Aesthetic Plastic Surgery

, Volume 37, Issue 3, pp 543–548

Prevention of Capsular Contracture with Guardix-SG® After Silicone Implant Insertion

Authors

  • Seong Oh Park
    • Department of Plastic and Reconstructive SurgerySeoul National University Hospital
  • Jihyeon Han
    • Department of Plastic and Reconstructive SurgerySeoul National University Hospital
  • Kyung Won Minn
    • Department of Plastic and Reconstructive SurgerySeoul National University Hospital
    • Department of Plastic and Reconstructive SurgerySeoul National University Hospital
Original Article Breast

DOI: 10.1007/s00266-013-0087-3

Cite this article as:
Park, S.O., Han, J., Minn, K.W. et al. Aesth Plast Surg (2013) 37: 543. doi:10.1007/s00266-013-0087-3

Abstract

Background

Capsular contracture is the most common side effect of breast implant insertion and the problem that breast surgeons seek to avoid the most. Previous animal studies have proved that an antiadhesive barrier solution (AABS) prevents peri-implant capsule formation. In this study, the authors sought to explore the effect that Guardix-SG®, an AABS that can encapsulate implants in the form of a gel, can have on capsular contracture.

Method

This study used 12 female New Zealand white rabbits weighing 2.5–3 kg. Implants were inserted into the subpanniculus carnosus plane through an incision in the bilateral midback area. Once the implant was inserted, 3 g of Guardix-SG® and normal saline were instilled into the left and right sides, respectively. The rabbits were killed 6 months after the procedure. The intracapsular pressure was measured using tonometry with a 38.2-g circular glass piece, and capsular thickness was measured by dyeing the biopsy specimen with hematoxylin and eosin and Masson’s trichrome stain. The myofibroblasts were quantitatively analyzed through monoclonal anti-alpha smooth muscle actin antibody immunohistochemistry staining.

Results

The intracapsular pressure in the control group (4.51 ± 0.98 mmHg) was significantly higher (p = 0.002) than in the study group (3.51 ± 0.4 mmHg). The average capsular thickness was significantly greater in the control group (0.33 ± 0.15 mm; p = 0.015). In the analysis, the interrelation between capsular thickness and intracapsular pressure was insignificant in both groups, as was the number of myofibroblasts in both groups (p = 0.582).

Conclusion

Through this study, the authors were able to demonstrate that capsular contracture can be suppressed in the rabbit model by instilling Guardix-SG® after insertion of cohesive gel implants in the subpanniculus carnosus plane.

Level of Evidence IV

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.

Keywords

Capsular contractureCohesive gel implantsGuardix-SGSilicone implant insertion

Background

Silicone breast implants are widely used to enhance small breast volumes and to correct breast deformities resulting from breast cancer resection. Our bodies naturally form a capsule around an implant as a means of isolating and forming a barrier against this foreign body. When this reaction is excessive, capsular contracture occurs. The mechanism and reason behind this phenomenon remain to be elucidated. An effective way to prevent such a phenomenon also remains to be found.

Guardix-SG® (Genewel, a Dongsung Company, Seongnam, Gyeonggi-do, South Korea) is an adhesion barrier bioresorbable membrane (ABBM) consisting of alginate and poloxamer. Materials already in use for the purpose of adhesion prevention, such as complexes made of hyaluronate and carbomethyl cellulose, are high-viscosity solutions. But Guardix-SG® has the ability to transform from the solution to a gel form at body temperature, enhancing its property as a physical barrier.

Previous studies have proved that application of an ABBM can suppress capsular contracture by reducing inflammation and fibrosis [1]. The authors sought to examine the effect of Guardix-SG®, a substance expected to have superior barrier-forming properties, on prevention of capsular contracture in the rabbit model.

Materials and Methods

This study used 12 female New Zealand white rabbits weighing 2.5–3 kg. The subjects underwent a 10-day quarantine period before the study and were raised in a setting with a 12-h light–dark cycle, a humidity of 50 ± 10 %, and a temperature of 22 ± 2 °C. The implants used were custom-made cohesive gel implants, 5 cm in diameter and 1 cm in height, manufactured by Hans Biomed Corp. (Seoul, Korea) (Fig. 1).
https://static-content.springer.com/image/art%3A10.1007%2Fs00266-013-0087-3/MediaObjects/266_2013_87_Fig1_HTML.jpg
Fig. 1

Custom-made smooth round cohesive gel implant (Hans Biomed). The implant had a diameter of 5 cm and a height of 1 cm

All experiment sessions were conducted by a single researcher in a standardized manner. Zoletil 15 mg/kg and Rumpun 5 mg/kg were injected into the rabbit’s thigh muscle for anesthesia. Hair removal was performed on and around the incision site, followed by injection of 2 % lidocaine in the area. An incision was made in the bilateral midback area, and the implant was inserted into the subpanniculus carnosus plane. Once the implant was inserted, 3 g of Guardix-SG® was injected into the left side and 3 g of normal saline into the right side.

The incision was closed in two layers with subdermal 4-0 Vicryl (Ethicon, Inc., Somerville, NJ, USA) and 4-0 interrupted nylon suture (Fig. 2). To prevent infection, cefazolin 20 mg/kg was injected intramuscularly just before the incision and then daily until postoperative day 3.
https://static-content.springer.com/image/art%3A10.1007%2Fs00266-013-0087-3/MediaObjects/266_2013_87_Fig2_HTML.jpg
Fig. 2

Intraoperative photographs. The red linear marks indicate incision lines, and the black circles indicate the implant pocket. The left side of the rabbit back was the experimental side, whereas the right side was the control side (top left). Instillation of Guardix-SG® after implant insertion (top right). Guardix-SG® in its gel form surrounding the implant (bottom left). View after wound repair (bottom right)

Generally, the severity of capsular contracture is graded according to Baker classification. However, because it is not practical to apply the Baker grade to rabbits, tonometry was used to compare the intracapular pressure of the control and study groups [2].

At 6 months after implant insertion, the rats were anesthetized with Zoletil and Rumpun, and their hair was removed. An area of skin 7 cm in diameter and 3.15 mm in thickness compressed by a circular piece of glass weighing 38.2 g was marked on the glass (Fig. 3). This was photographed with a digital camera, after which the rabbit was killed in a carbon dioxide chamber. The surface area was measured by analyzing the photograph using the ImageJ program (National Institutes of Health, Bethesda, MD, USA). Intracapsular pressure was calculated as follows:
$$ {\text{P}}\left( {{\text{intracapsular}}\;{\text{pressure}}} \right)\; = \;{\text{F}}\left( {\text{force}} \right)/{\text{A}}\left( {{\text{flattened}}\;{\text{area}}} \right)\; = \;{\text{weight}}\;{\text{of}}\;{\text{glasspiece}} \, \left( {38.2\;{\text{g}}} \right)\; \times \;{\text{gravity}}\left( {9.8\;{\text{m}}/{\text{s}}^{2} } \right)/{\text{surface}}\;{\text{ area}} . $$
(1)
The calculated pressure was converted to mmHg.
https://static-content.springer.com/image/art%3A10.1007%2Fs00266-013-0087-3/MediaObjects/266_2013_87_Fig3_HTML.jpg
Fig. 3

Analysis with tonometry. The area of skin compressed by the circular glass piece is marked in red, and the surface area is measured

For each implant, tissue 1 × 1 cm in size was obtained from three locations, for a total of 72 tissue pieces. For accurate measurement of capsule thickness, specimens were sampled in full thickness, from skin to the inner surface of the capsule. Hematoxylin and eosin, Masson’s trichrome, and monoclonal anti-alpha smooth muscle actin antibody (Sigma-Aldrich, Saint Louis, MO, USA) were used to dye the specimens immunohistochemically before observation under light microscopes.

Capsule thickness was measured by observation under light microscopes. Slides that showed a clear demarcation between the capsule and surrounding tissue were selected for measurement of capsule thickness at three different locations. The thickness was measured using Adobe photoshop CS3 (Adobe Systems Inc., San Jose, CA, USA, 2007). In addition, the interrelationship between capsular thickness and intracapsular pressure was analyzed.

Myofibroblasts were stained with monoclonal anti-alpha smooth muscle actin antibodies, and the density was measured at the same points used to measure capsule thickness. Locations were graded according to the density of myofibroblasts as follows: 0 (none), 1 (almost none), 2 (a small number), 3 (some), and 4 (many).

Statistical Analysis

Tonometry and capsular thickness were analyzed with the Wilcoxon matched-pair signed rank test, and Spearman’s rank coefficient was used to assess the association between the thickness of the capsule and the intracapsular pressure. A p value lower than 0.05 was considered significant. All statistical analyses were performed with SPSS version 18.0 for Windows (SPSS, Inc., Chicago, IL, USA).

Results

All the subject animals survived through the entire experiment. There was no apparent migration of implants, edema, or inflammation signs. Severe capsular contracture such as Baker grade 3 or 4 was not observed.

By application of tonometry, the amount of pressure applied on the implant was derived from the measured surface area of skin compressed by the circular glass piece. The intracapsular pressure in the control group (4.51 ± 0.98 mmHg) was significantly higher (p = 0.002) than in the study group (3.51 ± 0.4 mmHg) (Table 1).
Table 1

Intracapsular pressure (mmHg) measured by tonometry

Subject no.

Control group

Experimental group

1

4.22

3.90

2

3.97

2.85

3

4.19

4.00

4

3.59

3.07

5

4.22

3.92

6

3.73

3.45

7

7.34

3.33

8

4.29

2.97

9

4.03

3.45

10

4.58

4.10

11

4.35

3.77

12

5.62

3.29

Mean

4.51

3.51

p value

0.002

The average capsular thickness in the control group (0.33 ± 0.15 mm) was significantly greater (p = 0.015) than in the study group (0.28 ± 0.11 mm) (Fig. 4; Table 2).
https://static-content.springer.com/image/art%3A10.1007%2Fs00266-013-0087-3/MediaObjects/266_2013_87_Fig4_HTML.jpg
Fig. 4

Top left thick capsule of the control group with dense parallel collagen fiber (Masson’s trichrome, ×40). Top right poorly formed thin capsule of the experimental group with loosely organized collagen fiber (Masson’s trichrome, ×40). Bottom left thin distinct layer of myofibroblasts (anti-alpha smooth muscle actin antibody stain, ×40). Bottom right magnified view of myofibroblast stained with anti-alpha smooth muscle actin antibody (×200)

Table 2

Thickness of capsule (mm)

Subject no.

Control group

Experimental group

1

0.29

0.26

2

0.27

0.25

3

0.35

0.35

4

0.34

0.32

5

0.18

0.19

6

0.12

0.15

7

0.67

0.47

8

0.17

0.13

9

0.37

0.26

10

0.49

0.46

11

0.18

0.14

12

0.48

0.38

Mean

0.33

0.28

p value

0.015

The correlation between capsular thickness and intracapsular pressure, analyzed with Spearman’s rank coefficient, was insignificant in both the study group (p = 0.542) and the control group (p = 0.112).

The average number of myofibroblasts was 2.10 in the study group and 1.98 in the control group (p = 0.582), exhibiting no significant difference (Fig. 4) (Table 3).
Table 3

Quantitative analysis of myofibroblast

Subject no.

Control group

Experimental group

1

2.00

2.44

2

2.00

1.56

3

1.56

1.67

4

2.11

1.44

5

2.22

2.56

6

2.78

2.33

7

1.56

2.67

8

1.56

1.44

9

2.11

2.22

10

2.22

2.44

11

1.78

2.11

12

1.89

2.33

Mean

1.98

2.10

p value

0.582

Locations were graded according to the density of myofibroblasts: 0 (none), 1 (almost none), 2 (a small number), 3 (some), and 4 (many)

Discussion

Capsular contracture, the most common postoperative complication, occurs at a rate of 0.5 % to 50 % in patients receiving augmentation mammoplasty or reconstructive breast surgery [3, 4]. Because this complication can cause patients a great deal of pain and distort the appearance of their breasts, numerous attempts have been made to prevent this disastrous phenomenon.

Capsular contracture can be explained by two theories: subclinical infection theory and hypertrophic scar theory [5].

Subclinical infection, known to be caused by organisms such as Staphylococcus epidermidis, can be prevented to some degree by decontamination of the operation field and appropriate use of antibiotics [6, 7]. The main concept of the hypertrophic scar theory is that the level of fibroblast activation and the collagen material produced by fibroblasts play an important role in capsule formation and adhesion [8]. Theoretically, adhesion, which consists of fibrous bands formed between tissue and adjacent tissue or foreign bodies, can be reduced by ABBM. Friedman et al. [9] discovered that in the rat model, capsule formation after insertion of silicone discs can be delayed by AABM in the form of films. Lew et al. [1] also found that peri-implant capsule formation in the white rat model can be inhibited by a solution form of AABM.

Guardix SG®, the AABM used in our study, is a complex of alginate and poloxamer. Alginate, a form of hydrogel extracted from seaweed, is commonly used in clinical settings. Nagakura et al. [10] previously showed that pure viscous injectable alginate solution inhibits scar formation by forming a physical barrier against fibroblast invasion and stimulates wound healing in the surrounding tissue.

The main difference between the previously existing AABMs and Guardix SG® is the poloxamer component. Poloxamer, a complex of nonionic triblock copolymers of the central hydrophobic polypropylene and side hydrophilic polyethylene, is widely used as a surfactant due to its amphiphilic character. Poloxamer exists at room temperature in the form of solution but transforms into gel form at body temperature. Therefore, it is convenient to use and more efficient at forming a firm strong membrane around implants than other AABMs.

Oh et al. [11] found that poloxamer, with its anti-adhesion, nontoxic, less inflammation-inducing character, acts as a good anti-adhesion agent in the peritoneum adhesion model using rats. Reigel et al. [12] also demonstrated that poloxamer had an approximate 50 % anti-adhesive effect in a rabbit laminectomy model. Based on these two properties of Guardix SG®, the authors were able to form a hypothesis that Guardix-SG® effectively prevents capsular contracture.

Rabbits were selected as subject animals in this study because rabbits are known to form capsules similar to those of humans [13]. Rats and monkeys, on the other hand, exhibit increased amounts of capsular formation compared with humans [14].

In our study, the results were analyzed 6 months after insertion because assessment of capsular contracture should take place at least 6 months after implant insertion in the clinical setting. Previous animal studies involved result evaluation at 3–5 months postoperatively [13, 15, 16]. However, in humans, studies have shown that capsular contracture formation is about 90 % complete 9–12 months postoperatively [17], and in a proportion of individuals, capsular contracture continues to develop even 1 year postoperatively [18, 19]. We sought a more accurate evaluation of capsular contracture by lengthening the study and follow-up periods.

Tonometry, although not an accurate method, allows for subjective intracapsular pressure measurement. This method is derived from the Goldmann method used for intraocular pressure measurement. For a more accurate measurement, pressure monitoring devices can be used, but this involves the tiresome job of inserting the device within the capsule [13]. Tonometry was used in our study because it was thought to be a sufficient method for comparing study and control subjects, although the actual pressure values can be somewhat inaccurate.

The degree of capsular contracture in both this study and previous studies did not increase in proportion to myofibroblast density [20]. The lack of a difference in myofibroblast numbers between the study and control groups could be explained by findings from previous studies.

In our study, biopsies were performed 6 months after implant insertion. In a former study using rabbit models, the myofibroblast layer and capsule thickness tended to regress linearly with time after 5 months postoperatively [15]. Therefore, it can be presumed that in the process of regression, myofibroblasts, which are responsible for capsule formation, decrease in number in the implant-inserted group.

Additionally, in our study, myofibroblasts were found at layers more distant from the implant than those immediately adjacent to the implant, as shown in other studies with the biopsy performed at an earlier time. This finding could be attributed to the regression phenomenon as well. However, a well-planned study with varying biopsy timings is necessary to obtain a more definite relationship between the degree of regression and the elapsed time from implant insertion.

Conclusion

In this study, the authors were able to demonstrate that capsular contracture can be suppressed in the rabbit model by instilling Guardix-SG® after insertion of cohesive gel implants in the subpanniculus carnosus plane. This effect can possibly be applied with great advantage in the clinical setting. However, a long-term follow-up study in the human model should be conducted before clinical use of this substance is implemented.

Acknowledgments

This study was supported by Genewel, a Dongsung Company, Seongnam City, Korea.

Conflict of interest

None.

Copyright information

© Springer Science+Business Media New York and International Society of Aesthetic Plastic Surgery 2013