The surface topography of silicone breast implants mediates the foreign body response in mice, rabbits and humans

Authors: Doloff JC, Veiseh O, de Mezerville R, Sforza M, Perry TA, Haupt J, Jamiel M, Chambers C, Nash A, Aghlara-Fotovat S, Stelzel JL, Bauer SJ, Neshat SY, Hancock J, Araujo Romero N, Elizondo Hidalgo Y, Mora Leiva I, Mendonça Munhoz A, Bayat A, Kinney BM, Hodges HC, Miranda RN, Clemens MW, Langer R.

Journal: Nature Biomedical Engineering, October 2021

PMID: 34155355

Goal of the Study

The researchers investigated how the surface topography (roughness) of silicone breast implants affects the foreign body response (FBR)—the immune reaction that leads to inflammation and fibrotic capsule formation. They compared a wide range of implant textures in mice, rabbits, and humans to identify which surface design minimizes fibrosis and immune activation.

Key Findings

1. Implant surface roughness directly shapes the immune response.

The study investigated implants ranging from completely smooth (0 μm roughness) to highly textured (90 μm, similar to Biocell).

• Highly textured surfaces triggered the strongest inflammatory response, increased macrophage infiltration, T-cell and B-cell recruitment, and thick, sometimes double-layered capsules.

• These severe responses mirrored clinical complications seen in humans, such as capsular contracture, chronic inflammation, and the specific association of textured implants with BIA-ALCL (breast implant–associated anaplastic large cell lymphoma).

2. A moderate roughness of ~4 μm (SmoothSilk) produced the least inflammation and fibrosis. This surface performed better than both fully smooth and more aggressively textured surfaces.

Among all surfaces tested, implants with ~4 μm average roughness:

• Developed the thinnest, least fibrotic capsules

• Had reduced inflammatory cytokine expression

• Avoided double-capsule formation

• Recruited significantly fewer macrophages

3. Regulatory T cells (Tregs) play a crucial role.

The 4 μm surface uniquely increased levels of FOXP3+ regulatory T cells around the implant.

These Tregs:

• Suppressed pro-fibrotic macrophage activity

• Limited overall inflammation

• Helped keep capsule formation thin and soft

When tested in T-cell–deficient mice, the anti-fibrotic benefit of the 4 μm surface disappeared, proving that T-cells—especially Tregs—are essential for this protective effect.

4. Findings were consistent across animals and human tissues.

Rabbit studies (up to 1 year) and examination of human capsule tissues confirmed the same pattern:

• SmoothSilk (~4 μm) = thinnest capsules and lowest inflammatory markers

• Macrotextured implants (Biocell) = thick capsules, debris, strong immune activation, and in ALCL cases, aggressive T-cell–driven inflammation

Human specimens from Biocell-associated ALCL showed profoundly elevated inflammatory and cytotoxic T-cell gene signatures.

Conclusion

Implant surface topography strongly influences the foreign body response.

A finely controlled, micro-scale surface roughness—specifically around 4 μm—provides the optimal balance: it limits macrophage activation and fibrosis while supporting a protective regulatory T-cell response. This research suggests that such microtextured surfaces may offer the safest and most biocompatible design for long-term silicone breast implants, while highly textured implants pose greater inflammatory and oncologic risks.