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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, p. 1224-1233Article 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, p. 1224-1233
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, id: diva2:872702
Funder
Swedish Research Council FormasStiftelsen Olle Engkvist Byggmästare
Available from: 2015-11-19 Created: 2015-11-19 Last updated: 2018-03-15Bibliographically 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. p. 80
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
2. Oxidized Cladophora nanocellulose derivatives: Functionalization towards biocompatible materials
Open this publication in new window or tab >>Oxidized Cladophora nanocellulose derivatives: Functionalization towards biocompatible materials
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nanocellulose is a promising candidate for biomedical applications because of its enhanced mechanical properties, increased surface area and greater porosity compared to bulk cellulose.

This thesis investigates the functionalization of Cladophora nanocellulose and evaluates the influence of these modifications on physicochemical properties and biocompatibility of the material.

An electrochemically assisted TEMPO-mediated oxidation setup produced cellulose materials with varying degrees of carboxyl groups. This approach allowed control of the charge applied during the process and adjustment of the carboxylation. Carboxylated nanocellulose membranes had smaller surface area and total pore volume and a more compact structure than the membranes of the unmodified material. Moreover, the introduction of carboxyl groups resulted in membranes with an aligned fiber pattern; the alignment and aggregation of the fibers tended to increase with higher degrees of oxidation.

Cytocompatibility studies using fibroblasts and osteoblastic cells have shown that the bioinert Cladophora nanocellulose membranes can be rendered bioactive by the introduction of carboxyl groups. Nevertheless, at least 260 µmol g-1 carboxyl groups are required to obtain nanocellulose membranes that promote cell adhesion and spreading comparable to those observed when cells are cultured on tissue culture material.

In parallel, a periodate oxidation produced 10-20 µm 2,3-dialdehyde cellulose beads with very smooth and compact surfaces. This material was sulfonated up to 50% of the aldehyde groups, resulting in charged, porous structures that maintained the spherical shape. The mesoporous assembly could be tailored by altering the degree of sulfonation, which also produced variations in surface charge, ζ-potential, specific density, surface area and thermal stability.

Because the physicochemical properties make these sulfonated beads potential candidates for immunosorption and blood-related applications, they were further characterized regarding hemocompatibility. In vitro studies showed that both sulfonated beads and unmodified Cladophora nanocellulose did not present hemolytic activity. The pro-coagulant activity of the sulfonated beads was significantly lower than that of the unmodified nanocellulose; however, the material’s modifications did not diminish the activation of the complement system.

The results presented in this thesis show that it is possible to tailor the biocompatibility of Cladophora nanocellulose by introducing chemical modifications to its structure and by carefully tuning its physicochemical properties.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 75
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1649
Keyword
Cladophora nanocellulose, TEMPO oxidation, periodate oxidation, sulfonation, cellulose beads, surface properties, biomaterials, cell studies, hemocompatibility
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-346212 (URN)978-91-513-0280-5 (ISBN)
Public defence
2018-05-09, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:30 (English)
Opponent
Supervisors
Available from: 2018-04-17 Created: 2018-03-15 Last updated: 2018-04-17

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Hua, KaiRocha, IgorZhang, PengGustafsson, SimonStrømme, MariaMihranyan, AlbertFerraz, Natalia

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