| 1. |
- Basu, Alex, et al.
(author)
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Hemocompatibility of Ca2+-Crosslinked Nanocellulose Hydrogels : Toward Efficient Management of Hemostasis
- 2017
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In: Macromolecular Bioscience. - : Wiley. - 1616-5187 .- 1616-5195. ; 17:11
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Journal article (peer-reviewed)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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| 2. |
- Basu, Alex, et al.
(author)
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In Vitro and in Vivo Evaluation of the Wound Healing Properties of Nanofibrillated Cellulose Hydrogels
- 2018
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In: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 1:6, s. 1853-1863
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Journal article (peer-reviewed)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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| 3. |
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| 4. |
- Basu, Alex, et al.
(author)
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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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In: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 181, s. 345-350
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Journal article (peer-reviewed)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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| 5. |
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| 6. |
- Basu, Alex, et al.
(author)
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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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In: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 174, s. 299-308
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Journal article (peer-reviewed)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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| 7. |
- Basu, Alex, et al.
(author)
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Towards Tunable Protein-Carrier Wound Dressings Based on Nanocellulose Hydrogels Crosslinked with Calcium Ions
- 2018
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In: Nanomaterials. - : MDPI. - 2079-4991. ; 8:7
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Journal article (peer-reviewed)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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| 8. |
- Fernandez-Cruz, Maria Luisa, et al.
(author)
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Quality evaluation of human and environmental toxicity studies performed with nanomaterials – the GUIDEnano approach
- 2018
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In: Environmental Science: Nano. ; 5:2, s. 381-397
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Journal article (peer-reviewed)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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| 9. |
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| 10. |
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| 11. |
- Park, Margriet V. D. Z., et al.
(author)
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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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In: Nanotoxicology. - : TAYLOR & FRANCIS LTD. - 1743-5390 .- 1743-5404. ; 12:7, s. 652-676
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Journal article (peer-reviewed)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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| 12. |
- Rocha, Igor, et al.
(author)
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Blood Compatibility of Sulfonated Cladophora Nanocellulose Beads
- 2018
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In: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 23:3
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Journal article (peer-reviewed)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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| 13. |
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| 14. |
- Rocha, Igor, et al.
(author)
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Sulfonated Nanocellulose Beads as Potential Immunosorbents
- 2018
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In: Cellulose. - : Springer Science and Business Media LLC. - 0969-0239 .- 1572-882X. ; 28:3, s. 1899-1910
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Journal article (peer-reviewed)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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| 15. |
- Tummala, Gopi Krishna, 1986-, et al.
(author)
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Biocompatibility of nanocellulose-reinforced PVA hydrogel with human corneal epithelial cells for Ophthalmic applications
- 2019
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In: Journal of Functional Biomaterials. - : MDPI AG. - 2079-4983. ; 10:3
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Journal article (peer-reviewed)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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| 16. |
- Tummala, Gopi Krishna, 1986-
(author)
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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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Doctoral thesis (other academic/artistic)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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| 17. |
- Vall, Maria, et al.
(author)
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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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In: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:9
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Journal article (peer-reviewed)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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