No abstract

Burn injury increases the risk of morbidity and mortality by promoting severe hemodynamic shock and risk for local or systemic infection. Graft failure due to poor wound healing or infection remains a significant problem for burn subjects. The mechanisms by which local burn injury compromises the epithelial antimicrobial barrier function in the burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue, are largely unknown. The objective of this study was to establish defects in epidermal barrier function in human donor skin and burn margin, in order to identify potential mechanisms that may lead to graft failure and/or impaired burn wound healing. In the present study, we established that epidermal lipids and respective lipid synthesis enzymes were significantly reduced in both donor skin and burn margin. We further identified diverse changes in the gene expression and protein production of several candidate skin antimicrobial peptides (AMPs) in both donor skin and burn margin. These results also parallel changes in cutaneous AMP activity against common burn wound pathogens, aberrant production of epidermal proteases known to regulate barrier permeability and AMP activity, and greater production of pro-inflammatory cytokines known to be induced by AMPs. These findings suggest that impaired epidermal lipid and AMP regulation could contribute to graft failure and infectious complications in subjects with burn or other traumatic injury.

Background Recent work suggests that bacterial biofilms play a role in capsular contracture (CC). However, traditional culture techniques provide only a limited understanding of the bacterial communities present within the contracted breast. Next generation sequencing (NGS) represents an evolution of polymerase chain reaction technology that can sequence all DNA present in a given sample. Objectives The aim of this study was to utilize NGS to characterize the bacterial microbiome of the capsule in patients with CC following cosmetic breast augmentation. Methods We evaluated 32 consecutive patients with Baker grade III or IV CC following augmentation mammoplasty. Specimens were obtained from all contracted breasts (n = 53) during capsulectomy. Tissue specimens from contracted capsules as well as intraoperative swabs of the breast capsule and implant surfaces were obtained. Samples were sent to MicroGenDX Laboratories (Lubbock, TX) for NGS. Results Specimens collected from 18 of 32 patients (56%) revealed the presence of microbial DNA. The total number of positive samples was 22 of 53 (42%). Sequencing identified a total of 120 unique bacterial species and 6 unique fungal species. Specimens with microbial DNA yielded a mean [standard deviation] of 8.27 [4.8] microbial species per patient. The most frequently isolated species were Escherichia coli (25% of all isolates), Diaphorobacter nitroreducens (12%), Cutibacterium acnes (12%), Staphylococcus epidermidis (11%), fungal species (7%), and Staphylococcus aureus (6%). Conclusions NGS enables characterization of the bacterial ecosystem surrounding breast implants in unprecedented detail. This is a critical step towards understanding the role this microbiome plays in the development of CC. Level of Evidence: 4

Burn wound healing complications, such as graft failure or infection, are a major source of morbidity and mortality in burn patients. The mechanisms by which local burn injury alters epidermal barrier function in autologous donor skin and surrounding burn margin are largely undefined. We hypothesized that defects in the epidermal cholinergic system may impair epidermal barrier function and innate immune responses. The objective was to identify alterations in the epidermal cholinergic pathway, and their downstream targets, associated with inflammation and cell death. We established that protein levels, but not gene expression, of the α7 nicotinic acetylcholine receptor (CHRNA7) were significantly reduced in both donor and burn margin skin. Furthermore, the gene and protein levels of an endogenous allosteric modulator of CHRNA7, secreted mammalian Ly-6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP1) and acetylcholine were significantly elevated in donor and burn margin skin. As downstream proteins of inflammatory and cell death targets of nAChR activation, we found significant elevations in epidermal High Mobility Group Box Protein 1 (HMGB1) and caspase 3 in donor and burn margin skin. Lastly, we employed a novel in vitro keratinocyte burn model to establish that burn injury influences the gene expression of these cholinergic mediators and their downstream targets. These results indicate that defects in cholinergic mediators and inflammatory/apoptotic molecules in donor and burn margin skin may directly contribute to graft failure or infection in burn patients.