Improving hydroxyapatite coating ability on biodegradable metal through laser-induced hydrothermal coating in liquid precursor: Application in orthopedic implants.

During the past decade, there has been extensive research toward the possibility of exploring magnesium and its alloys as biocompatible and biodegradable materials for implantable applications. Its practical medical application, however, has been limited to specific areas owing to rapid corrosion in the initial stage and the consequent complications. Surface coatings can significantly reduce the initial corrosion of Mg alloys, and several studies have been carried out to improve the adhesion strength of the coating to the surfaces of the alloys. The composition of hydroxyapatite (HAp) is very similar to that of bone tissue; it is one of the most commonly used coating materials for bone-related implants owing to favorable osseointegration post-implantation. In this study, HAp was coated on Mg using nanosecond laser coating, combining the advantages of chemical and physical treatments. Photothermal heat generated in the liquid precursor by the laser improved the adhesion of the coating through the precipitation and growth of HAp at the localized nanosecond laser focal area and increased the corrosion resistance and cell adhesion of Mg. The physical, crystallographic, and chemical bondings were analyzed to explore the mechanism through which the surface adhesion between Mg and the HAp coating layer increased. The applicability of the coating to Mg screws used for clinical devices and improvement in its corrosion property were confirmed. The liquid environment-based laser surface coating technique offers a simple and quick process that does not require any chemical ligands, and therefore, overcomes a potential obstacle in its clinical use.

Biomimetic hydrogel blanket for conserving and recovering intrinsic cell properties.

BACKGROUND: Cells in the human body experience different growth environments and conditions, such as compressive pressure and oxygen concentrations, depending on the type and location of the tissue. Thus, a culture device that emulates the environment inside the body is required to study cells outside the body. METHODS: A blanket-type cell culture device (Direct Contact Pressing: DCP) was fabricated with an alginate-based hydrogel. Changes in cell morphology due to DCP pressure were observed using a phase contrast microscope. The changes in the oxygen permeability and pressure according to the hydrogel concentration of DCP were analyzed. To compare the effects of DCP with normal or artificial hypoxic cultures, cells were divided based on the culture technique: normal culture, DCP culture device, and artificial hypoxic environment. Changes in phenotype, genes, and glycosaminoglycan amounts according to each environment were evaluated. Based on this, the mechanism of each culture environment on the intrinsic properties of conserving chondrocytes was suggested. RESULTS: Chondrocytes live under pressure from the surrounding collagen tissue and experience a hypoxic environment because collagen inhibits oxygen permeability. By culturing the chondrocytes in a DCP environment, the capability of DCP to produce a low-oxygen and physical pressure environment was verified. When human primary chondrocytes, which require pressure and a low-oxygen environment during culture to maintain their innate properties, were cultured using the hydrogel blanket, the original shapes and properties of the chondrocytes were maintained. The intrinsic properties could be recovered even in aged cells that had lost their original cell properties. CONCLUSIONS: A DCP culture method using a biomimetic hydrogel blanket provides cells with an adjustable physical pressure and a low-oxygen environment. Through this technique, we could maintain the original cellular phenotypes and intrinsic properties of human primary chondrocytes. The results of this study can be applied to other cells that require special pressure and oxygen concentration control to maintain their intrinsic properties. Additionally, this technique has the potential to be applied to the re-differentiation of cells that have lost their original properties.

A Prospective Study of Pressure Injury Healing Rate and Time and Influencing Factors in an Acute Care Setting.

OBJECTIVE: To determine pressure injury (PI) healing rate and time and identify influencing factors. METHODS: A prospective cohort research design was used. Data collection was performed between May 2015 and August 2018. The study participants were 77 inpatients who developed at least one PI during their stay in a university hospital. Researchers assessed participants' demographic (age, sex); physical (incontinence, activity of daily living, and nutrition status); physiologic (serum total protein, albumin, and creatinine, blood glucose, and hemoglobin levels); and disease- (diagnosis, number of comorbidities, and cardiovascular comorbidity), wound- (PI stage and size at first detection, and Pressure Ulcer Scale for Healing score), and treatment-related (IV nutrition supply and albumin infusion) factors. RESULTS: Across the 77 patients, 91 PIs developed. Of these, 54 (59.3%) healed with a mean healing time of 17.63 days. The healing rate was better, and the healing time was shorter for stage 2 PIs compared with unstageable or deep-tissue PIs. Factors influencing PI healing rate were number of comorbidities, cardiovascular comorbidity, incontinence, PI stage at first detection, IV nutrition supply, and mean serum creatinine level. Factors influencing PI healing time were number of comorbidities, cardiovascular comorbidity, and PI stage at first detection. CONCLUSIONS: To reduce hospital stays, PI-related complications, and mortality, evidence-based management strategies for PIs are needed. The findings of the present study may contribute to the development of such strategies.

Monitoring Wound Healing with Topically Applied Optical NanoFlare mRNA Nanosensors.

An effective wound management strategy needs accurate assessment of wound status throughout the whole healing process. This can be achieved by examining molecular biomarkers including proteins, DNAs, and RNAs. However, existing methods for quantifying these biomarkers such as immunohistochemistry and quantitative polymerase chain reaction are usually laborious, resource-intensive, and disruptive. This article reports the development and utilization of mRNA nanosensors (i.e., NanoFlare) that are topically applied on cutaneous wounds to reveal the healing status through targeted and semi-quantitative examination of the mRNA biomarkers in skin cells. In 2D and 3D in vitro models, the efficacy and efficiency of these nanosensors are demonstrated in revealing the dynamic changes of mRNA biomarkers for different stages of wound development. In mouse models, this platform permits the tracking and identification of wound healing stages and a normal and diabetic wound healing process by wound healing index in real time.

Estimating the incubated river water quality indicator based on machine learning and deep learning paradigms: BOD5 Prediction.

As an indicator measured by incubating organic material from water samples in rivers, the most typical characteristic of water quality items is biochemical oxygen demand (BOD5) concentration, which is a stream pollutant with an extreme circumstance of organic loading and controlling aquatic behavior in the eco-environment. Leading monitoring approaches including machine leaning and deep learning have been evolved for a correct, trustworthy, and low-cost prediction of BOD5 concentration. The addressed research investigated the efficiency of three standalone models including machine learning (extreme learning machine (ELM) and support vector regression (SVR)) and deep learning (deep echo state network (Deep ESN)). In addition, the novel double-stage synthesis models (wavelet-extreme learning machine (Wavelet-ELM), wavelet-support vector regression (Wavelet-SVR), and wavelet-deep echo state network (Wavelet-Deep ESN)) were developed by integrating wavelet transformation (WT) with the different standalone models. Five input associations were supplied for evaluating standalone and double-stage synthesis models by determining diverse water quantity and quality items. The proposed models were assessed using the coefficient of determination (R2), Nash-Sutcliffe (NS) efficiency, and root mean square error (RMSE). The significance of addressed research can be found from the overall outcomes that the predictive accuracy of double-stage synthesis models were not always superior to that of standalone models. Overall results showed that the SVR with 3th distribution (NS = 0.915) and the Wavelet-SVR with 4th distribution (NS = 0.915) demonstrated more correct outcomes for predicting BOD5 concentration compared to alternative models at Hwangji station, and the Wavelet-SVR with 4th distribution (NS = 0.917) was judged to be the most superior model at Toilchun station. In most cases for predicting BOD5 concentration, the novel double-stage synthesis models can be utilized for efficient and organized data administration and regulation of water pollutants on both stations, South Korea.

Performance Improvement of Residue-Free Graphene Field-Effect Transistor Using Au-Assisted Transfer Method.

We report a novel graphene transfer technique for fabricating graphene field-effect transistors (FETs) that avoids detrimental organic contamination on a graphene surface. Instead of using an organic supporting film like poly(methyl methacrylate) (PMMA) for graphene transfer, Au film is directly deposited on the as-grown graphene substrate. Graphene FETs fabricated using the established organic film transfer method are easily contaminated by organic residues, while Au film protects graphene channels from these contaminants. In addition, this method can also simplify the device fabrication process, as the Au film acts as an electrode. We successfully fabricated graphene FETs with a clean surface and improved electrical properties using this Au-assisted transfer method.

Defect-Free Mechanical Graphene Transfer Using n-Doping Adhesive Gel Buffer.

The synthesis of uniform low-defect graphene on a catalytic metal substrate is getting closer to the industrial level. However, its practical application is still challenging due to the lack of an appropriate method for its scalable damage-free transfer to a device substrate. Here, an efficient approach for a defect-free, etchant-free, wrinkle-free, and large-area graphene transfer is demonstrated by exploiting a multifunctional viscoelastic polymer gel as a simultaneous shock-free adhesive and dopant layer. Initially, an amine-rich polymer solution in its liquid form allows for conformal coating on a graphene layer grown on a Cu substrate. The subsequent thermally cured soft gel enables the shock-free and wrinkle-free direct mechanical exfoliation of graphene from a substrate due to its strong charge-transfer interaction with graphene and excellent shock absorption. The adhesive gel with a high optical transparency works as an electron doping layer toward graphene, which exhibits significantly reduced sheet resistances without optical transmittance loss. Lastly, the transferred graphene layer shows high mechanical and chemical stabilities under the repeated bending test and exposure to various solvents. This gel-assisted mechanical transfer method can be a solution to connect the missing part between large-scale graphene synthesis and next-generation electronics and optoelectronic applications.

Super-Nernstian pH Sensor Based on Anomalous Charge Transfer Doping of Defect-Engineered Graphene.

The conventional pH sensor based on the graphene ion-sensitive field-effect transistor (Gr-ISFET), which operates with an electrostatic gating at the solution-graphene interface, cannot have a pH sensitivity above the Nernst limit (∼59 mV/pH). However, for accurate detection of the pH levels of an aqueous solution, an ultrasensitive pH sensor that can exceed the theoretical limit is required. In this study, a novel Gr-ISFET-based pH sensor is fabricated using proton-permeable defect-engineered graphene. The nanocrystalline graphene (nc-Gr) with numerous grain boundaries allows protons to penetrate the graphene layer and interact with the underlying pH-dependent charge-transfer dopant layer. We analyze the pH sensitivity of nc-Gr ISFETs by adjusting the grain boundary density of graphene and the functional group (OH-, NH2-, CH3-) on the SiO2 surface, confirming an unusual negative shift of the charge-neutral point (CNP) as the pH of the solution increases and a super-Nernstian pH response (approximately -140 mV/pH) under optimized conditions.

Lubricant-infused directly engraved nano-microstructures for mechanically durable endoscope lens with anti-biofouling and anti-fogging properties.

While a clear operating field during endoscopy is essential for accurate diagnosis and effective surgery, fogging or biofouling of the lens can cause loss of visibility during these procedures. Conventional cleaning methods such as the use of an irrigation unit, anti-fogging surfactant, or particle-based porous coatings infused with lubricants have been used but proven insufficient to prevent loss of visibility. Herein, a mechanically robust anti-fogging and anti-biofouling endoscope lens was developed by forming a lubricant-infused directly engraved nano-/micro-structured surface (LIDENS) on the lens. This structure was directly engraved onto the lens via line-by-line ablation with a femtosecond laser. This directly engraved nano/microstructure provides LIDENS lenses with superior mechanical robustness compared to lenses with conventional particle-based coatings, enabling the maintenance of clear visibility throughout typical procedures. The LIDENS lens was chemically modified with a fluorinated self-assembled monolayer (F-SAM) followed by infusion of medical-grade perfluorocarbon lubricants. This provides the lens with high transparency (> 70%) along with superior and long-lasting repellency towards various liquids. This excellent liquid repellency was also shown to be maintained during blood dipping, spraying, and droplet condensation experiments. We believe that endoscopic lenses with the LIDENS offer excellent benefits to endoscopic surgery by securing clear visibility for stable operation.

Femtosecond laser induced nano-textured micropatterning to regulate cell functions on implanted biomaterials.

Posterior capsular opacification (PCO) is the most common complication of cataract surgery. PCO is due to the proliferation, migration, and epithelial-to-mesenchymal transition of the residual lens epithelial cells (LECs) within the lens capsule. As surface topography influences cellular response, we investigated the effect of modulating the dimensions of periodic nano-textured patterns on the surface of an intraocular lens material to regulate lens epithelial cell functions such as cell adhesion, migration, orientation, and proliferation. Patterned poly(HEMA) samples were prepared by a femtosecond laser microfabrication, and the behaviors of human B-3 LECs were observed on groove/ridge patterns with widths varying from 5 to 40 µm. In the presence of ridge and groove patterns, the adherent cells elongated along the direction of the patterns, and f-actin of the cells was spread to a lesser extent on the nano-textured groove surfaces. Both single and collective cell migrations were significantly inhibited in the perpendicular direction of the patterns on the nano-textured micro-patterned samples. We also fabricated the patterns on the curved surface of a commercially available intraocular lens for in vivo evaluation. In vivo results showed that a patterned IOL could help suppress the progression of PCO by inhibiting cell migration from the edge to the center of the IOL. Our reports demonstrate that nano- and microscale topographical patterns on a biomaterial surface can regulate cellular behavior when it is implanted into animals.

Highly Efficient n-Type Doping of Graphene by Vacuum Annealed Amine-Rich Macromolecules.

Flexible transparent conducting electrodes (FTCE) are an essential component of next-generation flexible optoelectronic devices. Graphene is expected to be a promising material for the FTCE, because of its high transparency, large charge carrier mobilities, and outstanding chemical and mechanical stability. However, the electrical conductivity of graphene is still not good enough to be used as the electrode of an FTCE, which hinders its practical application. In this study, graphene was heavily n-type doped while maintaining high transmittance by adsorbing amine-rich macromolecules to graphene. The n-type charge-transfer doping of graphene was maximized by increasing the density of free amine in the macromolecule through a vacuum annealing process. The graphene adsorbed with the n-type dopants was stacked twice, resulting in a graphene FTCE with a sheet resistance of 38 ohm/sq and optical transmittance of 94.1%. The figure of merit (FoM) of the graphene electrode is as high as 158, which is significantly higher than the minimum standard for commercially available transparent electrodes (FoM = 35) as well as graphene electrodes doped with previously reported chemical doping methods. Furthermore, the n-doped graphene electrodes not only show outstanding flexibility but also maintain the doping effect even in high temperature (500 K) and high vacuum (~10-6 torr) conditions. These results show that the graphene doping proposed in this study is a promising approach for graphene-based next-generation FTCEs.

Tailoring H2O2 generation kinetics with magnesium alloys for efficient disinfection on titanium surface.

A new antibacterial strategy for Ti has been developed without the use of any external antibacterial agents and surface treatments. By combining Mg alloys with Ti, H2O2, which is an oxidizing agent that kills bacteria, was spontaneously generated near the surface of Ti. Importantly, the H2O2 formation kinetics can be precisely controlled by tailoring the degradation rates of Mg alloys connected to Ti. Through microstructural and electrochemical modification of Mg with alloying elements (Ca, Zn), the degradation rates of Mg alloys were controlled, and the H2O2 release kinetics was accelerated when the degradation rate of Mg alloys increased. With the introduction of an in vivo assessment platform comprised of Escherichia coli (E. coli) and transgenic zebrafish embryos, we are able to design optimized antibacterial systems (Ti-Mg and Ti-Mg-3wt% Zn) that can selectively eradicate E. coli while not harming the survival rate, development, and biological functions of zebrafish embryos. We envision that our antibacterial strategy based on utilization of sacrificial Mg alloys could broaden the current palette of antibacterial platforms for metals.

Toward Scalable Growth for Single-Crystal Graphene on Polycrystalline Metal Foil.

Despite the enormous potential of the single-crystalline two-dimensional (2D) materials for a wide range of future innovations and applications, 2D single-crystals are still suffering in industrialization due to the lack of efficient large-area production methods. In this work, we introduce a general approach for the scalable growth of single-crystalline graphene, which is a representative 2D material, through "transplanting" uniaxially aligned graphene "seedlings" onto a larger-area catalytic growth substrate. By inducing homoepitaxial growth of graphene from the edges of the seeds arrays without additional nucleations, we obtained single-crystalline graphene with an area four times larger than the mother graphene seed substrate. Moreover, the defect-healing process eliminated the inherent defects of seeds, ensuring the reliability and crystallinity of the single-crystalline graphene for industrialization.

Anti-Tumor Drug-Loaded Oxygen Nanobubbles for the Degradation of HIF-1α and the Upregulation of Reactive Oxygen Species in Tumor Cells.

Hypoxia is a key concern during the treatment of tumors, and hypoxia-inducible factor 1 alpha (HIF-1α) has been associated with increased tumor resistance to therapeutic modalities. In this study, doxorubicin-loaded oxygen nanobubbles (Dox/ONBs) were synthesized, and the effectiveness of drug delivery to MDA-MB-231 breast cancer and HeLa cells was evaluated. Dox/ONBs were characterized using optical and fluorescence microscopy, and size measurements were performed through nanoparticle tracking analysis (NTA). The working mechanism of Dox was evaluated using reactive oxygen species (ROS) assays, and cellular penetration was assessed with confocal microscopy. Hypoxic conditions were established to assess the effect of Dox/ONBs under hypoxic conditions compared with normoxic conditions. Our results indicate that Dox/ONBs are effective for drug delivery, enhancing oxygen levels, and ROS generation in tumor-derived cell lines.

DNA aptamer immobilized hydroxyapatite for enhancing angiogenesis and bone regeneration.

In this study, we developed aptamer-conjugated hydroxyapatite (Apt-HA) that promotes bone regeneration and angiogenesis. The 3R02 bivalent aptamer specific to vascular endothelial growth factor (VEGF) was grafted to the hydroxyapatite (HA) surface. Apt-HA was tested for its VEGF protein capture ability to determine the optimal aptamer concentration immobilized on the HA. Apt-HA showed higher VEGF protein capture ability, and faster growth of human umbilical vein endothelial cell (HUVEC) compared to a neat HA with no cytotoxic effects on human osteoblasts. To examine in vivo angiogenesis and bone regeneration, Apt-HA and HA were bilaterally implanted into rabbit tibial metaphyseal defects and analyzed after eight weeks using micro-CT, histology, and histomorphometry. Apt-HA showed significantly increased the volume of new bones, the percentage of bone, and the density of bone mineral in cortical bone. Apt-HA also exhibited the enhanced bone formation at the cortical region in a histomorphometric analysis. Finally, Apt-HA showed significantly increased blood vessel number compared to a neat HA. In summary, the engineered Apt-HA has potential as a bone graft material that may simultaneously promote bone regeneration and angiogenesis. STATEMENT OF SIGNIFICANCE: This work presents a functional hydroxyapatite bone graft using a DNA-based aptamer which overcomes the limitations of existing bone graft materials, which use bound signaling peptides. DNA aptamer immobilized hydroxyapatite enhances the in vitro proliferation of human umbilical vascular endothelial cells as well as in vivo angiogenesis and bone regeneration. DNA aptamer immobilized hydroxyapatite shows no cytotoxic effect on human osteoblasts.

Interface Engineering of Fully Metallic Stents Enabling Controllable H2O2 Generation for Antirestenosis.

Despite significant advances in the design of metallic materials for bare metal stents (BMSs), restenosis induced by the accumulation of smooth muscle cells (SMCs) has been a major constraint on improving the clinical efficacy of stent implantation. Here, a new strategy for avoiding this issue by utilizing hydrogen peroxide (H2O2) generated by the galvanic coupling of nitinol (NiTi) stents and biodegradable magnesium-zinc (Mg-Zn) alloys is reported. The amount of H2O2 released is carefully optimized via the biodegradability engineering of the alloys and by controlling the immersion time to selectively inhibit the proliferation and function of SMCs without harming vascular endothelial cells. Based on demonstrations of its unique capabilities, a fully metallic stent with antirestenotic functionality was successfully fabricated by depositing Mg layers onto commercialized NiTi stents. The introduction of surface engineering to yield a patterned Mg coating ensured the maintenance of a stable interface between Mg and NiTi during the process of NiTi stent expansion, showing high feasibility for clinical application. This new concept of an inert metal/degradable metal hybrid system based on galvanic metal coupling, biodegradability engineering, and surface patterning can serve as a novel way to construct functional and stable BMSs for preventing restenosis.

Synergistic effect of Korean red ginseng and Pueraria montana var. lobata against trimethyltin-induced cognitive impairment.

Many edible plant extracts exhibit biological activities. For example, the ethanol extract of Pueraria montana var. lobata (P. montana) inhibits acetylcholinesterase (AChE), and red ginseng is well known for promoting health. In this study the authors investigated the synergistic effect of P. montana and red ginseng extracts on AChE activity in vitro and in mouse brain tissues and trimethyltin (TMT)-induced cognitive impairment in a mouse model of TMT-induced neurodegeneration. A diet containing a mixture of P. montana and red ginseng extracts reversed learning and memory impairments in Y-maze and passive avoidance behavioral tests. In addition, the mixture inhibited AChE activity and lipid peroxidation synergistically.

Engineering oxygen nanobubbles for the effective reversal of hypoxia.

Hypoxia, which results from an inadequate supply of oxygen, is a major cause of concern in cancer therapy as it is associated with a reduction in the effectiveness of chemotherapy and radiotherapy in cancer treatment. Overexpression and stabilization of hypoxia-inducible factor 1α (HIF-1α) protein in tumours, due to hypoxia, results in poor prognosis and increased patient mortality. To increase oxygen tension in hypoxic areas, micro- and nanobubbles have been investigated by various researchers. In the present research, lipid-shelled oxygen nanobubbles (ONBs) were synthesized through a sonication method to reverse hypoxic conditions created in a custom-made hypoxic chamber. Release of oxygen gas from ONBs in deoxygenated water was evaluated by measuring dissolved oxygen. Hypoxic conditions were evaluated by performing in vitro experiments on MDA-MB231 breast cancer cells through the expression of HIF-1α and the fluorescence of image-iT™ hypoxia reagent. The results indicated the degradation of HIF-1α after the introduction of ONBs. We propose that ONBs are successful in reversing hypoxia, downregulating HIF-1α, and improving cellular conditions, leading to further medical applications.

Engineering copper nanoparticles synthesized on the surface of carbon nanotubes for anti-microbial and anti-biofilm applications.

Biofilms adhere to surfaces to produce extracellular polymeric substances (EPSs). EPSs grow and protect themselves from external stresses. Their formation causes a foul odor and may lead to chronic infectious diseases in animals and people. Biofilms also inhibit the contact between bacteria and antibiotics, thereby reducing their antibacterial activity. Thus, we describe novel nanostructures, a fusion of copper and multi-walled carbon nanotubes (MWCNTs), which increase antimicrobial activity against biofilms without being toxic to human cells. Simulations based on the stochastic response were performed to predict the efficiency of synthesizing nanostructures. The synthesized Cu/MWCNTs inhibit the growth of Methylobacterium spp., which forms biofilms; antimicrobial testing and cytotoxicity assessments showed that the Cu/MWCNTs were not cytotoxic to human cells. The Cu/MWCNTs come in direct contact with the bacterial cell surface, damage the cell wall, and cause secondary oxidation of reactive oxygen species. Furthermore, the Cu/MWCNTs release copper ions, which inhibit the quorum sensing in Methylobacterium spp., thereby inhibiting the expression of the genes that form biofilms. Additionally, we confirmed excellent electrical and thermal conductivity of Cu/MWCNTs as well as biofilm removal efficiency in the microfluidic channel.