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51.	Wang, Nan, 1988, et al. (författare) Improved Interfacial Bonding Strength and Reliability of Functionalized Graphene Oxide for Cement Reinforcement Applications 2020 Ingår i: Chemistry - A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 26:29, s. 6561-6568 Tidskriftsartikel (refereegranskat)abstract Poor bonding strength between nanomaterials and cement composites inevitably lead to the failure of reinforcement. Herein, a novel functionalization method for the fabrication of functionalized graphene oxide (FGO), which is capable of forming highly reliable covalent bonds with cement hydration products, and therefore, suitable for use as an efficient reinforcing agent for cement composites, is discussed. The bonding strength between cement and aggregates was improved more than 21 times with the reinforcement of FGO. The fabricated FGO also demonstrated many important features, including high reliability in cement pastes, good dispersibility, and efficient structural refinement of cement hydration products. With the incorporation of FGO, cement mortar samples demonstrated up to 40 % increased early and ultimate strength. Such results make the fast demolding and manufacture of light constructions become highly possible, and show strong advantages on improving productivity, saving cost, and reducing CO2 emissions in practical applications.
52.	Fornell, Anna, et al. (författare) Acoustic focusing of beads and cells in hydrogel droplets 2021 Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1 Tidskriftsartikel (refereegranskat)abstract The generation of hydrogel droplets using droplet microfluidics has emerged as a powerful tool with many applications in biology and medicine. Here, a microfluidic system to control the position of particles (beads or astrocyte cells) in hydrogel droplets using bulk acoustic standing waves is presented. The chip consisted of a droplet generator and a 380 µm wide acoustic focusing channel. Droplets comprising hydrogel precursor solution (polyethylene glycol tetraacrylate or a combination of polyethylene glycol tetraacrylate and gelatine methacrylate), photoinitiator and particles were generated. The droplets passed along the acoustic focusing channel where a half wavelength acoustic standing wave field was generated, and the particles were focused to the centre line of the droplets (i.e. the pressure nodal line) by the acoustic force. The droplets were cross-linked by exposure to UV-light, freezing the particles in their positions. With the acoustics applied, 89 ± 19% of the particles (polystyrene beads, 10 µm diameter) were positioned in an area ± 10% from the centre line. As proof-of-principle for biological particles, astrocytes were focused in hydrogel droplets using the same principle. The viability of the astrocytes after 7 days in culture was 72 ± 22% when exposed to the acoustic focusing compared with 70 ± 19% for samples not exposed to the acoustic focusing. This technology provides a platform to control the spatial position of bioparticles in hydrogel droplets, and opens up for the generation of more complex biological hydrogel structures.
53.	Ghandour, Salim, et al. (författare) Optimization of titanium spinal cages to maximize synthetic graft content in composite implants 2022 Konferensbidrag (refereegranskat)abstract Spinal fusion is the gold standard for treating patients with degenerative disc disease. Titanium alloys and PEEK are the two most common materials used to manufacture cages for spinal fusion, used to maintain disc height while the vertebrae fuse. Other materials, such as morselised bone, may be added to the cage to enhance the bioactivity. A monetite-based calcium phosphate has (as a composite implant in combination with titanium) shown potentially osteoinductive properties and may be a synthetic alternative to bone graft. Maximizing the ratio of calcium phosphate to titanium could be desirable to maximize bone ingrowth and fusion. Further, the calcium phosphate can be incorporated into the cage and stored ahead of surgery. The aim of this study was to topologically optimize cervical spine implants to incorporate a bioactive but mechanically weak material such as calcium phosphate.
54.	Carmona, Pierre, 1995 (författare) Structure evolution of phase-separated EC/HPC films for controlled drug release 2022 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport out of pharmaceutical pellets. The drug transport rate is determined by the structure of the porous films that are formed as the water-soluble HPC leaches out. In industry, the pellets are being coated using a fluidized bed spraying device, and layered films with varying porosity and structure are obtained. A detailed understanding of the formation mechanisms of the multilayered phase-separated structure during production is lacking. Here, we have investigated EC/HPC films produced by spin-coating, which mimics the industrial manufacturing process in a reproducible and well-controlled manner. This work is aimed to understand why the film structure is layered, and why it exhibits different porosities and structures by understanding the film formation mechanisms. The 2D and 3D structures of the EC/HPC films were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), focused ion beam SEM (FIB-SEM) and image analysis. The thickness of the films was measured by profilometry. To be able to understand the multilayer formation, we first studied the structure evolution in EC/HPC monolayer films. The effect of the EC/HPC ratio (from 15 to 85 wt% HPC) on the in-plane and cross-sectional structure evolution was determined. Bicontinuous structures were found for 30 to 40 wt% HPC and discontinuous structures were found for the fractions 15 to 22 and 45 to 85 wt% HPC. The growth of the characteristic length scale followed a power law, , with for bicontinuous structures, and 0.45 - 0.75 for discontinuous structures. An image analysis method to characterize the time-dependent 2D curvature evolution was developed. Two main coarsening mechanisms could be identified: interfacial tension-driven hydrodynamic growth for bicontinuous structures and diffusion-driven coalescence for discontinuous structures. The cross-sectional structure evolution shows that during shrinkage of the film, the phase-separated structure undergoes a transition from 3D to nearly 2D structure evolution along the surface. The shrinkage rate was found to be independent of the EC/HPC ratio. A new method to estimate part of the binodal curve in the ternary phase diagram for EC/HPC in ethanol has been developed. For multilayer films, the results showed that the inherent behaviour of the monolayer films have a strong impact on the formation of each new layer in multilayer films. A gradient in structure size with larger structures close to the substrate and smaller structures close to the air surface was found and explained by the redissolution of the layers already deposited during previous deposition cycles. By varying the EC/HPC ratio during the multilayer film production, we showed in situ that the layers do not mix. By varying the spin speed every other layer, we produced a layered film exhibiting varying porosity, proposing a possible explanation for obtaining a layered coating in the industrial process. The findings of this work provide a good understanding of the mechanisms responsible for the morphology development and enable tailoring of multilayer EC/HPC films structure for controlled drug release.
55.	Grandfield, K., et al. (författare) Atom probe tomography for biomaterials and biomineralization 2022 Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061. ; 148, s. 44-60 Tidskriftsartikel (refereegranskat)abstract Biominerals and biomaterials are part of our daily lives, from our skeleton and teeth to coral reefs and carbon-capturing single-cell organisms in the oceans, to engineered ceramics comprising our toothpaste and bone replacements. Many biominerals are hierarchically structured with remarkable material prop-erties that arise from their unique combination of organic and inorganic components. Such structural hierarchy is often formed through a process of biomineralization. However, many fundamental questions remain regarding mineralization events in bones or teeth, and near biomaterials, partly due to the chal-lenges in characterizing three-dimensional (3D) structure and chemical composition simultaneously at the nanometer scale. Atom probe tomography (APT) is a 3D characterization technique that combines both sub-nanometer spatial resolution and compositional sensitivity down to tens of parts per million. While APT is well-established in application to conventional engineering materials, recent years have seen its expansion into biomineralization research. Here, we focus our review on APT applications to biominerals, biomaterials and biointerfaces, providing a high-level summary of findings, as well as a primer on theory and best practices specific to the biomineralization community. We show that APT is a promising char-acterization tool, where its unique ability to quantify 3D chemical composition is not only complemen-tary to other microscopy techniques but could become an integral part of biomaterial research. With the emerging trends of correlative and cryogenic workflow, notwithstanding the challenges outlined herein, APT has the potential to improve understanding of a broader range of biomaterials, while deriving inno-vative perspectives on clinical applications and strategies for biomaterial design.Statement of significance Atom probe tomography (APT) is a three-dimensional characterization technique that can provide quanti-tative elemental and isotopic analysis with sub-nanometer resolution and compositional sensitivity down to tens of parts per million. These capabilities make it uniquely positioned for the analysis of biominer-alized materials, both natural and synthetic. Here, we review the various applications of APT to the field of biomineralization, including applications in biominerals, biomaterials, biointerfaces and other biolog-ical materials, such as cells or proteins. A brief but comprehensive summary of the relevant technical concepts, limitations, and future perspectives to enable growth in this field are also included. Although APT is relatively new to the field of biomineralization, it has shown the potential to transform our basic understanding of biomineralization mechanisms and better inform biomaterials design.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
56.	Huang, Tianwei, et al. (författare) Surface modulation of extracellular vesicles with cell-penetrating peptide-conjugated lipids for improvement of intracellular delivery to endothelial cells 2023 Ingår i: Regenerative Therapy. - : Elsevier. - 2352-3204 .- 2352-3204. ; 22, s. 90-98 Tidskriftsartikel (refereegranskat)abstract Exosomes (diameter 30-200 nm) are a subtype of extracellular vesicles secreted by cells containing DNA, microRNA (miRNA), and proteins. Exosomes are expected to be valuable as a means of delivering drugs or functional miRNAs in treatment of diseases. However, the delivery of exosomes is not sufficiently effective, even though exosomes have intrinsic delivery functions. Cell-penetrating peptides (CPPs) are short peptide families that facilitate cellular intake of molecules and vesicles. We previously reported that the modification of cells, and liposomes with CPP-conjugated-lipids, CPPs conjugated with poly (ethylene glycol)-conjugated phospholipids (PEG-lipid), that induce adhesion by CPPs, can be useful for cell-based assays and harvesting liposomes. In this study, we aimed to modulate the exosome surface using Tat peptide (YGRKKRRQRRR)-PEG-lipids to improve intracellular delivery to endothelial cells. We isolated and characterized exosomes from the medium of HEK 293 T cell cultures. Tat conjugated PEG -lipids with different spacer molecular weights and lipid types were incorporated into exosomes using fluorescein isothiocyanate labeling to optimize the number of Tat-PEG-lipids immobilized on the exo-some surface. The exosomes modified with Tat-PEG-lipids were incubated with human umbilical vein endothelial cells (HUVECs) to study the interaction. Tat conjugated with 5 kDa PEG and C16 lipids incorporated on the exosome surface were highly detected inside HUVECs by flow cytometry. Fluores-cence was negligible in HUVECs for control groups. Thus, Tat-PEG-lipids can be modified on the exosome surface, improving the intracellular delivery of exosomes.(c) 2022, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).
57.	Kruger, D., et al. (författare) High-resolution ex vivo analysis of the degradation and osseointegration of Mg-xGd implant screws in 3D 2022 Ingår i: Bioactive Materials. - : Elsevier BV. - 2452-199X. ; 13, s. 37-52 Tidskriftsartikel (refereegranskat)abstract Biodegradable magnesium (Mg) alloys can revolutionize osteosynthesis, because they have mechanical properties similar to those of the bone, and degrade over time, avoiding the need of removal surgery. However, they are not yet routinely applied because their degradation behavior is not fully understood. In this study we have investigated and quantified the degradation and osseointegration behavior of two biodegradable Mg alloys based on gadolinium (Gd) at high resolution. Mg-5Gd and Mg-10Gd screws were inserted in rat tibia for 4, 8 and 12 weeks. Afterward, the degradation rate and degradation homogeneity, as well as bone-to-implant interface, were studied with synchrotron radiation micro computed tomography and histology. Titanium (Ti) and polyether ether ketone (PEEK) were used as controls material to evaluate osseointegration. Our results showed that Mg-5Gd degraded faster and less homogeneously than Mg-10Gd. Both alloys gradually form a stable degradation layer at the interface and were surrounded by new bone tissue. The results were correlated to in vitro data obtained from the same material and shape. The average bone-to-implant contact of the Mg-xGd implants was comparable to that of Ti and higher than for PEEK. The results suggest that both Mg-xGd alloys are suitable as materials for bone implants.
58.	Mellgren, Torbjörn, 1986-, et al. (författare) Guided bone tissue regeneration using a hollow calcium phosphate based implant in a critical size rabbit radius defect 2021 Ingår i: Biomedical Materials. - : Institute of Physics Publishing (IOPP). - 1748-6041 .- 1748-605X. ; 16:3 Tidskriftsartikel (refereegranskat)abstract Long bone fractures are common and sometimes difficult to treat. Autologous bone (AB), bovine bone and calcium phosphates are used to stimulate bone growth with varying results. In the present study, a calcium phosphate cement (CPC) that previously showed promising grafting capabilities was evaluated for the first time in a long bone defect. A radius defect of 20 mm was created in 20 rabbits. The defect was filled by either a hollow CPC implant that had been manufactured as a replica of a rabbit radius through indirect 3D printing, or by particulate AB as control. Defect filling and bone formation was evaluated after 12 weeks by combining micro computed tomography (mu CT) and scoring of 3D images, together with histomorphometry and histology. The mu CT and histomorphometric evaluations showed a similar amount of filling of the defect (combining graft and bone) between the CPC and AB group, but the scoring of 3D images showed that the filling in the CPC group was significantly larger. Histologically the AB graft could not be distinguished from the new bone. The AB treated defects were found to be composed of more bone than the CPC group, including reorganised cancellous and cortical bone. Both the CPC and AB material was associated with new bone formation, also in the middle of the defect, which could result in closing of the otherwise critically sized gap. This study shows the potential for an indirectly 3D printed implant in guided bone regeneration in critically sized long bone defects.
59.	Zhang, Yuecheng (författare) Glycosylation in cancer and infection : the role of sialic acid 2021 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Sialic acids (SA), a group of nine-carbon backbone monosaccharides are abundantly expressed in vertebrates. They are usually linked to the terminal of glycan chains and play crucial roles in many biological processes, including cell adhesion, cell-cell interactions, immune modulation, cancer cell migration and invasion, as well as viral infections. To analyze and monitor SA expression, antibodies and glycan-binding lectins are typically used. However, high costs and poor stability limit the application in SA analysis. To overcome these drawbacks, an imprinting technique was used to synthesize an alternative SA receptor – SA molecularly imprinted polymers (SA-MIPs). Fluorescent molecules are embedded into the MIPs, facilitating the detection of MIPs binding to cells by flow cytometry and fluorescence microscopy. Firstly, core-shell SA imprinted MIPs were used to analyze SA expression in a panel of breast cancer cell lines. The SA expression of these cell lines was also tested by using the two glycan-binding lectins, MAL andSNA, which recognize α2,3 and α2,6 SA, respectively. Our results show that breast cancer cell lines express α2,3 and α2,6 SA dissimilarly, and hence present different SA-MIP binding patterns. The specificity of SA-MIPs was further verified by an inhibition assay using two pentavalent SA conjugates that interfere with the SAMIPs.Furthermore, the SA-MIP synthesis protocol has been improved by using silica-coated polystyrene particles. The polystyrene core particles are lighter and smaller, increasing MIP suspensibility and augmenting MIP-cancer cell interactions. The cancer cell binding properties and the specificity have been verified by using thirteen different cancer cell lines, showing that the SA-MIPs can be used as effective tools for SA expression analysis. The SA-MIPs were used to analyze the SA expression of in vitro cultured cells treated with soluble cytokines to mimic the tumor microenvironment. The SA expression of two cancer cell lines stimulated with soluble cytokines was analyzed by using lectins and SA-MIPs. The MIPbinding data correlated well with lectin staining results, demonstrating the potential of SA-MIPs to be used in the analysis of overexpressed SA in the tumor microenvironment. Furthermore, the involvement of SA in the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was assessed. The viral surface receptor-binding domain (RBD) recognizes and conjugates with receptors on host cells, triggering the infection. Although the interaction between the RBD and host cells has been extensively studied, the mechanism behind this reaction is not fully determined. In this study, the interaction between the viral RBD and a panel of human cell lines from tissues susceptible to viral infection was tested. Moreover, the role of SA in this interaction has also been tested and evaluated.
60.	Ekvall, Mikael T, et al. (författare) Size fractionation of high-density polyethylene breakdown nanoplastics reveals different toxic response in Daphnia magna 2022 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12, s. 3109-3109 Tidskriftsartikel (refereegranskat)abstract Plastic litter is a growing environmental problem. Recently, microplastics and nanoplastics, produced during breakdown processes in nature, have been in focus. Although there is a growing knowledge concerning microplastic, little is still known about the effect of nanoplastics. We have showed that mechanical breakdown of high-density polyethylene (HDPE), followed by filtration through 0.8 µm filters, produces material toxic to the freshwater zooplankton Daphnia magna and affected the reproduction in life-time tests. However, further size fractionation and purification reveals that the nanoplastics fraction is non-toxic at these concentrations, whereas the fraction with smaller sizes, below ~ 3 nm, is toxic. The HDPE nanoplastics are highly oxidized and with an average diameter of 110 nm. We conclude that mechanical breakdown of HDPE may cause environmental problems, but that the fraction of leached additives and short chain HDPE are more problematic than HDPE nanoplastics.
61.	Bharmoria, Pankaj, 1985, et al. (författare) Protein-olive oil-in-water nanoemulsions as encapsulation materials for curcumin acting as anticancer agent towards MDA-MB-231 cells 2021 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 11:1, s. 9099-9099 Tidskriftsartikel (refereegranskat)abstract The sustainable cellular delivery of the pleiotropic drug curcumin encounters drawbacks related to its fast autoxidation at the physiological pH, cytotoxicity of delivery vehicles and poor cellular uptake. A biomaterial compatible with curcumin and with the appropriate structure to allow the correct curcumin encapsulation considering its poor solubility in water, while maintaining its stability for a safe release was developed. In this work, the biomaterial developed started by the preparation of an oil-in-water nanoemulsion using with a cytocompatible copolymer (Pluronic F 127) coated with a positively charged protein (gelatin), designed as G-Cur-NE, to mitigate the cytotoxicity issue of curcumin. These G-Cur-NE showed excellent capacity to stabilize curcumin, to increase its bio-accessibility, while allowing to arrest its autoxidation during its successful application as an anticancer agent proved by the disintegration of MDA-MB-231 breast cancer cells as a proof of concept.
62.	Casanova, Elisa A., et al. (författare) SAXS imaging reveals optimized osseointegration properties of bioengineered oriented 3D-PLGA/aCaP scaffolds in a critical size bone defect model 2023 Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 294 Tidskriftsartikel (refereegranskat)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.
63.	Giubertoni, Giulia, et al. (författare) Strong reduction of the chain rigidity of hyaluronan by selective binding of Ca2+ ions 2021 Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 54:3, s. 1137-1146 Tidskriftsartikel (refereegranskat)abstract The biological functions of natural polyelectrolytes are strongly influenced by the presence of ions, which bind to the polymer chains and thereby modify their properties. Although the biological impact of such modifications is well recognized, a detailed molecular picture of the binding process and of the mechanisms that drive the subsequent structural changes in the polymer is lacking. Here, we study the molecular mechanism of the condensation of calcium, a divalent cation, on hyaluronan, a ubiquitous polymer in human tissues. By combining two-dimensional infrared spectroscopy experiments with molecular dynamics simulations, we find that calcium specifically binds to hyaluronan at millimolar concentrations. Because of its large size and charge, the calcium cation can bind simultaneously to the negatively charged carboxylate group and the amide group of adjacent saccharide units. Molecular dynamics simulations and single-chain force spectroscopy measurements provide evidence that the binding of the calcium ions weakens the intramolecular hydrogen-bond network of hyaluronan, increasing the flexibility of the polymer chain. We also observe that the binding of calcium to hyaluronan saturates at a maximum binding fraction of ∼10–15 mol %. This saturation indicates that the binding of Ca2+ strongly reduces the probability of subsequent binding of Ca2+ at neighboring binding sites, possibly as a result of enhanced conformational fluctuations and/or electrostatic repulsion effects. Our findings provide a detailed molecular picture of ion condensation and reveal the severe effect of a few, selective and localized electrostatic interactions on the rigidity of a polyelectrolyte chain.
64.	Iqbal, Muhammad Naeem, et al. (författare) Surface Effect of Nano-Roughened Yttria-Doped Zirconia on Salivary Protein Adhesion 2021 Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 14:21 Tidskriftsartikel (refereegranskat)abstract Biocompatibility of yttria (3 mol%) stabilized zirconia ceramics, 3Y-TZP, was affected to a large degree as a result of protein adsorption from human saliva that in turn depends on materials surface properties. Variable nano-roughness levels in 3Y-TZP discs were characterized and tested for specificity and selectivity with respect to size and uptake for human salivary protein.
65.	Liebi, Marianne, 1984, et al. (författare) 3D nanoscale analysis of bone healing around degrading Mg implants evaluated by X-ray scattering tensor tomography 2021 Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 134, s. 804-817 Tidskriftsartikel (refereegranskat)abstract The nanostructural adaptation of bone is crucial for its biocompatibility with orthopedic implants. The bone nanostructure also determines its mechanical properties and performance. However, the bone's temporal and spatial nanoadaptation around degrading implants remains largely unknown. Here, we present insights into this important bone adaptation by applying scanning electron microscopy, elemental analysis, and small-angle X-ray scattering tensor tomography (SASTT). We extend the novel SASTT reconstruction method and provide a 3D scattering reciprocal space map per voxel of the sample's volume. From this reconstruction, parameters such as the thickness of the bone mineral particles are quantified, which provide additional information on nanostructural adaptation of bone during healing. We selected a rat femoral bone and a degrading ZX10 magnesium implant as model system, and investigated it over the course of 18 months, using a sham as control. We observe that the bone's nanostructural adaptation starts with an initially fast interfacial bone growth close to the implant, which spreads by a re-orientation of the nanostructure in the bone volume around the implant, and is consolidated in the later degradation stages. These observations reveal the complex bulk bone-implant interactions and enable future research on the related biomechanical bone responses. Statement of significance: Traumatic bone injuries are among the most frequent causes of surgical treatment, and often require the placement of an implant. The ideal implant supports and induces bone formation, while being mechanically and chemically adapted to the bone structure, ensuring a gradual load transfer. While magnesium implants fulfill these requirements, the nanostructural changes during bone healing and implant degradation remain not completely elucidated. Here, we unveil these processes in rat femoral bones with ZX10 magnesium implants and show different stages of bone healing in such a model system.
66.	Thesleff, Alexander, 1986, et al. (författare) The effect of cortical thickness and thread profile dimensions on stress and strain in bone-anchored implants for amputation prostheses 2022 Ingår i: Journal of the Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 129 Tidskriftsartikel (refereegranskat)abstract Skeletal attachment of limb prostheses ensures load transfer between the prosthetic leg and the skeleton. For individuals with lower limb amputation, these loads may be of substantial magnitude. To optimize the design of such systems, knowledge about the structural interplay between implant design features, dimensional changes, and material properties of the implant and the surrounding bone is needed. Here, we present the results from a parametric finite element investigation on a generic bone-anchored implant system of screw design, exposed to external loads corresponding to average and high ambulatory loading. Of the investigated parameters, cortical thickness had the largest effect on the stress and strain in the bone-anchored implant and in the cortical bone. 36%–44% reductions in maximum longitudinal stress in the bone-anchored implant was observed as a result of increased cortical thickness from 2 mm to 5 mm. A change in thread depth from 1.5 mm to 0.75 mm resulted in 20%–22% and 10%–18% reductions in maximum longitudinal stress in the bone-anchored implant at 2 mm and 5 mm cortical thickness respectively. The effect of changes in the thread root radius was less prominent, with 8% reduction in the maximum longitudinal stress in the bone-anchored implant being the largest observed effect, resulting from an increased thread root radius from 0.1 mm to 0.5 mm at a thread depth of 1.5 mm. Autologous transplantation of bone tissue distal to the fixture resulted in reductions in the longitudinal stress in the percutaneous abutment. The observed stress reduction of 10%–31% was dependent on the stiffness of the transplanted bone graft and the cortical thickness of surrounding bone. Results from this investigation may guide structural design optimization for bone-anchored implant systems for attachment of limb prostheses. © 2022 The Authors
67.	Johansson, Martin L, et al. (författare) Clinical retrieval and analysis of percutaneous bone-anchored hearing implants using multiple analytical methodologies 2020 Ingår i: 11TH WORLD BIOMATERIALS CONGRESS 11 - 15 December 2020. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Introduction: The percutaneous bone-anchored hearing system (BAHS) is an established form of hearing treatment for conductive or mixed hearing loss and single sided deafness [1]. The system consists of a titanium implant inserted in the temporal bone and mounted with an abutment onto which a sound processor is attached. It is considered to be a successful treatment with generally good outcomes in terms of audiology and quality of life [2]. However, associated adverse outcomes, such as peri-abutment inflammation and infection, pain and numbness may necessitate intervention, device removal or implant loss [2, 3]. The clinician must rely on subjective clinical measurements, whereas information on the biological events at the tissue-BAHS interface remain inaccessible. Reports of analyses of planned, electively retrieved BAHS implants, performed under perfectly controlled circumstances, are rare [4, 5]. The aim with this study was to gain insight into the biological processes around percutaneous bone-conducting devices by analysing retrieved implants. Experimental methods: Through the establishment of a bilateral collaboration network with European clinics, a retrieval and analytical protocol have been implemented. This will allow correlation of the clinical data with the underpinning microbiological, molecular and morphological fingerprints at the tissue interface. Multiple analytical and correlative strategies have been used, enabling multiscale and multimodal investigation of the tissue interface. Different sampling procedures and analytical tools were employed, including X-ray micro-computed tomography (micro-CT), histology/histomorphometry, fluorescence in situ hybridization (FISH), microbiology, quantitative polymerase chain reaction (qPCR), backscattered electron scanning electron microscopy (BSE-SEM) and Raman spectroscopy. Results and discussions: So far, retrieval, preservation and investigation of six BAHS implants with surrounding tissue have been performed. Causes for removal (1-7 years after implantation) were chronic pain, recurrent inflammation, cancer and mechanical complications. After micro-CT analysis and the samples were embedded for histological and ultrastructural analyses. This presentation describes the sample preparation route allowing assessment of the different hierarchical levels of interest of the tissue interface. Examples of the results from the different analyses will be presented, with emphasis on correlating the clinical outcome with the analytical findings. Conclusions: The implementation of a retrieval protocol combined with a subsequent multi-scale analytical strategy enables a correlation between the clinical history of patients and the underpinning microbiological, molecular and morphological events in the tissues interfacing the electively removed or failed percutaneous bone-anchored hearing implants.
68.	Geng, HY, et al. (författare) Noble Metal Nanoparticle Biosensors: From Fundamental Studies toward Point-of-Care Diagnostics 2022 Ingår i: Accounts of chemical research. - : American Chemical Society (ACS). - 1520-4898 .- 0001-4842. ; 55:5, s. 593-604 Tidskriftsartikel (refereegranskat)
69.	Lin, YY, et al. (författare) High-Throughput Peptide Derivatization toward Supramolecular Diversification in Microtiter Plates 2021 Ingår i: ACS nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 15:3, s. 4034-4044 Tidskriftsartikel (refereegranskat)
70.	Omar, Omar, et al. (författare) In situ bone regeneration of large cranial defects using synthetic ceramic implants with a tailored composition and design 2020 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:43, s. 26660-26671 Tidskriftsartikel (refereegranskat)abstract The repair of large cranial defects with bone is a major clinical challenge that necessitates novel materials and engineering solutions. Three-dimensionally (3D) printed bioceramic (BioCer) implants consisting of additively manufactured titanium frames enveloped with CaP BioCer or titanium control implants with similar designs were implanted in the ovine skull and at s.c. sites and retrieved after 12 and 3 mo, respectively. Samples were collected for morphological, ultrastructural, and compositional analyses using histology, electron microscopy, and Raman spectroscopy. Here, we show that BioCer implants provide osteoinductive and microarchitectural cues that promote in situ bone regeneration at locations distant from existing host bone, whereas bone regeneration with inert titanium implants was confined to ingrowth from the defect boundaries. The BioCer implant promoted bone regeneration at nonosseous sites, and bone bonding to the implant was demonstrated at the ultrastructural level. BioCer transformed to carbonated apatite in vivo, and the regenerated bone displayed a molecular composition indistinguishable from that of native bone. Proof-of-principle that this approach may represent a shift from mere reconstruction to in situ regeneration was provided by a retrieved human specimen, showing that the BioCer was transformed into well-vascularized osteonal bone, with a morphology, ultrastructure, and composition similar to those of native human skull bone.
71.	Katsaros, Ioannis, et al. (författare) Bioactive Silicon Nitride Implant Surfaces with Maintained Antibacterial Properties 2022 Ingår i: Journal of Functional Biomaterials. - : MDPI. - 2079-4983. ; 13:3 Tidskriftsartikel (refereegranskat)abstract Silicon nitride (Si3N4) is a promising biomaterial, currently used in spinal fusion implants. Such implants should result in high vertebral union rates without major complications. However, pseudarthrosis remains an important complication that could lead to a need for implant replacement. Making silicon nitride implants more bioactive could lead to higher fusion rates, and reduce the incidence of pseudarthrosis. In this study, it was hypothesized that creating a highly negatively charged Si3N4 surface would enhance its bioactivity without affecting the antibacterial nature of the material. To this end, samples were thermally, chemically, and thermochemically treated. Apatite formation was examined for a 21-day immersion period as an in-vitro estimate of bioactivity. Staphylococcus aureus bacteria were inoculated on the surface of the samples, and their viability was investigated. It was found that the thermochemically and chemically treated samples exhibited enhanced bioactivity, as demonstrated by the increased spontaneous formation of apatite on their surface. All modified samples showed a reduction in the bacterial population; however, no statistically significant differences were noticed between groups. This study successfully demonstrated a simple method to improve the in vitro bioactivity of Si3N4 implants while maintaining the bacteriostatic properties.
72.	Skjöldebrand, Charlotte, et al. (författare) Si-Fe-C-N Coatings for Biomedical Applications : A Combinatorial Approach 2020 Ingår i: Materials. - : MDPI. - 1996-1944. ; 13:9 Tidskriftsartikel (refereegranskat)abstract Ceramic coatings may prolong the lifetime of joint implants. Certain ions and wear debris may however lead to negative biological effects. SiN-based materials may substantially reduce these effects, but still need optimization for the application. In this study, a combinatorial deposition method enabled an efficient evaluation of a range of Si-Fe-C-N coating compositions on the same sample. The results revealed compositional gradients of Si (26.0-33.9 at.%), Fe (9.6-20.9 at.%), C (8.2-13.9 at.%) and N (39.7-47.2 at.%), and low oxygen contaminations (0.3-0.6 at.%). The mechanical properties varied with a hardness (H) ranging between 13.7-17.3 GPa and an indentation modulus (M) between 190-212 GPa. Both H and M correlated with the Si (H and M increased as Si increased) and Fe (H and M decreased as Fe increased) content. A slightly columnar morphology was observed in cross-sections, as well as a surface roughness in the nm range. A cell study revealed adhering pre-osteogenic MC3T3 cells, with a morphology similar to that of cells seeded on a tissue culture plastic control. The investigated coatings could be considered for further investigation due to the ability to tune their mechanical properties while maintaining a smooth surface, together with their promising in vitro cell response.
73.	Rosendahl, Jennifer (författare) 3D Printed scaffolds as cancer microenvironment medels for drug discovery 2022 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Cancer is one of the most common diseases in the modern world and major efforts are made globally to develop new diagnostics and treatments. It originates from a cell which, at some point, has begun to divide and grow uncontrollably. The most common type is breast cancer, and like all other cancers there is a need of more efficient drug therapies. Drug development is an expensive and time-consuming process and in conventional pre-clinical evaluation, drugs are tested on cells grown in 2D followed by experimental studies in animals. Only the drug candidates with best efficacy and safety profiles are allowed to proceed to clinical trials in humans. A major problem is that the pre-clinical test methods most often do not adequately represent the microenvironment in the human body and only a portion of the drugs that show good effect in pre-clinical studies pass the clinical trials and reaches market. Failures in late development mean large losses both financially and in time, and better pre-clinical test methods are needed that can predict more accurate results for safety and efficacy. The behavior of cancer cells is strongly influenced by the surrounding microenvironment, but today’s drug development focuses mainly on the cells themselves and does not sufficiently take this into account. This thesis combines 3D printing and cell biology to develop new and more representative test systems, with the ambition to mimic the tumor microenvironment in three dimensions. By using patient tumor tissue and removing the original cells, we produce a cell-free extracellular matrix scaffold to which standardized reporter breast cancer cell lines are reintroduced. The cell lines grown in the patient derived scaffolds developed more stem cell properties and formed a more heterogeneous cell population compared to 2D cultures. Moreover, the gene expression profile could be linked to clinical data, such as relapse. In an attempt to synthetically mimic the human tumor tissue, we used an alginate-based biomaterial to print 3D scaffolds. Breast cancer cells cultured in the 3D printed scaffolds showed a more similar growth- and gene expression pattern to cells cultured in patient derived scaffolds indicating that we were able to simulate the human tumor microenvironment. Further, we showed that the cells cultured in both patient derived scaffolds and 3D printed scaffolds had a similar response to hypoxic conditions – which is an important factor in tumors. Finally, we also showed that nanocellulose could be used to 3D print and that cells cultured in these scaffolds demonstrated comparable results to cells grown in alginate-based 3D printed scaffolds.
74.	Gefen, Amit, et al. (författare) How should clinical wound care and management translate to effective engineering standard testing requirements from foam dressings? Mapping the existing gaps and needs 2023 Ingår i: Advances in wound care. - : Mary Ann Liebert. - 2162-1918 .- 2162-1934. ; 13:1 Tidskriftsartikel (refereegranskat)abstract SIGNIFICANCE: Wounds of all types remain one of the most important, expensive and common medical problems, e.g., up to approximately two-thirds of the work time of community nurses is spent on wound management. Many wounds are treated by means of dressings. The materials used in a dressing, their microarchitecture and how they are composed and constructed form the basis for the laboratory and clinical performances of any advanced dressing. Recent Advances: The established structure-function principle in material science is reviewed and analyzed in this article in the context of wound dressings. This principle states that the microstructure determines the physical, mechanical, and fluid transport and handling properties, all of which are critically important for, and relevant to the adequate performances of wound dressings.CRITICAL ISSUES: According to the above principle, once the clinical requirements for wound care and management are defined for a given wound type and etiology, it should be theoretically possible to translate clinically-relevant characteristics of dressings into physical test designs resulting specific metrics of materials, mechanical, and fluid transport and handling properties, all of which should be determined to meet the clinical objectives and be measurable through standardized bench testing.FUTURE DIRECTIONS: This multidisciplinary review article, written by an International Wound Dressing Technology Expert Panel, discusses the translation of clinical wound care and management into effective, basic engineering standard testing requirements from wound dressings with respect to material types, microarchitecture and properties, to achieve the desirable performance in supporting healing and improving the quality of life of patients.
75.	Shah, Furqan A. (författare) Towards refining Raman spectroscopy-based assessment of bone composition 2020 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1 Tidskriftsartikel (refereegranskat)abstract Various compositional parameters are derived using intensity ratios and integral area ratios of different spectral peaks and bands in the Raman spectrum of bone. The nu(1)-, nu(2)-,nu(3)-, nu(4) PO43-, and nu 1 CO32- bands represent the inorganic phase while amide I, amide III, Proline, Hydroxyproline, Phenylalanine, delta(CH3), delta(CH2), and nu(C-H) represent the organic phase. Here, using high-resolution Raman spectroscopy, it is demonstrated that all PO43- bands of bone either partially overlap with or are positioned close to spectral contributions from the organic component. Assigned to the organic component, a shoulder at 393 cm(-1) compromises accurate estimation of nu(2) PO43- integral area, i.e., phosphate/apatite content, with implications for apatite-to-collagen and carbonate-to-phosphate ratios. Another feature at 621 cm(-1) may be inaccurately interpreted as nu(4) PO43- band broadening. In the 1020-1080 cm(-1) range, the similar to 1047 cm(-1)nu(3) PO43- sub-component is obscured by the 1033 cm(-1) Phenylalanine peak, while the similar to 1076 cm(-1)nu(3) PO43- sub-component is masked by the nu(1) CO32- band. With nu(1) PO43- peak broadening, nu(2) PO43- integral area increases exponentially and individual peaks comprising the nu(4) PO43- band merge together. Therefore, nu(2) PO43- and nu(4) PO43- band profiles are sensitive to changes in mineral crystallinity.
76.	Chen, Song, et al. (författare) Formation of Amorphous Iron-Calcium Phosphate with High Stability 2023 Ingår i: Advanced Materials. - : John Wiley & Sons. - 0935-9648 .- 1521-4095. ; 35:33 Tidskriftsartikel (refereegranskat)abstract Amorphous iron-calcium phosphate (Fe-ACP) plays a vital role in the mechanical properties of teeth of some rodents, which are very hard, but its formation process and synthetic route remain unknown. Here, the synthesis and characterization of an iron-bearing amorphous calcium phosphate in the presence of ammonium iron citrate (AIC) are reported. The iron is distributed homogeneously on the nanometer scale in the resulting particles. The prepared Fe-ACP particles can be highly stable in aqueous media, including water, simulated body fluid, and acetate buffer solution (pH 4). In vitro study demonstrates that these particles have good biocompatibility and osteogenic properties. Subsequently, Spark Plasma Sintering (SPS) is utilized to consolidate the initial Fe-ACP powders. The results show that the hardness of the ceramics increases with the increase of iron content, but an excess of iron leads to a rapid decline in hardness. Calcium iron phosphate ceramics with a hardness of 4 GPa can be achieved, which is higher than that of human enamel. Furthermore, the ceramics composed of iron-calcium phosphates show enhanced acid resistance. This study provides a novel route to prepare Fe-ACP, and presents the potential role of Fe-ACP in biomineralization and as starting material to fabricate acid-resistant high-performance bioceramics.
77.	Abiodun Daramola, Olamide, et al. (författare) Biocompatible liposome and chitosan-coated CdTe/CdSe/ZnSe multi-core-multi-shell fluorescent nanoprobe for biomedical applications 2024 Ingår i: Journal of Photochemistry and Photobiology A. - : Elsevier. - 1010-6030 .- 1873-2666. ; 454 Tidskriftsartikel (refereegranskat)abstract Cadmium telluride (CdTe) semiconductor quantum dots (QDs) are brightly luminescent nanocrystals that have emerged as a new class of fluorescent probes for in vivo bioimaging and theranostic applications. CdTe QDs toxicity to normal human cells is minimized by coating with a less toxic ZnS and ZnSe shell forming a core–shell nanostructure. However, coating with ZnS or ZnSe shell is insufficient to prevent the leaching of toxic Cd metal ions. To further minimize toxicity, thiol dual capped CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots were coated with nanoliposome or liposome vesicles (CdTe/CdSe/ZnSe@liposome) and chitosan nanoparticles (CdTe/CdSe/ZnSe@ChitNPs) and their biocompatibility on HeLa and Vero cells were investigated. Different spectroscopic and microscopic techniques were used to elucidate nanocomposites' optical, morphological, and physicochemical properties. The coating of CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots were conducted at different formulations (F1, F2 and F3) and results from the fluorescence studies show that F3 demonstrated the best interaction for both liposome and ChitNPs composite. Exposure to 12 h UV illumination studies also reveals that CdTe/CdSe/ZnSe@liposome shows an enhancement in fluorescence compared to CdTe/CdSe/ZnSe@ChitNPs. The cytotoxicity of the formulations towards HeLa and Vero cells also depicted minimal toxicity compared to CdTe/CdSe/ZnSe QDs that shows much higher toxicity (IC50 = 0.09381 mg/ml). It was further observed that liposome coated multi-core-multi-shell QDs@F2 demonstrated lower toxicity (IC50 = 0.4364 mg/ml) compared to ChitNPs coated multi-core-multi-shell QDs@F2 (IC50 = 0.1618 mg/ml). Results from the florescence imaging studies reveal that CdTe/CdSe/ZnSe-multi-core-multi-shell QDs liposomes and ChitNPs composite retained most of their fluorescence and properties and could easily be tracked in cells and visualized around the nucleus. This indicates the successful internalization of the QDs in the cytosol. Therefore, these results shows that coating CdTe multi-core-mutli-shell QDs with liposomes and ChitNPs produce better biocompatibility compared to uncoated multi-core–shell QDs. However, liposome coated CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots show better optical properties, photostability and biocompatibility compared to CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots with ChitNPs coating. These particles therefore show good promise in cell-labelling and drug delivery studies.
78.	Chen, Jingjing, et al. (författare) Heat-transfer performance of twisted tubes for highly viscous food waste slurry from biogas plants 2022 Ingår i: Biotechnology for Biofuels and Bioproducts. - : Springer Nature. - 2731-3654. ; 15 Tidskriftsartikel (refereegranskat)abstract Background: The use of food waste as feedstock shows high production of biogas via anaerobic digestion, but requires efficient heat transfer in food waste slurry at heating and cooling processes. The lack of rheological properties hampered the research on the heat-transfer process for food waste slurry. Referentially, the twisted hexagonal and elliptical rubes have been proved as the optimal enhanced geometry for heat transfer of medium viscous slurries with non-Newtonian behavior and Newtonian fluids, respectively. It remains unknown whether improvements can be achieved by using twisted geometries in combination with food waste slurry in processes including heating and cooling.Results: Food waste slurry was observed to exhibit highly viscous, significant temperature-dependence, and strongly shear-thinning rheological characteristics. Experiments confirmed the heat-transfer enhancement of twisted hexagonal tubes for food waste slurry and validated the computational fluid dynamics-based simulations with an average deviation of 14.2%. Twisted hexagonal tubes were observed to be more effective at low-temperature differences and possess an enhancement factor of up to 2.75; while twisted elliptical tubes only exhibited limited heat-transfer enhancement at high Reynolds numbers. The heat-transfer enhancement achieved by twisted hexagonal tubes was attributed to the low dynamic viscosity in the boundary layer induced by the strong and continuous shear effect near the walls of the tube.Conclusions: This study determined the rheological properties of food waste slurry, confirmed the heat-transfer enhancement of the twisted hexagonal tubes experimentally and numerically, and revealed the mechanism of heat-transfer enhancement based on shear rate distributions.
79.	Li, Yuyang (författare) Synthesis and Characterization of Nanoprobes for X-Ray Fluorescence Computed Tomography (XFCT) Bio-imaging 2020 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract X-ray fluorescence computed tomography (XFCT) is an emerging biomedical imaging technique. The KTH-XFCT laboratory system offers a characteristic 24 keV emission line, and high spatial resolution (200 ?m) images. XFCT as a newly emerging modality also requires the exploration and development of suitable contrast agents. Nanomaterials have been widely used as contrast agents in many popular imaging modalities like MRI, PET, and CT. They have several advantages including long blood circulation time, high ratio of surface area to volume, and enhanced image contrast. However, the use of nanomaterials as contrast agents is limited by their biocompatibility and toxicity, which are determined by the physicochemical properties including size, morphology, surface chemistry. Therefore, the study on the synthesis and characterization of nanomaterials is an indispensable step. In this thesis, a group of elements (Y, Zr, Nb, Ru, Rh) are selected based on the X-ray K?-absorption energy, matching with the 24 keV emission line of KTH-XFCT source. Y, Zr, Nb, Ru and Rh based nanoparticles are synthesized by hydrothermal and polyol method, identified as the ceramic and metallic groups. XRF performance is demonstrated by the XFCT system. Metallic Ru and Rh nanoparticles are further selected to study the synthesis conditions and in vitro toxicity for their smaller TEM and hydrodynamic size. Surface properties are investigated to show the isoelectric point and polymer coating on the metallic nanoparticles. Morphological different Rh nanoparticles are obtained by introducing different additives during the synthesis, indicating the different cytotoxicity performance attributed to different morphologies. Silica coating is further performed on the surface of metallic and metallic nanoparticles to improve their biocompatibility. The in vitro toxicity assessment are performed on the murine macrophages and human ovarian cancer cell lines. X-ray fluorescence performance is evaluated for each nanoparticles by using soft-tissue equivalent holder and in situ small-animal imaging experiments. The results indicates the spatial resolution and detection sensitivity of the concentration of the metallic nanoparticles. In this work, we demonstrate the potential of a group selected nanomaterials as XFCT contrast agents for the first time, especially, investigate the synthesis, surface properties, in vitro toxicity as well as detection sensitivity of the metallic nanoparticles.
80.	Stepulane, Annija, 1994, et al. (författare) Lyotropic liquid crystal elastomers for drug delivery 2023 Ingår i: Colloids and Surfaces B: Biointerfaces. - 0927-7765 .- 1873-4367. ; 226 Tidskriftsartikel (refereegranskat)abstract Silicone elastomers like polydimethylsiloxane (PDMS) possess a combination of attractive material and biological properties motivating their widespread use in biomedical applications. Development of elastomers with capacity to deliver active therapeutic substances in the form of drugs is of particular interest to produce medical devices with added functionality. In this work, silicone-based lyotropic liquid crystal elastomers with drug-eluting functionality were developed using PDMS and triblock copolymer (diacrylated Pluronic F127, DA-F127). Various ternary PDMS–DA-F127–H2O compositions were explored and evaluated. Three compositions were found to have specific properties of interest and were further investigated for their nanostructure, mechanical properties, water retention capacity, and morphology. The ability of the elastomers to encapsulate and release polar and nonpolar substances was demonstrated using vancomycin and ibuprofen as model drugs. It was shown that the materials could deliver both types of drugs with a sustained release profile for up to 6 and 5 days for vancomycin and ibuprofen, respectively. This works demonstrates a lyotropic liquid crystal, silicone-based elastomer with tailorable mechanical properties, water retention capacity and ability to host and release polar and nonpolar active substances.
81.	Hellman, Lars (författare) Phenotypic and Functional Heterogeneity of Monocytes and Macrophages 2023 Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:19 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
82.	Micheletti, Chiara, et al. (författare) Ultrastructure and Nanoporosity of Human Bone Shown with Correlative On-Axis Electron and Spectroscopic Tomographies 2023 Ingår i: ACS Nano. - 1936-0851 .- 1936-086X. ; 17:24, s. 24710-24724 Tidskriftsartikel (refereegranskat)abstract Mineralized collagen fibrils are the building block units of bone at the nanoscale. While it is known that collagen fibrils are mineralized both inside their gap zones (intra-fibrillar mineralization) and on their outer surfaces (extra-fibrillar mineralization), a clear visualization of this architecture in three dimensions (3D), combining structural and compositional information over large volumes, but without compromising the resolution, remains challenging. In this study, we demonstrate the use of on-axis Z-contrast electron tomography (ET) with correlative energy-dispersive X-ray spectroscopy (EDX) tomography to examine rod-shaped samples with diameters up to 700 nm prepared from individual osteonal lamellae in the human femur. Our work mainly focuses on two aspects: (i) low-contrast nanosized circular spaces (“holes”) observed in sections of bone oriented perpendicular to the long axis of a long bone, and (ii) extra-fibrillar mineral, especially in terms of morphology and spatial relationship with respect to intra-fibrillar mineral and collagen fibrils. From our analyses, it emerges quite clearly that most “holes” are cross-sectional views of collagen fibrils. While this had been postulated before, our 3D reconstructions and reslicing along meaningful two-dimensional (2D) cross-sections provide a direct visual confirmation. Extra-fibrillar mineral appears to be composed of thin plates that are interconnected and span over several collagen fibrils, confirming that mineralization is cross-fibrillar, at least for the extra-fibrillar phase. EDX tomography shows mineral signatures (Ca and P) within the gap zones, but the signal appears weaker than that associated with the extra-fibrillar mineral, pointing toward the existence of dissimilarities between the two types of mineralization.
83.	Pless, Christian J., et al. (författare) Emerging strategies in 3D printed tissue models for in vitro biomedical research 2022 Ingår i: Bioprinting : From Multidisciplinary Design to Emerging Opportunities - From Multidisciplinary Design to Emerging Opportunities. - 9780323854306 - 9780323854313 ; , s. 207-246 Bokkapitel (refereegranskat)abstract 3D bioprinting has the potential to provide a unified framework for the manufacturing of tissue models for biomedical research, including drug discovery, disease modeling, and regenerative medicine. However, it remains challenging to 3D print replicas of human tissues that have accurate cell types, cellular densities, extracellular matrix compositions, and that can be assayed in a minimally invasive manner for chronic studies. Here, we review how recent breakthroughs in stem cell biology, tissue engineering, and materials science have led to novel 3D printing strategies that have the potential to solve these challenges.
84.	Osinger, Barbara, et al. (författare) Investigation of the phase formation in magnetron sputtered hard multicomponent (HfNbTiVZr)C coatings 2022 Ingår i: Materials & design. - : ELSEVIER SCI LTD. - 0264-1275 .- 1873-4197. ; 221 Tidskriftsartikel (refereegranskat)abstract Multicomponent carbides have gained interest especially for ultra-high temperature applications, due to their ceramic hardness, good oxidation resistance and enhanced strength. In this study the phase forma-tion, stability and mechanical properties of (HfNbTiVZr)C multicomponent carbide coatings were inves-tigated. Phase stability was predicted by the CALPHAD (CALculation of PHAse Diagrams) methods. This revealed that the multicomponent solid solution phase is only stable at elevated temperatures, namely above 2400 degrees C. At lower temperatures a phase mixture was predicted, with a particular tendency for V to segregate. Magnetron sputtered thin films deposited at 300 degrees C exhibited a single NaCl-type multicom-ponent carbide phase, which attributes to the kinetic stabilisation of simple structures during thin film growth. Films deposited at 700 degrees C, or exposed to UHV annealing at 1000 degrees C, however, revealed the decom-position of the single-phase multicomponent carbide by partial elemental segregation and formation of additional phases. Thus, confirming the CALPHAD predictions. These results underscore the importance of explicitly considering temperature when discussing the stability of multicomponent carbide materials, as well as the applicability of CALPHAD methods for predicting phase formation and driving forces in these materials. The latter being crucial for designing materials, such as carbides, that are used in appli-cations at elevated temperatures.
85.	Prasanna, A. P.S., et al. (författare) Multifunctional ZnO/SiO2 Core/Shell Nanoparticles for Bioimaging and Drug Delivery Application 2020 Ingår i: Journal of Fluorescence. - : Springer Science and Business Media LLC. - 1573-4994 .- 1053-0509. ; 30:5, s. 1075-1083 Tidskriftsartikel (refereegranskat)abstract Semiconducting nanoparticles with luminescent properties are used as detection probes and drug carriers in in-vitro and in-vivo analysis. ZnO nanoparticles, due to its biocompatibility and low cost, have shown potential application in bioimaging and drug delivery. Thus, ZnO/SiO2 core/shell nanoparticle was synthesised by wet chemical method for fluorescent probing and drug delivery application. The synthesised core/shell nanomaterial was characterized using XRD, FTIR, UV-VIS spectroscopy, Raman spectroscopy, TEM and PL analysis. The silicon shell enhances the photoluminescence and aqueous stability of the pure ZnO nanoparticles. The porous surface of the shell acts as a carrier for sustained release of curcumin. The synthesized core/shell particle shows high cell viability, hemocompatibility and promising florescent property. [Figure not available: see fulltext.].
86.	Chen, Yan-Ting, et al. (författare) Biomimetic Platelet Nanomotors for Site-Specific Thrombolysis and Ischemic Injury Alleviation 2023 Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 15:27, s. 32967-32983 Tidskriftsartikel (refereegranskat)abstract Due to the mortality associated with thrombosis and its highrecurrence rate, there is a need to investigate antithrombotic approaches.Noninvasive site-specific thrombolysis is a current approach being used; however,its usage is characterized by the following limitations: low targeting efficiency, poorability to penetrate clots, rapid half-life, lack of vascular restoration mechanisms,and risk of thrombus recurrence that is comparable to that of traditionalpharmacological thrombolysis agents. Therefore, it is vital to develop an alternativetechnique that can overcome the aforementioned limitations. To this end, a cottonball-shaped platelet (PLT)-mimetic self-assembly framework engineered with aphototherapeutic poly(3,4-ethylenedioxythiophene) (PEDOT) platform has beendeveloped. This platform is capable of delivering a synthetic peptide derived fromhirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotors fornoninvasive site-specific thrombolysis, effective anticoagulation, and vascularrestoration. Regulated by P-selectin mediation, the P6@PEDOT@PLT nanomotors target the thrombus site and subsequentlyrupture under near-infrared (NIR) irradiation, achieving desirable sequential drug delivery. Furthermore, the movement ability ofthe P6@PEDOT@PLT nanomotors under NIR irradiation enables effective penetration deep into thrombus lesions, enhancingbioavailability. Biodistribution analyses have shown that the administered P6@PEDOT@PLT nanomotors exhibit extendedcirculation time and metabolic capabilities. In addition, the photothermal therapy/photoelectric therapy combination cansignificantly augment the effectiveness (ca. 72%) of thrombolysis. Consequently, the precisely delivered drug and the resultantphototherapeutic-driven heat-shock protein, immunomodulatory, anti-inflammatory, and inhibitory plasminogen activator inhibitor1 (PAI-1) activities can restore vessels and effectively prevent rethrombosis. The described biomimetic P6@PEDOT@PLTnanomotors represent a promising option for improving the efficacy of antithrombotic therapy in thrombus-related illnesses.
87.	Chen, Zhixuan, et al. (författare) Effects of Zinc, Magnesium, and Iron Ions on Bone Tissue Engineering 2022 Ingår i: ACS Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 8:6, s. 2321-2335 Forskningsöversikt (refereegranskat)abstract Large-sized bone defects are a great challenge in clinics and considerably impair the quality of patients' daily life. Tissue engineering strategies using cells, scaffolds, and bioactive molecules to regulate the microenvironment in bone regeneration is a promising approach. Zinc, magnesium, and iron ions are natural elements in bone tissue and participate in many physiological processes of bone metabolism and therefore have great potential for bone tissue engineering and regeneration. In this review, we performed a systematic analysis on the effects of zinc, magnesium, and iron ions in bone tissue engineering. We focus on the role of these ions in properties of scaffolds (mechanical strength, degradation, osteogenesis, antibacterial properties, etc.). We hope that our summary of the current research achievements and our notifications of potential strategies to improve the effects of zinc, magnesium, and iron ions in scaffolds for bone repair and regeneration will find new inspiration and breakthroughs to inspire future research.
88.	Eriksson, Gustav, 1994, et al. (författare) Atomically Resolved Interfacial Analysis of Bone-Like Hydroxyapatite Nanoparticles on Titanium 2023 Ingår i: Advanced NanoBiomed Research. - 2699-9307. ; 3:10 Tidskriftsartikel (refereegranskat)abstract Titanium is commonly used for medical devices, including osseointegrating implants, owing to its biocompatibility and mechanical properties. Nanostructuring titanium implants is known to enhance the healing process by promoting bone growth on the implant surface. Hydroxyapatite nanoparticles, resembling natural bone mineral, have been used to further improve osseointegration. While previous studies have investigated the osseointegration of titanium implants using atom probe tomography, limited research has focused on the attachment of synthetic hydroxyapatite to titanium. Herein, electron microscopy and atom probe tomography are used to reveal the assembly of synthetic hydroxyapatite nanoparticles in the titanium oxide surface. By sputter coating with chromium, a suitable matrix is formed for detailed interfacial analysis. The results demonstrate the diffusion of calcium, phosphorus, and carbon from hydroxyapatite nanoparticles into the titanium oxide surface. Titanium is commonly used for medical devices, owing to its biocompatibility and mechanical properties. Nanostructuring titanium implants with hydroxyapatite nanoparticles, resembling natural bone mineral, enhances the healing process by promoting bone growth on the implant surface. Herein, atom probe tomography reveals the assembly of synthetic hydroxyapatite nanoparticles in the titanium oxide surface.image & COPY; 2023 WILEY-VCH GmbH
89.	Ghajeri, Farnaz, et al. (författare) The Influence of Residuals Combining Temperature and Reaction Time on Calcium Phosphate Transformation in a Precipitation Process 2022 Ingår i: Journal of Functional Biomaterials. - : MDPI. - 2079-4983. ; 13:1 Tidskriftsartikel (refereegranskat)abstract Precipitation is one of the most common processes to synthesize hydroxyapatite, which is the human body’s mineral forming bone and teeth, and the golden bioceramic material for bone repair. Generally, the washing step is important in the precipitation method to remove the residuals in solution and to stabilize the phase transformation. However, the influence of residuals in combination with the reaction temperature and time, on calcium phosphate formation, is not well studied. This could help us with a better understanding of the typical synthesis process. We used a fixed starting ion concentration and pH in our study and did not adjust it during the reaction. XRD, FTIR, ICP-OES, and SEM have been used to analyze the samples. The results showed that combining residuals with both reaction temperature and time can significantly influence calcium phosphate formation and transformation. Dicalcium phosphate dihydrate formation and transformation are sensitive to temperature. Increasing temperature (60◦C) can inhibit the formation of acidic calcium phosphate or transform it to other phases, and further the particle size. It was also observed that high reaction temperature (60◦C) results in higher precipitation efficiency than room temperature. A low ion concentration combining reaction temperature and time could still significantly influence the calcium phosphate transformation during the drying. © 2022 by the authors.
90.	Kallas, Pawel, et al. (författare) Protein-coated nanostructured surfaces affect the adhesion of Escherichia coli 2022 Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 14:20, s. 7736-7746 Tidskriftsartikel (refereegranskat)abstract Developing new implant surfaces with anti-adhesion bacterial properties used for medical devices remains a challenge. Here we describe a novel study investigating nanotopography influences on bacterial adhesion on surfaces with controlled interspatial nanopillar distances. The surfaces were coated with proteins (fibrinogen, collagen, serum and saliva) prior to E. coli-WT adhesion under flow conditions. PiFM provided chemical mapping and showed that proteins adsorbed both between and onto the nanopillars with a preference for areas between the nanopillars. E. coli-WT adhered least to protein-coated areas with low surface nanopillar coverage, most to surfaces coated with saliva, while human serum led to the lowest adhesion. Protein-coated nanostructured surfaces affected the adhesion of E. coli-WT.
91.	Karazisis, Dimitrios, 1977, et al. (författare) The effects of controlled nanotopography, machined topography and their combination on molecular activities, bone formation and biomechanical stability during osseointegration 2021 Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 136, s. 279-290 Tidskriftsartikel (refereegranskat)abstract The initial cellular and molecular activities at the bone interface of implants with controlled nanoscale topography and microscale roughness have previously been reported. However, the effects of such surface modifications on the development of osseointegration have not yet been determined. This study investigated the molecular events and the histological and biomechanical development of the bone interface in implants with nanoscale topography, microscale roughness or a combination of both. Polished and machined titanium implants with and without controlled nanopatterning (75 nm protrusions) were produced using colloidal lithography and coated with a thin titanium layer to unify the chemistry. The implants were inserted in rat tibiae and subjected to removal torque (RTQ) measurements, molecular analyses and histological analyses after 6, 21 and 28 days. The results showed that nanotopography superimposed on microrough, machined, surfaces promoted an early increase in RTQ and hence produced greater implant stability at 6 and 21 days. Two-way MANOVA revealed that the increased RTQ was influenced by microscale roughness and the combination of nanoscale and microscale topographies. Furthermore, increased bone-implant contact (BIC) was observed with the combined nanopatterned machined surface, although MANOVA results implied that the increased BIC was mainly dependent on microscale roughness. At the molecular level, the nanotopography, per se, and in synergy with microscale roughness, downregulated the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In conclusion, controlled nanotopography superimposed on microrough machined implants promoted implant stability during osseointegration. Nanoscale-driven mechanisms may involve attenuation of the inflammatory response at the titanium implant site. Statement of Significance: The role of combined implant microscale and nanotopography features for osseointegration is incompletely understood. Using colloidal lithography technique, we created an ordered nanotopography pattern superimposed on screwshaped implants with microscale topography. The midterm and late molecular, bone-implant contact and removal torque responses were analysed in vivo. Nanotopography superimposed on microrough, machined, surfaces promoted the implant stability, influenced by microscale topography and the combination of nanoscale and microscale topographies. Increased bone-implant contact was mainly dependent on microscale roughness whereas the nanotopography, per se, and in synergy with microscale roughness, attenuated the proinflammatory tumor necrosis factor alpha (TNF-α) expression. It is concluded that microscale and nanopatterns provide individual as well as synergistic effects on molecular, morphological and biomechanical implant-tissue processes in vivo.
92.	Liu, Dachuan, et al. (författare) Amorphous iron-calcium phosphate-mediated biomineralized scaffolds for vascularized bone regeneration 2023 Ingår i: Materials & design. - : Elsevier BV. - 0264-1275 .- 1873-4197. ; 235 Tidskriftsartikel (refereegranskat)abstract Construction of organic–inorganic composites similar to natural bone in terms of structure and composition has attracted extensive attention. However, the clinical applications of these composites are limited due to the insufficient osteogenic and mechanical properties. In nature, the presence of amorphous iron-calcium phosphate (Fe-ACP) strengthens the mechanical properties of some biominerals, and our previous study has revealed its synthetic route and in vitro osteogenic properties. However, the potential role of Fe-ACP on biomineralization and constructing biomimetic scaffolds for bone regeneration has not been studied. Herein, a biomimetic scaffold with good osteogenic property was fabricated based on the mineralization of Fe-ACP, with the assistance of ice-templated freeze-casting. The in vitro study showed that the mineralized scaffolds possessed favorable biocompatibility and osteogenic property. Moreover, the scaffolds promoted cell chemotaxis and angiogenic property by upregulating the hypoxia inducible factor-1α (HIF-1α). In vivo experiment demonstrated potent early osteogenesis along with angiogenesis and ultimately promoted bone regeneration. Overall, the mineralized scaffold mediated by Fe-ACP precursors provide a unique platform to enhance bone tissue repair.
93.	Pihl, Maria, 1978, et al. (författare) Osseointegration and antibacterial effect of an antimicrobial peptide releasing mesoporous titania implant 2021 Ingår i: Journal of Biomedical Materials Research - Part B Applied Biomaterials. - : Wiley. - 1552-4981 .- 1552-4973. ; 109:11, s. 1787-1795 Tidskriftsartikel (refereegranskat)abstract Medical devices such as orthopedic and dental implants may get infected by bacteria, which results in treatment using antibiotics. Since antibiotic resistance is increasing in society there is a need of finding alternative strategies for infection control. One potential strategy is the use of antimicrobial peptides, AMPs. In this study, we investigated the antibiofilm effect of the AMP, RRP9W4N, using a local drug-delivery system based on mesoporous titania covered titanium implants. Biofilm formation was studied in vitro using a safranine biofilm assay and LIVE/DEAD staining. Moreover, we investigated what effect the AMP had on osseointegration of commercially available titanium implants in vivo, using a rabbit tibia model. The results showed a sustained release of AMP with equal or even better antibiofilm properties than the traditionally used antibiotic Cloxacillin. In addition, no negative effects on osseointegration in vivo was observed. These combined results demonstrate the potential of using mesoporous titania as an AMP delivery system and the potential use of the AMP RRP9W4N for infection control of osseointegrating implants.
94.	Qayoom, Irfan, et al. (författare) A biphasic nanohydroxyapatite/calcium sulphate carrier containing Rifampicin and Isoniazid for local delivery gives sustained and effective antibiotic release and prevents biofilm formation 2020 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1 Tidskriftsartikel (refereegranskat)abstract Long term multiple systemic antibiotics form the cornerstone in the treatment of bone and joint tuberculosis, often combined with local surgical eradication. Implanted carriers for local drug delivery have recently been introduced to overcome some of the limitations associated with conventional treatment strategies. In this study, we used a calcium sulphate hemihydrate (CSH)/nanohydroxyapatite (nHAP) based nanocement (NC) biomaterial as a void filler as well as a local delivery carrier of two standard of care tuberculosis drugs, Rifampicin (RFP) and Isoniazid (INH). We observed that the antibiotics showed different release patterns where INH showed a burst release of 67% and 100% release alone and in combination within one week, respectively whereas RFP showed sustained release of 42% and 49% release alone and in combination over a period of 12 weeks, respectively indicating different possible interactions of antibiotics with nHAP. The interactions were studied using computational methodology, which showed that the binding energy of nHAP with RFP was 148 kcal/mol and INH was 11 kcal/mol, thus varying substantially resulting in RFP being retained in the nHAP matrix. Our findings suggest that a biphasic ceramic based drug delivery system could be a promising treatment alternative to bone and joint TB.
95.	Stepulane, Annija, 1994 (författare) Antibacterial elastomeric materials for biomedical applications 2022 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract An ageing population in combination with scientific and clinical advancements have led to a steady increase in the use of medical devices. Elastomeric biomaterials – materials displaying rubber-like mechanics – have found widespread applicability in the production of both short- and long-term medical devices. Despite the prevalence of such devices, issues with medical device-associated infections remain. By surface colonization of bacteria, systemic infection can arise resulting in patient suffering and increased burden on the healthcare system. Consequentially, development of antibacterial elastomers capable of withstanding bacterial surface colonization has been proposed as an effective strategy for prevention and mitigation of medical device-associated infections. In this thesis, two alternative strategies to develop antibacterial polydimethylsiloxane (PDMS) elastomers have been proposed and evaluated. In the first strategy, PDMS surface modification with multifunctional hydrogel microparticle coating has been developed. Using a coating of antimicrobial peptide (AMP) RRPRPRPRPWWWW-NH2 functionalized hydrogel particles, high antibacterial activity was reported against Staphylococcus epidermidis and Staphylococcus aureus. As an additional functionality, the ability of the coating to encapsulate and release therapeutic substances was investigated, resulting in a sustained delivery of polar, amphiphilic, and nonpolar drugs. In the second strategy, modification of bulk PDMS by synthesis of drug-eluting PDMShydrogel blends was proposed. PDMS and triblock copolymer (diacrylated Pluronic F127, DA-F127) hydrogel blends were prepared with varying ternary PDMS–DA-F127–H2O compositions. The test compositions chosen resulted in stable elastomers with tailorable mechanics and ordered self-assembled nanostructure. The variation in composition offered potential for sustained delivery of polar and nonpolar drugs, demonstrating potential for production of drug-eluting and antibacterial elastomeric devices with tailorable mechanics.
96.	Thesleff, Alexander, 1986, et al. (författare) Loads at the implant-prosthesis interface during free and aided ambulation in osseointegrated transfemoral prostheses 2020 Ingår i: IEEE Transactions on Medical Robotics and Bionics. - 2576-3202. ; 2:3, s. 497-505 Tidskriftsartikel (refereegranskat)abstract Bone-anchored attachment of amputation limb prostheses is increasingly becoming a clinically accepted alternative to conventional socket suspension. The direct transfer of loads demands that the percutaneous implant system and the residual bone withstand all forces and moments transferred from the prosthesis. This study presents load measurements recorded at the bone-anchored attachment in 20 individuals with unilateral transfemoral amputation performing the everyday ambulatory activities: level ground walking, stairs ascent/descent and slope ascent/descent. Mean peak values for the sample populations across activities ranged from 498–684 N for the resultant force, 26.5–39.8 Nm for the bending moment, and 3.1–5.5 Nm for the longitudinal moment. Significant differences with respect to level walking were found for the resultant force during stairs ascent, (higher, p = 0.002), and stairs descent, (lower, p = 0.005). Using a crutch reduced the peak resultant forces and the peak bending moments with averages ranging from 5.5–12.6 % and 13.2–15.6 %, respectively. Large inter-participant variations were observed and no single activity resulted in consistently higher loading of the bone-anchored attachment across the participants. Results from this study can guide future development of percutaneous osseointegrated implant systems for limb prostheses and their rehabilitation protocols.
97.	Thesleff, Alexander, 1986, et al. (författare) Low plasticity burnishing improves fretting fatigue resistance in bone-anchored implants for amputation prostheses 2022 Ingår i: Medical Engineering & Physics. - : Elsevier BV. - 1350-4533 .- 1873-4030. ; 100 Tidskriftsartikel (refereegranskat)abstract Fretting fatigue is a common problem for modular orthopedic implants which may lead to mechanical failure of the implant or inflammatory tissue responses due to excessive release of wear debris. Compressive residual stresses at the contacting surfaces may alleviate the problem. Here we investigate the potential of a surface enhancement method known as low plasticity burnishing (LPB) to increase the fretting fatigue resistance of bone-anchored implants for skeletal attachment of limb prostheses. Rotation bending fatigue tests performed on LPB treated and untreated test specimens demonstrate that the LPB treatment leads to statistically significantly increased resistance to fretting fatigue (LPB treated test specimens withstood on average 108,780 load cycles as compared with 37,845 load cycles for untreated test specimens, p = 0.004). LPB treated test specimens exhibited less wear at the modular interface as compared with untreated test specimens. This surface treatment may lead to reduced risk of fretting induced component failure and a reduced need for revision of implant system componentry.
98.	Uusitalo, Maja, 1996 (författare) Photothermal antibacterial biomaterials utilising gold nanorods and near-infrared light 2024 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract Biomaterials serve an integral role in modern medicine, providing essential functions for therapeutic, prosthetic, and diagnostic purposes. However, once introduced into a biological setting, biomaterials are prone to bacterial colonisation, resulting in hard-to-treat infections with severe clinical consequences. Biomaterial-associated infections (BAIs) are commonly caused by biofilm-forming bacteria. The reduced sensitivity of biofilm-forming bacteria to antibiotics, along with the increased occurrence of antibiotic resistant pathogens, significantly limits the effectiveness of conventional antibacterial strategies. As our growing life expectancy is accompanied by an increased use of biomaterials, there is a pressing need for novel strategies that can combat the infections associated with these materials. A promising approach is the development of antibacterial biomaterial modifications. In this thesis, a photothermal antibacterial modification strategy using surface-immobilised gold nanorods and near-infrared (NIR) light has been investigated. Procedures were developed for immobilisation of gold nanorods on glass and titanium substrates. Material characterisation was conducted using UV-Vis spectroscopy, electron microscopy, and X-ray photoelectron spectroscopy. In situ X-ray diffraction studies were performed to evaluate the photothermal properties of the gold nanorods on glass, and the in situ datasets were corroborated with scanning electron microscopy and UV-Vis spectroscopy characterisation. The findings revealed that the supported gold nanorods displayed a linear temperature increase with NIR laser power until an onset of morphological changes around 120 °C, and the slope of the temperature increase demonstrated a dependence on the surface coverage of gold nanorods. The in vitro antibacterial activity of the gold nanorods on glass and titanium upon illumination with NIR light was evaluated against Staphylococcus aureus. On titanium, the antibacterial activity was attributed to NIR light absorption of the titanium leading to heating of the substrate, with no evident effect from plasmonic heating of the gold nanorods. In contrast, on glass a significant NIR light-intensity dependent antimicrobial activity from plasmonic heating of the gold nanorods was observed. The findings provide insights into the photothermal behaviour of surface-immobilised gold nanorods and highlight the important role of the support material for the antibacterial activity of the systems. Altogether, the results are of relevance for advancing the design of antibacterial biomaterial modifications using supported gold nanorods and near-infrared light.
99.	Atefyekta, Saba, 1987, et al. (författare) Antimicrobial Peptide-Functionalized Mesoporous Hydrogels 2021 Ingår i: ACS Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 7:4, s. 1693-1702 Tidskriftsartikel (refereegranskat)abstract Antimicrobial peptides (AMPs) are seen as a promising replacement to conventional antibiotics for the prevention of skin wound infections. However, due to the short half-life of AMPs in biological environments, such as blood, their use in clinical applications has been limited. The covalent immobilization of AMPs onto suitable substrates is an effective solution to create contact-killing surfaces with increased long-term stability. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was covalently attached to amphiphilic and ordered mesoporous Pluronic F127 hydrogels made of cross-linked lyotropic liquid crystals through 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) chemistry. The AMP-hydrogels showed high antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, methicillin-resistant S. aureus (MRSA), and multidrug-resistant Escherichia coli for up to 24 h. Furthermore, the AMP-hydrogels did not present any toxicity to human fibroblasts. The AMPs retained their antimicrobial activity up to 48 h in human blood serum, which is a significant increase in stability compared to when used in dissolved state. A pilot in vivo rat model showed 10-100x less viable counts of S. aureus on AMP-hydrogels compared with control hydrogels during the first 3 days of infection. Studies performed on human whole blood showed that blood coagulated more readily in the presence of AMP-hydrogels as compared to hydrogels without AMPs, indicating potential hemostatic activity. Overall, the results suggest that the combination of amphiphilic hydrogels with covalently bonded AMPs has potential to be used as antibacterial wound dressing material to reduce infections and promote hemostatic activity as an alternative to antibiotics or other antimicrobial agents, whose use should be restricted.
100.	Afewerki, Samson, et al. (författare) Advances in dual functional antimicrobial and osteoinductive biomaterials for orthopaedic applications 2020 Ingår i: Nanomedicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 24 Forskningsöversikt (refereegranskat)abstract A vast growing problem in orthopaedic medicine is the increase of clinical cases with antibiotic resistant pathogenic microbes, which is predicted to cause higher mortality than all cancers combined by 2050. Bone infectious diseases limit the healing ability of tissues and increase the risk of future injuries due to pathologic tissue remodelling. The traditional treatment for bone infections has several drawbacks and limitations, such as lengthy antibiotic treatment, extensive surgical interventions, and removal of orthopaedic implants and/or prosthesis, all of these resulting in long-term rehabilitation. This is a huge burden to the public health system resulting in increased healthcare costs. Current technologies e.g. co-delivery systems, where antibacterial and osteoinductive agents are delivered encounter challenges such as site-specific delivery, sustained and prolonged release, and biocompatibility. In this review, these aspects are highlighted to promote the invention of the next generation biomaterials to prevent and/or treat bone infections and promote tissue regeneration.

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