Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis.

OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.

Surface-Functionalized Conducting Nanofibers for Electrically Stimulated Neural Cell Function.

Strategies involving the inclusion of cell-instructive chemical and topographical cues to smart biomaterials in combination with a suitable physical stimulus may be beneficial to enhance nerve-regeneration rate. In this regard, we investigated the surface functionalization of poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV)-based electroconductive electrospun nanofibers coupled with externally applied electrical stimulus for accelerated neuronal growth potential. In addition, the voltage-dependent conductive mechanism of the nanofibers was studied in depth to interlink intrinsic conductive properties with electrically stimulated neuronal expressions. Surface functionalization was accomplished using 3-aminopropyltriethoxysilane (APTES) and 1,6-hexanediamine (HDA) as an alternative to costly biomolecule coating (e.g., collagen) for cell adhesion. The nanofibers were uniform, porous, electrically conductive, mechanically strong, and stable under physiological conditions. Surface amination boosted biocompatibility, 3T3 cell adhesion, and spreading, while the neuronal model rat PC12 cell line showed better differentiation on surface-functionalized mats compared to nonfunctionalized mats. When coupled with electrical stimulation (ES), these mats showed comparable or faster neurite formation and elongation than the collagen-coated mats with no-ES conditions. The findings indicate that surface amination in combination with ES may provide an improved strategy to faster nerve regeneration using MEH-PPV-based neural scaffolds.

An adsorbent monolith device to augment the removal of uraemic toxins during haemodialysis.

Adsorbents designed with porosity which allows the removal of protein bound and high molecular weight uraemic toxins may improve the effectiveness of haemodialysis treatment of chronic kidney disease (CKD). A nanoporous activated carbon monolith prototype designed for direct blood contact was first assessed for its capacity to remove albumin bound marker toxins indoxyl sulphate (IS), p-cresyl sulphate (p-CS) and high molecular weight cytokine interleukin-6 in spiked healthy donor studies. Haemodialysis patient blood samples were then used to measure the presence of these markers in pre- and post-dialysis blood and their removal by adsorbent recirculation of post-dialysis blood samples. Nanopores (20-100 nm) were necessary for marker uraemic toxin removal during in vitro studies. Limited removal of IS and p-CS occurred during haemodialysis, whereas almost complete removal occurred following perfusion through the carbon monoliths suggesting a key role for such adsorbent therapies in CKD patient care.

Resveralogues protect HepG2 cells against cellular senescence induced by hepatotoxic metabolites.

Progressive liver disease and dysfunction cause toxic metabolites including ammonia and unconjugated bilirubin to accumulate in plasma. As the population ages alternatives to liver transplantation become increasingly important. One approach for use as a bridge to transplant or recovery is the use of bioartificial liver systems (BALS) containing primary or immortalised hepatocytes as ex-vivo replacements or supports for endogenous liver function. However, exposure to the hepatotoxic metabolites present in plasma causes the rapid failure of these cells to carry out their primary metabolic functions despite remaining viable. Hypothesizing that this loss of core hepatocyte phenotypes was caused by cell senescence we exposed HepG2 cell populations, grown in both standard two-dimensional tissue culture systems and in three dimensional cultures on novel alginate modified HEMA-MBA cryogels, to physiologically reflective concentrations of hepatotoxic metabolites and cytokines. HepG2 cells are forced into senescence by the toxic metabolites in under six hours (as measured by loss of thymidine analog incorporation or detectable Ki67 staining) which is associated with a ten to twenty-fold reduction in the capacity of the cultures to synthesise albumin or urea. This state of senescence induced by liver toxins (SILT) can be prevented by preincubation with either 2-5 µM resveratrol, its major in vivo metabolite dihydroresveratrol or a series of novel resveralogues with differential capacities to scavenge radicals and activate SIRT1 (including V29 which does not interact with the protein). SILT appears to be a previously unrecognised barrier to the development of BALS which can now be overcome using small molecules that are safe for human use at concentrations readily achievable in vivo.

Pristine Ti3C2Tx MXene Enables Flexible and Transparent Electrochemical Sensors.

In the era of the internet of things, there exists a pressing need for technologies that meet the stringent demands of wearable, self-powered, and seamlessly integrated devices. Current approaches to developing MXene-based electrochemical sensors involve either rigid or opaque components, limiting their use in niche applications. This study investigates the potential of pristine Ti3C2Tx electrodes for flexible and transparent electrochemical sensing, achieved through an exploration of how material characteristics (flake size, flake orientation, film geometry, and uniformity) impact the electrochemical activity of the outer sphere redox probe ruthenium hexamine using cyclic voltammetry. The optimized electrode made of stacked large Ti3C2Tx flakes demonstrated excellent reproducibility and resistance to bending conditions, suggesting their use for reliable, robust, and flexible sensors. Reducing electrode thickness resulted in an amplified faradaic-to-capacitance signal, which is advantageous for this application. This led to the deposition of transparent thin Ti3C2Tx films, which maintained their best performance up to 73% transparency. These findings underscore its promise for high-performance, tailored sensors, marking a significant stride in advancing MXene utilization in next-generation electrochemical sensing technologies. The results encourage the analytical electrochemistry field to take advantage of the unique properties that pristine Ti3C2Tx electrodes can provide in sensing through more parametric studies.

Examining porous bio-active glass as a potential osteo-odonto-keratoprosthetic skirt material.

Bio-active glass has been developed for use as a bone substitute with strong osteo-inductive capacity and the ability to form strong bonds with soft and hard tissue. The ability of this material to enhance tissue in-growth suggests its potential use as a substitute for the dental laminate of an osteo-odonto-keratoprosthesis. A preliminary in vitro investigation of porous bio-active glass as an OOKP skirt material was carried out. Porous glass structures were manufactured from bio-active glasses 1-98 and 28-04 containing varying oxide formulation (1-98, 28-04) and particle size range (250-315 µm for 1-98 and 28-04a, 315-500 µm for 28-04b). Dissolution of the porous glass structure and its effect on pH was measured. Structural 2D and 3D analysis of porous structures were performed. Cell culture experiments were carried out to study keratocyte adhesion and the inflammatory response induced by the porous glass materials. The dissolution results suggested that the porous structure made out of 1-98 dissolves faster than the structures made from glass 28-04. pH experiments showed that the dissolution of the porous glass increased the pH of the surrounding solution. The cell culture results showed that keratocytes adhered onto the surface of each of the porous glass structures, but cell adhesion and spreading was greatest for the 98a bio-glass. Cytokine production by all porous glass samples was similar to that of the negative control indicating that the glasses do not induce a cytokine driven inflammatory response. Cell culture results support the potential use of synthetic porous bio-glass as an OOKP skirt material in terms of limited inflammatory potential and capacity to induce and support tissue ingrowth.

Activation-dependent adsorption of cytokines and toxins related to liver failure to carbon beads.

In the course of severe pathological conditions, such as acute liver failure and sepsis, toxic metabolites and mediators of inflammation are released into the patient's circulation. One option for the supportive treatment of these conditions is plasmapheresis, in which plasma, after being separated from the cellular components of the blood, is cleansed by adsorption of harmful molecules on polymers or activated carbon. In this work, the adsorption characteristics of activated carbon beads with levels of activation ranging from 0 to 86% were assessed for both hydrophobic compounds accumulating in liver failure (bilirubin, cholic acid, phenol and tryptophan) and cytokines (tumor necrosis factor α and interleukin-6). Progressive activation resulted in significant gradual reduction of both bulk density and mean particle size, in an increase in the specific surface area, and to changes in pore size distribution with progressive broadening of micropores. These structural changes went hand in hand with enhanced adsorption of small adsorbates, such as IL-6 and cholic acid and, to a lesser extent, also of large molecules, such as TNF-α.

Moderating cellular inflammation using 2-dimensional titanium carbide MXene and graphene variants.

The effective control of microbial and metabolically derived biological toxins which negatively impact physical health remains a key challenge for the 21st century. 2-Dimensional graphene and MXene nanomaterials are relatively new additions to the field of biomedical materials with superior external surface areas suited to adsorptive remediation of biological toxins. However, relatively little is known about their physiological interactions with biological systems and, to date, no comparative biological studies have been done. This study compares titanium carbide MXene (Ti3C2Tx) in multilayered and delaminated forms with graphene variants to assess the impact of variable physical properties on cellular inflammatory response to endotoxin stimulus. No significant impact on cell metabolism or induction of inflammatory pathways leading to cell death was observed. No significant increase in markers of blood cell activation and haemolysis occurred. Whilst graphene nanoplatelets (GNP), graphene oxide (GO) and Ti3C2Tx showed insignificant antibacterial activity towards Escherichia coli, silver nanoparticle-modified GO (GO-Ag) induced bacterial cell death and at a lower dose than silver nanoparticles. All nanomaterials significantly reduced bacterial endotoxin induced THP-1 monocyte IL-8, IL-6 and TNF-α cytokine production by >99%, >99% and >80% respectively, compared to control groups. This study suggests the utility of these nanomaterials as adsorbents in blood contacting medical device applications for removal of inflammatory cytokines linked to poor outcome in patients with life-threatening infection.

Factors Affecting Posterior Capsule Opacification in the Development of Intraocular Lens Materials.

Posterior capsule opacification (PCO) is the most common complication arising from the corrective surgery used to treat cataract patients. PCO arises when lens epithelial cells (LEC) residing in the capsular bag post-surgery undergo hyper-proliferation and transdifferentiation into myofibroblasts, migrating from the posterior capsule over the visual axis of the newly implanted intraocular lens (IOL). The developmental pathways underlying PCO are yet to be fully understood and the current literature is contradictory regarding the impact of the recognised risk factors of PCO. The aim of this review is firstly to collate the known biochemical pathways that lead to PCO development, providing an up-to-date chronological overview from surgery to established PCO formation. Secondly, the risk factors of PCO are evaluated, focussing on the impact of IOLs' properties. Finally, the latest experimental model designs used in PCO research are discussed to demonstrate the ongoing development of clinical PCO models, the efficacy of newly developed IOL technology, and potential therapeutic interventions. This review will contribute to current PCO literature by presenting an updated overview of the known developmental pathways of PCO, an evaluation of the impact of the risk factors underlying its development, and the latest experimental models used to investigate PCO. Furthermore, the review should provide developmental routes for research into the investigation of potential therapeutic interventions and improvements in IOL design in the aid of preventing PCO for new and existing patients.

Biomimetic bone-like composites as osteo-odonto-keratoprosthesis skirt substitutes.

Osteo-odonto-keratoprostheses, incorporating dental laminate material as an anchoring skirt around a central poly(methyl methacrylate) (PMMA) optic, have been used to replace the cornea for many years. However, there are many intricacies associated with the use of autologous dental laminate material, surgical complexity and skirt erosion. Tissue engineering approaches to bone replacement may offer suitable alternatives in osteo-odonto-keratoprosthesis (OOKP) surgery. In this study, a hydrogel polymer composite was investigated as a synthetic substitute for the OOKP skirt. A novel high strength interpenetrating network (IPN) hydrogel composite with nano-crystalline hydroxyapatite (nHAp) coated poly (lactic-co-glycolic acid) PLGA microspheres was created to mimic the alveo-dental lamina by employing agarose and poly(ethylene glycol) diacrylate (PEGDA) polymers. The incorporation of nHAp coated PLGA microspheres into the hybrid IPN network provide a micro-environment similar to that of skeletal tissues and improve cellular response. Agarose was used as a first network to encapsulate keratocytes/3T3 fibroblasts and PEGDA (6000 Da) was used as a second network with varying concentrations (20 and 40 wt %) to produce a strong and biocompatible scaffold. An increased concentration of either agarose or PEG-DA and incorporation of nHAp coated PLGA microspheres led to an increase in the elastic modulus. The IPN hydrogel combinations supported the adhesion and proliferation of both fibroblast and ocular human keratocyte cell types during in in-vitro testing. The cells endured the encapsulation process into the IPN and remained viable at 1 week post-encapsulation in the presence of nHAp coated microspheres. The material did not induce significant production of inflammatory cytokine IL-6 in comparison to a positive control (p < 0.05) indicating non-inflammatory potential. The nHAp encapsulated composite IPN hydrogels are mechanically strong, cell supportive, non-inflammatory materials supporting their development as OOKP skirt substitutes using a new approach to dental laminate biomimicry in the OOKP skirt material.

Bioengineering a cryogel-derived bioartificial liver using particle image velocimetry defined fluid dynamics.

Bioartificial Liver (BAL) devices are extracorporeal systems designed to support or recover hepatic function in patients with liver failure. The design of an effective BAL remains an open challenge since it requires a complex co-optimisation of cell colonisation, biomaterial scaffold and BAL fluid dynamics. Building on previous evidence of suitability as a blood perfusion device for detoxification, the current study investigated the use of RGD-containing p(HEMA)-alginate cryogels as BAL scaffolds. Cryogels were modified with alginate to reduce protein fouling and functionalised with an RGD-containing peptide to increase hepatocyte adhesion. A novel approach for characterisation of the internal flow through the porous matrix was developed by employing Particle Image Velocimetry (PIV) to visualise flow inside cryogels. Based on PIV results, which showed the laminar nature of flow inside cryogel pores, a multi-layered bioreactor composed of spaced cryogel discs was designed to improve blood/hepatocyte mass exchange. The stacked bioreactor showed a significantly higher production of albumin and urea compared to the column version, with improved cell colonisation and proliferation over time. The cell-free cryogel-based device was tested for safety in a bile-duct ligation model of liver cirrhosis. Thus, a stacked bioreactor prototype was developed based on a surface-engineered cryogel design with optimised fluid dynamics for BAL use.

Multiple drug delivery from the drug-implants-laden silicone contact lens: Addressing the issue of burst drug release.

A fixed combination of bimatoprost/timolol eye drop solution is used to manage the elevated intra-ocular pressure in glaucoma patients, including individuals whose condition is poorly controlled by monotherapy. Eye drop solutions are generally given in high dose, due to poor ocular bioavailability. The high ocular dose of bimatoprost and timolol lead to hyperaemia and systemic cardiac side effects respectively. Here, we introduce multiple implant-laden contact lenses (IM) to passively deliver timolol, bimatoprost and hyaluronic acid at therapeutically relevant doses without high burst release. The drug-loaded implants were individually implanted in the outer periphery of the silicone contact lenses. Atomic force microscopy showed the smooth surface of the implant contact lens, as the implants were inside the contact lens matrix. The implant lens (IM) showed major loss of drugs [timolol = 60.60%, bimatoprost = 61.75% and HA = 46.03%] during the monomer extraction and wet sterilization, while the option of dry radiation sterilization (IM-R lens) and hydration for 24 h prior to use showed relatively lower loss of drugs [timolol = 16.87%, bimatoprost = 47.95% and HA = 24.41%]. The in-vitro drugs release data of IM-R lens, showed sustained release for 72 h, with low burst release in comparison to the soaked (SM) and direct drug-laden contact lenses (DL). The in vivo drug release data in the rabbit tear fluid showed sustained release using IM-R lens in comparison to the SM lens and eye drop therapy. The burst release with the IM-R lens was many folds reduced, which could bypass the side effects associated with multiple eye drop therapy. The in vivo pharmacodynamic study in the rabbit model showed peak and valley profile with multiple eye drop therapy, while IM-R lens showed prolong reduction in intra ocular pressure (IOP) for 120 h. The study demonstrates the application of implantation technology to deliver multiple drug through contact lenses to treat glaucoma.

Plackett-Burman design for screening of critical variables and their effects on the optical transparency and swelling of gatifloxacin-Pluronic-loaded contact lens.

The optical and swelling properties of gatifloxacin-loaded contact lens decrease owing to the precipitation of gatifloxacin (on hydration) in the matrix structure of the contact lens. This paper focuses on the use of Pluronic F68 both inside and outside (in the packaging solution) the contact lens to form micelles to dissolve the gatifloxacin precipitates and not limited to sustain the release of gatifloxacin. The aim of this study was to screen the critical variables affecting the optical and swelling properties of gatifloxacin-loaded contact lens. The independent variables investigated were the concentration of Pluronic F68 incorporated in the monomer solution to fabricate the lens (X1, %w/v), the concentration of Pluronic F68 in the packaging solution (X2, %w/v), the concentration of gatifloxacin incorporated in the monomer solution (X3, %w/v), the concentration of gatifloxacin incorporated in the packaging solution during autoclave (X4, %w/v), the concentration of gatifloxacin incorporated in the packaging solution during extraction (X5, %w/v), the time (stabilization time) after the addition of gatifloxacin and Pluronic F68 to the monomer solution before the fabrication of the lens (X6, h), the pH of the packaging solution (X7), the temperature of the extracted solution (X8, °C), and the curing time for fabricating the contact lens (X9, min). The gatifloxacin-loaded contact lenses were characterized for their optical transmittances after sterilization on day 1 (Y1, %), optical transmittances after 7 days of sterilization (Y2, %) and swelling percentages after 7 days of sterilization (Y3, %). The selected variables showed responses that were in the ranges 53.5% to 97.2%, 51.3% to 92.6%, and 50.3% to 83.7% for Y1, Y2, and Y3, respectively. The data suggest that the presence of Pluronic F68 inside the contact lens (X1) reduced the optical and swelling properties of the contact lens, whereas the presence of Pluronic F68 in the packaging solution (X2) improved them through micelle formation. The other variables (X3 to X9) did not exhibit significant effects on the swelling and transmittance. This study revealed the potential of Plackett-Burman design to screen the selected critical variables that affected the optical and swelling properties of gatifloxacin-loaded contact lens.

Inflammatory cytokine removal by an activated carbon device in a flowing system.

A prototype in-line filtration/adsorption device has been developed using novel synthetic pyrolysed carbon monoliths with controlled mesoporous domains of 2-50nm. Porosity was characterized by SEM and porosimetry. Removal of inflammatory cytokines TNF, IL-6, IL-1beta and IL-8 was assessed by filtering cytokine spiked human plasma through the walls of the carbon modules under pressure. The effect of carbon filtration on plasma clotting response and total plasma protein concentration was also assessed. Significant removal of the cytokines IL-6, IL-1beta and IL-8 was observed. Initially marked TNF removal diminished over time. The coagulation studies indicated that the carbon device does not exacerbate the propensity of blood plasma to clot. The total plasma protein concentration remained constant. The device offers a broader approach to the treatment of systemic inflammatory response syndrome (SIRS) by the removal of inflammatory mediators central to its progression.

Polymeric hydrogels for novel contact lens-based ophthalmic drug delivery systems: a review.

Only about 5% of drugs administrated by eye drops are bioavailable, and currently eye drops account for more than 90% of all ophthalmic formulations. The bioavailability of ophthalmic drugs can be improved by a soft contact lens-based ophthalmic drug delivery system. Several polymeric hydrogels have been investigated for soft contact lens-based ophthalmic drug delivery systems: (i) polymeric hydrogels for conventional contact lens to absorb and release ophthalmic drugs; (ii) polymeric hydrogels for piggyback contact lens combining with a drug plate or drug solution; (iii) surface-modified polymeric hydrogels to immobilize drugs on the surface of contact lenses; (iv) polymeric hydrogels for inclusion of drugs in a colloidal structure dispersed in the lens; (v) ion ligand-containing polymeric hydrogels; (vi) molecularly imprinted polymeric hydrogels which provide the contact lens with a high affinity and selectivity for a given drug. Polymeric hydrogels for these contact lens-based ophthalmic drug delivery systems, their advantages and drawbacks are critically analyzed in this review.

Amine-Functionalized Electrically Conductive Core-Sheath MEH-PPV:PCL Electrospun Nanofibers for Enhanced Cell-Biomaterial Interactions.

In the present study, a conducting polymer, poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) along with a biodegradable polymer poly(ε-caprolactone) (PCL) was used to prepare an electrically conductive, biocompatible, bioactive, and biodegradable nanofibrous scaffold for possible use in neural tissue engineering applications. Core-sheath electrospun nanofibers of PCL as the core and MEH-PPV as the sheath, were surface-functionalized with (3-aminopropyl) triethoxysilane (APTES) and 1,6-hexanediamine to obtain amine-functionalized surface to facilitate cell-biomaterial interactions with the aim of replacing the costly biomolecules such as collagen, fibronectin, laminin, and arginyl-glycyl-aspartic acid (RGD) peptide for surface modification. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed the formation of core-sheath morphology of the electrospun nanofibers, whereas Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) revealed successful incorporation of amine functionality after surface functionalization. Adhesion, spreading, and proliferation of 3T3 fibroblasts were enhanced on the surface-functionalized electrospun meshes, whereas the neuronal model rat pheochromocytoma 12 (PC12) cells also adhered and differentiated into sympathetic neurons on these meshes. Under a constant electric field of 500 mV for 2 h/day for 3 consecutive days, the PC12 cells displayed remarkable improvement in the neurite formation and outgrowth on the surface-functionalized meshes that was comparable to those on the collagen-coated meshes under no electrical signal. Electrical stimulation studies further demonstrated that electrically stimulated PC12 cells cultured on collagen I coated meshes yielded more and longer neurites than those of the unstimulated cells on the same scaffolds. The enhanced neurite growth and differentiation suggest the potential use of these scaffolds for neural tissue engineering applications.

Electrically conductive MEH-PPV:PCL electrospun nanofibres for electrical stimulation of rat PC12 pheochromocytoma cells.

The purpose of this study was to prepare an electrically conducting poly[2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) based nanofibrous scaffold and to investigate the synergetic effect of nanofibre structure and electrical stimulation on neuronal growth for possible use in nerve repair. Nanofibres were produced by electrospinning of blended MEH-PPV with polycaprolactone (PCL) at a ratio of 20 : 80, 40 : 60, 50 : 50 and 60 : 40 (v/v). A better electrical conductivity was achieved by using core-sheath structured nanofibres of PCL (core) and MEH-PPV (sheath) produced using the coaxial electrospinning technique. The highest electrical conductivity was observed in the core-sheath nanofibres, while it increased with increasing concentration of MEH-PPV for the blended electrospun nanofibres. The biocompatibility of the electrospun nanofibres was confirmed by MTS and live-dead staining assays using 3T3 fibroblasts and a neuronal rat pheochromocytoma (PC12) cell line. Beta (III) tubulin immunochemistry showed that PC12 cells differentiated into sympathetic neurons on these porous and stiffer electrospun nanofibres coated with collagen I. Improved cell morphology and attachment on the collagen I coated electrospun meshes has been confirmed by SEM analysis. Significant enhancement in neurite formation and neurite outgrowth of PC12 cells on the conductive scaffolds under electrical potential of 500 mV cm-1 for 2 h day-1 suggests the potential use of these scaffolds for nerve repair.

Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.

Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established. In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device. We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood. In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model. This work provides proof-of-concept evidence to support the development of such alternative detoxification platforms.

MXene Sorbents for Removal of Urea from Dialysate: A Step toward the Wearable Artificial Kidney.

The wearable artificial kidney can deliver continuous ambulatory dialysis for more than 3 million patients with end-stage renal disease. However, the efficient removal of urea is a key challenge in miniaturizing the device and making it light and small enough for practical use. Here, we show that two-dimensional titanium carbide (MXene) with the composition of Ti3C2T x, where T x represents surface termination groups such as -OH, -O-, and -F, can adsorb urea, reaching 99% removal efficiency from aqueous solution and 94% from dialysate at the initial urea concentration of 30 mg/dL, with the maximum urea adsorption capacity of 10.4 mg/g at room temperature. When tested at 37 °C, we achieved a 2-fold increase in urea removal efficiency from dialysate, with the maximum urea adsorption capacity of 21.7 mg/g. Ti3C2T x showed good hemocompatibility; it did not induce cell apoptosis or reduce the metabolizing cell fraction, indicating no impact on cell viability at concentrations of up to 200 µg/mL. The biocompatibility of Ti3C2T x and its selectivity for urea adsorption from dialysate open a new opportunity in designing a miniaturized dialysate regeneration system for a wearable artificial kidney.