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1.	Freij-Larsson, Christina, et al. (author) Adsorption behaviour of amphiphilic polymers at hydrophobic surfaces: Effects on protein adsorption 1996 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 17:22, s. 2199-2207 Journal article (peer-reviewed)abstract The adsorption of four different amphiphilic polymers to a model surface has been studied, and the effects of the adsorbed amphiphiles on the subsequent adsorption of fibrinogen (Fg) and human serum albumin (HSA) at the surfaces were investigated. The amphiphilic polymers were one commercially available ABA block copolymer, Pluronic PE9400 (PE94), composed of poly(ethylene oxide) (A-blocks) and poly(propylene oxide) (B-block), and three graft copolymers, two with backbones of poly(styrene-co-acrylamide) (STY) and one with a backbone of poly(methyl methacrylate-co-ethylhexyl methacrylate) (ACRY). The backbones carried poly(ethylene oxide) (PEG) grafts, The model surface was a hydrophobic methylated silica surface (HMS). The amphiphilic polymers were adsorbed at the HMS surface from an ethanol/water solution. The adsorption process was monitored by ellipsometry. After rinsing with phosphate buffered saline (PBS), protein was added and the continued adsorption measured by ellipsometry. Surfaces modified by adsorption of the amphiphilic polymers were also characterized by contact angle measurements and X-ray photoelectron spectroscopy (XPS). According to these measurements the amphiphilic polymers adsorbed in significant amounts at the HMS surface. A limited study by atomic force microscopy (AFM), as well as the XPS measurements, suggests that both single molecules and micellar aggregates adsorb at the surface. ACRY and PE94 gave the highest levels of adsorption. As compared to the Pluronic block copolymer the graft copolymers were more strongly attached to the HMS surface, as shown by less desorption on rinsing with solvent. The ellipsometric results show that the adsorption of HSA and Fg at HMS surfaces containing preadsorbed amphiphilic polymer was significantly reduced as compared to the bare HMS surface. ACRY and PE94 showed the largest effects. Both polymers gave more than a 20-fold reduction of the Fg adsorption and a 10-fold reduction of the HSA adsorption. The STY polymers reduced the protein adsorption by a factor of 2-3.
2.	Gabriel, B. L., et al. (author) Site-specific adhesion of Staphylococcus epidermidis (RP12) in Ti-Al-V metal systems 1994 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 15:8, s. 628-634 Journal article (peer-reviewed)abstract Staphylococcus epidermidis (RP12) adhesion patterns were studied on the following titanium (Ti)-aluminium (Al)-vanadium (V) metal systems: (i) microfabricated samples consisting of Ti, Al and V islands deposited onto Ti or V substrata, (ii) pure Ti, Al and V metals, and (iii) medical grade Ti6Al4-V alloy. All of these surfaces were covered with their respective oxides formed upon exposure of the metals to air. Quantitative analysis of the number of cells bound per unit area indicates that S. epidermidis (RP12) exhibits greatest adhesion to pure V surfaces. When exposed to surfaces having controlled spatial variations in chemical composition on the 10 mu m scale (microfabricated samples), the bacteria preferentially populate V islands versus Ti or Al substrata. In the case of the biphasic Ti6Al4V alloy, the bacteria tend to adhere to V-rich, mixed phase regions and phase boundaries. These findings demonstrate that enhanced and preferential adhesion of S. epidermidis (RP12) occurs on V surfaces in TI-Al-V metal systems and suggest that bacterial interactions are influenced by surface oxide composition.
3.	Wesslén, Bengt, et al. (author) Protein adsorption of poly(ether urethane) surfaces modified by amphiphilic and hydrophilic polymers 1994 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 15:4, s. 278-284 Journal article (peer-reviewed)abstract A commercial biomedical poly(ether urethane), Pellethane 2363-80AE, was surface modified through the use of amphiphilic polymeric additives, and through surface grafting with poly(ethylene glycol), PEG. Two different amphiphilic polymers, Polymer C and Pluronic PE9400, were used as additives. Polymer C, a segmented polyurethane, was prepared from PEG1500, 4,4'-diphenylmethane diisocyanate and a C-16-C18 monoglyceride chain extender. Pluronic PE9400 is a propylene oxide-ethylene oxide tri-block co-polymer obtained from BASF. Adsorption of human albumin and fibrinogen to the modified surfaces was studied by means of radiolabelled proteins. By contact angle measurements and X-ray photoelectron spectra the amphiphilic polymers were shown to accumulate at the polyurethane surfaces. Adsorption of fibrinogen, in particular, was significantly reduced by the amphiphilic additives to levels similar to those obtained for Pellethane surfaces grafted with PEG 20000. In vitro clotting times for citrate-buffered blood in contact with the amphiphilic surfaces increased as compared with the unmodified ones.
4.	Zhang, Y Z, et al. (author) Tissue response to commercial silicone and polyurethane elastomers after different sterilization procedures 1996 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 17:23, s. 2265-2272 Journal article (peer-reviewed)abstract Two different commercial polymeric materials, a silicone and a polyurethane (PUR), were studied with regard to correlations between the chemical and physical compositions of the polymer surfaces and the biological response on implantation. Test specimens of the materials were manufactured according to standard procedures. The specimens were implanted in rats for 10 and 90 days. Before implantation the polymers were sterilized in three different ways, namely, beta irradiation, ethylene oxide sterilization and steam sterilization. The polymers were characterized before and after the implantation with respect to the chemical composition and the morphology of the surfaces. After implantation the biological response was evaluated by counting numbers of macrophages, giant cells, fibroblasts and other cells present at the surfaces. The thickness of the fibrous capsule surrounding the test specimens was measured at the thickest and thinnest parts. PUR surfaces showed signs of degradation already after sterilization and after 10 to 90 days of implantation, pits and cracks appeared, especially in the ethylene oxide sterilized samples. However, differences in the biological responses were small and independent of the sterilization method. After 10 days of implantation the capsule thickness and the amounts of cell material adhering at the surfaces were different, and it appears that the silicone rubber induces more tissue response than PUR. The differences in the early tissue response evened out after 90 days implantation time and a steady state situation evolved, which was similar for the silicone and the polyurethane.
5.	Benesch, Johan, et al. (author) Blood protein adsorption onto chitosan 2002 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 23:12, s. 2561-2568 Journal article (peer-reviewed)abstract Chitosan was recently indicated to enhance osteogenesis, improve wound healing but to activate the coagulation and the complement systems. In the present study approximately 10nm thick chitosan film were prepared on aminopropyltriethoxysilane (APTES) coated silicon. The surfaces were incubated in serum or plasma and subsequently in antibodies towards key complement and contact activation of coagulation proteins. The deposited amounts were compared with those on hydrophilic and hydrophobic silicon, APTES and IgG coated reference samples. Although large amounts of serum deposited to chitosan only a weak transient activation of the complement system and no activation of the intrinsic pathway was observed. Upon acetylation the chitosan layer became a strong activator of the alternative pathway of the complement. After incubation in human plasma anti-fibrinogen deposited onto chitosan but not onto the acetylated chitosan, a finding that may explain previous observations of procoagulant activity by chitosan. Copyright © 2002 Elsevier Science Ltd.
6.	Carlson, Johan, et al. (author) An ultrasonic pulse-echo technique for monitoring the setting of CaSO4-based bone cement 2003 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 24:1, s. 71-77 Journal article (peer-reviewed)abstract We present a new ultrasonic technique for monitoring the entire setting process of injectable bone cement. The problem with existing standards is their subjectivity. Because of this the results are not comparable between different research groups. A strong advantage with the proposed technique is that it is non-invasive and non-destructive, since no manipulation of the cement sample is needed once the measurement has started. Furthermore, the results are reproducible with small variations. The testing was performed on calcium sulfate cement using an ultrasonic pulse-echo approach. The results show that the acoustic properties of the cement are strongly correlated with the setting time, the density, and the adiabatic bulk modulus. The measured initial and final setting times agree well with the Gillmore needles standard. An important difference compared to the standards, is that the technique presented here allows the user to follow the entire setting process on-line.
7.	Downs, Mark E.A., et al. (author) Optical and electrochemical detection of DNA 1988 In: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 9:1, s. 66-70 Journal article (peer-reviewed)abstract There is a growing demand for the production of a DNA biosensor with applications in medicine, the food industry, agriculture, veterinary science and environmental science. In this paper we describe methods for the optical and electrochemical detection of DNA using the enzyme horseradish peroxidase (EC 1.11.1.7) and glucose oxidase (EC 1.1.3.4). We have used bis-methylacridinium nitrate and luminol for the optical detection of DNA using a purpose built, inexpensive luminometer. Using this system detection limits of 10−11g of plasmid DNA have been observed. Electrochemical detection of DNA was carried out by the use of a fluoride ion selective electrode and stripping voltametry. DNA was detected down to 1 (10−9 − 10−10g of DNA by the enzymatic release of halogen ions from organohalogen compounds.
8.	Edlund, Ulrica, et al. (author) Sterilization, storage stability and in vivo biocompatibility of poly(trimethylene carbonate)/poly(adipic anhydride) blends 2000 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 21:9, s. 945-955 Journal article (peer-reviewed)abstract Biodegradable blends of poly(trimethylene carbonate) (PTMC) and poly(adipic anhydride) (PAA) have been proven to be strong candidates for controlled drug delivery polymers in vitro. We now report on the stability, sterilizability and in vivo local tissue response of these matrices. Blend matrices were sterilized by beta-radiation or ethylene oxide gas treatment, stored at different times and temperatures, and analyzed for changes in physicochemical properties. Moisture uptake at different relative humidities and storage times was determined. Sterilization procedures induced hydrolysis of the matrices. Ethylene oxide gas sterilization had a significantly more marked effect upon the matrix properties than radiation treatment. The onset of degradation was reflected in a decrease of crystallinity and molecular weight along with a change of blend composition. A similar onset of matrix degradation was observed upon storage in air. The physicochemical properties of the blends were well preserved upon storage under argon atmosphere. Biocompatibility of PTMC/PAA implants was assessed in the anterior chamber of rabbits eyes for 1 month. At selected post-operative time points, aqueous humor was analyzed for white blood cells and the corneal thickness was measured. The results suggest good biocompatability of PTMC-rich matrices, whereas fast eroding PAA-rich matrices caused inflammatory responses, due to a burst release of degradation products.
9.	Eriksson, Cecilia, et al. (author) Interactions between human whole blood and modified TiO2-surfaces : Influence of surface topography and oxide thickness on leukocyte adhesion and activation 2001 In: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 22:14, s. 1987-1996 Journal article (peer-reviewed)abstract An in vitro model (Nygren et al., J Lab Clin Med 129 (1997) 35-46) was used to investigate interactions between leukocytes and four modified TiO2-surfaces. Surface topography was measured using scanning electron microscopy and optical profilometry while Auger electron spectroscopy was used to determine surface composition and oxide thickness. The surfaces were either smooth or rough with either thin or thick oxides. All surfaces consisted of TiO2 covered by a carbonaceous layer. The surfaces were incubated with capillary blood for time periods of between 8 min and 32h. Immunofluorescence techniques together with computer aided image analysis and chemiluminescence technique were used to detect cell adhesion, expression of adhesion receptors and the zymosan-stimulated respiratory burst response. Leukocyte adhesion to the surfaces increased during the first hours of blood-material contact and then decreased. Polymorphonuclear granulocytes were the dominating leukocytes on all surfaces followed by monocytes. Cells adhering to rough surfaces had higher normalized expression of adhesive receptors than cells on smooth surfaces. Maximum respiratory burst response occurred earlier on the smooth than on the rough surfaces. In conclusion, topography had a greater impact than oxide thickness on most cellular reactions investigated, but the latter often had a dampening effect on the responses. (C) 2001 Elsevier Science Ltd. All rights reserved.
10.	Goransson, A., et al. (author) Bone formation after 4 weeks around blood-plasma-modified titanium implants with varying surface topographies : An in vivo study 2003 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 24:2, s. 197-205 Journal article (peer-reviewed)abstract The aim of the present study was to investigate and compare the stability and bone ingrowth capacity to screw-shaped titanium implants with five different surface treatments. The implants were: (1) standard turned with a thin blood plasma coat (TP), (2) NaOH-etched dito with pore size 0.2-0.3µm (E), (3) NaOH-etched with pore size 0.2-0.3µm and a thin blood plasma coat (EP), (4) electrochemically oxidised with pore size 1-2µm (O), (5) electrochemically oxidised with pore size 1-2µm and a thin blood plasma coat (OP). A total of 66 implants were divided into the above-described five groups and inserted for 4 weeks into tibia and femur of 11 rabbits. The implants were evaluated by resonance frequency (RF) measurements at the time of insertion and removal, and analysed histomorphometrically at removal. The RF measurements showed that the implant stability was lower in soft bone compared to dense and increased with time. No significant differences were observed between the different surface modifications. The histomorphometric analysis revealed no statistically significant differences between the implants regarding bone-to-metal contact (BMC) and bone area inside the threads (BA). The above results indicate that thin blood plasma-coated and non-coated screw-shaped titanium implants with turned, NaOH-etched and electrochemically etched surface profiles integrate similarly to bone at 1 month of implantation. © 2002 Elsevier Science Ltd. All rights reserved.
11.	Jansson, E., et al. (author) Ex vivo PMA-induced respiratory burst and TNF-a secretion elicited from inflammatory cells on machined and porous blood plasma clot-coated titanium 2002 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 23:13, s. 2803-2815 Journal article (peer-reviewed)abstract The release of inflammatory mediators around implants and normal wounds may differ due to the presence of the solid surface. In this study, machined and sub-micron porous titanium implants with and without a 100nm thick blood plasma clot were inserted subcutaneously in rat for 3 or 24h. The cell recruitment to the interfaces, in vivo secretion of TNF-a and the ex vivo PMA-induced production of reactive oxygen species were subsequently investigated. The thin plasma clot coating gave rise to an increased ex vivo PMA-stimulated oxygen radical production by implant-associated cells at both implantation times, and an increased cell recruitment at 24h. The total TNF-a secretion was highest at sham sites and plasma clot-coated porous titanium at 24h. After 24h, the cell-type pattern in the exudate around the porous plasma-coated implant was more similar to that found at sham sites than that adjacent to the non-coated implants. No differences were observed between the machined Ti and the machined sub-micron porous Ti. © 2002 Elsevier Science Ltd. All rights reserved.
12.	Jansson, Eva, et al. (author) In vitro preparation and ellipsometric characterization of thin blood plasma clot films on silicon 2001 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 22:13, s. 1803-1808 Journal article (peer-reviewed)abstract The wound-healing process around implants differs from that of a normal healing without the inserted material. In this work, the composition of a natural wound surface was mimicked through clotting of a thin human blood plasma film with approximate ellipsometric thickness of 100nm onto differently pretreated silicon surfaces. Their stability was investigated by incubations in sodium dodecyl sulphate (SDS) solutions. The enzymatic clot degradation was induced through addition of human tissue plasminogen activator (t-PA) to the plasma and the surface protein remnants after the degradation were analyzed with polyclonal antibodies. The results show that the plasma films were not SDS resistant on hydrophilic silicon. However, stability was obtained after preparation on hydrophobic silicon or when albumin or fibrinogen was immobilized to silicon before the plasma incubations. Different surfaces bound different polyclonal antibodies after the clot film degradation. The methods indicate a simple means to improve or reestablish a normal tissue inflammatory response around biomaterials. Copyright © 2001 Elsevier Science Ltd.
13.	Karlsson, Marjam, et al. (author) Initial in vitro interaction of osteoblasts with nano-porous alumina 2003 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 24:18, s. 3039-3046 Journal article (peer-reviewed)abstract In the present study we have used a characterised primary human cell culture model to investigate cellular interactions with nano-porous alumina. This material, prepared by anodisation, is being developed as a coating on titanium alloy implants. The structure of the alumina, as determined by X-ray diffraction and transmission electron microscopy, was amorphous. When studying cell/material interactions we used both biochemical and morphological parameters. Cell viability, proliferation and phenotype were assessed by measurement of redox reactions in the cells, cellular DNA, tritiated thymidine ([H-3]-TdR) incorporation and alkaline phosphatase (ALP) production. Results showed a normal osteoblastic growth pattern with increasing cell numbers during the first 2 weeks. A peak in cell proliferation was seen on day 3, after which cell growth decreased, followed by an increase in ALP production, thus indicating that the osteoblastic phenotype was retained on the alumina. Cell adhesion was observed, the osteoblast-like cells having a flattened morphology with filipodia attached to the pores of the material. SDS-PAGE and western blot measurements showed that the nano-porous alumina was able to adsorb fibronectin. Trace amounts of aluminium ions were measured in the surrounding medium, but no adverse effect on cell activity was observed.
14.	Lindblad, Mia, et al. (author) Cell and soft tissue interactions with methyl- and hydroxyl-terminated alkane thiols on gold surfaces 1997 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 18:15, s. 1059-1068 Journal article (peer-reviewed)
15.	Nimeri, G, et al. (author) The influence of plasma proteins and platelets on oxygen radical production and F-actin distribution in neutrophils adhering to polymer surfaces 2002 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 23:8, s. 1785-1795 Journal article (peer-reviewed)abstract It is well known that blood cell interactions with artificial surfaces might have deleterious effects on host tissue, however, the mechanisms involved are far from understood. In this study, neutrophil-platelet interaction on uncoated or protein-coated polymer surfaces was investigated. Cell spreading, reorganization of actin filaments and release of oxygen metabolites (measured as luminol-amplified chemiluminescence) were used as criteria for cell activation on positively charged, hydrophilic 1,2-diaminocyclohexane, and negatively charged, hydrophobic hexamethylene-disiloxane. The model surfaces were made by radio frequency plasma discharge polymerization. Neutrophil contact with the uncoated polymers induced a prolonged generation of oxygen radicals. Precoating of the polymer surfaces with human serum albumin (HSA) or fibrinogen, markedly reduced neutrophil activation, whereas coating with human immunoglobulin G (IgG), a well-known opsonin, resulted in significantly higher levels of cell activation. Consequently, protein coating overruled the activating effects of the polymer surfaces. The presence of unstimulated or thrombin-stimulated platelets markedly increased the reactivity of neutrophils against fibrinogen- and IgG-coated surfaces. However, neutrophils remained relatively unreactive in the presence of platelets on HSA-treated surfaces. Comparison of the different types of surfaces used, reveals a correlation between the degree of cell spreading, reorganization of the actin cytoskeleton and the amount of oxygen radicals produced. Our results suggest that the acute inflammatory reaction on a biomaterial surface is highly dependent on the nature and composition of the first adsorbed protein layer and the extent of platelet activation.
16.	Persson-Sjögren, Solveig, et al. (author) Effects of glass ionomers and dental resin composites on viability of beta-cells and insulin release in isolated islets of Langerhans. 2003 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 24:21, s. 3741-3746 Journal article (peer-reviewed)abstract Information on the biocompatibility of glass ionomers and resin composites is sparse. To extend the scale of biological testing we evaluated the influence of those materials on insulin secretion at whole organ level in vitro. The effects on insulin secretion of three glass ionomers and two resin composites, aged for 1 week, were studied in isolated mouse islets of Langerhans at basal (5.5mM) and at stimulatory (11.1mM) D-glucose concentrations. In addition, viability of single mouse beta-cells was evaluated. The effect of glass ionomer specimens aged for 1 and 4 months on insulin secretion at 11.1mM D-glucose was also studied. None of the materials affected the viability of the beta-cells. At 5.5mM D-glucose none of the materials affected the insulin secretion. At 11.1mM D-glucose, the glass ionomers only decreased the secretion and glass ionomers aged for 1 month still decreased insulin release whereas after 4 months ageing only one of the glass ionomers affected the release. The result shows a dynamic effect on insulin release of the elements and/or compounds released from the specimens.
17.	Suska, F., et al. (author) IL-1a, IL-1ß and TNF-a secretion during in vivo/ex vivo cellular interactions with titanium and copper 2003 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 24:3, s. 461-468 Journal article (peer-reviewed)abstract Titanium (Ti) and copper (Cu) were used to evaluate cytokine secretion around materials with different chemical properties. Ti disks were coated with Cu or left uncoated. The disks were inserted subcutaneously in rats for 1, 3, 12, 18, 24 and 48h. Interleukin-1a (IL-1a), IL-1ß and tumor necrosis factor-a (TNF-a) concentrations were measured in vivo around the materials, in sham operated sites, and after ex vivo incubation of surface adherent cells. Ti and Cu revealed distinct cytokine expression patterns. Cu recruited cells showed higher and prolonged release of IL-1a than Ti at longer times (>24h), whereas Ti exhibited a transient IL-1a response at earlier periods (<24h). An early enhanced secretion of TNF-a characterized Ti. Low amounts of IL-1ß were found around both materials. Sham site recruited cells produced lower levels of cytokines. The results after ex vivo incubations were similar to those in vivo. This study shows that material chemical properties influence early cytokine production. The Ti-associated transient rise of IL-1a and TNF-a may be of importance for the early tissue response around biocompatible materials, while a delayed high IL-1a expression could be a marker of inflammation induced by toxic materials. © 2002 Elsevier Science Ltd. All rights reserved.
18.	Tosatti, S., et al. (author) Peptide functionalized poly(L-lysine)-g-poly(ethylene glycol) on titanium : Resistance to protein adsorption in full heparinized human blood plasma 2003 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 24:27, s. 4949-4958 Journal article (peer-reviewed)abstract The graft copolymer poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its RGD- and RDG-functionalized derivatives (PLL-g-PEG/PEG-peptide) were assembled from aqueous solutions on titanium (oxide) surfaces. The polymers were characterized by NMR in order to determine quantitatively the grafting ratio, g (Lys monomer units/PEG side chains), and the fraction of the PEG side chains carrying the terminal peptide group. The titanium surfaces modified with the polymeric monomolecular adlayers were exposed to full heparinized blood plasma. The adsorbed masses were measured by in situ ellipsometry. The different PLL-g-PEG-coated surfaces showed, within the detection limit of the ellipsometric technique, no statistically significant protein adsorption during exposure to plasma for 30min at 22°C or 37°C, whereas clean, uncoated titanium surfaces adsorbed approximately 350ng/cm2 of plasma proteins. The high degree of resistance of the PEGylated surface to non-specific adsorption makes peptide-modified PLL-g-PEG a useful candidate for the surface modification of biomedical devices such as implants that are capable of eliciting specific interactions with integrin-type cell receptors even in the presence of full blood plasma. The results refer to short-term blood plasma exposure that cannot be extrapolated a priori to long-term clinical performance. © 2003 Elsevier Ltd. All rights reserved.
19.	Wetterö, Jonas, 1972-, et al. (author) On the binding of complement to solid artificial surfaces in vitro 2002 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 23:4, s. 981-991 Journal article (peer-reviewed)abstract Since the realization of a complement activation capacity by artificial surfaces upon contact with blood, a common belief has evolved that charged nucleophilic surface groups such as amine (–NH2) and hydroxyl (–OH) react with and eventually bind to the internal thioester in complement factor 3 (C3). A covalent amide or ester linkage is thereby supposed to form between C3b and the surface itself. In this report, we present complement surface binding data by null-ellipsometry for two nucleophilic surfaces (–NH2 and –OH), for surfaces with immunoglobulin G (IgG) covalently bound, and for IgG spontaneously pre-adsorbed to hydrophobic silicon. The results reveal that the plasma proteins that were deposited during complement activation became eluted by sodium dodecyl sulfate. Hence the direct covalent binding between C3 and solid nucleophilic surfaces seems to be only of moderate importance, at least during shorter serum incubations. This strongly suggests that the prevalent covalent linkage model between solid artificial surfaces and C3b is not accurate. Instead we suggest a more pronounced role for C3 associations to other adsorbed proteins and/or electrostatic and hydrophobic protein–surface interactions.
20.	Wetterö, Jonas, 1972-, et al. (author) Platelets stimulated by IgG-coated surfaces bind and activate neutrophils through a selectin-dependent pathway 2003 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 24:9, s. 1559-1573 Journal article (peer-reviewed)abstract Blood platelets bind rapidly to foreign surfaces and interact with adsorbed proteins and neutrophil granulocytes. We demonstrate by use of luminol-amplified chemiluminescence under stirred and non-stirred conditions that platelets at IgG-coated surfaces amplify the neutrophil extracellular release of reactive oxygen species (ROS). The neutrophil response involved tyrosine phosphorylation, but was only in part induced by neutrophil Fcγ-receptor stimulation. The platelet mediated effects were contact-dependent since the respiratory burst was inhibited when the IgG-stimulated platelets were removed by filtration, but not when they were fixed in paraformaldehyde. Bodipyphallacidin-staining of filamentous actin (F-actin) revealed that an actin-dependent platelet adhesion supported the subsequent adhesion and spreading of neutrophils. The neutrophil ROS-response was lowered when the interaction between platelet P-selectin (CD62P) and neutrophil P-selectin glycoprotein ligand-l (PSGL-1 or CD162) was inhibited. The blocking of L-selectin (CD62L) or blocking of the interaction between platelet glycoprotein (Gp) IIb/IIIa and neutrophil complement receptor 3 (CR3) showed no effect. We conclude that platelet activation on immobilized IgG trigger a contact-dependent “frustrated” phagocytosis by neutrophils, associated with a release of toxic ROS.
21.	Ajalloueian, Fatemeh, et al. (author) Constructs of electrospun PLGA, compressed collagen and minced urothelium for minimally manipulated autologous bladder tissue expansion 2014 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 35:22, s. 5741-5748 Journal article (peer-reviewed)abstract Bladder regeneration based on minced bladder mucosa in vivo expansion is an alternative to in vitro culturing of urothelial cells. Here, we present the design of a hybrid, electrospun poly(lactic-co-glycolide) (PLGA) - plastically compressed (PC) collagen scaffold that could allow in vivo bladder mucosa expansion. Optimisation of electrospinning was performed in order to obtain increased pore sizes and porosity to consolidate the construct and to support neovascularisation and tissue ingrowth. Tensile tests showed an increase in average tensile strength from 0.6 MPa for PC collagen to 3.57 MPa for the hybrid construct. The optimised PLGA support scaffold was placed between two collagen gels, and the minced tissue was distributed either on top or both on top and inside the construct prior to PC; this was then cultured for up to four weeks. Morphology, histology and SEM demonstrated that the construct maintained its integrity throughout cell culture. Cells from minced tissue migrated, expanded and re-organised to a confluent cell layer on the top of the construct after two weeks and formed a multilayered urothelium after four weeks. Cell morphology and phenotype was typical for urothelial mucosa during tissue culture. (C) 2014 Elsevier Ltd. All rights reserved.
22.	Ajalloueian, F, et al. (author) Retraction notice to: "Biomechanical and biocompatibility characteristics of electrospun polymeric tracheal scaffolds "[BIOMATERIALS 35/20 (2014) 5307-5315] 2019 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 199, s. 89-89 Journal article (peer-reviewed)
23.	Alarcon, Emilio I, et al. (author) The biocompatibility and antibacterial properties of collagen-stabilized, photochemically prepared silver nanoparticles 2012 In: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 33:19, s. 4947-4956 Journal article (peer-reviewed)abstract Spherical 3.5 nm diameter silver nanoparticles (AgNP) stabilized in type I collagen (AgNP@collagen) were prepared in minutes (5-15 min) at room temperature by a photochemical method initiated by UVA irradiation of a water-soluble non-toxic benzoin. This biocomposite was examined to evaluate its biocompatibility and its anti-bacterial properties and showed remarkable properties. Thus, while keratinocytes and fibroblasts were not affected by AgNP@collagen, it was bactericidal against Bacillus megaterium and E. coli but only bacteriostatic against S. epidermidis. In particular, the bactericidal properties displayed by AgNP@collagen were proven to be due to AgNP in AgNP@collagen, rather than to released silver ions, since equimolar concentrations of Ag are about four times less active than AgNP@collagen based on total Ag content. This new biocomposite was stable over a remarkable range of NaCl, phosphate, and 2-(N-morpholino)ethanesulfonic acid concentrations and for over one month at 4 degrees C. Circular dichroism studies show that the conformation of collagen in AgNP@collagen remains intact. Finally, we have compared the properties of AgNP@collagen with a similar biocomposite prepared using alpha-poly-L-Lysine and also with citrate stabilized AgNP; neither of these materials showed comparable biocompatibility, stability, or anti-bacterial activity.
24.	Almlöf, Martin, et al. (author) Molecular dynamics study of heparin based coatings 2008 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 29:33, s. 4463-4469 Journal article (peer-reviewed)abstract Heparin based surface coatings can be used to improve the biocompatibility of metallic surfaces such as vascular stents. Here, we report molecular dynamics simulations of a macromolecular conjugate of heparin used to prepare such surfaces. The structural properties of the heparin conjugate are investigated for different degrees of hydration, to allow comparison with spectroscopic results. The simulations show that the polymer becomes more compact with an increasing degree of inter-chain interactions as the hydration increases. This is also accompanied by changes in the interaction patterns among the heparin chains, where counter ions become looser associated with the disaccharide units and their strong interactions can be partly replaced by water molecules and heparin hydroxyl groups. The structural information that can be obtained from computer simulations of this type of coatings can be very valuable for understanding and further development of functional interfaces, since very little is known experimentally regarding their detailed structural properties. (C) 2008 Elsevier Ltd. All rights reserved.
25.	Alves-Lopes, JP, et al. (author) Testicular organoid generation by a novel in vitro three-layer gradient system 2017 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 130, s. 76-89 Journal article (peer-reviewed)
26.	Apelgren, Peter, et al. (author) Vascularization of tissue engineered cartilage-Sequential in vivo MRI display functional blood circulation 2021 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 276 Journal article (peer-reviewed)abstract Establishing functional circulation in bioengineered tissue after implantation is vital for the delivery of oxygen and nutrients to the cells. Native cartilage is avascular and thrives on diffusion, which in turn depends on proximity to circulation. Here, we investigate whether a gridded three-dimensional (3D) bioprinted construct would allow ingrowth of blood vessels and thus prove a functional concept for vascularization of bioengineered tissue. Twenty 10 x 10 x 3-mm 3Dbioprinted nanocellulose constructs containing human nasal chondrocytes or cell-free controls were subcutaneously implanted in 20 nude mice. Over the next 3 months, the mice were sequentially imaged with a 7 T small-animal MRI system, and the diffusion and perfusion parameters were analyzed. The chondrocytes survived and proliferated, and the shape of the constructs was well preserved. The diffusion coefficient was high and well preserved over time. The perfusion and diffusion patterns shown by MRI suggested that blood vessels develop over time in the 3D bioprinted constructs; the vessels were confirmed by histology and immunohistochemistry. We conclude that 3D bioprinted tissue with a gridded structure allows ingrowth of blood vessels and has the potential to be vascularized from the host. This is an essential step to take bioengineered tissue from the bench to clinical practice.
27.	Arvidsson, Sara, 1977-, et al. (author) Blood plasma contact activation on silicon, titanium and aluminium. 2007 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 28:7, s. 1346-54 Journal article (peer-reviewed)abstract In the present work, blood plasma protein deposition to spontaneously air oxidized silicon, titanium and aluminium was re-investigated in vitro. Immunological- and null ellipsometry methods were used to detect and quantitate adsorbed proteins, RIA methods to study the retention of preadsorbed 125I-HSA upon exposure to buffer or blood plasma, and kallikrein-specific colorimetric substrate S-2302 to follow the surface generation of kallikrein. The results show that the contact activation of coagulation and complement systems are connected on Si and Ti, but not on Al, via coagulation factor XII. Preadsorbed 125I-HSA was most readily displaced on silicon, followed by titanium and aluminium. The surfaces displayed different antibody binding patterns after short and long-time exposures to plasma. Titanium and silicon bound anti-HMWK after 1 min in plasma, but aluminium did not. When the plasma incubation time was prolonged up to 2h the anti-HMWK binding disappeared totally on titanium and decreased on silicon. During the same time period, anti-C3c binding increased to the three types of surfaces. Also, the anti-C3c binding onto Si and Ti, but not Al, disappeared after incubation in Factor XII deficient plasma or when a specific coagulation factor XII (Factor XII) inhibitor, corn trypsin inhibitor (CTI) was added to normal plasma. The surface contacted plasmas cleaved the kallikrein-specific reagent S-2302 both after single surface contact, and after reincubation of surfaces in fresh plasma. The results show that C3b and Factor XIIa and their degradation products were retained at the surfaces.
28.	Baiguera, S, et al. (author) Development of bioengineered human larynx 2011 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 32:19, s. 4433-4442 Journal article (peer-reviewed)
29.	Baiguera, S, et al. (author) Dynamic decellularization and cross-linking of rat tracheal matrix 2014 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 35:24, s. 6344-6350 Journal article (peer-reviewed)
30.	Baiguera, S, et al. (author) Electrospun gelatin scaffolds incorporating rat decellularized brain extracellular matrix for neural tissue engineering 2014 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 35:4, s. 1205-1214 Journal article (peer-reviewed)
31.	Baiguera, S, et al. (author) Long-term changes to in vitro preserved bioengineered human trachea and their implications for decellularized tissues 2012 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 33:14, s. 3662-3672 Journal article (peer-reviewed)
32.	Bayat, Narges, et al. (author) Vascular toxicity of ultra-small TiO2 nanoparticles and single walled carbon nanotubes in vitro and in vivo 2015 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 63, s. 1-13 Journal article (peer-reviewed)abstract Ultra-small nanoparticles (USNPs) at 1-3 nm are a subset of nanoparticles (NPs) that exhibit intermediate physicochemical properties between molecular dispersions and larger NPs. Despite interest in their utilization in applications such as theranostics, limited data about their toxicity exist. Here the effect of TiO2-USNPs on endothelial cells in vitro, and zebrafish embryos in vivo, was studied and compared to larger TiO2-NPs (30 nm) and to single walled carbon nanotubes (SWCNTs). In vitro exposure showed that TiO2-USNPs were neither cytotoxic, nor had oxidative ability, nevertheless were genotoxic. In vivo experiment in early developing zebrafish embryos in water at high concentrations of TiO2-USNPs caused mortality possibly by acidifying the water and caused malformations in the form of pericardial edema when injected. Myo1C involved in glomerular development of zebrafish embryos was upregulated in embryos exposed to TiO2-USNPs. They also exhibited anti-angiogenic effects both in vitro and in vivo plus decreased nitric oxide concentration. The larger TiO2-NPs were genotoxic but not cytotoxic. SWCNTs were cytotoxic in vitro and had the highest oxidative ability. Neither of these NPs had significant effects in vivo. To our knowledge this is the first study evaluating the effects of TiO2-USNPs on vascular toxicity in vitro and in vivo and this strategy could unravel USNPs potential applications.
33.	Bergknut, Niklas, et al. (author) The performance of a hydrogel nucleus pulposus prosthesis in an ex vivo canine model 2010 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 31, s. 6782-6788 Journal article (peer-reviewed)abstract Both on imaging and macroscopically, 9/10 NPPs appeared to have a near perfect fit and disc height was restored in 8/10 spinal segments. The NPP may thus be an acceptable treatment option for low back patients meeting the requirements for NPP treatment. (C) 2010 Elsevier Ltd. All rights reserved.
34.	Blau, Axel, et al. (author) Flexible, all-polymer microelectrode arrays for the capture of cardiac and neuronal signals 2011 In: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 32:7, s. 1778-1786 Journal article (peer-reviewed)abstract Microelectrode electrophysiology has become a widespread technique for the extracellular recording of bioelectrical signals. To date, electrodes are made of metals or inorganic semiconductors, or hybrids thereof. We demonstrate that these traditional conductors can be completely substituted by highly flexible electroconductive polymers. Pursuing a two-level replica-forming strategy, conductive areas for electrodes, leads and contact pads are defined as microchannels in poly(dimethylsiloxane) (PDMS) as a plastic carrier and track insulation material. These channels are coated by films of organic conductors such as polystyrenesulfonate-doped poly(3,4-ethylenedioxy-thiophene) (PEDOT:PSS) or filled with a graphite-PDMS (gPDMS) composite, either alone or in combination. The bendable, somewhat stretchable, non-cytotoxic and biostable all-polymer microelectrode arrays (polyMEAs) with a thickness below 500 μm and up to 60 electrodes reliably capture action potentials (APs) and local field potentials (LFPs) from acute preparations of heart muscle cells and retinal whole mounts, in vivo epicortical and epidural recordings as well as during long-term in vitro recordings from cortico-hippocampal co-cultures.
35.	Bodin, Aase Katarina, 1977, et al. (author) Tissue-engineered conduit using urine-derived stem cells seeded bacterial cellulose polymer in urinary reconstruction and diversion 2010 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 31:34, s. 8889-8901 Journal article (peer-reviewed)abstract The objective of this study was to generate bacterial cellulose (BC) scaffolds seeded with human urine-derived stem cells (USC) to form a tissue-engineered conduit for use in urinary diversion. Microporous BC scaffolds were synthesized and USC were induced to differentiate into urothelial and smooth muscle cells (SMC). Induced USC (10 6 cells/cm 2 ) were seeded onto BC under static and 3D dynamic (10 or 40 RPM) conditions and cultured for 2 weeks. The urothelial cells and SMC derived from USC formed multilayers on the BC scaffold surface, and some cells infiltrated into the scaffold. The urothelium derived from USC differentiation expressed urothelial markers (uroplakin Ia and AE1/AE3) and the SMC expressed SMC markers (α-smooth muscle actin and desmin). In addition, USC/BC scaffold constructs were implanted into athymic mice, and the cells were tracked using immunohistochemical staining for human nuclear antigen. In vivo, the cells appeared to differentiate and express urothelial and SMC markers. In conclusion, porous BC scaffolds allow 3 dimensional growth of USC, leading to formation of a multilayered urothelium and cell-matrix infiltration. Thus, cell-seeded BC scaffolds hold promise for use in tissue-engineered urinary conduits for urinary reconstruction. © 2010 Elsevier Ltd.
36.	Broos, Sissela, et al. (author) Synergistic augmentation of CD40-mediated activation of antigen-presenting cells by amphiphilic poly(γ-glutamic acid) nanoparticles. 2012 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 33:26, s. 6230-6239 Journal article (peer-reviewed)abstract Agonistic anti-CD40 monoclonal antibodies (mAbs) hold great potential for cancer immunotherapy. However, systemic administration of anti-CD40 mAbs can be associated with severe side effects, such as cytokine release syndrome and liver damage. With the aim to increase the immunostimulatory potency as well as to achieve a local drug retention of anti-CD40 mAbs, we linked an agonistic mAb to immune activating amphiphilic poly(γ-glutamic acid) nanoparticles (γ-PGA NPs). We demonstrate that adsorption of anti-CD40 mAb to γ-PGA NPs (anti-CD40-NPs) improved the stimulatory capacity of the CD40 agonist, resulting in upregulation of costimulatory CD80 and CD86 on antigen-presenting cells, as well as IL-12 secretion. Interestingly, anti-CD40-NPs induced strong synergistic proliferative effects in B cells, possibly resulting from a higher degree of CD40 multimerization, enabled by display of multiple anti-CD40 mAbs on the NPs. In addition, local treatment with anti-CD40-NPs, compared to only soluble CD40 agonist, resulted in a significant reduction in serum levels of IL-6, IL-10, IL-12 and TNF-α in a bladder cancer model. Taken together, our results suggest that anti-CD40-NPs are capable of synergistically enhancing the immunostimulatory effect induced by the CD40 agonist, as well as minimizing adverse side effects associated with systemic cytokine release. This concept of nanomedicine could play an important role in localized immunotherapy of cancer.
37.	Bäck, Jennie, et al. (author) Distinctive regulation of contact activation by antithrombin and C1-inhibitor on activated platelets and material surfaces 2009 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 30:34, s. 6573-6580 Journal article (peer-reviewed)abstract Activated human plate lets trigger FXII-mediated contact activation, which leads to the generation of FXIIa-antithrombin (AT) and FXIa-AT complexes. This suggests that contact activation takes place at different sites, on activated platelets and material surfaces, during therapeutic procedures involving biomaterials in contact with blood and is differentially regulated. Here we show that activation in platelet-poor plasma, platelet-rich plasma (PRP), and whole blood induced by glass, kaolin, and polyphosphate elicited high levels of FXIIa-C1-inhibitor (C1INH), low levels of FXIa-C1INH and KK-C1INH, and almost no AT complexes. Platelet activation, in both PRP and blood, led to the formation of FXIIa-AT, FXIa-AT, and kallikrein (KK)-AT but almost no C1INH complexes. In severe trauma patients, FXIIa-AT and FXIa-AT were correlated with the release of thrombospondin-1 (TSP-1) from activated platelets. In contrast, FXIIa-C1INH complexes were detected when the FXIIa-AT levels were low. No correlations were found between FXIIa-C1INH and FXIIa-AT or TSP-1. Inhibition of FXIIa on material surfaces was also shown to affect the function of aggregating platelets. In conclusion, formation of FXIIa-AT and FXIIa-C1INH complexes can help to distinguish between contact activation triggered by biomaterial surfaces and by activated platelets. Platelet aggregation studies also demonstrated that platelet function is influenced by material surface-mediated contact activation and that generation of FXIIa-AT complexes may serve as a new biomarker for thrombotic reactions during therapeutic procedures employing biomaterial devices.
38.	Bäckdahl, Henrik, 1977, et al. (author) Mechanical properties of bacterial cellulose and interactions with smooth muscle cells 2006 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 27:9, s. 2141-2149 Journal article (peer-reviewed)abstract Tissue engineered blood vessels (TEBV) represent an attractive approach for overcoming reconstructive problems associated with vascular diseases by providing small calibre vascular grafts. The aim of this study has been to evaluate a novel biomaterial, bacterial cellulose (BC), as a potential scaffold for TEBV. The morphology of the BC pellicle grown in static culture was investigated with SEM. Mechanical properties of BC were measured in Krebs solution and compared with the properties of porcine carotid arteries and ePTFE grafts. Attachment, proliferation and ingrowth of human smooth muscle cells (SMC) on the BC were analysed in vitro. The BC pellicle had an asymmetric structure composed of a fine network of nanofibrils similar to a collagen network. The shape of the stress-strain response of BC is reminiscent of the stress-strain response of the carotid artery, most probably due to the similarity in architecture of the nanofibrill networks. SMC adhered to and proliferated on the BC pellicle; an ingrowth of up to 40 microm was seen after 2 weeks of culture. BC exhibit attractive properties for use in future TEBV.
39.	Camire, Christopher, et al. (author) Correlating crystallinity and reactivity in an alpha-tricalcium phosphate. 2005 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 26:16, s. 2787-2794 Journal article (peer-reviewed)
40.	Cardemil, Carina, et al. (author) The effects of a systemic single dose of zoledronic acid on post-implantation bone remodelling and inflammation in an ovariectomised rat model. 2013 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 34:5, s. 1546-61 Journal article (peer-reviewed)abstract Bisphosphonates reverse the negative effects of ovariectomy on bone, but they have also been associated with adverse processes in human jawbone. The molecular events determining bone regeneration and implant integration in osteoporotic conditions, with and without bisphosphonate treatment, are unclear. In this study, ovariectomised rats, to which a single dose of saline (NaCl) or zoledronic acid (Zol) was administered, received titanium alloy implants in their tibiae and mandibles. An enzyme-linked immunosorbent assay, gene expression analysis and histomorphometry were performed. The results show that ovariectomy, per se, upregulated the expression of genes denoting bone formation in the tibia, bone remodelling in the mandible and apoptosis in the tibia and mandible. Zoledronic acid administration resulted in lower levels of a remodelling marker in serum and downregulated gene expression for inflammation, bone formation, angiogenesis and apoptosis, mainly in the mandible, after 28d of healing. Histomorphometry revealed improved bone-to-implant contact in the tibia, while the opposite was observed in the mandible. The present data show that a systemic single dose of zoledronic acid, in ovariectomised animals, results in site-specific differences in the regulation of genes involved in bone healing and regeneration in association with implant installation. These events occur in parallel with site-specific differences in the rate of osseointegration, indicating diverse tissue responses in the tibia and mandible after zoledronic acid treatment. The zoledronic acid effect on gene expression, during the late phase of healing in the mandible, suggests negative effects by the anti-resorptive agent on osseointegration at that particular site.
41.	Carlén, A, et al. (author) Surface characteristics and in vitro biofilm formation on glass ionomer and composite resin 2001 In: Biomaterials. - 0142-9612 .- 1878-5905. ; 22, s. 481-487 Journal article (peer-reviewed)abstract In the initial stages of dental plaque formation, early colonizing bacteria bind to receptor structures in the pellicle, a proteinaceous film formed instantly after cleaning of the tooth surface. Dental restorative materials with surface characteristics different from the tooth might affect pellicle formation and the ability of bacteria to colonize the oral cavity. in this study (i) roughness and chemical composition of glass ionomer and composite resin surfaces before and after polishing, and (ii) the adsorption of salivary proteins and bacterial adherence to the pellicle-coated surfaces were examined. Compared with unpolished composite resin, unpolished glass ionomer had higher surface roughness, contained more inorganic, positively charged components, collected more proteins, and promoted better bacterial adherence. Polishing had the most pronounced effect on the composite resin, giving an enlarged and a rougher surface with a more inorganic character. Polishing the composite resin also led to increased biofilm formation
42.	Carreras-Badosa, Gemma, et al. (author) NickFect type of cell-penetrating peptides present enhanced efficiency for microRNA-146a delivery into dendritic cells and during skin inflammation 2020 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 262 Journal article (peer-reviewed)abstract MicroRNAs (miRNAs) are post-transcriptional gene expression regulators with potential therapeutic applications. miR-146a is a negative regulator of inflammatory processes in both tissue-resident and specialized immune cells and may therefore have therapeutic effect in inflammatory skin diseases. PepFect (PF) and NickFect (NF) type of cell-penetrating peptides (CPPs) have previously been shown to deliver miRNA mimics and/or siRNAs into cell cultures and in vivo. Here, we first demonstrate that selected PF- and NF-type of CPPs support delivery of fluorescent labelled miRNA mimics into keratinocytes (KCs) and dendritic cells (DCs). Second, we show that both PF- and NF-miR-146a nanocomplexes were equally effective in KCs, while NFs were more efficient in DCs as assessed by downregulation of miR-146a-influenced genes. None of miRNA nanocomplexes with the tested CPPs influenced the viability of KCs and DCs nor caused activation of DCs according to CD86 and CD83 markers. Transmission electron microscopy analysis with Nanogold-labelled miR-146a mimics and assessment of endocytic trafficking pathways revealed endocytosis as an active route of delivery in both KCs and DCs for all tested CPPs. However, consistent with the higher efficiency, NF-delivered miR-146a was detected more often outside endosomes in DCs. Finally, pre-injection of NF71:miR-146a nanocomplexes was confirmed to suppress inflammatory responses in a mouse model of irritant contact dermatitis as shown by reduced ear swelling response and downregulation of pro-inflammatory cytokines, including IL-6, IL-1 beta, IL-33 and TNF-alpha. In conclusion, NF71 efficiently delivers miRNA mimics into KCs as well as DCs, and therefore may have advantage in therapeutic delivery of miRNAs in case of inflammatory skin diseases.
43.	Casanova, Elisa A., et al. (author) SAXS imaging reveals optimized osseointegration properties of bioengineered oriented 3D-PLGA/aCaP scaffolds in a critical size bone defect model 2023 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 294 Journal article (peer-reviewed)abstract Healing large bone defects remains challenging in orthopedic surgery and is often associated with poor outcomes and complications. A major issue with bioengineered constructs is achieving a continuous interface between host bone and graft to enhance biological processes and mechanical stability. In this study, we have developed a new bioengineering strategy to produce oriented biocompatible 3D PLGA/aCaP nanocomposites with enhanced osseointegration. Decellularized scaffolds -containing only extracellular matrix- or scaffolds seeded with adipose-derived mesenchymal stromal cells were tested in a mouse model for critical size bone defects. In parallel to micro-CT analysis, SAXS tensor tomography and 2D scanning SAXS were employed to determine the 3D arrangement and nanostructure within the critical-sized bone. Both newly developed scaffold types, seeded with cells or decellularized, showed high osseointegration, higher bone quality, increased alignment of collagen fibers and optimal alignment and size of hydroxyapatite minerals.
44.	Conceica, M, et al. (author) Engineered extracellular vesicle decoy receptor-mediated modulation of the IL6 trans-signalling pathway in muscle 2021 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 266, s. 120435- Journal article (peer-reviewed)
45.	Constantinidis, Ioannis, et al. (author) Non-invasive evaluation of alginate/poly-L-lysine/alginate microcapsules by magnetic resonance microscopy 2007 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 28:15, s. 2438-2445 Journal article (peer-reviewed)abstract In this report, we present data to demonstrate the utility of H-1 MR microscopy to non-invasively examine alginate/poly-L-lysine/ alginate (APA) microcapsules. Specifically, high-resolution images were used to visualize and quantify the poly-L-lysine (PLL) layer, and monitor temporal changes in the alginate gel microstructure during a month long in vitro culture. The thickness of the alginate/PLL layer was quantified to be 40.6 +/- 6.2 mu m regardless of the alginate composition used to generate the beads or the time of alginate/PLL interaction (2, 6, or 20 min). However, there was a notable difference in the contrast of the PLL layer that depended upon the guluronic content of the alginate and the alginate/PLL interaction time. The T-2 relaxation time and the apparent diffusion coefficient (ADC) of the alginate matrix were measured periodically throughout the month long culture period. Alginate beads generated with a high guluronic content alginate demonstrated a temporal decrease in T-2 over the duration of the experiment, while ADC was unaffected. This decrease in T-2 is attributed to a reorganization of the alginate microstructure due to periodic media exchanges that mimicked a regular feeding regiment for cultured cells. In beads coated with a PLL layer, this temporal decrease in T-2 was less pronounced suggesting that the PLL layer helped maintain the integrity of the initial alginate microstructure. Conversely, alginate beads generated with a high mannuronic content alginate (with or without a PLL layer) did not display temporal changes in either T-2 or ADC. This observation suggests that the microstructure of high mannuronic content alginate beads is less susceptible to culture conditions.
46.	Coutu, Daniel L, et al. (author) Hierarchical scaffold design for mesenchymal stem cell-based gene therapy of hemophilia B 2011 In: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 32:1, s. 295-305 Journal article (peer-reviewed)abstract Gene therapy for hemophilia B and other hereditary plasma protein deficiencies showed great promise in pre-clinical and early clinical trials. However, safety concerns about in vivo delivery of viral vectors and poor post-transplant survival of ex vivo modified cells remain key hurdles for clinical translation of gene therapy. We here describe a 3D scaffold system based on porous hydroxyapatite PLGA composites coated with biomineralized collagen 1. When combined with autologous gene-engineered factor IX (hFIX) positive mesenchymal stem cells (MSCs) and implanted in hemophilic mice, these scaffolds supported long-term engraftment and systemic protein delivery by MSCs in vivo. Optimization of the scaffolds at the macro-, micro- and nanoscales provided efficient cell delivery capacity, MSC self-renewal and osteogenesis respectively, concurrent with sustained delivery of hFIX. In conclusion, the use of gene-enhanced MSC-seeded scaffolds may be of practical use for treatment of hemophilia B and other plasma protein deficiencies.
47.	Curcio, E, et al. (author) Kinetics of oxygen uptake by cells potentially used in a tissue engineered trachea 2014 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 35:25, s. 6829-6837 Journal article (peer-reviewed)
48.	da Silva, Joakim, et al. (author) The cavity-to-cavity migration of leukaemic cells through 3D honey-combed hydrogels with adjustable internal dimension and stiffness 2010 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 31:8, s. 2201-2208 Journal article (peer-reviewed)abstract Whilst rigid, planar surfaces are often used to study cell migration, a physiological scenario requires three-dimensional (3D) scaffolds with tissue-like stiffness. This paper presents a method for fabricating periodic hydrogel scaffolds with a 3D honeycomb-like structure from colloidal crystal templates. The scaffolds, made of hydrogel-walled cavities interconnected by pores, have separately tuneable internal dimensions and adjustable gel stiffness down to that of soft tissues. In conjunction with confocal microscopy, these scaffolds were used to study the importance of cell compliance on invasive potential. Acute promyelocytic leukaemia (APL) cells were differentiated with all-trans retinoic acid (ATRA) and treated with paclitaxel. Their migration ability into the scaffolds' size-restricted pores, enabled by cell softening during ATRA differentiation, was significantly reduced by paclitaxel treatment, which interferes with cell shape recovery. These findings demonstrate the usability of the scaffolds for investigating factors that affect cell migration, and potentially other cell functions, in a realistic 3D tissue model.
49.	Dainiak, Maria B, et al. (author) Gelatin-fibrinogen cryogel dermal matrices for wound repair: Preparation, optimisation and in vitro study. 2010 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 31, s. 67-76 Journal article (peer-reviewed)abstract Macroporous sponge-like gelatin-fibrinogen (Gl-Fg) scaffolds cross-linked with different concentrations (0.05-0.5%) of glutaraldehyde (GA) were produced using cryogelation technology, which allows for the preparation of highly porous scaffolds without compromising their mechanical properties, and is a more cost-efficient process than freeze-drying. The produced Gl-Fg-GA(X) scaffolds had a uniform interconnected open porous structure with a porosity of up to 90-92% and a pore size distribution of 10-120mum. All of the obtained cryogels were elastic and mechanically stable, except for the Gl-Fg-GA(0.05) scaffolds. Swelling kinetics and degradation rate, but not the porous structure of the cryogels, were strongly dependent on the degree of cross-linking. A ten-fold increase in the degree of cross-linking resulted in an almost 80-fold decrease in the rate of degradation in a solution of protease. Cryogels were seeded with primary dermal fibroblasts and the densities observed on the surface, plus the expression levels of collagen types I and III observed 5 days post-seeding, were similar to those observed on a control dermal substitute material, Integra((R)). Fibroblast proliferation and migration within the scaffolds were relative to the GA content. Glucose consumption rate was 3-fold higher on Gl-Fg-GA(0.1) than on Gl-Fg-GA(0.5) cryogels 10 days post-seeding. An enhanced cell motility on cryogels with reducing GA crosslinking was obtained after long time culture. Particularly marked cell infiltration was seen in gels using 0.1% GA as a crosslinker. The scaffold started to disintegrate after 42 days of in vitro culturing. The described in vitro studies demonstrated good potential of Gl-Fg-GA(0.1) scaffolds as matrices for wound healing.
50.	Declercq, HA, et al. (author) Bone grafts engineered from human adipose-derived stem cells in dynamic 3D-environments 2013 In: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 34:4, s. 1004-1017 Journal article (peer-reviewed)

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