| 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. |
- 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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| 3. |
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| 4. |
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| 5. |
- 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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| 6. |
- 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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| 7. |
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| 8. |
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| 9. |
- 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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| 10. |
- 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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| 11. |
- 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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| 12. |
- 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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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- 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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| 18. |
- 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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| 19. |
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| 20. |
- 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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| 21. |
- 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
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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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| 22. |
- 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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| 23. |
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| 24. |
- 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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| 25. |
- Åberg, Ola, 1978-, et al.
(författare)
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Educational challenges for teaching nanotechnology : Part 1. Global and local perspectives for teaching nanotechnology
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In this study, systematic analysis of nanotechnology education programmes was carried out from a global and local perspective. Although several universities offer 3-4 year nanotechnology-centred educational programmes, in general the most common modes for nanotechnology education include either modular courses integrated in traditional scientific disciplines or 2-year specialised MSc programmes. Nanotechnology education has a number of peculiarities. For example, it is common to include “nano”-labelling of education for marketing purposes to attract students to study traditional disciplines. Another conclusion of the analysis is that specialised nanotechnology programmes require access to advanced characterisation equipment, which can be limiting for programmes with small number of students. The nanotechnology education in Sweden does not differ much from other countries in its structure. MSc programmes or modular courses in nanotechnology are offered by major universities. Lund University and KTH offer 2-year MSc programmes with specialisation in nanoscience, having strong focus on nanoelectronics and nanophysics, whereas Chalmers is offering nanoelectronics as a part of international 2-year Erasmus Mundus MSc programme in nanoscience and nanotechnology- EMMNano. The nanotechnology education at Uppsala University is conducted mainly through modular courses, with significantly higher number of courses specialised in life sciences applications than that at other major Swedish universities. At this time, it appears that no 2-year MSc programme is offered by major Swedish universities with specialisation in nanomedicine. Finally, extensive analysis of nanotechnology for life science education is conducted to highlight core concepts in the field.
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