Modulating mechanotransduction by inhibiting yes-associated protein (YAP) in mice yields wound regeneration without scarring. However, rodents are loose-skinned and fail to recapitulate key aspects of human wound repair. We sought to elucidate the effects of YAP inhibition in red Duroc pig wounds, the most human-like model of scarring. We show that one-time treatment with verteporfin, a YAP inhibitor, immediately after wounding is sufficient to prevent scarring and to drive wound regeneration in pigs. By performing single-cell RNA sequencing (scRNA-seq) on porcine wounds in conjunction with spatial proteomic analysis, we found perturbations in fibroblast dynamics with verteporfin treatment and the presence of putative pro-regenerative/profibrotic fibroblasts enriched in regenerating/scarring pig wounds, respectively. We also identified differences in enriched myeloid cell subpopulations after treatment and linked this observation to increased elaboration of interleukin-33 (IL-33) in regenerating wounds. Finally, we validated our findings in a xenograft wound model containing human neonatal foreskin engrafted onto nude mice and used scRNA-seq of human wound cells to draw parallels with fibroblast subpopulation dynamics in porcine wounds. Collectively, our findings provide support for the clinical translation of local mechanotransduction inhibitors to prevent human skin scarring, and they clarify a YAP/IL-33 signaling axis in large animal wound regeneration.

Surgical implants are increasingly used across multiple medical disciplines, with applications ranging from tissue reconstruction to improving compromised organ and limb function. Despite their significant potential for improving health and quality of life, biomaterial implant function is severely limited by the body’s immune response to its presence: this is known as the foreign body response and is characterized by chronic inflammation and fibrotic capsule formation. This response can result in life-threatening sequelae such as implant malfunction, superimposed infection and associated vessel thrombosis, in addition to soft tissue disfigurement. Patients may require frequent medical visits, as well as repeated invasive procedures, increasing the burden on an already strained healthcare system. Currently, the foreign body response and the cells and molecular mechanisms that mediate it are poorly understood. With applications across a wide array of surgical specialties, acellular dermal matrix has emerged as a potential solution to the fibrotic reaction seen with FBR. Though the mechanisms by which acellular dermal matrix decreases chronic fibrosis remain to be clearly characterized, animal studies across diverse surgical models point to its biomimetic properties that facilitate decreased periprosthetic inflammation and improved host cell incorporation.

Importance: Child abuse is a leading cause of morbidity in early childhood. Accurate detection remains challenging.Objective: To describe racial and ethnic disproportionalities in suspicion for child abuse (SCA) in pediatric patients admitted after traumatic injury.Design, Setting, and Participants: This retrospective, multicenter cross-sectional study performed between 2022 and 2024 examined a representative national sample of children and adolescents (aged <18 years) admitted for pediatric trauma indications from 2006 to 2019. Data were from the Kids’ Inpatient Database (KID), the largest publicly available all-payer pediatric inpatient care database. Patient demographics, injury severity, and hospitalization characteristics were classified by race and ethnicity and compared using univariate and multivariate regression. Statistical analysis was performed between March 2022 and October 2024.Exposure: The SCA subgroup was identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes corresponding to child and adolescent maltreatment.Main Outcome and Measure: The primary outcome was the racial and ethnic composition of pediatric patients admitted after traumatic injury with SCA vs those without SCA.Results: Among the weighted total of 634 309 pediatric patients with complete data included in the study, 13 579 patients had injuries attributable to SCA (SCA subgroup; mean [SD] age, 1.70 [0.04] years; 7650 male [56.3%]; 2868 Black [21.1%], 2293, Hispanic [16.9%], and 5675 White [41.8%]) and 620 730 patients did not (non-SCA subgroup; mean [SD] age, 9.70 [0.01] years; 395 158 male [63.7%]; 86 376 Black [13.9%], 108 406 Hispanic [17.5%], and 298 748 White [48.1%]). The racial and ethnic distribution of the non-SCA subgroup was similar to that of the 2010 US Census. In the SCA subgroup, Black patients (odds ratio [OR], 1.75; 95% CI, 1.65-1.85; P < .001) and Hispanic patients were overrepresented (OR, 1.11; 95% CI, 1.05-1.18; P < .001) and White patients were underrepresented compared with the Census. After controlling for socioeconomic factors and hospital characteristics among 504 365 (weighted) observations in White, Black, and Hispanic patients (493 530 patients without and 10 835 patients with SCA), Black race remained an independent risk factor associated with SCA (OR, 1.10; 95% CI, 1.03-1.17; P = .004), whereas Hispanic race was found to be a protective factor associated with decreased odds of SCA (OR, 0.71; 95% CI, 0.67-0.76; P < .001). Compared with White patients in the SCA subgroup, Black patients had a 26.5% (95% CI, 11.0%-44.3%) longer length of stay (P < .001) for mild to moderate injuries and a 40.1% (95% CI, 16.4%-68.5%) longer length of stay (P < .001) for serious injury.Conclusion and Relevance: In this study, Black children and adolescents were suspected to have experienced child abuse at higher rates than children and adolescents of other racial and ethnic backgrounds. More research is necessary to understand the origins of these disparities to reduce them in child abuse identification.