclasts. More importantly, in vivo evaluations including Micro-CT analysis, push-out test, and histological observations verified that Ti-Zn0.16 implants could efficiently promote new bone formation after implantation for 4 and 12 weeks, respectively. The resulting material thus has potential application in orthopedic field.