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Rocha, I., Lindh, J., Hong, J., Strömme, M., Mihranyan, A. & Ferraz, N. (2018). Blood Compatibility of Sulfonated Cladophora Nanocellulose Beads. Molecules, 23(3), Article ID 601.
Open this publication in new window or tab >>Blood Compatibility of Sulfonated Cladophora Nanocellulose Beads
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2018 (English)In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 23, no 3, article id 601Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
sulfonated beads; Cladophora nanocellulose; hemocompatibility; coagulation; complement system
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-346209 (URN)10.3390/molecules23030601 (DOI)
Funder
Knut and Alice Wallenberg Foundation
Available from: 2018-03-15 Created: 2018-03-15 Last updated: 2018-07-27Bibliographically approved
Liu, J., Bacher, M., Rosenau, T., Willfoer, S. & Mihranyan, A. (2018). Potentially Immunogenic Contaminants in Wood-Based and Bacterial Nanocellulose: Assessment of Endotoxin and (1,3)-β-d-Glucan Levels. Biomacromolecules, 19(1), 150-157
Open this publication in new window or tab >>Potentially Immunogenic Contaminants in Wood-Based and Bacterial Nanocellulose: Assessment of Endotoxin and (1,3)-β-d-Glucan Levels
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2018 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 19, no 1, p. 150-157Article in journal (Refereed) Published
Abstract [en]

Knowledge gaps in the biosafety data of the nanocellulose (NC) for biomedical use through various routes of administration call for closer look at health and exposure evaluation. This work evaluated the potentially immunogenic contaminants levels, for example, endotoxin and (1,3)-β-d-glucan, in four representative NCs, that is, wood-based NCs and bacterial cellulose (BC). The hot-water extracts were analyzed with ELISA assays, HPSEC-MALLS, GC, and NMR analysis. Varying levels of endotoxin and (1,3)-β-d-glucan contaminats were found in these widely used NCs. Although the β-(1,3)-d-glucan was not detected from the NMR spectra due to the small extract samples amount (2–7 mg), the anomerics and highly diastereotopic 6-CH2 signals may suggest the presence of β-(1,4)-linkages with β-(1,6) branching in the polysaccharides of NCs’ hot-water extracts, which were otherwise not detectable in the enzymatic assay. In all, the article highlights the importance of monitoring various water-soluble potentially immunogenic contaminants in NC for biomedical use.

National Category
Analytical Chemistry Biochemistry and Molecular Biology Polymer Chemistry Organic Chemistry Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-343880 (URN)10.1021/acs.biomac.7b01334 (DOI)000419998600015 ()29182312 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationStiftelsen Olle Engkvist Byggmästare
Available from: 2018-03-16 Created: 2018-03-16 Last updated: 2018-03-28Bibliographically approved
Rocha, I., Ferraz, N., Mihranyan, A., Strömme, M. & Lindh, J. (2018). Sulfonated Nanocellulose Beads as Potential Immunosorbents. Cellulose (London), 28(3), 1899-1910
Open this publication in new window or tab >>Sulfonated Nanocellulose Beads as Potential Immunosorbents
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2018 (English)In: Cellulose (London), ISSN 0969-0239, E-ISSN 1572-882X, Vol. 28, no 3, p. 1899-1910Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Periodate oxidation Dialdehyde cellulose, Surface group density, Sulfonated beads, Cytotoxicity
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-346207 (URN)10.1007/s10570-018-1661-2 (DOI)000427379200027 ()
Funder
Knut and Alice Wallenberg Foundation
Available from: 2018-03-15 Created: 2018-03-15 Last updated: 2018-05-18Bibliographically approved
Gustafsson, S. & Mihranyan, A. (2017). Investigating Protein Throughput, Vmax Values and Virus Removal Efficiency of the Paper Based Mille-Feuille Filter. In: : . Paper presented at ACS National Meeting - San Francisco 2017 253rd American Chemical Society National Meeting & Expo.
Open this publication in new window or tab >>Investigating Protein Throughput, Vmax Values and Virus Removal Efficiency of the Paper Based Mille-Feuille Filter
2017 (English)Conference paper, Poster (with or without abstract) (Refereed)
Abstract [en]

In this work we present Vmax values and throughput for the nanocellulose-based Mille-feuille virus removal filter paper as well as evaluate the affinity of different proteins for the cellulose surface using quartz crystal microbalance (QCMB). The Minute Virus of Mice (MVM) virus removal result for the Mille-feuille filter is also presented. The nanocellulose-based Mille-feuille filter is a non-woven, µm-thick filter paper with a narrow and tailorable pore size distribution, highly suitable for removing viruses of all sizes, including the worst case model Minute Virus of Mice (MVM). It is produced by hot-pressing method rather than by phase-inversion which is otherwise used to manufacture industrial analogues. Robust and cost-efficient virus removal processes are in high demand for the biotechnology industry, especially for the production of monoclonal antibodies derived from mammalian cell lines, therapeutic proteins derived from human plasma, and cell culture media. Non-woven filters have the advantage in contrast to regular phase-inversion made filters of a much higher porosity. For instance, the Mille-feuille filter has a porosity of 42% compared to 10-15% of the functional skin layer in asymmetric virus removal filters used today. In theory a higher porosity will result in higher flow rates. However, it also means that there is a larger filter area exposed to filtrate. Therefore investigating the surface affinity for proteins with different hydrophobicity and charge using QCMB is of great importance to be able to predict protein filtration behaviour. The presented work is a part of continuous efforts to develop a new class of highly efficient and affordable virus removal filters.

National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-332593 (URN)
Conference
ACS National Meeting - San Francisco 2017 253rd American Chemical Society National Meeting & Expo
Funder
Knut and Alice Wallenberg Foundation
Available from: 2017-10-30 Created: 2017-10-30 Last updated: 2017-12-08Bibliographically approved
Liu, J., Willfor, S. & Mihranyan, A. (2017). On importance of impurities, potential leachables and extractables in algal nanocellulose for biomedical use. Carbohydrate Polymers, 172, 11-19
Open this publication in new window or tab >>On importance of impurities, potential leachables and extractables in algal nanocellulose for biomedical use
2017 (English)In: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 172, p. 11-19Article in journal (Refereed) Published
Abstract [en]

Nanocellulose-based biomaterials for biomedical and pharmaceutical applications have been extensively explored. However, studies on different levels of impurities in the nanocellulose and their potential risks are lacking. This article is the most comprehensive to date survey of the importance and characterization kof possible leachables and extractables in nanocellulose for biomedical use. In particular, the (1,3)-beta-D-glucan interference in endotoxin detection in algal nanocellulose was addressed. Potential lipophilic and hydrophilic leachables, toxic heavy metals, and microbial contaminants are also monitored. As a model system, nanocellulose from Cladophora sp. algae is investigated. The leachable (1,3)-beta-D-glucan and endotoxin, which possess strong immunogenic potential, from the cellulose were minimized to clinically insignificant levels of 4.7 mu g/g and 2.5 EU/g, respectively. The levels of various impurities in the Cladophora cellulose are acceptable for future biomedical applications. The presented approach could be considered as a guideline for other types of nanocellulose.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2017
Keywords
Ultra-pure nanocellulose, (1, 3)-beta-D-glucan, Endotoxin, Microbial contamination, Biosafety
National Category
Textile, Rubber and Polymeric Materials Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-329888 (URN)10.1016/j.carbpol.2017.05.002 (DOI)000404697300002 ()28606516 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationStiftelsen Olle Engkvist Byggmästare
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2018-02-20Bibliographically approved
Gustafsson, S., Manukyan, L. & Mihranyan, A. (2017). Protein-Nanocellulose Interactions in Paper Filters for Advanced Separation Applications. Langmuir, 33(19), 4729-4736
Open this publication in new window or tab >>Protein-Nanocellulose Interactions in Paper Filters for Advanced Separation Applications
2017 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 33, no 19, p. 4729-4736Article in journal (Refereed) Published
Abstract [en]

Protein-based pharmaceutics are widely explored for healthcare applications, and 6 out of 10 best-selling drugs today are biologicals. The goal of this work was to evaluate the protein nanocellulose interactions in paper filter for advanced separation applications such as virus removal filtration and bioprocessing. The protein recovery was measured for bovine serum albumin (BSA), gamma-globulin, and lysozyme using biuret total protein reagent and polyacrylamide gel electrophoresis (PAGE), and the throughput was characterized in terms of flux values from fixed volume filtrations at various protein concentrations and under worst case experimental conditions. The affinity of cellulose to bind various proteins, such as BSA, lysozyme, gamma-globulin, and human IgG was quantified using a quartz crystal microbalance (QCMB) by developing a new method of fixing the cellulose fibers to the electrode surface without cellulose dissolution-precipitation. It was shown that the. mille-feuille filter exhibits high protein recovery, that is, similar to 99% for both BSA and lysozyme. However, gamma-globulin does not pass through the membrane due to its large size (i.e., >180 kDa). The PAGE data show no substantial change in the amount of dimers and trimers before and after filtration. QCMB analysis suggests a low affinity between the nanocellulose surface and proteins. The nanocellulose-based filter exhibits desirable inertness as a filtering material intended for protein purification.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2017
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-326244 (URN)10.1021/acs.langmuir.7b00566 (DOI)000401674900015 ()28441870 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationStiftelsen Olle Engkvist Byggmästare
Available from: 2017-08-10 Created: 2017-08-10 Last updated: 2017-11-23
Tummala, G. K., Joffre, T., Rojas, R., Persson, C. & Mihranyan, A. (2017). Strain-induced stiffening of nanocellulose-reinforced poly(vinyl alcohol) hydrogels mimicking collagenous soft tissues. Soft Matter, 13(21), 3936-3945
Open this publication in new window or tab >>Strain-induced stiffening of nanocellulose-reinforced poly(vinyl alcohol) hydrogels mimicking collagenous soft tissues
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2017 (English)In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 13, no 21, p. 3936-3945Article in journal (Refereed) Published
Abstract [en]

Soft tissues possess remarkable mechanical strength for their high water content, which is hard to mimic in synthetic materials. Here, we demonstrate how strain-induced stiffening in hydrogels plays a major role in mimicking the mechanical properties of collagenous soft tissues. In particular, nanocellulose reinforced polyvinyl alcohol (PVA) hydrogels of exceptionally high water content (90-93 wt%) are shown to exhibit collagen-like mechanical behavior typical for soft tissues. High water content and co-existence of both soft and rigid domains in the gel network are the main factors responsible for strain-induced stiffening. This observed effect due to the alignment of rigid components of the hydrogel is simulated through modeling and visualized through strain-induced birefringence experiments. Design parameters such as nanocellulose aspect ratio and solvent composition are also shown to be important to control the mechanical properties. In addition, owing to their transparency (90-95% at 550 nm) and hyperelastic properties (250-350% strain), the described hydrogels are promising materials for biomedical applications, especially in ophthalmology.

National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-326502 (URN)10.1039/c7sm00677b (DOI)000402744100012 ()28504291 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council Formas, 232-2014-202
Note

G. K. T. and T. J. contributed equally to this work.

Available from: 2017-07-13 Created: 2017-07-13 Last updated: 2018-08-06Bibliographically approved
Rocha, I., Ferraz, N., Mihranyan, A., Strömme, M. & Lindh, J. (2016). Chemical modifications of Cladophorananocellulose to provide a non-toxicmaterial with anticoagulant properties. In: : . Paper presented at 10th World Biomaterials Congress. Montreal, Canada
Open this publication in new window or tab >>Chemical modifications of Cladophorananocellulose to provide a non-toxicmaterial with anticoagulant properties
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2016 (English)Conference paper, Poster (with or without abstract) (Refereed)
Place, publisher, year, edition, pages
Montreal, Canada: , 2016
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-296229 (URN)
Conference
10th World Biomaterials Congress
Available from: 2016-06-14 Created: 2016-06-14 Last updated: 2016-11-30
Xu, C., Carlsson, D. O. & Mihranyan, A. (2016). Feasibility of using DNA-immobilized nanocellulose-based immunoadsorbent for systemic lupus erythematosus plasmapheresis. Colloids and Surfaces B: Biointerfaces, 143, 1-6
Open this publication in new window or tab >>Feasibility of using DNA-immobilized nanocellulose-based immunoadsorbent for systemic lupus erythematosus plasmapheresis
2016 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 143, p. 1-6Article in journal (Refereed) Published
Abstract [en]

The goal of this project was to study the feasibility of using a DNA-immobilized nanocellulose-based immunoadsorbent for possible application in medical apheresis such as systemic lupus erythematosus (SLE) treatment. Calf thymus DNA was bound to high surface area nanocellulose membrane at varying concentrations using UV-irradiation. The DNA-immobilized samples were characterized with scanning electron microscopy, atomic force microscopy, and phosphorus elemental analysis. The anti-ds-DNA IgG binding was tested in vitro using ELISA. The produced sample showed high affinity in vitro to bind anti-ds-DNA-antibodies from mice, as much as 80% of added IgG was bound by the membrane. Furthermore, the binding efficiency was quantitatively dependent on the amount of immobilized DNA onto nanocellulose membrane. The described nanocellulose membranes are interesting immunoadsorbents for continued clinical studies.

Keywords
Autoimmune diseases; DNA immobilization; Immunoadsorption; Nanocellulose; Systemic lupus erythematosus
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-287474 (URN)10.1016/j.colsurfb.2016.03.014 (DOI)000376696900001 ()27011345 (PubMedID)
External cooperation:
Funder
Knut and Alice Wallenberg FoundationGöran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of Technology
Available from: 2016-04-25 Created: 2016-04-25 Last updated: 2017-11-30Bibliographically approved
Tummala, G. K., Joffre, T., Lopes, V., Liszka, A., Buznyk, O., Ferraz, N., . . . Mihranyan, A. (2016). Hyperelastic Nanocellulose-Reinforced Hydrogel of High Water Content for Ophthalmic Applications. ACS Biomaterials Science and Engineering, 2(11), 2072-2079
Open this publication in new window or tab >>Hyperelastic Nanocellulose-Reinforced Hydrogel of High Water Content for Ophthalmic Applications
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2016 (English)In: ACS Biomaterials Science and Engineering, ISSN 2373-9878, Vol. 2, no 11, p. 2072-2079Article in journal (Refereed) Published
Abstract [en]

A nanocellulose-reinforced poly(vinyl alcohol) hydrogel material of exceptionally high water content for ophthalmic applications is presented (>90 wt %), which also features a hitherto unprecedented combination of optical, mechanical, viscoelastic, oxygen permeability, and biocompatibility properties. The hydrogel combines the desired softness with remarkable strain-dependent mechanical strength and thereby demonstrates hyperelastic, rubber-like mechanical properties. The observed unusual mechanical behavior is due to both high water content and the combination of relatively stiff cellulose nanowhiskers entangled in a soft polymer matrix of poly(vinyl alcohol) (PVA), thus mimicking the structural characteristics of the cornea's main constituents, i.e., water and collagen.

Keywords
biocompatibility, cellulose nanocrystals, contact lens, ophthalmic prosthesis, poly(vinyl alcohol)
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-310474 (URN)10.1021/acsbiomaterials.6b00484 (DOI)000388161200027 ()2-s2.0-84995379882 (Scopus ID)
Projects
WWSC
Funder
Knut and Alice Wallenberg FoundationVINNOVA, 2013-04645
Available from: 2016-12-16 Created: 2016-12-16 Last updated: 2018-03-19Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-8105-2317

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