For decades, silicone breast implants have been commonly utilized for breast augmentation and reconstructive surgery. However, breast implants can cause a variety of complications, including infection and implant rupture, and capsular contracture is one of the most challenging complications to treat [1,2].

Clinically, extreme cases of capsular contracture, according to the Baker categorization, cause aesthetic and functional difficulties, such as breast stiffening followed by pain at the surgical site and twisting of the prosthesis, resulting in severe pain for patients. The specific pathophysiology of capsular contracture has yet to be established. However, capsular contracture has been linked to various causes, including foreign body reactions to silicone and the membrane that surrounds it, the anatomical position of the prosthesis, preoperative or postoperative bacterial infection, and postoperative hematoma and seroma [3]. Its pathophysiology is associated with an inflammatory reaction that results in severe fibrosis. Many researchers have proposed various experiments to overcome capsular contracture.

Curcumin, a compound found in turmeric, is known to be active in various pharmacokinetics due to its antioxidant, antitumor, and anti-inflammatory activities. Curcumin’s anti-inflammatory response has previously been established in both cell culture and animal experimental models to be efficacious against ulcerative colitis, pancreatitis, arthritis, and chronic uveitis. Curcumin inhibits cyclooxygenase-2 (COX-2) activity, lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS) activity. The compound also suppresses inflammation by interfering with various inflammatory responses, such as the production of various inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interleukins (ILs), and monocyte chemoattractant proteins (MCPs) [4]. In particular, curcumin was found to reduce prostaglandin E2, which is the end product of the COX pathway that is known to activate fibroblasts involved in fibrosis, causing chronic inflammation [5].

Previous studies have observed decreased fibrous envelope formation around implants through the suppression of the inflammatory response [6,7]. For example, the injection of steroids into a capsule, the use of non-steroidal anti-inflammatory drugs, and leukotriene inhibitors insufficiently reduced fibrous envelope formation, although some studies did report a lower incidence of capsular contracture with these treatments [8-11]. Recent clinical trials have indicated that receptor antagonists play a role in the prevention of fibrous envelope formation. However, side effects can occur with each of these treatments. The injection of steroids can prolong wound healing [12]. The use of leukotriene receptor antagonists can lead to complications including liver toxicity, moderate to severe asthma, eosinophilia, pulmonary infiltrations, cardiomyopathy, and other signs of vasculitis [6,10,13,14]. In contrast, clinical trials have not reported side effects associated with curcumin, which is marketed as a dietary supplement [15,16].

This study hypothesized that the antioxidant and anti-inflammatory properties of curcumin would mitigate the chronic inflammatory responses that occur after silicone implant insertion. The researchers determined the degree of fibrous capsule formation and the number of inflammatory cells after administering curcumin in an experimental animal model using Sprague-Dawley rats.

None of the rats appeared to experience side effects or develop infections or inflammation. Examinations of the excised tissue samples revealed differences in gross and histologic findings between the groups. Dense fibrous capsules with well-defined margins from the adjacent tissue formed around each implant. All of the capsules were at least slightly hardened and slippery when palpated.

The thicknesses of the capsules in group B were significantly lower than those in group A. The capsules were established around the implants and comprised two well-differentiated layers. The inner layer, which was attached to the implants, and the outer loose connective tissue layer were connected to the adjacent normal connective tissue and the subcutaneous layer (Fig. 3).

In groups A and B, the mean thicknesses of the capsule adjacent to the implants were 177.4 µm and 145.9 µm, respectively (Table 1, Fig. 4). This result indicates that the thickness of the capsule in group B was significantly thinner than in group A (P < 0.05). A layer of epithelial-like cells lined the inner surface of the capsule with high cell density. The outer layer was thicker than the inner layer and had low cell density with loose connective tissue.

The number of inflammatory cells, including giant cells and eosinophils, was significantly lower in the experimental group. Group A had a mean inflammatory cell distribution of 7,070 cells/mm2, which was much higher than the mean distribution of 2,640 cells/mm2 in group B (P < 0.05) (Table 1).

This study showed a significantly lower overall decreasing tendency in the mean thickness of the capsule and the number of inflammatory cells in group B than in group A. Additionally, capsule thickness and inflammatory cell count were positively correlated (P < 0.01) (Fig. 5).

Capsular contracture after mammoplasty using implants is one of the most common and difficult-to-treat problems in the field of plastic and reconstructive surgery. However, as of this study, no definite causes and treatment methods have been established for capsular contracture. Therefore, it was hypothesized that the anti-inflammatory properties of curcumin would mitigate the chronic inflammatory response that occurred after silicone implant insertion, leading to a decrease in the rate of fibrous capsular contracture. We attempted to demonstrate this hypothesis through this experimental study.

Curcumin is a natural phytocompound found in turmeric with anti-inflammatory properties that has been used to treat chronic diseases. Its anti-inflammatory activity appears to be mediated via the suppression of COX-2, LOX, and iNOS induction, the release of cytokines such as interferon-γ and TNF-α, and the activation of transcription factors including nuclear factor kappa B (NF-κB) and activator protein 1. Toxicity studies conducted on animals have indicated no adverse effects due to prolonged use [18,19].

Many studies have shown that curcumin is a highly pleiotropic compound capable of interacting with a variety of molecular targets implicated in inflammation. However, the precise mechanism by which curcumin reduces inflammatory responses remains unknown. Curcumin inhibits inflammatory cytokines through a range of mechanisms. Curcumin regulates inflammatory responses by inhibiting the production of inflammatory cytokines (e.g., TNF-α; IL-1, IL-2, IL-6, IL-8, and IL-12; MCP; and migration inhibitory protein) and downregulating mitogen-activated and Janus kinases [20].

Curcumin’s suppression of NF-κB activation is most likely responsible for COX-2 and iNOS inhibition. NF-κB is a widespread eukaryotic transcription factor that regulates inflammation, cellular proliferation, and transformation. Curcumin has been hypothesized to reduce NF-κB activation and pro-inflammatory gene expression by inhibiting the phosphorylation of the inhibitory factor I-kappa B kinase [21]. The suppression of NF-κB activation inhibits the inflammatory process by downregulating COX-2 and iNOS. Curcumin also suppresses arachidonic acid metabolism and inflammation in the epidermis of animal models by downregulating the COX and LOX pathways [22].

In this experiment, the hypothesis that the curcumin might contribute to eventually reducing the thickness of the fibrous capsule surrounding the silicone implant in an animal model was demonstrated. Inflammation is considered to lead to increased capsule thickness, and this study verified the positive relationship between the number of inflammatory cells and capsule thickness. Therefore, the effects of anti-inflammatory and antioxidation activities of curcumin could help decrease inflammation and capsule formation.

However, the capsule was not as thick in rats as in humans, and capsule contracture did not occur in our experiment. Therefore, although the results indicate that curcumin might help to reduce the thickness of the capsule, it could not be determined whether it could prevent or relieve the formation of the capsule.

The study design had multiple limitations. First, the mammoplasty procedure is more complicated than merely placing silicone implants into patients’ backs. Furthermore, the dose of curcumin was not equivalent for each rat since the rats were allowed to eat unrestricted amounts of feed. Curcumin is also poorly absorbed due to limited systemic bioavailability. To compensate for these limitations, future research should involve rats that are fed the same doses of curcumin with saline. Analysis of curcumin serum levels and major metabolites via liquid chromatography-tandem spectrometry would help determine whether the doses are equivalent [5,23]. Since a variety of silicone implants are used in current clinical practice, it would also be beneficial to conduct an experiment to compare the effect of curcumin on capsule formation according to the type of implant.

The clinical applicability of experimental results seen in animal models has yet to be determined since rats and humans differ in terms of immune response and wound healing. Humans are more vulnerable to infections than rats. Capsules in rats are not hard and thick; therefore, to determine the degree of fibrotic change in capsules, not only does the capsule thickness need to be measured and analyzed, but a quantitative analysis must also be performed, including immunohistochemical staining such as Masson trichrome staining and picrosirius staining [24].

In conclusion, curcumin could significantly reduce inflammatory reactions, resulting in less fibrosis formation, as well as lower the incidence of capsular contracture. Long-term studies are needed to determine if curcumin can be used to develop safe and reasonable therapeutic strategies to reduce capsular formation, which frequently causes pain in patients with breast implants.