Surface engineering of porous silicon to optimise therapeutic antibody loading and release

Open Access Article. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.The proinflammatory cytokine, tumor necrosis factor-α (TNF-α), is elevated in several diseases such as uveitis, rheumatoid arthritis and non-healing chronic wounds. Adding Infliximab, a chimeric IgG1 monoclonal antibody raised against TNF-α, to chronic wound fluid can neutralise human TNF-α, thereby providing a potential therapeutic option for chronic wound healing. However, to avoid the need for repeated application in a clinical setting, and to protect the therapeutic antibody from the hostile environment of the wound, suitable delivery vehicles are required. Porous silicon (pSi) is a biodegradable high surface area material commonly employed for drug delivery applications. In this study, the use of pSi microparticles (pSi MPs) for the controlled release of Infliximab to disease environments, such as chronic wounds, is demonstrated. Surface chemistry and pore parameters for Infliximab loading are first optimised in pSi films and loading conditions are transferred to pSi MPs. Loading regimens exceeding 60 μg of Infliximab per mg of pSi are achieved. Infliximab is released with zero-order release kinetics over the course of 8 days. Critically, the released antibody remains functional and is able to sequester TNF-α over a weeklong timeframe; suitable for a clinical application in chronic wound therapy

Study of the Structure of Hyperbranched Polyglycerol Coatings and Their Antibiofouling and Antithrombotic Applications

While blood‐contacting materials are widely deployed in medicine in vascular stents, catheters, and cannulas, devices fail in situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials can provide significant benefits for patients in terms of safety and patency as well as substantial cost savings. Herein, a novel but simple strategy is described for coating a range of medical materials, that can be applied to objects of complex geometry, involving plasma‐grafting of an ultrathin hyperbranched polyglycerol coating (HPG). Plasma activation creates highly reactive surface oxygen moieties that readily react with glycidol. Irrespective of the substrate, coatings are uniform and pinhole free, comprising O─C─O repeats, with HPG chains packing in a fashion that holds reversibly binding proteins at the coating surface. In vitro assays with planar test samples show that HPG prevents platelet adhesion and activation, as well as reducing (>3 log) bacterial attachment and preventing biofilm formation. Ex vivo and preclinical studies show that HPG‐coated nitinol stents do not elicit thrombosis or restenosis, nor complement or neutrophil activation. Subcutaneous implantation of HPG coated disks under the skin of mice shows no evidence of toxicity nor inflammation

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Protein patterning on microplasma-activated PEO-like coatings

This paper reports a method for producing protein arrays on antifouling PEO-like coatings using a “non-contact” atmospheric pressure helium microplasma array. ToF-SIMS characterization of PEO-like coatings after short plasma treatment revealed the antifouling plasma polymer was largely modified/removed within the microplasma-exposed regions. Incubation of microplasma-patterned PEO-like coatings with a fluorescently labeled streptavidin resulted in selective and uniform protein adsorption within the modified regions. A protein sensing application was demonstrated where a target red fluorescent protein (RFP) was only captured on the anti-RFP functionalized regions. This indicates the adsorbed antibody protein on the microplasma-treated PEO-like regions retained its bioactivity.

Covalent Immobilization of Antibacterial Furanones via Photochemical Activation of Perfluorophenylazide

A tannin-degrading strain of Bacillus sp. AB1 was isolated from a garden soil by enrichment. This organism was able to utilize 1% (w/v) tannic acid-a gallotannin at 30°C and pH below 4.5 in a defined mineral medium where the acid was the sole source of carbon and energy under 96 h. Growth resulted in increase in OD concomitant with gradual decrease in pH of the culture medium. Analysis of the culture fluid by paper chromatography revealed glucose and gallic acid as major metabolites of tannic acid degradative pathway. Mineralization of tannic acid was informed when none of the metabolites was recovered after 96 h of incubation. The degradation potential of this isolate could be exploited for the production of tannase, improvement of livestock production and also detoxification of tannery effluents at extreme acidic conditions

Engineering of high-performance potassium-ion capacitors using polyaniline-derived N-doped carbon nanotubes anode and laser scribed graphene oxide cathode

Potassium (K) ion storage technology is recently receiving a great attention due to their low-cost and enormous abundance on the earth compared to lithium. However, the technology is still at a scientific research stage and exploring suitable electrode materials is a key challenge. Herein, we have engineered nitrogen doped carbon nanotubes (N-CNTs) as a promising anode material for K-ion storage through pyrolytic decomposition of polyaniline nanotubes (PAni-NTs). These N-CNTs delivers high reversible capacity with good rate performance and cycling stability. Taking advantage of these features, a potassium-ion hybrid capacitor (KIHC) is constructed using N-CNTs as battery-type anode and 3-dimensional (3D) laser scribed graphene (LSG) as capacitor-type cathode electrodes. The device displays a high energy density of 65 W h/kg, a high power output of 1000 W/kg, as well as a long cycling life (91% capacity retention over 5000 cycles). Thus, such an advanced energy storage system can satisfy the requirements of high power and high energy densities simultaneously in diverse applications at low-cost.</p

Microplasma jet treatment of bovine serum albumin coatings for controlling enzyme and cell attachment

We investigated a new approach to control protein and cell attachment inside 96-well polystyrene plates. The wells were first coated with bovine serum albumin (BSA) to inhibit cell and protein attachment. The BSA-coated wells were then treated with a helium microplasma jet for increasing times that resulted in gradual removal of BSA from the surface. It was found that the amount of enzyme and cell attachment could be controlled in the wells where BSA was only partially removed by the microplasma jet. In addition to the surface coverage of BSA, the new surface chemistry induced by the microplasma jet treatment also had an important role in the control of enzyme and cell attachment. In summary, microplasma jet treatment of BSA-coated polystyrene wells is a simple and effective method for controlling enzyme and cell attachment. This might find use for high-throughput screening of new cell culture platforms where control over the level protein, enzyme or cell adherence is needed in order to maintain a specific cell function

Microplasma Array Patterning of Reactive Oxygen and Nitrogen Species onto Polystyrene

We investigate an approach for the patterning of reactive oxygen and nitrogen species (RONS) onto polystyrene using atmospheric-pressure microplasma arrays. The spectrally integrated and time-resolved optical emission from the array is characterized with respect to the applied voltage, applied-voltage frequency and pressure; and the array is used to achieve spatially resolved modification of polystyrene at three pressures: 500, 760, and 1000 Torr. As determined by time-of-flight secondary ion mass spectrometry (ToF-SIMS), regions over which surface modification occurs are clearly restricted to areas that are exposed to individual microplasma cavities. Analysis of the negative-ion ToF-SIMS mass spectra from the center of the modified microspots shows that the level of oxidation is dependent on the operating pressure, and closely correlated with the spatial distribution of the optical emission. The functional groups that are generated by the microplasma array on the polystyrene surface are shown to readily participate in an oxidative reaction in phosphate buffered saline solution (pH 7.4). Patterns of oxidized and chemically reactive functionalities could potentially be applied to the future development of biomaterial surfaces, where spatial control over biomolecule or cell function is needed

Microplasma patterning of bonded microchannels using high-precision "injected" electrodes

A rapid, high-precision method for localised plasma-treatment of bonded PDMS microchannels is demonstrated. Patterned electrodes were prepared by injection of molten gallium into preformed microchannel guides. The electrode guides were prepared without any additional fabrication steps compared to conventional microchannel fabrication. Alignment of the "injected" electrodes is precisely controlled by the photomask design, rather than positioning accuracy of alignment tools. Surface modification is detected using a fluorescent dye (Rhodamine B), revealing a well-defined micropattern with regions less than 100 mu m along the length of the microchannel

On the Effect of Monomer Chemistry on Growth Mechanisms of Nonfouling PEG-like Plasma Polymers

It has been shown that both ions and neutral species may contribute to plasma polymer growth. However, the relative contribution from these mechanisms remains unclear. We present data elucidating the importance of considering monomer structure with respect to which the growth mechanism dominates for nonfouling PEG-like plasma polymers. The deposition rate for saturated monomers is directly linked with ion flux to the substrate. For unsaturated monomers, the neutral flux also plays a role, particularly at low power. Increased fragmentation of the monomer at high power reduces the ability of unsaturated monomers to grow via neutral grafting. Chemical characterization by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) confirm the role that plasma phase fragmentation plays in determining the deposition rate and surface chemistry of the deposited film. The simple experimental method used here may also be used to determine which mechanisms dominate plasma deposition for other monomers. This knowledge may enable significant improvement in future reactor design and process control