| 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
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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
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Ingår i: Journal of Biomedical Materials Research. Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 104:3, s. 620-629
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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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