Functional Genomics Unique to Week 20 Post Wounding in the Deep Cone/Fat Dome of the Duroc/Yorkshire Porcine Model of Fibroproliferative Scarring

Background: Hypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1) there has been no validated animal model; 2) human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3) tissues typically have been homogenized, mixing cell populations; and 4) gene-by-gene studies are incomplete.Methodology/Principal Findings: We have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc( pigmented fibroproliferative)/Yorkshire( non-pigmented non-fibroproliferative) porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model.Conclusions/Significance: 1) the scars are still thick at forty-six weeks post wounding further validating the model. 2) the differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3) the findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. in the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring.The National Institute on Disability and Rehabilitation ResearchThe National Institutes of HealthThe Washington State Council of Fire Fighters Burn FoundationThe Northwest Burn FoundationUniv Washington, Dept Surg, Div Plast Surg, Seattle, WA 98195 USAIowa State Univ, Dept Anim Sci, Ames, IA USAUniv Washington, Dept Biostat, Seattle, WA 98195 USAMahidol Univ, Ramathibodi Hosp, Dept Surg, Bangkok 10700, ThailandUniv Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USAUniversidade Federal de São Paulo, Div Plast Surg, Dept Surg, São Paulo, BrazilUniversidade Federal de São Paulo, Div Plast Surg, Dept Surg, São Paulo, BrazilThe National Institute on Disability and Rehabilitation Research: H133G050022The National Institutes of Health: 1R21GM074673The National Institutes of Health: 5U54GM062119-09Web of Scienc

Inhalation injury is associated with long-term employment outcomes in the burn population: Findings from a cross-sectional examination of the Burn Model System National Database.

IntroductionInhalation injuries carry significant acute care burden including prolonged ventilator days and length of stay. However, few studies have examined post-acute outcomes of inhalation injury survivors. This study compares the long-term outcomes of burn survivors with and without inhalation injury.MethodsData collected by the Burn Model System National Database from 1993 to 2019 were analyzed. Demographic and clinical characteristics for adult burn survivors with and without inhalation injury were examined. Outcomes included employment status, Short Form-12/Veterans Rand-12 Physical Composite Score (SF-12/VR-12 PCS), Short Form-12/Veterans Rand-12 Mental Composite Score (SF-12/VR-12 MCS), and Satisfaction With Life Scale (SWLS) at 24 months post-injury. Regression models were used to assess the impacts of sociodemographic and clinical covariates on long-term outcome measures. All models controlled for demographic and clinical characteristics.ResultsData from 1,871 individuals were analyzed (208 with inhalation injury; 1,663 without inhalation injury). The inhalation injury population had a median age of 40.1 years, 68.8% were male, and 69% were White, non-Hispanic. Individuals that sustained an inhalation injury had larger burn size, more operations, and longer lengths of hospital stay (pConclusionsBurn survivors with inhalation injury were significantly less likely to be employed at 24 months post-injury compared to survivors without inhalation injury. However, other health-related quality of life outcomes were similar between groups. This study suggests distinct long-term outcomes in adult burn survivors with inhalation injury which may inform future resource allocation and treatment paradigms