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Towards Tunable Protein-Carrier Wound Dressings Based on Nanocellulose Hydrogels Crosslinked with Calcium Ions
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. (Nanotechnology and Functional Materials)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. (Nanotechnology and Functional Materials)ORCID iD: 0000-0002-5496-9664
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. (Nanotechnology and Functional Materials)
2018 (English)In: Nanomaterials, E-ISSN 2079-4991, Vol. 8, no 7, article id 550Article in journal (Refereed) Published
Abstract [en]

A Ca2+-crosslinked wood-based nanofibrillated cellulose (NFC) hydrogel was investigated to build knowledge toward the use of nanocellulose for topical drug delivery applications in a chronic wound healing context. Proteins of varying size and isoelectric point were loaded into the hydrogel in a simple soaking procedure. The release of the proteins from the hydrogel was monitored and kinetics determining parameters of the release processes were assessed. The integrity of the hydrogel and proteins were also studied. The results showed that electrostatic interactions between the proteins and the negatively-charged NFC hydrogel structure played a central role in the loading process. The release of the proteins were governed by Fickian diffusion. An increased protein size, as well as a positive protein charge facilitated a slower and more sustained release process from the hydrogel matrix. At the same time, the positively-charged protein was shown to increase the post-loading hydrogel strength. Released proteins maintained structural stability and activity, thus indicating that the Ca2+-crosslinked NFC hydrogel could function as a carrier of therapeutic proteins without compromising protein function. It is foreseen that, by utilizing tunable charge properties of the NFC hydrogel, release profiles can be tailored to meet very specific treatment needs.

Place, publisher, year, edition, pages
MDPI, 2018. Vol. 8, no 7, article id 550
Keywords [en]
nanofibrillated cellulose, ion-crosslinked, drug delivery, wound healing, chronic wounds
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
URN: urn:nbn:se:uu:diva-362722DOI: 10.3390/nano8070550ISI: 000442523100101PubMedID: 30036970OAI: oai:DiVA.org:uu-362722DiVA, id: diva2:1254365
Funder
Swedish Research Council Formas, 942-2015-475Available from: 2018-10-09 Created: 2018-10-09 Last updated: 2018-10-30Bibliographically approved
In thesis
1. Ion-Crosslinked Nanocellulose Hydrogels for Advanced Wound Care Applications
Open this publication in new window or tab >>Ion-Crosslinked Nanocellulose Hydrogels for Advanced Wound Care Applications
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A current trend in the field of wound care is the development of wound healing materials that are designed to address specific types of wounds or underlying pathologies to achieve improved healing. At the same time, there is a societal drive to replace synthetic materials with renewable alternatives. The work presented in this thesis was therefore carried out to investigate the use of wood nanocellulose, produced from the world’s most abundant biopolymer, cellulose, in advanced wound care applications.

Wood-based nanofibrillated cellulose (NFC) was chemically functionalized and crosslinked using calcium to obtain a self-standing hydrogel. The NFC hydrogel was evaluated in terms of its physicochemical properties, biocompatibility, blood interactions, bacterial interactions, in vivo wound healing ability and, finally, as a protein carrier. Parallel with the assessment of the NFC hydrogel, modified versions of the material were tested to investigate the tunability of the above-mentioned characteristics.

The ability of the hydrogel to maintain a moist wound bed was demonstrated. Evaluation of the biocompatibility showed that the material was cytocompatible and did not trigger inflammatory mechanisms. Furthermore, the NFC hydrogel supported cell proliferation, and was shown to possess hemostatic properties. It was also discovered that the material had a slight bacteriostatic effect and the ability to act as a barrier against bacteria. When tested in vivo, the hydrogel was found to significantly improve wound healing.

Modifications through the incorporation of additives to the hydrogel matrix, as well as exchange of the crosslinking ion, were shown to influence the biological response to the material. Moreover, the results presented here demonstrate the possibility of using the NFC hydrogel as a protein carrier; the easily adjustable charge property being identified as a central parameter for manipulation to regulate the release profile.

In conclusion, this work has demonstrated the extensive wound healing ability of the calcium-crosslinked NFC hydrogel, and represents an important milestone in the research on NFC towards advanced wound care applications. It is expected that the easily modifiable nature of the material can be exploited to further develop the NFC hydrogel to suit the treatment needs for a broad range of wound types.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 81
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1731
Keywords
nanofibrillated cellulose, wood nanocellulose, ion crosslinking, hydrogel, wound healing, biocompatibility, blood interactions, bacterial interactions, protein carrier, nanotherapeutic
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-363087 (URN)978-91-513-0474-8 (ISBN)
Public defence
2018-11-30, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:30 (English)
Opponent
Supervisors
Available from: 2018-11-09 Created: 2018-10-12 Last updated: 2018-11-19

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Basu, AlexStrömme, MariaFerraz, Natalia

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