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Transition from bioinert to bioactive material by tailoring the biological cell response to carboxylated nanocellulose
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Minist Educ Brazil, CAPES Fdn, BR-70040020 Brasilia, DF, Brazil.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
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2016 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 17, no 3, 1224-1233 p.Article in journal (Refereed) Published
Abstract [en]

This work presents an insight into the relationship between cell response and physicochemical properties of Cladophora cellulose (CC) by investigating the effect of CC functional group density on the response of model cell lines. CC was carboxylated by electrochemical TEMPO-mediated oxidation. By varying the amount of charge passed through the electrolysis setup, CC materials with different degrees of oxidation were obtained. The effect of carboxyl group density on the material’s physicochemical properties was investigated together with the response of human dermal fibroblasts (hDF) and human osteoblastic cells (Saos-2) to the carboxylated CC films. The introduction of carboxyl groups resulted in CC films with decreased specific surface area and smaller total pore volume compared with the unmodified CC (u-CC). While u-CC films presented a porous network of randomly oriented fibers, a compact and aligned fiber pattern was depicted for the carboxylated-CC films. The decrease in surface area and total pore volume, and the orientation and aggregation of the fibers tended to augment parallel to the increase in the carboxyl group density. hDF and Saos-2 cells presented poor cell adhesion and spreading on u-CC, which gradually increased for the carboxylated CC as the degree of oxidation increased. It was found that a threshold value in carboxyl group density needs be reached to obtain a carboxylated-CC film with cytocompatibility comparable to commercial tissue culture material. Hence, this study demonstrates that a normally bioinert nanomaterial can be rendered bioactive by carefully tuning the density of charged groups on the material surface, a finding that not only may contribute to the fundamental understanding of biointerface phenomena, but also to the development of bioinert/bioactive materials.

Place, publisher, year, edition, pages
2016. Vol. 17, no 3, 1224-1233 p.
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
URN: urn:nbn:se:uu:diva-267300DOI: 10.1021/acs.biomac.6b00053ISI: 000372391800056OAI: oai:DiVA.org:uu-267300DiVA: diva2:872702
Funder
Swedish Research Council FormasStiftelsen Olle Engkvist Byggmästare
Available from: 2015-11-19 Created: 2015-11-19 Last updated: 2017-12-01Bibliographically approved
In thesis
1. 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, KaiRocha, IgorZhang, PengGustafsson, SimonStrømme, MariaMihranyan, AlbertFerraz, Natalia

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