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.

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.

Toll-Like Receptors (TLRs) Expression in Contracted Capsules Compared to Uncontracted Capsules.

INTRODUCTION: The etiology of capsular contracture after surgical implantation of breast implants remains unclear, but an important role is seen for the immune system. Toll-like receptors are immune receptors recognizing both pathogen-associated molecular patterns and damage-associated molecular patterns. The former are present on bacteria such as Staphylococcus epidermidis (bacteria earlier associated with capsular contracture), and the latter are released after (mechanical) stress. The aim of this study was to investigate the expression of TLRs 1-10 in relation to capsular contracture. MATERIALS AND METHODS: Fifty consecutive breast capsules were collected during implant removal or replacement. The extent of capsular contracture was scored according to the Baker score. A sample specimen (0.5 cm3) was obtained from all tissues. cDNA was synthesized from isolated mRNA from the collected specimens. PCR analyses were conducted to test for cDNA presence and to quantify concentration. TLR1-10 expression was measured for each of the Baker scores separately and compared to all Baker scores. RESULTS: Expression of all TLRs in all Baker scores was seen. TLR2 and TLR6 were more often present in contracted samples (Baker 3 or 4) compared to uncontracted samples (Baker 1 or 2) [Baker 2 vs. 3 (p = 0.034) and Baker 2 vs. 3 (p = 0.003), respectively]. None of the TLRs displayed a significantly higher expression in contracted capsules compared to uncontracted capsules. CONCLUSION: This study shows that TLR2 and TLR6 are more often expressed in contracted capsules compared to non-contracted capsules however not in higher concentrations. 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 .

Controlled clinical trial with pirfenidone in the treatment of breast capsular contracture: association of TGF-ß polymorphisms.

BACKGROUND: Breast capsular contracture (BCC) is a commonly adverse event postmammoplastly characterized by an immune response mediated by cytokines and transforming growth factor (TGF)-ß1 resulting in excessive synthesis and deposit of extracellular matrix around the breast implant. Presence of TGF-ß1 polymorphisms has been associated as a risk factor to develop fibroproliferative diseases. METHODS: This open, controlled, prospective, and pilot clinical trial with 6 months duration was carried out to evaluate the efficacy of 1800 mg a day, of oral Pirfenidone (PFD) in the treatment of BCC (Baker Score III/IV) postmammoplasty. Twenty BCC cases received PFD and 14 BCC control cases underwent capsulectomy after 6 months of enrollment. Both groups were followed up for 6 more months up to 12 months to determine the relapse in the absence of PFD. Determination of TGF-ß1 polymorphisms was performed to establish a correlation with capsular contracture. RESULTS: PFD group experienced BCC-reduction in all breasts 6 months after enrollment. Only 1 of 20 cases relapsed after follow-up. In capsulectomy group, 2 of 14 cases presented progression to grade IV during presurgical period. All capsulectomy cases relapsed at end of follow-up. Nearly hundred percent of all patients studied in this protocol had a profibrogenic homozygous TGF-ß1 polymorphism (codon 25; genotype Arg25Arg). CONCLUSIONS: PFD is useful to improve BCC (Baker Score III/IV) postmammoplasty with no relapse after drug administration. There is also an association between capsular contracture and the presence of homozygous G/G TGF-ß1 genotype.

Tumour necrosis factor-α expression is associated with increased severity of periprosthetic breast capsular contracture.

BACKGROUND: The pathogenesis of periprosthetic capsular contracture following breast implant surgery is unclear. The aim of this study was to identify the expression of tumour necrosis factor-α (TNF-α), collagen type III α(1) (COL3A1), transforming growth factor-ß(1) (TGF-ß(1)) and connective tissue growth factor (CTGF) in different Baker grades of breast capsular contracture. METHODS: Seven periprosthetic breast capsule specimens were collected from 6 patients. TNF-α, COL3A1, TGF-ß(1) and CTGF gene expression were analysed using real-time quantitative polymerase chain reaction. Immunohistolocalisation of TNF-α was performed on paraffin-embedded sections. Significant correlations were analysed using the Pearson correlation coefficient. RESULTS: TNF-α expression was associated with increased Baker grade of capsular contracture (Pearson correlation, r = 0.558; p = 0.02). COL3A1 gene expression was reduced with increasing severity of contracture (r = -0.490; p = 0.05). There were no significant correlations between TGF-ß(1) and CTGF expression with Baker grade. Positive TNF-α staining in breast capsules was localised to fibroblasts, macrophages, and extracellularly close to the prosthesis. CONCLUSION: The increased expression of TNF-α may play a key role in the inflammatory response associated with capsular contracture. The corresponding decrease in COL3A1 may contribute to the change in capsular physical properties seen in capsular contracture.