Surface Texturization of Breast Implants Impacts Extracellular Matrix and Inflammatory Gene Expression in Asymptomatic Capsules.

BACKGROUND: Texturing processes have been designed to improve biocompatibility and mechanical anchoring of breast implants. However, a high degree of texturing has been associated with severe abnormalities. In this study, the authors aimed to determine whether implant surface topography could also affect physiology of asymptomatic capsules. METHODS: The authors collected topographic measurements from 17 different breast implant devices by interferometry and radiographic microtomography. Morphologic structures were analyzed statistically to obtain a robust breast implant surface classification. The authors obtained three topographic categories of textured implants (i.e., "peak and valleys," "open cavities," and "semiopened cavities") based on the cross-sectional aspects. The authors simultaneously collected 31 Baker grade I capsules, sorted them according to the new classification, established their molecular profile, and examined the tissue organization. RESULTS: Each of the categories showed distinct expression patterns of genes associated with the extracellular matrix (Timp and Mmp members) and inflammatory response (Saa1, Tnsf11, and Il8), despite originating from healthy capsules. In addition, slight variations were observed in the organization of capsular tissues at the histologic level. CONCLUSIONS: The authors combined a novel surface implant classification system and gene profiling analysis to show that implant surface topography is a bioactive cue that can trigger gene expression changes in surrounding tissue, even in Baker grade I capsules. The authors' new classification system avoids confusion regarding the word "texture," and could be transposed to implant ranges of every manufacturer. This new classification could prove useful in studies on potential links between specific texturizations and the incidence of certain breast-implant associated complications.

Role of mechanical and thermal damage in pericapsular inflammatory response to injectable silicone in a rabbit model.

Silicone is used widely for tissue augmentation in humans. However, late complications, such as delayed inflammation and capsular contracture, remain uncharacterized, despite their importance. In the present study, we aimed to determine whether mechanical and thermal damage induce capsular inflammation around a foreign body, and elucidate the biological mechanism underlying this phenomenon. We injected silicone into the subcutaneous layer of the skin of New Zealand white rabbits. The rabbits were divided into two groups: the control group received no treatment; in the experimental group, external force was applied near the injection silicone using high-intensity focused ultrasound (HIFU). Tissues near the injected silicone were harvested from both groups on Days 4, 7, and 30 after HIFU treatment for comparative analysis. Visual and histological examinations showed clearly increased inflammation in the experimental group compared with that in the control group. Furthermore, capsular tissue from the experimental group displayed markedly increased collagen production. Immunofluorescence revealed marked activation of macrophages in the early stages of inflammation (Days 4 and 7 after HIFU treatment), which decreased on Day 30. Assessment of cytokine activation showed significantly increased expression of heat shock protein (HSP)27, HSP60, HSP70, toll-like receptor (TLR)2, TLR4, and interleukin-8 in the experimental group. The expression of transforming growth factor-ß1 did not increase significantly in the experimental group. In conclusion, damage to tissues around the injected silicone induced capsular inflammation. Macrophages and damage-associated molecular pattern molecules were involved in the early stages of inflammation. HSP release activated TLRs, which subsequently activated innate immunity and induced the inflammatory response.

Current Approaches Including Novel Nano/Microtechniques to Reduce Silicone Implant-Induced Contracture with Adverse Immune Responses.

Capsular contracture, which is the pathologic development of fibrous capsules around implants, is a major complication of reconstructive and aesthetic breast surgeries. Capsular contracture can cause implant failure with breast hardening, deformity, and severe pain. The exact mechanisms underlying this complication remain unclear. In addition, anaplastic large cell lymphoma is now widely recognized as a very rare disease associated with breast implants. Foreign body reactions are an inevitable common denominator of capsular contracture. A number of studies have focused on the associated immune responses and their regulation. The present article provides an overview of the currently available techniques, including novel nano/microtechniques, to reduce silicone implant-induced contracture and associated foreign body responses.

The aetiopathogenesis of capsular contracture: A systematic review of the literature.

BACKGROUND: Capsular contracture is the most frequent complication after breast augmentation or reconstruction with breast implants. The immune system plays a prominent role in capsular contracture formation, albeit to an unknown extent. Bacterial contamination in situ has been hypothesized to be causative for capsular contracture. How this relates to the immunological processes involved is unknown. This article aims to provide an overview of immunological and bacterial factors involved in development of capsular contracture. MATERIALS AND METHODS: We undertook a systematic literature review focused on immunological factors and microbiota in relation to capsular contraction around implants. This systematic review was performed in accordance with the PRISMA guidelines. PubMed, EMBASE, and the Cochrane databases were searched from inception up to October 2016. Included studies were assessed for the following variables: subject characteristics, number of capsules, primary indication for surgery, surgical procedure, follow-up or implant duration, study methods, type of antibiotics or medical therapies and outcomes related to microbiota and immunological factors. RESULTS: Data on immunological factors and bacterial contamination were retrieved from 64 included studies. Notably the presence of macrophages and Staphylococcus epidermidis within capsules was often associated with capsular contracture. CONCLUSION: This review provides a clear overview of the immunological factors associated with capsular contracture and provides a hypothetical immunological model for development of the disease. Furthermore, an overview of bacterial contamination and associations with capsular contracture has been provided. Follow-up research may result in clinical recommendations to prevent capsular contracture.

Further evidence that human acellular dermal matrix decreases inflammatory markers of capsule formation in implant-based breast reconstruction.

BACKGROUND: Human acellular dermal matrix (HADM; previously termed "acellular cadaveric dermis") may limit inflammatory changes believed to play a role in capsular contracture, a common complication of implant-based breast reconstruction. OBJECTIVES: Differences between HADM and native breast capsule specimens were evaluated by immunohistochemical analysis of key inflammatory markers involved in capsule formation. METHODS: Twenty consecutive patients underwent immediate, 2-stage, implant-based breast reconstruction with dual-plane HADM. During tissue expander-implant exchange, full-thickness biopsies of biointegrated HADM and native breast capsule (internal control) from the tissue-expander envelope were obtained. Immunohistochemical analysis was performed for endothelial cells (CD31), B cells (CD20), T cells (CD3), macrophages (CD68), collagen I and III, and myofibroblasts (α-smooth muscle actin). Observed levels of marker labeling were semiquantitatively scored from 0 (none) to 3 (severe) by a blinded histopathologist and were statistically analyzed with the Wilcoxon rank sum test. RESULTS: A bilateral sample was obtained from 1 patient; all other samples were unilateral. Compared with capsule samples from native breast tissue, HADM samples had significantly lower levels of all inflammatory markers (P < .001). CONCLUSIONS: These lower levels of inflammatory markers support previous evidence that HADM may inhibit inflammatory and profibrotic signaling characteristics of breast capsule development and decrease the risk of capsular contracture. Further investigation is needed to determine the mechanism by which HADM inhibits these inflammatory cells, whether HADM reduces the incidence of breast capsular contracture, and if so, the longevity of this effect.

Chronic biofilm infection in breast implants is associated with an increased T-cell lymphocytic infiltrate: implications for breast implant-associated lymphoma.

BACKGROUND: Biofilm infection of breast implants significantly potentiates capsular contracture. This study investigated whether chronic biofilm infection could promote T-cell hyperplasia. METHODS: In the pig study, 12 textured and 12 smooth implants were inserted into three adult pigs. Implants were left in situ for a mean period of 8.75 months. In the human study, 57 capsules from patients with Baker grade IV contracture were collected prospectively over a 4-year period. Biofilm and surrounding lymphocytes were analyzed using culture, nucleic acid, and visualization techniques. RESULTS: In the pig study, all samples were positive for bacterial biofilm. There was a significant correlation between the bacterial numbers and grade of capsular contracture (p = 0.04). Quantitative real-time polymerase chain reaction showed that all lymphocytes were significantly more numerous on textured compared with smooth implants (p < 0.001). T cells accounted for the majority of the lymphocytic infiltrate. Imaging confirmed the presence of activated lymphocytes. In the human study, all capsules were positive for biofilm. Analysis of lymphocyte numbers showed a T-cell predominance (p < 0.001). There was a significant linear correlation between the number of T and B cells and the number of detected bacteria (p < 0.001). Subset analysis showed a significantly higher number of bacteria for polyurethane implants (p < 0.005). CONCLUSIONS: Chronic biofilm infection around breast prostheses produces an increased T-cell response both in the pig and in humans. A possible link between bacterial biofilm and T-cell hyperplasia is significant in light of breast implant-associated anaplastic large-cell lymphoma. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.

Biomedical implant capsule formation: lessons learned and the road ahead.

Clinicians and investigators have been implanting biomedical devices into patients and experimental animals for centuries. There is a characteristic complex inflammatory response to the presence of the biomedical device with diverse cell signaling, followed by migration of fibroblasts to the implant surface and the eventual walling off of the implant in a collagen capsule. If the device is to interact with the surrounding tissues, the collagen envelope will eventually incapacitate the device or myofibroblasts can cause capsular contracture with resulting distortion, migration, or firmness. This review analyzes the various tactics used in the past to modify or control capsule formation with suggestions for future investigative approaches.

T regulatory cells and TH17 cells in peri-silicone implant capsular fibrosis.

BACKGROUND: The authors investigated the immunological mechanisms underlying extensive peri-silicone implant capsule formation, one of the most frequent postoperative complications in patients receiving silicone mammary implants. METHODS: The authors studied immune response activation by phenotypic and functional characterization of lymphocytes accumulated within this tissue. Intracapsular lymphoid cells and autologous peripheral blood mononuclear cells were isolated and analyzed by flow cytometry. The proportion of T regulatory cells (CD4+ CD25(high) Foxp3+ CD127), the cytokine profiles, and the T cell receptor repertoire of these cells were examined. Intracapsular T regulatory cells were then further analyzed by immunohistochemistry and functional suppression assays. RESULTS: In comparison with peripheral blood, the cellular composition of intracapsular lymphocytes showed a predominance of CD4+ cells. Intracapsular T cells predominantly produced interleukin-17, interleukin-6, interleukin-8, transforming growth factor-ß1, and interferon-γ, suggesting a TH1/TH17-weighted local immune response. Intracapsular T cells displayed a restricted T cell receptor α/ß repertoire. The intact suppressive potential of T regulatory cells was demonstrated in crossover experiments with activated peripheral T cells. They did not, however, suppress intracapsular T cells. Interestingly, ratios of intracapsular T regulatory cells were inversely proportional to the clinical degree of capsular fibrosis. CONCLUSION: The authors' results indicate that silicone implants trigger a specific, antigen-driven local immune response through activated TH1/TH17 cells, suggesting that ensuing fibrosis is promoted by the production of profibrotic cytokines as a consequence of faltering function of local T regulatory cells.