The cellular and molecular properties of capsule surrounding silicone implants in humans vary uniquely according to the tissue type adjacent to the implant.

The foreign body reaction (FBR) to biomaterials results in fibrous encapsulation. Excessive capsule fibrosis (capsular contracture) is a major challenge to the long-term stability of implants. Clinical data suggests that the tissue type in contact with silicone breast implants alters susceptibility to developing capsular contracture; however, the tissue-specific inflammatory and fibrotic characteristics of capsule have not been well characterized at the cellular and molecular level. In this study, 60 breast implant capsule samples are collected from patients and stratified by the adjacent tissue type including subcutaneous tissue, glandular breast tissue, or muscle tissue. Capsule thickness, collagen organization, immune and fibrotic cellular populations, and expression of inflammatory and fibrotic markers is quantified with histological staining, immunohistochemistry, and real-time PCR. The findings suggest there are significant differences in M1-like macrophages, CD4+ T cells, CD26+ fibroblasts, and expression of IL-1ß, IL-6, TGF-ß, and collagen type 1 depending on the tissue type abutting the implant. Subglandular breast implant capsule displays a significant increase in inflammatory and fibrotic markers. These findings suggest that the tissue microenvironment contributes uniquely to the FBR. This data could provide new avenues for research and clinical applications to improve the site-specific biocompatibility and longevity of implantable devices.

Altered Foreign Body Response at the Posterior Surface Compared to the Anterior Surface of Human Silicone Breast Implants.

Soft implantable devices are crucial to optimizing form and function for many patients. However, periprosthetic capsule fibrosis is one of the major challenges limiting the use of implants. Currently, little is understood about how spatial and temporal factors influence capsule physiology and how the local capsule environment affects the implant structure. In this work, we analyzed breast implant capsule specimens with staining, immunohistochemistry, and real-time polymerase chain reaction to investigate spatiotemporal differences in inflammation and fibrosis. We demonstrated that in comparison to the anterior capsule against the convex surface of breast implants, the posterior capsule against the flat surface of the breast implant displays several features of a dysregulated foreign body reaction including increased capsule thickness, abnormal extracellular remodeling, and infiltration of macrophages. Furthermore, the expression of pro-inflammatory cytokines increased in the posterior capsule across the lifespan of the device, but not in the anterior capsule. We also analyzed the surface oxidation of breast explant samples with XPS analysis. No significant differences in surface oxidation were identified either spatially or temporally. Collectively, our results support spatiotemporal heterogeneity in inflammation and fibrosis within the breast implant capsule. These findings presented here provide a more detailed picture of the complexity of the foreign body reaction surrounding implants destined for human use and could lead to key research avenues and clinical applications to treat periprosthetic fibrosis and improve device longevity.

Obesity alters monocyte developmental trajectories to enhance metastasis.

Obesity is characterized by chronic systemic inflammation and enhances cancer metastasis and mortality. Obesity promotes breast cancer metastasis to lung in a neutrophil-dependent manner; however, the upstream regulatory mechanisms of this process remain unknown. Here, we show that obesity-induced monocytes underlie neutrophil activation and breast cancer lung metastasis. Using mass cytometry, obesity favors the expansion of myeloid lineages while restricting lymphoid cells within the peripheral blood. RNA sequencing and flow cytometry revealed that obesity-associated monocytes resemble professional antigen-presenting cells due to a shift in their development and exhibit enhanced MHCII expression and CXCL2 production. Monocyte induction of the CXCL2-CXCR2 axis underlies neutrophil activation and release of neutrophil extracellular traps to promote metastasis, and enhancement of this signaling axis is observed in lung metastases from obese cancer patients. Our findings provide mechanistic insight into the relationship between obesity and cancer by broadening our understanding of the interactive role that myeloid cells play in this process.

Mouse Models of Obesity to Study the Tumor-Immune Microenvironment.

Obesity is associated with chronic, low-grade systemic inflammation and leads to changes in the immune microenvironment of various tissues. As a result, obesity is associated with increased risk of cancer and a worse prognosis in patients. Given the prevalence of obesity worldwide, understanding the fundamental biology governing the relationship between obesity and cancer is critical. In this chapter, we describe preclinical models of obesity that can be combined with standard tumor models and techniques to study the tumor-immune microenvironment. We also discuss important considerations when planning experiments involving these models.

The ICU Bridge Program: volunteers bridging medicine and people together.

BACKGROUND: The intensive care unit (ICU) is an emotionally taxing environment. Patients and family members are at an increased risk of long-term physical and psychological consequences of critical illness, known collectively as post-intensive care syndrome (PICS). These environmental strains can lead to a high incidence of staff turnover and burnout. AIM: The ICU Bridge Program (ICUBP) is a student-led organization that attempts to mitigate these stressors on patients, family, and staff, by assigning university volunteers to ICUs across Montreal. SETTING: ICU. PARTICIPANTS: ICU volunteers, staff, patients, and families. PROGRAM DESCRIPTION: The ICUBP volunteers support staff by orienting patients and families, while using effective communication strategies to provide comfort and promote a calm environment. The presence of volunteer visitors is helpful to patients who do not have the support of family members and/or friends. The program provides students with profound learning experiences by allowing them to shadow multidisciplinary teams, gaining a privileged and varied exposure to an acute medical environment, while developing their communications skills. PROGRAM EVALUATION: The program reassesses its methods and impact via internal student-designed surveys distributed on a yearly basis to staff and volunteers. DISCUSSION: Research is warranted to assess the impact of the program on ICU patients, visitors, staff, and volunteers.