Early tissue reaction to textured breast implant surfaces.

Capsular contracture around breast implants with smooth surfaces continues to be an unpredictable complication. Some surgeons believe that silicone implants covered with porous polyurethane foam have a lowered potential to contract. These textured implants are not as biocompatible as silicone. Recently, silicone implants with textured surfaces have been introduced with the hope that the incidence of unacceptable implant contracture will be reduced. Using a rat implant model, the tissue reaction to textured implant surfaces was assessed. The implant surfaces evaluated were Silastic II, Siltex, MISTI, Biocell, Silastic MSI, and Même. Disks of each implant material were implanted under the dorsal skin of rats for a period of 28 days. Each implant with its surrounding tissue was excised, processed for histological analysis, and assessed for the tissue's response to the implant with particular emphasis on the formation of a continuous collagen capsule. The results indicated that the magnitude of surface texturing influenced the development of a complete capsule. Implant surfaces with a texture of less than 150 microns in height or depth (Silastic II, Siltex, and MISTI) resulted in the formation of complete capsules. An implant (Biocell) with irregular texturing (200-350 microns) produced an organized capsule over most of its surface with localized interruptions of the capsule at the sites of its deepest cavities. Implant surfaces with texturing that exceeded 350 microns in height or depth (Silastic MSI and Même) resulted in inhibition of the formation of a continuous capsule during this 28-day study.     

The influence of vitamin E on capsule formation and contracture around silicone implants

An attempt was made to determine if the tissue response to surgical trauma and foreign body stimulus (silicone implants) could be altered using vitamin E in rats. The animals were divided into four groups: Group A served as controls, Group B were treated by intramuscular vitamin E, Group C were treated topically with vitamin E around the prosthesis, and Group D were treated topically with croton oil around the prosthesis. The animals in each group were killed at 2 week, 1 month, and 3 months intervals. The intraprosthetic pressure in each prosthesis was recorded using a strain gauge transducer. The capsules were then removed and examined histologically using a light microscope and the thickness of pseudocapsules was measured with an ocular micrometer. In Group B significantly thinner pseudocapsules were observed at 2 weeks, but there was no comparable difference either in thickness or degree of contracture (as measured by intraprosthetic pressures) between Groups A and B at 2 months and 3 months. In Group C, the pseudocapsules were significantly thicker at all tested periods and showed noticeable contracture at 3 months. In group D the pseudocapsules were thickest and cellular infiltrate more marked than in the other groups.     

Macrophage interleukin 1 response to injected silicone in a rat model.

Observations of silicone granuloma formation and migration of silicone to regional lymph nodes have indicated a need for more research into the possible immunological responses to silicone. The present study was undertaken to assess the effect of injected silicone particles on the ability of splenic macrophages to produce interleukin 1 (IL-1) and to determine the relative quantities produced. Lewis rats were divided into 4 groups: Group 1 animals (n = 3) were injected subcutaneously with sterile saline (2.5 ml) and served as control animals; Group 2 animals (n = 3) also served as control subjects, but macrophages isolated from these animals were exposed to lipopolysaccharide (LPS); Group 3 animals (n = 3) were injected subcutaneously with Freund's complete adjuvant (FCA) (2.5 ml) to serve as FCA control animals; and Group 4 animals (n = 3) received a subcutaneous injection of a sonicated slurry of equal parts FCA and silicone (2.5 ml each). IL-1 production was not significantly increased in splenic macrophages from animals exposed to the silicone slurry (p greater than 0.20) 8 months after injection as compared with control animals or animals given FCA alone. Macrophages exposed to LPS, a known mitogen, had significantly elevated IL-1 production. Subcutaneously injected silicone particles did not elicit an increase in IL-1 production in rat macrophages.     

Structure of the capsules around silicone elastomer implants

Summary Experiments were carried out on rats to determine tissue reactions to silicone rods and sheeting for up to 8 months after implantation. The connective tissue capsule forming around an implant within a few weeks is a structure well supplied with blood vessels which has an inner lining of fibrocytes and histiocytes. A typical feature of the capsules, at any time during the experimental period, was the presence of variable numbers of histiocytes in the capsule wall, in conjunction with different degrees of vascularization. Encapsulation of silicone implants does not lead to a steady state, the capsule remaining an unstable, reactive membrane.     

Capsule around silicone implants in diabetic rats: histological and biochemical study

Polydimethylsiloxane (silicone) implants were subcutaneously placed in the back of diabetic and normal rats. After three months the rats were killed and the fibrous capsule around the implants was histologically and biochemically examined. A significant quantitative difference (p less than 0.001) was found in the thickness of the capsules, which were two to three times thicker in the diabetic animals. The biochemistry showed an increase of neutral salt-soluble collagen in the diabetic group; electrophoresis revealed only type I collagen in the diabetic and type I and III in the normal rats. From this experimental trial it seems that diabetes mellitus is another factor in formation of a thick capsule around silicone implants.     

The fate of the fibrous capsule after saline implant removal

After removal of a silicone breast implant, if a capsulectomy is not performed, the residual capsule may persist, become calcified, and appear on routine mammograms. The fate of the capsule around saline implants is less clear. The purpose of this study was to determine the fate of the capsule around saline-filled implants in an animal model. Rats were implanted with 6-ml tissue expanders, which were left in place for 4 months. The implants were then removed and the capsules around the injection port (smooth surface) and tissue expander (textured surface) were examined sequentially. The capsules contracted and dissipated gradually over a year in association with a pericapsular vascular proliferation. It may not be necessary to perform a capsulectomy at the time of saline implant removal.     

Intraluminal cyclosporine A reduces capsular thickness around silicone implants in rats

One theory of the cause of connective tissue capsule formation around silicone mammary prostheses is based on an immunological interaction. In an in vitro pilot study, it is shown that intraluminal cyclosporine A, a potent T-lymphocyte-specific immunosuppressive agent, can diffuse slowly through the outer shell of a standard double-lumen silicone breast implant. Round silicone tissue expanders containing 50 mg of cyclosporine A were implanted subcutaneously in 10 rats. Ten animals served as controls. Evaluation was performed after three months. A significant decrease in collagen capsular thickness of 21.6 +/- 5.4 microns (mean +/- standard deviation was measured histomorphometrically in the treated group compared with 39.6 +/- 8.6 microns in the control group (p less than 0.001).     

Zafirlukast Pocket Delivery Impairs the Capsule Healing Around Textured Implants in Rats

Background  The aim of this study was to investigate the effects of zafirlukast on capsule thickness, collagen fiber density, and myofibroblast cell count of the healing tissue around silicone textured implants in rats. Methods  Thirty-six male Wistar rats were divided (n = 18) into two groups. In one group, two parallel incisions (1.5 cm long) were made into the right and left sides of the spine. Two pockets were then created in which shell-shaped textured implants were inserted. The left-side pocket was injected with 0.2 ml of saline solution (SSG) and the right-side pocket with a dose of 1.25 mg/kg of zafirlukast (ZLG). The other 18 rats (sham, SG) had only one pocket created, followed by the placement of an implant and injection of 0.2 ml of saline solution. The rats were euthanized on the 7th, 35th, or 90th days followed by careful dissection of the implant. The capsules and peri-implant tissues were prepared for histologic analysis. An ANOVA test and Tukey test were applied (p < 0.05). Results  ZL was effective in impairing the capsule thickness on the 35th and 90th days compared to the other two groups (sham and saline). Not only was it effective in impairing the collagen density on the 35th and 90th days, but it also showed the same effect in the SSG (systemic); fewer myofibroblasts were counted on the 90th day in the ZLG compared to the SG group; the number of myofibroblasts was significantly lower in the ZLG than in the SSG. Conclusions  Pocket delivery of one dose of Zafirlukast was effective in impairing capsule formation around the textured implant.     

The new low bleed mammary prosthesis: An experimental study in mice

A new low bleed implant of silicone gel for mammary prosthesis has been investigated in mice. The barrier membrane is extremely effective in stopping silicone bleed. No adverse reactions to this implant were noted. Most of the capsules surrounding the implant were thin.Presented at the California Society of Plastic Surgeons meeting, Coronado, California, March 23, 1980.     

Halofuginone inhibits collagen deposition in fibrous capsules around implants

Fibrous capsule formation around implants remains a difficult problem that has been studied for decades. The etiology is elusive, but the end result is the deposition of a dense collagenous capsule around implanted materials. The purpose of this study was to determine the effects of a type I collagen synthesis inhibitor, halofuginone, on fibrous capsule formation around implanted materials. Silastic disks were implanted subcutaneously into 4 groups of adult male rats for up to 8 weeks. Group 1 received drug throughout the study, group 2 received drug during the first half only, group 3 received drug during the second half only, and the control group received no drug. Implants were removed and histology of the capsules was examined. A collagen index score was calculated from digital images of trichrome-stained histologic sections, which permitted semiquantitative comparison of collagen content among the 4 groups. The collagen index values clearly indicate that halofuginone effectively inhibited collagen deposition within the capsule around the implanted disks. Halofuginone treatment also resulted in a decrease in the collagen index score in rat skin, indicating that halofuginone may affect preexisting collagenous structures. The ability of halofuginone to inhibit collagen deposition in new and preexisting fibrous capsules suggests that it may be a useful adjunct to minimize the formation of capsules around implantable prostheses.     

Silicone granuloma following closed capsulotomy of mammary prosthesis

Rupture of the silicone prosthesis can occur following external closed compression capsulotomy for fibrous capsules that develop after augmentation mammaplasty. The forces needed to rupture the fibrous capsule can cause silicone gel from the prosthesis to be pressure injected into the breast tissue and surrounding musculature. Film-screen mammography can be utilized to diagnose prosthetic rupture.     

Silicon assays in women with and without silicone gel breast implants--a review.

During the past 5 years, as the failure properties of silicone gel breast implants have emerged, there has been considerable interest in measuring the levels of silicone and silicon in blood, serum, breast milk, and body tissues. Assays have been done in control patients without implant exposure, and in patients with silicone gel implants in an attempt to predict implant failure. Nuclear magnetic resonance measurements of silicone compounds have not been helpful because of their low sensitivity of detection. However, all compounds containing the element silicon, which includes silicone, have been measured accurately. Modern techniques, such as electrothermal atomic absorption spectrometry, direct-current plasma emission spectrometry, and inductively coupled plasma emission spectroscopy have allowed precise measurement of silicon in body fluids and tissues. Using these techniques, recent studies have demonstrated consistent levels of silicon in the blood and plasma of control women without exposure to implants. In one study, plasma silicon was shown to be 140 +/- 10 ng per milliliter. In four other studies, serum silicon levels in control patients were the following: mean, 130 +/- 70 ng per milliliter; mean, 170 +/- 100 ng per milliliter; median, 100 ng per milliliter (range, 30-209 ng per milliliter); and 10 to 250 ng per milliliter. Three independent studies have shown that women with silicone gel implants have higher blood and serum silicon levels than control subjects, but their values were still within the range of control subjects. One study has shown that the mean silicon level in breast milk was not significantly different between 15 implant patients and 34 control patients. The measurement of silicon in control breast tissue has shown consistent results in three different studies, with most tests varying from <0.2 to 2.2 microg per gram dry weight. Three studies have shown that capsules from women with silicone gel breast implants had markedly elevated silicon levels compared with control breast tissue. Median silicon levels varied from 9,980 to 14,390 microg per gram dry weight. There was no significant difference in capsule silicon level between intact and ruptured implants or associated with implant duration in situ or year of implantation. Four studies have shown that capsules from saline implants had elevated levels of silicon compared with control tissue, but their silicon levels were much lower than those of gel implants. The median levels of silicon in the capsules of these studies were as follows: 7.7, 71.5, 198, and 1,100 microg per gram dry weight. Based on current knowledge, because of the large variability among patients, the use of silicon measurements in blood, serum, breast milk, or implant capsule tissue has no clinical role for the effective monitoring of implant leakage in women with silicone gel breast implants.     

微小组合乳房假体与传统单一假体包膜挛缩的比较研究

目的 了解微小组合硅凝胶乳房假体置入肌层下的包膜挛缩特点,并与传统单一大假体进行比较.方法 30只大白兔,每只大白兔背部两侧肌层下分别置入10ml微小硅凝胶假体4个、40 ml传统硅凝胶乳房大假体1个.3个月时进行包膜挛缩Baker评级,压缩实验,包膜切开后裂开宽度,包膜厚度的比较,取包膜样本切片进行HE染色,镜下观察比较包膜特点.结果 微小组合假体Baker评级、包膜裂开最大宽度、包膜厚度均明显低于大假体组（P＜0.01）.假体压缩率明显高于大假体组（P＜0.01）.微小组合假体形成的包膜较传统假体包膜凸凹不平,胶原排列较屈曲且膜薄.结论 微小组合假体较传统假体有更低程度的包膜挛缩,有一定的隆乳术应用前景.     

A new testis prosthesis material: polymethylmethacrylate

INTRODUCTION: Silicone has been the standard prosthesis material for the last three decades but new materials are being searched because of the known disadvantages of silicone such as migration and high cost. We wanted to test in rats whether or not polymethylmethacrylate could be an alternative to silicone. MATERIALS AND METHODS: We prepared polymethylmethacrylate and silicone testis prostheses which were similar to testis size of rats. Eleven rats were implanted with polymethylmethacrylate, 11 others were implanted with a silicone prosthesis and sham operation was performed in 10 rats. Three months later the scrotums of the animals were removed with the prosthesis for a quantitative analysis of the chronic inflammation and fibrotic reaction and to measure the thickness of the capsule. RESULT: Rejection and infection were not observed in any of the prosthesis-implanted rats. Both prosthesis groups displayed increased vascularization, hemosiderin accumulation and fibrotic and hyalinized tissue formation that replaced the muscle. Chronic inflammation was measured and found to be higher in the polymethylmethacrylate group and the difference was not found to be significant. The average thicknesses of the capsules around the polymethylmethacrylate and silicone groups were found to be 58.4 and 46.8 microm, respectively, and that difference was not significant again. CONCLUSIONS: In the short term polymethylmethacrylate was equally well tolerated, but the low cost of polymethylmethacrylate made it more advantageous.     

Sustained delivery of difluoromethylornithine (DFMO) by means of implantable ceramic devices

A total of 25 Sprague-Dawley albino male rats were assigned to five groups, each group consisting of five rats. Polylactic acid-impregnated ALCAP capsules filled with 40 mg DFMO were implanted subcutaneously (sc) or intraperitoneally (ip) in group I and II rats, respectively. Rats in group III were implanted with empty ALCAP capsules (ALCAP control). Group IV rats were administered orally 3% DFMO in drinking water. Rats in group V served as control. Blood samples were collected every week for six weeks via the tail artery. The concentration of DFMO was determined by a modified ninhydrin hydrindantin method. Data obtained in this investigation showed that the levels of DFMO in the serum of rats in groups I and II were 41.87 +/- 6.8 and 237.62 +/- 13.3 micrograms/mL, respectively. Body, spleen, liver, prostate, seminal vesicles, and testicular weights of the controls and DFMO treated rats were not significantly different (p less than 0.05) over the entire duration of this study. The diarrhea often noted in rats treated orally with DFMO was not observed in rats implanted with ALCAP capsules filled with DFMO. The results of this study suggest that (1) polymer-impregnated ALCAP ceramic capsules can be used to deliver DFMO in a sustained manner for long durations of time, (2) side effects associated with oral administration of DFMO can be avoided by using DFMO-filled ALCAP ceramic implants, and (3) a ceramic system can be designed to deliver DFMO and drugs such as DFMO in a sustained manner over long periods of time in humans.     

Residual silicone detection using mri following previous breast implant removal: Case reports

The current controversy surrounding the safety of silicone gel breast implants has resulted in an increasing number being removed. Although previous reports have suggested that remnants of the implant capsule are reabsorbed after explantation surgery, the persistence of the capsule in fact may be associated with implant fragments and silicone gel leakage. In this study we have used magnetic resonance imaging (MRI) to identify residual silicone gel and silicone granulomas following the removal of silicone gel breast implants. Four representative clinical case reports are presented. These patients, who had residual silicone present in their bodies, presented to us with breast pain, palpable masses, or abnormal calcific mass densities apparent on a mammogram. High-resolution MRI images were found to be helpful in identifying local and remote collections of silicone gel, silicone granulomas, and residual capsules that were incompletely removed from previous explantation surgery. MRI breast images demonstrated high resolution and provided the accurate anatomical locations of residual silicone gel and silicone granulomas in all the regions of breast parenchyma, chest wall muscles, and axillae. Patients with persistent local symptoms following explantation surgery may benefit from an evaluation of the breast using MRI.     

毛发作为填充物的实验及临床应用

目的 探讨毛发作为整形外科充填物的可行性。方法 在大白兔背部及腹部植入灭菌的毛发小团与置入的固体硅胶对比，并初步试用于临床3例。结果 3－4个月后植入毛发的周围组织有很少量炎症细胞，9个月后炎症细胞消失，无植入物排斥反应、肉芽肿形成和毛发退化。临床应用除1例双颞部因感染被迫取出外，余均良好。结论 毛发是整形外科的一种有应用前途的填充物。     

The Influence of External Ultrasound on the Histologic Architecture of the Organic Capsule Around Smooth Silicone Implants: Experimental Study in Rats

BACKGROUND: Capsular contracture is the main complication related to breast silicone implants, and its prevention remains a medical challenge. The authors present experimental research examining the effect of external ultrasound on the formation and contracture of peri-implant capsules. METHODS: In this study, 42 male Wistar rats had a 2-mm smooth surface implant placed in a dorsal submuscular pocket. They then were separated into "ultrasound" and "control" groups that received repeated external applications either with or without the ultrasound power on. Ultrasound applications were given three times a week for a period of 90 days. After that, both groups were housed under the same conditions with no application scheduled. Five animals of each group, killed at 30, 60, 90, and 180 days, had their implants removed along with the capsule, which received a special histologic preparation via annular sectioning that provided wide circumferential observation of the capsular tissue. Sections were stained with hematoxylin/eosin stain, Masson's trichrome stain, and Pricrosirius Red stain for regular microscopic evaluation under normal and polarized light. RESULTS: Histologic data showed that capsules from the ultrasound and control groups had statistically significant differences. Ultrasound application developed a capsular architecture similar to that shown within textured silicone implants, and its effect had an early definition with subsequent stabilization. CONCLUSION: The authors conclude that early and repeated external ultrasound application enhances the thickness, cellular count, and vascularity of smooth silicone capsular tissue, whereas it diminishes the pattern of parallel orientation of collagen fibers.     

Effect of Amniotic Fluid on Peri-implant Capsular Formation

Although commonly used biomaterials are physically and chemically stable, nonimmunogenic, and nontoxic, implanted and blood-contact biomaterials trigger a wide variety of unwanted responses, including inflammation, thrombosis, infection, and fibrosis. Peri-implant fibrosis is the response most commonly seen by plastic surgeons. In this study, the authors hypothesized that as hyaluronic acid (HA) reduces scar formation by inhibiting the activity of mononuclear phagocytes and lymphocytes, human amniotic fluid (HAF), which contains high concentrations of HA, HA-stimulating activator (HASA), and other factors, might prevent the formation of fibrous capsules and capsule contracture when applied intraluminally. Two 1 x 1-cm silicone blocks were placed dorsally into separate surgically created pockets underneath the panniculus carnosus muscle, distant from the incisions, in each of the 10 rats in the study. At the time of implant insertion, 2 ml of HAF was instilled into the cranially located pockets in group 1, whereas 2 ml of saline solution was instilled into the caudally located pockets in group 2. After 6 months, intracapsular static and dynamic pressure measurements were made, and then all the peri-implant capsules were excised and fixed in 10% neutral buffered formaldehyde. The thicknesses of the capsules were measured in three different areas of each section, and a mean was calculated. Capsular firmness, according to the static and dynamic pressure readings, was significantly greater in the control group, which had saline solution introduced into the pocket, than in the treatment group, which had HAF used in the same manner. The mean total thickness of the capsules surrounding the implants was 876.7 μm in the control group, as comparied with 466.8 μm in the HAF-treated group. This difference was statistically significant (p < 0.001). Because of its ability to reduce capsular thickness and firmness and also because it can be stored in a freezer if it is prepared in a cell-free manner, HAF would appear to be a useful adjunct in the prevention of capsular contracture formation.     

Lack of Lymph Node Reaction to Subcutaneously Injected Silicone Gel: Histological and Computer Aided Morphometric Study in Rats

The gel of silicone implants may bleed through the elastomeric envelope or may come into contact with the body because of rupture of the implant. We have studied the effects of free silicone gel injected into the subcutaneous space in rats and analysed the morphological features of the axillary and inguinal lymph nodes. Ninety six Wistar rats had 3 cm³ of silicone gel injected into their subcutaneous, space and 96 Wistar rats (the control group) had distilled water injected into their subcutaneous space. The animals were killed on days 1, 3, 7, 9, 15, 30, 60, 90, 120, 180, 270, and 365 after the injection. There was no detectable silicone and no damage to the lymph nodes on routine histopathological analysis. Small amounts of silicone that could migrate to lymph nodes could result in hyperplasia. To evaluate this possibility, a morphometric study based on a computer aided system compared the area of lymph node sections between treated and control animals, and showed no difference between treated and control groups. If silicone did migrate, it did not provoke morphological signs or hyperplasia in the lymph nodes.