Capsular Contracture In Silicone Breast Implants: Insights From Rat Models

VIEIRA, VILBERTO J.; D'ACAMPORA, ARMANDO; NEVES, FERNANDA S.; MENDES, PAULO R.; VASCONCELLOS, ZULMAR A. DE; NEVES, RODRIGO D'EÇA; FIGUEIREDO, CLAUDIA P.

doi:10.1590/0001-3765201620150874

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Biomedical Sciences • An. Acad. Bras. Ciênc. 88 (3) • Sept 2016 • https://doi.org/10.1590/0001-3765201620150874 copy

Capsular Contracture In Silicone Breast Implants: Insights From Rat Models

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Breast augmentation with silicone implants is one of the most common procedures performed by plastic surgeons around the world. Capsular contracture is a frequent complication in breast augmentation and reconstructive surgery, that requires invasive intervention. The inflammatory response to implanted mammary prostheses appears to be directly associated to capsular contracture. This review discusses the evidences from rat models studies, on the role of inflammation and fibrosis in capsular contraction and its relation to silicone breast implants surface.

Key words:
capsular contracture; silicone breast implant; breast augmentation; smooth silicone implants; textured silicone implants; polyurethane-coated silicone implants

Implant Generation	Period	Characteristics
First Generation	1962-1970	Thick, two-piece shell Smooth surface Anatomically-shaped (teardrop) Viscous silicone gel
Second Generation	1970-1982	Thin, slightly permeable shell Smooth surface Round shape Less viscous silicone gel
Third Generation	1982-1992	Thick, strong, low-bleed shell Smooth surface Round shape More viscous silicone gel
Fourth Generation	1993-present	Thick, strong, low-bleed shell Smooth and textured surfaces Round and anatomically-shaped More viscous (cohesive) silicone gel
Fifth Generation	1993-present	Thick, strong, low-bleed shell Smooth and textured surfaces Round and diverse anatomical shapes Enhanced cohesive and stable gel

Reference	Conclusions
Bastos et al. 2007BASTOS EM, NETO MS, ALVES MTS, GARCIA EB, SANTOS RA, HEINK T, PEREIRA JB and FERREIRA JM. 2007b. Histologic Analysis of Zafirlukast's Effect on Capsule Formation Around Silicone Implants. Aesth Plast Surg 31: 559-565.	Systemic leukotriene receptor antagonist (Zafirlukast) treatment reduced inflammatory parameters, myofibroblasts, collagen density and capsular thickness in periprosthetic tissue of animals with textured surface silicone prostheses. Treatment with leukotriene antagonist had no effect in capsular tissue of smooth silicone implants.
Bastos et al. 2012BASTOS EM, SABINO NETO M, GARCIA EB, VEIGA DF, HAN YA, DENADAI R, SANTOS RDE A and FERREIRA LM. 2012. Effect of zafirlukast on capsular contracture around silicone implants in rats. Acta Cir Bras 27: 1-6.	Systemic Zafirlukast treatment reduces capsular contracture-related factors, surrounding textured silicone implants only. Results suggest that smooth and textured surface silicone prostheses have different mechanisms to induce capsular contracture.
Bergmann et al. 2014BERGMANN PA, TAMOURIDIS G, LOHMEYER JA, MAUSS KL, BECKER B, KNOBLOCH J, MAILANDER P and SIEMERS F. 2014. The effect of a bacterial contamination on the formation of capsular contracture with polyurethane breast implants in comparison with textured silicone implants: an animal study. JPRAS 67: 1364-1370.	Bacterial infection induces thicker capsule formation and increases inflammatory response. PU-coated implants drives thicker capsule formation and intense local inflammatory processes when compared to textured implants. However, periprosthetic tissue surrounding PU implants showed lower expression of parallel myofibrils.
Cardenas-Camarena et al. 2005	Local electrostimulation regulates periprosthetic capsule formation in both textured and smooth surface silicone prostheses when transplanted into rats.
Gancedo et al. 2008GANCEDO M, RUIZ-CORRO L, SALAZAR-MONTES A, RINCON AR and ARMENDARIZ-BORUNDA J. 2008. Pirfenidone prevents capsular contracture after mammary implantation. Aesth Plast Surg 32: 32-40.	Systemic treatment with Pirfenidone (PFD), an anti-fibrotic drug used for pulmonary fibrosis, decreases inflammation, TGF-β1 levels, and capsular thickness, compared with vehicle-treated animals. Histological analysis shows no differences between textured and smooth periprosthetic tissue.
Mendes et al. 2008MENDES PR, BINS-ELY J, LIMA EA, VASCONCELLOS ZA, D'ACAMPORA AJ and NEVES RD. 2008. Histological study on acute inflammatory reaction to polyurethane-coated silicone implants in rats. Acta Cir Bras 23: 93-101.	PU-coated silicone implants induce inflammatory response in periprosthetic tissue histologically-patterned as chronic foreign body granulomas. Histological changes induced by Staphylococcus epidermidis inoculation were dose-independent.
Vieira et al. 2010VIEIRA VJ, D'ACAMPORA AJ, MARCOS AB, DI GIUNTA G, DE VASCONCELLOS ZA, BINS-ELY J, D'ECA NEVES R and FIGUEIREDO CP. 2010. Vascular endothelial growth factor overexpression positively modulates the characteristics of periprosthetic tissue of polyurethane-coated silicone breast implant in rats. Plast Reconstr Surg 126: 1899-1910.	Periprosthetic tissue of PU-coated silicone implants was thicker and showed intense vascularization and inflammatory response, compared with textured implants. In addition, PU-coated implants had a softer capsule and increased VEGF and TGF-β1 levels in capsular tissue than textured surface prostheses.
Zimman et al. 2007ZIMMAN OA, TOBLLI J, STELLA I, FERDER M, FERDER L and INSERRA F. 2007. The effects of angiotensin-converting-enzyme inhibitors on the fibrous envelope around mammary implants. Plast Reconstr Surg 120: 2025-2033.	Systemic enalapril treatment reduced inflammatory and fibrotic processes in the periprostethic tissue from both textured and smooth surface silicone implants.

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[1] Correspondence to: Claudia Pinto Figueiredo E-mail: claufig@gmail.com

Reference	Title	Study Design
Bastos et al. 2007BASTOS EM, NETO MS, ALVES MTS, GARCIA EB, SANTOS RA, HEINK T, PEREIRA JB and FERREIRA JM. 2007b. Histologic Analysis of Zafirlukast's Effect on Capsule Formation Around Silicone Implants. Aesth Plast Surg 31: 559-565.	*"Histologic analysis of zafirlukast's effect on capsule formation around silicone implants".*	Animals: 32 adult female Wistar rats. Groups: 3 groups that received both smooth and textured surface silicone mini-implant. Intervention: Intraperitoneal treatment with either vehicle or zafirlukast (1.25 or 5 mg/kg/day; for 90 days). Follow up: 90 days. Capsular evaluation: Histological (HE, trichrome and picrosirius red stain), and immunohistochemistry (anti-α-SMA antibody) analyses.
Bastos et al. 2012BASTOS EM, SABINO NETO M, GARCIA EB, VEIGA DF, HAN YA, DENADAI R, SANTOS RDE A and FERREIRA LM. 2012. Effect of zafirlukast on capsular contracture around silicone implants in rats. Acta Cir Bras 27: 1-6.	*"Effect of zafirlukast on capsular contracture around silicone implants in rats".*	Animals: 40 adult female Wistar rats. Groups: 4 groups that received both smooth and textured surface silicone mini-implant. Intervention: Intraperitoneal treatment with either zafirlukast (1.25 mg/kg/day; during 90 days) or vehicle. Follow up: 90 days. Capsular evaluation: Intra-implant pressure measurement.
Bergmann et al. 2014BERGMANN PA, TAMOURIDIS G, LOHMEYER JA, MAUSS KL, BECKER B, KNOBLOCH J, MAILANDER P and SIEMERS F. 2014. The effect of a bacterial contamination on the formation of capsular contracture with polyurethane breast implants in comparison with textured silicone implants: an animal study. JPRAS 67: 1364-1370.	*"The effect of a bacterial contamination on the formation of capsular contracture with polyurethane breast implants in comparison with textured silicone implants: an animal study".*	Animals: 80 adult female Wistar rats. Groups: 4 groups that received either textured surface or PU-coated silicone mini-implant. Intervention: Implant inoculation with vehicle or a standard volume of Staphylococcus epidermidis. Follow up: 60 days. Capsular evaluation: Histological (HE, trichrome, naphthol-ASD-acetatesterase and picrosirius red stain), immunohistochemistry (anti-CD3, anti-CD138, anti-Lysozyme, anti-Pax5 and anti-α-SMA antibodies), and microbiological analyses.
Cardenas-Camarena et al. 2005	*"Electrostimulation: uses and applications for periprosthetic capsular contracture: experimental model".*	Animals: 40 adult female Wistar rats; Groups: 10 groups that received both smooth and textured surface silicone min-implant. Intervention: Different protocols of local electrostimulation from the 3rd to the 15th postoperative day. Follow up: 16 days; Capsular evaluation: Histological (HE) analyses.
Gancedo et al. 2008GANCEDO M, RUIZ-CORRO L, SALAZAR-MONTES A, RINCON AR and ARMENDARIZ-BORUNDA J. 2008. Pirfenidone prevents capsular contracture after mammary implantation. Aesth Plast Surg 32: 32-40.	*"Pirfenidone prevents capsular contracture after mammary implantation".*	Animals: 20 adult female Wistar rats. Groups: 2 groups that received both smooth and textured surface silicone mini-implant. Intervention: Intraperitoneal treatment with vehicle or Pirfenidone (PFD) (200 mg/Kg/day, for 60 days). Follow up: 60 days. Capsular evaluation: Histological (HE, trichrome, picrosirius red stain), immunohistochemistry (anti-TGF-β1, anti-α-SMA antibodies), and real-time PCR (TGF-β and collagen αI) analyses.
Mendes et al. 2008MENDES PR, BINS-ELY J, LIMA EA, VASCONCELLOS ZA, D'ACAMPORA AJ and NEVES RD. 2008. Histological study on acute inflammatory reaction to polyurethane-coated silicone implants in rats. Acta Cir Bras 23: 93-101.	*"Histological study on acute inflammatory reaction to polyurethane-coated silicone implants in rats".*	Animals: 35 adult female Wistar rats. Groups: 7 groups that received PU-coated silicone mini-implant. Intervention: Contamination of implant cavity with 10¹, 10³, or 10⁵ bacteria/mL with implant immersions in anti-microbial solution or saline. Follow up: 30 days. Capsular evaluation: Histological (HE and picrosirius red stain) analyses.
Vieira et al. 2010VIEIRA VJ, D'ACAMPORA AJ, MARCOS AB, DI GIUNTA G, DE VASCONCELLOS ZA, BINS-ELY J, D'ECA NEVES R and FIGUEIREDO CP. 2010. Vascular endothelial growth factor overexpression positively modulates the characteristics of periprosthetic tissue of polyurethane-coated silicone breast implant in rats. Plast Reconstr Surg 126: 1899-1910.	*"Vascular endothelial growth factor overexpression positively modulates the characteristics of periprosthetic tissue of polyurethane-coated silicone breast implant in rats".*	Animals: 34 adult female Wistar rats. Groups: 4 groups that received textured surface or PU-coated silicone mini-implant. Intervention: no intervention. Follow up: 30 and 60 days. Capsular evaluation: Histological (HE, trichrome, picrosirius red stain), immunohistochemistry (anti-VEGF, anti-TGF-β1, anti-α-SMA, and anti-MPX antibodies) analysis.
Zimman et al. 2007ZIMMAN OA, TOBLLI J, STELLA I, FERDER M, FERDER L and INSERRA F. 2007. The effects of angiotensin-converting-enzyme inhibitors on the fibrous envelope around mammary implants. Plast Reconstr Surg 120: 2025-2033.	*"The effects of angiotensin-converting-enzyme inhibitors on the fibrous envelope around mammary implants".*	Animals: 24 adult female Wistar rats. Groups: 4 groups that received either smooth or textured surface silicone mini-implants. Intervention: angiotensin-converting enzyme inhibitor enalapril administered in drinking water, ad libitum. Follow up: 90 days. Capsular evaluation: Histological (HE, trichrome, picrosirius red stain), and immunohistochemistry (anti-TGF-β1 and anti-collagen type III antibodies) analysis.