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.

The Effect of 3-Dimensional-Printed Sequential Dual Drug-Releasing Patch on the Capsule Formation Around the Silicone Implant in a Rat Model.

BACKGROUND: Implant-based breast reconstruction is associated with increased risk of early infection and late-stage capsular contracture. OBJECTIVES: We evaluated the feasibility of a dual drug-releasing patch that enabled the controlled delivery of antibiotics and immunosuppressants in a temporally and spatially appropriate manner to the implant site. METHODS: The efficacy of a dual drug-releasing patch, which was 3-dimensional-printed (3D-printed) with tissue-derived biomaterial ink, was evaluated in rats with silicone implants. The groups included implant only (n = 10); implant plus bacterial inoculation (n = 14); implant, bacterial inoculation, and patch loaded with gentamycin placed on the ventral side of the implant (n = 10), and implant, bacterial inoculation, and patch loaded with gentamycin and triamcinolone acetonide (n = 9). Histologic and immunohistochemical analyses were performed 8 weeks after implantation. RESULTS: The 2 drugs were sequentially released from the dual drug-releasing patch and exhibited different release profiles. Compared to the animals with bacterial inoculation, those with the antibiotic-only and the dual drug-releasing patch exhibited thinner capsules and lower myofibroblast activity and inflammation, indicating better tissue integration and less foreign body response. These effects were more pronounced with the dual drug-releasing patch than with the antibiotic-only patch. CONCLUSIONS: The 3D-printed dual drug-releasing patch effectively reduced inflammation and capsule formation in a rat model of silicone breast reconstruction. The beneficial effect of the dual drug-releasing patch was better than that of the antibiotic-only patch, indicating its therapeutic potential as a novel approach to preventing capsular contracture while reducing concerns of systemic side effects.

Polyurethane Implants in Revisional Breast Augmentation: A Prospective 5-Year Study.

BACKGROUND: Revisional surgery for aesthetic breast augmentation remains a challenging procedure. Polyurethane (PU) implants have been found to avoid capsular contracture recurrence as well as to prevent implant displacement by bio-integrating with the pocket. OBJECTIVES: Our study aimed to assess the use of PU implants in breast revisional surgery and to provide an algorithm. METHODS: Over a 5-year period, a prospective study was conducted involving consecutive patients undergoing implant revision. Patient demographics, previous breast procedures, and specific surgical details were documented. Postoperative outcomes were followed up. RESULTS: Out of 92 patients (184 breasts), 78 (156 breasts) were included in the analysis. The average age was 47.5, with a BMI of 22.3 and a mean follow-up of 5 years. A majority (63%) represented secondary revisional cases, while 37% were tertiary cases. Implant size averaged 296 cc, with 53% placed in retropectoral position and 47% prepectoral. Significantly more implants in secondary cases were changed from prepectoral to retropectoral (P = .005), and in tertiary changed from retropectoral to prepectoral (P = .002). Complete capsulectomy was performed in 61.5% and partial in 25.6%. Additional lipofilling was performed in 32%, and concurrent mastopexy in 40%. Revisional surgery in our series had a 1.9% acute complication rate, 4.5% longer-term reoperation rate for corrections, 0.6% implant exchange rate, and no recurrent capsular contracture. CONCLUSIONS: This is the first study to provide data on outcomes of revisional breast augmentation surgery with PU implants. It shows that polyurethane implants offer consistent stability and have low rates of recurrent capsular contracture in revisional surgery.

Systematic Review of Capsular Contracture Management following Breast Augmentation: An Update.

BACKGROUND: Capsular contracture is one of the most frequent indications for revision following breast augmentation. Management goals focus on restoring breast aesthetics and minimizing subsequent recurrence of capsular contracture. As new data emerge, close review of the data are merited to build evidence-based clinical guidelines to inform surgical practice and management of capsular contracture. METHODS: A systematic review of the MEDLINE, Embase, and Cochrane Database of Systematic Reviews databases was conducted to characterize the surgical management of capsular contracture in revision breast augmentations. The primary endpoint was capsular contracture recurrence rate. RESULTS: The review was conducted in November of 2021. Primary search revealed 14,163 results. Initial screening by title left 1223 articles. Abstract review left 90 articles for full-text review, of which 34 were ultimately included and were all observational in nature. CONCLUSIONS: Capsular contracture management remains an important topic, with limited high-level evidence for establishing clear evidence-based treatment guidelines. Although more evidence is required to assess the effects of capsulectomy, implant exchange, and plane change, these appear to be useful mechanisms for reducing recurrent capsular contracture. There is more evidence regarding the use of acellular dermal matrix, although this still requires long-term follow-up studies. New developments regarding textured implants limit the revision breast augmentation surgeon to smooth devices.

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.

Toward a Consensus Aproach for Assessing Capsular Contracture Severity and Progression: A Systematic Review.

BACKGROUND: Breast implants are the most commonly used medical devices in plastic surgery, and capsular contracture (CC) is one of the most common complications. However, our assessment of CC is based largely on Baker grade, which is problematically subjective and affords only four possible values. METHODS: The authors performed a systematic review concluding in September of 2021 in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. It identified 19 articles that propose approaches to measuring CC. RESULTS: In addition to Baker grade, the authors identified several modalities reported to measure CC. These included magnetic resonance imaging, ultrasonography, sonoelastography, mammacompliance measuring devices, applanation tonometry, histologic evaluation, and serology. Capsule thickness and other measures of CC inconsistently correlated with Baker grade, whereas the presence of synovial metaplasia was consistently associated with Baker grade I and II, but not III and IV capsules. CONCLUSIONS: There remains no particular method to reliably and specifically measure the contracture of capsules that form around breast implants. As such, we would recommend that research investigators use more than one modality to measure CC. Other variables that can impact breast implant stiffness and associated discomfort beyond CC need to be considered when evaluating patient outcomes. Given the value placed on CC outcomes in assessing breast implant safety, and the prevalence of breast implants overall, the need for a more reliable approach to measuring this outcome persists.

Devil's Advocate: Evidence-Based Recommendation for "One Breast-One Insertion Funnel" Policy.

BACKGROUND: Rates of capsular contracture have reduced significantly since the use of insertion funnels to place breast implants became routine. However, due to financial constraints, the same funnel is usually used for implantation of both sides. OBJECTIVES: The aim of this study was to determine whether the risk of capsular contracture is higher for the second breast when the same insertion funnel is used for both breasts. METHODS: The authors collected a sample of the insertion funnel tip immediately after removing the funnel from its sterile packaging and another tip sample after the funnel had been used to insert the first implant. These samples were sent for microbiological culture evaluations. Capsular contracture rates in the first implanted breast vs the second implanted breast were then retrospectively analyzed. RESULTS: All samples taken from the funnel before the first implantation showed no bacterial growth. All 10 samples taken from the funnel after the first implantation showed organism growth (8 were positive for Staphylococcus epidermidis and 2 for Cutibacterium acnes). Retrospective analysis of the results revealed that the overall capsular contracture rate had reduced after the authors began to use insertion funnels. However, this complication was still more common on the second implanted breast. CONCLUSIONS: Surgeons should consider the use of separate insertion funnels for each breast. This might help to slightly reduce the incidence of capsular contracture.See the abstract translated into Hindi, Portuguese, Korean, German, Italian, Arabic, and Chinese (Simplified and Traditional) online here: https://doi.org/10.1093/asj/sjad288.

Efficacy of Acellular Dermal Matrix Type in Treatment of Capsular Contracture in Breast Augmentation: A Systematic Review and Meta-Analysis.

BACKGROUND: Capsular contracture is a known complication of breast augmentation and is among the top reasons for revisional breast augmentation procedures. The use of acellular dermal matrix (ADM) has been shown to reduce the rate of capsular contracture in breast reconstruction and augmentation, theorizing that it acts as a protective barrier between the implant capsule and inflammatory process responsible for capsular contracture. The role of ADM in treatment of capsular contracture has been investigated in numerous studies, with a variety of ADMs. OBJECTIVES: The aim of this study was to perform a systematic review of existing literature on the use of ADM for treatment of capsular contracture in aesthetic breast augmentation patients to investigate differences in efficacy of ADM types. METHODS: The PubMed, Embase, and CINAHL databases were systematically reviewed for articles pertaining to capsular contracture, acellular dermal matrices, and breast augmentation. Number of patients, type of ADM, Baker grade, follow-up time, complication rate, and capsular contracture rate were recorded from identified articles. Data was pooled from studies to calculate a capsular contracture rate for each ADM type, with a chi-squared test performed for analysis. Identified studies with a comparative group were included in a meta-analysis utilizing risk ratio (RR) to assess the efficacy of ADM. RESULTS: Nine articles including ADM for treatment of capsular contracture in breast augmentation met criteria for inclusion, with a total of 481 breasts. Strattice was the most commonly utilized ADM (n = 391), followed by AlloDerm (n = 57). There was a statistically significant difference in efficacy of ADM among the studied ADM types (P < .001). AlloDerm, FlexHD, and DermaMatrix had the lowest capsular contracture rates (0%). NeoForm and SurgiMend had the highest capsular contracture rates (each 25%, but with n = 4 and n = 8, respectively). Strattice had a capsular contracture rate of 1.53% in the pooled data, and meta-analysis showed that Strattice reduced the risk of capsular contracture (RR 0.14 [95% CI 0.06, 0.31]) compared with conventional treatment. CONCLUSIONS: Acellular dermal matrices appear to be effective at treating capsular contracture after breast augmentation while maintaining a low complication rate. Overall capsular contracture rates are low with the use of ADM. There is a statistically significant difference in efficacy among ADM types. Meta-analysis shows that Strattice is effective at reducing the risk of capsular contracture in breast augmentation patients when compared to conventional treatment. Future research, especially in the form of randomized controlled trials, is needed to further investigate the efficacy of various ADMs in the treatment of capsular contracture.

Use of Antimicrobial Irrigation and Incidence of Capsular Contracture in Breast Augmentation and Immediate Implant-Based Breast Reconstruction.

Capsular contracture (CC) is one of the most common complications of implant-based breast reconstruction or augmentation surgery. Common risk factors of CC include biofilm, surgical site infections, history of prior CC or fibrosis, history of radiation therapy, and implant characteristics. Though bacterial contamination of breast protheses is associated with adverse sequelae, there are not universally accepted guidelines and limited best practice recommendations for antimicrobial breast pocket irrigation. Despite advanced molecular biology, the exact mechanism of this complication is not fully understood. Interventions that decrease the rate of CC include antibiotic prophylaxis or irrigation, acellular dermal matrix, leukotriene inhibitors, surgical techniques, and others. However, there is inconsistent evidence supporting these risk factors, and the current data was based on broad heterogeneous studies. The objective of this review was to provide a summary of the current data of contributing risk factors as well as preventative and treatment measures for CC.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 http://www.springer.com/00266.

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.

The Keller Funnel, Capsular Contracture, and Conflict of Interest: A Review.

BACKGROUND: The Keller funnel (Allergan; AbbVie Inc, North Chicago, IL) is commonly used to insert breast implants as part of a "no touch" protocol. Many plastic surgeons believe that this device reduces the risk of capsular contracture. This review was undertaken to evaluate the evidence regarding any reduction in capsular contracture rate, other possible benefits, safety and to investigate financial conflict of interest. METHODS: A PubMed electronic literature search was conducted to identify studies comparing capsular contracture rates with and without the Keller funnel. The Open Payments database was accessed for information regarding corporate payments to plastic surgeons. RESULTS: Two retrospective historical case-control studies, published in 2016 and 2018, were identified. Both studies had important confounders, including implant type and placement, which are known to affect capsular contracture rates. Major financial conflicts of interest were present. Most authors did not disclose these conflicts, which totaled more than $1 million and were usually categorized as gifts from Allergan, which purchased the Keller funnel in 2017. DISCUSSION: Financial conflict of interest, along with publication bias, creates a bias toward publication of positive findings. No reliable evidence supports a "no touch" technique, which is a misnomer because manual handling of implants is unavoidable, even when using a funnel. Recent microbiological studies do not support a specific bacterial etiology for capsular contracture. No evidence supports contamination by the surgeon touching the implant. Among other proposed benefits, such as reduced operating time, less contamination, a shorter incision, and less implant trauma, only a slightly shorter incision (1 cm) is supported by the evidence. The cost is $150 per funnel. CONCLUSIONS: No reliable evidence supports the use of a Keller funnel to reduce the risk of capsular contracture. Both supportive studies contain confounding variables, limited follow-up time, and no plausible scientific basis for efficacy. Institutional review board approval of studies on human subjects is not optional. Financial conflicts of interest are extraordinary in their magnitude and potential for creating undue influence. Greater transparency and honest disclosures are needed.

Capsular Contracture Rate in Augmentation Mammoplasty With Motiva Breast Implant Insertion: A Single-Center Experience in Korea.

BACKGROUND: Capsular contracture is the most common complication following breast implant surgery, and the implant shell characteristics are important in preventing this complication. OBJECTIVES: The aim of this study was to evaluate the capsular contracture rate for SmoothSilk Motiva implants (Establishment Labs Holdings Inc., New York, NY) in females who underwent primary and revisional breast augmentation over a 3-year period. METHODS: A total of 1324 cases that took place from 2017 to 2020 were retrospectively analyzed, with 1027 being primary surgeries and 297 being revisional surgeries. RESULTS: In the 1324 cases of augmentation mammoplasty with SmoothSilk Motiva implants, the overall capsular contracture rate was 1.8% (n = 24). The capsular contracture rate in the 1027 primary surgery cases was 1.07% (n = 11), and the capsular contracture rate in the 297 revisional surgery cases was significantly different at 4.39% (n = 13, P = .0001). More specifically, the capsular contracture rate in 182 revisional surgery for cases without capsular contracture was 1.12% (n = 2), and it showed no statistically significant difference from the rate in primary surgery cases (P = .965). However, the rate in 115 revisional surgery for cases with capsular contracture was 9.57% (n = 11), and it showed a statistically significant difference from the rate in primary surgery cases (P = .000) and the rate in revisional surgery for cases without capsular contracture (P = .001). CONCLUSIONS: Augmentation mammoplasty with SmoothSilk Motiva implants demonstrated a lower rate of capsular contracture than traditional smooth or textured implants. Revisional surgery for cases without capsular contracture showed a similar rate of capsular contracture to primary surgery cases, but the rates were higher in revisional surgery for cases with capsular contracture.

Incision and Capsular Contracture Risk: Is There a Relationship in Breast Augmentation and Augmentation/Mastopexy?

BACKGROUND: Breast implants can be introduced through a variety of incisions, most commonly an inframammary incision, but also a periareolar incision or an axillary incision. Usually, the implant is inserted through the same incision used in performing an augmentation/mastopexy. Some authors use a separate inframammary incision. Capsular contracture is the most common complication of breast augmentation. One theory holds that it is caused by an infected biofilm, prompting surgeons to minimize implant handling, known as the "no touch" technique. This review was undertaken to investigate the relationship, if any, between the access incision and the risk of capsular contracture. METHODS: An electronic literature search was conducted to identify publications comparing capsular contracture rates by the access incision. RESULTS: Ten studies were evaluated. Most were retrospective series. Three were prospective core studies. Some studies reported an increased risk of capsular contracture for a periareolar incision; a similar number did not. One study supported a separate inframammary incision at the time of vertical augmentation/mastopexy. DISCUSSION: Bacterial studies in the last decade show that the resident bacteria on the skin surface and within breast tissue are similar. Sophisticated microbiological evaluation of breast capsules reveals that the microbiome relates to the patient, as opposed to a specific bacterial profile for capsular contracture. A review of the statistics used in determining an advantage for a separate incision at the time of vertical augmentation/mastopexy reveals that there is no statistically significant risk reduction when using an additional inframammary incision, which adds an unnecessary scar. CONCLUSIONS: The access incision at the time of breast augmentation or augmentation/mastopexy is unlikely to affect the capsular contracture risk. There is no need to make a separate incision to insert the implant at the time of augmentation/mastopexy, or to isolate the implant from contact with breast parenchyma. Little evidence supports the "no touch" technique. The etiology of capsular contracture remains unknown.

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 .

Baker Grade IV Capsular Contracture Is Correlated with an Increased Amount of Silicone Material: An Intrapatient Study.

BACKGROUND: Breast implant surgery is one of the most frequently performed procedures by plastic surgeons worldwide. However, the relationship between silicone leakage and the most common complication, capsular contracture, is far from understood. This study aimed to compare Baker grade I with Baker grade IV capsules regarding their silicone content in an intradonor setting, using two previously validated imaging techniques. METHODS: Twenty-two donor-matched capsules from 11 patients experiencing unilateral complaints were included after bilateral explantation surgery. All capsules were examined using both stimulated Raman scattering (SRS) imaging and staining with modified oil red O (MORO). Evaluation was done visually for qualitative and semiquantitative assessment and automated for quantitative analysis. RESULTS: Using both SRS and MORO techniques, silicone was found in more Baker grade IV capsules (eight of 11 and 11 of 11, respectively) than in Baker grade I capsules (three of 11 and five of 11, respectively). Baker grade IV capsules also showed significantly more silicone content compared with the Baker grade I capsules. This was true for semiquantitative assessment for both SRS and MORO techniques ( P = 0.019 and P = 0.006, respectively), whereas quantitative analysis proved to be significant for MORO alone ( P = 0.026 versus P = 0.248 for SRS, respectively). CONCLUSIONS: In this study, a significant correlation between capsule silicone content and capsular contracture is shown. An extensive and continued foreign body response to silicone particles is likely to be responsible. Considering the widespread use of silicone breast implants, these results affect many women worldwide and warrant a more focused research effort. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

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.

Identification of Drug Compounds for Capsular Contracture Based on Text Mining and Deep Learning.

BACKGROUND: Capsular contracture is a common and unpredictable complication after breast implant placement. Currently, the pathogenesis of capsular contracture is unclear, and the effectiveness of nonsurgical treatment is still doubtful. The authors' study aimed to investigate new drug therapies for capsular contracture by using computational methods. METHODS: Genes related to capsular contracture were identified by text mining and GeneCodis. Then, the candidate key genes were selected through protein-protein interaction analysis in Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. Drugs targeting the candidate genes with relation to capsular contracture were screened out in Pharmaprojects. Based on the drug-target interaction analysis by DeepPurpose, candidate drugs with highest predicted binding affinity were obtained eventually. RESULTS: The authors' study identified 55 genes related to capsular contracture. Gene set enrichment analysis and protein-protein interaction analysis generated eight candidate genes. One hundred drugs targeting the candidate genes were selected. The seven candidate drugs with the highest predicted binding affinity were determined by DeepPurpose, including tumor necrosis factor alpha antagonist, estrogen receptor agonist, insulin-like growth factor 1 receptor, tyrosine kinase inhibitor, and matrix metallopeptidase 1 inhibitor. CONCLUSION: Text mining and DeepPurpose can be used as a promising tool for drug discovery in exploring nonsurgical treatment to capsular contracture. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

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.

Stem Cell-Enriched Hybrid Breast Reconstruction Reduces Risk for Capsular Contracture in a Hybrid Breast Model.

BACKGROUND: Hybrid breast reconstruction (HBR) combines silicone implants with fat grafting to improve implant coverage, treating local tissue deficiencies and leading to a more natural breast appearance. Recent data also indicated less capsular contracture after HBR. The authors developed a novel technique and animal model of cell-assisted (CA) HBR to illuminate its effects on capsular contracture. METHODS: Animals received silicone implants in a dorsal submuscular pocket. Although animals of the HBR group received fat grafting around the implant without stem cell enrichment, rats of the CA-HBR1 and the CA-HBR2 groups received stem cell-enriched fat grafting with 2 × 10 6 and 4 × 10 6 adipose-derived stem cells immediately after implant insertion. On day 60, animals underwent sonography and elastography imaging and were euthanized, and outcome analysis was performed by means of histology, immunohistochemistry, chemical collagen quantification, and gene expression analysis. RESULTS: With this novel technique, long-term survival of adipose-derived stem cells within the implant pocket was demonstrated after 60 days after implant insertion. CA-HBR led to significantly reduced thickness and collagen density of capsular contractures. In addition, CA-HBR resulted in reduced fibrotic responses with less occurrence of collagen type I and transforming growth factor-ß in capsule tissue. Moreover, the addition of stem cells suppressed fibrotic and inflammatory responses on a genetic level with significant underexpression of collagen type I and transforming growth factor-ß1. CONCLUSIONS: With this new technique and animal model, the authors observed a preventive effect on capsular contracture substantiating the basis of clinical outcomes of HBR. The authors propose that the addition of stem cells to HBR might booster its beneficial results. CLINICAL RELEVANCE STATEMENT: Stem cell-enriched fat grafting around silicone implants may reduce the risk for capsular contracture after silicone breast implantation. While fat grafting alone already shows beneficial effects, the addition of stem cells to the fat graft can potentiate this effect.