For centuries, silver has been recognized for its antibacterial properties. With the development of nanotechnology, silver nanoparticles (AgNPs) have garnered significant attention for their diverse uses in antimicrobial gel formulations, dressings for wound healing, orthopedic applications, medical catheters and instruments, implants, and contact lens coatings. A major focus has been determining AgNPs’ physical, chemical, and biological characteristics and their potential to be incorporated in biocomposite materials, particularly hydrogel scaffolds, for burn and wound healing. Though AgNPs have been rigorously explored and extensively utilized in medical and nonmedical applications, important research is still needed to elucidate their antibacterial activity when incorporated in wound-healing scaffolds. In this review, we provide an up-to-date, 10-yr (2010–2019), comprehensive literature review on advancements in the understanding of AgNP characteristics, including the particles’ preparation and mechanisms of activity, and we explore various hydrogel scaffolds for delivering AgNPs.

Introduction: The aim of this study was to investigate whether 14-3-3η, a specific isoform of a family of proteins regulating processes such as cellular signalling, activates cell-signalling pathways and induces factors known to contribute to the pathophysiology of rheumatoid arthritis (RA). We also investigated whether 14-3-3η is associated with more severe disease in both early and established RA. Methods: We investigated the effect of 14-3-3η on the activation of RA-relevant signalling cascades and induction of proinflammatory mediators that contribute to the joint damage process. 14-3-3η titres from 33 patients with early RA (mean RA duration = 1.8 months) and from 40 patients with established RA were measured in serum drawn at the 3-year time point of the Behandel Strategieën study. The relationship between 14-3-3η titres and standard clinical variables was investigated by correlation analysis. The association with radiographic damage and radiographic progression over at least a 2-year period was investigated using univariate and multivariate regression analyses. Results: 14-3-3η activated selected members of the mitogen-activated protein kinase (MAPK) family, mainly extracellular regulated kinase 1/2 and c-Jun kinase, but not p38MAPK. Activation by 14-3-3η, using levels spanning the concentration range found in RA patient serum, resulted in the induction of inflammatory transcripts such as interleukin 1 (IL-1) and IL-6 and factors linked to the joint damage process, such as receptor activator of nuclear factor κB ligand and matrix metalloproteinase 1. Serum 14-3-3η correlated significantly with rheumatoid factor (RF) (r = 0.43) and anticitrullinated protein antibodies (ACPAs) (r = 0.31) in the early RA cohort, but not with C-reactive protein (CRP) or the Disease Activity Score in 28 joints in either cohort. Serum 14-3-3η concentrations were significantly higher in patients with radiographically assessed joint damage and in those who had radiographic progression. By multivariate analysis, we show that 14-3-3η complemented markers such as CRP, RF and ACPA in informing RA radiographic status and/or progression. Conclusions: Extracellular 14-3-3η activates key signalling cascades and induces factors associated with the pathogenesis of RA at concentrations found in patients with RA, and its expression is higher in patients with radiographic damage and RA progression.

Autologous split thickness skin graft is necessary for the survival of patients with large burns and skin defects. It is not clear how a thin split thickness skin graft becomes remarkably thicker within a few weeks following transplantation. Here, we hypothesized that growth of split thickness graft should be from bottom up probably through conversion of immune cells into collagen producing skin cells. We tested this hypothesis in a preclinical porcine model by grafting split thickness meshed skin (0.508 mm thickness, meshed at 3:1 ratio) on full thickness wounds in pigs. New tissue formation was evaluated on days 10 and 20 postoperation through histological analysis and co-staining for immune cell markers (CD45) and type I collagen. The findings revealed that a split thickness graft grew from bottom up and reached to almost the same level as uninjured skin within 60 days postoperation. The result of immune-staining identified a large number of cells, which co-expressed immune cell marker (CD45) and collagen on day 10 postoperation. Interestingly, as the number of these cells reduced on day 20, most of these cells became positive for collagen production. In another set of experiments, we tested whether immune cells can convert to collagen producing cells in vitro. The results showed that mouse adherent immune cells started to express type 1 procollagen and α-smooth muscle actin when cultured in the presence of fibroblast conditioned media. In conclusion, the early thickening of split thickness graft is likely happening through a major contribution of infiltrated immune cells that convert into mainly collagen producing fibroblasts in large skin injuries.

It is well-understood that wound care poses a significant burden on the healthcare system and patient well-being. As such, it is imperative to develop efficient methods that facilitate tissue repair. Our group previously developed a nutritional gel scaffold, proven to accelerate wound repair. Due to its gel-like properties, this scaffold requires a time-consuming reconstitution, and is optimized for cavernous wounds. This pilot study examined the feasibility of a powdered form of this scaffold to accelerate healing of full-thickness wounds, thus broadening the range of applications, while providing a practical product. Splinted full-thickness wounds were generated on the backs of 6 mice, and treated with either powder, the original gel scaffold, or no treatment. Feasibility and efficacy of the powder was assessed through comparison of clinical wound measurements and histological assessments. There was a significant effect of treatment on rate of epithelialization [H(3) = 8.346, p = 0.0024] and on days to epithelial closure [H(3) = 8.482, p = 0.0061]. Post hoc analysis revealed that while requiring no reconstitution and simple to apply, the powder was sufficient to accelerate epithelialization compared to untreated wounds (p < 0.05). Furthermore, our results suggest that application of this powder did not alter certain processes associated with healing progress, such as epidermal thickness and collagen deposition. As such, this powder may provide a novel alternative to our previously developed gel scaffold by accelerating epithelialization, while providing a practical product. Future studies necessitate further evaluation of healing measures with a larger sample size.