Effects and formulation of silver nanoscaffolds on cytotoxicity dependent ion release kinetics towards enhanced excision wound healing patterns in Wistar albino rats†

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Abstract

Wound tissue regeneration and angiogenesis are dynamic processes that send physiological signals to the body. Thus, designing novel nanoscaffolds by understanding their surface modifications and toxicological response in a biological system with a potent anti-inflammatory response is a viable solution. In this respect, inspired by the surface chemistry, in the present work we focus on the chemical optimization of silver nanoscaffolds using surface cappings in order to understand their kinetic release behaviour in simulated wound fluids (SWF), to analyze their blood compatibility in human lymphocytes and erythrocytes and then embed them in a chitosan-agarose matrix (CAM) as a productive drug delivery system to evaluate in vivo excision wound tissue regeneration efficiency in Wistar rats. In this regard, polyvinyl alcohol capped silver nanocomposites (PVA-AgNPs) exhibit a dominant antibacterial efficacy with the sustained and controlled release of silver ions and percentage cell mortality and percentage hemolysis of only 10% and 16% compared with uncapped-AgNPs or silver bandaids (SBDs). Also, PVA-AgNP impregnated CAM (PVA-CAM) shows positive effects through their anti-inflammatory and angiogenic properties, with a nearly 95% healing effect within 9 days. The complete development of collagen and fibroblast constituents was also monitored in PVA-CAM by hematoxylin & eosin (H & E) and Masson trichrome (MT) staining. These results provide a clear insight into the development of a potent therapeutic formulation using CAM as a scaffold incorporated with surface functionalized PVA-AgNPs as a bioeffective and biocompatible polymer for the fabrication of efficacious silver wound dressing scaffolds in clinical practice.

Abstract

A sustained and controlled release of silver ions from AgNPs is driven by greater percentage of wound contraction with minimal cytotoxic behavioural rates and effective antibacterial activity.

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Most cited references 9

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Controlled release of biologically active silver from nanosilver surfaces.

Jingyu Liu, David A Sonshine, Saira Shervani … (2010)

Major pathways in the antibacterial activity and eukaryotic toxicity of nanosilver involve the silver cation and its soluble complexes, which are well established thiol toxicants. Through these pathways, nanosilver behaves in analogy to a drug delivery system, in which the particle contains a concentrated inventory of an active species, the ion, which is transported to and released near biological target sites. Although the importance of silver ion in the biological response to nanosilver is widely recognized, the drug delivery paradigm has not been well developed for this system, and there is significant potential to improve nanosilver technologies through controlled release formulations. This article applies elements of the drug delivery paradigm to nanosilver dissolution and presents a systematic study of chemical concepts for controlled release. After presenting thermodynamic calculations of silver species partitioning in biological media, the rates of oxidative silver dissolution are measured for nanoparticles and macroscopic foils and used to derive unified area-based release kinetics. A variety of competing chemical approaches are demonstrated for controlling the ion release rate over 4 orders of magnitude. Release can be systematically slowed by thiol and citrate ligand binding, formation of sulfidic coatings, or the scavenging of peroxy-intermediates. Release can be accelerated by preoxidation or particle size reduction, while polymer coatings with complexation sites alter the release profile by storing and releasing inventories of surface-bound silver. Finally, the ability to tune biological activity is demonstrated through a bacterial inhibition zone assay carried out on selected formulations of controlled release nanosilver.