Soft Tissues and Materials Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments Jasmina Stojkovska 1 , Zeljka Djurdjevic 1 , Ivan Jancic 2 , Biljana Bufan 2 , Marina Milenkovic 2 , Radmila Jankovic 3 , Vesna Miskovic-Stankovic 1 and Bojana Obradovic 1 Abstract In the present study, possibilities for using novel nanocomposites based on alginate and silver nanoparticles for wound treatment were investigated in a second-degree thermal burn model in Wistar rats. Silver nanoparticles (AgNPs) were electrochemically synthesized in alginate solutions that were further utilized to obtain the Ag/alginate solution and microfibers for subsequent in vivo studies. Daily applications of the Ag/alginate colloid solution, containing AgNPs, alginate and ascorbic acid (G3), wet Ag/alginate microfibers containing AgNPs (G5) and dry Ag/alginate microfibers containing AgNPs (G6) were compared to treatments with a commercial cream containing silver sulfadiazine (G2) and a commercial Ca-alginate wound dressing containing silver ions (G4), as well as to the untreated controls (G1). Results of the in vivo study have shown faster healing in treated wounds, which completely healed on day 19 (G4, G5 and G6) and 21 (G2 and G3) after the thermal injury, while the period for complete reepitelization of untreated wounds (G1) was 25 days. The macroscopic analysis has shown that scabs fell off between day 10 and 12 after the thermal injury induction in treated groups, whereas between day 15 and 16 in the control group. These macroscopic findings were supported by the results of histopathological analyses, which have shown enhanced granulation and reepithelization, reduced inflam- mation and improved organization of the extracellular matrix in treated groups without adverse effects. Among the treated groups, dressings based on Ca-alginate (G4-G6) induced enhanced healing as compared to the other two groups (G2, G3), which could be attributed to additional stimuli of released Ca 2þ . The obtained results indicated potentials of novel nanocomposites based on alginate and AgNPs for therapeutic applications in wound treatments. Keywords Nanocomposites, alginate, silver nanoparticles, Ag/alginate colloid solution, microfibers, rat model, second degree thermal burn Introduction Burn wounds are one of the most common injuries, while deep, necrotic, and infected burns, although less frequent, present a serious clinical problem. It is well known that skin burn injuries result in loss of the skin protective function as a barrier to microorganisms leading to high risks of infections. Currently, numerous research studies are focused on developing antimicro- bial wound dressings especially active against microor- ganisms resistant to antibiotics. 1 Alginate is one of the commonly used base components of various wound dressings due to high water sorption capacity, softness, flexibility and biocompatibility. 2,3 Alginate is a naturally derived polysaccharide that forms biocom- patible hydrogels under mild conditions in the presence of divalent cations such as Ca 2þ . Dressings based on Ca-alginate hydrogels regulate moisture levels, 1 Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia 2 Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia 3 School of Medicine, University of Belgrade, Belgrade, Serbia Corresponding author: Bojana Obradovic, Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, Belgrade 11000, Serbia. Email: bojana@tmf.bg.ac.rs Journal of Biomaterials Applications 0(0) 1–15 ! The Author(s) 2018 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0885328218759564 journals.sagepub.com/home/jba