Leucine-Rich Repeat Containing 15-Mediated Cell Adhesion Is Essential for Integrin Signaling in TGF-ß1-Induced PDL Fibroblastic Differentiation.

Human periodontal ligament cells (hPDLCs) cultured from periodontal ligament (PDL) tissue contain postnatal stem cells that can be differentiated into PDL fibroblasts. We obtained PDL fibroblasts from hPDLCs by treatment with low concentrations of TGF-ß1. Since the extracellular matrix and cell surface molecules play an important role in differentiation, we had previously developed a series of monoclonal antibodies against PDL fibroblast-specific cell surface molecules. One of these, the anti-PDL51 antibody, recognized a protein that was significantly upregulated in TGF-ß1-induced PDL fibroblasts and highly accumulated in the PDL region of the tooth root. Mass spectrometry revealed that the antigen recognized by the anti-PDL51 antibody was leucine-rich repeat containing 15 (LRRC15), and this antibody specifically recognized the extracellular glycosylated moiety of LRRC15. Experiments presented here show that as fibroblastic differentiation progresses, increased amounts of LRRC15 localized at the cell surface and membrane. Inhibition of LRRC15 by siRNA-mediated depletion and by antibody blocking resulted in downregulation of the representative PDL fibroblastic markers. Moreover, following LRRC15 inhibition, the directed and elongated cell phenotypes disappeared, and the long processes of the end of the cell body were no longer found. Through a specific interaction between integrin ß1 and LRRC15, the focal adhesion kinase signaling pathway was activated in PDL fibroblasts. Furthermore, it was shown that increased LRRC15 was important for the activation of the integrin-mediated cell adhesion signal pathway for regulation of cellular functions, including fibroblastic differentiation, proliferation, and cell migration arising from the expression of PDL-related genes in TGF-ß1-induced PDL fibroblastic differentiation.

A Novel Fabrication of Heterogeneous Saponified Poly(Vinyl Alcohol)/Pullulan Blend Film for Improved Wound Healing Application.

In this study, a novel film of poly(vinyl alcohol) (PVA)/pullulan (PULL) with improved surface characteristics was prepared from poly(vinyl acetate) (PVAc)/PULL blend films with various mass ratios after the saponification treatment in a heterogeneous medium. According to proton nuclear magnetic resonance (1H-NMR), Fourier transform infrared, and X-ray diffraction results, it was established that the successful fabrication of saponified PVA/PULL (100/0, 90/10, and 80/20) films could be obtained from PVAc/PULL (100/0, 90/10, and 80/20) films, respectively, after 72 h saponification at 50 °C. The degree of saponification calculated from 1H-NMR analysis results showed that fully saponified PVA was obtained from all studied films. Improved hydrophilic characteristics of the saponified films were revealed by a water contact angle test. Moreover, the saponified films showed improved mechanical behavior, and the micrographs of saponified films showed higher surface roughness than the unsaponified films. This kind of saponified film can be widely used for biomedical applications. Moreover, the reported saponified film dressing extended the lifespan of dressing as determined by its self-healing capacity and considerably advanced in vivo wound-healing development, which was attributed to its multifunctional characteristics, meaning that saponified film dressings are promising candidates for full-thickness skin wound healing.

Taking Oral Sulfate Tablets with Simethicone for Bowel Preparation Leads to Higher Adenoma Detection Rate than Polyethylene Glycol: A Propensity Score Analysis.

BACKGROUND: Efficient bowel preparation is essential for preventing colorectal cancer by improving endoscopic adenoma detection. Tablet for bowel preparation containing sulfate salts, OSTs (oral sulfate tablets), has been developed and it is gaining more popularity. However, its efficacy compared to standard preparation agent, PEG-AA (polyethylene glycol), has not been well discovered. We assessed the efficacy of PEG and OSTs using a real-time clinical data warehouse (CDW) model. METHODS: We performed a propensity score-matched (PSM) analysis of consecutive adult patients undergoing colonoscopy who received PEG-AA or OSTs prior to colonoscopy at a tertiary academic hospital. The endoscopic records of 992 adult patients were retrospectively analyzed. The clinical data warehouse collected data including bowel preparation, insertion time, observation time, and the detection of polyps and adenomas. Multivariate regression analysis was performed to reveal the factors associated with endoscopic outcomes. RESULTS: Among 992 patients included in the study, 770 and 222 patients received PEG-AA and OSTs, respectively. Among the propensity score-matched population (n = 1897), OSTs resulted in better bowel cleansing quality (8.16 vs 7.84, p = 0.014) and a higher adenoma detection rate (38.6% vs 27.1%, p = 0.003). Using PEG-AA, older age, inadequate bowel preparation (BBPS score < 6) and endoscopy by fellows were found to be factors associated with poor adenoma detection. In the elderly over 65 years of age, a significant difference in cleansing quality between the two groups (7.21 vs 8.19, p < 0.001) was found, but its impact on ADR was not prominent (49.5% vs 45.4%, p = 0.653). CONCLUSIONS: OSTs with simethicone achieved better endoscopic cleanliness, improving adenoma detection rate compared to the conventional PEG-AA protocol. The synergistic effect of both the convenience of taking tablets and the reduction of intraluminal bubble by adjunctive simethicone improves the clinical efficacy of colonoscopy.

Changes in oral bioaccessibility of heavy metals in non-digestive sucking habits due to the formation of complexes between digestive fluid components and metals/metalloids.

Humans, especially infants, are exposed to harmful substances through various means, including non-nutritive sucking behaviors. Here, we compared the "one-compartment model" and the "three-compartment model" within the "suck model" to assess the oral bioaccessibility of heavy metals in various products and evaluated whether these models can be employed to assess 12 heavy metals present in consumer products. Several certified reference materials, including plastic, paint, glass, and metals, were employed to ensure sample homogeneity. By comparing the two models, we validated that a considerable amount of complexes were formed between saliva components and the extracted heavy metals and that some of these complexes dissociated during reactions with the gastric/intestinal fluids. Furthermore, we observed that in the cases of Cu and Pb, additional complexes were formed as a result of reactions with gastric/intestinal fluids. We measured the total concentrations of the extracted heavy metals using artificial saliva through acid digestion and found that up to 99.7% of the heavy metals participated in the formation of complexes, depending on the characteristics of the sample (e.g., composition) and the target element. This result indicates that the current suck model may notably underestimate the oral bioaccessibility of heavy metals in products associated with sucking behaviors. Therefore, we propose a more conservative and simpler test method for assessing oral bioaccessibility of heavy metals that involves measuring the total concentrations of heavy metals extracted from consumer products using artificial saliva. By doing so, we can account for potential variations in the digestive milieu (e.g., due to ingested food) and the inconsistency in complex formation-dissociation characteristics.

Genetic Background and Kinetics Define Wound Bed Extracellular Vesicles in a Mouse Model of Cutaneous Injury.

Extracellular vesicles (EVs) have an important role in mediating intercellular signaling in inflammation and affect the kinetics of wound healing, however, an understanding of the mechanisms regulating these responses remains limited. Therefore, we have focused on the use of cutaneous injury models in which to study the biology of EVs on the inflammatory phase of wound healing. For this, the foreign body response using sterile subcutaneous polyvinylalcohol (PVA) sponges is ideally suited for the parallel analysis of immune cells and EVs without the need for tissue dissociation, which would introduce additional variables. We have previously used this model to identify mediators of EV biogenesis, establishing that control of how EVs are made affects their payload and biological activity. These studies in normal mice led us to consider how conditions such as immunodeficiency and obsesity affect the profile of immune cells and EVs in this model using genetically defined mutant mice. Since EVs are intrinsically heterogenous in biological fluids, we have focused our studies on a novel technology, vesicle flow cytometry (vFC) to quantify changes in EVs in mouse models. Here, we show that myeloid-derived immune cells and EVs express proteins relevant in antigen presentation in PVA sponge implants that have distinct profiles in wildtype, immune-deficient (NOD scid) vs. diabetic (Leprdb) mice. Together, these results establish a foundation for the parallel analysis of both immune cells and EVs with technologies that begin to address the heterogeneity of intercellular communication in the wound bed.

Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles.

BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that release extracellular vesicles (EVs). EVs contain various growth factors and antioxidants that can positively affect the surrounding cells. Nanoscale MSC-derived EVs, such as exosomes, have been developed as bio-stable nano-type materials. However, some issues, such as low yield and difficulty in quantification, limit their use. We hypothesized that enhancing exosome production using nanoparticles would stimulate the release of intracellular molecules. RESULTS: The aim of this study was to elucidate the molecular mechanisms of exosome generation by comparing the internalization of surface-modified, positively charged nanoparticles and exosome generation from MSCs. We determined that Rab7, a late endosome and auto-phagosome marker, was increased upon exosome expression and was associated with autophagosome formation. CONCLUSIONS: It was concluded that the nanoparticles we developed were transported to the lysosome by clathrin-mediated endocytosis. additionally, entered nanoparticles stimulated that autophagy related factors to release exosome from the MSC. MSC-derived exosomes using nanoparticles may increase exosome yield and enable the discovery of nanoparticle-induced genetic factors.

Three-dimensional electrodes enhance electricity generation and nitrogen removal of microbial fuel cells.

One of the critical problems for practical application of microbial fuel cells (MFCs) is the poor electron transfer between microbial cells and anode. Hence, good biocompatibility and high specific surface area of electrodes are indispensable for MFC scale-up. In this study, three-dimensional electrode MFC (3DEMFC) was developed by filling biochar between anode and cathode. Three types of biochar electrodes (biochar, biochar and zeolite mixture, and MgO-modified biochar) were employed, and the performance of 3DEMFCs treating nitrogen in wastewater was investigated. The results showed that the highest power density of MFCs was 4.45 ± 0.21 W m-3 achieved by 3DEMFC filled with MgO-modified biochar, and the overall power generation of 3DEMFCs (2.40 ± 0.28 ~ 4.45 ± 0.21 W m-3) was higher than that of MFC without biochar (1.31 ± 0.24 W m-3). The linear sweep voltammetry (LSV) results also demonstrated biochar addition to MFC was conducive to electron transfer between microbes and anode and MgO-modified biochar presented the highest coulombs transfer ability. Moreover, the highest removal efficiencies of ammonium, total nitrogen, and COD (93.6 ± 3.2%, 84.8 ± 2%, and 91.6 ± 1.3%, respectively) were achieved by 3DEMFC containing MgO-modified biochar, and simultaneous short-cut nitrification and denitrification were observed in MFCs. Furthermore, the SEM images displayed the bacteria adhesion on biochar and the biofilm dry weights of MgO-modified biochar after experiment was the highest of 103 ± 4 mg g-1 among three kinds of biochar electrodes. Therefore, the power generation and nitrogen removal conspicuously enhanced in 3DEMFCs and biochar exhibited excellent biocompatibility and distinct electrochemical performance for MFC practical applications in wastewater treatment.

Transport of citrate and polymer coated gold nanoparticles (AuNPs) in porous media: Effect of surface property and Darcy velocity.

With the release of nanoparticles (NPs) into the subsurface, it is imperative to better understand the fate and transport of NPs in porous media. Three types of stable AuNPs were used as model NPs to investigate the impact of surface coatings (type and coverage) and water velocity on the NP transport in a porous media (column studies). The NPs were electrostatic stabilized citrate AuNPs and sterically stabilized AuNPs with amphiphilic block co-polymer (PVA-COOH) in two particle/polymer ratios (weak vs. strong stabilization). The citrate AuNPs transport was sensitive to ionic changes in the mixing front of the plume, where destabilization occurred, and will therefore depend on the size/type of release. Blocking of deposition sites by aggregates was seen to facilitate transport, whereby a higher flow velocity (larger shadow zone) also resulted in better transport. The polymeric surface coating had great impact with steric repulsion as a main force contributing to the transport of NPs in the porous media. Sufficient polymer coating was crucial to obtain highly unfavorable attachment conditions (very low α) where the enhanced NP mobility was independent of the water velocity (comparable to solute tracer). Without sufficient steric stabilization, the transport and recovery was significantly reduced compared to the solute tracer, but increased with increasing water velocity. This highlights the importance of sufficient surface coating to achieve enhanced mobility, but also the increased risk of spreading to down-gradient receptors. For the (weakly) sterically stabilized NPs, the loss of polymer through ligand exchange with the porous media negates transport.

Structurally Stable, Antifouling, and Easily Renewable Reduced Graphene Oxide Membrane with a Carbon Nanotube Protective Layer.

The excellent permeability and selectivity of reduced graphene oxide (rGO) membranes have been demonstrated both theoretically and experimentally; however, strategies for the fabrication of highly stable, antifouling rGO membranes with facile recovery after fouling have rarely been investigated. In this work, we report a structurally durable rGO-based hollow fiber membrane that allows high-pressure (at least 1 bar) back-flushing. This is achieved by sandwiching the rGO layer between a carbon nanotube (CNT) protective layer and a polyacrylonitrile (PAN) support. The CNT layer could also function as a prefiltration and pre-adsorption microsystem and endow a higher resistance against fouling. This is experimentally confirmed by the much higher normalized permeance (0.82-0.92) of the CNT/rGO/PAN membranes than the simple rGO/PAN membranes (0.42-0.53) under the same operating conditions. Additionally, under a low cathode potential (0.9 V), the membrane could easily be renewed after fouling by simple back-flushing with a flux recovery ratio of ∼96%. An investigation of the mechanism indicates that electrostatic repulsive forces promote the desorption of charged organic foulants (e.g., humic acid and dyes) from the rGO and CNT layers, and they can subsequently be removed from the membrane with water.

Fish Collagen Surgical Compress Repairing Characteristics on Wound Healing Process In Vivo.

The development of biomaterials with the potential to accelerate wound healing is a great challenge in biomedicine. In this study, four types of samples including pepsin soluble collagen sponge (PCS), acid soluble collagen sponge (ACS), bovine collagen electrospun I (BCE I) and bovine collagen electrospun II (BCE II) were used as wound dressing materials. We showed that the PCS, ACS, BCE I and BCE II treated rats increased the percentage of wound contraction, reduced the inflammatory infiltration, and accelerated the epithelization and healing. PCS, ACS, BCE I, and BCE II significantly enhanced the total protein and hydroxyproline level in rats. ACS could induce more fibroblasts proliferation and differentiation than PCS, however, both PCS and ACS had a lower effect than BCE I and BCE II. PCS, ACS, BCE I, and BCE II could regulate deposition of collagen, which led to excellent alignment in the wound healing process. There were similar effects on inducing the level of cytokines including EGF, FGF, and vascular endothelial marker CD31 among these four groups. Accordingly, this study disclosed that collagens (PCS and ACS) from tilapia skin and bovine collagen electrospun (BCE I and BCE II) have significant bioactivity and could accelerate wound healing rapidly and effectively in rat model.

Clinical Factors and Cellular Responses of In Situ Human Alveolar Bone-Derived Mesenchymal Stromal Cells Associated With Early Periimplant Marginal Bone Loss: A Prospective Cohort Pilot Study.

PURPOSE: To investigate clinical factors and cellular responses of in situ human alveolar bone-derived mesenchymal stromal cells involved in early periimplant marginal bone loss. MATERIALS AND METHODS: Thirty-seven completely or partially edentulous patients were enrolled in this study. Periapical radiographs were taken at the time of implant surgery, at 3-month follow-up, and at 1-year follow-up. Univariate analysis and multiple logistic regression were performed to investigate the associations between marginal bone loss and study variables. The mRNA expression levels of 21 bone-remodeling- and tissue-healing-associated genes were analyzed by subgroup. RESULTS: Thirty-one patients with 98 implants were followed. The incidence and mean amount of bone loss were higher for overdentures than for other prosthesis and higher for the maxilla than for the mandible. The bone loss group showed lower mRNA expression levels of runt-related transcription factor-2, bone morphogenetic protein-2, and peroxisome proliferator-activated receptor gamma-2 and higher receptor activator of NKκB ligand/osteoprotegerin (RANKL/OPG) ratio. CONCLUSION: Within the limitations of the study, certain genes involved in bone remodeling (runt-related transcription factor-2 [Runx-2], bone morphogenetic protein-2 [BMP-2], and peroxisome proliferator-activated receptor gamma-2 [PPARγ-2]) and RANKL/OPG are correlated with early periimplant bone loss, with the type of suprastructure and the involved jaw being significant clinical factors.

Tablet Formulation of a Polymeric Solid Dispersion Containing Amorphous Alkalinized Telmisartan.

To overcome the poor dissolution of telmisartan (TMS) at weak acidic pH, amorphous alkalinized TMS (AAT) was prepared by introducing sodium hydroxide as a selective alkalizer. AAT-containing polymeric solid dispersions were prepared by a solvent evaporation method; these solid dispersions were AAT-PEG, AAT-PVP, AAT-POL, and AAT-SOL for the polymers of PEG 6000, PVP K30, Poloxamer 407, and Soluplus, respectively. The characteristics of the different formulations were observed by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. To compare the supersaturation behavior, a dissolution test was performed at 37 ± 0.5 °C either in 900 ml (plain condition) or 500 ml (limited condition) of pH 6.8-simulated intestinal fluid used as a medium. AAT-SOL exhibited enhanced dissolution, indicating the probability of extended supersaturation in the limited condition. AAT-SOL was further formulated into a tablet by introducing other excipients, Vivapur 105 and Croscarmellose, as a binder and superdisintegrant, respectively, using a direct compression method. The selected AAT-SOL tablet was superior to Micardis (the reference product) in the aspect of supersaturation maintenance during dissolution in the limited condition, suggesting that it is a promising candidate for practical development that can replace the commercial product in the future.

Preparation of Ag/Au bimetallic nanostructures and their application in surface-enhanced fluorescence.

An effective substrate for surface-enhanced fluorescence, which consists of cluster Ag/Au bimetallic nanostructures on a copper surface, was synthesized via a multi-stage galvanic replacement reaction of a Ag cluster in a chlorauric acid (HAuCl4) solution at room temperature. The fabricated silver/gold bimetallic cluster were found to yield large surface-enhanced fluorescence (SEF) enhancement factors for rhodamine 6G probe molecules deposited on the substrate, and also the fluorescence efficiency is critically dependent on the period of nanostructure growth. With the help of proper control reaction conditions, such as the reaction time, and concentration of reaction solutions, the maximum fluorescence enhanced effect was obtained. Therefore, the bimetallic nanostructure substrate also can be adapted to studies in SEF, which will expand the application of SEF.

Macrophage depletion ameliorates glycerol-induced acute kidney injury in mice.

BACKGROUND: This study was conducted to elucidate the role of renal macrophages in the development of acute kidney injury (AKI) in a glycerol (Gly)-induced rhabdomyolysis mouse model. METHODS: The experimental model of rhabdomyolysis requires injecting 50% Gly (10 ml/kg) intramuscularly into mice. Control mice were injected into the tail vein with the liposomal vehicle. Liposome-encapsulated clodronate (LEC)-only mice were injected with LEC. Gly-only mice were injected with Gly into a hind limb. LEC+Gly-treated mice were injected intravenously with 100 µl of LEC 24 h prior to Gly injection. Mice were sacrificed 24 h after Gly injection. RESULTS: Gly injection increased the serum creatinine level, and induced tubular damage. Renal CD45(+)CD11b(+)Ly6c(+) or CD45(+)CD11b(+)Ly6c(+)F4/80(+) macrophages were decreased by pretreatment with LEC in both normal and injured kidneys. Macrophage depletion prevented Gly-induced apoptotic death of tubular epithelial cells by decreasing caspase-9, ERK and p53, while increasing Bcl-2 expression. Expression of the inflammatory mediators NF-κB, MCP-1, ICAM-1, iNOS and COX-2 were also decreased with LEC pretreatment of mice injected with Gly. CONCLUSION: These results support the hypothesis that depletion of macrophages prevents renal dysfunction by abrogating apoptosis and attenuating inflammation during AKI.

A new method of alkalinity remediation for Cd-contaminated groundwater by PAAS-modified MgCO3/Mg(OH)2 colloid.

Mg(OH)2 dissolves slowly and can provide a long-term source of alkalinity, thus a promising alternative reagent for the in situ remediation of heavy metal polluted groundwater. Unfortunately, it exhibits a relatively poor stabilization effect on heavy metal Cd due to the higher solubility of the resulting stabilized product, Cd(OH)2. To overcome this limitation, we investigated the use of MgCO3/Mg(OH)2 colloid modified by sodium polyacrylate (PAAS) to remove Cd from groundwater. Through ultrasonic dispersion, the molecular chains of PAAS are broken, causing a transformation from flocculation to surface modification, resulting in the production of a stable colloid. The colloidal particles of MgCO3/Mg(OH)2 have a smaller size and a negatively charged surface, which significantly enhances their migration ability in aquifers. The combination of MgCO3 and Mg(OH)2 provides a complementary effect, where MgCO3 effectively precipitates Cd in the aquifer while Mg(OH)2 maintains the required pH level for stabilization. The optimal compounding ratio of MgCO3 to Mg(OH)2 for achieving the best stabilization effect on Cd is found to be 1:1. Column experiments demonstrate that the injection of MgCO3/Mg(OH)2 colloid substantially enhances Cd stability, reducing the exchangeable fraction of Cd in aquifer media from 88.61% to a range of 22.50-34.38%. Based on these results, the MgCO3/Mg(OH)2 colloid shows great potential as a reactive medium for remediating Cd-contaminated groundwater.

Preparation of healing-promoting and fibrosis-inhibiting asymmetric poly(ethylene glycol-b-L-phenylalanine)/cRGD-modified hyaluronate sponges and their applications in hemorrhage and nasal mucosa repair.

Acute or chromic bleeding, such as epistaxis, requires hemostatic materials to assist hemostasis. Even in complex cases, hemostatic materials must have other functions, including the promotion of healing and prevention of adhesion. Herein, a series of fibrosis-suppressive functional cRGD-modified crosslinking hyaluronic acid sponges were prepared. The in vitro hemostatic efficiency and mechanism were determined using blood clotting time, blood coagulation index, lactate dehydrogenase (LDH) and thromboxane B2 (TX-B2) ELISA, and proteomics. Among the prepared sponges, both poly(ethylene-b-L-Phe) (PEBP)-and cRGD contained SPN4 and exhibited the highest platelet concentration and activation efficiency as well as the most effective coagulative effect. In addition, no significant cytotoxicity was observed for the sponges in rat airway epithelial cells. The in vivo hemostatic and adhesion-preventive effects of the sponges were evaluated using rat models of liver injury and sidewall defect-cecum abrasion. PEBP-containing sponges effectively prevented postoperative adhesion and cRGD-modified sponges exhibited excellent hemostatic effects. Finally, the comprehensive repair effects of the sponges were evaluated using a rabbit maxillary sinus mucosal injury model, based on CT, MRI examination, and pathological staining. SPN4 exhibited the best comprehensive reparative effects, including the promotion of mucosal repair and infection inhibition. Thus, SPN4 is a promising multifunctional hemostatic material.

Subsidence of polyetheretherketone cage after minimally invasive transforaminal lumbar interbody fusion.

STUDY DESIGN: A retrospective case series. OBJECTIVE: The aim of this study was to determine the rate of cage subsidence after minimally invasive transforaminal lumbar interbody fusion (MITLIF) conducted using a polyetheretherketone (PEEK) cage, and to identify associated risk factors. SUMMARY OF BACKGROUND DATA: Although various rates of cage subsidence after lumbar interbody fusion have been reported, few studies have addressed subsidence rate after MITLIF using PEEK cage. METHODS: A total of 104 consecutive patients who had undergone MITLIF using a PEEK cage with a minimum follow-up of 2 years were included in this study. Cage subsidence was defined to have occurred when a cage was observed to sink into an adjacent vertebral body by ≥2 mm on the postoperative or serial follow-up lateral radiographs. The demographic variables considered to affect cage subsidence were the following: age, sex, body mass index, bone mineral density, diagnosis, number of fusion segment, and the quality/quantity of back muscle, and the cage-related variables considered were: level of fusion, intervertebral angle, cage size, cage position, and postoperative distraction of disc height. Logistic regression analysis was conducted to explore relations between these variables and cage subsidence. RESULTS: : For the 122 cages inserted, the rate of cage subsidence was 14.8% (18 cages), and cage subsidence occurred within 7.2±8.5 (1-25) months of surgery. The odds ratios for factors found to significantly increase the risk of cage subsidence were; 1.950 (95% confidence interval, 1.002-4.224) for L5-S1 level, and 1.018 (95% confidence interval, 1.000-1.066) for anterior cage position. CONCLUSIONS: The rate of PEEK cage subsidence after MITLIF was relatively low. End-plate manipulation and cage insertion during MITLIF were not influenced by a small operation window.

Ultra-soft and highly stretchable tissue-adhesive hydrogel based multifunctional implantable sensor for monitoring of overactive bladder.

A highly stretchable and tissue-adhesive multifunctional sensor based on structurally engineered islets embedded in ultra-soft hydrogel is reported for monitoring of bladder activity in overactive bladder (OAB) induced rat and anesthetized pig. The use of hydrogel yielded a much lower sensor modulus (1 kPa) compared to that of the bladder (300 kPa), while the strong adhesiveness of the hydrogel (adhesive strength: 260.86 N/m) allowed firm attachment onto the bladder. The change in resistance of printed liquid metal particle thin-film lines under strain were used to detect bladder inflation and deflation; due to the high stretchability and reliability of the lines, surface strains of 200% could be measured repeatedly. Au electrodes coated with Platinum black were used to detect electromyography (EMG). These electrodes were placed on structurally engineered rigid islets so that no interfacial fracture occurs under high strains associated with bladder expansion. On the OAB induced rat, stronger signals (change in resistance and EMG root-mean-square) were detected near intra-bladder pressure maxima, thus showing correlation to bladder activity. Moreover, using robot-assisted laparoscopic surgery, the sensor was placed onto the bladder of an anesthetized pig. Under voiding and filling, bladder strain and EMG were once again monitored. These results confirm that our proposed sensor is a highly feasible, clinically relevant implantable device for continuous monitoring OAB for diagnosis and treatment.

Implantable Multi-Cross-Linked Membrane-Ionogel Assembly for Reversible Non-Faradaic Neurostimulation.

Neural interfaces play a major role in modulating neural signals for therapeutic purposes. To meet the demand of conformable neural interfaces for developing bioelectronic medicine, recent studies have focused on the performance of electrical neurostimulators employing soft conductors such as conducting polymers and electronic or ionic conductive hydrogels. However, faradaic charge injection at the interface of the electrode and nerve tissue causes irreversible gas evolution, oxidation of electrodes, and reduction of biological ions, thus causing undesired tissue damage and electrode degradation. Here we report a conformable neural interface engineering based on multicross-linked membrane-ionogel assembly (termed McMiA), which enables nonfaradaic neurostimulation without irreversible charge transfer reaction. The McMiA consists of a genipin-cross-linked biopolymeric ionogel coupled with a dopamine-cross-linked graphene oxide membrane to prevent ion exchange between biological and synthetic McMiA ions and to function as a bioadhesive forming covalent bonds with the target tissues. In addition, the demonstration of bioelectronic medicine via the McMiA-based neurostimulation of sciatic nerves shows the enhanced clinical utility in treating the overactive bladder syndrome. As the McMiA-based neural interface is soft, robust for bioadhesion, and stable in a physiological environment, it can offer significant advancement in biocompatibility and long-term operability for neural interface engineering.

The cytocompatibility and osseointegration of the Ti implants with XPEED® surfaces.

OBJECTIVES: This study evaluated cytocompatibility and osseointegration of the titanium (Ti) implants with resorbable blast media (RBM) surfaces produced by grit-blasting or XPEED(®) surfaces by coating of the nanostructured calcium. MATERIAL AND METHODS: Ti implants with XPEED(®) surfaces were hydrothermally prepared from Ti implants with RBM surfaces in a solution containing alkaline calcium. The surface characteristics were evaluated by using a scanning electron microscope (SEM) and surface roughness measuring system. Apatite formation was measured with SEM after immersion in modified-simulated body fluid and the amount of calcium released was measured by inductively coupled plasma optical emission. The cell proliferation was investigated by MTT assay and the cell attachment was evaluated by SEM in MC3T3-E1 pre-osteoblast cells. Thirty implants with RBM surfaces and 30 implants with XPEED(®) surfaces were placed in the proximal tibiae and in the femoral condyles of 10 New Zealand White rabbits. The osseointegration was evaluated by a removal torque test in the proximal tibiae and by histomorphometric analysis in the femoral condyles 4 weeks after implantation. RESULTS: The Ti implants with XPEED(®) surfaces showed a similar surface morphology and surface roughness to those of the Ti implants with RBM surfaces. The amount of calcium ions released from the surface of the Ti implants with XPEED(®) surfaces was much more than the Ti implants with RBM surfaces (P < 0.05). The cell proliferation and cell attachment of the Ti implants showed a similar pattern to those of the Ti implants with RBM surfaces (P > 0.1). Apatite deposition significantly increased in all surfaces of the Ti implants with XPEED(®) surfaces. The removable torque value (P = 0.038) and percentage of bone-to-implant contact (BIC%) (P = 0.03) was enhanced in the Ti implants with XPEED(®) surfaces. CONCLUSION: The Ti implants with XPEED(®) surfaces significantly enhanced apatite formation, removal torque value, and the BIC%. The Ti implants with XPEED(®) surfaces may induce strong bone integration by improving osseointegration of grit-blasted Ti implants in areas of poor quality bone.