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Translational study between structure and biological response of nanocellulose from wood and green algae
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. (Nanoteknologi och funktionella material)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. (Nanoteknologi och funktionella material)
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2014 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 4, no 6, 2892-2903 p.Article in journal (Refereed) Published
Abstract [en]

The influence of nanostructure on the cytocompatibility of cellulose films is analyzed providing insight into how physicochemical properties of surface modified microfibrillated cellulose (MFC) and Cladophora nanocellulose (CC) affect the materials cytocompatibility. CC is modified through TEMPO-mediated oxidation and glycidyltrimethylammonium chloride (EPTMAC) condensation to obtain anionic and cationic nanocellulose samples respectively, while anionic and cationic MFC samples are obtained by carboxymethylation and EPTMAC condensation respectively. Films of unmodified, anionic and cationic MFC and CC are prepared by vacuum filtration and characterized in terms of specific surface area, pore size distribution, degree of crystallinity, surface charge and water content. Human dermal fibroblasts are exposed to culture medium extracts of the films in an indirect contact cytotoxicity test. Moreover, cell adhesion and viability are evaluated in a direct contact assay and the effects of the physicochemical properties on cell behavior are discussed. In the indirect cytotoxicity test no toxic leachables are detected, evidencing that the CC and MFC materials are non-cytotoxic, independently ofthe chemical treatment that they have been subjected to. The direct contact tests show that carboxymethylated-MFC presents a more cytocompatible profile than unmodified and trimethylammonium-MFC. TEMPO-CC promotes fibroblast adhesion and presents cell viability comparable to the results obtained with the tissue culture material Thermanox. We hypothesize that the distinct aligned nanofiber structure present in the TEMPO-CC films is responsible for the improved cell adhesion. Thus, by controlling the surface properties of cellulose nanofibers, such as chemistry, charge, and orientation, cell adhesion properties can be promoted.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2014. Vol. 4, no 6, 2892-2903 p.
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
URN: urn:nbn:se:uu:diva-211744DOI: 10.1039/C3RA45553JISI: 000329037100044OAI: oai:DiVA.org:uu-211744DiVA: diva2:668522
Available from: 2013-11-30 Created: 2013-11-30 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Structural and Electrochemical Properties of Functionalized Nanocellulose Materials and Their Biocompatibility
Open this publication in new window or tab >>Structural and Electrochemical Properties of Functionalized Nanocellulose Materials and Their Biocompatibility
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nanocellulose has received considerable interest during the last decade because it is renewable and biodegradable, and has excellent mechanical properties, nanoscale dimensions and wide functionalization possibilities. It is considered to be a unique and versatile platform on which new functional materials can be based.

This thesis focuses on nanocellulose from wood (NFC) and from Cladophora algae (CNC), functionalized with surface charges or coated with the conducting polymer polypyrrole (PPy), aiming to study the influence of synthesis processes on structural and electrochemical properties of such materials and assess their biocompatibility.

The most important results of the work demonstrated that 1) CNC was oxidized to the same extent using electrochemical TEMPO-mediated oxidation as with conventional TEMPO processes, which may facilitate easier reuse of the reaction medium; 2) NFC and CNC films with or without surface charges were non-cytotoxic as assessed by indirect in vitro testing. Anionic TEMPO-CNC films promoted fibroblast adhesion and proliferation in direct in vitro cytocompatibility testing, possibly due to its aligned fibril structure; 3) Rinsing of PPy-coated nanocellulose fibrils, which after drying into free-standing porous composites are applicable for energy storage and electrochemically controlled ion extraction, significantly degraded the PPy coating, unless acidic rinsing was employed. Only minor degradation was observed during long-term ambient storage; 4) Variations in the drying method as well as type and amount of nanocellulose offered ways of tailoring the porosities of nanocellulose/PPy composites between 30% and 98%, with increments of ~10%. Supercritical CO2-drying generated composites with the largest specific surface area yet reported for nanocellulose/conducting polymer composites (246 m2/g). The electrochemical oxidation rate was found to be controlled by the composite porosity; 5) In blood compatibility assessments for potential hemodialysis applications, heparinization of CNC/PPy composites was required to obtain thrombogenic properties comparable to commercial hemodialysis membranes. The pro-inflammatory characteristics of non-heparinized and heparinized composites were, to some extent, superior to commercial membranes. The heparin coating did not affect the solute extraction capacity of the composite.

The presented results are deemed to be useful for tuning the properties of systems based on the studied materials in e.g. energy storage, ion exchange and biomaterial applications.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 73 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1109
Keyword
Nanocellulose, nanofibrillated cellulose, Cladophora cellulose, polypyrrole, TEMPO-mediated oxidation, composite, porosity, cytocompatibility, blood compatibility
National Category
Nano Technology Materials Engineering Physical Sciences Chemical Sciences
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-215090 (URN)978-91-554-8842-0 (ISBN)
Public defence
2014-02-25, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:30 (English)
Opponent
Supervisors
Available from: 2014-02-03 Created: 2014-01-10 Last updated: 2014-09-11
2. Nanocellulose for Biomedical Applications: Modification, Characterisation and Biocompatibility Studies
Open this publication in new window or tab >>Nanocellulose for Biomedical Applications: Modification, Characterisation and Biocompatibility Studies
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In the past decade there has been increasing interest in exploring the use of nanocellulose in medicine. However, the influence of the physicochemical properties of nanocellulose on the material´s biocompatibility has not been fully investigated. 

In this thesis, thin films of nanocellulose from wood (NFC) and from Cladophora algae (CC) were modified by the addition of charged groups on their surfaces and the influence of these modifications on the material´s physicochemical properties and on cell responses in vitro was studied.

The results indicate that the introduction of charged groups on the surface of NFC and CC results in films with decreased surface area, smaller average pore size and a more compact structure compared with the films of unmodified nanocelluloses. Furthermore, the fibres in the carboxyl-modified CC films were uniquely aggregated and aligned, a state which tended to become more prevalent with increased surface-group density.

The biocompatibility studies showed that NFC films containing hydroxypropyltrime-thylammonium (HPTMA) groups presented a more cytocompatible surface than unmodified NFC and carboxymethylated NFC regarding human dermal fibroblasts. Carboxymethyl groups resulted in NFC films that promoted inflammation, while HPTMA groups had a passivating effect in terms of inflammatory response. 

On the other hand, both modified CC films behaved as inert materials in terms of the inflammatory response of monocytes/macrophages and, under pro-inflammatory stimuli, they suppressed secretion of the pro-inflammatory cytokine TNF-α, with the effects of the carboxylated CC film more pronounced than those of the HPTMA CC material. 

Carboxyl CC films showed good cytocompatibility with fibroblasts and osteoblastic cells. However, it was necessary to reach a threshold value in carboxyl-group density to obtain CC films with cytocompatibility comparable to that of commercial tissue culture material. 

The studies presented here highlight the ability of the nanocellulose films to modulate cell behaviour and provide a foundation for the design of nanocellulose-based materials that trigger specific cell responses. The bioactivity of nanocellulose may be optimized by careful tuning of the surface properties.

The outcomes of this thesis are foreseen to contribute to our fundamental understanding of the biointerface phenomena between cells and nanocellulose as well as to enable engineering of bioinert, bioactive, and bioadaptive materials.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 80 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1320
Keyword
Nanocellulose, nanofibrillated cellulose, Cladophora cellulose, biocompatibility, inflammation, surface modification, surface group density, surface topography
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-267301 (URN)978-91-554-9416-2 (ISBN)
Public defence
2016-01-27, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:30 (English)
Opponent
Supervisors
Available from: 2015-12-18 Created: 2015-11-19 Last updated: 2016-01-13

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Hua, KaiCarlsson, Daniel OttoStrömme, MariaMihranyan, AlbertFerraz, Natalia

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