Delayed application of silver nanoparticles reveals the role of early inflammation in burn wound healing

Abstract

Burn injury is common, and antimicrobial agents are often applied immediately to prevent wound infection and excessive inflammatory response. Although inflammation is essential for clearing bacteria and creating an environment conducive to the healing process, it is unclear what time-frame inflammation should be present for optimal wound healing. This study critically investigated the role of early inflammation in burn wound healing, and also revealed the molecular mechanisms underlying the pro-healing effects of silver nanoparticles (AgNPs). We created a burn injury mouse model using wild-type and Smad3−/− mice, which were topically treated with AgNPs at different post-burn days, and examined the healing processes of the various groups. We also delineated the molecular pathways underlying the anti-inflammation and pro-healing effects of AgNPs by morphological and histological analysis, immuno-histochemistry, and western blotting. Our results showed that (1) AgNPs regulated pro-inflammatory cytokine IL-6 production of keratinocytes and neutrophils infiltration through KGF-2/p38 signaling pathway, (2) Topical AgNPs treatment immediately after burn injury significantly supressed early inflammation but resulted in delayed healing, (3) A short delay in AgNPs application (post-burn day 3 in our model) allowed early inflammation in a controlled manner, and led to optimal burn wound healing. Thus, our current study showed that some degree of early inflammation was beneficial, but prolonged inflammation was detrimental for burn wound healing. Further evaluation and clinical translation of this finding is warranted.

Preparation of Electrospun Small Intestinal Submucosa/Poly(caprolactone-co-Lactide-co-glycolide) Nanofiber Sheet as a Potential Drug Carrier

“…The Dex-S/P(5:1)-NS showed a gradual decrease in macrophage infiltration, but AgS-S/P(5:1)-NS suppressed macrophage infiltration at 2 weeks and then slightly increased at 3 weeks. This result indicates that sustained drug release is required to suppress macrophage infiltration because Dex and AgS display potent inflammatory suppressive properties [ 30 , 31 , 32 ].…”

Human Mesenchymal Stromal Cell-Derived Exosomes Promote In Vitro Wound Healing by Modulating the Biological Properties of Skin Keratinocytes and Fibroblasts and Stimulating Angiogenesis

“…The data showed the important role of the culture system in conferring certain therapeutic features to MSC-derived products. Nevertheless, Zhang and collaborators showed that the initial inflammation is beneficial for the resolution of the lesion [28]; thus, using MSCderived exosomes as treatment for skin injuries can positively impact the progression of the normal healing process.…”

The Efficacy of Silver-Based Electrospun Antimicrobial Dressing in Accelerating the Regeneration of Partial Thickness Burn Wounds Using a Porcine Model

“…The final phase is the remodeling phase, where the burn wound completely heals and forms scars as collagen and elastin continue to deposit and reform. This phase lasts for several months or years [ 2 , 44 , 45 ]. According to the results above, wounds treated with UrgoTul and Aquacel showed better recovery, which was indicated through higher wound closure and collagen formation rates, new skin structure formation and a low density of inflammatory cells inside the wounds.…”

“…According to the results above, wounds treated with UrgoTul and Aquacel showed better recovery, which was indicated through higher wound closure and collagen formation rates, new skin structure formation and a low density of inflammatory cells inside the wounds. Although inflammation plays an important role in the healing process, prolonged inflammation could cause impaired wound healing that delays tissue repair [ 2 , 45 , 46 ]. On the other hand, although the healing rate was not as high as those treated with UrgoTul and Aquacel, PCLGelAg samples still showed better recovery of damaged skin when compared with normal gauze treatment and effectiveness in antibacterial properties.…”