| 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. |
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| 3. |
- Arnell, Robert, et al.
(författare)
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Analytical Characterization of Chiral Drug-Protein Interactions: Comparison between the Optical Biosensor (Surface Plasmon Resonance) Assay and the HPLC Perturbation Method
- 2006
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Ingår i: Analytical Chemistry. ; 78:5, s. 1682-1689
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Tidskriftsartikel (refereegranskat)abstract
- Two modern, fundamentally different methods were used for a detailed investigation of enantioselective drug-protein interactions, a surface plasmon resonance (SPR)-based Biacore 2000 biosensor assay and the previously validated HPLC perturbation method (HPLC-PM). This is the first time SPR has been used for this purpose. The fundamental features of the two methods were investigated, and the consequences for operation and data evaluation were addressed. With HPLC-PM, chiral data could be obtained directly from the racemic mixture, whereas a separate analysis of each pure enantiomer was required to obtain chiral data with SPR. It was shown that if chirality is not attributed in the SPR analysis, misleading average racemic binding constants will be obtained. Both drug and protein consumption were considerably higher with HPLC-PM. HPLC-PM was found to be best suited for measurements of weak affinity interactions, whereas the SPR method was best for strong interactions. With both methods, the presence of DMSO in the samples severely affected the interactions, introducing errors. The binding of the -blockers alprenolol and propranolol to Cel7a cellulase was used as a model system. These methods gave results that agreed quite well qualitatively, but considerable quantitative deviations were sometimes obtained.
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| 4. |
- 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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| 5. |
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| 6. |
- 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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| 7. |
- Basu, Alex
(författare)
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Ion-Crosslinked Nanocellulose Hydrogels for Advanced Wound Care Applications
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A current trend in the field of wound care is the development of wound healing materials that are designed to address specific types of wounds or underlying pathologies to achieve improved healing. At the same time, there is a societal drive to replace synthetic materials with renewable alternatives. The work presented in this thesis was therefore carried out to investigate the use of wood nanocellulose, produced from the world’s most abundant biopolymer, cellulose, in advanced wound care applications.Wood-based nanofibrillated cellulose (NFC) was chemically functionalized and crosslinked using calcium to obtain a self-standing hydrogel. The NFC hydrogel was evaluated in terms of its physicochemical properties, biocompatibility, blood interactions, bacterial interactions, in vivo wound healing ability and, finally, as a protein carrier. Parallel with the assessment of the NFC hydrogel, modified versions of the material were tested to investigate the tunability of the above-mentioned characteristics.The ability of the hydrogel to maintain a moist wound bed was demonstrated. Evaluation of the biocompatibility showed that the material was cytocompatible and did not trigger inflammatory mechanisms. Furthermore, the NFC hydrogel supported cell proliferation, and was shown to possess hemostatic properties. It was also discovered that the material had a slight bacteriostatic effect and the ability to act as a barrier against bacteria. When tested in vivo, the hydrogel was found to significantly improve wound healing.Modifications through the incorporation of additives to the hydrogel matrix, as well as exchange of the crosslinking ion, were shown to influence the biological response to the material. Moreover, the results presented here demonstrate the possibility of using the NFC hydrogel as a protein carrier; the easily adjustable charge property being identified as a central parameter for manipulation to regulate the release profile.In conclusion, this work has demonstrated the extensive wound healing ability of the calcium-crosslinked NFC hydrogel, and represents an important milestone in the research on NFC towards advanced wound care applications. It is expected that the easily modifiable nature of the material can be exploited to further develop the NFC hydrogel to suit the treatment needs for a broad range of wound types.
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| 8. |
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| 9. |
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| 10. |
- 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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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- 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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| 18. |
- 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
-
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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| 19. |
- 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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| 20. |
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| 21. |
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| 22. |
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| 23. |
- 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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| 24. |
- 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
-
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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| 25. |
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| 26. |
- Brena, Beatriz M., et al.
(författare)
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ITREOH building of regional capacity to monitor recreational water : development of a non-commercial microcystin ELISA and its impact on public health policy
- 2006
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Ingår i: International journal of occupational and environmental health. - 1077-3525 .- 2049-3967. ; 12:4, s. 377-385
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Tidskriftsartikel (refereegranskat)abstract
- In 2001, a University of California, Davis-University of the Republic, Montevideo, partnership created a Fogarty ITREOH program to exploit the potential of ELISA to provide a low-cost environmental analysis attractive to economically distressed countries of temperate South America. This paper describes the development and validation of an ELISA method for the determination of Cyanobacteria microcystin toxins in algal blooms, which release hepatotoxic metabolites that can reach toxic levels in rivers, lakes, or coastal estuaries used for recreation or water supplies. The assay made possible the first systematic monitoring of water from the Rio de la Plata at Montevideo over two summers. The project has been integrated into a bi-national effort to monitor the Rio de la Plata.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Erjefält, Jonas S., et al.
(författare)
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Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19
- 2022
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 83
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Severe COVID-19 lung disease exhibits a high degree of spatial and temporal heterogeneity, with different histological features coexisting within a single individual. It is important to capture the disease complexity to support patient management and treatment strategies. We provide spatially decoded analyses on the immunopathology of diffuse alveolar damage (DAD) patterns and factors that modulate immune and structural changes in fatal COVID-19. Methods: We spatially quantified the immune and structural cells in exudative, intermediate, and advanced DAD through multiplex immunohistochemistry in autopsy lung tissue of 18 COVID-19 patients. Cytokine profiling, viral, bacteria, and fungi detection, and transcriptome analyses were performed. Findings: Spatial DAD progression was associated with expansion of immune cells, macrophages, CD8+ T cells, fibroblasts, and (lymph)angiogenesis. Viral load correlated positively with exudative DAD and negatively with disease/hospital length. In all cases, enteric bacteria were isolated, and Candida parapsilosis in eight cases. Cytokines correlated mainly with macrophages and CD8+T cells. Pro-coagulation and acute repair were enriched pathways in exudative DAD whereas intermediate/advanced DAD had a molecular profile of elevated humoral and innate immune responses and extracellular matrix production. Interpretation: Unraveling the spatial and molecular immunopathology of COVID-19 cases exposes the responses to SARS-CoV-2-induced exudative DAD and subsequent immune-modulatory and remodeling changes in proliferative/advanced DAD that occur side-by-side together with secondary infections in the lungs. These complex features have important implications for disease management and the development of novel treatments. Funding: CNPq, Bill and Melinda Gates Foundation, HC-Convida, FAPESP, Regeneron Pharmaceuticals, and the Swedish Heart & Lung Foundation.
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| 32. |
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| 33. |
- 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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| 34. |
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| 35. |
- 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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| 36. |
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| 37. |
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| 38. |
- Ferraz, Natalia, et al.
(författare)
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Haemocompatibility and ion exchange capability of nanocellulose polypyrrole membranes intended for blood purification
- 2012
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 9:73, s. 1943-1955
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Tidskriftsartikel (refereegranskat)abstract
- Composites of nanocellulose and the conductive polymer polypyrrole (PPy) are presented as candidates for a new generation of haemodialysis membranes. The composites may combine active ion exchange with passive ultrafiltration, and the large surface area (about 80 m2 g−1) could potentially provide compact dialysers. Herein, the haemocompatibility of the novel membranes and the feasibility of effectively removing small uraemic toxins by potential-controlled ion exchange were studied. The thrombogenic properties of the composites were improved by applying a stable heparin coating. In terms of platelet adhesion and thrombin generation, the composites were comparable with haemocompatible polymer polysulphone, and regarding complement activation, the composites were more biocompatible than commercially available membranes. It was possible to extract phosphate and oxalate ions from solutions with physiological pH and the same tonicity as that of the blood. The exchange capacity of the materials was found to be 600 ± 26 and 706 ± 31 μmol g−1 in a 0.1 M solution (pH 7.4) and in an isotonic solution of phosphate, respectively. The corresponding values with oxalate were 523 ± 5 in a 0.1 M solution (pH 7.4) and 610 ± 1 μmol g−1 in an isotonic solution. The heparinized PPy–cellulose composite is consequently a promising haemodialysis material, with respect to both potential-controlled extraction of small uraemic toxins and haemocompatibility.
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| 39. |
- Ferraz, Natalia, et al.
(författare)
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In vitro and in vivo toxicity of rinsed and aged nanocellulose-polypyrrole composites
- 2012
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Ingår i: Journal of Biomedical Materials Research. Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 100A:8, s. 2128-2138
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Tidskriftsartikel (refereegranskat)abstract
- Novel composites of nanocellulose and the conducting polymer polypyrrole (PPy) are herein suggested as potential candidates for active ion-extraction membranes in electrochemically controlled hemodialysis. This work has defined processing parameters to obtain a biocompatible nanocellulose-PPy composite and for the first time, the effect of the composite ageing on cell viability has been studied.The influence of rinsing and extraction process steps, as well as ageing under different conditions (i.e. in air, at –20 ˚C and in argon), on the electroactivity and cytotoxicity of a PPy-nanocellulose composite has been investigated. The biocompatibility evaluation was based on indirect toxicity assays with fibroblasts and monocyte cell lines and an acute toxicity test in mice, while the electroactivity was evaluated by cyclic voltammetry experiments.The as-prepared composite did not induce any cytotoxic response in vitro or in vivo. Extensive rinsing and 48 hour incubation in biological buffer previous to the preparation of the culture medium extracts were, however, necessary to obtain a non-cytotoxic composite. The as-prepared composite was also found to exhibit acceptable electrochemical performance, which was retained upon 4 weeks storage in argon atmosphere. It was shown that ageing of the composite had a negative effect on biocompatibility, regardless of the storage condition. Thus, to allow for long time storage of electroactive nanocellulose-PPy hemodialysis membranes, the degradation of PPy upon storage must be controlled. The present results show that the biocompatibility of PPy composites depends on the rinsing and pre-treatment of the composite material as well as the aging of the material.
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| 40. |
- Ferraz, Natalia, et al.
(författare)
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Influence of nanoporesize on platelet adhesion and activation
- 2008
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 19:9, s. 3115-21
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Tidskriftsartikel (refereegranskat)abstract
- In this study we have evaluated the influence of biomaterial nano-topography on platelet adhesion and activation. Nano-porous alumina membranes with pore diameters of 20 and 200 nm were incubated with whole blood and platelet rich plasma. Platelet number, adhesion and activation were determined by using a coulter hematology analyzer, scanning electron microscopy, immunocytochemical staining in combination with light microscopy and by enzyme immunoassay. Special attention was paid to cell morphology, microparticle generation, P-selectin expression and beta-TG production. Very few platelets were found on the 200 nm alumina as compared to the 20 nm membrane. The platelets found on the 20 nm membrane showed signs of activation such as spread morphology and protruding filipodia as well as P-selectin expression. However no microparticles were detected on this surface. Despite the fact that very few platelets were found on the 200 nm alumina in contrast to the 20 nm membrane many microparticles were detected on this surface. Interestingly, all microparticles were found inside circular shaped areas of approximately 3 mum in diameter. Since this is the approximate size of a platelet we speculate that this is evidence of transient, non-adherent platelet contact with the surface, which has triggered platelet microparticle generation. To the authors knowledge, this is the first study that demonstrates how nanotexture can influence platelet microparticle generation. The study highlights the importance of understanding molecular and cellular events on nano-level when designing new biomaterials.
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| 41. |
- Ferraz, Natalia, et al.
(författare)
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Is there a future for electrochemically assisted hemodialysis? : focus on the application of polypyrrole-nanocellulose composites
- 2014
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Ingår i: Nanomedicine. - : Future Medicine Ltd. - 1743-5889 .- 1748-6963. ; 9:7, s. 1095-1110
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Tidskriftsartikel (refereegranskat)abstract
- This work summarizes the various aspects of using electrochemically assisted solute removal techniques in hemodialysis with a focus on blood electrodialysis and electrochemically controlled uremic retention solute removal using polypyrrole. In particular, the feasibility of using highly porous conductive polypyrrole-Cladophora cellulose membranes for hemodialysis are overviewed as a part of our dedicated research efforts during the past 4 years. The potential benefits and the current limitations associated with using the electrochemically controlled uremic retention solute removal techniques are discussed in detail.
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| 42. |
- Ferraz, Natalia, et al.
(författare)
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Is there a future for electrochemically assisted hemodialysis? : Focus on the application of polypyrrole-nanocellulose composites
- 2014
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Ingår i: Nanomedicine. - 1743-5889 .- 1748-6963. ; 9:7, s. 1095-1110
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Forskningsöversikt (refereegranskat)abstract
- This work summarizes the various aspects of using electrochemically assisted solute removal techniques in hemodialysis with a focus on blood electrodialysis and electrochemically controlled uremic retention solute removal using polypyrrole. In particular, the feasibility of using highly porous conductive polypyrrole-Cladophora cellulose membranes for hemodialysis are overviewed as a part of our dedicated research efforts during the past 4 years. The potential benefits and the current limitations associated with using the electrochemically controlled uremic retention solute removal techniques are discussed in detail.
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| 43. |
- Ferraz, Natalia, et al.
(författare)
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Membrane characterization and solute diffusion in porous composite nanocellulose membranes for hemodialysis
- 2013
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Ingår i: Cellulose. - : Springer. - 0969-0239 .- 1572-882X. ; 20:6, s. 2959-2970
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Tidskriftsartikel (refereegranskat)abstract
- The membrane and solute diffusion properties of Cladophora cellulose and polypyrrole (PPy) functionalized Cladophora cellulose were analyzed to investigate the feasibility of using electroactive membranes in hemodialysis. The membranes were characterized with scanning electron microscopy, zeta-potentiometry, He-pycnometry, N-2 gas adsorption, and Hg porosimetry. The diffusion properties across the studied membranes for three model uremic toxins, i.e. creatinine, vitamin B12 and bovine serum albumin, were also analyzed. The characterization work revealed that the studied membranes present an open structure of weakly negatively charged nanofibers with an average pore size of 21 and 53 nm for pristine cellulose and PPy-Cladophora cellulose, respectively. The results showed that the diffusion of uremic toxins across the PPy-Cladophora cellulose membrane was faster than through pure cellulose membrane, which was related to the higher porosity and larger average pore size of the former. Since it was found that the average pore size of the membranes was larger than the hydrodynamic radius of the studied model solutes, it was concluded that these types of membranes are favorable to expand the Mw spectrum of uremic toxins to also include conditions associated with accumulation of large pathologic proteins during hemodialysis. The large average pore size of the composite membrane could also be exploited to ensure high-fluxes of solutes through the membrane while simultaneously extracting ions by an externally applied electric current.
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| 44. |
- 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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| 45. |
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| 46. |
- Ferraz, Natalia, et al.
(författare)
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Nanoporesize affects complement activation
- 2008
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Ingår i: Journal of biomedical materials research. Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 87:3, s. 575-81
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we have shown the vast importance of biomaterial nanotexture when evaluating inflammatory response. For the first time in an in vitro whole blood system, we have proven that a small increase in nanoporesize, specifically 180 nm (from 20 to 200 nm), has a huge effect on the complement system. The study was done using nanoporous aluminiumoxide, a material that previously has been evaluated for potential implant use, showing good biocompatibility. This material can easily be manufactured with different pore sizes making it an excellent candidate to govern specific protein and cellular events at the tissue-material interface. We performed whole blood studies, looking at complement activation after blood contact with two pore size alumina membranes (pore diameters, 20 and 200 nm). The fluid phase was analyzed for complement soluble components, C3a and sC5b-9. In addition, surface adsorbed proteins were eluted and dot blots were performed to detect IgG, IgM, C1q, and C3. All results point to the fact that 200 nm pore size membranes are more complement activating. Significantly, higher values of complement soluble components were found after whole blood contact with 200 nm alumina and all studied proteins adsorbed more readily to this membrane than to the 20 nm pore size membrane. We hypothesize that the difference in complement activation between our two test materials is caused by the type and the amount of adsorbed proteins, as well as their conformation and orientation. The different protein patterns created on the two alumina membranes are most likely a consequence of the material topography.
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| 47. |
- 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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| 48. |
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| 49. |
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| 50. |
- 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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