Preclinical functional characterization methods of nanocomposite hydrogels containing silver nanoparticles for biomedical applications

Stojkovska, Jasmina; Zvicer, Jovana; Obradovic, Bojana

doi:10.1007/s00253-020-10521-2

Mini-Review
Published: 06 April 2020

Preclinical functional characterization methods of nanocomposite hydrogels containing silver nanoparticles for biomedical applications

Jasmina Stojkovska^1,2,
Jovana Zvicer¹ &
Bojana Obradovic¹

Applied Microbiology and Biotechnology volume 104, pages 4643–4658 (2020)Cite this article

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5 Citations
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Abstract

Nanocomposite hydrogels that contain silver nanoparticles (AgNPs) are especially attractive for various biomedical applications (e.g., antimicrobial wound dressings, coatings and soft tissue implants) due to strong antimicrobial activity of released silver nanoparticles and/or ions over prolonged times. However, all potential biomedical products have to be thoroughly specified fulfilling strict safety requirements. Characterization of nanocomposites is additionally complicated due to potential harmful effects of nanoparticles and accumulation in cells and tissues. This paper summarizes methods for preclinical characterization of hydrogel nanocomposites containing AgNPs with the particular attention on Ag/alginate hydrogels. Standard physicochemical characterization methods include transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM), UV–visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR). Functional in vitro characterization relies on different methods for estimation of silver release, antimicrobial activity, and nanocomposite cytotoxicity. Here, we specially focus on utilization of 3D bioreactor systems that mimic native physiological environments with the aim to reliably predict nanocomposite behavior during implementation and so to decrease the need for animal experimentation. These systems were shown to provide more accurate and relevant data on silver release and cytotoxicity as compared to static systems such as 2D cell monolayer cultures. Finally, nanocomposites are evaluated in vivo in different animal models, which are in the case of wound dressings typically mice, rats, and pigs. The present review provides a basis for defining a strategy for comprehensive and efficient preclinical characterization of novel nanocomposites attractive not only for those containing AgNPs but also other metallic nanoparticles aimed for biomedical applications.

Key points

• A platform for devising comprehensive preclinical evaluation of nanocomposites.

• Biomimetic bioreactors provide reliable functional nanocomposite evaluation.

• Cells in 2D cultures are more sensitive to silver nanoparticles than in 3D cultures.

• Biomimetic bioreactor 3D cell/tissue cultures can address the in vitro-in vivo gap.

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Funding

This work was funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant III 45019).

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Affiliations

Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
Jasmina Stojkovska, Jovana Zvicer & Bojana Obradovic
Innovation Center of the Faculty of Technology and Metallurgy, Belgrade, Serbia
Jasmina Stojkovska

Authors

Jasmina Stojkovska
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Jovana Zvicer
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Bojana Obradovic
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Contributions

JS reviewed the literature and wrote sections on physicochemical characterization, antimicrobial activity studies, and in vivo studies. JZ reviewed the literature and wrote sections on evaluation of mechanical properties, silver release, and cytotoxicity. BO conceived the manuscript and wrote the “Introduction” and “Summary.” All the authors read and approved the manuscript.

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Correspondence to Bojana Obradovic.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Stojkovska, J., Zvicer, J. & Obradovic, B. Preclinical functional characterization methods of nanocomposite hydrogels containing silver nanoparticles for biomedical applications. Appl Microbiol Biotechnol 104, 4643–4658 (2020). https://doi.org/10.1007/s00253-020-10521-2

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Received: 04 January 2020
Revised: 04 January 2020
Accepted: 03 March 2020
Published: 06 April 2020
Issue Date: June 2020
DOI: https://doi.org/10.1007/s00253-020-10521-2

Keywords

Alginate
Silver release
Cytotoxicity
Antimicrobial
Biomimetic bioreactor
In vitro – In vivo gap