Simvastatin Reduces Capsular Fibrosis around Silicone Implants

Capsular fibrosis and contracture occurs in most breast reconstruction patients who undergo radiotherapy, and there is no definitive solution for its prevention. Simvastatin was effective at reducing fibrosis in various models. Peri-implant capsular formation is the result of tissue fibrosis development in irradiated breasts. The purpose of this study was to examine the effect of simvastatin on peri-implant fibrosis in rats. Eighteen male Sprague-Dawley rats were allocated to an experimental group (9 rats, 18 implants) or a control group (9 rats, 18 implants). Two hemispherical silicone implants, 10 mm in diameter, were inserted in subpanniculus pockets in each rat. The next day, 10-Gy of radiation from a clinical accelerator was targeted at the implants. Simvastatin (15 mg/kg/day) was administered by oral gavage in the experimental group, while animals in the control group received water. At 12 weeks post-implantation, peri-implant capsules were harvested and examined histologically and by real-time polymerase chain reaction. The average capsular thickness was 371.2 μm in the simvastatin group and 491.2 μm in the control group. The fibrosis ratio was significantly different, with 32.33% in the simvastatin group and 58.44% in the control group (P < 0.001). Connective tissue growth factor (CTGF) and transforming growth factor (TGF)-β1 gene expression decreased significantly in the simvastatin group compared to the control group (P < 0.001). This study shows that simvastatin reduces radiation-induced capsular fibrosis around silicone implants in rats. This finding offers an alternative therapeutic strategy for reducing capsular fibrosis and contracture after implant-based breast reconstruction.

Simvastatin Reduces Capsular Fibrosis around Silicone Implants

Capsular fibrosis and contracture occurs in most breast reconstruction patients who undergo radiotherapy, and there is no definitive solution for its prevention. Simvastatin was effective at reducing fibrosis in various models. Peri-implant capsular formation is the result of tissue fibrosis development in irradiated breasts. The purpose of this study was to examine the effect of simvastatin on peri-implant fibrosis in rats. Eighteen male Sprague-Dawley rats were allocated to an experimental group (9 rats, 18 implants) or a control group (9 rats, 18 implants). Two hemispherical silicone implants, 10 mm in diameter, were inserted in subpanniculus pockets in each rat. The next day, 10-Gy of radiation from a clinical accelerator was targeted at the implants. Simvastatin (15 mg/kg/day) was administered by oral gavage in the experimental group, while animals in the control group received water. At 12 weeks post-implantation, peri-implant capsules were harvested and examined histologically and by real-time polymerase chain reaction. The average capsular thickness was 371.2 μm in the simvastatin group and 491.2 μm in the control group. The fibrosis ratio was significantly different, with 32.33% in the simvastatin group and 58.44% in the control group (P < 0.001). Connective tissue growth factor (CTGF) and transforming growth factor (TGF)-β1 gene expression decreased significantly in the simvastatin group compared to the control group (P < 0.001). This study shows that simvastatin reduces radiation-induced capsular fibrosis around silicone implants in rats. This finding offers an alternative therapeutic strategy for reducing capsular fibrosis and contracture after implant-based breast reconstruction.

Healing reaction to mammary prostheses covered by textured silicone and silicone foam in rats / Reação capsular aos revestimentos de próteses mamárias de silicone texturizado e espuma de silicone em ratos

PURPOSE: To compare the capsular reaction to two different coverings of silicone prosthesis through the biophysical characteristic of adherence and microscopical aspects of the inflammatory reaction and collagen formation. METHODS: Thirty two Wistar rats were used. In the dorsum of each animal a silicone elastomer with a smooth superficies and another coated with texturized silicone (Mentor) was implanted. Another one, with the same smooth superficies and other coated with silicone foam (Lifesil), making up in each side, of the dorsum, the texturized and silicone foam group respectively. The animals were split into four groups to be evaluated at 7, 14, 30 and 60 days. On the evaluation dates the implant adherence was verified witch a tensiometer and the values in kgf were obtained. The material was sent to histological analysis with hematoxilin-eosin and picrosirius colorations, to evaluate the inflammatory reaction and collagen synthesis, respectively. The obtained data were submitted to statistical treatment. RESULTS: There was more adherence of the tissue to the silicone foam (P<0,001). The inflammatory reaction was more intense in the same group, but without statistical significance. The number of giant cells and granulomas were more frequent in the silicone foam group. There was statistical significance at the 60 days for granulomas (P<0,028) and for all subgroups about number of giant cells (P< 0,012 to P<0,036). The thickness of the capsule in the silicone foam group was bigger, with statistical significance at seven days (P<0,028) and 60 days (P<0,012). The collagen deposition showed no difference in statistical analysis. CONCLUSION: The capsular reaction to the silicone foam showed stronger adherence, bigger thickness and had more number of granulomas and giant cells. No difference was observed in the intensity of inflammatory reaction in relation to type I and III collagen, when compared to the texturized cover.

OBJETIVO: Comparar a reação capsular de dois revestimentos de próteses de silicone através da característica biofísica de aderência e dos aspectos microscópicos de reação inflamatória e formação de colágeno. MÉTODOS: Implantaram-se no dorso de 32 ratos duas membranas de silicone ambas possuindo uma superfície lisa e outra diferindo em sua estrutura. Estes revestimentos foram de espuma de silicone (LifeSil) ou silicone texturizado (Mentor). Os dois grupos foram divididos em quatro sub-grupos conforme o tempo de pós-operatório avaliado: 7, 14, 30 e 60 dias. Obteve-se material para análise biofísica de aderência, a qual foi realizada com tensiômetro para obtenção de valores em kgf. O estudo microscópico da reação inflamatória e síntese de colágeno foi realizado com colorações de hematoxilina-eosina e picrosirius. Os dados foram submetidos a testes para avaliação da significância estatística. RESULTADOS: Houve maior aderência do revestimento de espuma de silicone ao tecido capsular, sendo este valor estatisticamente significativo (P<0,001). Quanto à reação inflamatória observou-se maior intensidade também neste grupo, porém sem significância estatística. Na contagem de células gigantes e granulomas os valores foram maiores para o grupo espuma de silicone com significância estatística no sub-grupo 60 dias (P<0,028) para número de granulomas; e em todos os sub-grupos (variando de P<0,012 a P<0,036) para o número de células gigantes. A reação capsular à espuma de silicone foi mais espessa, com significância estatística nos sub-grupos sete dias (P<0,028) e 60 dias (P<0,012). No estudo da síntese de colágeno, as diferenças não foram significantes estatisticamente. CONCLUSÃO: A reação capsular ao revestimento de espuma de silicone apresentou características de ter maior aderência ao tecido peri-implante, ser mais espesso, possuir maior número de granulomas e células gigantes de corpo estranho. Não demonstrou diferença quanto à intensidade da reação ...

Comparison between textured silicone implants and those bonded with expanded polytetrafluoroethylene in rats

PURPOSE: Comparison of the inflammatory reaction promoted by textured silicone implants and that caused by the implant bonded with e-ptfe. METHODS: One-hundred and fifty rats were divided into three equal groups (control, silicone, and bonded e-ptfe). These groups were subdivided into five groups, according to the second operation, i.e., 7,30,60,90 and 180 days. Histology of the peri-implant tissue was analyzed by morphometry with blood count (neutrophilos, lymphocytes, macrophages, fibroblasts and capillaries). RESULTS: Comparison of subgroups 7,30,60,90, 180 days: - neutrophils: silicone: > in subgroup 7 days; bonded e-ptfe: > in subgroups 7 and 30 days; - lymphocytes: silicone: > in subgroup 7 and 180 days; bonded e-ptfe: > in subgroup 180 days; - macrophages: silicone: > in subgroup 7 and 60 days; bonded e-ptfe: > in subgroup 7,30 and 60 days; - fibroblasts: silicone: > in subgroup 30 and 60 days;- vascular volume: silicone: in subgroup 7, 60 and 90 days; bonded e-ptfe: > in subgroup 7 days. Comparison of groups: neutrophils : 7 days: > in silicone and bonded e-ptfe; 30 days: > in bonded e-ptfe; - lymphocytes: - 7,30,90 and 180 days: in the control; macrophages: - 7,30 and 60 days: > in silicone & bonded e-ptfe; 180 days > in silicone; fibroblasts: - 7,30 and 90 days: > in silicone and bonded e-ptfe; 180 days: > in bonded e-ptfe; vascular volume 7,60,90 and 180 days: > in silicone and bonded e-ptfe; 30 days: > in bonded e-ptfe. CONCLUSIONS: The acute stage of the inflammatory response was more severe and irregular in the silicone implant; both the silicone implant and the silicone bonded with e-ptfe promoted chronic inflammatory reaction and weak foreign body inflammatory response. These reactions were greater in the silicone implant group.

OBJETIVO: Comparar a reação inflamatória provocada pelo implante de silicone texturizado, com aquela causada por este recoberto com PTFE-E. MÉTODOS: Foram utilizadas 150 ratas, divididos em três grupos igruais (controle, silicone e recoberto PTFE-E). Os grupos foram subdivididos em cinco subgrupos, ou seja, 7, 30, 60, 90 e 180 dias, de acordo com a data do segundo ato operatório. O tecido perimplante foi analisado histologicamente, por meio de técnica morfométrica, com contagem de neutrófilos, linfócitos, macrófagos, fibroblastos e capilares. RESULTADOS: Comparação dos subgrupos 7, 30, 60, 90 180 dias: - neutrófilos - silicone: > no subgrupo 7 dias; rec-ptfe: > nos subgrupos 7 e 30 dias; - linfócitos: silicone: > no subgrupo 7 e 180 dias; rec-ptfe: > no subgrupo 180 dias; - macrófagos: silicone: > no subgrupo 7 e 60 dias; rec-ptfe: > no subgrupo 7, 30 e 60 dias; - fibroblastos: silicone: > no subgrupo 30 e 60 dias; - volume vascular: silicone: > no subrupo 7, 60 e 90 dias; rec-ptfe: > no subgrupo 7 dias . Comparação dos gurpos: - neutrófilos - 7 dias: > no silicone e rec-ptfe; 30 dias: > no rec-ptfe; - linfócitos - 7, 30, 90 e 180 dias: > no controle; - macrófagos - 7, 30 e 60 dias: > no silcone e rec-ptfe; 180 dias: > no silicone; - fibroblastos - 7, 30 e 90 dias: > no silicone e rec-ptfe; 180 dias: > no rec-ptfe; - volume vascular - 7, 60, 90 e 180 dias: > no silicone e rec-ptfe; 30 dias: > no rec-ptfe. CONCLUSÕES: A fase aguda da reação inflamatória foi mais intensa e irregular no implante de silicone; tanto o implante de silicone como o de silicone recoberto por ptfe-e induziram a reação inflamatória crônica e a fraca reação inflamatória tipo corpo estranho. Estas forram maiores no implante de silicone.