| 1. |
- Jing, Yujia, 1985
(författare)
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Hyperthermia-responsive liposomal systems
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract Sophisticated liposomal systems are emerging at an increasing rate to meet the demands for multifunctional drug carriers in chemotherapies in combined with hyperthermia. For example, liposomal drug carriers for temperature-controlled drug release under hyperthermic conditions have recently been tested in clinical trials. More advanced designs of liposomes are expected to release encapsulated contents and activate hidden surface-functions in response to heat stimulus. Towards this aim, the present thesis is focused on formulating asymmetric lipid systems that can preserve functional moieties, and reactivate the targeted function as well as release the encapsulated compounds upon local heating. The design of the asymmetric liposomal systems utilizes the heat-activated transmembrane lipid diffusion during gel to liquid-crystalline phase transitions of the lipid membranes.Rational design of advanced liposomal drug-delivery systems will require understanding of the physicochemical properties of lipid membranes under, e.g., hyperthermic conditions. Here, supported lipid membranes on planar solid surfaces were used for model studies of lipid composition yielding a gel to liquid crystalline phase-transition temperature in the range 40 – 45 °C. It was found that the liposome-to-membrane formation process is not only size-dependent but also governed by temperature. Two methods of preparing supported asymmetric lipid membranes were investigated. As a proof-of-concept, the upper leaflets were either replaced or chemically transformed by enzymatic hydrolysis. The processes were monitored using surface sensitive techniques such as quartz crystal microbalance with dissipation (QCM-D) and dual polarization interferometry (DPI). The asymmetric structures were stable at a room temperature, while lipid flip-flop was induced upon increasing of the temperature. Transmembrane lipid exchange in the asymmetric structure under hyperthermic conditions was demonstrated by detecting, through streptavidin binding, biotinylated lipids appearing at the top leaflet which were first located in the lower leaflet. The protocols developed for the supported lipid systems were adapted for the preparation of asymmetric liposomes. Biotinylated asymmetric liposomes were used as a model system to demonstrate the principle of heat-activated targeting of asymmetric liposomes to streptavidin-coated surfaces. More biologically relevant interaction was utilized to replace the biotin-streptavidin function, where asymmetric cationic liposomes were binding to anionic supported membrane immobilized surfaces upon heating. The described strategies for assembly of asymmetric supported membranes provide a guide to the development of multifunctional drug carriers. The protocols used in experiments with supported membranes were readily adapted to the preparation of asymmetric liposomes. The ongoing study tests the asymmetric liposomes in vitro, which is designed to demonstrate hyperthermia treatment can enhance accumulation of liposomes in FaDu cells, and at the same time activate release of the encapsulated components. The results of in vitro tests can be used to analyze the feasibility of utilizing the asymmetric liposomes as a platform in vivo to explore further improvement in their functions upon microwave hyperthermia.
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| 2. |
- Orru, Anna Maria, 1976, et al.
(författare)
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AHA! festival 2015
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The AHA festival investigates the borders between art and science in a three-day event at the Chalmers University of Technology hosted by the Department of Architecture. An international festival intended to provide enlightening experiences, staging surprises, new thoughts and displaced perspectives that lead to alternative modes of thinking about the space between art and science. We invite scientists (physicists, historians, mathematicians, medical students), artists (dancers, musicians, painters, poets, chefs) and not least architects, who reside in these borderlands and wish to share their vision and work. The key intention is to celebrate both art and science as key knowledge building devices.
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| 3. |
- Söderlund, Zackarias
(författare)
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Engineering the extracellular matrix to model diseases and orchestrate regeneration
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The extracellular matrix is not only a scaffold to which cells attach, but it is also a matrix that communicates cell signals. Because of the interplay between cells and the extracellular matrix, changes in the extracellular matrix can steer cell fate. This opens up the opportunity to design and engineer the extracellular matrix to communicate changes to the cells. Thus, this thesis has focused on understanding which parameters and signals influence cells, but also on how to utilise this knowledge to engineer a completely defined extracellular matrix. The extracellular matrix can be modulated in several ways, such as cell attachment, degradation properties, porosity, stiffness as well as being easily functionalised with molecules of interest using click chemistry.Two of the papers in this thesis focus on the development of new tools for glycosaminoglycan research to get a better understanding of how this can be modulated to steer cell signalling. Glycosaminoglycans bind growth factors, which can then either act as a co-receptor to increase the potency of the growth factor or to protect the growth factors from being broken down or inactivated. The tools that we have developed open the possibility to better study the production of glycosaminoglycans from different types of cells and better understand what changes occur in glycosaminoglycan synthesis during disease.The second two papers in this thesis focus on understanding the extracellular matrix. Article number one focuses on the effect of different extracellular matrices and stretch on cells and their secretome. Article number two, which has been the focus of this thesis, utilises the new findings in the other articles about glycosaminoglycans and the extracellular matrix to create a synthetic and defined extracellular matrix. This extracellular matrix is modified with glycosaminoglycans to have a slow release of growth factors to instruct cells to differentiate both in vitro and in vivo.
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| 4. |
- Palmquist, Anders, 1977, et al.
(författare)
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Complex geometry and integrated macro-porosity: Clinical applications of electron beam melting to fabricate bespoke bone-anchored implants
- 2023
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 156, s. 125-145
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Forskningsöversikt (refereegranskat)abstract
- The last decade has witnessed rapid advancements in manufacturing technologies for biomedical implants. Additive manufacturing (or 3D printing) has broken down major barriers in the way of producing complex 3D geometries. Electron beam melting (EBM) is one such 3D printing process applicable to metals and alloys. EBM offers build rates up to two orders of magnitude greater than comparable laser-based technologies and a high vacuum environment to prevent accumulation of trace elements. These features make EBM particularly advantageous for materials susceptible to spontaneous oxidation and nitrogen pick-up when exposed to air (e.g., titanium and titanium-based alloys). For skeletal reconstruction(s), anatomical mimickry and integrated macro-porous architecture to facilitate bone ingrowth are undoubtedly the key features of EBM manufactured implants. Using finite element modelling of physiological loading conditions, the design of a prosthesis may be further personalised. This review looks at the many unique clinical applications of EBM in skeletal repair and the ground-breaking innovations in prosthetic rehabilitation. From a simple acetabular cup to the fifth toe, from the hand-wrist complex to the shoulder, and from vertebral replacement to cranio-maxillofacial reconstruction, EBM has experienced it all. While sternocostal reconstructions might be rare, the repair of long bones using EBM manufactured implants is becoming exceedingly frequent. Despite the various merits, several challenges remain yet untackled. Nevertheless, with the capability to produce osseointegrating implants of any conceivable shape/size, and permissive of bone ingrowth and functional loading, EBM can pave the way for numerous fascinating and novel applications in skeletal repair, regeneration, and rehabilitation. Statement of significance: Electron beam melting (EBM) offers unparalleled possibilities in producing contaminant-free, complex and intricate geometries from alloys of biomedical interest, including Ti6Al4V and CoCr. We review the diverse range of clinical applications of EBM in skeletal repair, both as mass produced off-the-shelf implants and personalised, patient-specific prostheses. From replacing large volumes of disease-affected bone to complex, multi-material reconstructions, almost every part of the human skeleton has been replaced with an EBM manufactured analog to achieve macroscopic anatomical-mimickry. However, various questions regarding long-term performance of patient-specific implants remain unaddressed. Directions for further development include designing personalised implants and prostheses based on simulated loading conditions and accounting for trabecular bone microstructure with respect to physiological factors such as patient's age and disease status.
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| 5. |
- Apelgren, Peter, et al.
(författare)
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Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo.
- 2017
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage repair and replacement is a major challenge in plastic reconstructive surgery. The development of a process capable of creating a patient-specific cartilage framework would be a major breakthrough. Here, we described methods for creating human cartilage in vivo and quantitatively assessing the proliferative capacity and cartilage-formation ability in mono- and co-cultures of human chondrocytes and human mesenchymal stem cells in a three-dimensional (3D)-bioprinted hydrogel scaffold. The 3D-bioprinted constructs (5 × 5 × 1.2 mm) were produced using nanofibrillated cellulose and alginate in combination with human chondrocytes and human mesenchymal stem cells using a 3D-extrusion bioprinter. Immediately following bioprinting, the constructs were implanted subcutaneously on the back of 48 nude mice and explanted after 30 and 60 days, respectively, for morphological and immunohistochemical examination. During explantation, the constructs were easy to handle, and the majority had retained their macroscopic grid appearance. Constructs consisting of human nasal chondrocytes showed good proliferation ability, with 17.2% of the surface areas covered with proliferating chondrocytes after 60 days. In constructs comprising a mixture of chondrocytes and stem cells, an additional proliferative effect was observed involving chondrocyte production of glycosaminoglycans and type 2 collagen. This clinically highly relevant study revealed 3D bioprinting as a promising technology for the creation of human cartilage.
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| 6. |
- Dietrich, Franciele, et al.
(författare)
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Effect of storage and preconditioning of healing rat Achilles tendon on structural and mechanical properties
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Tendon tissue storage and preconditioning are often used in biomechanical experiments and whether this generates alterations in tissue properties is essential to know. The effect of storage and preconditioning on dense connective tissues, like tendons, is fairly understood. However, healing tendons are unlike and contain a loose connective tissue. Therefore, we investigated if storage of healing tendons in the fridge or freezer changed the mechanical properties compared to fresh tendons, using a pull-to-failure or a creep test. Tissue morphology and cell viability were also evaluated. Additionally, two preconditioning levels were tested. Rats underwent Achilles tendon transection and were euthanized 12 days postoperatively. Statistical analyzes were done with one-way ANOVA or Student’s t-test. Tissue force and stress were unaltered by storage and preconditioning compared to fresh samples, while high preconditioning increased the stiffness and modulus (p ≤ 0.007). Furthermore, both storage conditions did not modify the viscoelastic properties of the healing tendon, but altered transverse area, gap length, and water content. Cell viability was reduced after freezing. In conclusion, preconditioning on healing tissues can introduce mechanical data bias when having extensive tissue strength diversity. Storage can be used before biomechanical testing if structural properties are measured on the day of testing.
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| 7. |
- Sukhovey, Yurij G., et al.
(författare)
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Difference between the biologic and chronologic age as an individualized indicator for the skin care intensity selection : skin topography and immune system state studies, parameter correlations with age difference
- 2019
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Ingår i: Biomedical Dermatology. - : Springer Nature. - 2398-8460. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Present research addresses the issue of skin aging and corresponding skin treatment individualization. Particular research question was on the developing of simplified criterion supporting patient-specific decision on the necessity and intensity of skin treatment. Basing on the published results and a wide pool of experimental data, we have formulated a hypothesis that a difference between biologic and chronologic age can be used as an express criterion of skin aging.Methods: In present paper, we report the results of studies with 80 volunteers between 15 and 65 years of age, linking parameters reflecting immune state, skin state, and topography to the difference between biologic and chronologic age. Facial skin topography, skin moisture, sebum level, and skin elasticity were studied using commercial devices. Blood immunology studies were performed using venous blood samples. Correlations between all measured parameters and age difference were calculated. Also, cross correlations between skin cell profile and blood immune profile parameters, and skin roughness parameters were calculated.Results: Age dependencies of the blood immunological parameters on the biologic and chronologic age difference are less pronounced as compared to the changes in skin cell profile parameters. However, the changes in the tendencies when biologic age becomes equal to chronologic one are visible for all studied parameters.All measured skin roughness parameters show correlations with age difference, but average skin roughness and depth of the deepest profile valley have the largest correlation coefficient values. Many of the measured skin cell profile and blood immunology parameters show strong correlations with average skin roughness and deepest profile valley, with some of the coefficients exceeding 0.5–0.6.Conclusions: Basing on own experiments and published research results, it is possible to suggest using the difference between calculated biologic age and chronologic age as an individualized criterion supporting decisions on skin treatment strategy. Further research involving larger numbers of participants and aiming on optimizing the expressions for calculating biologic age could lead to reliable and easily available express criterion supporting the decision making for an individualized skin treatment.
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| 8. |
- Cardemil, Carina, et al.
(författare)
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Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats.
- 2013
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Ingår i: PLosOne. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.
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| 9. |
- Karlsson, Johan, 1984, et al.
(författare)
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Stem cell homing using local delivery of plerixafor and stromal derived growth factor-1alpha for improved bone regeneration around Ti-implants
- 2016
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Ingår i: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 104:10, s. 2466-2475
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Tidskriftsartikel (refereegranskat)abstract
- Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF-1a/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF-1a from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone-implant anchorage and bone-formation along the surface of the implants when plerixafor and SDF-1a were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments.
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| 10. |
- Andersson, Marlene, et al.
(författare)
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Biomimetic spinning of artificial spider silk from a chimeric minispidroin
- 2017
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Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 254
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Tidskriftsartikel (refereegranskat)abstract
- Herein we present a chimeric recombinant spider silk protein (spidroin) whose aqueous solubility equals that of native spider silk dope and a spinning device that is based solely on aqueous buffers, shear forces and lowered pH. The process recapitulates the complex molecular mechanisms that dictate native spider silk spinning and is highly efficient; spidroin from one liter of bacterial shake-flask culture is enough to spin a kilometer of the hitherto toughest as-spun artificial spider silk fiber.
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| 11. |
- Apelgren, Peter, et al.
(författare)
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In Vivo Human Cartilage Formation in Three-Dimensional Bioprinted Constructs with a Novel Bacterial Nanocellulose Bioink
- 2019
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Ingår i: Acs Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 5:5, s. 2482-2490
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial nanocellulose (BNC) is a 3D network of nanofibrils exhibiting excellent biocompatibility. Here, we present the aqueous counter collision (ACC) method of BNC disassembly to create bioink with suitable properties for cartilage-specific 3D-bioprinting. BNC was disentangled by ACC, and fibril characteristics were analyzed. Bioink printing fidelity and shear-thinning properties were evaluated. Cell-laden bioprinted grid constructs (5 X 5 X 1 mm(3)) containing human nasal chondrocytes (10 M mL(-1)) were implanted in nude mice and explanted after 30 and 60 days. Both ACC and hydrolysis resulted in significantly reduced fiber lengths, with ACC resulting in longer fibrils and fewer negative charges relative to hydrolysis. Moreover, ACC-BNC bioink showed outstanding printability, postprinting mechanical stability, and structural integrity. In vivo, cell-laden structures were rapidly integrated, maintained structural integrity, and showed chondrocyte proliferation, with 32.8 +/- 13.8 cells per mm(2) observed after 30 days and 85.6 +/- 30.0 cells per mm(2) at day 60 (p = 0.002). Furthermore, a full-thickness skin graft was attached and integrated completely on top of the 3D-bioprinted construct. The novel ACC disentanglement technique makes BNC biomaterial highly suitable for 3D-bioprinting and clinical translation, suggesting cell-laden 3D-bioprinted ACC-BNC as a promising solution for cartilage repair.
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| 12. |
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| 13. |
- Asif, Sana, et al.
(författare)
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Heparinization of cell surfaces with short peptide-conjugated PEG-lipid regulates thromboinflammation in transplantation of human MSCs and hepatocytes
- 2016
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 35, s. 194-205
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Tidskriftsartikel (refereegranskat)abstract
- Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 14. |
- Asif, Sana, M.D, PhD student, et al.
(författare)
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Validation of an MPC polymer coating to attenuate surface- induced cross-talk between the complement and coagulation systems in whole blood in in vitro and in vivo models
- 2019
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Ingår i: Macromolecular Bioscience. - : Wiley-VCH Verlagsgesellschaft. - 1616-5187 .- 1616-5195. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- Artificial surfaces that come into contact with blood induce an immediate activation of the cascade systems of the blood, leading to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Heparin coating has been used to improve hemocompatibility, and another approach is 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings. Here, the aim is to evaluate the hemocompatibility of MPC polymer coating by studying the interactions with coagulation and complement systems using human blood in vitro model and pig in vivo model. The stability of the coatings is investigated in vitro and MPC polymer-coated catheters are tested in vivo by insertion into the external jugular vein of pigs to monitor the catheters' antithrombotic properties. There is no significant activation of platelets or of the coagulation and complement systems in the MPC polymer-coated one, which was superior in hemocompatibility to non-coated matrix surfaces. The protective effect of the MPC polymer coat does not decline after incubation in human plasma for up to 2 weeks. With MPC polymer-coated catheters, it is possible to easily draw blood from pig for 4 days in contrast to the case for non-coated catheters, in which substantial clotting is seen.
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| 15. |
- Barreto Henriksson, Helena, et al.
(författare)
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Determination of mechanical and rheological properties of a cell-loaded peptide gel during ECM production
- 2019
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 563, s. 437-444
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Tidskriftsartikel (refereegranskat)abstract
- The development of an injectable biomaterial that supports cell survival and maintains or promotes nucleus pulposus (NP) phenotype could aid delivery of cells to degenerated NPs causing low back pain. Mesenchymal cells were loaded and grown in a synthetic peptide gel, PuraMatrix (R). Cells were observed within the gels over 0-28 days, and accumulation of glycosaminoglycans were detected by histological staining. The mechanical properties of the cell-loaded constructs, and the change of the mechanical properties were studied using stress relaxation of the gels under compression and confinement. The PuraMatrix (R) gel was shown to relax fast on compression indicating that the fluid could easily flow out of the gel, and thus indicating the presence of large pores/voids. The presence of these pores/voids was further supported by high mobility of dextran molecules, determined using fluorescence recovery after photo bleaching. The stress required to deform the cell-loaded constructs to a specific strain increases at day 21, at which point the presence of glycosaminoglycans within the cell-loaded constructs was also observed. The results provide evidence of changes in mechanical properties of the PuraMatrix (R) matrix upon excretion of the extracellular matrix by the cells.
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| 16. |
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| 17. |
- Fursatz, Marian, et al.
(författare)
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Functionalization of bacterial cellulose wound dressings with the antimicrobial peptide ε-poly-L-Lysine
- 2018
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Ingår i: Biomedical Materials. - : Institute of Physics Publishing (IOPP). - 1748-6041 .- 1748-605X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Wound dressings based on bacterial cellulose (BC) can form a soft and conformable protective layer that can stimulate wound healing while preventing bacteria from entering the wound. Bacteria already present in the wound can, however, thrive in the moist environment created by the BC dressing which can aggravate the healing process. Possibilities to render the BC antimicrobial without affecting the beneficial structural and mechanical properties of the material would hence be highly attractive. Here we present methods for functionalization of BC with ε-Poly-L-Lysine (ε-PLL), a non-toxic biopolymer with broad-spectrum antimicrobial activity. Low molecular weight ε-PLL was cross-linked in pristine BC membranes and to carboxymethyl cellulose (CMC) functionalized BC using carbodiimide chemistry. The functionalization of BC with ε-PLL inhibited growth of S. epidermidis on the membranes but did not affect the cytocompatibility to cultured human fibroblasts as compared to native BC. The functionalization had no significant effects on the nanofibrous structure and mechanical properties of the BC. The possibility to functionalize BC with ε-PLL is a promising, green and versatile approach to improve the performance of BC in wound care and other biomedical applications.
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| 18. |
- Georgiou, Melanie, et al.
(författare)
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Engineered neural tissue with aligned, differentiated adipose-derived stem cells promotes peripheral nerve regeneration across a critical sized defect in rat sciatic nerve
- 2015
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 37, s. 242-251
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Tidskriftsartikel (refereegranskat)abstract
- Adipose-derived stem cells were isolated from rats and differentiated to a Schwann cell-like phenotype in vitro. The differentiated cells (dADSCs) underwent self-alignment in a tethered type-1 collagen gel, followed by stabilisation to generate engineered neural tissue (EngNT-dADSC). The pro-regenerative phenotype of dADSCs was enhanced by this process, and the columns of aligned dADSCs in the aligned collagen matrix supported and guided neurite extension in vitro. EngNT-dADSC sheets were rolled to form peripheral nerve repair constructs that were implanted within NeuraWrap conduits to bridge a 15 mm gap in rat sciatic nerve. After 8 weeks regeneration was assessed using immunofluorescence imaging and transmission electron microscopy and compared to empty conduit and nerve graft controls. The proportion of axons detected in the distal stump was 3.5 fold greater in constructs containing EngNT-dADSC than empty tube controls. Our novel combination of technologies that can organise autologous therapeutic cells-within an artificial tissue construct provides a promising new cellular biomaterial for peripheral nerve repair.
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| 19. |
- Halling Linder, Cecilia, 1975-
(författare)
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Biochemical and functional properties of mammalian bone alkaline phosphatase isoforms during osteogenesis
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The human skeleton is a living and dynamic tissue that constantly is being renewed in a process called bone remodeling. Old bone is resorbed by osteoclasts and new bone is formed by osteoblasts. Bone is a composite material made up by mineral crystals in the form of hydroxyapatite (calcium and phosphate) that provides the hardness of bone, and collagen fibrils that provides elasticity and flexibility. Alkaline phosphatase (ALP) is a family of enzymes that is present in most species and catalyzes the hydrolysis of various phosphomonoesters at alkaline pH. Despite the generalized use of ALP as a biochemical marker of bone formation, the precise function of bone ALP (BALP) is only now becoming clear. Three circulating human BALP isoforms (B1, B2, and B/I) can be distinguished in healthy individuals and a fourth isoform (B1x) has been discovered in patients with chronic kidney disease and in bone tissue.Paper I. Three endogenous phosphocompounds, (i.e., inorganic pyrophosphate (PPi), pyridoxal 5′-phosphate (PLP) and phosphoethanolamine (PEA)), have been suggested to serve as physiological substrates for BALP. The BALP isoforms display different catalytic properties towards PPi and PLP, which is attributed to their distinct N-linked glycosylation patterns. The catalytic activity, using PEA as substrate, was barely detectable for all BALP isoforms indicating that PEA is not a physiological substrate for BALP.Paper II. Mouse serum ALP is frequently measured and interpreted in mammalian bone research. However, little is known about the circulating ALPs in mice and their relation to human ALP. We characterized the circulating and tissue-derived mouse ALP isozymes and isoforms from mixed strains of wild-type and knockout mice. All four BALP isoforms (B/I, B1x, B1, and B2) were identified in mouse serum and bone tissues, in good correspondence with those found in human bones. All mouse tissues, except liver, contained significant ALP activities. This is a notable difference as human liver contains vast amounts of ALP.Paper III. The objective of this study was to investigate the binding properties of human collagen type I to human BALP, including the two BALP isoforms B1 and B2, together with ALP from human liver, human placenta and E. coli. A surface plasmon resonance-based analysis showed that BALP binds stronger to collagen type I in comparison with ALPs expressed in non-mineralizing tissues. The B2 isoform binds significantly stronger to collagen type I in comparison with the B1 isoform, indicating that glycosylation differences in human ALPs are of crucial importance for protein–protein interactions with collagen type I.Paper IV. Tartrate-resistant acid phosphatase (TRAP) is highly expressed in osteoclasts and frequently used as a marker of bone resorption. Intriguingly, recent studies show that TRAP is also expressed in osteoblasts and osteocytes. TRAP displays enzymatic activity towards the endogenous substrates for BALP, i.e., PPi and PLP. Both TRAP and BALP can alleviate the inhibitory effect of osteopontin on mineralization by dephosphorylation, which suggests a novel role for TRAP in skeletal mineralization.
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| 20. |
- Hansson, Magnus L., et al.
(författare)
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Artificial spider silk supports and guides neurite extension in vitro
- 2021
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Ingår i: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 35:11
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Tidskriftsartikel (refereegranskat)abstract
- Surgical intervention with the use of autografts is considered the gold standard to treat peripheral nerve injuries. However, a biomaterial that supports and guides nerve growth would be an attractive alternative to overcome problems with limited availability, morbidity at the site of harvest, and nerve mismatches related to autografts. Native spider silk is a promising material for construction of nerve guidance conduit (NGC), as it enables regeneration of cm-long nerve injuries in sheep, but regulatory requirements for medical devices demand synthetic materials. Here, we use a recombinant spider silk protein (NT2RepCT) and a functionalized variant carrying a peptide derived from vitronectin (VN-NT2RepCT) as substrates for nerve growth support and neurite extension, using a dorsal root ganglion cell line, ND7/23. Two-dimensional coatings were benchmarked against poly-d-lysine and recombinant laminins. Both spider silk coatings performed as the control substrates with regards to proliferation, survival, and neurite growth. Furthermore, NT2RepCT and VN-NT2RepCT spun into continuous fibers in a biomimetic spinning set-up support cell survival, neurite growth, and guidance to an even larger extent than native spider silk. Thus, artificial spider silk is a promising biomaterial for development of NGCs.
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| 21. |
- Huang, Shan, et al.
(författare)
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Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood.
- 2016
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Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 77, s. 111-119
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inappropriate and uncontrolled activation of the cascade systems in the blood is a driving force in adverse inflammatory and thrombotic reactions elicited by biomaterials, but limited data are available on the activation of the contact system by polymers and the present study was undertaken to investigate these mechanisms in established models.METHODS: Polymer particles were incubated in (1) EDTA-plasma (10 mM) to monitor the adsorption of 20 selected proteins; (2) lepirudin-anticoagulated plasma to evaluate contact system activation, monitored by the formation of complexes between the generated proteases factor[F]XIIa, FXIa and kallikrein and the serpins C1-inhibitor [C1INH] and antithrombin [AT]; (3) lepirudin-anticoagulated whole blood to determine cytokine release.RESULTS: Strong negative correlations were found between 10 cytokines and the ratio of deposited FXII/C1INH, generated FXIIa-C1INH complexes, and kallikrein-C1INH complexes. Formation of FXIIa-C1INH complexes correlated negatively with the amount of C3a and positively with deposited IgG.CONCLUSIONS: A reciprocal relationship was found between activation of the contact system and the complement system induced by the polymers studied here. The ratios of FXII/C1INH or C4/C4BP, adsorbed from EDTA-plasma are useful surrogate markers for cytokine release and inflammatory response to materials intended for blood contact.
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| 22. |
- Islam, Mohammad Mirazul, et al.
(författare)
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Fabrication of a human recombinant collagen-based corneal substitute using carbodiimide chemistry
- 2013
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Ingår i: Methods in Molecular Biology. - Totowa, NJ : Humana Press. - 1064-3745 .- 1940-6029. - 9781627034319 ; 1014, s. 157-164
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Tidskriftsartikel (refereegranskat)abstract
- Human recombinant collagen can be cross-linked with a variety of chemical cross-linking agents. Cross-linking methods can be tuned to confer collagen-based scaffolds with specific physical properties, improved antigenicity and thermal stability without impeding the ability of the material to integrate into the surrounding tissue and to promote regeneration. Here, we describe a method to cross-link human recombinant collagen using a water soluble carbodiimide. Carbodiimides are referred to as zero-length cross-linking agents as they are not incorporated into the final cross-link and thus pose minimal risk with respect to cytotoxicity. The resulting collagen-based scaffold possesses properties comparable to that of the human cornea and is thus suitable for use as a corneal substitute.
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| 23. |
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| 24. |
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| 25. |
- Karlsson, Johan, 1984, et al.
(författare)
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The effect of alendronate on biomineralization at the bone/implant interface
- 2016
-
Ingår i: Journal of Biomedical Materials Research. Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 104:3, s. 620-629
-
Tidskriftsartikel (refereegranskat)abstract
- A recent approach to improve the osseointegration of implants is to utilize local drug administration. The presence of an osteoporosis drug may influence both bone quantity and quality at the bone/implant interface. Despite this, the performance of bone-anchoring implants is traditionally evaluated only by quantitative measurements. In the present study, the osteoporosis drug alendronate (ALN) was administrated from mesoporous titania thin films that were coated onto titanium implants. The effect that the drug had on biomineralization was explored both in vitro using simulated body fluid (SBF) and in vivo in a rat tibia model. The SBF study showed that the apatite formation was completely hindered at a high concentration of ALN (0.1 mg/mL). However, when ALN was administrated from the mesoporous coating the surface became completely covered with apatite. Ex vivo characterization of the bone/implant interface using Raman spectroscopy demonstrated that the presence of ALN enhanced the bone mineralization, and that the chemical signature of newly formed bone in the presence of ALN had a higher resemblance to the pre-existing mature bone than to the bone formed without drug. Taken together, this study demonstrates the importance of evaluating the quality of the formed bone to better understand the performance of implants.
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| 26. |
- Kumosa, Lucas, et al.
(författare)
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Profound alterations in brain tissue linked to hypoxic episode after device implantation
- 2021
-
Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612. ; 278, s. 1-13
-
Tidskriftsartikel (refereegranskat)abstract
- To enable authentic interfacing with neuronal structures in the brain, preventing alterations of tissue during implantation of devices is critical. By transiently implanting oxygen microsensors into rat cortex cerebri for 2 h, substantial and long lasting (>1 h) hypoxia is routinely generated in surrounding tissues; this hypoxia is linked to implantation generated compressive forces. Preferential loss of larger neurons and reduced metabolic components in surviving neurons indicates decreased viability one week after such hypoxic, compressive implantations. By devising an implantation method that relaxes compressive forces; magnitude and duration of hypoxia generated following such an implantation are ameliorated and neurons appear similar to naïve tissues. In line with these observations, astrocyte proliferation was significantly more pronounced for more hypoxic, compressive implantations. Surprisingly, astrocyte processes were frequently found to traverse cellular boundaries into nearby neuronal nuclei, indicating injury induction of a previously not described astrocyte-neuron interaction. Found more frequently in less hypoxic, force-relaxed insertions and thus correlating to a more beneficial outcome, this finding may suggest a novel protective mechanism. In conclusion, substantial and long lasting insertion induced hypoxia around brain implants, a previously overlooked factor, is linked to significant adverse alterations in nervous tissue.
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| 27. |
- Lin, CH, et al.
(författare)
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In Vitro Study of Human Immune Responses to Hyaluronic Acid Hydrogels, Recombinant Spidroins and Human Neural Progenitor Cells of Relevance to Spinal Cord Injury Repair
- 2021
-
Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:7
-
Tidskriftsartikel (refereegranskat)abstract
- Scaffolds of recombinant spider silk protein (spidroin) and hyaluronic acid (HA) hydrogel hold promise in combination with cell therapy for spinal cord injury. However, little is known concerning the human immune response to these biomaterials and grafted human neural stem/progenitor cells (hNPCs). Here, we analyzed short- and long-term in vitro activation of immune cells in human peripheral blood mononuclear cells (hPBMCs) cultured with/without recombinant spidroins, HA hydrogels, and/or allogeneic hNPCs to assess potential host–donor interactions. Viability, proliferation and phenotype of hPBMCs were analyzed using NucleoCounter and flow cytometry. hPBMC viability was confirmed after exposure to the different biomaterials. Short-term (15 h) co-cultures of hPBMCs with spidroins, but not with HA hydrogel, resulted in a significant increase in the proportion of activated CD69+ CD4+ T cells, CD8+ T cells, B cells and NK cells, which likely was caused by residual endotoxins from the Escherichia coli expression system. The observed spidroin-induced hPBMC activation was not altered by hNPCs. It is resource-effective to evaluate human compatibility of novel biomaterials early in development of the production process to, when necessary, make alterations to minimize rejection risk. Here, we present a method to evaluate biomaterials and hPBMC compatibility in conjunction with allogeneic human cells.
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| 28. |
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| 29. |
- Nygren, Håkan, 1952, et al.
(författare)
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Mineralization at Titanium Surfaces is a Two-Step Process.
- 2016
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Ingår i: Journal of functional biomaterials. - : MDPI AG. - 2079-4983. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Mapping the initial reaction of implants with blood or cell culture medium is important for the understanding of the healing process in bone. In the present study, the formation of low crystalline carbonated hydroxyapatite (CHA) onto commercially pure titanium (Ti) implants from cell culture medium and blood, is described as an early event in bone healing at implants. The Ti-implants were incubated with cell culture medium (DMEM) or whole blood and the surface concentration of Ca, P and HA was analyzed by XPS, EDX and Tof-SIMS. After incubation with DMEM for 16 h and 72 h, EDX and XPS analysis showed stable levels of Ca and P on the Ti-surface. ESEM images showed an even distribution of Ca and P. Further analysis of the XPS results indicated that CHA was formed at the implants. Analysis with ToF-SIMS yielded high m.w. fragments of HA, such as Ca₂PO4 at m/z 174.9 and Ca₃PO₅ at m/z 230.8, as secondary ions at the Ti-surfaces. Analysis of implants incubated in blood for 16 h, with ToF-SIMS, showed initial formation of CHA yielding CaOH as secondary ion. The results indicate that early mineralization at Ti-surfaces is an important step in the healing of implants into bone.
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| 30. |
- Odeberg, Jacob, et al.
(författare)
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A novel cysteine-linked antibacterial surface coating significantly inhibits bacterial colonization of nasal silicone prongs in a phase one pre-clinical trial
- 2018
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Ingår i: Materials science & engineering. C, biomimetic materials, sensors and systems. - : ELSEVIER SCIENCE BV. - 0928-4931 .- 1873-0191. ; 93, s. 782-789
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Tidskriftsartikel (refereegranskat)abstract
- Ventilator associated pneumonia and sepsis are frequent complications in neonatal care. Bacterial colonization of medical devices and interfaces used for respiratory support may contribute by functioning as a bacterial reservoir seeding bacteria into airways. We have developed an antibacterial surface coating based on a cysteine ligand covalently coupled via a spacer to a carboxylic backbone layer on an acrylic acid grafted silicone surface. This coating was applied on a commercially available nasal prong and the antibacterial effect was evaluated both in vitro and in vivo in a first-in-human phase 1 trial. The coated nasal prongs had strong antibacterial activity against both Gram-negative and Gram-positive bacteria in vitro. In a randomized pre-clinical trial study of 24 + 24 healthy adult volunteers who carried coated or non-coated nasal prongs for 18 h, a (10)log difference in mean bacterial colonization of 5.82 (p < 0.0001) was observed. These results show that this coating technique can prevent colonization by the normal skin and mucosal flora, and thus represent a promising novel technology for reduction of medical device-associated hospital acquired infections.
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| 31. |
- Padma, Arvind M., et al.
(författare)
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Protocols for Rat Uterus Isolation and Decellularization: Applications for Uterus Tissue Engineering and 3D Cell Culturing.
- 2018
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Ingår i: Decellularized Scaffolds and Organogenesis. Kursad Turksen (red.). - New York, NY : Springer. - 1940-6029. - 9781493976553 ; , s. 161-175
-
Bokkapitel (refereegranskat)abstract
- Sophisticated culturing conditions are required to grow cells in a three-dimensional (3D) environment. Cells then require a type of scaffold rich in proteins, growth factors, and signaling molecules that simulates their natural environment. Tissues from all species of animals have an organ-specific extracellular matrix (ECM) structure that plays a key role in cell proliferation and migration. Hence, the scaffold composition plays a significant role for any successful 3D cell culturing system. We developed a whole rat uterus ECM scaffold by the perfusion of detergents and ionic solutions through the vascular system of an isolated normal rat uterus in a process termed "decellularization." The generated rat uterus scaffolds consist of a cell-free ECM structure similar to that of the normal rat uterus, and are thus excellent platforms on to which new cells can be added. Rat uterus 3D cell culturing systems based on these scaffolds could become valuable to decidual differentiation- and embryo implantation studies, or for investigating invasion mechanisms of endometrial cancer cells. They could also be used for the creation of tissue engineered uterine tissue, for partial or whole organogenesis developed for transplantation applications to treat absolute uterine infertility. This is a condition affecting about 1 in 500 women, and is only treatable by a uterus transplantation. This article provides valuable troubleshooting notes and describes in detail how to generate rat uterus scaffolds, including the delicate surgery required to isolate the uterus with an intact vascular tree which facilitates vascular perfusion and re-transplantation.
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| 32. |
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| 33. |
- Pulkkinen, Hertta, et al.
(författare)
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Recombinant human type II collagen as a material for cartilage tissue engineering.
- 2008
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Ingår i: International Journal of Artificial Organs. - : Wichtig Editore Srl. - 0391-3988 .- 1724-6040. ; 31:11, s. 960-969
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Collagen type II is the major component of cartilage and would be an optimal scaffold material for reconstruction of injured cartilage tissue. In this study, the feasibility of recombinant human type II collagen gel as a 3-dimensional culture system for bovine chondrocytes was evaluated in vitro.METHODS: Bovine chondrocytes (4x106 cells) were seeded within collagen gels and cultivated for up to 4 weeks. The gels were investigated with confocal microscopy, histology, and biochemical assays.RESULTS: Confocal microscopy revealed that the cells maintained their viability during the entire cultivation period. The chondrocytes were evenly distributed inside the gels, and the number of cells and the amount of the extracellular matrix increased during cultivation. The chondrocytes maintained their round phenotype during the 4-week cultivation period. The glycosaminoglycan levels of the tissue increased during the experiment. The relative levels of aggrecan and type II collagen mRNA measured with realtime polymerase chain reaction (PCR) showed an increase at 1 week.CONCLUSION: Our results imply that recombinant human type II collagen is a promising biomaterial for cartilage tissue engineering, allowing homogeneous distribution in the gel and biosynthesis of extracellular matrix components.
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| 34. |
- Raina, Deepak Bushan, et al.
(författare)
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A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm3) as compared to rhBMP-2 alone (10.9 ± 2.1 mm3) when analyzed using micro computed tomography (μ-CT) (p 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone.
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| 35. |
- Shah, Furqan A., et al.
(författare)
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Bioactive glass and glass-ceramic scaffolds for bone tissue engineering
- 2018
-
Ingår i: Bioactive Glasses (Second Edition). - 9780081009369 ; , s. 201-33
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Bioactive glasses and glass-ceramics are a diverse group of materials possessing a unique set of physicochemical properties that make them useful for bone repair. Scaffolds for bone tissue engineering are subject to many requirements including biocompatibility, osteogenesis, biodegradability, and mechanical competence, all of which must be considered in the design features. This chapter addresses various scaffold fabrication techniques for melt-derived and sol-gel-derived compositions, polymer-based organic-inorganic composites, calcium phosphate-based inorganic-inorganic composites, bioactive bone cements, scaffolds based on glass compositions containing specific therapeutic ions, and hybrid materials where the organic and inorganic phases interact at the molecular level. The most important achievements, challenges and potential solutions, as well as the most promising areas of future research involving bioactive glasses and glass-ceramics for bone tissue engineering are presented.
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| 36. |
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| 37. |
- Trentin, Danielle S, et al.
(författare)
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Natural green coating inhibits adhesion of clinically important bacteria
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5, s. 8287-
-
Tidskriftsartikel (refereegranskat)abstract
- Despite many advances, biomaterial-associated infections continue to be a major clinical problem. In order to minimize bacterial adhesion, material surface modifications are currently being investigated and natural products possess large potential for the design of innovative surface coatings. We report the bioguided phytochemical investigation of Pityrocarpa moniliformis and the characterization of tannins by mass spectrometry. It was demonstrated that B-type linked proanthocyanidins-coated surfaces, here termed Green coatings, reduced Gram-positive bacterial adhesion and supported mammalian cell spreading. The proposed mechanism of bacterial attachment inhibition is based on electrostatic repulsion, high hydrophilicity and the steric hindrance provided by the coating that blocks bacterium-substratum interactions. This work shows the applicability of a prototype Green-coated surface that aims to promote necessary mammalian tissue compatibility, while reducing bacterial colonization.
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| 38. |
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| 39. |
- Willander, Hanna, et al.
(författare)
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BRICHOS Domains Efficiently Delay Fibrillation of Amyloid beta-Peptide
- 2012
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:37, s. 31608-31617
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid diseases such as Alzheimer, Parkinson, and prion diseases are associated with a specific form of protein mis-folding and aggregation into oligomers and fibrils rich in beta-sheet structure. The BRICHOS domain consisting of similar to 100 residues is found in membrane proteins associated with degenerative and proliferative disease, including lung fibrosis (surfactant protein C precursor; pro-SP-C) and familial dementia (Bri2). We find that recombinant BRICHOS domains from Bri2 and pro-SP-C prevent fibril formation of amyloid beta-peptides (A beta(40) and A beta(42)) far below the stoichiometric ratio. Kinetic experiments show that a main effect of BRICHOS is to prolong the lag time in a concentration-dependent, quantitative, and reproducible manner. An ongoing aggregation process is retarded if BRICHOS is added at any time during the lag phase, but it is too late to interfere at the end of the process. Results from circular dichroism and NMR spectroscopy, as well as analytical size exclusion chromatography, imply that A beta is maintained as an unstructured monomer during the extended lag phase in the presence of BRICHOS. Electron microscopy shows that although the process is delayed, typical amyloid fibrils are eventually formed also when BRICHOS is present. Structural BRICHOS models display a conserved array of tyrosine rings on a five-stranded beta-sheet, with inter-hydroxyl distances suited for hydrogen-bonding peptides in an extended beta-conformation. Our data imply that the inhibitory mechanism is reliant on BRICHOS interfering with molecular events during the lag phase.
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| 40. |
- Iseri, Emre
(författare)
-
Microfluidic Compartmentalization for Smart Materials, Medical Diagnostics and Cell Therapy
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The organisation of fluids in small compartments is ubiquitous in nature, such as in the cellular composition of all life. This work explores several engineering avenues where microscale fluid compartmentalization can bring novel material properties or novel functionality in life sciences or medicine. Here, we introduce four unique compartmentalization methods: 1) 3D fluid self-organisation in microscaffolds (FLUID3EAMS), 2) 2D microcapillary arrays on a dipstick (Digital Dipstick), 3) a sliding microfluidic platform with cross-flow (Slip-X-Chip), and 4) compartmentalization by cutting of soft solid matter (Solidify & Cut). These methods were used in a wide range of applications. Within the area of smart materials, we applied FLUID3EAMS to synthesize materials with temperature-tuneable permeability and surface energy and to establish, in a well-controlled fashion, tissue-like materials in the form of 3D droplet interface bilayer networks. Solidify & Cut was used to form soft composites with a new type of magnetic behaviour, rotation-induced ferromagnetism, that allows easy reprogramming of the magnetization of magnetopolymers. Within the area of medical diagnostics, we applied Digital Dipstick to perform rapid digital bacterial culture in a dipstick format and obtained clinically relevant diagnostic results on samples from patients with a urinary tract infection. Furthermore, Slip-X-Chip enables particle concentration and washing as new functions in sliding microfluidic platforms, which significantly expands their potential application area. Finally, within the area of cell therapy, we explored the microencapsulation of high concentrations of therapeutic cells and presented a novel technique to fabricate core-shell microcapsules by exploiting the superior material properties of spider silk membranes.
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| 41. |
- Micheletti, Chiara, et al.
(författare)
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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.
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| 42. |
- Pless, Christian J., et al.
(författare)
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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.
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| 43. |
- Rasmusson, Lars, 1962, et al.
(författare)
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Autogena stamceller för benrekonstruktion av defekter i käkarna
- 2018
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Ingår i: Tandläkartidningen. - 0039-6982. ; 109:11, s. 104-108
-
Tidskriftsartikel (refereegranskat)abstract
- Fallbeskrivning av 2 patienter som efter misslyckad rekonstruktion av underkäken med autologa bentransplantat rekonstruerades med ben utvunnet ur stamceller från patientens egen fettvävnad. Differentiering och cellvitalitet kunde bekräftas före re-implantation. Moget ben kunde konstateras kliniskt, histologiskt och radiologiskt efter 1 år.
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| 44. |
- Albrektsson, Tomas, 1945, et al.
(författare)
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An Imbalance of the Immune System Instead of a Disease Behind Marginal Bone Loss Around Oral Implants: Position Paper
- 2020
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Ingår i: The International journal of oral & maxillofacial implants. - : Quintessence Publishing. - 1942-4434 .- 0882-2786. ; 35:3, s. 495-502
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this paper is to present evidence that supports the notion that the primary reason behind marginal bone loss and implant failure is immune-based and that bacterial actions in the great majority of problematic cases are of a secondary nature. MATERIALS AND METHODS: The paper is written as a narrative review. RESULTS: Evidence is presented that commercially pure titanium is not biologically inert, but instead activates the innate immune system of the body. For its function, the clinical implant is dependent on an immune/inflammatory defense against bacteria. Biologic models such as ligature studies have incorrectly assumed that the primary response causing marginal bone loss is due to bacterial action. In reality, bacterial actions are secondary to an imbalance of the innate immune system caused by the combination of titanium implants and ligatures, ie, nonself. This immunologic imbalance may lead to marginal bone resorption even in the absence of bacteria. CONCLUSION: Marginal bone loss and imminent oral implant failure cannot be properly analyzed without a clear understanding of immunologically caused tissue responses.
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| 45. |
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| 46. |
- Asa'ad, Farah, 1983, et al.
(författare)
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Expression of MicroRNAs in Periodontal and Peri-Implant Diseases: A Systematic Review and Meta-Analysis.
- 2020
-
Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 21:11
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this review was to evaluate the expression patterns of miRNAs in periodontal and peri-implant diseases, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker.Human and animal studies were included when evaluating expression of miRNAs between health and different forms/stages of diseases, in which microarray and/or real-time polymerase chain reaction (RT-PCR) was carried out to detect fold changes in gene expression. After full-text analysis, 43 articles were considered for a qualitative assessment, and 16 miRNAs were selected to perform meta-analysis.Based on human studies, results showed an overall upregulation of most of the evaluated miRNAs in periodontitis, with miRNA-142-3p and miRNA-146a being the most conclusive on both microarray and RT-PCR values and potentially serving as diagnostic biomarkers for disease activity. Conversely, miR-155 was the only miRNA revealing a statistically significant difference (SSD) (p < 0.05*) in experimental periodontitis models from RT-PCR values. Scarce scientific evidence is available from peri-implant diseases, however, most explored miRNAs in peri-implantitis were downregulated except for miR-145.Although our results revealed that a distinct differential expression of specific miRNAs can be noted between the state of health and disease, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases. MeSH Terms: periodontitis, peri-implantitis, epigenomics, microarray analysis, real-time polymerase chain reaction, microRNAs.Scientific background: Although most research identified different expression levels of miRNAs in periodontal and peri-implant diseases compared to their counterparts, their actual role in the pathogenesis of these conditions remains unclear. Therefore, we aimed to present a systematic review and meta-analysis on the expression patterns of miRNAs in periodontitis and peri-implantitis, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker.In periodontitis-related studies, miRNA-142-3p and miRNA-146a were the most conclusive on both microarray and RT-PCR values. Scarce scientific evidence is available from peri-implant diseases.Both miRNA-142-3p and miRNA-146a might serve as future diagnostic biomarkers for disease activity in periodontitis. Yet, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases.
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| 47. |
- Asa'ad, Farah, 1983, et al.
(författare)
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Genetic and Epigenetic Susceptibility of Peri-Implantitis
- 2022
-
Ingår i: Unfolding Peri-implantitis: Diagnosis, Prevention. - Spain : Quintessence. - 9788489873896
-
Bokkapitel (refereegranskat)abstract
- Peri-implantitis is a destructive disease of implant-supporting tissues induced by bacterial biofilm, which provokes an inflammatory host response, influenced by environmental, genetic, and epigenetic factors. Genetics is the science that deals with genes, heredity, and the variations that occur in our genes and DNA, while epigenetics refers to alterations in the gene expression that are not encoded in the DNA sequence, which result in the remodeling of the chromatin and activation or inactivation of a gene. There are three major epigenetic mechanisms: DNA methylation, histone modifications, and microRNAs. The relationship between genetics, epigenetics, and peri-implantitis has been the subject of interest in the recent years; therefore, we aim in this chapter to present the state of the art on the role of genetic and epigenetic mechanisms in peri-implantitis.
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| 48. |
- Baş, Yağmur, et al.
(författare)
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Preparation and Characterization of Softwood and Hardwood Nanofibril Hydrogels: Toward Wound Dressing Applications
- 2023
-
Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 24:12, s. 5605-5619
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Tidskriftsartikel (refereegranskat)abstract
- Hydrogels of cellulose nanofibrils (CNFs) are promising wound dressing candidates due to their biocompatibility, high water absorption, and transparency. Herein, two different commercially available wood species, softwood and hardwood, were subjected to TEMPO-mediated oxidation to proceed with delignification and oxidation in a one-pot process, and thereafter, nanofibrils were isolated using a high-pressure microfluidizer. Furthermore, transparent nanofibril hydrogel networks were prepared by vacuum filtration. Nanofibril properties and network performance correlated with oxidation were investigated and compared with commercially available TEMPO-oxidized pulp nanofibrils and their networks. Softwood nanofibril hydrogel networks exhibited the best mechanical properties, and in vitro toxicological risk assessment showed no detrimental effect for any of the studied hydrogels on human fibroblast or keratinocyte cells. This study demonstrates a straightforward processing route for direct oxidation of different wood species to obtain nanofibril hydrogels for potential use as wound dressings, with softwood having the most potential.
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| 49. |
- Ferrantino, Luca, et al.
(författare)
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Aesthetic Outcomes of Non-functional Immediately Restored Single Post-extraction Implants with and without Connective Tissue Graft: A Multicenter Randomized Controlled Trial.
- 2021
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Ingår i: Clinical oral implants research. - : Wiley. - 1600-0501 .- 0905-7161. ; 32:6, s. 684-694
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Tidskriftsartikel (refereegranskat)abstract
- To compare the one-year aesthetic results of flapless single implants, placed in fresh extraction sockets with bone replacement and immediate provisional restoration with or without a connective tissue graft (CGT).The present study proposes a partially blinded multicenter parallel randomized controlled trial, where computer-generated tables were used for central randomization to allocate treatments. 59 out of the 60 patients screened by eight private practices in Northern Italy fulfilled the inclusion criteria. Immediate implants was placed in a fresh extraction socket with a non-functional immediate provisional restoration with (Test group) or without (Control group) a CGT. The primary outcome variable was the implant Crown Aesthetic Index (ICAI) at the 1-year follow-up.ICAI for the 59 randomized patients (Test group = 31, Control group = 28) at the 1-year follow-up was 4.69 (95% CI = 3.16 - 6.22) for the Test group and 3.45 (95%CI = 1.83-5.08) for the Control group, without statistically significant difference between the two groups (p=0.086). One implant failure was recorded in each group, resulting in an implant survival rate of 96.8% [95%CI = 83.3 - 99.9] for the Test group and 96.4% [95%CI = 81.7 -99.9] for the Control group. Other secondary outcome variables and complication rates were comparable across the two groups.Within the limitations of the present clinical trial, the results suggested that the adjunct use of CTG is not mandatory to achieve successful aesthetic outcomes for a well-planned immediate implant placement with immediate non-functional provisional restoration in a fresh extraction socket.
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| 50. |
- Ghandour, Salim, et al.
(författare)
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Optimization of titanium spinal cages to maximize synthetic graft content in composite implants
- 2022
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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.
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