Biomineralized interpenetrating network hydrogels for bone tissue engineering

Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but their use is limited by inadequate mechanical strength and poor biocompatibility. In this study, to better mimic the mineral component and the mechanical strength of natural bone, two biocompatible materials, 2-hydroxyethyl agarose and poly(ethylene glycol) diacrylate, were combined with nanocrystalline hydroxyapatite (nHAp)-coated poly(lactic-co-glycolic acid) (PLGA) microspheres. A novel composite interpenetrating network (IPN) hydrogel scaffold was created to investigate its mechanical and osteoconductive performance for bone tissue engineering-related applications. The inclusion of nHAp-coated PLGA microspheres in an IPN hydrogel led to an increase in compressive modulus. In the absence of nHAp-coated microspheres, cell viability dropped to 59·1% at 3 weeks post-encapsulation. However, by incorporating nHAp-coated microspheres, cell viability improved to 80·6%. The capacity of composite IPN hydrogels to promote bone formation in cell culture was assessed. In the presence of mineralised microspheres, a composite IPN gel showed a significant increase in alkaline phosphatase activity and calcium (Ca) deposition following 3 weeks of incubation when compared with plain IPNs. This technology may be also applied to other cell-based applications where the improved mechanical integrity and osteoconductivity of cell-containing IPN hydrogels may be used to mimic bone tissue replacement. </jats:p

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

Rapid Adsorption of Proinflammatory Cytokines by Graphene Nanoplatelets and their Composites for Extracorporeal Detoxification

Sepsis is a complex clinical syndrome that features excessive release of cytokines and other inflammatory mediators that could lead to organ dysfunction. Despite different treatment and management options, sepsis associated high morbidity and mortality rates remain. This has prompted intensive research into alternative therapeutic approaches such as targeted removal of sepsis related molecules using extracorporeal hemoperfusion. In this study, we explore the use of graphene nanoplatelets (GNP) as low-cost alternative hemosorbents for rapid removal of a broad spectrum of proinflammatory cytokine markers. Firstly, the physical characteristics, cytotoxicity, and cytokine marker adsorption profile of GNP were assessed. The results not only confirmed the surface characteristics of GNP and their ability to rapidly remove cytokine markers, but also indicated a low cytotoxicity towards the hepatic cell line HepG2. GNP were then incorporated into a freestanding flexible GNP-poly(tetrafluoroethylene) film with preserved surface characteristics and cytokine adsorption profile for potential use in hemoperfusion applications

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

A perspective on the applications of energy-cyber-physical systems (e-CPSs) in ultra-low emission coal-fired power plants

To address the issue of air pollution in coal-fired power plants in China, the ultra-low emission (ULE) technology was proposed to control SO2, NOx and particulates, and ULE air pollution control devices have been quickly applied across the country. Although the ULE devices could work effectively for simultaneous removal of multi-pollutant, there is a great potential to efficiently control the emissions and to reduce the energy consumption by application of the energy-cyber-physical systems (e-CPSs). In order to explore the possibilities, the general conceptual overview of cyber-physical systems was first introduced, and then the feasible application in ultra-low emission coal-fired power plants were elaborated, along with an overview of major building blocks of such CPSs, including hardware components, devices for ultra-low emission air pollution control, industrial cloud, industrial software, and accompanying security systems. The perspective and benefits of application of e-CPSs in ultra-low emission coal-fired power plants were discussed, as a new modern approach for achieving more effective, efficient and reliable ULE air pollution control devices and the processes

Rapid Adsorption of Proinflammatory Cytokines by Graphene Nanoplatelets and Their Composites for Extracorporeal Detoxification

Sepsis is a complex clinical syndrome that features excessive release of cytokines and other inflammatory mediators that could lead to organ dysfunction. Despite different treatment and management options, sepsis associated high morbidity and mortality rates remain. This has prompted intensive research into alternative therapeutic approaches such as targeted removal of sepsis related molecules using extracorporeal hemoperfusion. In this study, we explore the use of graphene nanoplatelets (GNP) as low-cost alternative hemosorbents for rapid removal of a broad spectrum of proinflammatory cytokine markers. Firstly, the physical characteristics, cytotoxicity, and cytokine marker adsorption profile of GNP were assessed. The results not only confirmed the surface characteristics of GNP and their ability to rapidly remove cytokine markers, but also indicated a low cytotoxicity towards the hepatic cell line HepG2. GNP were then incorporated into a freestanding flexible GNP-poly(tetrafluoroethylene) film with preserved surface characteristics and cytokine adsorption profile for potential use in hemoperfusion applications

A haemocompatible and scalable nanoporous adsorbent monolith synthesised using a novel lignin binder route to augment the adsorption of poorly removed uraemic toxins in haemodialysis

Nanoporous adsorbents are promising materials to augment the efficacy of haemodialysis for the treatment of end stage renal disease where mortality rates remain unacceptably high despite improvements in membrane technology. Complications are linked in part to inefficient removal of protein bound and high molecular weight uremic toxins including key marker molecules albumin bound indoxyl sulphate (IS) and p-cresyl sulphate (PCS) and large inflammatory cytokines such as IL-6. The following study describes the assessment of a nanoporous activated carbon monolith produced using a novel binder synthesis route for scale up as an in line device to augment haemodialysis through adsorption of these toxins. Small and large monoliths were synthesised using an optimised ratio of lignin binder to porous resin of 1 in 4. Small monoliths showing combined significant IS, p-CS and IL-6 adsorption were used to measure haemocompatibility in an ex vivo healthy donor blood perfusion model, assessing coagulation, platelet, granulocyte, t cell and complement activation, haemolysis, adsorption of electrolytes and plasma proteins. The small monoliths were tested in a niave rat model and showed stable blood gas values, blood pressure, blood biochemistry and the absence of coagulopathies. These monoliths were scaled up to a clinically relevant size and were able to maintain adsorption of protein bound uremic toxins IS, PCS and high molecular weight cytokines TNF and IL-6 over 60 minutes using a flow rate of 300 mL/min without platelet activation. The nanoporous monoliths where haemocompatible and retained adsorptive efficacy on scale up with negligible pressure drop across the system indicating potential for use as an in-line device to improve haemodialysis efficacy by adsorption of otherwise poorly removed uraemic toxins

Determination of reference intervals of serum levels of human epididymis protein 4 (HE4) in Chinese women

The detailed numbers of subjects from different centers. (DOCX 17.3 kb