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Reduced Tonicity Stimulates an Inflammatory Response in Nucleus Pulposus Tissue That Can Be Limited by a COX-2-Specific Inhibitor
In intervertebral disc herniation with nucleus pulposus (NP) extrusion, the elicited inflammatory response is considered a key pain mechanism. However, inflammatory cytokines are reported in extruded herniated tissue, even before monocyte infiltration, suggesting that the tissue itself initiates the inflammation. Since herniated tissue swells, we investigated whether this simple mechanobiological stimulus alone could provoke an inflammatory response that could cause pain. Furthermore, we investigated whether sustained-release cyclooxygenase-2 (COX2) inhibitor would be beneficial in such conditions. Healthy bovine NP explants were allowed to swell freely or confined. The swelling explants were treated with Celecoxib, applied either as a bolus or in sustained-release. Swelling explants produced elevated levels of interleukin-6 (IL-6) and prostaglandin E2 (PGE2) for 28 days, while confined explants did not. Both a high concentration bolus and 10 times lower concentration in sustained release completely inhibited PGE2 production, but did not affect IL-6 production. Swelling of NP tissue, without the inflammatory system response, can trigger cytokine production and Celecoxib, even in bolus form, may be useful for pain control in extruded disc herniation.
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[Abstract]
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Thermoreversible hydrogels as a drug release platform in degenerative disc disease: an in vitro study
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Reducing friction in low velocity sliding contacts involving skin equivalent silicone rubber
The effect of binding decamethyl-cyclopentasiloxane (silicone oil) to polymeric coating structures based on polyacrylic acid grafted with poly(ethylene glycol), Wacker 1100, Wacker 1650 or poly(dimethylsiloxane) is discussed and compared with the tribological test results for the water or dodecane lubricated situation. Friction was measured at low velocity sliding for a flat-on-flat configuration. A specific silicone rubber is used as counter surface based on a FIFA test to measure skin / surface friction in quality assessments of artificial turf. The results show promising combinations for which friction was reduced with 92% compared to dry conditions.
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[Abstract]
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Temperature-induced hybrid hydrogels as a scaffold for nucleus pulposus replacement
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Enzymatically triggered release of dye model compounds from zeinparticles
tA responsive release system consisting of biocide encapsulated by the hydrophobic protein zein wasinvestigated, in which a biocide will be released if growth of micro-organisms occurs. Because biociderelease is difficult to detect, a model system using dyes with different size, polarity and charge wasdeveloped first to study the applicability of the zein matrix as an enzyme triggered responsive releasesystem. The responsive release efficiency was highest for dyes with a positive charge, that have limitedflexibility and the possibility of aromatic interactions with the matrix. The positively charged dyes showeda larger effect than negatively charged dyes. Additives were shown to enhance the release efficiency ofthe system. The most efficient release system combines the dye methyl violet with the additive oleic acid.These compounds interact to form a larger, more hydrophobic moiety. A plasticizing effect is thoughtalso to be important, since even without clear specific interactions between dye and additives, releaseproperties are enhanced. The charge of the additives seemed to be more important than their size, andboth hydrophobic and ionic interactions were shown to play a role.
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[Abstract]
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Novel protease-based diagnostic devices for detection of wound infection
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2013
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Author: |
Heinzle, A.
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Papen-Botterhuis, N.E.
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Schiffer, D.
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Schneider, K.P.
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Binder, B.
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Schintler, M.
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Haaksman, I.K.
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Lenting, H.B.
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Gübitz, G.M.
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Sigl, E.
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Keywords: |
Materials · High Tech Systems & Materials · Industrial Innovation · Fluid Mechanics Chemistry & Energetics · RMC - Responsive Materials & Coating · TS - Technical Sciences
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A gelatinase-based device for fast detection of wound infection was developed. Collective gelatinolytic activity in infected wounds was 23 times higher (p ≤ 0.001) than in noninfected wounds and blisters according to the clinical and microbiological description of the wounds. Enzyme activities of critical wounds showed 12-fold elevated enzyme activities compared with noninfected wounds and blisters. Upon incubation of gelatin-based devices with infected wound fluids, an incubation time of 30 minutes led to a clearly visible dye release. A 32-fold color increase was measured after 60 minutes. Both matrix metalloproteinases and elastases contributed to collective gelatinolytic enzyme activity as shown by zymography and inhibition experiments. The metalloproteinase inhibitor 1,10-phenanthroline (targeting matrix metalloproteinases) and the serine protease inhibitor phenylmethlysulfonyl fluoride (targeting human neutrophil elastase) inhibited gelatinolytic activity in infected wound fluid samples by 11-37% and 60-95%, respectively. Staphylococcus aureus and Pseudomonas aeruginosa, both known for gelatinase production, were isolated in infected wound samples. © 2013 by the Wound Healing Society.
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[Abstract]
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Microencapsulation of salts for enhanced thermochemical storage materials
Thermochemical storage is a new and emerging long-term thermal storage for residential use (cooling, heating & domestic hot water generation), offering high thermal storage density without the need for thermal insulation during storage (Fig. 1). However, existing materials for thermochemical storage either suffer from practical issues like limited physical and mechanical stability and severe corrosivity (salt hydrates), or thermal storage capacities that are too low to substantially cover seasonal storage adequately (zeolites and silicagel. To overcome the corrosion and stability problems with salt hydrate thermochemical materials and to make them more suitable for use in thermochemical reactor systems, microencapsulation is proposed. A suitable encapsulation material was assessed, having an open structure for good vapor transport, being capable of high loading fraction and therefore still a high storage density, and being flexible, stable and cheap. Initial experiments yield promising results on this material exhibiting high storage capacity, good reversibility and ease of use. Surprisingly, lower dehydration temperatures as compared to the non-encapsulated material were found, enabling the use of other salt hydrates with higher dehydration temperatures.
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[Abstract]
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Novel encapsulation technology for the preparation of core-shell microparticles
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2010
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Author: |
Cate, A.T. ten
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Pieterse, G.
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Eversdijk, J.
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Brouwers, L.A.
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Craenmehr, E.G.
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Ee, R.J. van
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Rijfers, A.
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Papen-Botterhuis, N.E.
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Houben, R.J.
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Bommel, K.J.C. van
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Keywords: |
Electronics · article · methodology · microcapsule · pharmaceutics · Capsules · Technology, Pharmaceutical · Fluid Mechanics Chemistry & Energetics · RMC - Responsive Materials & Coating · TS - Technical Sciences
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Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model
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2015
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Author: |
Willems, N.
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Yang, H.Y.
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Langelaan, M.L.P.
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Tellegen, A.R.
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Grinwis, G.C.M.
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Kranenburg, H.J.C.
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Riemers, F.M.
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Plomp, S.G.M.
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Craenmehr, E.G.M.
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Dhert, W.J.A.
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Papen-Botterhuis, N.E.
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Meij, B.P.
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Creemers, L.B.
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Tryfonidou, M.A.
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Keywords: |
Health · Celecoxib · CXB · Magnesium ferrite layered double hydroxide · Poly N isopropylacrylamide · prostaglandin E2 · Biocompatibility · Hydrogel · Intervertebral disk degeneration · IVD · Intradiscal controlled delivery · Healthy Living · Nano Technology · MAS - Materials Solutions · TS - Technical Sciences
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Introduction: Chronic low back pain due to intervertebral disc (IVD) degeneration is associated with increased levels of inflammatory mediators. Current medical treatment consists of oral anti-inflammatory drugs to alleviate pain. In this study, the efficacy and safety of a novel thermoreversible poly-N-isopropylacrylamide MgFe-layered double hydroxide (pNIPAAM MgFe-LDH) hydrogel was evaluated for intradiscal controlled delivery of the selective cyclooxygenase (COX) 2 inhibitor and anti-inflammatory drug celecoxib (CXB). Methods: Degradation, release behavior, and the ability of a CXB-loaded pNIPAAM MgFe-LDH hydrogel to suppress prostaglandin E2 (PGE2) levels in a controlled manner in the presence of a proinflammatory stimulus (TNF-aα) were evaluated in vitro. Biocompatibility was evaluated histologically after subcutaneous injection in mice. Safety of intradiscal application of the loaded and unloaded hydrogels was studied in a canine model of spontaneous mild IVD degeneration by histological, biomolecular, and biochemical evaluation. After the hydrogel was shown to be biocompatible and safe, an in vivo dose-response study was performed in order to determine safety and efficacy of the pNIPAAM MgFe-LDH hydrogel for intradiscal controlled delivery of CXB. Results: CXB release correlated to hydrogel degradation in vitro. Furthermore, controlled release from CXB-loaded hydrogels was demonstrated to suppress PGE2 levels in the presence of TNF-aα. The hydrogel was shown to exhibit a good biocompatibility upon subcutaneous injection in mice. Upon intradiscal injection in a canine model, the hydrogel exhibited excellent biocompatibility based on histological evaluation of the treated IVDs. Gene expression and biochemical analyses supported the finding that no substantial negative effects of the hydrogel were observed. Safety of application was further confirmed by the absence of clinical symptoms, IVD herniation or progression of degeneration. Controlled release of CXB resulted in a nonsignificant maximal inhibition (approximately 35 %) of PGE2 levels in the mildly degenerated canine IVDs. Conclusions: In conclusion, this study showed biocompatibility and safe intradiscal application of an MgFe LDH-pNIPAAM hydrogel. Controlled release of CXB resulted in only limited inhibition of PGE2 in this model with mild IVD degeneration, and further studies should concentrate on application of controlled release from this type of hydrogel in animal models with more severe IVD degeneration. cop. 2015 Willems et al.
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[Abstract]
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A novel injectable thermoresponsive and cytocompatible gel of poly(N-isopropylacrylamide) with layered double hydroxides facilitates siRNA delivery into chondrocytes in 3D culture
article |
2015
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Author: |
Yang, H.Y.
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Ee, R.J. van
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Timmer, K.
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Craenmehr, E.G.M.
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Huang, J.H.
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Öner, C.
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Dhert, W.J.A.
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Kragten, A.H.M.
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Willems, N.
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Grinwis, G.C.M.
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Tryfonidou, M.A.
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Papen-Botterhuis, N.E.
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Creemers, L.B.
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Keywords: |
Materials Health · Injectable hydrogel · siRNA delivery · Poly(N-isopropylacrylamide) · Layered double hydroxides · Chondrocytes · Healthy Living · Nano Technology · MAS - Materials Solutions · TS - Technical Sciences
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Hybrid hydrogels composed of poly(N-isopropylacrylamide) (pNIPAAM) and layered double hydroxides (LDHs) are presented in this study as novel injectable and thermoresponsive materials for siRNA delivery, which could specifically target several negative regulators of tissue homeostasis in cartilaginous tissues. Effectiveness of siRNA transfection using pNIPAAM formulated with either MgAl–LDH or MgFe–LDH platelets was investigated using osteoarthritic chondrocytes. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an endogenous model gene to evaluate the extent of silencing. No significant adverse effects of pNIPAAM/LDH hydrogels on cell viability were noticed. Cellular uptake of fluorescently labeled siRNA was greatly enhanced (>75%) in pNIPAAM/LDH hydrogel constructs compared to alginate, hyaluronan and fibrin gels, and was absent in pNIPAAM hydrogel without LDH platelets. When using siRNA against GAPDH, 82–98% reduction of gene expression was found in both types of pNIPAAM/LDH hydrogel constructs after 6 days of culturing. In the pNIPAAM/MgAl–LDH hybrid hydrogel, 80–95% of GAPDH enzyme activity was reduced in parallel with gene. Our findings show that the combination of a cytocompatible hydrogel and therapeutic RNA oligonucleotides is feasible. Thus it might hold promise in treating degeneration of cartilaginous tissues by providing supporting scaffolds for cells and interference with locally produced degenerative factors.
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[Abstract]
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