Plastic Surgery Research Council

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Differential Gene Expression in Capsules from Smooth versus Textured Silicone Implants
Giulia Daneshgaran, BS1, Daniel Gardner, MD2, Annie Chen, MD1, Solmaz Niknam-Bienia, MD1, Vinaya Soundararajan, MD1, Maxwell B. Johnson, MD1, Alexander Fedenko, MD, PhD1, Regina Y. Baker, MD1, Alex K. Wong, MD1.
1University of Southern California, Los Angeles, CA, USA, 2University of California, Irvine, Irvine, CA, USA.

PURPOSE: Capsular contracture is the most common complication of implant-based breast surgery in the US, leading to abnormal breast contour, increased firmness, and pain to touch. It is known that smooth implants have higher rates of capsular contracture. Assessing the effect of implant texture on contracture pathogenesis may help identify therapeutic targets. The purpose of this study is to elucidate the pathogenesis of capsular contracture by examining RNA expression in a rat model of capsular formation around textured and smooth silicone implants, with pathological correlation.
METHODS: Ten Fischer rats underwent miniature smooth or textured silicone implant insertion into a subcutaneous flank pocket. Six weeks postoperatively, implant capsules were harvested for histological and molecular analysis. RNA sequencing was performed to identify target genes expressed in extracted capsules. Selected gene expression levels were confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Implant capsules collected from patients with and without capsular contracture were analyzed and correlated with results from our animal model.
RESULTS: RNA sequencing data was subjected to the Probability of Positive Log Ratio (PPLR) algorithm. Transcripts were identified for further characterization using cutoff values of PPLR >= 0.975 (2-fold increase) or a PPLR <= 0.025 (2-fold decrease). We identified 18,555 transcripts that met PPLR inclusion criteria. Quantitative RT-PCR was performed for matrix metalloproteinase 3 (MMP3), troponin T3 (TNNT3), and neuregulin 1 (NRG1). Expression of MMP3 and TNNT3 was downregulated in smooth implant capsules, with a fold difference of -2.04 (p=<0.006) and -3.03 (p=<0.0056), respectively. Expression of NRG1 was upregulated in smooth implant capsules with a fold difference of +2.65 (p=<0.0001). IHC staining of capsules extracted from our animal model was consistent with differential expression patterns, with smooth implant capsules expressing less MMP3 and TNNT3, and more NRG1 than textured implant capsules. Similarly, IHC staining of human specimens revealed that contracted capsules had lower expression of MMP3 and TNNT3, and greater expression of NRG1 compared to healthy capsules.
CONCLUSION: We demonstrate that capsules around smooth and textured implants have different histological appearances and different patterns of gene expression. Importantly, pathological correlation reveals that contracted capsules have expression patterns for MMP3, TNNT3 and NRG1 that are consistent with capsules derived from smooth implants, which are known to have higher contracture rates. These results may help elucidate the mechanism of capsular contracture and identify potential genes for the development of future therapeutic targets for this condition.


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