| 1. |
- Aimonen, Kukka, et al.
(författare)
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Role of Surface Chemistry in the In Vitro Lung Response to Nanofibrillated Cellulose
- 2021
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Ingår i: Nanomaterials. - : MDPI. - 2079-4991. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Wood-derived nanofibrillated cellulose (NFC) has emerged as a sustainable material with a wide range of applications and increasing presence in the market. Surface charges are introduced during the preparation of NFC to facilitate the defibrillation process, which may also alter the toxicological properties of NFC. In the present study, we examined the in vitro toxicity of NFCs with five surface chemistries: nonfunctionalized, carboxymethylated, phosphorylated, sulfoethylated, and hydroxypropyltrimethylammonium-substituted. The NFC samples were characterized for surface functional group density, surface charge, and fiber morphology. Fibril aggregates predominated in the nonfunctionalized NFC, while individual nanofibrils were observed in the functionalized NFCs. Differences in surface group density among the functionalized NFCs were reflected in the fiber thickness of these samples. In human bronchial epithelial (BEAS-2B) cells, all NFCs showed low cytotoxicity (CellTiter-GloVR luminescent cell viability assay) which never exceeded 10% at any exposure time. None of the NFCs induced genotoxic effects, as evaluated by the alkaline comet assay and the cytokinesis-block micronucleus assay. The nonfunctionalized and carboxymethylated NFCs were able to increase intracellular reactive oxygen species (ROS) formation (chloromethyl derivative of 2 ',7 '-dichlorodihydrofluorescein diacetate assay). However, ROS induction did not result in increased DNA or chromosome damage.
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| 2. |
- Basu, Alex, et al.
(författare)
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Hemocompatibility of Ca2+-Crosslinked Nanocellulose Hydrogels : Toward Efficient Management of Hemostasis
- 2017
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Ingår i: Macromolecular Bioscience. - : Wiley. - 1616-5187 .- 1616-5195. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- The present work investigates Ca2+-crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing—the blood. Hydrogels of wood-derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet-free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.
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| 3. |
- Basu, Alex, et al.
(författare)
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In Vitro and in Vivo Evaluation of the Wound Healing Properties of Nanofibrillated Cellulose Hydrogels
- 2018
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 1:6, s. 1853-1863
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Tidskriftsartikel (refereegranskat)abstract
- Current trends in wound care research move toward the development of wound healing dressings designed to treat different types of wounds (e.g., burns and chronic wounds) and toward tailoring treatments for different stages of the wound healing process. In this context, the development of advanced nanotherapeutic materials is highlighted as a promising strategy to efficiently control specific phases of the wound healing process. Here, Ca2+-cross-linked wood-derived nanofibrillated cellulose (NFC) hydrogels are evaluated as wound healing dressings. In vitro biocompatibility assays were performed to study the interaction of the NFC hydrogels with cellular processes that are tightly related to wound healing. Moreover, an in vivo dermo-epidermic full thickness wound healing model in rat was used to uncover the wound healing ability of the Ca2+-cross-linked NFC hydrogels. The in vitro experiments showed that the NFC hydrogels were able to support fibroblast and keratinocyte proliferation. A potential effect of the hydrogels on triggering keratinocyte differentiation was furthermore proposed. In vivo, the NFC hydrogels stimulated healing without causing any adverse local tissue effects, potentially owing to their moisture-donating properties and the herein discussed aiding effect of the Ca2+-cross-linker on epidermal generation. Thus, this work extensively demonstrates the wound healing ability of NFC hydrogels and presents an important milestone in the research on NFC toward advanced wound healing applications.
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| 4. |
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| 5. |
- Basu, Alex, et al.
(författare)
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Ion-crosslinked wood-derived nanocellulose hydrogels with tunable antibacterial properties : Candidate materials for advanced wound care applications
- 2018
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 181, s. 345-350
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Tidskriftsartikel (refereegranskat)abstract
- Development of advanced dressings with antimicrobial properties for the treatment of infected wounds is an important approach in the fight against evolution of antibiotic resistant bacterial strains. Herein, the effects of ion-crosslinked nanocellulose hydrogels on bacteria commonly found in infected wounds were investigated in vitro. By using divalent calcium or copper ions as crosslinking agents, different antibacterial properties against the bacterial strains Staphylococcus epidermidis and Pseudomonas aeruginosa were obtained. Calcium crosslinked hydrogels were found to retard S. epidermidis growth (up to 266% increase in lag time, 36% increase in doubling time) and inhibited P. aeruginosa biofilm formation, while copper crosslinked hydrogels prevented S. epidermidis growth and were bacteriostatic towards P. aeruginosa (49% increase in lag time, 78% increase in doubling time). The wound dressing candidates furthermore displayed barrier properties towards both S. epidermidis and P. aeruginosa, hence making them interesting for further development of advanced wound dressings with tunable antibacterial properties.
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| 6. |
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| 7. |
- Basu, Alex, et al.
(författare)
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On the use of ion-crosslinked nanocellulose hydrogels for wound healing solutions : Physicochemical properties and application-oriented biocompatibility studies
- 2017
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 174, s. 299-308
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Tidskriftsartikel (refereegranskat)abstract
- Calcium ion-crosslinked nanofibrillated cellulose (NFC) hydrogels were investigated as potential materials for wound healing dressings. The physicochemical properties of the hydrogels were examined by rheology and water retention tests. Skin cells and monocytes were selected for application-oriented bio-compatibility studies. The NFC hydrogels presented entangled fibrous networks and solid-like behavior. Water retention tests showed the material's potential to maintain a suitable moist environment for different type of wounds. The hydrogels did not affect dermal fibroblasts monolayer cultures upon directcontact, as cell monolayers remained intact after application, incubation and removal of the materials. Inflammatory response studies with blood-derived mononuclear cells revealed the inert nature of the hydrogels in terms of cytokine secretion and reactive oxygen species production. Results highlight the great potential of ion-crosslinked NFC hydrogels for the development of advanced wound dressings, where further functionalization of the material could lead to improved properties towards the healing of specific wound types.
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| 8. |
- Basu, Alex, et al.
(författare)
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Towards Tunable Protein-Carrier Wound Dressings Based on Nanocellulose Hydrogels Crosslinked with Calcium Ions
- 2018
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Ingår i: Nanomaterials. - : MDPI. - 2079-4991. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- A Ca2+-crosslinked wood-based nanofibrillated cellulose (NFC) hydrogel was investigated to build knowledge toward the use of nanocellulose for topical drug delivery applications in a chronic wound healing context. Proteins of varying size and isoelectric point were loaded into the hydrogel in a simple soaking procedure. The release of the proteins from the hydrogel was monitored and kinetics determining parameters of the release processes were assessed. The integrity of the hydrogel and proteins were also studied. The results showed that electrostatic interactions between the proteins and the negatively-charged NFC hydrogel structure played a central role in the loading process. The release of the proteins were governed by Fickian diffusion. An increased protein size, as well as a positive protein charge facilitated a slower and more sustained release process from the hydrogel matrix. At the same time, the positively-charged protein was shown to increase the post-loading hydrogel strength. Released proteins maintained structural stability and activity, thus indicating that the Ca2+-crosslinked NFC hydrogel could function as a carrier of therapeutic proteins without compromising protein function. It is foreseen that, by utilizing tunable charge properties of the NFC hydrogel, release profiles can be tailored to meet very specific treatment needs.
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| 9. |
- Blasi Romero, Anna
(författare)
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Bioactive nanocellulose materials for the treatment of chronic wounds
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic wounds represent a burden for the healthcare system and significantly affect the quality of life of the patients. There is currently a lack of efficient treatments but new, improved therapeutic approaches are under development. Suggested innovative wound care therapies consist on the topical administration of bioactive compounds aimed at restoring the balance in the wound environment and promoting the healing. However, their effectiveness is limited due to the highly oxidative and proteolytic environment in the chronic wound. In the work presented in this thesis, a series of bioactive nanocellulose-based materials were developed with the aim of addressing some of the present demands in chronic wound care. Wood-derived cellulose nanofibrils (CNFs) were functionalized with selected bioactive molecules expected to endow CNFs with the ability to modulate the chronic wound environment. Different chemical approaches were explored to combine CNFs with the following biomolecules: the amino acid cysteine, the peptide oligoproline and the host defense peptide KR-12. Materials were characterized in terms of chemical structure, degree of substitution and bioactivity.The immobilization of cysteine onto CNFs (cys-CNF) provided the material with radical oxygen species (ROS) scavenging properties and the ability to inhibit protease activity, properties that were related to the presence of free thiol groups on the nanofibers. Storage conditions in an inert atmosphere or in the form of aerogel were proposed to assure the long-term activity of the cys-CNF material. Investigations on the use of the ROS-sensitive oligoproline to crosslink CNFs provided optimized protocols to maximize peptide substitution and the degree of crosslinking. The oligoproline-CNF materials were sensitive to ROS-mediated cleavage and provided a protective effect to cells exposed to oxidative conditions. Moreover, the feasibility of preparing ROS-responsive drug delivery hydrogels based on the oligoproline-CNF was demonstrated, with indications that tuning the length of the oligoproline peptide could be exploited to tailor the release rate of small proteins. CNF materials with antibacterial properties and the ability to modulate the response of pro-inflammatory macrophages were obtained by immobilizing KR-12 derivatives onto CNFs. This study highlighted the importance in the selection of the conjugation chemistry to preserve the activity of the peptide once immobilized. To conclude, this work has contributed with valuable strategies to develop bioactive CNF-based materials with the potential of paving the way for advanced solutions in the field of chronic wound care.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Blasi-Romero, Anna, et al.
(författare)
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In Vitro Investigation of Thiol-Functionalized Cellulose Nanofibrils as a Chronic Wound Environment Modulator
- 2021
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Ingår i: Polymers. - : MDPI. - 2073-4360. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- There is currently a huge need for new, improved therapeutic approaches for the treatment of chronic wounds. One promising strategy is to develop wound dressings capable of modulating the chronic wound environment (e.g., by controlling the high levels of reactive oxygen species (ROS) and proteases). Here, we selected the thiol-containing amino acid cysteine to endow wood-derived cellulose nanofibrils (CNF) with bioactivity toward the modulation of ROS levels and protease activity. Cysteine was covalently incorporated into CNF and the functionalized material, herein referred as cys-CNF, was characterized in terms of chemical structure, degree of substitution, radical scavenging capacity, and inhibition of protease activity. The stability of the thiol groups was evaluated over time, and an in vitro cytotoxicity study with human dermal fibroblasts was performed to evaluate the safety profile of cys-CNF. Results showed that cys-CNF was able to efficiently control the activity of the metalloprotease collagenase and to inhibit the free radical DPPH (1,1-Diphenyl-2-picrylhydrazyl radical), activities that were correlated with the presence of free thiol groups on the nanofibers. The stability study showed that the reactivity of the thiol groups challenged the bioactivity over time. Nevertheless, preparing the material as an aerogel and storing it in an inert atmosphere were shown to be valid approaches to increase the stability of the thiol groups in cys-CNF. No signs of toxicity were observed on the dermal fibroblasts when exposed to cys-CNF (concentration range 0.1-0.5 mg/mL). The present work highlights cys-CNF as a promising novel material for the development of bioactive wound dressings for the treatment of chronic wounds.
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| 14. |
- Blasi Romero, Anna, et al.
(författare)
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KR-12 derivatives endow nanocellulose with antibacterial and anti-inflammatory properties : Role of conjugation chemistry
- 2023
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Ingår i: ACS Applied Materials and Interfaces. - 1944-8244 .- 1944-8252. ; 15:20, s. 24186-24196
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Tidskriftsartikel (refereegranskat)abstract
- This work combines the wound-healing-related properties of the host defense peptide KR-12 with wood-derived cellulose nanofibrils (CNFs) to obtain bioactive materials, foreseen as a promising solution to treat chronic wounds. Amine coupling through carbodiimide chemistry, thiol-ene click chemistry, and Cu(I)-catalyzed azide-alkyne cycloaddition were investigated as methods to covalently immobilize KR-12 derivatives onto CNFs. The effects of different coupling chemistries on the bioactivity of the KR12-CNF conjugates were evaluated by assessing their antibacterial activities against Escherichia coli and Staphylococcus aureus. Potential cytotoxic effects and the capacity of the materials to modulate the inflammatory response of lipopolysaccharide (LPS)-stimulated RAW 245.6 macrophages were also investigated. The results show that KR-12 endowed CNFs with antibacterial activity against E. coli and exhibited anti-inflammatory properties and those conjugated by thiol-ene chemistry were the most bioactive. This finding is attributed to a favorable peptide conformation and accessibility (as shown by molecular dynamics simulations), driven by the selective chemistry and length of the linker in the conjugate. The results represent an advancement in the development of CNF-based materials for chronic wound care. This study provides new insights into the effect of the conjugation chemistry on the bioactivity of immobilized host defense peptides, which we believe to be of great value for the use of host defense peptides as therapeutic agents.
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| 15. |
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| 16. |
- Fernandez-Cruz, Maria Luisa, et al.
(författare)
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Quality evaluation of human and environmental toxicity studies performed with nanomaterials – the GUIDEnano approach
- 2018
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Ingår i: Environmental Science: Nano. ; 5:2, s. 381-397
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Tidskriftsartikel (refereegranskat)abstract
- The European Union FP-7 project GUIDEnano developed a web-based guidance tool, which guides users to assess human and environmental risks of nanomaterial-enabled products throughout their life cycle. One of the aims in the GUIDEnano hazard assessment strategy is to derive safety limit values based on existing human toxicity and ecotoxicological studies. Clear criteria needed to be established to select studies that could be used for such purpose. In the present paper, we present an approach for a systematical and quantitative evaluation of the quality of environmental and human toxicity studies performed with nanomaterials. The approach builds upon previous initiatives and includes refinements to facilitate its application by users with limited toxicological expertise. It covers in vivo and in vitro human toxicity studies as well as ecotoxicological studies addressing the toxicity to all environmental compartments. A scoring system related to test design and reporting considerations was developed following the principles of the Klimisch score (K score). In addition, the approach includes a scoring system based on the physicochemical properties that have been characterized and reported for the nanomaterial, including properties characterized in the exposure medium (S score). These two scores (K and S) are combined to obtain an overall quality score (Q score) that can be used to select studies, to weight different studies, and/or to introduce uncertainty factors in the risk assessment process. During its development, the approach has been tested and refined with 137 peer-reviewed articles. The final quality assessment approach and the results of its evaluation are presented here.
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| 17. |
- Ferraz, Natalia, 1976-
(författare)
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Effect of Surface Nanotopography on Blood-Biomaterial Interactions
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biologically inspired materials are being developed with the aim of improving the integration of medical implants and minimizing non-desirable host reactions. A promising strategy is the design of topographically patterned surfaces that resemble those found in the extracellular environment. Nanoporous alumina has been recognized as a potential biomaterial and as an important template for the fabrication of nanostructures. In this thesis in vitro studies were done to elucidate the role of alumina nanoporosity on the inflammatory response. Specifically, by comparing alumina membranes with two pore sizes (20 and 200 nm in diameter). Complement and platelet activation were evaluated as well as monocyte/macrophage behaviour. Whole blood was incubated with the alumina membranes and thereafter the biomaterial surfaces were evaluated in terms of protein and platelet adhesion as well as procoagulant properties. The fluid phase was analyzed for complement activation products and platelet activation markers. Besides, human mononuclear cells were cultured on the alumina membranes and cell adhesion, viability, morphology and release of pro-inflammatory cytokines were evaluated. The results indicated that nanoporous alumina with 200 nm pores promotes higher complement activation than alumina with 20 nm pores. In addition, platelet response to nanoporous alumina was found to be highly dependent on the material porosity, as reflected by differences in adhesion, PMP generation and procoagulant characteristics. A clear difference in monocyte/macrophage adhesion and activation was found between the two pore size alumina membranes. Few but highly activated cells adhered to the 200 nm membrane in contrast to many but less activated monocytes/macrophages on the 20 nm surface. The outcome of this work emphasizes that nanotopography plays an important role in the host response to biomaterials. Better understanding of molecular interactions on nano-level will undoubtedly play a significant role in biomaterial implant development and will contribute to design strategies for controlling specific biological events.
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| 18. |
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| 19. |
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| 20. |
- Ferraz, Natalia, 1976-
(författare)
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Nanobiomaterials
- 2021
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Ingår i: NFM Krusenberg conference 2021. - Uppsala.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 21. |
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| 22. |
- Ferraz, Natalia, 1976-, et al.
(författare)
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Nanoporosity of alumina surfaces induces different patterns of activation in adhering monocytes/macrophages
- 2010
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Ingår i: International Journal of Biomaterials. - : Hindawi Limited. - 1687-8787 .- 1687-8795. ; 2010, s. 402715-
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Tidskriftsartikel (refereegranskat)abstract
- The present study shows that alumina nanotopography affects monocyte/macrophage behaviour. Human mononuclear cells cultured on alumina membranes with pore diameters of 20 and 200 nm were evaluated in terms of cell adhesion, viability, morphology and release of pro-inflammatory cytokines. After 24 hours, cell adhesion was assessed by means of light microscopy and cell viability by measuring LDH release. The inflammatory response was evaluated by quantifying interleukin-1ß and tumour necrosis factor-α. Finally, scanning electron microscopy was used to study cell morphology. Results showed pronounced differences in cell number, morphology and cytokine release depending on the nanoporosity. Few but highly activated cells were found on the 200 nm porous alumina, while relatively larger number of cells was found on the 20 nm porous surface. However, despite their larger number, the cells adhering on the 20 nm surface exhibited reduced pro-inflammatory activity. It can be speculated that the difference in surface topography may lead to distinct protein adsorption patterns and therefore to different degree of cell activation. The data of this paper emphasize the role played by the material nanotexture in dictating cell responses and implies that nanotopography could be exploited for controlling the inflammatory response to implants.
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| 23. |
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| 24. |
- Ferraz, Natalia, 1976-, et al.
(författare)
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Procoagulant behavior and platelet microparticle generation on nanoporous alumina
- 2010
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Ingår i: Journal of biomaterials applications. - : SAGE. - 0885-3282 .- 1530-8022. ; 24:8, s. 675-692
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Tidskriftsartikel (refereegranskat)abstract
- In the present work, we have investigated platelet microparticle(PMP) generation in whole blood after contact with nanoporous alumina.Alumina membranes with pore sizes of 20 and 200nm in diameter were incubated with whole blood and the number of PMP in the fluid phase was determined by flow cytometry. The role of the complement system in PMP generation was investigated using an analog of the potent complement inhibitor compstatin. Moreover, the procoagulant activity of the two pore size membranes were compared by measuring thrombin formation. Results indicated that PMP were not present in the fluid phase after whole blood contact with either of the alumina membranes. However, scanning electron microscope micrographs clearly showed the presence of PMP clusters on the 200nm pore size alumina, while PMP were practically absent on the 20nm membrane. We probed no influence of complement activation in PMP generation and adhesion and we hypothesize that other specific material-related protein–platelet interactions are taking place. A clear difference in procoagulant activity between the membranes could also be seen, 20nm alumina showed 100% higher procoagulant activity than 200nm membrane. By combining surface evaluation and flow cytometry analyses of the fluid phase, we are able to conclude that 200nm pore size alumina promotes PMP generation and adhesion while the 20nm membrane does not appreciably cause any release or adhesion of PMP, thus indicating a direct connection between PMP generation and nanoporosity.
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| 25. |
- Ferraz, Natalia, 1976-
(författare)
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The Guide Nano Project
- 2014
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Ingår i: NFM conference, Prague 16-18th June 2014..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 26. |
- Ferraz, Natalia, 1976-, et al.
(författare)
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Time sequence of blood activation by nanoporous alumina : Studies on platelets and complement system
- 2010
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Ingår i: Microscopy research and technique (Print). - : Wiley-Liss Inc.. - 1059-910X .- 1097-0029. ; 73:12, s. 1101-1109
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Tidskriftsartikel (refereegranskat)abstract
- In the present work the time sequence of blood activation by alumina membranes with different porosities (20 and 200 nm in diameter) was studied. The membranes were incubated with whole blood from 2 min to 4 h. Platelet adhesion and activation in addition to complement activation were monitored at different time points. Evaluation of platelet adhesion and activation was done by determining the change in platelet number and the levels of thrombospondin-1 in the fluid phase. Scanning electron microscopy studies were done to further evaluate platelet adhesion and morphology. Immunocytochemical staining was used to evaluate the presence of CD41 and CD62P antigens on the material surface. Complement activation was monitored by measuring C3a and sC5b-9 in plasma samples by means of enzyme immunoassays. Both alumina membranes displayed similar complement activation time profiles, with levels of C3a and sC5b-9 increasing with incubation time. A statistically significant difference between the membranes was found after 60 min of incubation. Platelet activation characteristics and time profile were different between the two membranes. Platelet adhesion increased over time for the 20 nm surface, while the clusters of microparticles on the 200 nm surface did not appreciably change during the course of the experiment. The release of thrombospondin-1 increased with time for both membranes, however much later for the 200 nm alumina (240 min) as compared to the 20 nm membrane (60 min). The surface topography of the alumina most probably influence protein transition rate, which in turn affects material-platelet activation kinetics.
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| 27. |
- Kerr White, John, et al.
(författare)
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A Synthetic Cyclized Antimicrobial Peptide with Potent Effects against Drug-Resistant Skin Pathogens
- 2023
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Ingår i: ACS - Infectious Diseases. - : American Chemical Society (ACS). - 2373-8227. ; 9:5, s. 1056-1063
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Tidskriftsartikel (refereegranskat)abstract
- Dermal infections requiring treatment are usually treated with conventional antibiotics, but the rise of bacterial resistance to first-line antibiotics warrants alternative therapeutics. Here, we report that a backbone-cyclized antimicrobial peptide, CD4-PP, designed from the human host defense peptide LL-37, has strong direct antibacterial effects on antibiotic sensitive as well as resistant-type strains and clinical isolates of common skin pathogens in the low (<2) μM range. In addition, it influences innate immunity in keratinocytes, and treatment with CD4-PP is able to clear bacterial infections in infected keratinocytes. Additionally, CD4-PP treatment significantly reduces the wound area in a lawn of keratinocytes infected with MRSA. In conclusion, CD4-PP has the potential to serve as a future drug treating wounds infected with antibiotic-resistant bacteria.
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| 28. |
- Larsson, Lisa, et al.
(författare)
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Biocompatibility of a Zr-Based Metallic Glass Enabled by Additive Manufacturing
- 2022
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 5:12, s. 5741-5753
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Tidskriftsartikel (refereegranskat)abstract
- The present work explored the use of the selective laser melting (SLM) technique to develop a Zr-based bulk metallic glass (BMG) and investigate the influence of the process parameters on obtaining different levels of surface roughness. Moreover, the potential of the additively manufactured BMG Zr59.3Cu28.8Al10.4Nb1.5 (trade name AMLOY-ZR01) as an implant material was studied by evaluating the osteoblastic cell response to the alloy and its stability under simulated biological environments. The materials were characterized in terms of degree of crystallinity, surface roughness, and morphology, followed by a systematic investigation of the response of the MC3T3-E1 preosteoblastic cell line to the as-printed samples. The materials supported cell proliferation and differentiation of the preosteoblastic cells, with results comparable to the reference material Ti-6Al-4V. The surface microroughness and surface morphology (porous or groove-type laser tracks) investigated in this study did not have a significant effect on modulating the cell response. Ion release experiments showed a large increase in ion release under inflammatory conditions as compared to regular physiological conditions, which could be attributed to the increased local corrosion under inflammatory conditions. The findings in this work showed that the surface roughness of the additively manufactured BMG AMLOY-ZR01 can be tailored by controlling the laser power applied during the SLM process. The favorable cell response to the as-printed AMLOY-ZR01 represents of a significant advancement of the investigation of additively manufactured BMGs for orthopedic applications, while the results of the ion release study highlights the effect that inflammatory conditions could have on the degradation of the alloy.
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| 29. |
- Lopes, Viviana R., et al.
(författare)
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In Vitro Biological Impact of Nanocellulose Fibers on Human Gut Bacteria and Gastrointestinal Cells
- 2020
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Ingår i: Nanomaterials. - : MDPI. - 2079-4991. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Wood-derived nanofibrillated cellulose (NFC) has long been recognized as a valuable nanomaterial for food-related applications. However, the safety of NFC cannot be predicted just from the chemical nature of cellulose, and there is a need to establish the effect of the nanofibers on the gastrointestinal tract, to reassure the safe use of NFC in food-related products. The present work selected the intestinal cells Caco-2 and the gut bacteria Escherichia coli and Lactobacillus reuteri to evaluate the in vitro biological response to NFC. NFC materials with different surface modifications (carboxymethylation, hydroxypropyltrimethylammonium substitution, phosphorylation and sulfoethylation) and unmodified NFC were investigated. The materials were characterized in terms of surface functional group content, fiber morphology, zeta potential and degree of crystallinity. The Caco-2 cell response to the materials was evaluated by assessing metabolic activity and cell membrane integrity. The effects of the NFC materials on the model bacteria were evaluated by measuring bacterial growth (optical density at 600 nm) and by determining colony forming units counts after NFC exposure. Results showed no sign of cytotoxicity in Caco-2 cells exposed to the NFC materials, and NFC surface functionalization did not impact the cell response. Interestingly, a bacteriostatic effect on E. coli was observed while the materials did not affect the growth of L. reuteri. The present findings are foreseen to contribute to increase the knowledge about the potential oral toxicity of NFC and, in turn, add to the development of safe NFC-based food products.
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| 30. |
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| 31. |
- Marattukalam, Jithin James, et al.
(författare)
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Exploring the use of selective laser melting to control the surface roughness of a Zr-based bulk metallic glass: surface characterization, ion release and osteoblastic cell response
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Zr-based bulk metallic glasses (BMGs) have attracted attention as promising candidates for orthopedic applications due to their relatively low Young´s modulus, excellent corrosion and wear resistance, and high strength. The challenge for BMGs as potential biomaterials is their production in large dimensions and complex geometries, a problem that can be addressed by additive manufacturing techniques. The present work explored the use of selective laser melting to develop a Zr-based BMG (Zr59.3Cu28.8Al10.4Nb1.5, trade name AMLOY-ZR01) and investigated the influence of the process parameters on obtaining different levels of surface roughness with the ultimate aim of modulating the material biocompatibility. The materials were characterized in terms of the degree of crystallinity, surface roughness, and morphology, followed by a systematic investigation of the response of the MC3T3-E1 pre-osteoblastic cell line to the as-printed samples. The substrates supported cell proliferation and differentiation of the pre-osteoblastic cells, with results comparable to the reference material Ti6A14V. The surface microroughness and surface morphology (porous or groove-type laser tracks) under study did not have a significant effect on modulating the cell response. Ion release experiments performed under regular physiological and inflammatory test conditions showed a large increase in ion release under inflammatory conditions as compared to regular physiological conditions. The findings in this work showed that the additively manufactured AMLOY-ZR01 is a promising BMG for orthopedic applications, and highlighted the effect that inflammatory conditions could have on the degradation of the alloy.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Palo Nieto, Carlos, et al.
(författare)
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Developing reactive oxygen species-sensitive cellulose nanofibers for chronic wound care
- 2022
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Konferensbidrag (refereegranskat)abstract
- There is an increasing interest in developing bio-responsive materials using reactive oxygen species (ROS) as biological stimulus.1 These materials, with the potential to be used in several biomedical applications, i.e. wound healing,2 should have the capacity to specifically reduce the excess of ROS at sites of inflammation and promote tissue healing. Wood derived cellulose nanofibrils (CNFs) have emerged as an interesting nanomaterial with highly tunable properties that could be of value for wound care applications. In our group, we have demonstrated the ability of CNF-based hydrogels to aid in the healing of acute wounds,3 being an excellent platform for the development of bioactive wound healing dressings. In the present work, ROS-sensitive peptides were covalently incorporated into carboxymethylated CNFs (c-CNF) using two well-known chemical reactions; amine coupling through EDC/NHS activation and reductive amination. The obtained materials were characterized in terms of chemical structure (CP/MAS 13C-NMR spectroscopy), degree of substitution (elemental analysis of nitrogen content) and degree of crosslinking (ninhydrin test).The new synthetized biomaterials (figure 1) showed susceptibility to an oxidative environment and their ROS scavenging properties were confirmed by their cell-protective effect in the presence of high levels of ROS. These results serve as an excellent starting point for the development of CNF-based dressings capable of promoting the resolution of chronic wounds.
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| 36. |
- Palo-Nieto, Carlos, 1985-, et al.
(författare)
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Functionalization of cellulose nanofibrils to develop novel ROS-sensitive biomaterials
- 2023
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Ingår i: Materials Advances. - : Royal Society of Chemistry. - 2633-5409. ; 4:6, s. 1555-1565
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Tidskriftsartikel (refereegranskat)abstract
- Wood derived cellulose nanofibrils (CNFs) have emerged as an interesting material for biomedical applications. Functionalization of the nanofibrils with bioactive molecules is a potent tool to tailor CNF materials for specific applications in biomedicine. The present work proposes the functionalization of CNFs with a reactive oxygen species (ROS)-sensitive oligopeptide to develop a novel CNF-based material for the treatment of medical conditions associated with high levels of ROS such as chronic wounds. Oligoproline peptides of two different lengths (5 and 10 proline units) were covalently incorporated onto the CNF surface, several water-based chemical approaches were explored and the reaction conditions to maximize peptide substitution and the degree of fibre crosslinking were optimized. The chemical structure, degree of peptide substitution, degree of fibre crosslinking, surface morphology and ROS-sensitivity of the oligoproline–CNF materials were characterized. Double-crosslinked CNF hydrogels (Ca2+–oligoproline–CNF) were further prepared and the ability of the hydrogels to protect cells from an oxidative environment was investigated in vitro with human dermal fibroblasts, as a first evaluation of the potential of the novel CNF material to be used in chronic wound therapies. Optimization of the reaction conditions resulted in a degree of peptide substitution of 102 ± 10 μmol g−1 CNF irrespective of the oligoproline length and a degree of crosslinking of 55–80% depending on the number of proline units. The results showed that the oligoproline covalently attached to CNFs via carbodiimide chemistry maintained its ability to respond to ROS and that the responsiveness in terms of viscoelastic properties depended on the length of the oligopeptide, with the hydrogel being more responsive when functionalized with 10 proline units compared with 5 proline units. Furthermore, the double crosslinked Ca2+–oligoproline–CNF hydrogels promoted the survival of human dermal fibroblasts exposed to high levels of ROS. This study is the first one to provide an insight into the development of ROS-sensitive materials based on CNFs and opens up possibilities for further investigation on the use of these novel materials in chronic wound care.
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| 37. |
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| 38. |
- Park, Margriet V. D. Z., et al.
(författare)
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Development of a systematic method to assess similarity between nanomaterials for human hazard evaluation purposes - lessons learnt
- 2018
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Ingår i: Nanotoxicology. - : TAYLOR & FRANCIS LTD. - 1743-5390 .- 1743-5404. ; 12:7, s. 652-676
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Tidskriftsartikel (refereegranskat)abstract
- Within the EU FP-7 GUIDEnano project, a methodology was developed to systematically quantify the similarity between a nanomaterial (NM) that has been tested in toxicity studies and the NM for which risk needs to be evaluated, for the purpose of extrapolating toxicity data between the two materials. The methodology is a first attempt to use current knowledge on NM property-hazard relationships to develop a series of pragmatic and systematic rules for assessing NM similarity. Moreover, the methodology takes into account the practical feasibility, in that it is based on generally available NM characterization information. In addition to presenting this methodology, the lessons learnt and the challenges faced during its development are reported here. We conclude that there is a large gap between the information that is ideally needed and its application to real cases. The current database on property-hazard relationships is still very limited, which hinders the agreement on the key NM properties constituting the basis of the similarity assessment and the development of associated science-based and unequivocal rules. Currently, one of the most challenging NM properties to systematically assess in terms of similarity between two NMs is surface coating and functionalization, which lacks standardized parameters for description and characterization methodology. Standardization of characterization methods that lead to quantitative, unambiguous, and measurable parameters describing NM properties are necessary in order to build a sufficiently robust property-hazard database that allows for evidence-based refinement of our methodology, or any other attempt to systematically assess the similarity of NMs.
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| 39. |
- Rocha, Igor, et al.
(författare)
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Blood Compatibility of Sulfonated Cladophora Nanocellulose Beads
- 2018
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 23:3
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Tidskriftsartikel (refereegranskat)abstract
- Sulfonated cellulose beads were prepared by oxidation of Cladophora nanocellulose to 2,3-dialdehyde cellulose followed by sulfonation using bisulfite. The physicochemical properties of the sulfonated beads, i.e., high surface area, high degree of oxidation, spherical shape, and the possibility of tailoring the porosity, make them interesting candidates for the development of immunosorbent platforms, including their application in extracorporeal blood treatments. A desired property for materials used in such applications is blood compatibility; therefore in the present work, we investigate the hemocompatibility of the sulfonated cellulose beads using an in vitro whole blood model. Complement system activation (C3a and sC5b-9 levels), coagulation activation (thrombin-antithrombin (TAT) levels) and hemolysis were evaluated after whole blood contact with the sulfonated beads and the results were compared with the values obtained with the unmodified Cladophora nanocellulose. Results showed that neither of the cellulosic materials presented hemolytic activity. A marked decrease in TAT levels was observed after blood contact with the sulfonated beads, compared with Cladophora nanocellulose. However, the chemical modification did not promote an improvement in Cladophora nanocellulose hemocompatibility in terms of complement system activation. Even though the sulfonated beads presented a significant reduction in pro-coagulant activity compared with the unmodified material, further modification strategies need to be investigated to control the complement activation by the cellulosic materials.
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| 40. |
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| 41. |
- Rocha, Igor, et al.
(författare)
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Sulfonated Nanocellulose Beads as Potential Immunosorbents
- 2018
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Ingår i: Cellulose. - : Springer Science and Business Media LLC. - 0969-0239 .- 1572-882X. ; 28:3, s. 1899-1910
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Tidskriftsartikel (refereegranskat)abstract
- Herein 2,3-dialdehyde cellulose beads prepared from Cladophora green algae nanocellulose were sulfonated and characterized by FTIR, conductometric titration, elemental analysis, SEM, ζ-potential, nitrogen adsorption–desorption and laser diffraction, aiming for its application as a potential immunosorbent material. Porous beads were prepared at mild reaction conditions in water and were chemically modified by sulfonation and reduction. The obtained 15 µm sized sulfonated beads were found to be highly charged and to have a high surface area of ~ 100 m2 g−1 and pore sizes between 20 and 60 nm, adequate for usage as immunosorbents. After reduction of remaining aldehyde groups, the beads could be classified as non-cytotoxic in indirect toxicity studies with human dermal fibroblasts as a first screening of their biocompatibility. The observed properties make the sulfonated cellulose beads interesting for further development as matrix material in immunosorbent devices.
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| 42. |
- Sun, Rui, et al.
(författare)
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Highly Porous Amorphous Calcium Phosphate for Drug Delivery and Bio-Medical Applications
- 2020
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Ingår i: Nanomaterials. - : MDPI. - 2079-4991. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Amorphous calcium phosphate (ACP) has shown significant effects on the biomineralization and promising applications in bio-medicine. However, the limited stability and porosity of ACP material restrict its practical applications. A storage stable highly porous ACP with Brunauer–Emmett–Teller surface area of over 400 m2/g was synthesized by introducing phosphoric acid to a methanol suspension containing amorphous calcium carbonate nanoparticles. Electron microscopy revealed that the porous ACP was constructed with aggregated ACP nanoparticles with dimensions of several nanometers. Large angle X-ray scattering revealed a short-range atomic order of <20 Å in the ACP nanoparticles. The synthesized ACP demonstrated long-term stability and did not crystallize even after storage for over 14 months in air. The stability of the ACP in water and an α-MEM cell culture medium were also examined. The stability of ACP could be tuned by adjusting its chemical composition. The ACP synthesized in this work was cytocompatible and acted as drug carriers for the bisphosphonate drug alendronate (AL) in vitro. AL-loaded ACP released 25% of the loaded AL in the first 22 days. These properties make ACP a promising candidate material for potential application in biomedical fields such as drug delivery and bone healing.
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| 43. |
- Tummala, Gopi Krishna, 1986-, et al.
(författare)
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Biocompatibility of nanocellulose-reinforced PVA hydrogel with human corneal epithelial cells for Ophthalmic applications
- 2019
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Ingår i: Journal of Functional Biomaterials. - : MDPI AG. - 2079-4983. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Transparent composite hydrogel in the form of a contact lens made from poly(vinyl alcohol) (PVA) and cellulose nanocrystals (CNCs) was subjected to in vitro biocompatibility evaluation with human corneal epithelial cells (HCE-2 cells). The cell response to direct contact with the hydrogels was investigated by placing the samples on top of confluent cell layers and evaluating cell viability, morphology, and cell layer integrity subsequent to 24 h culture and removal of the hydrogels. To further characterize the lens-cell interactions, HCE-2 cells were seeded on the hydrogels, with and without simulated tear fluid (STF) pre-conditioning, and cell viability and morphology were evaluated. Furthermore, protein adsorption on the hydrogel surface was investigated by incubating the materials with STF, followed by protein elution and quantification. The hydrogel material was found to have affinity towards protein adsorption, most probably due to the interactions between the positively charged lysozyme and the negatively charged CNCs embedded in the PVA matrix. The direct contact experiment demonstrated that the physical presence of the lenses did not affect corneal epithelial cell monolayers in terms of integrity nor cell metabolic activity. Moreover, it was found that viable corneal cells adhered to the hydrogel, showing the typical morphology of epithelial cells and that such response was not influenced by the STF pre-conditioning of the hydrogel surface. The results of the study confirm that PVA-CNC hydrogel is a promising ophthalmic biomaterial, motivating future in vitro and in vivo biocompatibility studies.
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| 44. |
- Tummala, Gopi Krishna, 1986-
(författare)
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Hydrogels of Poly(vinyl alcohol) and Nanocellulose for Ophthalmic Applications : Synthesis, Characterization, Biocompatibility and Drug Delivery Studies
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hydrogels are commonly used materials in ophthalmic care as contact lenses, bandage lenses, corneal implants, and cornea regeneration scaffolds. Hydrogels can be produced by physical, chemical, or radiation crosslinking of hydrophilic polymers. Poly(vinyl alcohol) (PVA) is a hydrophilic polymer that has been long known to the scientific community and is used in ophthalmic formulations.In this thesis, PVA was reinforced with nanocellulose to obtain self-standing hydrogels. Cryo-gelation technique was used to obtain transparent hydrogels from PVA dissolved in DMSO-water mixed solvent. The properties of these hydrogels were analyzed to explore the possibility of their application for ophthalmic use as a drug delivery vehicle and as cornea regeneration implant.The results indicate that oxidized nanocellulose can be combined with PVA to produce transparent, elastic, macroporous and high-water content hydrogel lenses. The water-filled macroporous structure of these hydrogels aids with oxygen transport and can enhance comfort while worn. The developed hydrogel also features moderate UV-light blocking properties in addition to high transparency. Furthermore, it was observed that the light scattering due to surface roughness of the hydrogel increases with measurement time, due to the rapid evaporation of the water layer from the surface of the hydrogel film.Mechanical analysis results revealed that the hydrogels exhibited a strain-induced stiffening behavior, which is usually noticed in hyper-elastic materials and collagenous soft tissues. The results of this study suggest that in order to mimic collagenous behavior, the material should possess high water content and a specific structural architecture combining soft and rigid elements as building blocks.Furthermore, PVA-CNC composite hydrogel showed no toxic effects on the corneal cells in both direct and indirect contact studies. It was found that the hydrogel promoted cell attachment and was stable when sutured ex vivo to a porcine excised cornea.To study enzyme-triggered drug release, hydrogel lenses loaded with chitosan-poly(acrylic acid) nanoparticles were exposed to lysozyme, an enzyme present in the eye. Nanoparticles were shown to disintegrate due to the hydrolysis of chitosan chains by lysozyme. Overall, with these distinctive properties, PVA-CNC hydrogel has great potential as an ophthalmic biomaterial for therapeutic and cornea regeneration applications.
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| 45. |
- Vall, Maria, et al.
(författare)
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Exploring the use of amine modified mesoporous magnesium carbonate for the delivery of salicylic acid in topical formulations: : in vitro cytotoxicity and drug release studies
- 2019
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:9
-
Tidskriftsartikel (refereegranskat)abstract
- Salicylic acid (SA) has for a long time been used to treat various skin disorders due to its anti-inflammatory, bacteriostatic, and antifungal properties. In the present work, mesoporous magnesium carbonate (MMC), a promising drug carrier, was modified with 3-aminopropyl-triethoxysilane to enable loading of SA. The amine modified MMC (aMMC) was successfully loaded with 8 wt.% of SA via a solvent evaporation method. SA was later completely released from the carrier in less than 15 min. Furthermore, the cytotoxicity of the functionalized material was evaluated. aMMC was found to be non-toxic for human dermal fibroblast cells with particle concentration of up to 1000 µg/mL when exposed for 48 h. The presented results form the basis of future development of aMMC as a potential carrier for SA in dermatological applications.
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| 46. |
- White, John Kerr, et al.
(författare)
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A stable cyclized antimicrobial peptide derived from LL-37 with host immunomodulatory effects and activity against uropathogens
- 2022
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Nature. - 1420-682X .- 1420-9071. ; 79:8
-
Tidskriftsartikel (refereegranskat)abstract
- The increasing antibiotic resistance among uropathogenic bacteria warrants alternative therapeutic strategies. We demonstrate the potential of the synthetic peptide CD4-PP, designed by dimerization and backbone cyclization of the shortest antimicrobial region of human cathelicidin, LL-37. CD4-PP is active against clinical and type strains of common uropathogens Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa at concentrations substantially below cellular cytotoxic levels and induced membrane deformation and leakage in E. coli and P. aeruginosa. Furthermore, CD4-PP treatment prevented the formation of new biofilm and dissolved mature biofilm created by E. coli and P. aeruginosa and targeted curli amyloid in E. coli biofilms. In addition, CD4-PP also induced production of LL-37 by uroepithelial cells and increased the expression of tight junction proteins claudin-14 and occludin. During uroepithelial cell infection, CD4-PP significantly reduced uropathogen survival when treatment was given at the start of infection. Low micromolar of CD4-PP treatment initiated after 2 h was successful with all tested species, except P. aeruginosa where CD4-PP was unable to reduce survival, which could be attributed by early biofilm formation. Finally, we demonstrated that urinary catheter pieces coated with saline fluid supplemented with CD4-PP reduced the attachment of E. coli, giving it a potential clinical application.
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| 47. |
- Wu, Lulu
(författare)
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Development of Nanocellulose Materials for Nano-filtration and Microfluidic Cell Culture
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nanocellulose, cellulose nanofibrils or nanocrystals, is an interesting material for a wide range of applications. It can be obtained from abundant sources (higher plants, bacteria and algae), and presents many advantages to be used in the biomedical field such as biological safety, high surface area, porosity, and tailorable rheological properties. This thesis selected two different areas to explore the use of nanocellulose materials in life sciences: bioprocessing of biological products and cell culture in microfluidic systems. The production of biopharmaceutical products (e.g. plasma-derived proteins) requires bioactive raw materials of animal or human origin, which present a viral risk. Virus contamination is one of the biggest challenges in the bioprocessing of such biological products, with size-exclusion virus filtration signalled as the preferred method. Commercial virus removal filters tend to have relatively low fluxes, which results in expensive industrial processes and the use of filters based on synthetic polymers is associated with environmental burden. When considering the application of microfluidic devices in cell research, the development of cheap and readily available nano- or micro-biomaterials that are easy to process and integrate is expected to advance the understanding of the relationship between cells and the microenvironment.The first part of the thesis focussed on Cladophora algae-derived cellulose nanofibrils virus removal filters (CCF-VFs) and investigated their application in the bioprocessing of plasma-derived proteins and stem cell differentiation medium. The second part explored the use of wood-derived cellulose nanofibrils (CNFs) as a cell culture substrate in microfluidics. Here, a concentric circular patterned CNF substrate was incorporated into a microfluidic chip to study the role of topography and shear stress in guiding the alignment of human umbilical vein endothelial cells (HUVECs). In conclusion, CCF-VFs show great potential to be integrated into the bioprocessing of plasma-derived products to remove viruses. The first evaluation of CCF-VFs in stem cell culture medium filtration showed promising results. Aligned CNFs were successfully integrated into microfluidic chips as a tool to study the role of mechanical cues on cell alignment.
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| 48. |
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| 49. |
- Wu, Lulu, et al.
(författare)
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Microfluidic system with integrated nanocellulose cell culture substrate to study alignment of human umbilical vein endothelial cells in relation to external physical cues
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this work, aligned cationic cellulose nanofibrils (c-CNF) were integrated into a microfluidic channel to guide cell attachment of human umbilical vein endothelial cells (HUVECs) and the effect of different mechanical cues on cell orientation was investigated. The on-chip cultured cells were exposed to external stimuli by the c-CNF topography and a fluid flow-induced shear stress, either separately or combined. Fluorescent images of the c-CNF pattern stained with calcofluor white and HUVECs stained for F-actin fibers and cell nuclei were obtained and used to quantify orientation of the CNFs, the F-actin fibers and the cell nuclei together with the eccentricity of the nuclei. Compared to the control, where the cells were cultured on a smooth surface in static conditions, cells cultured on the c-CNF pattern alone showed a clear alignment to the underlying microtopography. Cells cultured on a smooth surface responded slightly to the external mechanical stimuli indicating that the cell orientation was more strongly affected by c-CNF topography than the shear stress. With these results, we established a platform that can de-couple external mechanical stimuli originating from surface topography and shear stress to increase our understanding of how cells react to these factors when cultured in microfluidic in vitro systems.
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| 50. |
- Åberg, Ola, 1978-, et al.
(författare)
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Educational challenges for teaching nanotechnology : Part 2. Pedagogic content development for teaching nanotechnology in life sciences
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The present work aims to provide a framework for teaching nanotechnology for life sciences applications, with special focus on nanotechnology-enabled treatments based on advanced physical and biological principles. By expanding and adapting the so-called “Big Ideas” of NSE to further include core elements of cell and molecular biology, an eight-level learning progression is suggested. The challenges of teaching nanotechnology are further addressed in different learning contexts to highlight the importance of size-dependent physical and biological interactions. A number of core nanomedicine concepts are discussed, including, e.g., directed self-assembly, enhance permeability and retention effect, protein corona, size-dependent cellular uptake, disease-specific environment, and theranostics. The outcome of this work will be useful for educators designing curriculum with specialization in nanomedicine.
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