What is silica?

Amorphous pyrogenic silica: Properties, toxicity, and risks in breast implants

Silicone (SiO2) is found in biogenic, crystalline, and synthetic amorphous forms. Biogenic silica (e.g. diatomaceous earth) is used in food and filtration, while crystalline silica (e.g. quartz) is essential in construction and electronics, but is classified by the IARC as carcinogenic (Carcinogenic-1). Synthetic amorphous silica (SAS), such as pyrogenic and precipitated silica, serves as filler in rubber, polymers, and medical implants, such as silicone breast implants. The properties vary by type, particle size, and surface treatment.

Amorph versus Crystalline

1. What is pyrogenic amorphous nano-silica (trimethylsilyl modified)?

• Pyrogenic silica: Produced by flame hydrolysis at high temperatures, resulting in nanoformat particles (5,7 nm). It is amorphous (non-crystalline) but reactive through a large surface.
• Trimethylsilyl (TMS) modification: A chemical treatment that makes silica hydrophobic by binding TMS groups to the surface, often used in implant envelopes (21,27% pyrogenic silica).

2. Toxicity to macrophages: Mechanisms

Pyrogenic nanosilica can damage macrophages, important immune cells, through:

• Direct cell damage: After phagocytosis, nano-silica causes lysosomal destabilization, oxidative stress (ROS production), and mitochondrial toxicity. TMS groups can activate the NLRP3 inflammasome, making inflammation worse.
• Chronic inflammation: Death of macrophages results in the release of pro-inflammatory cytokines (IL-1β, TNF-α), reduced clearance of silica, and persistent immune activation. Studies such as Shanklin's work, suggest increased levels of angiotensin converting enzyme (ACE) and soluble IL-2 receptors in some patients with implants, suggesting immune dysregulation.
• Possible link to BIA-ALCL: Chronic macrophage activation can stimulate T-cell proliferation via IL-2 and cause genomic instability by ROS, potentially contributing to BIA-ALCL (CD30+ T-cells). This remains a hypothesis that requires further research.

3. Toxicology

• Silicosis-like reactions: Due to its large surface, pyrogenic nano-silica is more toxic than larger particles and can cause granulomas, even in lymph nodes, similar to crystalline silica.
• Long-term effects: TMS groups may hydrolyze slowly in vivo, releasing reactive silanol groups (Si-OH) triggering immune responses. This can cause cumulative toxicity, similar to asbestos or quartz.
• Bioaccumulation: Nano-silica accumulates in lymph nodes, liver, spleen, and periprosthetic tissue, which promotes chronic inflammation and granuloma formation, as seen in capsular contracture.
• Regulatory gaps: Nanomaterials in implants are not yet subject to strict regulation. Pyrogenic silica may fall under "hazardous nanomaterials" according to REACH/EFSA guidelines.

4. Implications for breast implants

In silicone breast implants (with 21,27% pyrogenic silica in the envelope) degradation of TMS treatment and PDMS matrix may release silica particles. This may:

• Stimulate chronic inflammation, such as hairstyle contracture, due to macrophage activation and fibrosis.
• Systemic symptoms such as fatigue or autoimmune symptoms (Breast Implant Illness), as reported in some patients.
• Possibly contributing to BIA-ALCL through prolonged T-cell stimulation, although this remains speculative.

5. What's needed?

• Better materials: More stable TMS treatments and more sustainable envelopes to minimise silica migration.
• Research: Targeted studies on pyrogenic silica toxicity in implants, including long-term effects and BIA-ALCL risk derivatives.
• Regulation: Stricter guidelines for nanomaterials in medical devices.

Many RAW264.7 cell studies

RAW264.7 cells are a Mouse immune cell line, specifically a murine Macrophages-like celline which originally comes from a tumor in a male BALB/c mouse. They are very often used in laboratory research as a model for macrophages.

Comparison with human macrophages:

Can you translate toxicity into humans in RAW264.7?

Careful: partially, but not automatically.

• ✔️ Benefits:
  RAW264.7 react to LPS (lipophysaccharide), phagocytic particles, produce cytokines such as TNF-α and IL-6 . This makes them suitable for the screen inflammatory reactions and cell culture toxicity.
• ⚠️ Restrictions:
  • Species differences: Mouse reactions are not always identical to human reactions.
  • Cancer cell line: They've been transformed, which means they can behave differently than normal cells.
  • No complex interaction: In a human body other cell types, tissues and immune signals are also involved.

Conclusion:

If anything is toxic to RAW264.7 cells, it is a strong signal that the potential is harmful to macrophages and therefore possible to the immune system. But it's no conclusive evidence of toxicity in humans. It's a first indication, after which testing with human cells or animal models is often carried out.

^{Disclaimer:
The information on this website is intended for informational purposes and is based on carefully collected scientific research. The topics and hypotheses discussed have not yet been widely recognised within the medical community. We are not doctors and do not give medical or legal advice. No rights can be derived from the content of this website. Stichting SVS accepts no liability for any consequences, damage, complaints or legal proceedings arising from the use of this information.}