Study Of The Physicochemical Properties, Cytocompatibility, And Comparison Of The Postoperative Of Capsular Contracture Based On The Breast Implant Materials

Background:Breast augmentation with prosthetic implants is a common procedure in plastic and reconstructive surgery. According to a published survey, over 300,000 people received mammaplasty with prosthetic implants in 2011 alone. As a complication of mammaplasty with prosthetic implants, capsular contracture has drawn increasing attention; early reports indicated an incidence rate of over 30%. At present, the mechanism of capsular contracture is still unclear, and the process appears to be multifactorial. Some surgeons believe that capsular contracture is a result of cystic fibrosis after long after prosthetic implantation. Based on the characteristics of the prosthesis, Pajkos et al. proposed a microbiological hypothesis that a low-grade bacterial infection or biofilm formation around the implantsmay lead to a robust inflammatory response, and the immune reaction can lead to the secretion of profibrotic cytokines and subsequent contracture. Others researchers have proposed that collagen deposition is also risk factor for the onset of capsular contracture. Furthermore, capsular contracture is hypothetically considered a form of hypertrophic scar tissue investing a foreign body or surgically implanted device. Finally, the rupture, deformation or leakage of prosthetic implants is also likely to cause cystic fibrosis and capsular contracture.There are various clinical breast augmentation prosthesis materials, among which the smooth surface breast augmentation materials and rough surface breast augmentation materials are the most common types. According to some reports, the capsular contracture rate of the rough surface breast augmentation materials is smaller than the smooth surface breast augmentation materials. While, several other reports demonstrate that the two rates have no much difference. At the same time, some reports demonstrate that there is a close relationship between the mechanism of the capsular contracture and the formation of the collagen fibers and cells. Therefore, based on the study of materials’ physical and chemical properties, we try to find the differences between those two materials through comparison and analysis. This will lay a solid foundation for developing a new type of breast augmentation materials with better physical and chemical properties. Then, we studied the cell’s adhesion on different materials, so as to provide basis for the study of the mechanism of capsular contracture.At present, an increasing number of researchers are shifting their research focus to the biocompatibility of bioprostheses. The type of implant material used has the most direct impact on a prosthesis’ s biocompatibility. In breast reconstruction and augmentation, the implantation of different types of prostheses has been considered a primary factor that affects postoperative capsular contracture. With an increasing number of clinical studies, other risk factors have also garnered attention, such as the implant material and surgical approach used, but without support from multifactorial evidence-based medicine. Therefore, this study included clinical studies related to capsular contracture after prosthesis implantation and compared the effects of smooth and textured implants on postoperative capsular contracture through cumulative meta-analysis. Based on these findings, comprehensive analyses were performed for other potential risk factors for capsular contracture in the surgical procedure to provide rational support, from the perspective of evidence-based medicine, for reducing the incidence of capsular contracture after prosthetic implantation.Materials and Methods:1. Using common clinical breast augmentation materials: a piece of smooth surface breast augmentation material and a piece of rough surface breast augmentation material. Choose two parts on each piece of material as the experimental samples, and label them with S-1, S-2, R-1 and R-2. After a series of pretreatment, use the atomic force microscope to observe the appearance of the sample materials and compare and analyze the difference between them. The roughness, skewness and kurtosis of the surface of the prosthesis materials are obtained through observing a scanned image with the laser microscope Olympus LEXT. The scanned area is 644 × 642μm, with a cut-off wavelength of 80μm, and the scale of measure area is100μm. Use the deionized water in the water contact angle measurement; dribble the deionized water on the surface of the four samples, and test them after 0.5 to 1 minutes; choose three points with a distance of 5-8 mm from each other to check for 6 times and get the average value. To ensure the repeatability of the experiment, all of the above experiments were made for five times.2. First, make sure to use foreskin tissue of a child to extract fibroblast(the foreskin tissue is from the General Surgery Department of Second Affiliated Hospital of The Third Military Medical University). We culture the fibroblast by digestion and isolation according to the actual conditions. Same as the first trial, we choose four samples(S-1, S-2, R-1 and R-2) as research subjects. Inoculate fibroblast in each six-hole surfaces of the smooth or rough surface prosthetic material, and then put them in a incubator(37℃,5% CO2). Pay attention to adjust the cell density during incubating(the cell density is about 5×105 cells/ml). Dye the cytoskeleton of fibroblast(Actin-Tracker Green diluent and dark incubation in the conservatory for 60 minutes), and then put it under the confocal laser scanning microscope BX53 and observe the cytoskeleton formation of fibroblast on the breast augmentation materials. Meanwhile, observe and compare the adhesion of fibroblast on the surface of the prosthetic material. The observation involves, 1) the immunofluorescence staining of cell adhesion-associated protein OPN, Vinculin, Zyxin and Talin; 2) the comparison of the multiplication capacity of fibroblast on the materials’ surface(with CCK-8); 3) Check the expression condition of fibroblast adhesion-associated protein on different materials by Western Blot.3. After checking electronic document database, such as PubMed, EMBASE, Web of Science, Google scholar, CBM, CMCI/CMCC, Database of the Cochrane Library etc., we collected relative clinical researches about capsular contracture after the implanting of different prosthesis. At the same time the document inclusion criteria and exclusion criteria were developed. The inclusion of RCT is reviewed according to the quality assessment of Cocharne, and the retrospective study is reviewed according to Newcastle-Ottawa Scale. The quality assessment includes two steps: First, two researchers of the research group review the inclusive document by blind method and give a score, and then, if there is divergence, a third researcher will be involved in the evaluating work, and give the final score. Accumulate the extraction data based on ascending order of sample capacity, and choose the random effect model to amalgamate, with an amalgamation norm of relative risk(RR) and 95%CI, and analyze according to impregnating material, implanting position and operative incision and follow up by Meta analysis; Publicize bias with Begg’s test and Eeeg’ s test at the same time; make sensitivity analysis by converting the amalgamation results into fixed effect model, with the help of Stata 11.0 and Rveman 5.0.Results:1. In the test on the physical and chemical properties of different prosthesis materials, atomic force microscope shows that the surface of smooth surface materials is regular, ridge-shaped and in good order, and there are rock-shaped formations and groove marks on both smooth and rough surfaces. According to our observation, the appearance of smooth surface materials is caused by peristalsis to the implant template of silica gel during the curing process. And there are many bulges and deep cracks on the rough surface. In comparison with the smooth surface materials, the rough surface materials’ coefficient of roughness is larger, while its negative skewness is smaller which indicates more groove mark in the surface. In contrast, the positive skewness of smooth surface samples means more spikes in its surface. Meanwhile, the higher kurtosis coefficient of smooth surface samples demonstrates the spikes on the surface would recur frequently. Comparatively, the lower kurtosis coefficient of rough surface samples demonstrates that they are more irregular than smooth surface samples. The water contact angle measurement shows the water contact angle of R-1 is 148°, the biggest one, with 1.9° more or less, while the water contact angle of S-2 is 107.2°, the smallest one, with 0.5° more or less.2. The number of cells grown on prosthesis material tells that the cells developed on S-1 and S-2 is much fewer than that on R-1 and R-2, and CCK-8 cell proliferation experiment proved this result, too. According to the cells growth state, the cytoskeletal protein expressed by fibroblast on rough surface materials, with irregular cells arrangement, is much more than that on smooth surface materials. Meanwhile, it can be preliminary deduced that the filopodia protruded from rough surface materials has better adhesion than that from smooth surface materials. Moreover, the expression condition of cell adhesion-associated protein OPN, Vinculin, Zyxin and Talin on rough surface materials is better than that on smooth surface materials. The expression condition of cell adhesion-associated protein in fibroblast, which is tested by Western blot, demonstrates that the expression of rough surface group is obviously more than that of the smooth surface group. The overall expression rank of cell adhesion-associated protein is OPN > Vinculin > Talin > Zyxin.3. Clinical association analysis says that the capsular contracture rate of the smooth surface prosthesis material is smaller than that of the rough one after surgery. In a subgroup analysis, all the “prosthesis impregnating material”, “implanting position” and “operative incision” may have an effect on the capsular contracture. And with the follow up time prolonged, more people suffer the capsular contracture.Conclusion:1. With more humps and grooves, and more obvious hydrophobicity, rough surface prosthesis material is more irregular than the smooth surface prosthesis material. The physical and chemical properties of the rough surface material are more conducive for the adhesion and hyperplasia of fibroblast.2. The hyperplasia rate of fibroblast on the rough surface material is bigger than that on the smooth one, and the adhesion is tighter, and more cell adhesion-associated proteins are secreted. All these demonstrate that rough surface materials are more conducive for the growth of fibroblast. The closer adhesion between cells and rough surface materials demonstrates smaller reject reaction between fibroblast and rough surface materials, which are more conducive for the amalgamation between the prosthesis and body. The irregular arrangement of cells’ formation on rough surface materials demonstrates the disunity of the contractility caused by adhesion, and the offset between different powers, which cut the capsular contracture rate down.3. According to clinical association analysis, the capsular contracture rate of the smooth surface prosthesis material is smaller than that of the rough one after surgery. During the research, we found that small sample capacity might lead to negative results of the experiment, and better surgical operation, rational impregnating material and reasonable operational manner may also cut down the capsular contracture rate.