Development and Validation of a Diagnostic Histopathological Scoring System for Capsular Contracture Based on 720 Breast Implant Capsules.

BACKGROUND: Capsular contracture is traditionally evaluated with the Baker classification, but this has notable limitations regarding reproducibility and objectivity. OBJECTIVES: The aim of this study was to develop and validate procedure-specific histopathological scoring systems to assess capsular contracture severity. METHODS: Biopsies of breast implant capsules were used to develop histopathological scoring systems for patients following breast augmentation and breast reconstruction. Ten histological parameters were evaluated by multivariable logistic regression to identify those most associated with capsular contracture. Significant parameters (P < .05) were selected for the scoring systems and assigned weighted scores (1-10). Validation was assessed from the area under the curve (AUC) and the mean absolute error (MAE). RESULTS: A total of 720 biopsies from 542 patients were included. Four parameters were selected for the augmentation scoring system, namely, collagen layer thickness, fiber organization, inflammatory infiltration, and calcification, providing a combined maximum score of 26. The AUC and MAE for the augmentation scoring system were 81% and 0.8%, which is considered strong. Three parameters were selected for the reconstruction scoring system, namely, fiber organization, collagen layer cellularity, and inflammatory infiltration, providing a combined maximum score of 19. The AUC and MAE of the reconstruction scoring system were 72% and 7.1%, which is considered good. CONCLUSIONS: The new histopathological scoring systems provide an objective, reproducible, and accurate assessment of capsular contracture severity. We propose these novel scoring systems as a valuable tool for confirming capsular contracture diagnosis in the clinical setting, for research, and for implant manufacturers and insurance providers in need of a confirmed capsular contracture diagnosis.

CD248 Regulates Inflammation and Encapsulation in Silicone-Related Capsule Formation.

BACKGROUND: Capsular contracture is the most common reason for having a secondary breast implant operation. The failure of the implanted device and discomfort are related to foreign body response, which involves a pathologic encapsulation. An up-regulated expression of CD248 was previously demonstrated to modulate inflammation and fibrosis. The authors hypothesized that CD248 contributes to foreign body reaction and contracture during silicone-stimulated capsule formation. METHODS: A murine capsular contracture model was established to correlate CD248 with capsular contracture. The timing and site of CD248 expression were characterized by protein analysis and histologic examination. The capsules between wild-type mice and CD248 knockout mice were compared in this model to verify the possible role of CD248 in silicone-related capsule formation. RESULTS: CD248 was expressed in the peri-silicone implant capsule by stromal fibroblast and perivascular fibroblast. CD248 was overexpressed on day 4 and down to a constant level, but it was still up-regulated through day 21 to day 56 after silicone implantation. The CD248 knockout mice showed a prolonged inflammation period, whereas the wild-type mice developed a thinner but more collagenous capsule. CONCLUSIONS: In conclusion, an effective murine capsular contracture model was established to study the relationship between CD248 and capsular contracture. CD248 may play a role in inflammation and encapsulation during silicone implantation. CD248 deletion in mice contributed to a loose and irregular collagen bundle in a capsule area, implying a decrease in contracture. Therefore, CD248 could be a potential therapeutic target in capsular contracture. CLINICAL RELEVANCE STATEMENT: CD248 may play a role in inflammation and encapsulation during silicone implantation. It could be a potential therapeutic target in clinical capsular contracture.

Reducing Peri-implant Capsule Thickness in Submuscular Rodent Model of Breast Reconstruction With Delayed Radiotherapy.

INTRODUCTION: Capsular contracture remains the most common complication following device-based breast reconstruction, occurring in up to 50% of women who also undergo adjuvant radiotherapy either before or after device-based reconstruction. While certain risk factors for capsular contracture have been identified, there remains no clinically effective method of prevention. The purpose of the present study is to determine the effect of coating the implant with the novel small molecule Met-Z2-Y12, with and without delayed, targeted radiotherapy, on capsule thickness and morphologic change around smooth silicone implants placed under the latissimus dorsi in a rodent model. METHODS: Twenty-four female Sprague Dawley rats each had 2 mL smooth round silicone breast implants implanted bilaterally under the latissimus dorsi muscle. Twelve received uncoated implants and twelve received implants coated with Met-Z2-Y12. Half of the animals from each group received targeted radiotherapy (20 Gray) on postoperative day ten. At three and 6 months after implantation, the tissue surrounding the implants was harvested for analysis of capsular histology including capsule thickness. Additionally, microCT scans were qualitatively analyzed for morphologic change. RESULTS: Capsules surrounding Met-Z2-Y12-coated implants were significantly thinner (P = 0.006). The greatest difference in capsule thickness was seen in the irradiated 6-month groups, where mean capsule thickness was 79.1 ± 27.3 µm for uncoated versus 50.9 ± 9.6 µm for Met-Z2-Y12-coated implants (P = 0.038). At the time of explant, there were no capsular morphologic differences between the groups either grossly or per microCT. CONCLUSIONS: Met-Z2-Y12 coating of smooth silicone breast implants significantly reduces capsule thickness in a rodent model of submuscular breast reconstruction with delayed radiotherapy.

Breast Implant Capsule: A Murine Model Comparing Capsular Contracture Susceptibility Among Six Breast Implants Available in the Market.

BACKGROUND: Breast implant capsule development and behavior are mainly determined by implant surface combined with other external factors such as intraoperative contamination, radiation or concomitant pharmacologic treatment. Thus, there are several diseases: capsular contracture, breast implant illness or Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL), that have been correlated with the specific type of implant placed. This is the first study to compare all major implant and texture models available in the market on the development and behave of the capsules. Through a histopathological analysis, we compared the behavior of different implant surfaces and how different cellular and histological properties give rise to different susceptibilities to develop capsular contracture among these devices. METHODS: A total of 48 Wistar female rats were used to implant 6 different types of breast implants. Mentor®, McGhan®, Polytech polyurethane®, Xtralane®, Motiva® and Natrelle Smooth® implants were employed; 20 rats received Motiva®, Xtralane® and Polytech polyurethane®, and 28 rats received Mentor®, McGhan® and Natrelle Smooth® implants. The capsules were removed five weeks after the implants placement. Further histological analysis compared capsule composition, collagen density and cellularity. RESULTS: High texturization implants showed the highest levels of collagen and cellularity along the capsule. However, polyurethane implants capsules behaved differently regarding capsule composition, with the thickest capsules but fewer collagen and myofibroblasts than expected, despite being generally considered as a macrotexturized implant. Nanotextured implants and microtextured implants histological findings showed similar characteristics and less susceptibility to develop a capsular contracture compared with smooth implants. CONCLUSIONS: This study shows the relevance of the breast implant surface on the definitive capsules' development, since this is one of the most differentiated factors that determine the incidence of capsular contracture and probably other diseases like BIA-ALCL. A correlation of these findings with clinical cases will help to unify implant classification criteria based on their shell and their estimated incidence of capsule-associated pathologies. Up to this point, the establishment of additional groups is recommended as nanotexturized implants seem to behave differently to pure smooth surfaces and polyurethane implants present diverse features from macro- or microtextured implants. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Difference in the Occurrence of Capsular Contracture According to Tissue Characteristics in an Irradiated Rat Model.

BACKGROUND: This study was performed to evaluate the hypothesis that capsule formation varies according to the radiation dose in muscle tissues; chest wall tissues, including the ribs; and acellular dermal matrices (ADM) that are in contact with the silicone implant. METHODS: In this study, 20 Sprague-Dawley rats underwent submuscular plane implant reconstruction using ADM. They were divided into four groups: an unradiated control group ( n = 5), nonfractionated radiation at a dose of 10 Gy ( n = 5), nonfractionated radiation at a dose of 20 Gy ( n = 5), and fractionated radiation at a dose of 35 Gy ( n = 5). Three months after surgery, hardness was measured, and histologic and immunochemical analyses of the capsule tissues of the ADM, muscle tissues, and chest wall tissues were analyzed. RESULTS: As the radiation dose increased, the silicone implant became harder, but no significant difference in capsule thickness according to the radiation dose was observed. Based on the tissue in contact with the silicone implant, ADM had a thinner capsule thickness than the muscle tissues, as well as less inflammation and less neovascularization compared with the other tissues. CONCLUSIONS: This study describes a new rat model of clinically relevant implant-based breast reconstruction using a submuscular plane and ADM with irradiation. The ADM in contact with the silicone implant, even after irradiation, was protected from radiation compared with the other tissues. CLINICAL RELEVANCE STATEMENT: These research results could support the use of ADM in implant-based breast reconstruction for prevention of the capsular contracture, even after radiation.

An Antifibrotic Breast Implant Surface Coating Significantly Reduces Periprosthetic Capsule Formation.

BACKGROUND: The body responds to prosthetic materials with an inflammatory foreign body response and deposition of a fibrous capsule, which may be deleterious to the function of the device and cause significant discomfort for the patient. Capsular contracture (CC) is the most common complication of aesthetic and reconstructive breast surgery. The source of significant patient morbidity, it can result in pain, suboptimal aesthetic outcomes, implant failure, and increased costs. The underlying mechanism remains unknown. Treatment is limited to reoperation and capsule excision, but recurrence rates remain high. In this study, the authors altered the surface chemistry of silicone implants with a proprietary anti-inflammatory coating to reduce capsule formation. METHODS: Silicone implants were coated with Met-Z2-Y12, a biocompatible, anti-inflammatory surface modification. Uncoated and Met-Z2-Y12-coated implants were implanted in C57BL/6 mice. After 21, 90, or 180 days, periprosthetic tissue was removed for histologic analysis. RESULTS: The authors compared mean capsule thickness at three time points. At 21, 90, and 180 days, there was a statistically significant reduction in capsule thickness of Met-Z2-Y12-coated implants compared with uncoated implants ( P < 0.05). CONCLUSIONS: Coating the surface of silicone implants with Met-Z2-Y12 significantly reduced acute and chronic capsule formation in a mouse model for implant-based breast augmentation and reconstruction. As capsule formation obligatorily precedes CC, these results suggest contracture itself may be significantly attenuated. Furthermore, as periprosthetic capsule formation is a complication without anatomical boundaries, this chemistry may have additional applications beyond breast implants, to a myriad of other implantable medical devices. CLINICAL RELEVANCE STATEMENT: Coating of the silicone implant surface with Met-Z2-Y12 alters the periprosthetic capsule architecture and significantly reduces capsule thickness for at least 6 months postoperatively in a murine model. This is a promising step forward in the development of a therapy to prevent capsular contracture.

Histologic and Immunohistochemical Evaluation of Human Breast Capsules Formed around Five Different Expander Surfaces.

BACKGROUND: Polyurethane (PU) coating and implant texturization were designed to reduce the incidence of capsular contracture (CC), even if the link between surface type and CC remains unclear. To date, the etiopathogenetic aspects have not been fully clarified. The aim of this study was to evaluate capsules formed around five different breast expanders. METHODS: Thirty patients were divided into randomized groups implanted with five different expanders: smooth, coated with PU foam (poly), with a low-microtextured, high-microtextured, and macrotextured surface (L-micro, H-micro, macro). Specimens of the capsules were removed at implant reconstruction and evaluated for morphology and immunohistochemistry expression of α-smooth muscle actin (α-SMA), collagen type I and III, CD68, CD34, and CD3. Remodeling Combined Index was also evaluated. RESULTS: Expression of α-SMA was significantly increased in smooth capsules versus poly, low-microtextured, and high-microtextured groups ( P = 0.007; P = 0.010; P = 0.028), whereas the prevalence of collagen type I in smooth capsules and collagen type III in poly capsules identified a stable versus an unstable tissue. Remodeling Combined Index and α-SMA showed an inverted correlation. CD68 and CD34 cellular expression increased significantly in poly capsules with respect to smooth ( P < 0.001; P < 0.001) and macrotextured groups ( P < 0.001; P < 0.001). CD3 showed no significant difference among the groups. CONCLUSION: In this human study, the authors observed that increased tissue remodeling and reduced myofibroblast activation, along with the inflammatory infiltration and neoangiogenesis, especially in the poly and low-microtextured groups, might promote the formation of an unstable and less fibrotic capsule, lowering the risk of CC. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The role of fat grafting on contracted breast implant capsules: A retrospective comparative histological and immunohistochemical study.

Capsular contracture, a common complication of breast implant reconstruction following postmastectomy radiotherapy (PMRT), represents a challenge for plastic surgeons. Regenerative surgery with multiple autologous fat grafts (lipobed) before replacing the implant has been proven to be a satisfactory approach in the radio-damaged breast. Currently, in literature, there are no data available on the histological features of irradiated capsules after regenerative surgery. We enrolled 80 patients after immediate subpectoral alloplastic breast reconstruction, with indication for revision surgery due to grade IV capsular contracture developed after PMRT. Forty patients were undergoing multiple fat grafting (lipobed group, mean age 48) and 40 patients were not undergoing multiple fat grafting (non-regenerative surgery (NRS) group, mean age 49). The removed capsules were addressed to histological and immunohistochemical assessment. The capsules of the lipobed group patients compared with NRS group patients showed: a lower mean thickness (602.17 versus 670.43 µm; P = 0.013), a lower collagen fiber alignment (median value of angle deviation: 30.34 versus 18.38; P = 0.001), a lower immunohistochemical positivity for myofibroblasts (α-smooth muscle actin [α-SMA] expression: 12.5% versus 52.5%; P = 0.00), a higher immunohistochemical positivity for estrogen receptor-ß (ER-ß; 80% versus 20%; P = 0.00), and a lower immunohistochemical positivity for estrogen receptor-α (ER-α; 53.3% versus 16.7%; P = 0.00). The histological and immunohistochemical differences found are possibly due to alterations in the extracellular microenvironment determined by grafted fat.

Acellular Dermal Matrix-Associated Contracture: A Clinical and Histologic Analysis of Patients Undergoing Prosthetic Breast Reconstruction.

BACKGROUND: Capsular contracture is a well-recognized complication following prosthetic breast reconstruction. It has been the authors' observation that some patients undergoing breast reconstruction experience contracture specifically of the acellular dermal matrix placed at the time of their tissue expander insertion. The goal of the authors' study was to identify clinical and histologic findings associated with the development of acellular dermal matrix-associated contracture. METHODS: The authors performed a retrospective cohort study of all patients undergoing bilateral implant-based breast reconstruction performed by the senior author (M.S.A.). Patients were excluded if they had radiation therapy to the breast. Patients with suspected acellular dermal matrix-associated contracture were identified by clinical photographs and review of operative notes. Histologic analysis was performed on specimens taken from two patients with acellular dermal matrix contracture. RESULTS: The authors included a total of 46 patients (92 breasts), of which 19 breasts had suspected acellular dermal matrix-associated contracture. Acellular dermal matrix contracture was less common in direct-to-implant reconstruction (4.2 percent versus 26.5 percent; p = 0.020) and more common in breasts that had seromas (0 percent versus 15.8 percent; p = 0.001) or complications requiring early expander replacement. Contracted acellular dermal matrix had less vascularity and a lower collagen I-to-collagen III ratio, and was twice as thick as noncontracted acellular dermal matrix. CONCLUSIONS: The authors have described a distinct phenomenon of acellular dermal matrix-associated contracture that occurs in a small subset of breasts where acellular dermal matrix is used. This merits further investigation. Future work will be required to better characterize the clinical factors that make acellular dermal matrix-associated contracture more likely to occur. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Angiotensin-Converting Enzyme Inhibitor Reduces Radiation-Induced Periprosthetic Capsular Fibrosis.

BACKGROUND: The capsular contracture is one of the main complications after radiotherapy in patients with implant-based reconstruction. The aim of this study is to evaluate the efficacy of ramipril for the prevention of radiation-induced fibrosis around the silicone implant. MATERIALS AND METHODS: Thirty Wistar rats in 5 groups were used. Group 1: implant; group 2: implant + radiation; group 3: ramipril + implant; group 4: ramipril + implant + radiation; group 5: sham. Ramipril treatment was started 5 d before surgery and continued for 12 wk after surgery. A mini silicone implant was placed in the back of the rats. A single fraction of 21.5 Gy radiation was applied. Tissues were examined histologically and immunohistochemically (TGF-ß1, MMP-2, and TIMP-2 expression). The alteration of plasma TGF-ß1 levels was examined before and after the experiment. RESULTS: After applying implant or implant + radiation, capsular thickness, percentage of fibrotic area, tissue and plasma TGF-ß1 levels significantly increased, and MMP-2/TIMP-2 ratio significantly decreased compared with the sham group. In ramipril-treated groups, the decrease in capsular thickness, fibrosis, TGF-ß1 positivity, and an increase in MMP-2/TIMP-2 ratio were found significant. In the ramipril + implant + radiation group, the alteration values of TGF-ß1 dramatically decreased. CONCLUSIONS: Our results show that ramipril reduces radiation-induced fibrosis and contracture. The results of our study may be important for the design of the clinical trials required to investigate the effective and safe doses of ramipril, which is an inexpensive and easily tolerated drug, on humans.

Does methylene blue increases capsular contracture in immediate breast reconstruction with silicone implant? An experimental study.

Recently, most of the immediate breast reconstructions following mastectomy are being carried out with the use of silicone implants. In these patients, methylene blue is being used for the detection of sentinel lymph nodes. This experimental study was performed to determine the effect of methylene blue on capsular contracture around breast implants. Thirty-two Sprague Dawley rats were divided into 4 groups. Custom made silicone blocks were placed on the back of animals. In group 1, the incision was closed without performing any additional procedure. In group 2 (control), 0.1 mL of 0.9% normal saline was instilled into the pocket. Group 3 and 4 (study groups) received 0.1 and 0.2 mL of 1% methylene blue, respectively. On postoperative day 60, implants and capsular tissue were extracted. Capsule formation was evaluated both macroscopically and microscopically. The histological evaluation included capsule thickness, inflammation, neovascularization, and fibrosis gradients. Regarding capsule thickness, there were statistically significant differences between groups 1-3, 1-4, 2-3, and 2-4. Although there were more moderate and severe inflammation gradients in groups III and IV, there was no significant difference regarding inflammation severity between control and study groups. In respect of vascular proliferation, there was a statistically significant difference between control and study groups. Similarly, fibrosis gradients were higher in both groups 3 and 4. The study showed that the injection of methylene blue around silicone implants enhanced the formation of capsular contracture. In this case, the degree of contracture was independent of the dose given. Abbreviations: CC: capsular contracture; MM: methylene blue; SLNB: sentinel lymph node biopsy; NS: normal saline; H&E: hematoxylin and eosin; D: dorsal; V: ventral; L: lateral; n: frequency.

The Effect of Omega-3 Fatty Acids on Capsular Tissue around the Breast Implants.

BACKGROUND: One of the most common complications of the use of foreign material, in both reconstructive and cosmetic breast surgery, is capsular contracture. Historically, research on capsular contracture has focused mainly on reducing bacterial contamination through antibiotic solutions. Only secondary studies have focused on pharmacological control of the inflammation process, with particular attention paid to the main inflammation pathway, the arachidonic acid cascade. An important role in the arachidonic acid cascade is played by the omega-3 fatty acids, which are found mainly in oily fish and food supplements. The goal of the present study was to investigate the effects of omega-3 supplements on capsule contraction. METHODS: Female C57BL/6 mice were implanted with custom-made silicone gel implants and divided into two groups. The treated group received omega-3 oil daily while the control group received water daily by gavage. After mice were euthanized, samples of capsules were collected to evaluate thickness and transforming growth factor (TGF)-ß expression. RESULTS: The results showed that capsules in the omega-3 group were thinner and more transparent than those found in the control group. In addition, a significant downregulation of the TGF-ß2 gene transcript was observed in the omega-3 group. CONCLUSIONS: Omega-3 supplementation seems to be effective in reducing the occurrence of capsular formation, mainly through inhibition of the TGF-ß pathway and impairment of collagen deposit. Omega-3 supplementation is a simple and promising method that could be used to prevent or at least reduce capsular contracture after silicone implant surgery.

Hypoxia-induced epithelial-mesenchymal transition and fibrosis for the development of breast capsular contracture.

Fibrosis has been considered as a major cause of capsular contracture. Hypoxia has widely emerged as one of the driving factors for fibrotic diseases. The aim of this study was to examine the association between hypoxia-induced fibrosis and breast capsular contracture formation. Fibrosis, epithelial-mesenchymal transition (EMT), expression levels of hypoxia-inducible factor-1α (HIF-1α), vimentin, fibronectin, and matrix metalloproteinase-9 (MMP-9) in tissues from patients with capsular contracture were determined according to the Baker classification system. Normal breast skin cells in patients with capsular contracture after implant-based breast surgery and NIH3T3 mouse fibroblasts were cultured with cobalt chloride (CoCl2) to mimic hypoxic conditions. Treatment responses were determined by detecting the expression of HIF-1α, vimentin, fibronectin, N-cadherin, snail, twist, occludin, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2, as well as phosphorylated ERK. The expression levels of HIF-1α, vimentin, fibronectin, and fibrosis as well as EMT were positively correlated with the severity of capsular contracture. MMP-9 expression was negatively correlated the Baker score. Hypoxia up-regulated the expression of HIF-1α, vimentin, fibronectin, N-cadherin, snail, twist, TIMP-1 and -2, as well as phosphorylated ERK in normal breast skin cells and NIH3T3. Nonetheless, the expression levels of MMP-9 and occludin were down-regulated in response to CoCl2 treatment. This study is the first to demonstrate the association of hypoxia-induced fibrosis and capsular contracture.

Long-term studies on the integration of acellular porcine dermis as an implant shell and the effect on capsular fibrosis around silicone implants in a rat model.

Acellular dermal matrices have recently increasingly been used in alloplastic breast reconstruction with silicone breast implants. Among these matrices, acellular porcine dermis (APD) is frequently applied, but long-term data on tissue integration and capsular fibrosis formation are still missing. Silicone prostheses with (group A) and without (group B) APD as an implant-covering shell were implanted in male Lewis rats. At 3, 12, and 52 weeks after implantation, the constructs were explanted. Molecular biological and immunohistochemical analyses were performed afterwards. On comparing the collagenous layer and the newly formed myofibroblast-rich layer around the implants of both groups, it became apparent that in group A, these layers were thinner, followed by a lower expression of TGFß1 after 12 and 52 weeks. Further, in this group, at the endpoint of 52 weeks, a lower amount of CD68-positive cells in the collagenous and myofibroblast-rich layers were observed and the expression of TNFα was reduced, while the number of Ki67-positive cells was significantly higher with time. Furthermore, MMP1 expression in group A was lower than that in group B, and the calculated ratio of MMP1:TIMP1 expression was higher. The long-term results clearly show a reduction in inflammatory and fibrotic tissue reaction when APD is used to cover silicone prostheses. These experimental data will be of considerable importance for implant-based breast surgery, as they indicate a potential benefit in the reduction of capsular fibrosis formation of an interposition of APD between the recipient and the silicone implant.

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.

Smooth Muscle Alpha Actin Immunoexpression (α-Sma) and CD-117 Antibody (C-Kit) in Capsules Formed by Polyurethane Foam-Coated Silicone Implants and with Textured Surface: A Study on Rats.

BACKGROUND: One of the undesirable complications that might occur after breast augmentation with silicone implants is capsular contracture. In its etiology, the relations between mast cells and myofibroblasts play an important role in collagen synthesis. Mast cells are able to activate fibroblasts into myofibroblasts, through paracrine secretions, inducing collagen production. The objectives of this study were to analyze the myofibroblast concentration through the α-SMA immunomarker and evaluate the intensity of mast cell expression against the C-Kit immunomarker. MATERIAL AND METHOD: Sixty-four Wistar rats were used, divided into two groups (polyurethane foam and textured surface) with 32 animals in each. The animals received silicone implants on the back, below the panniculus carnosus, and after the determined period, they were killed and the capsules formed around the implants were studied. The capsules were analyzed employing the immunohistochemical technique, with the α-SMA and C-Kit immunomarkers in subgroups of 30, 50, 70 and 90 days. RESULTS: The myofibroblast concentration was higher in the polyurethane group when compared to the textured group (30 days p = 0.105; 50 days p = 0.247; 70 days p = 0.014 and 90 days p = 0.536). The intensity of mast cell expression was more pronounced in the polyurethane group when compared to the textured group (30 days p = 0.798; 50 days p = 0.537; 70 days p = 0.094 and 90 days p = 0.536). CONCLUSIONS: Polyurethane-coated implants induced higher concentrations of myofibroblasts and higher expression of mast cells, when compared to the textured surface implants. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Step Forward Toward the Understanding of the Long-Term Pathogenesis of Double Capsule Formation in Macrotextured Implants: A Prospective Histological Analysis.

BACKGROUND: Although increasingly reported in the literature, most plastic surgeons cannot define the etiology of double capsules. Often an incidental finding at implant exchange, double capsules are frequently associated with macrotextured devices. Several mechanisms have been proposed, including at the forefront that shearing causes a delamination of the periprosthetic capsule into a double capsule. OBJECTIVES: This study was designed to confirm the hypothesis that mechanical forces are involved in formation of double capsules by histological analysis. METHODS: A prospective analysis of consecutive implants with double capsules removed over 2 years was performed. Data collected at the time of surgery included Baker classification, reason for explant, implant manufacturer and style, and any presence of a seroma associated with the capsule. Specimens were sent for analysis by histology utilizing hematoxylin and eosin and alpha-smooth muscle actin staining techniques. RESULTS: Eight double capsules were collected for specimen analysis. All capsules demonstrated evidence of granulation tissue, alpha-smooth muscle actin positive myofibroblasts, and folds with embedded texture. Fibrosis surrounded weak areas with presence of layering and splitting, creating a potential space that is prone to separation. Tears and folds from granulomatous reaction are also present within the outer layer of the double capsule, which can only be explained by a mechanical shearing force as a pathogenic mechanism. CONCLUSIONS: Understanding the pathogenesis of double capsules may allow plastic surgeons to refine their indications for macrotextured implants while providing guidance to patients on avoidance of activities that produce shear-forces. The findings support the hypothesis that shearing forces delaminate the capsule into 2 separate distinct capsules.

The Histological Composition of Capsular Contracture Focussed on the Inner Layer of the Capsule: An Intra-Donor Baker-I Versus Baker-IV Comparison.

BACKGROUND: Capsular contracture remains one of the major complications after breast implantation surgery. The extent of capsular contraction is scored using the Baker scale. The aim of this study was to compare intra-individual Baker-I with Baker-IV capsules, and in particular the prevalence and histological properties of the inner capsule layer. METHODS: Twenty capsules from ten patients were included after bilateral explantation surgery due to unilateral capsular contracture (Baker-IV) after cosmetic augmentation with textured implants. All capsules underwent (immune-)histochemical analysis: haematoxylin-eosin (morphology), CD68 (macrophages), cytokeratin (epithelial cells) and vimentin (fibroblasts), and were visually scored for cell density and the presence of an inner layer and measured for thickness. RESULTS: Baker-IV (n = 10) capsules were significantly thicker compared to Baker-I (n = 10) capsules (P = 0.004). An inner layer was present in 8 Baker-I capsules. All Baker-I capsules were vimentin and CD68-positive and cytokeratin-negative. Positive vimentin was seen throughout the inner layer, and CD-68 staining was observed adjacent to the intermediate capsule layer. In contrast, only 2 Baker-IV capsules had an inner layer, of which only 1 showed the same profile as Baker-I capsules (P = 0.016). No cytokeratin positivity was seen in any capsule. In Baker-IV capsules, outer layers showed more positivity for both vimentin and CD68. CONCLUSION: The inner layer is morphologically consistent with synovial metaplasia and is more prevalent in healthy, uncontracted Baker-I capsules. This inverse relation between the presence of the inner layer and higher Baker classification or pathological contracture could indicate a protective role of the inner layer against capsular contracture formation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Non-linear optical microscopy and histological analysis of collagen, elastin and lysyl oxidase expression in breast capsular contracture.

BACKGROUND: Capsular contracture is one of the most common complications in surgical interventions for aesthetic breast augmentation or post-mastectomy breast reconstruction involving the use of silicone prostheses. Although the precise cause of capsular contracture is yet unknown, the leading hypothesis is that it is caused by long-term unresolved foreign body reaction towards the silicone breast implant. To authors' best knowledge, this is the first study that elucidates the presence of lysyl oxidase (LOX)-an enzyme that is involved in collagen and elastin crosslinking within fibrous capsules harvested from patients with severe capsular contracture. It was hypothesized that over-expression of LOX plays a role in the irreversible crosslinking of collagen and elastin which, in turn, stabilizes the fibrous proteins and contributes to the progression of capsular contracture. METHODS: Eight fibrous capsules were collected from patients undergoing capsulectomy procedure, biomechanical testing was performed for compressive Young's moduli and evaluated for Type I and II collagen, elastin and LOX by means of non-linear optical microscopy and immunohistology techniques. RESULTS: Observations revealed the heterogeneity of tissue structure within and among the collected fibrous capsules. Regardless of the tissue structure, it has been shown that LOX expression was intensified at the implant-to-tissue interface. CONCLUSION: Our results indicate the involvement of LOX in the initiation of fibrous capsule formation which ultimately contributes towards the progression of capsular contracture.